Biomedical subjects
Publications and source records attributed to A Agarwal.
Unsuspected tracheal injury during endoscopic hemithyroidectomy is described. The diagnosis was delayed because of absent symptomatology. Surgical repair was planned but deferred because of infection. The patient was managed with a tracheostomy tube and antibiotics, and the wound healed completely without any residual abnormality or complications.
BACKGROUND: Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in human spermatozoa has been implicated in the pathogenesis of male infertility. In this study, variations in ROS production, DNA structure (as measured by the sperm chromatin structure assay) and lipid composition, were studied in human spermatozoa at different stages of maturation. METHODS: Sperm subsets were isolated by discontinuous density gradient centrifugation of semen samples obtained from healthy donors and from infertility patients. RESULTS: DNA damage and ROS production were highest in immature spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in immature germ cells and immature spermatozoa, and lowest in mature spermatozoa. The relative proportion of ROS-producing immature spermatozoa in the sample was directly correlated with DNA damage in mature spermatozoa, and inversely correlated with the recovery of motile spermatozoa. There was no correlation between DNA damage and sperm morphology in mature spermatozoa. CONCLUSIONS: The high levels of ROS production and DNA damage observed in immature spermatozoa may be indicative of derangements in the regulation of spermiogenesis. DNA damage in mature spermatozoa may be the result of oxidative damage by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis.
BACKGROUND: Reactive oxygen species (ROS)-mediated damage to human spermatozoa has been implicated in the pathogenesis of male infertility. Although ROS production by human spermatozoa has been extensively studied, the cell-to-cell variation in ROS production by spermatozoa at different stages of maturation has never been investigated. METHODS: In this study, we determined ROS production by subsets of human spermatozoa at different stages of maturation isolated by density gradient centrifugation of ejaculated spermatozoa obtained from healthy donors and from patients attending a clinic for infertility screening. RESULTS: Four different fractions were obtained. ROS production was highest in immature spermatozoa with abnormal head morphology and cytoplasmic retention and lowest in mature spermatozoa and immature germ cells (P < 0.01). ROS production was highest in immature spermatozoa from males with abnormal semen parameters compared with donors (P < 0.0001) or patients with normal semen parameters (P = 0.015). ROS production by immature spermatozoa was inversely correlated with the recovery of motile, mature spermatozoa in the high density fraction 4 (P = 0.01). CONCLUSIONS: The results of this study indicate that there is significant cell-to-cell variation in ROS production in subsets of spermatozoa at different stages of maturation and that oxidative damage of mature spermatozoa by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis may be an important cause of male infertility.
Insertion of cranial pins for stabilization of the head can result in a marked hypertensive response, which may adversely affect cerebral hemodynamics. The efficacy of a subanesthetic dose of intravenous ketamine (0.5 mg/kg) and/or lidocaine infiltration (1%) at pin fixation sites before pinning was studied in a prospective, double-blind, placebo-controlled, randomized trial of 40 patients. The subjects were divided into four groups of 10. Patients belonging to the placebo and lidocaine groups received intravenous normal saline (NS), followed by local infiltration with NS at pin insertion sites in the placebo group and 1% lidocaine in the lidocaine group. Patients belonging to the ketamine and ketamine-lidocaine groups received intravenous ketamine followed by local infiltration with NS in the ketamine group, and lidocaine infiltration in the ketamine-lidocaine group. Heart rate (HR) and invasive mean blood pressure (MBP) were recorded before intravenous medication and then at various time intervals until 15 minutes after pin fixation. Intergroup comparison of MBP and HR by 2-way analysis of variance revealed a significant difference between the groups and various time points (P < .05). Post hoc analysis revealed maximum increase in MBP each hour in the placebo group. Mean blood pressure response in the ketamine group was similar to the placebo group. Significant attenuation of MBP and HR was observed in the lidocaine and ketamine-lidocaine groups (P < .05). A minimal increase in HR was observed in the lidocaine-ketamine group. The current study demonstrates maximum attenuation of hemodynamic responses when a subanesthetic dose of intravenous ketamine (0.5 mg/kg) is administered with 1% lidocaine infiltration.
An unusual case of massive oropharyngeal swelling and macroglossia occurring after cervical spine surgery performed on a patient in the prone position is described. Possible etiological factors are reviewed, and measures to prevent these complications are suggested.
This case report describes fulminant hepatic failure in a 53-year-old female caused by inadvertent rechallenging with diclofenac, treated by orthotopic liver transplantation. The case also illustrates the hazards of using both generic and non-generic drug prescribing, with drugs that are known to be toxic. The literature on non-steroidal anti-inflammatory drugs and hepatoxicity is reviewed.
Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation, releasing iron, carbon monoxide, and biliverdin. Induction of HO-1 occurs as an adaptive and protective response to several inflammatory stimuli. The transcription factor activator protein-1 (AP-1) has been implicated in the activation of the HO-1 gene. To elucidate the molecular mechanism of HO-1 induction, we examined the effects of diferuloylmethane (curcumin), an inhibitor of the transcription factor AP-1. Surprisingly, curcumin by itself was a very potent inducer of HO-1. Curcumin has anti-inflammatory, antioxidant, and renoprotective effects. To evaluate the mechanism of curcumin-mediated induction of HO-1, confluent human renal proximal tubule cells were exposed to curcumin (1-8 microM). We observed a time- and dose-dependent induction of HO-1 mRNA that was associated with increased HO-1 protein. Coincubation of curcumin with actinomycin D completely blocked the upregulation of HO-1 mRNA. Blockade of nuclear factor-kappaB (NF-kappaB) with an IkappaBalpha phosphorylation inhibitor attenuated curcumin-mediated induction of HO-1 mRNA and protein. These data demonstrate that curcumin induces HO-1 mRNA and protein in renal proximal tubule cells. HO-1 induction by curcumin is mediated, at least in part, via transcriptional mechanisms and involves the NF-kappaB pathway.
Patients evaluated for chest pain with angiographically normal coronary arteries are usually labelled syndrome X. A portion of these patients may not have a cardiac cause for their symptoms. The authors aimed to study a subset within this group who showed the phenomenon of slow coronary flow (SCF) as evidenced by a slow antegrade progression of the dye on the coronary arteriogram to see if this could be used as a marker of myocardial ischemia. This observational study included 207 patients being evaluated for suspected coronary artery disease and found to have normal coronary angiograms. SCF was seen in 49 of these patients (23.7%) while the remaining 158 (76.3%) had normal coronary flow (NCF), as detected by the corrected thrombosis in myocardial infarction (TIMI) frame count method (TIMI frame count more than 2 SD of normal). Forty of the 49 patients (82%) in the SCF group had classical angina as compared with only 51 of the 158 patients (32%) in the NCF group (p<0.01). Also, a definitively positive exercise test was observed more commonly in the SCF group than in the NCF group (71% vs 42%, p < 0.01). The authors conclude that SCF patients constitute a definite subset within the wide spectrum of syndrome X and that the phenomenon of SCF could be used as a marker for myocardial ischemia.
Clinically significant enlargement of the thyroid owing to amyloid deposition is a rare occurrence. A 23-yr-old female, a case of juvenile rheumatoid arthritis, developed rapidly increasing thyromegaly during the course of her illness with complaints of dyspnea and dysphagia. Thyroid function tests were within normal limits. Fine-needle aspiration cytology proved inconclusive. Total thyroidectomy was done for symptomatic relief with a preoperative clinical impression of malignancy. Histopathologic findings were consistent with amyloid goiter. The findings of this case are presented, to emphasize the difficulties in making a definite preoperative diagnosis, along with a brief review of the literature.
The ability to transfer immunoregulatory, cytoprotective, or antiapoptotic genes into pancreatic islet cells may allow enhanced posttransplantation survival of islet allografts and inhibition of recurrent autoimmune destruction of these cells in type 1 diabetes. However, transient transgene expression and the tendency to induce host inflammatory responses have limited previous gene delivery studies using viral transfer vectors. We demonstrate here that recombinant adeno-associated virus (rAAV) serotype 2, a vector that can overcome these limitations, effectively transduces both human and murine pancreatic islet cells with reporter genes as well as potentially important immunoregulatory cytokine genes (interleukin-4, interleukin-10), although a very high multiplicity of infection (10,000 infectious units/islet equivalent) was required. This requirement was alleviated by switching to rAAV serotype 5, which efficiently transduced islets at a multiplicity of infection of 100. Although adenovirus (Ad) coinfection was required for efficient ex vivo expression at early time points, islets transduced without Ad expressed efficiently when they were transplanted under the renal capsule and allowed to survive in vivo. The rAAV-delivered transgenes did not interfere with islet cell insulin production and were expressed in both beta- and non-beta-cells. We believe rAAV will provide a useful tool to deliver therapeutic genes for modulating immune responses against islet cells and markedly enhance longterm graft survival.
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PURPOSE: We determined whether varicocele treatment before intrauterine insemination significantly affects intrauterine insemination success rates. MATERIALS AND METHODS: A total of 58 infertile couples, of whom the women had normal evaluations and men had abnormal semen analyses and a history of varicocele, were included in this study. They were identified after reviewing the charts of all women undergoing intrauterine insemination for male factor infertility at our center. Of the men 24 participated in 63 intrauterine insemination cycles without varicocele treatment, while in the remaining 34 varicocele was treated before a total of 101 intrauterine insemination cycles. Variables associated with pregnancy or live birth were analyzed using repeat measures logistic regression with generalized estimating equation techniques. An initial stepwise generalized estimating equation was performed without including varicocele treatment status. Subsequently varicocele treatment status and the significant associated factors were included in analysis. The semen characteristics of untreated and treated varicocele groups were compared with repeat measures analysis of variance. RESULTS: On pre-wash semen analysis patients with untreated varicocele had significantly higher mean motility plus or minus standard error than patients whose varicoceles were treated (48.6% +/- 2.3% versus 38.1% +/- 1.8%, p = 0.02). However, no statistically significant difference was noted in the mean post-wash total motile sperm count in the treated and untreated groups (7.2 +/- 1.0 versus 14.8 +/- 2.6, p = 0.1). Despite these findings the pregnancy and live birth rates per cycle were significantly higher in patients in whom varicocele was treated than in those without varicocele treatment (11.8% versus 6.3%, p = 0.04 and 11.8% versus 1.6%, p = 0.007, respectively). CONCLUSIONS: Varicocele treatment may not improve semen characteristics in all men but it appears to improve pregnancy and live birth rates among couples undergoing intrauterine insemination for male factor infertility. A functional factor not measured on routine semen analysis may affect pregnancy rates in this setting. Men should be screened for varicocele before intrauterine insemination is initiated for male factor infertility.
PURPOSE: While detecting bladder cancer, bladder tumor markers demonstrate improved sensitivity compared with urinary cytology but the current limitation is the low specificity and positive predictive value, that is high false-positive rate. We examined the clinical categories of the false-positive results, established relative exclusion criteria, and recalculated the specificity and positive predictive value of this assay with these criteria. MATERIALS AND METHODS: A total of 608 patients considered at risk for bladder cancer presented to a urology clinic and submitted a single urine sample. Of the 608 patients 529 (87%) presented with de novo hematuria or chronic voiding symptoms without a diagnosis of bladder cancer. There were 79 (13.0%) patients being monitored with a known history of bladder cancer. Each urine sample was examined via cytology, urinalysis, culture and NMP22 protein assay. All patients underwent office cystoscopy, and transurethral resection and/or biopsy if a bladder tumor was suspected. RESULTS: Of the 608 patients 226 (37.2%) presented with microscopic hematuria, 143 (23.5%) with gross hematuria and 239 (39.3%) had chronic symptoms of urinary frequency or dysuria. There were 52 (8.6%) patients who had histologically confirmed bladder cancer. Of these 52 cancers NMP22 detected 46 (88.5%), whereas cytology identified only 16 (30.8%). When atypical cytology was considered positive, cytology detected 32 (61.5%) cases. In the 135 patients with increased NMP22 values the 46 identified tumors were accompanied by 89 false-positive values yielding a specificity of 83.9% and a positive predictive value of 34.1%. These false-positive results were divided into 6 clinical categories. Exclusion of these categories improved the specificity and positive predictive value of NMP22 to 99.2% and 92.0%, respectively, yielding results similar to urinary cytology (99.8% and 94.1%). CONCLUSIONS: Awareness and exclusion of the categories of false-positive results can increase the specificity and positive predictive value of NMP22, enhancing the clinical use of this urinary tumor marker.
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Seventy-two patients, 50 women and 22 men, were operated on for Graves' disease. Their median age was 35 years. The indications for surgery included patients with large goitre, relapse after antithyroid drug (ATD) therapy, allergic reactions to ATD, non-compliance and finally an associated nodule with suspicion of carcinoma. Patients were rendered euthyroid with ATD before surgery and were pretreated with Lugol's iodine. Standard subtotal thyroidectomy was performed in 64 patients, total thyroidectomy in 7 patients, and one patient underwent a completion thyroidectomy after an initial subtotal thyroidectomy. The weight of the thyroid remnant on either side was estimated emperically between 3 g and 5 g. There was no postoperative death or thyrotoxic crisis. There was no case of permanent recurrent laryngeal nerve damage or hypoparathyroidism. Eight patients (11.1%) had temporary unilateral vocal cord palsy and 4 patients (5.5%) had temporary hypocalcemia. One patient (1.4%) developed recurrent hyperthyroidism. Postoperative transient hypothyroidism developed in 87.5% cases, all within the first postoperative year. The functional results at 2 years were as follows: Out of 47 cases followed 31 patients (65.9%) became euthyroid while 15 (31.9%) were still hypothyroid and requited long term substitutive treatment. Ophthalmopathy worsened in only one patient. Thyroidectomy has reasonable role in the management of Graves' disease, because the patients have had their diseases rapidly terminated, were hospitalised for an average period of only 3.5 days and have had no permanent functional insult except for hypothyroidism.
Molecular methods are being frequently used for the study of soil microbial communities as majority of naturally occurring microbial populations are non-culturable. In the present study, we describe a protocol of DNA extraction from diverse soils using a combination of heat, enzyme (lysozyme) and guanidine thiocyanate. The efficacy of the procedure was evaluated in terms of yield, purity and duration of extraction. The protocol was effective for neutral, acidic as well as alkaline soils (pH range 4.5-8.5). The extracted soil DNA was observed with negligible shearing on agarose gel and the time taken for restriction digestion was very less. Further, the DNA extracted was almost completely devoid of contaminants and pure enough which could be used for PCR amplification and Southern hybridization.
INTRODUCTION: Parathyroid carcinoma is a rare tumor with an incidence of 0.5 to 4%. Preoperative differentiation from benign adenoma is very difficult. Several features, though nonspecific, have been used in differentiating parathyroid carcinoma from the adenoma. MATERIAL AND METHOD: A retrospective analysis during the period of nine years, four cases of parathyroid carcinoma were diagnosed on the basis of per-operative local invasion and on histological evidence of capsular invasion and vascular invasion. RESULT: We have different observations to make. Diagnosis of parathyroid carcinoma which was done on the basis of intra operative suspicion only. One patient died on 6th post operative day due to development of pancreatitis. At the follow-up of two years there was no local recurrence or distant metastasis. CONCLUSION: It is preferable to have a high index of suspicion for parathyroid carcinoma when these features are present than to miss the opportunity for surgical cure by failing to consider it in the differential diagnosis.