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1.
J Endocrinol Invest ; 31(10): 882-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19092293

RESUMO

Imaging of the adrenals by endoscopic ultrasound (EUS) is a valuable technique for detection and localization of adrenal lesions, but endosonomorphological tumor distinction remains difficult. In this single-center study, the amount of blood flow in common adrenal lesions, such as adrenal adenomas, adrenal hyperplasia, and pheochromocytomas, was visualized by color-coded duplex EUS (CD-EUS) and was retrospectively analysed. Therefore, we reviewed our EUS database to evaluate and correlate the perfusion patterns of common adrenal lesions with histologically confirmed diagnosis, possible malignancy, and endosonomorphological features such as echogeneity, echostructure, and tumor size. CD-EUS was performed using an endosonoscope Pentax FG 32 UA with a longitudinal 7.5 MHz sector array and Hitachi EUB 525 ultrasound system. In 38 consecutive patients (male=19; female=19; age: mean 53+/-16 yr SD), perfusion patterns of 46 histologically confirmed adrenal, para- or extra-adrenal lesions of adrenal origin (adenoma: no.=20; nodular hyperplasia: no.=11; pheochromocytoma: no.=15; diameter 26+/-15 mm, range 6-70 mm) were analyzed and classified semiquantitatively as "not" (no.=24), "slightly" (no.=12), "moderately" (no.=4) or "highly" (no.=6) hypervascularized. Compared to adenomas (p=0.003) and nodular hyperplasia (p=0.047), pheochromocytomas showed a significantly higher grade of perfusion. There was no relationship between perfusion patterns and localization of pheochromocytomas (adrenal: 8; paraadrenal: 3; extra-adrenal: 4). Vascularization was not statistically associated with tumor echogeneity, echostructure, malignancy or tumor size. CD-EUS is an additional tool for adrenal endosonographic tumor distinction and seems to improve the endosonographic detection of pheochromocytomas by visualization of hypervascularization. As an overlap of perfusion patterns exists, CD-EUS findings must be interpreted in the context of clinical, laboratory and chemical results.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/diagnóstico por imagem , Adenoma Adrenocortical/patologia , Adulto , Idoso , Endossonografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/patologia , Ultrassonografia Doppler em Cores
2.
Growth Horm IGF Res ; 17(4): 307-14, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17462934

RESUMO

OBJECTIVE: Genetic factors play an expanding role in understanding growth hormone (GH) disorders, therefore the German KIMS Pharmacogenetics Study was initiated with the aim of genotyping various GH-/IGF-I-axis-related genes of GH-deficient adult patients to investigate genotype:phenotype relationships and response to GH therapy. PATIENTS AND METHODS: 129 consecutively enrolled GH-deficient adult patients were genotyped for variant 1 (V1) of the alternatively spliced noncoding exons in the 5'-untranslated region and for the nine coding exons of the GH receptor (GHR) gene, which obviously play a striking role in the function of the GH-IGF-I-axis. After detection of a heterozygous, non-synonymous mutation R179C in exon 6 in one single patient with acquired GH-deficiency (GHD) in late adulthood, analysis of her clinical data followed, leading to the diagnosis of mild short stature (-1.5SD). For further endocrine evaluation, five pituitary stimulation tests (arginine) of this patient were statistically compared to stimulation tests (arginine) of ten GH-deficient control patients, retrospectively. RESULTS: The formerly in patients with Laron syndrome and idiopathic short stature reported mutation R179C leads to an amino acid change from an arginine residue (codon CGC) to a cysteine residue (codon TGC) in position 179 of the extracellular domain of the GHR. Statistical analysis revealed significant decreased IGF-I/GH(0) ratio (p=0.004) and IGF-I/GH(max) ratio (p=0.001) of the index patient compared to the control patients, implying growth hormone resistance of the index patient at the level of the GHR, according to the detected R179C mutation. CONCLUSIONS: This study reports on the unusual case of a patient with mild short stature, who acquired GHD in late adulthood due to a non-secreting pituitary adenoma and get additionally diagnosed for pre-existing growth hormone insensitivity due to a formerly in two short statured patients described, single, heterozygous, non-synonymous mutation in the GHR. Our findings support the theory that heterozygous mutations in the GHR gene can have mild phenotypical consequences.


Assuntos
Transtornos do Crescimento/sangue , Transtornos do Crescimento/genética , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/deficiência , Fator de Crescimento Insulin-Like I/análise , Mutação Puntual , Receptores da Somatotropina/genética , Adulto , Idade de Início , Substituição de Aminoácidos/genética , Arginina/genética , Estatura , Cisteína/genética , Feminino , Genótipo , Humanos , Síndrome de Laron/genética , Masculino , Pessoa de Meia-Idade
3.
Int J Clin Pharmacol Ther ; 44(2): 51-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16502763

