RESUMO
Human natural killer (NK) cells play an important role in anti-viral immunity. However, studying their activation kinetics during infection is highly problematic. A clinical trial of a therapeutic virus provided an opportunity to study human NK cell activation in vivo in a controlled manner. Ten colorectal cancer patients with liver metastases received between one and five doses of oncolytic reovirus prior to surgical resection of their tumour. NK cell surface expression of the interferon-inducible molecules CD69 and tetherin peaked 24-48 h post-infection, coincident with a peak of interferon-induced gene expression. The interferon response and NK cell activation were transient, declining by 96 h post-infection. Furthermore, neither NK cell activation nor the interferon response were sustained in patients undergoing multiple rounds of virus treatment. These results show that reovirus modulates human NK cell activity in vivo and suggest that this may contribute to any therapeutic effect of this oncolytic virus. Detection of a single, transient peak of activation, despite multiple treatment rounds, has implications for the design of reovirus-based therapy. Furthermore, our results suggest the existence of a post-infection refractory period when the interferon response and NK cell activation are blunted. This refractory period has been observed previously in animal models and may underlie the enhanced susceptibility to secondary infections that is seen following viral infection.
Assuntos
Imunidade Celular , Células Matadoras Naturais/imunologia , Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos/imunologia , Reoviridae/imunologia , Idoso , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Feminino , Humanos , Interferons/imunologia , Células Matadoras Naturais/patologia , Lectinas Tipo C/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/terapiaRESUMO
Pentabrominated diphenyl ether (PBDE) flame retardants have been phased out in Europe and in the United States, but these lipid soluble chemicals persist in the environment and are found human and animal tissues. PBDEs have limited genotoxic activity. However, in a 2-year cancer study of a PBDE mixture (DE-71) (0, 3, 15, or 50â¯mg/kg (rats); 0, 3, 30, or 100â¯mg/kg (mice)) there were treatment-related liver tumors in male and female Wistar Han rats [Crl:WI(Han) after in utero/postnatal/adult exposure, and in male and female B6C3F1 mice, after adult exposure. In addition, there was evidence for a treatment-related carcinogenic effect in the thyroid and pituitary gland tumor in male rats, and in the uterus (stromal polyps/stromal sarcomas) in female rats. The treatment-related liver tumors in female rats were unrelated to the AhR genotype status, and occurred in animals with wild, mutant, or heterozygous Ah receptor. The liver tumors in rats and mice had treatment-related Hras and Ctnnb mutations, respectively. The PBDE carcinogenic activity could be related to oxidative damage, disruption of hormone homeostasis, and molecular and epigenetic changes in target tissue. Further work is needed to compare the PBDE toxic effects in rodents and humans.
RESUMO
A cDNA preparation, synthesized by using Saccharomyces cerevisiae mitochondrial RNA as template and oligodeoxythymidylic acid as primer, was found to specifically hybridize to the mitochondrial 21S rRNA by the following criteria: (i) it hybridizes only to the 21S RNA species in mitochondrial RNA and not to RNA from a [rho0] mutant, and (ii) it hybridizes to fragments in restriction digests of mitochondrial DNA that contain the 21S rRNA gene but not to nuclear DNA. This cDNA was used as a probe to demonstrate that a 2.6-fold decrease in the cellular level of the mitochondrial large rRNA is associated with glucose repression of mitochondrial function in S. cerevisiae. A corresponding decrease in the level of mitochondrial DNA was not observed.
Assuntos
Mitocôndrias/metabolismo , RNA Fúngico/metabolismo , RNA Ribossômico/metabolismo , Saccharomyces cerevisiae/metabolismo , DNA , Glucose/farmacologia , Mitocôndrias/efeitos dos fármacos , Hibridização de Ácido Nucleico , Saccharomyces cerevisiae/efeitos dos fármacosRESUMO
We examined Saccharomyces cerevisiae mitochondrial RNA for polyadenylate. Using hybridization to [3H]polyuridylate as the assay for adenylate sequences, we found adenylate-rich oligonucleotides approximately 8 residues long. Longer polyadenylate was not detected. Most of the adenylate-rich sequence is associated with the large mitochondrial rRNA. The remainder is associated with the 10-12S group of transcripts.
