RESUMO
STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.
Assuntos
Criopreservação , Preservação da Fertilidade/métodos , Infertilidade Masculina/terapia , Testículo , Adolescente , Adulto , Fatores Etários , Antineoplásicos/efeitos adversos , Biópsia , Criança , Pré-Escolar , Preservação da Fertilidade/normas , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Humanos , Infertilidade Masculina/etiologia , Masculino , Neoplasias/complicações , Neoplasias/terapia , Radioterapia/efeitos adversos , Contagem de Espermatozoides , Recuperação Espermática , Espermatogônias/fisiologia , Adulto JovemRESUMO
A novel intramolecular Prins cyclization of (Z)-2-(5-hydroxypent-2-enyl)phenol with various aldehydes has been achieved using 10 mol% In(OTf)(3) and 30 mol% TsOH to produce the cis-fused hexahydropyrano[4,3-b]chromene derivatives in good yields, while the coupling of (E)-2-(5-hydroxypent-2-enyl)phenol with aldehydes under similar conditions affords the corresponding trans-fused hexahydropyrano[4,3-b]chromene derivatives.
Assuntos
Benzopiranos/síntese química , Piranos/síntese química , Antimaláricos/química , Benzopiranos/química , Ciclização , Modelos Moleculares , Estrutura Molecular , Piranos/química , EstereoisomerismoRESUMO
Previous studies have revealed that genetic factors may be involved in regulating the mechanism of infertility, e.g., MTHFR gene polymorphism in the development of male infertility. The aim of this study is to examine whether an association exists between MTHFR C677T polymorphism and male infertility. The study was carried out by means of a PCR-RFLP assay in 206 infertile men and 230 ethnically matched controls. The statistical analysis using two-sided Fisher's exact test and Pearson chi-squared test showed CT genotype is associated nonsignificantly with male infertility (OR = 1.19, 95% CI = 0.71-1.97). Because of the lack of TT homozygotes in the controls, a combined odds ratio of CT and TT homozygotes against the control has been calculated (OR = 1.36, 95% CI = 0.83-2.22), and the same was insignificant. The overall results of the study indicate that MTHFR C677T polymorphism is not associated with male infertility.
Assuntos
Infertilidade Masculina/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Adulto , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA , Genótipo , Homozigoto , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Anti neural antibodies are known to play a role in the immunopathogenesis of nerve damage in leprosy and HIV/AIDS. Myelin Protein zero (P0) and ceramide are two nerve components which maintain the integrity of the peripheral nerve. The present study was undertaken to identify antibodies to myelin P0 and ceramide in the sera of treated leprosy patients, HIV positive individuals and healthy subjects using enzyme linked immunosorbant assay (ELISA). The results revealed that treated leprosy patients continue to have significantly elevated myelin P0 and ceramide antibody levels as compared to healthy subjects (P < 0.05). The elevated antibody response to myelin P0 and ceramide in leprosy patients indicate a low grade autoimmune activity that perpetuates nerve damage in treated leprosy. There was no significant difference in the myelin P0 and ceramide antibody levels between HIV positive and healthy subjects (P > 0.05) suggesting that these antibodies do not play a role in early HIV infection.