RESUMO

OBJECTIVE: The drugs most commonly used to treat diabetes mellitus are sulfonylureas, biguanides and insulin. The most serious effects seen in overdose with these agents are hypoglycemia or lactic acidosis which may be fatal or cause cerebral defects. The present investigation analyzes inquiries made to a regional poisons unit involving overdoses with sulfonylureas, biguanides and insulin. PATIENTS AND METHODS: A total of 218,070 made inquiries between 1995 and 2004 were evaluated. The inquiries were received by telephone and a standardized questionnaire was sent subsequently to the physicians calling for follow-up information. The cases were analyzed with regard to gender, age, etiology, symptoms and clinical outcome. RESULTS: 263 inquiries concerning sulfonylureas (48.3% female, 49.4% male, 2.3% sex unknown, average age 39.1 +/- 26.8 years), 172 concerning biguanides (60.5% female, 37.2% male, 2.3% sex unknown, average age 41.5 +/- 24.1 years), and 191 concerning insulin (53.9% female, 41.9% male, 4.2% sex unknown, average age 44.6 +/- 16.7) were made. In cases involving sulfonylureas, the etiology was deliberate self-poisoning in 62.7% and accidental in 31.9% (biguanides 60.5% and 29.1%, insulin 85.3% and 9.4%). Using the Poisoning Severity Score, no symptoms were observed in 41.4% of the patients with sulfonylurea overdose (biguanides 40.1%, insulin 22.5%), minor symptoms in 37.6% (biguanides 32.6%, insulin 33.5%), major symptoms in 14.4% (biguanides 13.4%, insulin 26.2%) and serious symptoms in 4.6% (biguanides 12.2%, insulin 14.7%). Returned questionnaires reporting clinical outcomes showed that a full recovery occurred in most patients (sulfonylureas 97.4%, biguanides 93.0%, insulin 94.4%), cerebral defects persisted in 1.8% of the cases involving sulfonylureas (biguanides 1.5%, insulin 2.4%), and that 0.9% of the patients with sulfonylurea overdose died (biguanides 6.1%, insulin 3.6%). CONCLUSIONS: Sulfonylureas were the most frequently observed medication in cases of overdose with antidiabetic agents. Insulin overdose caused the highest number of major and serious symptoms. Overdose with biguanides led to the most deaths.


Assuntos
Biguanidas/intoxicação , Overdose de Drogas/epidemiologia , Hipoglicemiantes/intoxicação , Insulina/intoxicação , Centros de Controle de Intoxicações/estatística & dados numéricos , Compostos de Sulfonilureia/intoxicação , Adulto , Distribuição por Idade , Overdose de Drogas/terapia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Índice de Gravidade de Doença
4.
Toxicology ; 206(1): 153-67, 2005 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-15590115

RESUMO

An important application of hepatocyte cultures is identification of drugs acting as inducers of biotransformation enzymes that alter metabolic clearance of other therapeutic agents. In the present study we optimized an in vitro system with hepatocytes cultured in alginate microspheres that allow studies of enzyme induction with excellent sensitivity. Induction factors obtained with standard inducers, such as 3-methylcholanthrene or phenobarbital, were higher compared to those with conventional hepatocyte co-cultures on collagen coated dishes. This is illustrated by activities of 7-ethoxyresorufin-O-deethylase (EROD) after incubation with 5 microM 3-methylcholanthrene (3-MC), a standard inducer for cytochrome P4501A1 and 1A2. Mean activities for solvent controls and 3-MC exposed cells were 2.99 and 449 pmol/min/mg protein (induction factor: 150) for hepatocytes cultured in microspheres compared to 2.72 and 80.6 pmol/min/mg (induction factor: 29.6) for hepatocytes on collagen coated dishes. To compare these in vitro data to the in vivo situation male Sprague Dawley rats, the same strain that was used also for the in vitro studies, were exposed to 3-MC in vivo using a protocol that guarantees maximal induction. Activities were 29.2 and 1656 pmol/min/mg in liver homogenate of solvent and 3-MC treated animals (induction factor: 56.7). Thus, the absolute activities of 3-MC exposed hepatocytes in microspheres are lower compared to the in vivo situation. However, the induction factor in vitro was even higher compared to the in vivo situation (150-fold versus 56.7-fold). A similar scenario was observed using phenobarbital (0.75 mM) for induction of CYP2B and 3A isoenzymes: induction factors for testosterone hydroxylation in position 16beta were 127.5- and 50.4-fold for hepatocytes in microspheres and conventionally cultured hepatocytes, respectively. The new in vitro system with hepatocytes embedded in solid alginate microspheres offers several technical advantages: (i) the solid alginate microspheres can be liquefied within 60s, allowing a fast and complete harvest of hepatocytes; (ii) alginate capsules are stable allowing transport and mechanical stress; (iii) high numbers of hepatocytes can be encapsulated in short periods; (iv) defined cell numbers between 600 hepatocytes, the approximate number of cells in one capsule, and 18 x 10(6) hepatocytes, the number of hepatocytes in 6 ml alginate, can be transferred to a culture dish or flask. Thus, encapsulated hepatocytes allow a flexible organization of experiments with respect to cell number. In conclusion, we optimized a technique for encapsulation of hepatocytes in alginate microspheres that allows identification of enzyme induction with an improved sensitivity compared to existing systems.