Assuntos
Mitocôndrias , Poli A/análise , RNA Fúngico/análise , Saccharomyces cerevisiae/genética , Composição de Bases , Cromatografia de Afinidade , Hibridização de Ácido Nucleico , Poli U , RNA Ribossômico/análise , Ribonucleases/farmacologiaRESUMO
The synethesis of a new retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide, which has useful biological properties, is described. This retinoid was more potent than retinyl acetate in reversing keratinization caused by retinoid deficiency in tracheal organ culture. It was markedly less toxic than retinyl acetate when fed p.o. to rats over 2-week or 6-month periods. It was an effective agent for inhibition of the development of breast cancer induced in rats by N-nitroso-N-methylurea, although it was not as potent as retinyl acetate in this regard. However, the lesser toxicity of 4-hydroxyphenylretinamide makes it a superior agent for prevention of breast cancer. High-pressure liquid chromatographic analyses of liver and breast extracts from rats treated for 6 months with retinoids show the pharmacokinetic basis for the superiority of 4-hydroxyphenylretinamide; this retinoid and its metabolites were found in high concentrations in breast tissue, without any measurable accumulation in the liver or evident liver toxicity. In contrast, chronic feeding of retinyl acetate caused marked deposition of retinyl esters in the liver and severe hepatotoxicity. Whole mounts of rat mammary glands, made after chronic feeding of 4-hydroxyphenylretinamide, showed that it had a marked antiproliferative effect on mammary epithelium.
Assuntos
Neoplasias Mamárias Experimentais/prevenção & controle , Tretinoína/análogos & derivados , Vitamina A/análogos & derivados , Animais , Feminino , Fígado/metabolismo , Glândulas Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/induzido quimicamente , Metilnitrosoureia , Técnicas de Cultura de Órgãos , Ratos , Traqueia/efeitos dos fármacos , Tretinoína/farmacologia , Vitamina A/metabolismo , Deficiência de Vitamina A/tratamento farmacológicoRESUMO
BACKGROUND: Ballistic fractures are devastating injuries often necessitating extensive reconstructive surgery or amputation, particularly if associated with high-energy transfer wounds. Infective complications are common, particularly in the austere environment encountered in war. We present the management and early outcome of these injuries with reference to the mechanism of injury and bony injury. METHOD: Data on ballistic fractures was collected prospectively during the 'war-fighting' phase of the 2003 Gulf Conflict, between 19th March and 20th May. Fractures were scored using the Red Cross Fracture classification and early outcome analysed. RESULTS: Thirty-nine patients, with 50 ballistic fractures, were treated by British military surgeons. Patients were predominantly Iraqi (90%) and 50 per cent of ballistic fractures were caused by bullets. Seventeen upper limb fractures and 33 lower limb fractures were sustained. There were seven traumatic amputations, and a further 2 limbs were amputated primarily. Methods of primary stabilisation for the remaining 41 fractures were: external fixation (22%), POP (14.5%), K-wires (14.5%) traction (10%), and no stabilisation (39%). Seven individuals were evacuated early after primary surgery, hence 43 ballistic fractures were available for follow-up. 13/43 (30%) of wounds became infected, 5/43 (11.5%) were deep infections necessitating surgical drainage. There were 4 late amputations (9.5%), 3 of which had initially been managed by external fixation. Infection occurred significantly more often in gunshot fractures (10/21, 48%), wounds closed primarily against the principles of war surgery (415, 80%) and intra-articular fractures (3/3, 100%) (p=0.022, 0.024 and 0.023 respectively). Differing methods of stabilisation had no bearing on the rate of postoperative infection. CONCLUSION: Ballistic fractures remain a challenge for trauma surgeons in times of war and still have a poor prognosis. Further work is required to determine the optimal treatment of these injuries during conflicts. In addition, there still seems to be a continued need to re-learn the principles of war surgery in order to minimise complications and optimise functional recovery.