Assuntos
Autoanticorpos/imunologia , Ceramidas/imunologia , Hanseníase/imunologia , Proteína P0 da Mielina/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Infecções por HIV/complicações , Humanos , Imuno-Histoquímica , Hanseníase/complicações , Doenças do Sistema Nervoso Periférico/complicaçõesRESUMO
INTRODUCTION: Bilateral ureteral reimplantation at the time of the complete primary repair of bladder exstrophy (BUR-CPRE) has been proposed and has demonstrated favorable outcomes in the past. However, the potential benefits, including prevention of vesicoureteral reflux (VUR) and renal scarring must be tempered with any risks of reimplantation, persistent VUR, and the potential for overtreatment. We aimed to determine the impact of BUR-CPRE on reflux rates, renogram findings and bladder capacity. METHODS: An IRB approved registry of children treated for bladder exstrophy epispadias complex (BEEC) during a long-term international collaboration hosted in a region with high prevalence of BEEC was queried. Children undergoing primary CPRE for bladder exstrophy (BE) were identified. Surgical procedure and outcome measures nuclear medicine dimercaptosuccinic acid (DMSA) scintigraphy scans, voiding cystourethrogram (VCUG), and urodynamic study (UDS) were assessed for presence and degree of VUR, renogram abnormalities, and bladder capacity. RESULTS: A total cohort of 147 patients with BEEC was queried; 52 children (37 males, 71%) underwent primary CPRE for BE between 2009 and 2019 at median age of 1.1 years (IQR 0.6-1.9 years) with median follow up 4.4 years (IQR 2.4-6.4 years). BUR-CPRE was performed in 22/52 (42%). After BUR-CPRE, children were less likely to have VUR (any VUR present in 9 of 20 with imaging (45%) compared to 23 of 26 with imaging (82%) in the CPRE alone group (p = 0.007)). VUR in the BUR-CPRE group tended to be unilateral and lower grade in comparison to the CPRE alone group. DMSA abnormalities were less common in the BUR-CPRE group (4/19 (21%) vs.12/27 (44%)), although the difference did not reach statistical significance (p = 0.1). At 4 years follow-up, the BUR-CPRE group had a larger bladder capacity (p = 0.016). DISCUSSION: After BUR-CPRE, children had a lower rate of VUR, and when present, VUR was more often unilateral and lower grade compared to the CPRE alone group. Fewer numbers of children in the BUR-CPRE group depicted DMSA abnormalities. No children developed obstruction after BUR-CPRE and none have undergone repeat reimplantation. We documented a larger bladder capacity at the time of maximum follow-up available (4 years)-but further data are needed to confirm this observation. CONCLUSION: BUR-CPRE decreases the incidence and severity of VUR after CPRE, but the clinical significance of this remains unclear. We are encouraged by these initial results, but since BUR-CPRE does not uniformly eliminate VUR, we continue to proceed carefully in the well selected patient.
Assuntos
Extrofia Vesical , Refluxo Vesicoureteral , Extrofia Vesical/diagnóstico por imagem , Extrofia Vesical/cirurgia , Criança , Humanos , Lactente , Masculino , Reimplante , Estudos Retrospectivos , Refluxo Vesicoureteral/diagnóstico por imagem , Refluxo Vesicoureteral/cirurgiaRESUMO
BACKGROUND & OBJECTIVE: Automobile exhaust consists of many toxic components and is considered to be a major health concern in urban areas. Traffic policemen are occupationally exposed to vehicular exhaust during the traffic control. Hence, the present study was aimed to evaluate genotoxic effects of vehicular exhaust in traffic policemen in Hyderabad, south India. METHODS: Analysis of chromosomal aberrations was carried out in 136 traffic policemen, including 78 non smokers and 58 smokers who were exposed to vehicular exhaust for a period of 1-28 yr. For comparison, 115 healthy males including 69 non smokers and 46 smokers of the same age group and socio-economic status (who were not exposed to any chemical or radiation at their workplace) were studied. RESULTS: A significant increase (P<0.05) was observed in the mean frequency of chromosomal aberrations in non smoker and smoker traffic policemen (6.48 and 8.96 respectively) when compared to their respective control groups (3.35 and 4.30). According to the age a significant increase in the frequency of chromosomal aberrations was observed both in control and exposed groups (P<0.05). As the duration of exposure increased in traffic policemen, there was a corresponding increase in the frequency of chromosomal aberrations. INTERPRETATION & CONCLUSION: Cytogenetic damage was more pronounced in smokers when compared to non smokers. Age and duration of exposure also appear to play a vital role in causing cytogenetic damage. Thus the present study suggests that the induction of cytogenetic damage might be due to the cumulative effect of smoking, age and duration of exposure to vehicular exhaust.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Emissões de Veículos/toxicidade , Adulto , Estudos de Casos e Controles , Aberrações Cromossômicas , Análise Citogenética , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Mutagênicos/toxicidade , Exposição Ocupacional , Polícia , Adulto JovemRESUMO
INTRODUCTION: Obesity has been thought to increase the risk of complications and need for additional resources with surgery, but only a limited amount of evidence is available in the pediatric population. OBJECTIVE: The objectives were to describe the weight status of pediatric and adolescent patients undergoing a continent urinary tract reconstruction and to determine the association between obesity and 30-day postoperative morbidity. STUDY DESIGN: A retrospective cohort study was performed for pediatric and adolescent patients aged up to 20 years who underwent a continent urinary tract reconstruction between January 2010 and November 2016. Weight status was stratified by the body mass index (BMI) for age z-scores as follows: underweight (<5th percentile), normal (5th to <85th percentiles), overweight (85th to <95th percentiles), and obese (≥95th percentile). Primary outcomes included the duration of intensive care and hospitalization as well as re-admissions and complications within 30 days. RESULTS: A total of 182 continent reconstructions were identified during the study period. Demographic and peri-operative data are provided in the Table. Weight status was not associated with any primary outcomes on univariate or multivariate analysis. There was also no association in an analysis between the non-overweight or non-obese group (BMI for age z-score <85th) and overweight or obese group (BMI for age z-score ≥85th percentiles); a subgroup analysis between patients with and without myelomeningocele; or a subgroup analysis for wound, infectious, or high-grade (Clavien-Dindo grades III or higher) complications. DISCUSSION: Obesity has been consistently associated with an increased risk of surgical site infections and wound complications after a wide variety of surgeries in adults. The results from the present study conflict with those of the few available studies in the pediatric population. The high-risk nature of the present cohort may have mitigated any effect of obesity on 30-day postoperative morbidity. The limitations of the present study include its retrospective design at a single center and the potential misclassification of weight status with the BMI. CONCLUSIONS: Almost 30% of pediatric and adolescent patients undergoing a continent urinary tract reconstruction were overweight or obese. Obesity as determined by the BMI was not associated with 30-day postoperative morbidity.
