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Background: Silent inflammatory bowel disease (IBD) is a condition in which individuals with the active disease experience minor to no pain. Voltage-gated Na + (Na V ) channels expressed in sensory neurons play a major role in pain perception. Previously, we reported that a Na V 1.8 genetic polymorphism (A1073V, rs6795970) was more common in a cohort of silent IBD patients. The expression of this variant (1073V) in rat sympathetic neurons activated at more depolarized potentials when compared to the more common variant (1073A). In this study, we investigated whether expression of either Na V 1.8 variant in rat sensory neurons would exhibit different biophysical characteristics than previously observed in sympathetic neurons., Methods: Endogenous Na V 1.8 channels were first silenced in DRG neurons and then either 1073A or 1073V human Na V 1.8 cDNA constructs were transfected. Na V 1.8 currents were recorded with the whole-cell patch-clamp technique., Key Results: The results indicate that 1073A and 1073V Na V 1.8 channels exhibited similar activation values. However, the slope factor (k) for activation determined for this same group of neurons decreased by 5 mV, suggesting an increase in voltage sensitivity. Comparison of inactivation parameters indicated that 1073V channels were shifted to more depolarized potentials than 1073A-expressing neurons, imparting a proexcitatory characteristic., Conclusions and Inferences: These findings differ from previous observations in other expression models and underscore the challenges with heterologous expression systems. Therefore, the use of human sensory neurons derived from induced pluripotent stem cells may help address these inconsistencies and better determine the effect of the polymorphism present in IBD patients., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

In the present study, the effects of prolonged obstruction in different regions of the human epididymis on its histology and on the spermatozoa retained at the site of obstruction were assessed. Men who were confirmed of having obstruction of the epididymis underwent vasoepididymostomy (VEA) for surgical correction of the obstruction. At the time of surgery, fluid from the epididymal tubule above the site of obstruction was aspirated and examined for sperm profile. Epididymal tissue, collected at the site of obstruction, was processed for assessment of histological changes and also used to identify the site of obstruction. Prolonged obstruction of the epididymis has caused degeneration of the epididymal epithelium, gradual decrease in the diameter of the tubule and tubular lumen and increase in the intertubular connective tissue. Sperm aspirated from the caput epididymal fluid showed sluggish pattern of motility only in one out of the six subjects, whereas spermatozoa collected from the cauda epididymal fluid showed rapid linear progressive motility in one of three subjects. A major percentage of spermatozoa in the aspirated fluid showed various types of morphological abnormalities, irrespective of the site of obstruction. These results are discussed in relation to the role of the epididymis in investing spermatozoa with motility and fertilizing capacity.

Background: The catchment area of the patients under study was the sub-Himalayan plains, which are recognized as iodine-deficient areas., Methods: A retrospective analysis of 1576 surgically treated patients with thyroid disorders is presented. The indications for surgery were hyperthyroidism or cytologically diagnosed malignancy and large size, pressure symptoms, cosmesis, suspicious cytologic findings for malignancy, and clinical suspicion of malignancy in clinically benign euthyroid goiters., Results: Histologically, 83 of 703 solitary thyroid nodules, 36 of 329 clinically benign euthyroid multinodular goiters, and four of 181 Graves' disease were cancers. Of all follicular cell cancers in this study, 132 were papillary, 83 were follicular, and 38 were anaplastic and squamous cell cancers. The different histologic types exhibited an aggressive clinical behavior, with advanced lesions with cervical lymph node involvement and distant metastases frequently seen at presentation. Locoregional recurrence occurred frequently even after radical surgical ablation, and overall mortality caused by the disease was high., Conclusions: Even well-differentiated cancers pursued a virulent clinical course with high mortality, despite routine radical surgical and radionuclide ablation., (2005 Wiley Periodicals, Inc.)