Assuntos
Amputação Traumática/cirurgia , Fixação de Fratura/métodos , Fraturas Ósseas/cirurgia , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/cirurgia , Amputação Traumática/complicações , Fixação de Fratura/efeitos adversos , Fraturas Ósseas/classificação , Fraturas Ósseas/complicações , Fraturas Ósseas/etiologia , Guerra do Golfo , Humanos , Infecções/complicações , Militares , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Infecção da Ferida Cirúrgica , Reino UnidoRESUMO
Ex vivo and in vitro observations implicate superoxide as a mediator of cell injury in diabetes, but in vivo evidence is lacking. In the current studies, parameters of glomerular injury were examined in hemizygous nondiabetic transgenic mice (SOD) and streptozotocin-diabetic (D) transgenic mice (D-SOD), which overexpress human cytoplasmic Cu2+/Zn2+ superoxide dismutase (SOD-1), and in corresponding wild-type littermates (WT, D-WT) after 4 months of diabetes. In both SOD and D-SOD mice, renal cortical SOD-1 activity was twofold higher than values in the WT mice; blood glucose and glycosylated hemoglobin (GHb) levels did not differ in the two diabetic groups. Urinary albumin excretion, fractional albumin clearance, urinary transforming growth factor-beta (TGF-beta) excretion, glomerular volume, glomerular content of immunoreactive TGF-beta, and collagen alpha1 (IV) and renal cortical malondialdehyde (MDA) levels were significantly higher in D-WT mice compared with corresponding values in D-SOD mice. Glomerular volume, glomerular content of TGF-beta and collagen IV, renal cortical MDA, and urinary excretion of TGF-beta in D-SOD mice did not differ significantly from corresponding values in either the nondiabetic SOD or WT mice. In separate groups of mice studied after 8 months of diabetes, mesangial matrix area, calculated as a fraction of total glomerular tuft area, and plasma creatinine were significantly higher in D-WT but not in D-SOD mice, compared with corresponding values in the nondiabetic mice. In vitro infection of mesangial cells (MC) with a recombinant adenovirus encoding human SOD-1 increased SOD-1 activity threefold over control cells and prevented the reduction of aconitase activity, an index of cellular superoxide, and the increase in collagen synthesis that otherwise occurred in control MC in response to culture with 300 or 500 mg/dl glucose. Thus, increases in cellular SOD-1 activity attenuate diabetic renal injury in vivo and also prevent stimulation of MC matrix protein synthesis induced in vitro by high glucose.
Assuntos
Nefropatias Diabéticas/prevenção & controle , Glomérulos Renais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Aconitato Hidratase/metabolismo , Animais , Células Cultivadas , Colágeno/antagonistas & inibidores , Creatinina/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/etiologia , Mesângio Glomerular/efeitos dos fármacos , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Glucose/farmacologia , Humanos , Córtex Renal/enzimologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos/genética , Oxirredução/efeitos dos fármacos , Valores de Referência , Superóxido Dismutase/genéticaRESUMO
Expression of the genes encoding several matrix proteins, including the laminin gamma1 and beta1 subunits, is increased in glomeruli or renal cortex from diabetic animals or in mesangial cells cultured in high concentrations of glucose. Transforming growth factor (TGF)-beta1 and IGF-1 have been implicated as mediators of this response. In the present study, we assessed the influence of high glucose concentrations and the roles of TGF-beta1 and IGF-1 in the regulation of laminin C1 gene expression in cultured mesangial cells. Culture of normal rat mesangial cells (RMC) or SV40-transformed mouse mesangial (MES-13) cells in 500 mg/dl D-glucose for 2 days to 3 weeks significantly increased laminin C1 mRNA abundance compared with cells