Assuntos
Índice de Massa Corporal , Obesidade/complicações , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/epidemiologia , Incontinência Urinária/cirurgia , Sistema Urinário/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Morbidade/tendências , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Incontinência Urinária/complicações , Incontinência Urinária/fisiopatologia , Urodinâmica/fisiologia , Adulto JovemRESUMO
Pathogenic mitochondrial DNA mutations are most often implicated in inherited and acquired hearing impairment. The current review mainly focuses on the 12S rRNA mitochondrial gene mutations associated with non-syndromic deafness without or after aminoglycosides exposure. Aminoglycoside-induced and nonsyndromic deafness has been shown to have a genetic susceptibility and the pathogenic mitochondrial 12S rRNA A1555G mutation was identified as the primary factor underlying the hearing loss in many familial as well as in genetically unrelated cases, particularly in Asian populations where aminoglycoside antibiotics are commonly used even for minor infections. Many families were shown to transmit the aminoglycoside ototoxicity through matrilineal inheritance and the A1555G mutation in the 12S rRNA gene was frequently identified. The aminoglycoside antibiotics are believed to target the mitochondrial ribosome in the cochlea resulting in abnormal RNA processing or decreased efficiency of translation thereby leading to irreversible auditory dysfunction. Such cases may have a genetic predisposition to aminoglycoside ototoxicity following autosomal dominant, autosomal recessive, X-linked, or mitochondrial pattern of inheritance.
Assuntos
Aminoglicosídeos/efeitos adversos , Antibacterianos/efeitos adversos , Genes Mitocondriais , Perda Auditiva/genética , RNA Ribossômico/genética , Genes de RNAr , Perda Auditiva/induzido quimicamente , Humanos , MutaçãoRESUMO
INTRODUCTION: A nutritional assessment is a critical but often neglected aspect of a preoperative evaluation. Malnutrition is clearly associated with worse surgical outcomes in adults undergoing major abdominal surgery, whereas a paucity of evidence is available in the pediatric population. OBJECTIVE: The objectives were to describe the preoperative nutritional status of pediatric and adolescent patients undergoing continent urinary tract reconstruction and to determine the association among malnutrition, use of total parenteral nutrition (TPN), and surgical outcomes. STUDY DESIGN: A retrospective cohort study was performed for patients aged up to 20 years who underwent continent urinary tract reconstruction between January 2012 and November 2016. Malnutrition was classified with body mass index and height for age z-scores on admission as well as change in z-scores and weight over the 3-6 months before surgery. Primary outcomes included the duration of intensive care and hospitalization as well as readmissions and complications within 30 days. RESULTS: A total of 123 patients who underwent 130 continent urinary tract reconstructions were identified during the study period. Demographic and perioperative data are provided in the Table. Anthropometric and biochemical measurements as well as the early initiation of TPN (≤2 days) were not associated with any primary outcomes. In a subgroup analysis of patients with a bowel anastomosis, the early initiation of TPN was an independent predictor for duration of hospitalization (P < 0.0001) and 30-day complications (odds ratio 9.51, P = 0.005) after adjusting for other statistically significant and clinically relevant variables. DISCUSSION: The few available studies on surgical nutrition have primarily focused on infants and young children undergoing cardiac surgery and provided no consensus on a preoperative nutritional assessment. The findings on TPN from the present study favorably compare with a growing body of evidence in adult and pediatric critically ill and surgical patients. The limitations of the present study include its retrospective design at a single institution, potential misclassification of nutritional status, and selection bias from the initiation of TPN at the discretion of the primary surgeon. CONCLUSIONS: Malnutrition was identified in greater than 20% of pediatric and adolescent patients undergoing continent urinary tract reconstruction. Anthropometric and biochemical parameters were not associated with surgical outcomes, although the early initiation of TPN did not offer any benefit for nutritional support. In a subset of patients with a bowel anastomosis, TPN was associated with worse surgical outcomes, including a longer duration of hospitalization and development of 30-day complications.
