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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 181 records · Page 10Linked to original sources

Measurement of colonic transit time using radionuclide imaging: analysis by condensed images.

A polymer-coated capsule has been used in eight volunteer subjects to deliver 111In-resin into the ileocaecal region. The images were acquired for up to 3 days to follow transit through the colon. Expressing the results of individual studies is difficult and time-activity curves for each region are confusing. Calculation of the geometric centre indicates only where the middle of the activity has reached. We describe a new method of presenting colonic transit data as parametric images. The parametric images show the amount of activity in each area of interest as the study progresses. This is readily understood and allows segmental movement of the isotope, either forward or retrograde, to be examined. The geometric mean of activity in four areas of the colon were also calculated. Four hours after reaching the ileocaecal region, 65% (S.D. 24%) of the activity was in the caecum and 26% (S.D. 20%) in the transverse colon. By 24 h three controls had excreted most of the activity, in two the activity was mainly in the rectum and in two there was still some activity in the transverse colon. A protocol for colonic transit studies, problems with analysis and a new method of presentation of data are discussed.

Acrylic Resins

The prevalence of anal sphincter defects in faecal incontinence: a prospective endosonic study.

Forty six patients (median age 61 years; 42 women) with faecal incontinence and 16 age and sex matched controls undergoing a restorative proctocolectomy were assessed by clinical examination, anorectal physiology, and anal endosonography. Forty patients (87%) with faecal incontinence had a sphincter defect demonstrated on anal endosonography (31 external and 21 internal anal sphincter defects). The commonest cause of faecal incontinence was obstetric trauma. This occurred in 35 women, 30 of whom exhibited a morphological defect in the anorectal sphincter complex. In 22 of these patients with a history of a perineal tear or episiotomy, 21 (95%) had a sphincter defect. Sphincter defects were commonly located at the level of the midanal canal.

Adult

Antral volume and propulsion-retropulsion in response to upper intestinal nutrients in a canine model.

We measured antral volumes and propulsion-retropulsion for individual peristaltic cycles using the dynamic spatial reconstructor in three female mongrel dogs. Our aim was to quantify the effect of intestinal perfusion of equicaloric, isotonic, and isomolar nutrients (maltose, 32.5 mg/100 ml; casein hydrolysate, 32.5 mg/100 ml; and oleic acid 15.5 mg/100 ml) at a rate of 10 ml/min in the upper small intestine on total antral volume and the propulsion-retropulsion function of the "antral pump." Isotonic saline was used as a control solution. Isotonic gastrografin (600 ml) was instilled intragastrically as a meal. A 6-channel perfused manometric assembly was used to record antral phasic pressure activity. Antral volume was significantly lower (P < 0.05) in response to fat perfusion compared with other nutrients or isotonic saline. The propulsion-retropulsion ratio was also significantly reduced (P < 0.05) in response to fat perfusion in the upper small intestine. Our study, therefore, indicates that the fraction of a liquid meal delivered to the antrum is determined, at least in part, by the upper small intestinal nutrients and also that the presence of fat in the small intestine alters the propulsion-retropulsion function of the antrum.

Animal Nutritional Physiological Phenomena

Selective inhibition of the cutaneous late but not immediate allergic response to antigens by misoprostol, a PGE analog. Results of a double-blind, placebo-controlled randomized study.

The objective of this study was to investigate the effect of misoprostol on allergen-induced cutaneous immediate- and late-phase allergic reactions in a double-blind placebo-controlled randomized study. We also studied the mechanism of antiallergic effects of misoprostol. A total of 16 dust mite-allergic patients received misoprostol (200 micrograms) or placebo and then had skin testing on 2 different days. The immediate- and late-phase skin response was monitored for 6 h. Skin biopsy was obtained from 5 selected donors at 5 h. In vitro studies included the effect of misoprostol on eosinophil chemotaxis, eosinophil survival, basophil histamine release, and cytokine production by lymphocytes. All subjects developed an immediate wheal reaction and a late-phase induration in response to dust mite allergens after taking placebo. Misoprostol selectively inhibited the late- but not the immediate-phase response (p < 0.05). Histologic studies revealed a trend toward a reduced number of inflammatory cells in the skin dermis after misoprostol treatment. Misoprostol significantly (p < 0.05) inhibited eosinophil chemotaxis and the production of granulocyte-macrophage colony-stimulating factor by lymphocytes at concentrations > or = 10(-8) M. However, at significantly lower concentrations (> or = 10(-12) M) misoprostol blocked cytokine-stimulated eosinophil survival. Thus, misoprostol has potent antiallergic effects and blocks the cutaneous late-phase allergic inflammation.

