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Biomedical subjects

A Srivastava

Publications and source records attributed to A Srivastava.

At least 145 records · Page 8Linked to original sources

Neuropsychiatric manifestations in patients of primary hyperparathyroidism and outcome following surgery.

BACKGROUND: A wide variety of psychiatric symptoms ranging from mild personality changes to severe depression and psychosis have been described in patients of PHPT. However, the psychiatric profile in Indian patients remains a mystery. It remains to be seen if surgery can alleviate the psychiatric morbidity and improve the quality of life of patients. Although, the pathophysiology remains largely unknown, we attempted to see if psychiatric morbidity correlated with serum calcium values. OBJECTIVE: a) To study the nature and severity of neuropsychiatric manifestations in patients of hyperparathyroidism before surgery and their outcome after surgery b) To study their correlation with levels of serum calcium. MATERIAL AND METHODS: This prospective study documented the occurrence of psychiatric symptoms among 14 patients of primary hyperparathyroidism (group I). 13 patients of gall stone disease (group II) and 12 patients of thyromegaly, undergoing total thyroidectomy (Group III) constituted the control groups. The relationship between such symptoms and degree of hypercalcemia was also studied. Assessment of psychologic symptoms, using the CPRS scale (validated in Hindi) and the scale for Memory and Intelligence for use in Hindi speaking population was carried out preoperatively and at 1 wk, 6 wk, 3, and 6 months postoperatively. OBSERVATIONS: The hyperaparathyroid group had significantly higher levels of total serum calcium and PTH preoperatively, with biochemical normalization postoperatively. The preoperative CPRS rating of the 14 patients with primary hyperparathyroidism revealed pronounced psychiatric symptoms, with a mean total CPRS score of 20 +/- 8.7, compared with 10.5 +/- 6.9(II) and 12.7 +/- 5.6 (III) in the control groups. Statistically significant improvement was seen in the CPRS score, maximally at 6 weeks post operatively for the following symptoms: Sadness, lassitude, ache and pains, and fatigability. There was no memory and intelligence impairment in any of the groups pre or post operatively. No correlation was found between the serum calcium levels and the psychiatric morbidity. CONCLUSIONS: The psychologic symptom distress is multidimensional and symptoms significantly improved by 6 weeks post parathyroidectomy. There was no memory and intelligence impairment in any of the groups pre or post operatively. No correlation was found between serum calcium levels and psychiatric morbidity.

Adolescent↗

Spectrum of Schwartz-Jampel syndrome includes micromelic chondrodysplasia, kyphomelic dysplasia, and Burton disease.

Follow-up and re-evaluation of four patients originally described as examples of severe infantile "micromelic chondrodysplasia" resembling Kniest disease, "kyphomelic dysplasia," and "Burton skeletal dysplasia" revealed the diagnosis of Schwartz-Jampel syndrome (SJS, myotonic chondrodysplasia) in all of them. SJS may be suspected in neonates with Kniest-like chondrodysplasia, congenital bowing of shortened femora and tibiae, and facial manifestations consisting of a small mouth, micrognathia, and possibly pursed lips. The disorder must be differentiated from the Stüve-Wiedemann syndrome, a genetically distinct myotonic chondrodysplasia with similar clinical but different skeletal changes and an unfavorable early prognosis. The demise of "kyphomelic dysplasia" as a nosological entity reemphasizes the symptomatic nature of congenital bowing of the long bones.

Abnormalities, Multiple↗

Traveler's diarrhea at sea: three outbreaks of waterborne enterotoxigenic Escherichia coli on cruise ships.