cultured in 100 mg/dl D-glucose. IGF-1 also increased laminin C1 mRNA abundance in RMC or MES-13 cells, whereas TGF-beta1 was without effect. The influence of raising the medium glucose concentration on laminin C1 promoter activity was further studied in MES-13 cells that had been stably transfected with a reporter gene containing the promoter linked to luciferase. Culture in 500 mg/dl D-glucose for 4 h to at least 1 week increased laminin C1 promoter activity compared with cells maintained in 100 mg/dl glucose. In contrast, culture of cells in medium that contained 400 mg/dl mannitol or 400 mg/dl L-glucose in addition to 100 mg/dl D-glucose did not increase laminin C1 promoter activity. The ability of high glucose to increase laminin C1 promoter activity was absolutely dependent on the presence of serum. Consistent with results obtained with mRNA, TGF-beta1 had no influence on promoter activity in stable integrants. Whereas IGF-1 transiently increased promoter activity in stable integrants, the increase was not sustained (6 h). Moreover, neutralizing antibody to TGF-beta or to IGF-1 receptor did not suppress increases in laminin C1 promoter activity induced by culture of stable integrants in high glucose. Several inhibitors of protein kinase C, including bisindolylmaleimide (GFX), myristoylated PKC inhibitor peptide, and LY333531, were also without effect on increases in laminin C1 promoter activity induced by culture in high glucose. Exposure to the NO donor (+/-)-s-nitroso-n-acetylpenicillamine (SNAP) blocked increases in laminin C1 promoter activity induced by serum and by culture in high glucose without influencing promoter activity in cells cultured in the absence of serum and in 100 mg/dl glucose. The ability of high glucose concentrations and IGF-1 to increase laminin C1 promoter activity in cultured mesangial cells, and the suppression of glucose actions by the NO donor SNAP, provide potential mechanisms whereby the synthesis of the laminin gamma1 chain may be regulated in the glomerulus in diabetes. Of note, the mechanism by which high glucose increases laminin C1 promoter activity appears to differ from mechanisms previously described for some other glucose actions on matrix protein synthesis. In this regard, TGF-beta and protein kinase C were not implicated as mediators of the effect of high glucose on laminin C1 promoter activity.
Assuntos
Mesângio Glomerular/metabolismo , Laminina/genética , Regiões Promotoras Genéticas , Animais , Transformação Celular Viral , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Proteína Quinase C/metabolismo , RNA Mensageiro/metabolismo , Ratos , Vírus 40 dos Símios , Transfecção , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVE: To review external fixation in the management of war injuries. METHOD: We prospectively followed up 15 external fixators (14 patients) applied in the management of war injuries. All these patients were treated at 202 Field Hospital during the 2003 Gulf Conflict. RESULTS: Of the 15 fixators, 13 (86.7%) required early revision or removal due to complications of the injury or the fixator. Instability was a problem with 10 fixators (67%), pin loosening was noted with 5 fixators (33%) involving twelve pins, and a significant pin track infection developed at 14 pin sites (3 fixators - 20%), which failed to resolve despite intravenous antibiotics. CONCLUSIONS: This study demonstrates a very high early complication rate of external fixation in the management of military injuries and cautions against its universal acceptance. If used, consideration must be given to the optimum time of frame application, whether at the time of initial debridement or at a later operation, and the optimal frame design, which will depend on the specific bone and fracture pattern. Pin site care must also be considered, particularly with the restrictions imposed by the military environment.