Assuntos
Estado Nutricional , Nutrição Parenteral Total/estatística & dados numéricos , Doenças Urológicas/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Desnutrição/complicações , Desnutrição/diagnóstico , Cuidados Pré-Operatórios , Estudos Retrospectivos , Doenças Urológicas/complicaçõesRESUMO
The objective of the present study was to evaluate the protective effect of Phyllanthus emblica against clastogenicity induced by lead nitrate on the incidence of sperm head abnormalities in the germ cells of mice. At higher concentration of lead, a significant increase in the percentage of sperm head abnormalities was noted but when animals primed with Phyllanthus fruit extract (PFE), a reduction in the frequency of sperm head abnormalities was observed. It can be suggested from the above study that Phyllanthus emblica plays a key role in inhibition of heavy metal mutagenesis in mammals.
Assuntos
Chumbo/toxicidade , Mutagênicos/toxicidade , Nitratos/toxicidade , Phyllanthus/química , Substâncias Protetoras/farmacologia , Espermatozoides/efeitos dos fármacos , Animais , Frutas/química , Masculino , Camundongos , Extratos Vegetais/farmacologia , Espermatozoides/patologiaRESUMO
Calcineurin, a Ca(2+)-Calmodulin dependent protein phosphatase, is important for Ca(2+) mediated signal transduction. The main objective of this study was to examine the potential role of calcineurin in idiopathic mental handicap. Calcineurin levels were estimated in 20 children in the age group of 5-16 years with idiopathic mental handicap attending the Special. Education Centre for the Mentally Handicapped in Hyderabad. The results of the present study showed decreased activity of serum calcineurin in children with idiopathic mental handicap compared to those of normal subjects in the same age group. The observations thus suggest impaired calcineurin activity in children with mental handicap. Calcineurin that is involved in biosynthesis and release of neurotransmitters at the synaptic terminal brain is affected thereby causing brain damage and leading to mental handicap. Impaired calcineurin activity was already indicated in many human diseases such as Down's syndrome, Alzheimers, Brain ischemia, cardiac hypertrophy etc. It is therefore necessary to check the calcineurin levels in children with mental handicap to understand the role of calcineurin in the causation of Mental handicap.
RESUMO
INTRODUCTION: Patients with anorectal malformations (ARMs) have a high incidence of genitourinary anomalies. Those with a recto-bladder neck fistula may represent a high-risk group, but their long-term urologic outcomes are poorly described. OBJECTIVE: To evaluate the clinical and urodynamic outcomes in a large cohort of patients with an ARM subtype of recto-bladder neck fistula. MATERIALS AND METHODS: A retrospective cohort study was performed of patients who had been treated for a recto-bladder neck fistula at the present institution since 2007. The primary outcomes were the ability to achieve urinary continence after 4 years of age, and development of a mildly decreased glomerular filtration rate (GFR) or worse (<89 ml/min/1.73 m2). Continence was defined as the ability to store urine for 3-4 h during the day and 8 h overnight without leakage. RESULTS: Demographic and clinical data are provided in the Summary Table. The most recent urodynamic findings included the presence of detrusor overactivity in 30 (75%) patients, median leak point pressure of 56.0 cmH2O (range, 14-140), median functional cystometric capacity at 40 cmH2O of 125.5% age-expected capacity (range, 36-473%), and median maximum cystometric capacity of 131.0% age-expected capacity (range, 44-473%). A mildly decreased GFR or worse developed in 13 (24%) patients. Of the 52 (78%) patients who were followed by pediatric urology at the present institution with a median follow-up of 30.9 months (range, 0.0-86.8), 35 (67%) were at least 4 years of age and could be assessed for continence. Continence was achieved in five (14%) patients voiding spontaneously and 15 (43%) performing CIC. Recurrent urinary tract infections (UTI) (OR 0.70, P = 0.006) were an independent predictor of incontinence, while urethral anomalies (OR 1.40, P = 0.03) were an independent predictor of chronic kidney disease (CKD) on multiple logistic regression analysis. DISCUSSION: The findings favorably compared with other studies, but were more robust due to the size of the cohort and breadth of urologic evaluation. Limitations included the retrospective design at a single institution. Incomplete clinical data and misclassification of continence may have lead to bias. CONCLUSIONS: This large cohort of patients with an ARM subtype of recto-bladder neck fistula had a high incidence of genitourinary anomalies. They were rarely able to achieve continence with spontaneous voiding alone and were at risk of developing CKD, both of which were likely multifocal in origin. Long-term urologic follow-up is warranted for patients with a recto-bladder neck fistula.