Enterotoxigenic Escherichia coli (ETEC) has become the leading bacterial cause of gastroenteritis outbreaks on cruise ships. Investigation of recent outbreaks of ETEC gastroenteritis on 3 cruise ships indicated that all were associated with consuming beverages with ice cubes on board the ship (relative risk [RR], 1.4, 95% confidence interval [CI], 1.0-1.9, P=.02; RR, 1.9, 95% CI, 1.3-2. 9, P<.001; and RR, 1.3, 95% CI, 1.0-1.6, P<.01), and 2 were associated with drinking unbottled water (RR, 2.7, 95% CI, 1.8-4.1, P<.001; RR, 1.7, 95% CI, 1.3-2.3, P<.001). Multiple ETEC serotypes were detected in patients' stool specimens in each of the 3 outbreaks, and 12 (38%) of 32 isolates were resistant to > or =3 antimicrobial agents. ETEC appears to be emerging as a waterborne pathogen on cruise ships. Water bunkered in overseas ports was the likely source of ETEC infection in these outbreaks. To ensure passenger safety, cruise ships that take on water in foreign ports must ensure that water treatment and monitoring systems function properly.

Adult↗

Relation of physical activity to risk of testicular cancer.

In North America and most Western European countries, testicular cancer is often cited as the most common cancer among young and middle-aged men, and yet few studies have examined the relation between modifiable factors and testicular cancer risk. Data collected between 1995 and 1996 in Ontario, Canada, as part of the Enhanced Cancer Surveillance Study were used to examine the relation between the frequency of recreational, and intensity of occupational, physical activity at various life periods, including cumulative and averaged lifetime activity and risk of testicular cancer. Analysis of 212 cases and 251 controls revealed that relatively high frequency of participation in moderate and strenuous recreational activity in the midteens may have an adverse effect on risk of testicular cancer (odds ratio = 2.36, 95% confidence interval: 1.20, 4.64 for moderate activity of greater than five times a week compared with three times or less a month and odds ratio = 2.58, 95% confidence interval: 1.14, 5.85 for strenuous activity of greater than five times a week compared with less than once a month). Moderate or strenuous occupational demands in one's 20s also increased risk of disease.

Adult↗

Effects of dietary calcium depletion and repletion on dynamic determinants of tibial bone volume in two inbred strains of mice.

As an adjunct to our efforts to identify the genes that determine peak bone density, we examined phenotypic differences between two inbred strains of mice, C3H/HeJ (C3H) and C57BL/6J (B6), which are of similar size but differ with respect to peak bone density (e.g., C3H mice have 53% higher femoral bone density than B6 mice). The current studies were intended to compare the skeletal responses of C3H and B6 mice to 2 weeks of dietary calcium (Ca) depletion, followed by 2 weeks of Ca repletion. Initial studies showed that: (a) femur dry weight decreased during Ca depletion in both C3H and B6 mice (by 25% and 19%, respectively, p < 0.001) and most of this loss was recovered during Ca repletion; and (b) serum alkaline phosphatase (ALP) activity increased during Ca depletion, in both strains of mice (p < 0.001), and returned to normal after Ca repletion. Histological analyses of ground cross sections prepared at the tibiofibular junction showed that Ca-depletion increased medullary area in both C3H and B6 mice (indicating endosteal bone loss, p < 0.01), with reversal during Ca repletion. There were no effects of Ca depletion or repletion on periosteal bone growth. Endosteal bone forming surface and endosteal mineral apposition decreased during Ca depletion and increased during repletion in both C3H and B6 mice (p < 0.05). Net bone formation decreased during Ca depletion in C3H mice, but not B6 mice (p < 0.01), and was normal during Ca repletion in both strains. Endosteal bone resorbing surface and net bone resorption increased during Ca depletion and decreased during repletion in both strains (p < 0.01). A supplemental study (of Ca depletion without repletion) confirmed the effects of Ca depletion on femoral dry weight and serum ALP activity (p < 0.001 for each). This supplemental study also showed that Ca deficiency increased serum parathyroid hormone (PTH) (p < 0.05) and decreased (tibial) cortical bone area and cortical mineral content (p < 0.05 to p < 0.001) in both strains of mice. Together, these data demonstrate that the skeletal responses to Ca depletion and repletion are, qualitatively, similar in C3H and B6 mice.

Alkaline Phosphatase↗

Unusual extra-axial central nervous system involvement of non-Hodgkin's lymphoma: magnetic resonance imaging.