Assuntos
Fixadores Externos/efeitos adversos , Fixação de Fratura , Fraturas Ósseas/cirurgia , Guerra , Ferimentos por Arma de Fogo/cirurgia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Iraque , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Falha de Tratamento , Reino UnidoRESUMO
LincRNA-p21 is a long noncoding RNA and a transcriptional target of p53 and HIF-1α. LincRNA-p21 regulates gene expression in cis and trans, mRNA translation, protein stability, the Warburg effect, and p53-dependent apoptosis and cell cycle arrest in doxorubicin-treated mouse embryo fibroblasts. p53 plays a key role in the response of skin keratinocytes to UVB-induced DNA damage by inducing cell cycle arrest and apoptosis. In skin cancer development, UVB-induced mutation of p53 allows keratinocytes upon successive UVB exposures to evade apoptosis and cell cycle arrest. We hypothesized that lincRNA-p21 has a key functional role in UVB-induced apoptosis and/or cell cycle arrest in keratinocytes and loss of lincRNA-p21 function results in the evasion of apoptosis and/or cell cycle arrest. We observed that lincRNA-p21 transcripts are highly inducible by UVB in mouse and human keratinocytes in culture and in mouse skin in vivo. LincRNA-p21 is regulated at the transcriptional level in response to UVB, and the UVB induction of lincRNA-p21 in keratinocytes and in vivo in mouse epidermis is primarily through a p53-dependent pathway. Knockdown of lincRNA-p21 blocked UVB-induced apoptosis in mouse and human keratinocytes, and lincRNA-p21 was responsible for the majority of UVB-induced and p53-mediated apoptosis in keratinocytes. Knockdown of lincRNA-p21 had no effect on cell proliferation in untreated or UVB-treated keratinocytes. An early event in skin cancer is the mutation of a single p53 allele. We observed that a mutant p53(+/R172H) allele expressed in mouse epidermis (K5Cre(+/tg);LSLp53(+/R172H)) showed a significant dominant-negative inhibitory effect on UVB-induced lincRNA-p21 transcription and apoptosis in epidermis. We conclude lincRNA-p21 is highly inducible by UVB and has a key role in triggering UVB-induced apoptotic death. We propose that the mutation of a single p53 allele provides a pro-oncogenic function early in skin cancer development through a dominant inhibitory effect on UVB-induced lincRNA-p21 expression and the subsequent evasion of UVB-induced apoptosis.
Assuntos
Apoptose/genética , RNA Longo não Codificante/biossíntese , Neoplasias Cutâneas/genética , Proteína Supressora de Tumor p53/genética , Animais , Apoptose/efeitos da radiação , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Queratinócitos/efeitos da radiação , Camundongos , RNA Longo não Codificante/genética , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Neoplasias Cutâneas/patologia , Raios UltravioletaRESUMO
Previous population studies of hearing loss have been limited to children with moderate to profound impairment, and have reported that heritability accounts for at least 50% of congenital or early-onset cases. The present study was designed to assess genetic factors associated with late-onset hearing impairment in an adult population. A brief family history and audiologic questionnaire was sent to approximately 11,200 members of the consumer organization, Self Help for the Hard of Hearing, Inc., and 4,039 questionnaires were returned. All respondents reported having at least one previous audiologic exam. Reported data were verified against audiograms when available. Regardless of the reported causes, 49% of early-onset cases (< or = 20 years of age) had one or two parent(s) with some form of hearing loss compared with 62% in later-onset cases. As expected, mean age at onset was substantially younger for cases with positive family histories than cases with negative family histories. Results from nuclear segregation analysis showed that fully recessive and dominant models failed to explain the early- or late-onset hearing loss data. In this nationwide survey, the large proportion of cases with positive family histories clearly indicates the importance of genetic factors in adult-onset forms of hearing loss. Comparison with younger-onset cases will permit further delineation of differences in inheritance patterns. This study should identify more homogeneous groups of adult-onset families for further genetic study, and provide empiric information for use in genetic counselling.