Assuntos
Alginatos/química , Indução Enzimática/efeitos dos fármacos , Ácido Glucurônico/química , Hepatócitos/citologia , Hepatócitos/enzimologia , Ácidos Hexurônicos/química , Fígado/enzimologia , Tecnologia Farmacêutica/métodos , Animais , Técnicas de Cultura de Células , Células Cultivadas , Técnicas de Cocultura , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP2B1/biossíntese , Glutationa Transferase/biossíntese , Hepatócitos/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Metilcolantreno/farmacologia , Microesferas , Fenobarbital/farmacologia , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Clin Toxicol (Phila) ; 43(6): 575-81, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16255340

RESUMO

BACKGROUND: Poisonings with rodenticides containing hydrogen phosphide-releasing compounds may lead to deleterious organ dysfunction and death. Since data of hydrogen phosphide poisonings is limited to case reports/series, this study was intended to elucidate hydrogen phosphide poisonings based on a 20-year data collection. METHODS: Explorative data analysis of the Poison Center Mainz database looking for route of exposure, symptoms, and severity using the Poisoning Severity Score. RESULTS: From 1983-2003, 188 hydrogen phosphide poisonings were reported. Sixty-five percent of these were unintentional residential, 28% attempts to commit suicide (intentional), 5% occupational, and 2% undetermined. In the majority of intentional poisonings the poison was ingested, whereas in unintentional poisoning of adults inhalation exposure dominated, caused by inappropriate self-protection from the released hydrogen phosphide gas during usage. Frequently observed symptoms in unintentional poisonings were nausea, vomiting, pain, coughing, and dizziness with no further worsening of symptoms. In intentional poisonings frequent symptoms were vomiting, somnolence, seizures, coma, and shock with two initially fatal poisonings. Follow-up on these cases showed a significant worsening of symptoms and a two-fold increase in fatal poisonings. CONCLUSION: Route of exposure, severity of symptoms, and the necessary treatment differs substantially between unintentional and intentional poisonings. In this study, two initially symptomatic intentional poisonings were later reported fatal. Careful monitoring is recommended in symptomatic intentional poisonings.


Assuntos
Fosfinas/intoxicação , Rodenticidas/intoxicação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Centros de Controle de Intoxicações , Intoxicação/epidemiologia , Intoxicação/terapia , Suicídio , Fatores de Tempo
6.
Clin Toxicol (Phila) ; 43(1): 31-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15732444

RESUMO

OBJECTIVE: Renal insufficiency is less common than liver failure in acetaminophen overdose but renal tubular damage occurs even in the absence of hepatotoxicity. Data published on this topic are rare consisting mostly of case reports or reports in a small number of patients. Presently, a larger number of patients with renal insufficiency associated with acetaminophen overdose should be analyzed using a multicenter approach. STUDY DESIGN: Retrospective analysis of patients with acetaminophen-related nephrotoxicity reported to a poison center network from 1995 to 2003. Renal insufficiency was defined as elevated serum creatinine of more than double of the normal range (>2.4 mg/dL [212 micromol/L]). Patients were classified into 4 groups (A: creatinine 2.4-5.0 mg/dL, B: creatinine>5.0 mg/dL requiring no dialysis, C: creatinine>5.0 mg/dL requiring dialysis, D: creatinine>5.0 mg/dL with fatal outcome). RESULTS: Seventeen patients were included (8 female, 9 male, average age 31.7 +/- 21.1 yrs) with 6 patients in group A (B: 7, C: 2, D: 2). In 5 patients renal insufficiency occurred without elevation of liver enzymes. Regarding possible risk factors 5 patients concomitantly ingested nephrotoxic substances, 4 presented with dehydration due to vomiting, 4 with chronic excessive dosing (overdose) of acetaminophen, 3 showed pre-existing renal insufficiency, 2 pre-existing liver disease and 2 died with multiple organ failure. CONCLUSIONS: Renal insufficiency in acetaminophen overdose mostly resolved without dialysis and occurred isolated without hepatotoxicity in less than one-third of the investigated patients. Conditions which might play a role as influencing factors for renal complications included concomitant ingestion of nephrotoxic drugs, dehydration, chronic excessive dosing (overdose) of acetaminophen, pre-existing renal or liver disease and multiple organ failure. Renal function should be monitored in acetaminophen overdose particularly in patients showing the latter comorbidity.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Insuficiência Renal/epidemiologia , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Idoso , Overdose de Drogas/epidemiologia , Overdose de Drogas/etiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Centros de Controle de Intoxicações/estatística & dados numéricos , Insuficiência Renal/induzido quimicamente
7.
J Appl Biomater Biomech ; 3(1): 11-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-20799235

RESUMO

OBJECTIVE: This study aimed to investigate specific inflammatory pathomechanisms, i.e. the expression of the stem cell factor receptor KIT (CD117) in tissue specimens from patients with aseptic hip prosthesis loosening (AHPL) with special emphasis on colocalization with the mast cell specific marker tryptase. METHODS: Immunohistochemical analysis of CD117 was performed in tissue specimens from 10 patients with aseptically loosened acetabular components of failed non-cement total hip replacements and compared to control samples obtained at primary hip surgery (n=4). The CD117 expressing cells were characterized further with mast cell tryptase (MCT) by serial section analysis and a double staining method. CD117 and MCT expression was examined by semi-quantitative analysis. Additionally, double labeling of the CD117 or MCT expression by immunohistochemistry and of polyethylene (PE) particles by Oil Red reaction was performed. RESULTS: In AHPL, CD117 was almost exclusively detected in MCT positive cells. Co-expression tended to be highly correlated (r=0.86, p<0.01). CD117 was found mainly in two regions: first, in perivascular lymphocyte-rich areas and; secondly, near macrophages and multinucleated giant cells (MGC). PE particles were not detected in CD117 and MCT positive cells. In control samples, CD117/MCT positive cells were less frequent. CONCLUSION: This is the first report on CD117 expression in AHPL. CD117 is almost exclusively expressed in a distinct mast cell subgroup. As an important growth factor receptor, CD117 could play a major role in recruitment and activation of mast cells in AHPL. Furthermore, mast cells do not contain significant amounts of PE particles. However, it remains to be investigated whether this cell population could influence phagocytosis of PE particles. (Journal of Applied Biomaterials and Biome-chanics 2005; 3: 11-7).

8.
Metabolism ; 53(7): 918-21, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15254887

RESUMO

Weight loss reduces bone mass and increases the risk of osteoporosis. This study was undertaken to assess changes of bone metabolism following Roux-en-Y gastric bypass (RYGB) and adjustable silicone gastric banding (ASGB) as compared to nonoperated controls of morbidly obese subjects. Fourteen female and 5 male patients with a mean (+/-SEM) age of 44.3 +/- 1.8 years participated in the 24-month prospective study. Nine patients underwent ASGB, 4 patients RYGB operation, and 6 patients were included in the control group. Bone metabolism was assessed by determination of serum parathyroid hormone (PTH), osteocalcin, urinary deoxypyridinoline, and dual energy x-ray absorptiometry (DXA) before, and 6, 12, and 24 months after intervention. The body mass index (BMI) decreased from 41.0 +/- 1.1 to 34.0 +/- 1.4 kg/m2 in the ASGB group (P = .001), from 42.7 +/- 2.2 to 30.5 +/- 2.2 kg/m2 in the RYGB group (P = .006), and remained unchanged in the control group (from 41.2 +/- 1.2 to 41.4 +/- 1.4 kg/m2) after 24 months. Bone mineral content (BMC) showed no significant change in the ASGB group (from 3,079 +/- 140 to 3,064 +/- 129 g) and in the control group (from 2,945 +/- 130 to 2,940 +/- 111 g), whereas it decreased from 2,968 +/- 111 to 2,621 +/- 139 g in the RYGB group (P = .005). The loss in BMC was accompanied by significant increases in urinary deoxypyridinoline (P < .05) and in serum osteocalcin (P < .01) after RYGB, suggesting both, increased bone resorption and increased bone formation. The authors were aware of the fact that the study groups were small and conclusions need to be regarded as preliminary. However, the RYGB operation resulted in enhanced weight loss and significant net loss of bone mass in comparison to ASGB and obese control subjects. Patients losing large amounts of body weight should be monitored regularly regarding prevention of osteoporosis.


Assuntos
Densidade Óssea/fisiologia , Obesidade Mórbida/terapia , Estômago/cirurgia , Absorciometria de Fóton , Aminoácidos/uso terapêutico , Anastomose em-Y de Roux , Composição Corporal/fisiologia , Índice de Massa Corporal , Constrição , Feminino , Derivação Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue
9.
Exp Clin Endocrinol Diabetes ; 112(4): 187-90, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15127322

RESUMO

Metformin is widely used in the treatment of type 2 diabetes, though it is recognized to be associated with the risk of lactic acidosis. A case of pronounced lactic acidosis with cardiac arrest (pH 6.60, lactate 17.5 mmol/l, base excess - 30, standard bicarbonate 2.5 mmol/l, core body temperature 27.8 degrees C) is presented in a 61-year-old woman under metformin therapy. The key laboratory abnormalities observed during the intensive care treatment including repeated hemodialysis are described. The patient showed a complete recovery with residually reduced mental capabilities. Furthermore, an explorative data analysis of our poison center database from 1995 until 2003 concerning metformin was performed. In 109 inquiries for metformin a lactic acidosis (mean pH 6.87 +/- 0.11, mean lactate 20.9 +/- 8.1 mmol/l) was present in 14 cases (9 female, 5 male, average age 57.7 years) with 8 patients under regular metformin therapy and 6 patients who ingested large amounts of metformin to attempt suicide. 4 patients did not survive the severe metabolic disturbance. The present report demonstrates that metformin-associated lactic acidosis is a rare but critical complication of metformin therapy of type 2 diabetes as well as in acute suicidal ingestion of metformin. Early diagnosis and rapid correction of the metabolic acidosis using hemodialysis provides the possibility of a positive outcome even in severe cases. If metformin-associated lactic acidosis is suspected we recommend early involvement of a poison center.


Assuntos
Acidose Láctica/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Centros de Controle de Intoxicações , Feminino , Humanos , Hipoglicemiantes/intoxicação , Metformina/intoxicação , Pessoa de Meia-Idade , Tentativa de Suicídio
10.
Exp Clin Endocrinol Diabetes ; 110(8): 416-9, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12518253

RESUMO

Pharmacokinetic and pharmacodynamic profiles of the rapid-acting insulin analogues lispro and aspart were compared in a randomized, double-blind crossover study of 20 fasting healthy men following a single subcutaneous injection. Either insulin lispro or aspart, 0.05 U/kg-body-weight, was injected subcutaneously and followed by determination of 5-h profiles of plasma glucose, serum C-peptide and insulin concentrations. Lowest glucose concentrations were observed after 50 min in the aspart group (3.2 +/- 0.1 mmol/l versus lispro 3.5 +/- 0.1 mmol/l; p = 0.026) and after 60 min in the lispro group (3.4 +/- 0.1 mmol/l). For blood glucose t min was 59.3 +/- 3.4 min in the aspart and 63.5 +/- 5.3 min in the lispro group (ns). After 40 min a lower C-peptide was determined for aspart (225 +/- 21 pmol/l versus lispro 309 +/- 33 pmol/l; p = 0.031), whereas minimal C-peptide concentrations were reached in both groups after 105 min (lispro 117 +/- 21 pmol/l versus aspart 105 +/- 18 pmol/l). The maximal concentration of insulin was detected in both groups after 40 min (lispro 20.8 +/- 1.1 mU/l versus aspart 24.6 +/- 1.3 mU/l; p = 0.032). For insulin t max was 33.0 +/- 2.6 min in the aspart versus 33.3 +/- 2.6 min in the lispro group (ns). The present results indicate a more rapid absorption of insulin aspart in comparison to insulin lispro. Higher insulin concentrations after subcutaneus injection may be advantageous in meal-related treatment of diabetes.


Assuntos
Hipoglicemiantes/farmacocinética , Insulina/análogos & derivados , Insulina/farmacocinética , Adulto , Glicemia/análise , Peptídeo C/sangue , Estudos Cross-Over , Método Duplo-Cego , Humanos , Insulina/sangue , Insulina Aspart , Insulina Lispro , Masculino , Radioimunoensaio
11.
Acta Diabetol ; 40(3): 123-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14605968

RESUMO

Large amounts and excellent viabilities of pancreatic islets are prerequisites for recent advances in islet transplantation. Cryopreservation has been shown to enlarge transplanted cell mass, but has been accompanied by reduced viability. In this study rat pancreatic islets were differentiated into small (<200 micro m), medium (200-400 micrometers) and large (>400 micrometers) categories and their susceptibilities to different freezing conditions were evaluated: concentration of cryoprotectant (0.7-3.1 M), equilibration (15 vs. 45 min, 22 degrees C vs. on ice) and post-thaw removal of cryoprotectant (15 vs. 30 min, stepwise vs. one-step). The most prominent finding was a negative correlation between islet size and viability observed in non-frozen islets to a minor degree (r=-0.44) and significantly enhanced after cryopreservation (r<-0.8). The concentration of cryoprotectant showed the most significant influence on viability affecting small, medium and large islets. Different techniques of equilibration with the cryoprotectant resulted in significant changes of islet viability of medium islets, whereas small and large islets were unaffected. For different techniques of removal of the cryoprotectant, no significant influence on viabilities was found. We conclude that large islets represented a highly susceptible population concerning damage due to cryopreservation.


Assuntos
Criopreservação/métodos , Ilhotas Pancreáticas/citologia , Preservação de Tecido , Trifosfato de Adenosina/metabolismo , Animais , Tamanho Celular , Sobrevivência Celular , Ilhotas Pancreáticas/metabolismo , Masculino , Pâncreas/citologia , Pâncreas/fisiologia , Pancreatectomia , Perfusão , Ratos , Ratos Sprague-Dawley
12.
Int J Clin Pharmacol Ther ; 42(5): 277-80, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15176650