Assuntos
Malformações Anorretais/fisiopatologia , Malformações Anorretais/cirurgia , Fístula Retal/fisiopatologia , Fístula Retal/cirurgia , Fístula da Bexiga Urinária/fisiopatologia , Fístula da Bexiga Urinária/cirurgia , Malformações Anorretais/complicações , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Fístula Retal/complicações , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Fístula da Bexiga Urinária/complicações , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , UrodinâmicaRESUMO
INTRODUCTION: Stomal stenosis is the most common complication after the creation of a continent catheterizable channel (CCC), but is challenging to treat. OBJECTIVE: To describe early experience with triamcinolone injection for the treatment of stomal stenosis. MATERIALS AND METHODS: A retrospective review was performed of patients who had undergone a triamcinolone injection (40 mg/ml) for the treatment of stomal stenosis at the present institution. The primary outcome of success was defined as a patient-reported or caregiver-reported return to ease with catheterization, and avoidance of stomal revision or indwelling catheter. The cost of care with various techniques for the treatment of stomal stenosis was also assessed by representing the cost as a percentage of charges for a re-operative Monti ileovesicostomy. RESULTS: A total of 22 injections were performed in 18 CCCs of 17 patients. Demographic and clinical data are provided in the Summary Table. Thirteen CCCs (72%) were successfully treated with a single injection. Three patients (10%) required a total of five repeat injections at a median of 5.1 months between injections (IQR, 4.6-12.4). One patient required a stomal revision at 34.9 months after the initial injection, while one patient also required a Chait cecostomy catheter. The median length of time for ease with catheterization was 11.6 months (IQR, 3.5-18.0) after the initial injection, and 10.4 months (IQR, 4.5-16.0) after any injection. No adverse effects or complications occurred from the injection. There were no variables associated with failure after the initial or any injection on univariate analysis. Represented as a percentage of charges for a reoperative Monti ileovesicostomy, the cost of care was 11.3% for a stomal revision, 5.8% for triamcinolone injection in the operating room, and 0.3% as an office-based procedure. DISCUSSION: The success rate for triamcinolone injection favorably compared with other options for the treatment of stomal stenosis. It surpassed the reported success rate of stomal dilation and approached that of stomal revision. Other studies have similarly observed a minimal risk of adverse effects and complications from both topical and intralesional corticosteroids. The limitations of the present study included its retrospective design at a single institution. A larger cohort of patients with a longer follow-up is necessary to determine its long-term durability. CONCLUSIONS: Triamcinolone injection was an effective and well-tolerated option for the treatment of stomal stenosis in any cutaneous stoma, thereby avoiding the need for a more invasive and costly stomal revision.