Assuntos
Transtornos da Audição/genética , Adulto , Idade de Início , Audiometria , Demografia , Feminino , Transtornos da Audição/epidemiologia , Humanos , MasculinoRESUMO
BACKGROUND: A number of studies have indicated excessive offending behavior among people with schizophrenia; however, sexual offending has not been widely described. METHOD: This study reports on a subgroup of 15 men with schizophrenia, diagnosed according to ICD-10 guidelines, in a secure hospital who had committed sexual offenses or shown antisocial sexual behavior. A comparison group comprised 55 male patients with schizophrenia and a history of violent behavior who were being treated in the same hospitals as the study group. RESULTS: In 12 of the 15 cases, the sexual offending/behavior postdated illness onset and occurred in the context of psychotic symptoms. Although 12 of the offenders were known to psychiatric services, contact was erratic and only 4 were taking medication. At assessment, those with sexual offenses or antisocial sexual behavior were twice as likely as the larger study sample to report unimpaired sexual interest. This may be of particular relevance in that the group also reported difficulty in forming close personal relationships. CONCLUSION: Illness-related factors appear to make an important contribution to sexual offending by this group of patients, highlighting the need for comprehensive and vigorous treatment.
Assuntos
Transtorno da Personalidade Antissocial/psicologia , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Delitos Sexuais/psicologia , Comportamento Sexual/psicologia , Adolescente , Adulto , Idade de Início , Transtorno da Personalidade Antissocial/epidemiologia , Comorbidade , Comportamento Perigoso , Diagnóstico Diferencial , Inglaterra/epidemiologia , Psiquiatria Legal , Hospitalização , Humanos , Relações Interpessoais , Masculino , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Esquizofrenia/epidemiologia , Esquizofrenia/terapia , Delitos Sexuais/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Apoio Social , Violência/psicologia , Violência/estatística & dados numéricos , País de Gales/epidemiologiaRESUMO
OBJECTIVE: To compare the efficacy and safety of intramuscular cefoperazone and intramuscular ceftriaxone in the treatment of nursing home-acquired pneumonia in the nursing home setting. DESIGN: A randomized clinical trial. SETTING: Skilled nursing wards at the Veterans Home of California. PATIENTS: 104 residents of skilled nursing wards, aged 65 years or older. INTERVENTIONS: Intramuscular administration of either cefoperazone or ceftriaxone. MEASUREMENTS: The variables analyzed for baseline comparability were demographics (age, sex), clinical variables (duration in nursing home; presence of sputum, fever, cough, or leukocyte count), and clinical symptoms and signs. Efficacy was assessed by days of therapy, final maximum temperature, and clinical and bacteriological response. RESULTS: Fifty residents received cefoperazone, 1 gm every 12 hours, intramuscularly. Fifty-four residents received ceftriaxone, 1 gm every 24 hours, intramuscularly. The total duration of treatment was scheduled for 10 days. Clinical cure was seen in 45 (90%) of the cefoperazone treatment group and 51 (94%) of the ceftriaxone treatment group, with a mean duration of therapy of 10.30 and 9.90 days, respectively. Satisfactory sputum specimens were collected in 71% of the treated residents; the most common isolate was Streptococcus pneumoniae, followed by Haemophilus influenzae and Staphylococcus aureus, respectively. The overall mortality was 4.5% at long-term follow-up. Both agents were well tolerated and no therapy was discontinued due to intramuscular pain or abnormal laboratory values. CONCLUSIONS: Intramuscular cefoperazone and intramuscular ceftriaxone are safe and effective in the treatment of nursing home-acquired pneumonia. The clinical outcomes in both treatment groups support their use within this select population without the need for transferring the patient to an acute care hospital. Clinical studies are needed to evaluate the impact of such therapy on the control of health care expenditures within the nursing home facility.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Cefoperazona/administração & dosagem , Ceftriaxona/administração & dosagem , Infecção Hospitalar/tratamento farmacológico , Casas de Saúde , Pneumonia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intramusculares , Masculino , Pneumonia/microbiologiaRESUMO
An elderly female who had suffered a stroke was admitted to the Jewish Institute for Geriatric Care (JIGC) for rehabilitation. Three years previously she was found to have a pituitary macroadenoma (prolactinoma) that was treated with radiation therapy. She had been on thyroid replacement for secondary hypothyroidism. Upon admission she was found to have severe cognitive impairment in association with a low plasma cortisol level. After treatment with prednisone there was a dramatic improvement in cognitive function and the patient was able to participate in a rehabilitation program.
Assuntos
Transtornos Cognitivos/etiologia , Delírio/etiologia , Hidrocortisona/deficiência , Hipopituitarismo/complicações , Atividades Cotidianas , Idoso , Feminino , Humanos , Hipopituitarismo/tratamento farmacológico , Prednisona/uso terapêuticoRESUMO
Previous studies have found that social support may reduce mortality after myocardial infarction and reduce overall mortality among the elderly. To determine whether social support also influences the recovery of function among patients who have had hip fractures and to describe other potential predictors of recovery after hip fracture, 111 patients with hip fractures were interviewed and examined before discharge from the hospital. The functional status of surviving patients was assessed again 6 months later. Patients who had a greater number of social supports had more complete recovery of their prefracture level of function (r = .21; P = .04). This association was strongest for patients over 60 years old (r = .31; P = .006); among these patients, this association remained statistically significant after adjustment for other significant (P less than .05) predictors of recovery: arm strength, mental status, and serum albumin. Additional studies should be done to test whether interventions to increase social supports can improve the recovery of function among elderly patients with hip fractures and other illnesses. In the meantime, health professionals should counsel elderly patients about the potential rehabilitative and preventive benefits of social supports.
Assuntos
Atividades Cotidianas , Fraturas do Quadril/reabilitação , Meio Social , Apoio Social , Idoso , Consumo de Bebidas Alcoólicas , Depressão/diagnóstico , Feminino , Seguimentos , Humanos , Renda , Relações Interpessoais , Locomoção , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Esforço Físico , Estudos ProspectivosRESUMO
Superoxide has been implicated in the cellular signalling pathways, which regulate growth of mesangial cells (MC) and vascular smooth muscle cells. Manganese (Mn)(2+)-dependent superoxide dismutase (SOD-2) is primarily responsible for metabolism of superoxide produced in mitochondria by respiratory chain activity during aerobic metabolism of glucose and other substrates. In the current studies, we examined the role of superoxide in the stimulation of collagen accumulation induced in MC by culture in media containing a high concentration of glucose. Aconitase, an iron sulfur enzyme whose activity is inhibited by superoxide, was used as an index of cellular superoxide production and action. SV-40-transformed mouse MC were cultured in media containing 100 (low) or 500 (high) mg/dL D-glucose and infected with a recombinant adenoviral (Ad) vector encoding either human mitochondrial Mn(2+) SOD-2 or green fluorescent protein (GFP). In cells infected with SOD-2 (SOD-2-Ad) and cultured in low glucose, SOD-2 activity was 5-fold higher than in cells infected with GFP (GFP-Ad), whereas Cu(2+)/Zn(2+) cytoplasmic SOD (SOD-1) did not differ; culture in high-glucose media did not alter SOD-2 or SOD-1 activity in either GFD-Ad or SOD-2-Ad. In GFP-Ad, high glucose suppressed aconitase activity and increased collagen accumulation compared with corresponding values in low glucose. In SOD-2-Ad, high glucose failed to suppress aconitase activity or increase collagen accumulation. Addition of exogenous (presumably extracellular) SOD to GFP-Ad had no effect on the stimulation of collagen accumulation by high glucose. Analogous to the effects of SOD-2-Ad, diphenylene iodonium (DPI), a nonspecific inhibitor of the production of superoxide by mitochondrial respiration and other nicotinamide adenine dinucleotide (phosphate) (NAD)(P)H oxidase activities, reduced collagen accumulation in GFP-Ad cultured in low glucose and blocked stimulation of collagen accumulation induced by culture in high glucose. These results support a role for increased cellular superoxide production derived from NAD(P)H oxidase activity in the stimulation of collagen accumulation induced in MC by high glucose and demonstrate that an increase in mitochondrial SOD-2 activity suppresses this response.