The MR imaging findings in a patient with non-Hodgkin's lymphoma with unusual involvement of the sella, pituitary stalk and left parasellar region are reported here. On the basis of the MR imaging findings, the initial differential diagnosis included invasive pituitary adenoma, a granulomatous lesion and en plaque meningioma. Trans-sphenoidal biopsy of the sellar mass showed chronic inflammatory changes and the patient was initially treated for tuberculosis. Because follow-up imaging showed the lesion to be progressive, a biopsy was done of an enlarged right inguinal lymph node. This revealed non-Hodgkin's lymphoma.

Adult↗

Pep3p/Pep5p complex: a putative docking factor at multiple steps of vesicular transport to the vacuole of Saccharomyces cerevisiae.

Pep3p and Pep5p are known to be necessary for trafficking of hydrolase precursors to the vacuole and for vacuolar biogenesis. These proteins are present in a hetero-oligomeric complex that mediates transport at the vacuolar membrane. PEP5 interacts genetically with VPS8, implicating Pep5p in the earlier Golgi to endosome step and/or in recycling from the endosome to the Golgi. To understand further the cellular roles of Pep3p and Pep5p, we isolated and characterized a set of pep3 conditional mutants. Characterization of mutants revealed that pep3(ts) mutants are defective in the endosomal and nonendosomal Golgi to vacuole transport pathways, in the cytoplasm to vacuole targeting pathway, in recycling from the endosome back to the late Golgi, and in endocytosis. PEP3 interacts genetically with two members of the endosomal SNARE complex, PEP12 (t-SNARE) and PEP7 (homologue of mammalian EEA1); Pep3p and Pep5p associate physically with Pep7p as revealed by two-hybrid analysis. Our results suggest that a core Pep3p/Pep5p complex promotes vesicular docking/fusion reactions in conjunction with SNARE proteins at multiple steps in transport routes to the vacuole. We propose that this complex may be responsible for tethering transport vesicles on target membranes.

Adaptor Proteins, Vesicular Transport↗

Evaluation of the urological complications of living related renal transplantation at a single center during the last 10 years: impact of the Double-J* stent.

PURPOSE: We evaluated the impact of the routine use of Double-J stents for decreasing urological complications in living related renal transplantation at a single center during the last 10 years. MATERIALS AND METHODS: Our 3-phase longitudinal study included 670 consecutive living related renal transplants from 1989 to 1998. In phase 1 from 1989 to 1993 a stent was introduced as and when required in only 15 of 170 patients. In phase 2 from January 1994 to April 1995 we randomized 57 and 43 cases to stenting and no stenting, respectively. The stent was removed after 4 weeks. In phase 3 from May 1995 to December 1998 all patients received a stent, which was removed 10 to 14 days just before discharge home. We reviewed urological complications at various time frames to determine the impact of routine Double-J stenting on decreasing urological complications. RESULTS: In phase 1 the major ureteral complication rate was 8.8%, which decreased to 3% in phase 2 when half of our cases were stented. In phase 3 there was only 1 ureteral complication (0.04%) in 400 patients, of whom all received a stent. The overall ureteral complication rate in nonstented and stented cases was 8.5% (18 of 213) and 0.22% (1 of 457). There was no difference in urological complications or stent related problems whether the stent was removed at 4 or 2 weeks. However, stent removal at 2 weeks eliminated the possibility of a forgotten stent, avoided repeat hospitalization for stent removal and decreased the cost. Routine stenting was cost-effective and almost eliminated urological complications. CONCLUSIONS: Routine Double-J stenting prevents ureteral complications. Early removal at 2 weeks is advisable. The short duration of stenting is effective and saves the cost of repeat hospitalization at a later date.

Adolescent↗

Impaired intracellular trafficking of adeno-associated virus type 2 vectors limits efficient transduction of murine fibroblasts.

Although adeno-associated virus type 2 (AAV) has gained attention as a potentially useful alternative to the more commonly used retrovirus- and adenovirus-based vectors for human gene therapy, efficient gene transfer and transgene expression by AAV vectors require that the following two obstacles be overcome. First, the target cell must express the receptor and the coreceptor for AAV infection, and second, the cell must allow for viral second-strand DNA synthesis. We now describe a third obstacle, impaired intracellular trafficking of AAV to the nucleus, which results in the lack of transgene expression in murine fibroblasts which do express the AAV receptor and the coreceptor and which are permissive for viral second-strand DNA synthesis. We document that AAV vectors bind efficiently and gain entry successfully into NIH 3T3 cells, but trafficking into the nucleus is significantly impaired in these cells. In contrast, viral trafficking to the nucleus in cells known to be efficiently transduced by AAV vectors is both rapid and efficient. The demonstration of yet another obstacle in AAV-mediated gene transfer has implications for the optimal use of these vectors in human gene therapy.

3T3 Cells↗

Expanding the living related donor pool in renal transplantation: use of marginal donors.

PURPOSE: In a living related transplantation program it is not always possible to find an ideal donor. Sometimes the only available donor in the family has some benign disease or suboptimal renal anatomy or physiology, or is too old to be accepted and defined as a marginal donor. However, with proper screening the donor pool can be increased by accepting these marginal donors and treating the benign diseases which is beneficial to the donor. We evaluate the outcome of grafts from marginal donors. MATERIALS AND METHODS: From July 1988 to August 1997, 581 live related transplantations were performed. Of the donors 52 were older than 60 years and 34 had associated benign renal or nonrenal anomaly or disease. These donors were accepted after thorough questioning and consultation with family members. The recipients of graft from elderly donors were evaluated for the number of rejections, serum creatinine at last followup and graft survival. RESULTS: Of the recipients 52 received grafts from elderly donors with a mean age of 62.6+/-3.7 years. Mean followup was 34.14+/-0.7 months. The 2 and 5-year actuarial graft survival was 96% and 74%, respectively. Creatinine was normal (less than 1.5) in 37% of recipients and 1.5 to 2.5 mg.% in 46%. The rejection rate in postoperative month 1 was 29%. All donors underwent simultaneous surgery to treat the benign disease, and all did well after surgery. CONCLUSIONS: By accepting these marginal donors a 14.6% increase in the living related donor pool was achieved without compromising recipient or donor safety. Otherwise these recipients would have been forced to undergo unrelated transplantation or be maintained on dialysis, which is particularly difficult in a developing country. Donors with associated disease benefited from cure.

Female↗

Long-term followup of elderly donors in a live related renal transplant program.

PURPOSE: It is a concern that elderly donors may have increased risks in the perioperative period due to age related changes in various organ systems. Nephrosclerosis, atherosclerosis and low glomerular filtration rate may portend a poor graft outcome. We performed a study to determine function and outcome of kidneys from elderly donors. MATERIALS AND METHODS: A retrospective analysis of our live related transplant program from November 1989 to December 1998 revealed that 112 donors were older than 55 years (range 55 to 81). Of the recipients of these kidneys from elderly donors 98 had a followup of more than 2 years (group 1), and they were compared to a cohort of 87 patients whose kidney donors were younger than 45 years (group 2). Allograft function was evaluated by serum creatinine and differential glomerular filtration rate was determined by (99m)technetium diethylenetriamine pentaacetic acid renal scan. All donors were followed regularly. RESULTS: Mean donor age plus or minus standard deviation was 57.4 +/- 4.3 and 31.4 +/- 7.6 years in groups 1 and 2, respectively. Mean followup plus or minus standard deviation was 42.44 +/- 20.46 months in group 1 and 40.04 +/- 27.28 months in group 2. The 1-year graft survival rate was 91.84% and 88. 51%, and the 5-year graft survival rate was 72.72% and 75.13% in groups 1 and 2, respectively. Serum creatinine was 1.5 +/- 0.65 and 1.7 +/- 1.52 mg./dl. in group 1 and 1.4 +/- 0.55 and 1.5 +/- 1.41 mg. /dl. in group 2 at 1 year and last followup, respectively. Glomerular filtration rate was 37.2 +/- 11.2 and 37.3 +/- 10.7 ml. per minute in group 1 and it was 45.3 +/- 8.6 and 47.7 +/- 11.3 ml. per minute in group 2 at 1 year and last followup, respectively. Acute rejection rate was significantly higher in group 1 (42%) compared to group 2 (19%). Both groups were comparable in terms of infectious episodes, antihypertensive requirement and incidence of acute tubular necrosis. There was no added morbidity for elderly compared to younger donors. CONCLUSIONS: In view of acute donor shortage and if properly screened, elderly kidneys can be used without increasing the risk to donor or compromising graft outcome.

Adult↗

Association between polymorphism in p21(Waf1/Cip1) cyclin-dependent kinase inhibitor gene and human oral cancer.

The cyclin-dependent kinase inhibitor gene p21(Waf1/Cip1) plays a central role in inducing cellular growth arrest, terminal differentiation, and apoptosis. Alterations in this gene may adversely affect regulation of these processes and increase susceptibility for cancer. We have recently reported a novel polymorphism in the p21(Waf1/Cip1) gene in the Indian population and its association with esophageal cancer. An A-->G transition at codon 149 resulted in amino acid substitution from aspartate to glycine in the proliferating cell nuclear antigen binding COOH-terminal domain of p21(Waf1/Cip1) that may affect PCNA-p21(Waf1/Cip1) interactions, thereby affecting regulation of cellular proliferation, and may increase susceptibility for development of cancer. In a parallel study in our laboratory, we searched for putative p21(Waf1/Cip1) mutations in oral premalignant and malignant lesions. No somatic mutation was detected in exon 2 of p21(Waf1/Cip1). Interestingly, a codon 149 polymorphism variant (A-->G) was identified in 11 of 30 (37%) premalignant lesions (7 of 19 hyperplastic lesions and 4 of 11 dysplastic lesions) and 11 of 30 (37%) squamous cell carcinomas (SCCs). This codon 149 variant was also identified in paired lymphocytes of all of the patients with premalignant lesions and SCCs harboring the variant allele, suggesting the occurrence of a polymorphism. Lymphocyte DNA isolated from 50 unrelated age- and gender-matched healthy subjects was screened for this polymorphism. Seven of 50 (14%) normal controls harbored the A-->G codon 149 variant allele. Immunohistochemical analysis of p21(Waf1/Cip1) protein expression showed immunoreactivity in 19 of these 30 (63%) oral premalignant lesions and 16 of 30 (53%) SCCs. The most intriguing features of the study were: (a) the significant increase in frequency of this polymorphism not only in patients with oral SCCs (P = 0.038), but also in patients with premalignant lesions (P = 0.038), compared with normal controls; and (b) the significantly higher frequency of p21(Waf1/Cip1) variants (codon 149) in oral premalignant lesions (10 of 11 cases) and SCCs (11 of 11 cases) with wild-type p53 (P = 0.045) than in lesions with p53 mutations, suggesting that this polymorphism affects the p53 pathway and may play a vital role in oral tumorigenesis. Furthermore, overexpression of p21 protein in oral lesions harboring missense mutations in the p53 gene suggest a p53-independent role for p21 in the pathogenesis of oral cancer.

Adult↗

Endoscopic injection sclerotherapy control of intractable hematuria following radiation-induced hemorrhagic cystitis. A novel approach.

OBJECTIVE: To establish the utility of endoscopic sclerotherapy using 1% ethoxysclerol for the control of intractable hematuria following post-irradiation telangiectatic cystitis (PTC). METHODS: Our experience of treating 4 patients (one female and three male) with massive exsanguinating hematuria resulting from PTC, using a combined intralesional and perilesional injection of 1% ethoxysclerol, is presented. Observation on the distribution, grading of telangiectasis and pattern of bleeding are made. RESULTS: A dramatic and lasting cessation of the hematuria in all the 4 patients was achieved during the follow-up period varying from 1 month to 4 years. CONCLUSION: Endoscopic injection sclerotherapy is a simple, highly effective, less invasive new technique in the management of massive and intractable hematuria due to radiation-induced telangiectasia of the urinary bladder.

Adult↗