Assuntos
Anti-Inflamatórios/administração & dosagem , Cistostomia/efeitos adversos , Estomas Cirúrgicos/patologia , Triancinolona/administração & dosagem , Cateterismo Urinário/efeitos adversos , Criança , Constrição Patológica , Feminino , Humanos , Injeções , Masculino , Estudos Retrospectivos , Cateterismo Urinário/instrumentaçãoRESUMO
INTRODUCTION: Botulinum toxin injection (BTI) has been advocated as a second line therapy in management of neuropathic bladder in pediatric population for refractory patients to conventional medical management such as anticholinergics. The purpose was to review the safety and efficacy of BTI in children with neuropathic bladder refractory to conservative non-surgical measures. We hypothesized that BTI would be an effective alternative to bladder augmentation in certain patients but not all. METHODS: We retrospectively identified 22 patients with neuropathic bladder due to any condition who underwent urologic BTI at our hospital since 2010. Multiple clinicopathologic variables were examined including the following: demographics, use of anticholinergics, the presence of anticholinergic refractoriness or intolerance, dosage of BTI, urodynamic variables, and continence status. RESULTS: The mean patient age at time of BTI was 10 years with a follow up of 12 months. Indications for BTI were anti-cholinergic refractory (AR) urodynamic parameters and/or incontinence and anticholinergic intolerance (AI). Nearly all patients received 300 Units at BTI into detrusor. No complications occurred from BTI. Overall 54% had improved continence after the initial BTI whereas 45% had achieved complete continence between catheterizations. Cystometric capacity increased by 46% and maximum detrusor pressure decreased by 43% following initial BTI (See Table). 75% of AI patients were continent between CIC after BTI compared to 50% of AR patients (P = 0.002). The observed mean duration of clinical improvement after initial BTI was 4.6 months and four patients underwent repeat BTI. Pre BTI % of age expected bladder capacity Post BTI % of age expected bladder capacity % Improvement in Urodynamic Parameter P value Cystometric Capacity (mL) 227 60 331 87 46 0.008 Maximum Detrusor Pressure (cm H2O) 63 44 43 0.002 Compliance (mL/cm H2O) 4.3 8.8 104 0.001. DISCUSSION: Our results are comparable to existing literature with respect to urodynamic parameters. The observed differences may be due to heterogenous patient population of various etiologies of neuropathic bladder and no uniform criteria to proceed with bladder augmentation. The AR patients in our cohort may have had a higher degree of bladder fibrosis which BTI would be less likely to impact and explain the differences in clinical response between AR and AI patients. CONCLUSIONS: BTI is a safe and effective treatment option for pediatric patients with neuropathic bladder refractory to standard therapy. The degree of continence observed after BTI in our series was higher for AI rather than AR patients.
Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Bexiga Urinaria Neurogênica/tratamento farmacológico , Urodinâmica/fisiologia , Administração Intravesical , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Fármacos Neuromusculares/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Bexiga Urinaria Neurogênica/fisiopatologia , Adulto JovemRESUMO
Studies have reported a wide range of inflammatory responses in the nerve, skin and plasma of leprosy patients. The expression levels of each biomolecule was individualistic, however could be categorized as high and low based on their statistical mean level. Here we report for the first time, expression of a set of biomolecules relating with each other in a defined proportion. The hypothesis of this paper is that the segregation of high and low combinations of a set of biomolecules follows either classical Mendelian dihybrid ratio or epistatic ratios. This hypothesis was tested for 17 molecules in three tissues; nerve, skin and plasma and were confirmed to interact in 9:7, 9:3:4, 12:3:1, 13:3, 15:1 epistatic proportions. These findings suggest that there could be a significant role of networking of molecules in defined epistatic proportions and could be important in pathophysiology of peripheral nerve.
Assuntos
Epistasia Genética , Inflamação/genética , Hanseníase/patologia , Algoritmos , Antígenos de Bactérias/imunologia , Genes Recessivos , Humanos , Inflamação/imunologia , Hanseníase/genética , Hanseníase/imunologia , Modelos Genéticos , Modelos Estatísticos , Neurônios/metabolismo , Nervos Periféricos/fisiopatologia , Fenótipo , Plasma/metabolismo , Estudos Retrospectivos , Pele/metabolismo , Resultado do TratamentoRESUMO
Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues having an aminoalkyl group as a linker between the chroman ring and 4-[5-(2,4-dioxo-1, 3-thiazolidinyl)methyl]phenoxy moiety seem to be better than troglitazone. In vitro transactivation assays of PPARgamma have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.
Assuntos
Cromanos/síntese química , Hipoglicemiantes/síntese química , Hipolipemiantes/síntese química , Tiazóis/síntese química , Animais , Glicemia/metabolismo , Cromanos/química , Cromanos/farmacocinética , Cromanos/farmacologia , Feminino , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacocinética , Hipolipemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/agonistas , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacocinética , Tiazóis/farmacologia , Fatores de Transcrição/agonistas , Triglicerídeos/sangueRESUMO
Three infants with significant left-to-right intracardiac shunts and moderate cardiac disability failed to thrive primarily because of a complete distaste for food. They refused to feed, spat out food introduced into their mouths, and vomited food that reached their stomachs. These severe feeding difficulties were relieved by intracardiac repair, and we conclude that in some unusual instances such feeding disorders constitute the indication for operation.