Although serum thyroglobulin (STg) is a useful tumour marker to detect the recurrence of tumour in well differentiated thyroid carcinoma, it has as yet not been reported to be of value in predicting the behaviour of thyroid cancer. In the present study of 20 patients, the measurement of preoperative Stg/thyroid mass has been utilised to find out Tg synthesizing capacity of the tumour. This ratio was significantly higher in the patients with follicular variety than in papillary thyroid carcinoma. It was significantly higher in the metastasis group than in the group of patients without metastasis. The patients with functioning metastasis had a higher than average value of this 'ratio' than those with non functioning metastasis, though the difference was not statistically significant. Despite the limitation of a small number of patients included in this study, it is possible to highlight the possible utility of preoperative Stg estimation as a tumour marker in categorization of the patients of carcinoma of the thyroid gland.

Eighteen patients of Cushing's Disease, who had undergone bilateral "total" adrenalectomy 2 to 10 years back, were evaluated for residual adrenocortical function and for any evidence of Nelson's Syndrome. Surprisingly, all patients were discovered to have measurable plasma cortisol, albeit in the subnormal range. The standard criteria for accepting "completeness of adrenalectomy" were fulfilled in 16 patients. It was possible to wean one patient off replacement therapy. Thus, the dose of replacement steroids needs to be regulated according to the blood steroid levels in order to avoid unnecessary hypercortisolism. Radiological evidence of pituitary tumor diagnosed Nelson's Syndrome in 2 patients. Nelson's Syndrome was further suspected in 8 others who showed pigmentation. One of these had an enlarged sella and an erosion of the dorsum sellae, but had a normal CT scan. Another patient had evidence of incidental pituitary pathology (incidentaloma) which resolved spontaneously. Contrast enhanced CT scans of the sella are necessary for early detection of Nelson's Syndrome.

Ultrastructural changes in the efferent duct and in different regions of the epididymis in men with obstructive azoospermia were compared with corresponding tissues collected from men of proven fertility who underwent castration due to malignancy of the prostate. Major degenerative changes were seen in the efferent duct and the caput epididymidis of men with obstruction at the caput epididymidis which may have been induced by fluid pressure due to defective absorption of testicular fluid in the caput epididymidis. These degenerative changes included decrease in tubular and lumen diameter of the caput and the cauda epididymides, decrease in height of the stereocilia, reduction in rough endoplasmic reticulum and Golgi material, and presence of lipofuscin and osmiophilic dense bodies. The degenerative changes were less when the site of obstruction was in the cauda epididymidis since fluid reabsorption would continue to take place normally in the caput epididymidis. In men who had undergone vasoepididymostomy (VEA), the ejaculated spermatozoa showed a high percentage of morphological abnormalities which may have occurred due to adverse effects of long-term obstruction on spermatogenesis.

Attempts were made to validate RIA for prolactin (PRL), LH and FSH in semen from normospermic, oligospermic and azoospermic subjects. The RIA used to measure PRL and LH in semen fulfilled the criteria of reliability, whereas low levels of FSH in semen precluded the validation of FSH assay in semen. Semen levels of PRL and LH were significantly (P < 0.05) higher than serum levels in all groups of subjects investigated. Semen levels of FSH in azoospermic men after vasoepididymostomy (VEA), were significantly (P < 0.05) higher compared to azoospermic men prior to surgery. Serum levels of PRL were significantly higher (P < 0.05) in normospermic men compared to oligospermic and azoospermic men prior to and after surgery. Semen levels of PRL in normospermic men were comparable with oligospermic and azoospermic subjects prior to and after surgery. Serum levels of LH in oligospermic and azoospermic men who did not undergo surgery and in men reporting oligospermia after VEA were comparable to normospermic subjects but in men showing azoospermia post surgically, serum LH levels were significantly (P < 0.005) elevated. Semen levels of LH in men reporting azoospermia before surgery and in subjects showing oligospermia or azoospermia post surgically were significantly lower (P < 0.05) compared to men with normal sperm count. Serum levels of FSH were significantly elevated (P < 0.05) compared to semen levels in oligospermic men prior to surgery but this increase was not seen in post VEA subjects. These results were discussed.

The ability of germ cells (spermatocytes and spermatids) and spermatozoa present in human ejaculate to metabolize steroids was studied in men with obstructive infertility who had undergone vasoepididymostomy as corrective surgery. Steroid metabolism by spermatozoa in men who had undergone vasovasostomy was also investigated. Germ cells converted testosterone mainly to androstenedione. In addition to androstenedione, dihydrotestosterone and androstanediols were also formed in incubations using spermatids. Both types of germ cells converted estradiol to estrone. Spermatozoa from subjects who had undergone vasoepididymostomy or vasovasostomy converted testosterone to androstenedione as in normal men, while spermatozoa from infertile subjects converted testosterone mainly to dihydrotestosterone. Seminal fluid, free of germ cells, did not show steroid-metabolizing capability.

The histology of different regions of human epididymis in men undergoing vasoepididymostomy to correct epididymal obstruction was studied. The data indicate major degenerative changes in intertubular connective tissue and in the epididymal epithelium. These include increase in connective tissue thickness and its infiltration by leucocytes in some cases, decrease in tubular diameter, degeneration and/or vacuolation of cytoplasm of nonciliated cells of efferent duct and principal cells of epididymis and presence of multinucleate giant cells in the epididymal lumen. These histological abnormalities are discussed in relation to the role such epididymis can play in sperm maturation following vasoepididymostomy.

Fine needle aspiration cytology (FNAC) was used as a preliminary diagnostic procedure in evaluating discrete, asymptomatic cervical lymphadenopathy of more than four weeks duration. Benign pathologies were encountered in 294/359 patients (82%); of these 86% had tuberculosis. Even in the elderly, a large number of patients (25/78) harboured tubercular lymph glands. FNAC obtained adequate material for cytologic diagnosis in 97.5% and had an overall accuracy rate of 97%. Malignancy was correctly diagnosed in 100%; in tuberculosis the accuracy rate of 96% with a 3.5% false negative results. FNAC is reliable as the initial evaluating procedure even in benign disorders; it is also cheap, speedy and easy to perform, with no complications, making it suitable for wider application in developing countries with scant resources.

A retrospective analysis of 206 cases of thyroid carcinoma treated at a single surgical service in a region with endemic goitre is presented. In contrast to the marked female preponderance in surgically treated benign thyroid disorders, the frequency of thyroid carcinoma was almost equal in the two sexes (males/females = 100/106). The duration of symptoms was, as a rule, short and there was a predominance of advanced lesions (T3N3M1) even among the well-differentiated tumours. Papillary carcinoma was the most common histologic type (45%) but its proportion was considerably lower than usually reported from non-endemic regions. The average TSH level was significantly elevated in the carcinoma group and associated adenomatous changes were found in 40/100 cases which might suggest an etiologic role of increased TSH stimulation. Since most thyroid carcinomas had a very malignant clinical behaviour, surgical treatment aimed at near-total thyroidectomy which was performed in 62% of the cases. During a follow-up of up to eleven years recurrence in the remaining contralateral lobe occurred in 23% of patients with hemithyroidectomy and loco-regional recurrence was seen in 29% of patients with near-total thyroidectomy. Mortality was high in all histologic types, further underlining the aggressive biologic behaviour of thyroid cancers in an endemic area.

We report 408 cases of autonomously functioning thyroid nodule (AFTN); 85.5% occurred in female patients, for a male-female ratio of 1:6. Eighty-nine patients (21.8%) were hyperthyroid, 76 of them being female, also yielding a male-female ratio of 1:6. There was a linear increase in the incidence of hyperthyroidism with age and with an increase in the size of the nodule, especially for nodules more than 3 cm in diameter. There was a significantly higher incidence of hyperthyroidism for nodules of the same size when they occurred in patients more than 40 years of age. There was a corresponding increase in hyperthyroidism with an increase in the length of time after the initial detection of the nodule; this finding was significantly greater in patients more than 40 years of age. Thus, the age of the patient was found to be a more important determinant in the production of hyperthyroidism associated with an AFTN than either the size of the nodule or the duration of symptoms.

There is controversy about the most appropriate treatment for patients with thyroid cancer. This study analyses our experience with 206 cases of thyroid cancer from an endemic goiterous area. There were 100 males and 106 females; patients presented at an earlier age with a short history. Thyroid cancers demonstrated an aggressive biological behaviour with an advanced stage at presentation (overt cancers in 51 per cent) and a relentless course with a mortality rate of 24.2 per cent for the well-differentiated tumours. Near-total thyroidectomy was performed in 126 patients. Multicentric foci of tumour were seen in 17.2 per cent of the well-differentiated cancers and 25.2 per cent of the cases of well-differentiated cancers who underwent near-total thyroidectomy developed loco-regional recurrence. Hemithyroidectomy was performed in 35 patients who refused completion total thyroidectomy at a second stage; 16.7 per cent of these patients developed a recurrence in the remaining contralateral lobe. Thus in our patients from an endemic goiterous area, near-total thyroidectomy is the treatment of choice particularly because of the frequent occurrence of follicular and anaplastic cancers (in 44.2 per cent) and because the course of the disease is more virulent.

Leiomyosarcoma of the colon, excluding that of the rectum, is extremely rare. We report a case of leiomyosarcoma of the ascending colon with a brief review of literature. The clinical manifestations in our case were typical: abdominal pain, diarrhea, anorexia, and a palpable tumor that was firm, smooth, and mobile inspite of its bulk. Toxic features, cachexia and weight loss were less prominent. Morphologically the tumor was of dumbbell type with intracolic and extracolic components. The microscopic picture, consisting of spindle-shaped smooth-muscle cells with pleomorphism and one to three mitotic figures per high-power field, was characteristic. In the absence of local spread, a hemicolectomy was considered curative, but our patient developed extensive metastasis in 25 months. The correlation between mitotic activity of the tumor and prognosis in our case was consistent with that reported in literature.

Four cases of thyroid carcinoma occurring in 140 cases of Graves' disease are presented herein. A standard workup of the patients was done to establish hyperthyroidism and all cases of cancer were diagnosed on receipt of histopathology. There were three cases of papillary carcinoma and one case of follicular carcinoma with one cancer being encountered in the 'cold' area of the thyrotoxic gland. The incidence of malignancy in thyrotoxicosis, however, was not found to be higher than that in other thyroid disorders.

Surgery for male obstructive infertility is not always successful. A number of clinical and operative findings, not previously reported, may influence the outcome. We have studied 182 patients with azoospermia who underwent vasoepididymostomy. The pre-operative and operative findings which adversely affected the function of the anastomosis were identified. The presence of spermatozoa in the semen sample was taken to mean a successful anastomosis. Abnormal testicular histology was an adverse pre-operative finding. Adverse operative findings included non-canalisation of the epididymal tubules and hypoplasia of the epididymis; both factors were associated with a high failure rate (almost 100%). The anastomosis was a failure in 78% of the patients when no fluid was seen on sectioning the epididymis. In the absence of adverse findings the success rate of vasoepididymostomy was 59%. Pre-operative testicular biopsy, together with careful observation and recording of findings before and during surgery, are recommended to avoid needless exploration and anastomosis.

A retrospective review of 143 cases of carcinoma of the gall bladder is presented. The disease was more common in females in the 5th and 6th decades. Pain, anorexia, weight loss and jaundice were the common presenting symptoms, and hepatomegaly and palpable gall bladder the common signs. Laboratory and radiological investigations were merely confirmatory as the diagnosis in a majority of the cases was clinically obvious. Aspiration cytology and laparoscopic biopsy were of help in obtaining histological diagnosis. Only 47 patients were considered fit enough to undergo laparotomy. In a majority of these patients biopsy alone was possible while palliative procedures were performed in the others. The operative mortality was 18% even in this selected group of patients, due to the poor general condition and the advanced stage of the disease at the time of diagnosis. Curative resection may be possible and long term survival is expected in incidentally found carcinoma at cholecystectomy. The only hope lies in prevention by prompt treatment of patients with benign biliary disease.

Copper wire was inserted into the vas deferens and its effect of the reproductive system and fertility performance of rats was investigated. The copper wire was 100% effective as a contraceptive for up to 4 months if placed correctly, and resulted in decapitation of most of the spermatozoa. No differences between the rats with an intravasal copper wire and the sham-operated controls were found for the weights of the gonads and accessory sex glands or for protein, RNA, DNA and fructose concentrations. The intravasal copper device appears to be promising for the development of a long-term method for male contraception.