RESUMO

OBJECTIVE: Overdoses with insulin are common, and cases of hypoglycemic coma can be fatal and cause cerebral defects. However, data published on this topic are rare, consisting mostly of case reports or reports in a small number of patients. The present investigation analyzes inquiries made to a regional poisons unit involving overdoses with insulin. PATIENTS AND METHODS: A total of 175,890 inquiries for the years 1995-2003 (until September) were evaluated. 160 inquiries were received by telephone concerning insulin overdoses, and a standardized questionnaire was sent to the physicians asking for follow-up information. The cases were analyzed in regard to etiology, type of insulin used, concomitant substances being taken by the patient, symptoms and clinical outcome. RESULTS: Of the 160 inquiries investigated, 53.1% of the patients were female, 43.1% male and in 3.8% the sex of the patient was unknown. The average age was 44.7 years. 89.4% involved suicidal or parasuicidal cases, 5.0% were accidental overdoses and 1.9% involved cases of criminal overdose (3.7% were for other reasons). Rapidly acting insulins (57.8%) were used more commonly than long-acting formulations (42.8%). Benzodiazepines were the most frequently ingested concomitant medication (37.5%) with ethanol 15.6%, antihypertensive drugs 12.5% and antidepressants 10.0%. Most patients presented with a delay of 2-3 hours after insulin administration (15.0%). Almost 50% of the patients presented within the first 6 hours. According to the Poisoning Severity Score, no symptoms were observed in 16.8% of the patients, minor symptoms in 36.8%, major symptoms in 25.2% and serious symptoms in 21.3%. Information concerning the clinical outcome (75 cases) showed that a full recovery occurred in most patients (94.7%), but in 2.7% there were cerebral defects and 2.7% of the patients died. CONCLUSIONS: The etiology of overdoses with insulin was mainly deliberate self-poisoning. Physicians should take into account that long-acting insulin formulations and concomitant substances were frequently used. For overdoses with insulin, relatively high rates of serious symptoms and deaths were observed.


Assuntos
Hipoglicemiantes/intoxicação , Insulina/intoxicação , Comportamento Autodestrutivo/epidemiologia , Adulto , Overdose de Drogas , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Centros de Controle de Intoxicações , Suicídio/estatística & dados numéricos
13.
Klin Padiatr ; 218(1): 31-3, 2006.
Artigo em Alemão | MEDLINE | ID: mdl-16432773

RESUMO

BACKGROUND: Drug poisonings in childhood account with about one fourth for the most important group of poisonings in this age group. METHOD: From 1995 to 2004 the inquiries to a poison centre regarding drug poisonings of children < or = 6 years of age were analyzed. Additionally, a standardized questionnaire was sent for follow-up information. RESULTS: During the study period a total number of 17 553 cases of drug poisonings in childhood was determined and follow-up information was obtained for 8 590 cases (48.9 %). Boys were more likely to be affected (53.4 %) and most children were between 2 and 4 years of age (57.5 %). Mostly oral contraceptives, homeopathic drugs, nonsteroidal anti-inflammatory drugs, sodium fluoride and paracetamol were ingested. In 97.8 % of the reported cases none or minor symptoms and in 1.5 % medium or major symptoms (1 death) were observed. In the latter group of patients mostly neuroleptics, antihistaminics, nonsteroidal anti-inflammatory drugs, beta2-sympathomimetics and paracetamol were ingested. In most cases the application of fluids (47.3 %) or activated charcoal (32.0 %) was sufficient. CONCLUSIONS: Severe symptoms have rarely been observed in drug poisonings and in most children a treatment by non-professionals was sufficient. Most frequently activated charcoal was currently used for primary poison elimination. We suggest an early involvement of a poison centre in drug intoxications.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Centros de Controle de Intoxicações/estatística & dados numéricos , Intoxicação/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Alemanha , Inquéritos Epidemiológicos , Humanos , Incidência , Lactente , Masculino , Intoxicação/prevenção & controle , Fatores de Risco
14.
Dtsch Med Wochenschr ; 130(16): 1002-6, 2005 Apr 22.
Artigo em Alemão | MEDLINE | ID: mdl-15830312

RESUMO

BACKGROUND AND OBJECTIVE: Systemic fibrinolysis has become an important therapeutical option in patients with thrombotic occlusion of coronary or pulmonary arteries. In view of the hemorrhagic risk systemic fibrinolytic therapy for retinal vessel occlusion has been discussed controversial. In the present case study results and complications of systemic fibrinolysis should be investigated in patients with central retinal artery occlusion. PATIENTS AND METHODS: From 1995 to 2002 a case series of 19 consecutive patients (8 female, 11 male, age: 63.2+/-14,3 years) with central retinal artery occlusion were treated by systemic application of urokinase using a standardized scheme. The latency from initial symptoms until the initiation of therapy and the medical history of the patients were documented. Visual acuity was determined on admission and before discharge and possible complications were documented. Additionally, screening investigations for genetic thrombophilia were performed. RESULTS: 15 patients showed an improvement of the visual acuity (79 %, 95 %-KI: 54 %-94 %). For 3 patients no improvement and for one patient a decrease of the visual acuity was determined. Hemorrhagic complications were observed in two patients (11 %, 95 %-KI: 1 %-33 %). As these minor bleedings were self-limiting the fibrinolytic therapy was discontinued only in one patient. As risk factors most commonly arterial hypertension (68 %) and smoking (26 %) were identified. In 4 patients a genetic thrombophilia was diagnosed. CONCLUSIONS: Considering the poor prognosis of central retinal artery occlusion and the disappointing results of conservative treatment, an improvement of the visual acuity in the absence of critical complications was observed with systemic fibrinolytic therapy in the presented case study. However, only controlled trials can provide proof for the effect of fibrinolysis versus spontaneous improvement.