Assuntos
Colágeno/metabolismo , Mesângio Glomerular/metabolismo , Glucose/metabolismo , Superóxido Dismutase/biossíntese , Aconitato Hidratase/metabolismo , Adenoviridae/genética , Animais , Células Cultivadas , Meios de Cultura/farmacologia , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica , Mesângio Glomerular/citologia , Mesângio Glomerular/efeitos dos fármacos , Glucose/farmacologia , Proteínas de Fluorescência Verde , Humanos , Proteínas Luminescentes/biossíntese , Proteínas Luminescentes/genética , Camundongos , NADPH Oxidases/metabolismo , Oniocompostos/farmacologia , Superóxido Dismutase/genética , Superóxido Dismutase-1 , Transfecção , TransgenesRESUMO
An efficient method of mapping the networks of members of the general population is described. The method permits examination of the effect of several social participation and social network variables on the well-being of 1,050 subjects. Specifically, an index of avowed happiness is regressed on measures of network size, network density, number of instrumental supporters, number of confidants, kin as a major network component, number of dependent others, number of social contexts, and range of socializing. The regression procedure is carried out separately for male and female subjects. Results show that network size is the best predictor of the well-being of men while range of socializing is the best predictor of the well-being of women. These findings are explained in terms of men's and women's differing social responsibility. In conclusion it is suggested that mental health workers may benefit from an understanding of the differing stresses and supports that networks offer men and women.
Assuntos
Ajustamento Social , Adolescente , Adulto , Feminino , Felicidade , Humanos , Relações Interpessoais , Masculino , Valores de Referência , Análise de Regressão , Fatores Sexuais , Meio SocialRESUMO
The elderly patient with acute abdominal disease may present with a classical clinical picture. However, the presentation often is atypical and perplexes the physician. The factors involved include altered anatomical features, fear of being placed in an institution, difficulty in communicating with the physician and family members, diminished response to infection, and multiple coexisting diseases. Awareness of the atypical clinical presentations and the judicious use of special investigations will enable the clinician to make earlier and more accurate diagnoses and, thus, reduce morbidity and mortality.
Assuntos
Gastroenteropatias/diagnóstico , Abdome Agudo , Doença Aguda , Idoso , Aorta Abdominal , Aneurisma Aórtico/diagnóstico , Apendicite/diagnóstico , Doenças Biliares/diagnóstico , Diverticulite/diagnóstico , Humanos , Obstrução Intestinal/diagnóstico , Oclusão Vascular Mesentérica/diagnóstico , Úlcera Péptica/diagnóstico , Volvo Gástrico/diagnóstico , Doenças Urológicas/diagnósticoRESUMO
Geriatric failure to thrive (GFTT) is a syndrome associated with functional decline, depression and malnutrition. Adverse drug reactions are cited as one of the most common causes of GFTT. Two distinct drug-related issues should be considered. Firstly, failure to provide appropriate treatment for conditions such as anaemia, depression, nutritional deficiencies and pain may precipitate GFTT. Secondly, drug-induced functional decline and decreased nutrient intake may cause or contribute to the syndrome. Pharmacological intervention may include discontinuing potentially offending agents for a trial period, or drug treatment of anorexia and depression.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Insuficiência de Crescimento/induzido quimicamente , Idoso , Depressão/complicações , Insuficiência de Crescimento/diagnóstico , Insuficiência de Crescimento/terapia , Humanos , Distúrbios Nutricionais/complicaçõesRESUMO
Data from several samples in the United States and England are drawn upon to examine how and to what extent the social networks of parents differ from those of men and women without children. The social contact patterns found to be associated with parenthood involve (1) a shift in the composition of the networks, and especially an increased emphasis on kin connections; (2) a shift in the frequency with which people are seen; and (3) an absolute reduction in network size for non-working mothers in the lowest social class. The paper briefly considers the health-related implications of these network differences, with special reference to several recent studies that have found exceptionally high rates of depression among women with young children.