Adult

North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin.

In 224 twin pairs (132 monozygotic, 86 dizygotic, and 6 of uncertain zygosity) in whom the index twin had developed IDDM before 30 yr of age, 51 of the co-twins (38 monozygotic, 10 dizygotic, and 3 of uncertain zygosity) subsequently became diabetic. On the basis of concordance ratios, which were significantly discrepant (P < 0.01) between monozygotic and dizygotic twins, the substantial genetic role in IDDM etiology is confirmed. For the monozygotic co-twin of an IDDM case, the relative risk is significantly related to an early age at proband diagnosis (P < 0.01 for 0-4 vs. 5-9 yr of age). However, among monozygotic co-twins at any age, IDDM risk decreases as time passes after the proband diagnosis (P < 0.01 for 0-23 vs. > or = 24 mo after a proband diagnosis at 5-9 yr of age). Moreover, a structural-equation analysis suggests a profound contribution to liability (as much as 79%) from the twins' shared environment. Risk to like-sex male dizygotic co-twins is as high as that to monozygotic co-twins, significantly higher than that to like-sex female dizygotic co-twins (P < 0.005), and even higher than that to male co-twins in unlike-sex dizygotic pairs (P < 0.05). Overall, the risk to the dizygotic co-twin of a case is significantly higher (P < 0.001) than that to a non-twin sibling, as reported in the literature. The observed male excess is consistent with reported patterns of IDDM in experimental animals, and in certain circumstances in humans. Taken together, these observations suggest an important early acquired determinant of IDDM, independent of genetic determinants. On the basis of Kaplan-Meier IDDM-free survival curves, if the proband is diagnosed before 15 yr of age, the long-term risk to the co-twin is estimated at 44% (monozygotic) and 19% (dizygotic); it reaches 65% for the co-twin of a monozygotic proband diagnosed before 5 yr of age. An IDDM discordant period of no more than 3 yr was observed in 60% of the pairs destined to become concordant, offering a very brief window for intervention following the recognition of high risk.

Age Factors

Adrenal cortical adenoma and adrenal metastasis of renal cell carcinoma: immunohistochemical and DNA ploidy analysis.

Renal cell carcinoma can have solitary adrenal metastasis years or even decades after resection of the primary tumor. The difficulty in distinguishing an adrenocortical adenoma from a solitary metastasis of a renal cell carcinoma prompted us to study 10 adrenal adenomas, 11 primary renal cell carcinomas, and three renal cell carcinomas metastatic to the adrenal gland by immunohistochemical stains and flow cytometry to determine if these techniques could help make the distinction. Immunohistochemical staining was performed for detection of cytokeratin, vimentin, and epithelial membrane antigen (EMA). Cytokeratin, vimentin, and EMA were detected in 10/11, 9/11, and 11/11 primary renal cell carcinomas, respectively, and 1/3, 2/3, and 3/3 metastatic renal cell carcinomas, respectively. All cases of adrenal adenoma were negative for the three antigens. DNA content analysis by flow cytometry showed no evidence of an abnormal DNA stemline in any of the cases except one renal cell carcinoma. We conclude that staining for EMA is consistently strongly positive in primary and metastatic renal cell carcinomas and consistently negative in adrenal adenomas, proving to be a useful distinguishing marker. Cytokeratin and vimentin, although uniformly absent in adrenal adenomas, are variably and often only weakly positive in renal cell carcinomas, and therefore of less help in making the distinction. Flow cytometry analysis has no discriminatory value in these cases.

Adenoma

Familial tumoral calcinosis. A clinical, histopathologic, and ultrastructural study with an analysis of its calcifying process and pathogenesis.

We describe histopathologic and ultrastructural changes in tumoral calcinosis (TC) occurring in seven siblings from a single family. Tumoral calcinosis appears to be triggered by bleeding followed by aggregation of foamy histiocytes. These in turn are transformed, with participation of collagenolysis, into cystic cavities lined by osteoclast-like giant cells and histiocytes--the lesion resembling adventitious bursae. Movement and friction, forces generated from the periarticular location of the TC lesions, putatively are key to this transformation. Concomitantly, two calcifying events develop, possibly driven by concurrent hyperphosphatemia or endogenous hypervitaminosis D. One occurs on membranous fragments in antiprotease-containing large cytoplasmic vesicles within osteoclast-like giant cells and mononuclear cells lining the TC cavities; the second, in the TC locules on membranous and cellular debris derived from cavity-lining cells and erythrocytes. The TC cavities ultimately fill with calcified material, losing their synovial-like lining, become encapsulated by fibrous tissue, and ossify. Hydroxyapatite may gain entrance to capillary lumens and embolize to the lung. We conclude that TC represents a disordered reparative process that often is exaggerated because episodes of bleeding, caused by TC-induced vascular injury, provoke development of new lesions. The capricious response of TC to treatment is correlated with its morphologic features.

Adult

Clinical implications of tumor volume measurement in stage I adenocarcinoma of the cervix.

OBJECTIVE: To evaluate the prognostic significance of three-dimensional determination of tumor size in stage I cervical adenocarcinoma. METHODS: Tumor volume was measured using hematoxylin and eosin-stained sections of cone biopsy and hysterectomy specimens from 36 patients with stage I adenocarcinoma of the cervix. The volume was then correlated with pelvic lymphatic spread and clinical outcome. RESULTS: The subjects were followed for a mean (+/- SEM) of 63 +/- 8 months. No recurrence or lymphatic seeding was encountered in the 22 tumors measuring no more than 500 mm3. Two of 25 tumors (8%) having up to 5 mm depth of stromal invasion had lymph node metastasis, one of which was 1.5 mm, compared with four of 11 (36%) in the group with deeper than 5 mm invasion (P < .02). The depth of stromal invasion predicted recurrence less significantly. Among the 25 tumors with up to 5 mm stromal invasion, two recurred, compared with three of 11 with more than 5 mm invasion (P < .1). Two women who had tumor volumes below 500 mm3 and depths of stromal invasion up to 8.5 mm were disease-free at 52 and 96 months of follow-up. On the other hand, tumors with 2.6 and 3.8 mm stromal invasion, but with volumes exceeding 500 mm3, recurred. CONCLUSION: Tumor volume is a better predictor of pelvic lymph node metastasis and recurrence than is the depth of stromal invasion in stage I cervical adenocarcinoma.

Adenocarcinoma

Leiomyosarcoma of the orbit: diagnosis of its recurrence by fine-needle aspiration cytology.

An 8 1/2-yr-old boy with proptosis was diagnosed to have low-grade leiomyosarcoma of the orbit following lateral orbitotomy and histology of an incompletely excised intraconal mass. He received chemotherapy but had recurrence of proptosis at the age of 12 yr. Ultrasonography revealed a solid mass and its fine-needle aspiration cytology features were consistent with recurrence of leiomyosarcoma. A year later, the cytodiagnosis was confirmed by histology of the excised tumor from a second lateral orbitotomy. Masson's trichrome stain confirmed the smooth muscle nature of the neoplasm and ultrastructural features were in favor of leiomyosarcoma. The patient received intermittent chemotherapy, and is clinically free from disease at the age of 17 yr.

Antineoplastic Combined Chemotherapy Protocols

Noninvasive assessment of systolic and diastolic left ventricular function in patients with chronic severe anemia: a combined M-mode, two-dimensional, and Doppler echocardiographic study.

Thirty-one patients with chronic severe anemia of more than 3 months' duration (hemoglobin less than 7 gm/dl) and no underlying heart disease were studied by means of M-mode, two-dimensional, and Doppler echocardiography; an equal number of normal control subjects was also studied. There are conflicting reports regarding the influence of chronic severe anemia on systolic myocardial function, but diastolic function has not been systematically assessed. It is also uncertain whether anemia alone can cause heart failure in a structurally normal heart. We therefore performed a detailed study of echocardiographic indexes of systolic and diastolic left ventricular function in these patients. We found that patients with anemia have significantly faster heart rates and lower diastolic and mean blood pressures than normal subjects. They also have a significantly elevated cardiac output and stroke volume and larger left ventricles. Left ventricular contractility, assessed by the end-systolic stress-dimension relationship, was enhanced. There was no systematic evidence of diastolic dysfunction by Doppler assessment of mitral inflow. There was also no clinical evidence of congestive heart failure. We conclude that chronic severe anemia leads to a hyperdynamic state with systolic hyperfunction and no impairment of diastolic function. Anemia does not lead to congestive heart failure in the absence of underlying heart disease.

Adult

Abnormal REM sleep in the irritable bowel syndrome.

Motor abnormalities of the small bowel that occur only during the waking state have been reported in the irritable bowel syndrome (IBS), suggesting that central nervous system arousal is a necessary condition for expression of the disorder and that it may reflect inappropriate brain-gut interaction. This possible relationship was explored further by synchronous polysomnography and recording of upper small bowel motility in six healthy subjects and six patients with IBS. During sleep, there was no difference in the patterns of intestinal motility between the two groups. There was no difference between the rapid eye movement (REM) latency or number of REM episodes, but the proportion of REM sleep was markedly increased (36.5% +/- 5.7% vs. 18.2% +/- 5.7%; P less than 0.01) in the IBS group, although the duration of sleep was similar (468 +/- 13 minutes in IBS vs. 444 +/- 10 minutes in controls; P greater than 0.1). Sleep apnea was detected in three of six patients with IBS but was not seen in controls. The data are consistent with the model of IBS as a disorder of brain-gut interaction.

Adult

Dendrocyte population in cutaneous and extracutaneous Kaposi's sarcoma.

In order to investigate the hypothesis that the spindle cells of Kaposi's sarcoma originate from dendrocytes, we stained 22 cases of cutaneous and extracutaneous Kaposi's sarcoma for the presence of factor XIIIa. We selected eight lesions from the skin, five from the oral mucosa, four from gastrointestinal mucosa, three from lymph nodes, and one each from esophagus and conjunctiva for this study. The majority of cutaneous and lymph node Kaposi's sarcoma lesions had a considerable number of dendrocytes admixed with the spindle tumor cells. Of the five oral mucosal lesions only three showed a focal presence of dendrocytes. No dendrocytes were observed in the lesions biopsied from the gastrointestinal mucosa, esophagus, and conjunctiva. Our findings suggest that the proliferation of dendrocytes seen within the lesions of Kaposi's sarcoma in the skin and lymph nodes probably represents a nonspecific host response in organs where they are normally present, and it is unlikely that they constitute the neoplastic cells of Kaposi's sarcoma.

Dendritic Cells

Transitional cell carcinoma with rhabdoid features.

We discuss the light-microscopic, immunohistochemical, electron-microscopic, and flow cytometric analysis in a case of invasive transitional cell carcinoma of the renal pelvis with rhabdoid features and glandular metaplasia. This tumor demonstrated in situ rhabdoid transformation of the transitional epithelium, which has not been described before. Electron-microscopic examination of the rhabdoid cells revealed whorled aggregates of intermediate filaments. There was also evidence of mucin-filled intracellular lumina on light and electron microscopy in both in situ and invasive components of the tumor. Our findings lend support to the view that tumors with "rhabdoid" features in adults and perhaps some children represent a heterogeneous group of neoplasms, some of which may just be unusual morphologic variants of a transitional cell carcinoma, in contrast to the distinct clinicopathologic entity of childhood renal rhabdoid tumors.

Adult