Assuntos
Ativadores de Plasminogênio/uso terapêutico , Oclusão da Artéria Retiniana/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Acuidade Visual/efeitos dos fármacos , Contraindicações , Feminino , Hemorragia/induzido quimicamente , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Ativadores de Plasminogênio/efeitos adversos , Ativadores de Plasminogênio/farmacologia , Prognóstico , Fatores de Risco , Fumar/efeitos adversos , Terapia Trombolítica/efeitos adversos , Trombofilia/complicações , Trombofilia/genética , Ativador de Plasminogênio Tipo Uroquinase/efeitos adversos , Ativador de Plasminogênio Tipo Uroquinase/farmacologia
15.
Heart ; 91(2): e14, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15657204

RESUMO

Clopidogrel, in combination with aspirin, is commonly used for the prevention of thrombosis in patients who have received coronary artery stents. As a rare but critical complication, clopidogrel associated thrombotic thrombocytopenic purpura (TTP) has previously been described. A 78 year old man presented with unstable angina and filiform subtotal stenosis of the left anterior descending artery. He was treated with balloon angioplasty and stent implantation. After four days the patient again had angina caused by stent thrombosis, which was treated with balloon angioplasty. During hospital stay the typical course of clopidogrel associated TTP was observed with thrombocytopenia and petechial purpura occurring 14 days after drug initiation and prompt response to therapeutic plasma exchanges. These findings strongly suggest that clopidogrel may have increased platelet activation and aggregation in this immunologically susceptible patient, ultimately leading to a stent thrombosis.


Assuntos
Prótese Vascular , Estenose Coronária/terapia , Trombose Coronária/etiologia , Inibidores da Agregação Plaquetária/efeitos adversos , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Ticlopidina/análogos & derivados , Ticlopidina/efeitos adversos , Idoso , Angina Instável/etiologia , Angina Instável/terapia , Clopidogrel , Reestenose Coronária/etiologia , Humanos , Masculino , Falha de Prótese , Recidiva , Stents
16.
Praxis (Bern 1994) ; 90(37): 1569-74, 2001 Sep 13.
Artigo em Alemão | MEDLINE | ID: mdl-11594122

RESUMO

The prevalence of obesity is increasing world wide, resulting in morbidity, mortality, and reduced quality of life. The aim of this study was to assess comorbidities and complaints of subjects with morbid obesity in comparison to milder forms of overweight. Therefore, 299 patients visiting our obesity consultation were examined and surveyed prospectively. 41% of the subjects were morbidly obese showing a significantly higher prevalence of arterial hypertension, edema, dyspnea, eczema and depression. Additionally, sleepiness, reduced work capacity, physical inactivity, disadvantages in social life and disturbed eating habits were observed more frequent. Evaluation of subjects with morbid obesity should include a large spectrum of complications, in order to be able to offer a comprehensive support and treatment.


Assuntos
Obesidade Mórbida/complicações , Adulto , Índice de Massa Corporal , Comorbidade , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Encaminhamento e Consulta/estatística & dados numéricos , Suíça/epidemiologia
17.
Z Kardiol ; 93 Suppl 4: IV9-15, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15085361

RESUMO

Cardiac dysrhythmias are common in acute intoxications. However, epidemiological data is rare and restricted to specific substances. From 1995 to 2003 (until September) 91 285 inquiries of physicians and paramedics to a poison center regarding acute intoxications were analyzed revealing 9888 patients (10.8%) suffering from disturbances of the cardiac rhythm. In a first step of the explorative data analysis dysrhythmias were graduated into three categories (I: tachycardia/bradycardia; II: arrhythmia/conduction disorder; III: ventricular dysrhythmia/cardiac arrest) and the frequencies of the involved substances were determined. In a second step substances which resulted to be of significant interest were investigated for their specific pattern of dysrhythmias. For category I (n = 8730) predominantly tricyclic antidepressants, neuroleptics, benzodiazepines, betablockers, and nonsteroidal antiinflammatory drugs were registered (II: [n = 949] tricyclic antidepressants, digitalis glycosides, benzodiazepines, neuroleptics, Ca antagonists; III: [n = 209] tricyclic antidepressants, neuroleptics, sotalol, ethanol, central nervous system stimulants). Tricyclic antidepressants resulted in 23.4% of the reported cases in symptoms of category I (II: 2.3%, III: 0.6%; n = 8535). The highest rates of dysrhythmias were observed for sotalol (I: 34.7%, II: 21.6%, III: 8.0%; n = 176) as compared to the lowest rates found for paracetamol (I: 5.2%, II: 0.3%, III: 0.1%; n = 6429). The present investigation provided a comprehensive clinical overview about the frequency of dysrhythmias and involved substances during acute poisonings in emergency medicine. Furthermore, the specific effects of selected substances concerning dysrhythmias could be determined in view of a clinical database.


Assuntos
Arritmias Cardíacas/classificação , Arritmias Cardíacas/epidemiologia , Centros de Controle de Intoxicações/estatística & dados numéricos , Intoxicação/classificação , Intoxicação/epidemiologia , Doença Aguda , Arritmias Cardíacas/diagnóstico , Comorbidade , Bases de Dados Factuais , Alemanha/epidemiologia , Humanos , Intoxicação/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença
18.
Dtsch Med Wochenschr ; 127(40): 2053-6, 2002 Oct 04.
Artigo em Alemão | MEDLINE | ID: mdl-12373636

RESUMO

BACKGROUND AND OBJECTIVE: Antidepressant drugs are frequently used in deliberate self-poisoning resulting in a major risk for the patients due to their cardiac and central-nervous toxicity. In the present study the cases of intoxications consulting our Poison Center should be analysed illustrating recent results and trends about self-poisoning with antidepressants. PATIENTS AND METHODS: During the study period from 1995 to 2001 35 394 inquiries concerning deliberate self-poisoning were registered in our Poison Center. The substance used, age and gender of the patient as well as the degree of the observed symptoms were documented. Thereby, antidepressant drugs were grouped in tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI) and other antidepressants. RESULTS: The use of antidepressants in deliberate self-poisoning continuously increased during the study period from 17.3 % to 22.9 % with SSRI and other antidepressants being observed more frequently as compared to TCA. Antidepressant drugs were mainly used from female patients and in the age group between 35 and 54 years. Antidepressant drugs caused severe intoxications and deaths more frequently as the remainder substances with TCA showing higher rates of complications as compared to SSRI and other antidepressants. CONCLUSIONS: In recent years, an increasing importance of antidepressant drugs in deliberate self-poisoning was determined particularly concerning female and middle-aged patients. Due to the changing prescribing patterns larger numbers of intoxications with SSRI and other antidepressants were observed representing an advantage with respect to the reduced rate of complications known for these substances as compared to TCA. Nevertheless, the averagely more severe symptoms present in the three groups of antidepressants in comparison to the remainder drug overdoses demonstrated the need for hospitalization and monitoring of intoxications with antidepressants.


Assuntos
Antidepressivos/intoxicação , Intoxicação/mortalidade , Tentativa de Suicídio/tendências , Suicídio/tendências , Adolescente , Adulto , Fatores Etários , Idoso , Antidepressivos Tricíclicos/intoxicação , Causas de Morte , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/intoxicação , Fatores Sexuais
19.
Cell Tissue Res ; 287(2): 255-61, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8995196

RESUMO

Under the transmission electron microscope, synaptic ribbons (SRs) of the mammalian pineal gland appear as rod-like organelles. Their three-dimensional structure is not precisely known. In the present study, pineal SRs were investigated using serial sections obtained from rats killed at noon and midnight. The shape of the SRs was reconstructed based on SR profile length and the number of sections in which the profiles were contained. The results obtained show that SRs are basically flat plate-like structures with polymorphic lateral edges. Reconstructions of SRs revealed that they had average dimensions of 300x150x35 nm and were 19.3% larger at night than at day; the difference in SR size points to perhaps major differences in synaptic function between day and night.


Assuntos
Glândula Pineal/ultraestrutura , Sinapses/ultraestrutura , Animais , Ritmo Circadiano , Exocitose/fisiologia , Masculino , Microscopia Eletrônica , Glândula Pineal/metabolismo , Ratos , Ratos Sprague-Dawley , Sinapses/metabolismo
20.
J Anat ; 191 ( Pt 3): 399-405, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9418996

RESUMO

The disector is the only objective method for quantifying particles of variable size in a given volume. With this method, cell organelles are identified on adjacent sections, but only those present in one section are counted. When counting extremely rare structures in transmission electron microscope sections (physical disector), the usual procedure of counting on electron micrographs is limited for economic reasons (e.g. micrographs highly outnumbering the investigated structures). Hence, to apply this unbiased stereological method, a modification of the physical disector concerning 3 aspects has been developed. (1) The prerequisite of screening large corresponding tissue areas (here approximately 65000 microm2) was fulfilled by examining tissue areas along the edges of ultrathin sections. (2) The size of the counting frame was determined by measuring the lengths of the section margins (minus a guard area) by means of a Morphomat. This value was multiplied by the width of the investigated tissue zone, corresponding to the diameter of the electron microscope viewing screen. (3) Disector counting was carried out simultaneously on both sections (bidirectional disector) to improve efficiency. In the present study tiny synaptic bodies (SBs) were quantitated by disector in a rat pineal gland, yielding approximately 30 SBs/1000 microm3. By contrast, single section profile counts of SBs amounted to 90 SBs/20000 microm2. Since the presently described adaptation of the disector is time-consuming, it is proposed to determine a proportion factor allowing to estimate number of structures per volume based on single section profile counts. This would decrease the evaluation time by more than 50%.


Assuntos
Glândula Pineal/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Animais , Masculino , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley
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