Assuntos
Comunicação Interventricular/fisiopatologia , Transtornos da Nutrição do Lactente/etiologia , Circulação Pulmonar , Transtornos da Alimentação e da Ingestão de Alimentos/dietoterapia , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Feminino , Insuficiência Cardíaca/complicações , Comunicação Interventricular/cirurgia , Humanos , Lactente , Transtornos da Nutrição do Lactente/dietoterapia , Recém-Nascido , Masculino , Veias Pulmonares/anormalidades , Veias Pulmonares/cirurgia , Vômito/etiologiaRESUMO
We studied 25 children in India with acute lymphoblastic leukemia; all of them were less than 15 years old. The karyotypes, determined with banding techniques, were correlated with clinical data. Thirteen of these patients had an adequate chromosome analysis and two others were in remission when samples were obtained. For the remaining ten, specimens were inadequate for cytogenetic analysis. Thirty-one percent of the 13 patients had a normal karyotype. The most common abnormal pattern was a hyperdiploid karyotype with greater than 50 chromosomes observed in 38% of the patients. Two patients had a Ph chromosome. Other chromosome changes, such as t(8;14), del(6), t(4;11), or t(1;19), were not seen in our series. A correlation between the karyotype and response rate and survival time was noted. Patients with a normal karyotype had a good prognosis, whereas, hyperdiploidy (greater than 50 chromosomes) and a low white blood cell count were associated with poor prognoses. Trisomy for the long arm of chromosome #1 (bands 1q25 to 1q32), which was seen in most of our patients with hyperdiploidy, also indicated a poor prognosis. Of the 25 patients, eight were from agricultural areas where they were often exposed to pesticides; there was no correlation between a history of such exposure and the karyotype of the leukemic cells.
Assuntos
Aberrações Cromossômicas , Leucemia Linfoide/genética , Adolescente , Criança , Pré-Escolar , Bandeamento Cromossômico , Feminino , Humanos , Índia , Cariotipagem , Leucemia Linfoide/diagnóstico , Masculino , Ploidias , PrognósticoRESUMO
In the present study 61 male pesticide applicators who worked in cotton fields and regularly sprayed pesticides such as DDT, BHC, endosulfan, malathion, methyl parathion, phosphamidon, dimethoate, monocrotophos, quinalphos fenvelrate, and cypermethrin were analyzed for sister chromatid exchanges, mitotic index, and cell cycle kinetics in peripheral lymphocytes. Subjects who handled pesticides were non-smokers and teetotalers and the data were compared with the matched control group. Statistical analysis revealed that the frequency of sister chromatid exchanges was significantly higher among the pesticide applicators at all the durations of exposure when compared to controls. Subjects exposed to pesticides also showed cell cycle delay and decrease in mitotic index when compared to the control group.
Assuntos
Doenças Profissionais/induzido quimicamente , Praguicidas/efeitos adversos , Troca de Cromátide Irmã/efeitos dos fármacos , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Doenças Profissionais/genéticaRESUMO
OBJECTIVE: To evaluate the role of the environmental estrogens polychlorinated biphenyls (PCBs) and phthalate esters (PEs) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology. DESIGN: Randomized controlled study. SETTING: Tertiary care referral infertility clinic and academic research center. PATIENT(S): Twenty-one infertile men with sperm counts <20 million/mL and/or rapid progressive motility <25% and/or <30% normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception. Semen and blood samples were obtained as part of the treatment protocol. MAIN OUTCOME MEASURE(S): Evaluation of semen parameters such as ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity, sperm chromatin stability, and sperm nuclear DNA integrity. RESULT(S): PCBs were detected in the seminal plasma of infertile men but not in controls, and the concentration of PEs was significantly higher in infertile men compared with controls. Ejaculate volume, sperm count, progressive motility, normal morphology, and fertilizing capacity were significantly lower in infertile men compared with controls. The highest average PCB and PE concentrations were found in urban fish eaters, followed by rural fish eaters, urban vegetarians, and rural vegetarians. The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls. CONCLUSION(S): PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology.