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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 109 records · Page 6Linked to original sources

Primary repair of obstetric anal sphincter rupture using the overlap technique.

OBJECTIVE: To evaluate the feasibility of a new technique of primary overlap anal sphincter repair instead of end-to-end repair. SETTING: A teaching hospital and a district general hospital. METHODS: Between June 1995 and November 1996, two obstetricians repaired 32 anal sphincters ruptured during vaginal delivery. A ruptured internal sphincter was repaired separately and the torn ends of the external sphincter were overlapped and sutured with 3/0 polydioxanone sulphate sutures (Ethicon, Edinburgh, UK). MAIN OUTCOME MEASURES: Bowel function, clinical assessment, anal endosonography and manometry performed at a mean of 140 days after delivery. RESULTS: Eight percent of the women experienced incontinence of flatus. Fifteen percent had persistent sonographic external sphincter defects, and 44% had internal sphincter defects. The maximum mean resting pressure was 58 mmHg (range 37-135) and the mean maximum incremental squeeze pressure 54 mmHg (range 8-104). None had defaecatory difficulty and no complications were encountered with the new technique of repair. CONCLUSIONS: Reservations regarding the feasibility of the overlap technique of primary repair are unfounded, as both subjective and objective outcomes are favourable compared with other studies using end-to-end approximation. A multicentre randomised study of the overlap vs end-to-end repair technique is now planned.

Adolescent↗

Rhabdomyolysis complicating unrecognized hypophosphatemia in an alcoholic patient.

Rhabdomyolysis occurring as a complication of hypophosphatemia has been infrequently described. A 58-year-old male with a history of daily alcohol consumption presented with two generalized tonic clonic seizures secondary to hypovolemic hyponatremia. He was volume-resuscitated, and antiepileptic medication was administered. After three days of hospitalization, the patient developed severe rhabdomyolysis despite the absence of further seizure activity. Serum phosphate levels were depressed. He was treated with intravenous mannitol, alkaline diuresis, and intravenous and oral phosphate supplementation. He recovered uneventfully. Hypophosphatemia can potentially lead to multisystem organ dysfunction including severe rhabdomyolysis. It is, therefore, important to maintain a low threshold for measuring serum phosphate levels in patients admitted to hospital.

Alcoholism↗

Cellular immune response to retinal S-antigen and interphotoreceptor retinoid-binding protein fragments in Eales' disease patients.

The role of retinal antigens in Eales' disease was studied in 24 patients and an equal number of healthy controls. Lymphocyte proliferative responses were tested in vitro against native S-antigen, its uveitopathogenic peptides (peptide M and peptide G), yeast histone H3 peptide and uveitopathogenic fragment of interphotoreceptor retinoid-binding protein (IRBP; R16) to establish their role in the pathogenesis of Eales' disease. Out of 24 Eales' disease patients, 6 showed significant proliferative response against S-antigen, its uveitogenic fragments or IRBP. None among the controls showed any response to any retinal antigen used in this study. There was no statistically significant difference in the response to purified protein derivative between patients and controls. These results suggest that retinal antigens may play a role in the etiopathogenesis of Eales' disease. An extraneous agent that could result in exposure of normally sequestered uveitopathogenic antigens of the immune system, leading to an exuberant immune response in the eye may initiate the disease.

Adolescent↗

Comparison of different techniques for detection of Gal-GalNAc, an early marker of colonic neoplasia.

The tumor marker, D-galactose-beta [1-3]-N-acetyl-D-galactosamine (Gal-GalNAc, also known as T-antigen) can be identified by a very simple galactose oxidase-Schiff's (GOS) reaction either on tissues or on rectal mucus samples from patients with colorectal neoplasms. Gal-GalNAc is expressed in the neoplastic mucosa as well as the remote non-neoplastic mucosa. It is, however, not expressed in colonic mucosa of normal subjects. We studied the expression of Gal-GalNAc by GOS reaction, lectin reactivity and immunocytochemistry in 10 normal, .45 precancerous [5 Crohn's disease, 15 ulcerative colitis (5 without dysplasia and 10 with dysplasia), 25 tubular adenomas], and 25 adenocarcinoma cases. Normal mucosa remote from tubular adenoma and adenocarcinoma was also studied. The GOS method was compared with reactivity of the lectin jacalin and immunostaining with antibody to T antigen (Anti-Tag Ab). GOS reaction was negative in all of the 10 normal specimens. Of the 5 Crohn's disease specimens, 2 were positive and 3 negative. In the 5 ulcerative colitis cases without dysplasia, positive reaction was seen in 2 cases and negative in 3. Of the 10 cases of ulcerative colitis with dysplasia, 5 showed positivity in dysplastic areas, and 3 of these were also positive in remote non dysplastic mucosa. Twenty of 25 tubular adenomas yielded a positive reaction in the adenoma, 14 of them showing positivity also in remote mucosa; 3 cases showed a positive reaction only in remote mucosa. Of the 25 adenocarcinomas, 21 showed a positive reaction in the adenocarcinoma as well as the remote mucosa. GOS reaction was intense in well differentiated adenocarcinoma and weak in poorly differentiated adenocarcinoma. Intense reaction was also seen in the intracellular mucus of some aberrant crypts and morphologically normal crypts remote from adenocarcinoma and tubular adenoma. GOS reaction showed an overall sensitivity of 75.7% and specificity of 100% for cancer and precancerous lesions. Jacalin reactivity was slightly more sensitive (84.3%) but less specific (80%) and Tag Ab reactivity even less sensitive (50%) but as specific (100%) for neoplastic and dysplastic mucosa. We conclude that the detection of the carbohydrate moiety Gal-GalNAc varies with the technique used. Compared to other techniques, GOS reaction is extremely simple and has a high degree of sensitivity and specificity. It can be used for detection of this tumor marker in remote non-neoplastic mucosa of patients with neoplasia or at risk of developing neoplasia. It, therefore, could be used as a cost effective screening test in rectal biopsy specimens of such patients.

Adenocarcinoma↗

Screening relatives of patients with colorectal cancer: the need for continuing education.

Individuals at risk of familial colorectal cancer may be identified from their pedigree but screening guidelines are limited. We wished to assess the opinion of consultants in the region of the value of screening for familial colorectal cancer. All consultant general surgeons and consultant gastroenterologists in South (West) Thames received a questionnaire. This considered the current screening practice of the consultant for colorectal cancer, their opinion of screening patients with a positive family history, and their screening regimen for particular family history scenarios. Seventy-one (62.8%) of consultants replied. Forty-two consultants regularly performed screening colonoscopy (72%) with a median of 15 patients each year (range 2-130). Of these, 23 said that the number screened was limited by resources. Three percent thought regular screening of individual at increased risk of developing colorectal cancer should be yearly, 42% 3 yearly, and 42% 5 yearly. Regarding the risk of dying from colorectal cancer, 14% would screen for a risk of greater than 1 in 6, 45% 1 in 10, 18% 1 in 20, and 10% 1 in 50. Only half of the consultants agreed with published guidelines regarding the age of an index case of colorectal cancer below which they would screen 1st degree relatives. There was substantial variation in suggested screening regimens for the sample family pedigrees. There is wide variation in indications for and clinical practice of screening for familial colorectal cancer and evidence-based refinement of guidelines and increased specialist referral could rationalise resources.

Colorectal Neoplasms↗

A case of lateral facial clefts with Fallot tetralogy, duodenal stenosis and intestinal malrotation: a new multiple congenital anomaly syndrome?

Multiple congenital malformations in a Caucasian female infant are described which include lateral facial clefts, malformed external ears, cleft palate, Fallot tetralogy, duodenal stenosis and intestinal malrotation. There were no associated limb or spinal anomalies. This case appears to be an example of a new multiple congenital anomaly syndrome.

Abnormalities, Multiple↗

Improved high altitude hypoxic tolerance and amelioration of anorexia and hypophagia in rats on oral glutamate supplementation.

BACKGROUND: The objective of this study is to evaluate the efficacy of oral glutamic acid supplementation in promoting hypoxic tolerance. METHODS: The experiments were conducted in albino rats by exposing them to three levels of hypoxia in a simulated environment for varying periods of time. The parameters studied include: gasping time at 35,000 ft (10,668 m), food and water intake, and heart to body weight (b.w.) ratio at 25,000 ft (7620 m), tolerance to composite stress at 15,000 ft (4572 m) and biodistribution of glutamate (glu). RESULTS: Supplementation of Glu (27 mg x kg(-1) b.w.) as glutamic acid dissolved in normal saline resulted in 4.8 times enhanced hypoxic tolerance (time taken for appearance of first gasp), 23% body weight gain and 24% increase in food consumption over control during hypoxia. When animals were subjected to composite stress of cold, hypoxia and restraint (CHR), the Glu fed animals showed higher resistance to fall in rectal temperature than the control group. Hypoxia significantly enhanced heart to body weight ratio compared with control, and Glu supplementation reduced and brought it down to that of control. CONCLUSION: The study reveals that Glu in optimal doses may be a conditionally essential amino acid resulting in enhanced tolerance to hypoxia and cold.

Administration, Oral↗

Psychosocial characteristics of literate blinds: a study.

Blindness leaves a person in a state of physical, psychosocial and economic dependence. Aberrant mental attitudes and even frank mental illnesses can develop among the aged blinds. The present study shows that acceptance towards their disability was much higher (in 68.75% cases) among the aged blinds in group 'A' (mean age 42.2 years) than the younger student (in 47% cases) in group 'B' (mean age 17.6 years) All the younger blinds were found to be optimistic for their future but the level for this mental attitude among older subjects was relatively lower (in 68.75% cases). The aberrant mental attitude like rejection, guilt and aggressiveness which reflected negative attitude towards life were more prevalent among students. Older blinds were found to be relatively more shameful for their disability (in 43.75% cases). The negative attitude towards life was evaluated to be present among 12.5% cases in group 'A' and among 76.5% cases in group 'B'. Anxiety and depression were the mental illnesses evaluated among blind and were displayed by 6.25% and 0% cases in group 'A' i.e. the group of teachers and trained workers and in 35.3% and 43.7% cases among group 'B' i.e. the group of blind students respectively. Aberrant mental attitudes have shown no definite relation with the age at the onset of blindness or otherwise they appeared to change with age.

Adolescent↗

Monte Carlo simulation of photon scattering in biological tissue models.

Monte Carlo simulation of photon scattering, with and without abnormal tissue placed at various locations in the rectangular, semi-circular and semi-elliptical tissue models, has been carried out. The absorption coefficient of the tissue considered as abnormal is high and its scattering coefficient low compared to that of the control tissue. The placement of the abnormality at various locations within the models affects the transmission and surface emission of photons at various locations. The scattered photons originating from deeper layers make the maximum contribution at farther distances from the beam entry point. The contribution of various layers to photon scattering provides valuable data on variability of internal composition. Introduction.

Models, Anatomic↗

Distribution of the interstitial cells of Cajal in the human anorectum.

The interstitial cells of Cajal are proposed to have a role in the control of gut motility. The aim of this study was to establish the distribution of interstitial cells of Cajal in the wall of the normal human anorectum. Interstitial cells of Cajal express the proto-oncogene c-kit. Interstitial cells of Cajal were identified in the colon by immunohistochemical staining, using a rabbit polyclonal anti-c-kit antibody. Anorectal tissue was obtained at surgical resection for carcinoma of the colorectum. Density of interstitial cells of Cajal was graded. Statistical analysis was performed using chi2 tests. In the longitudinal and circular muscle layers of the rectum interstitial cells of Cajal were seen in the bulk of the muscle layer. In the intermuscular plane interstitial cells of Cajal encased the myenteric plexus. Interstitial cells of Cajal were found at the inner margin of the circular muscle and in association with neural elements of the submuscular plexus. Within the internal anal sphincter interstitial cells of Cajal were infrequently scattered among the muscle fibres. The density of interstitial cells of Cajal in the internal anal sphincter was significantly lower than that observed in the circular muscle layer of the rectum (P = 0.014). In conclusion, interstitial cells of Cajal are evenly distributed in the layers of the muscularis propria of the rectum, but have a lower density in the internal anal sphincter.

Aged↗

Ethnic differences in expression of susceptibility marker(s) in rheumatic fever/rheumatic heart disease patients.

The ability of monoclonal antibodies (MAb) against a human B lymphocyte alloantigen has been suggested to discriminate between rheumatic fever "susceptible" individuals and persons with a lower risk of developing RF. However, while such MAb have been reported to identify a majority of RF/RHD patients in some populations, a reduced discriminatory ability has been observed in others. Antigenic variation in the RF marker(s) may exist among ethnic groups which reduce the discriminatory ability of these monoclonal antibodies. We developed MAb using B lymphocytes from RF patients of North Indian ethnic origin. In this same population we compared the new MAb (PGI/MN II) with a previously described MAb of Caucasian ethnic origin (D8/17). In three groups: acute rheumatic fever patients (no evidence of previous attacks of rheumatic fever), patients with chronic rheumatic heart disease and normal controls from the same population, we found a greater discriminating ability of PGI/MNII MAb to identify Indian RF/RHD patients than with the D8/17 MAb. Further, sixty percent of 142 siblings of the RF/RHD patients were "positive" when tested with PGI/MN II. The data from these studies suggest that before such MAb can be used for identification of RF "susceptibles" in public health programs, variation among ethnic populations must be assessed.

Adolescent↗

Recognizable inherited syndrome of progressive central nervous system degeneration and generalized intracranial calcification with overlapping phenotype of the syndrome of Aicardi and Goutières.

Five boys and two girls from a large consanguineous British Muslim family of Pakistani origin are described. All presented from infancy to early childhood with progressive moderate to severe developmental delay, postnatal microcephaly, spastic quadriplegia, refractory seizures, and visual handicap. Cerebrospinal fluid (CSF) pleocytosis was present in three children. Neuroimaging with computerized tomography on three boys and a girl showed generalized cortical atrophy, dilatation of the lateral, third, and fourth ventricles, widening of the surface CSF spaces, hypoplasia of the posterior fossa structures, and multiple and solitary calcifications in the cerebral cortex and punctate calcifications involving basal ganglia, cerebellum, and the Sylvian fissure. Histopathological examination of the brain from three boys and one girl confirmed generalized cortical and cerebellar atrophy with widespread calcifications within the cortical grey and white matter, the basal ganglia, the cerebellum, and in some areas along the capillaries. Investigations excluded a possible nongenetic cause. Parental consanguinity favor autosomal recessive inheritance. This appears to be a recognizable syndrome overlapping the syndrome of Aicardi and Goutières (MIM 225750).

Basal Ganglia Diseases↗

Allylamine and beta-aminopropionitrile induced aortic medial necrosis: mechanisms of synergism.

We have developed a model of aortic smooth muscle necrosis in adult Sprague Dawley rats by feeding them two vascular toxins (allylamine HCl, or AA, and beta-aminopropionitrile, or betaAPN) in concert for 10 days. Either toxin given alone does not cause aortic lesions. In order to shed light on the mechanism of the synergistic action of these two toxins we fed known modulators of AA or betaAPN toxicity to rats concurrently with the two toxins. As modulators we used (a) semicarbazide (98 mg/kg/day, given 4 h prior to toxins), a known inhibitor of the vascular enzyme SSAO which metabolizes AA; (b) L-cysteine (1.5% in rat chow, beginning 3 days prior to toxins), which has been shown to reduce the toxic effects of betaAPN; and (c) phenelzine sulphate (3 mg/kg/day, given 4 h prior to toxins), an inhibitor of SSAO and potentiator of betaAPN toxicity. Rats were fed various combinations of the toxins and modulators by gavage: water (n = 8); (AA, 100 mg/kg/day) AA + phenelzine (n = 8); AA + semicarbazide (n = 8); AA + L-cysteine (n = 11); (betaAPN, 1 g/kg/day) betaAPN + phenelzine (n = 8); betaAPN + semicarbazide (n = 8); betaAPN + L-cysteine (n = 8); (AA, 100 mg + betaAPN, 1 g/kg/day) AA + betaAPN + phenelzine (n = 9), AA + betaAPN + semicarbazide (n = 8); AA + betaAPN + L-cysteine (n = 12); phenelzine (3 mg/kg/day) (n = 4); semicarbazide (98 mg/kg/day) (n = 4) and L-cysteine (1.5% in rat chow) (n = 4). We found that phenelzine sulphate (a drug previously used in the treatment of hypertension) when given with AA reproduced the AA + betaAPN induced aortic lesions. Phenelzine + betaAPN caused no lesions, but when combined with AA + betaAPN, aortic lesions were intensified and included marked secondary degeneration of the vascular wall. Semicarbazide was found to completely obviate the vascular toxicity of AA + betaAPN. L-Cysteine feeding markedly decreased the incidence and severity of vascular lesions in AA + betaAPN treated rats, but did not change the incidence or severity of heart lesions caused by AA alone. These data indicate that the synergistic necrotizing toxicity of AA + betaAPN is primarily an AA effect. We postulate that some modulating influence of betaAPN (or phenelzine) on tissue distribution, metabolism, or detoxification pathways of AA increases AA's acute vascular toxicity, whereas semicarbazide offers protection by inhibiting the initial deamination of AA to a highly reactive aldehyde.

Allylamine↗

Gene therapy with p53 and a fragment of thrombospondin I inhibits human breast cancer in vivo.

We recently reported that a p53 encoding plasmid (BAP-p53) complexed to liposomes administered intravenously markedly attenuates the growth of a malignant human breast tumor. We now have found that systemically delivered liposomes complexed to a plasmid expressing an established antiangiogenic peptide of thrombospondin I (BAP-TSPf) decreased the growth of MDA-MB-435 tumors compared to controls in nude mice. Compared to BAP-p53, the BAP-TSPf group had a similar antitumor efficacy. More importantly, liposomes complexed with BAP-TSPf and BAP-p53 synergistically decreased the growth of MDA-MB-435 tumors when compared to either BAP-p53 or BAP-TSPf alone. Furthermore, we also determined that the combination therapy of p53 and TSPf inhibited endothelial cells in vitro more than either p53 or TSPf alone. There was also a significant decrease of the blood vessel density in the combination p53 and TSPf treatment group compared to the control groups. These results suggest that liposomes complexed to a tumor suppressor and antiangiogenic genes may be effective in treating metastatic tumors.

Animals↗

In vivo gene therapy with a cationic polymer markedly enhances the antitumor activity of antiangiogenic genes.

A cationic polymer, Superfect, when complexed to the therapeutic genes, p53 and a TSP fragment, displays a much greater antitumor activity compared to cationic liposomes. At the dosages used, this polymer did not demonstrate any nonspecific antitumor effects in contrast to the liposome carriers. These in vivo findings should further stimulate the development of carrier polymers as well as expedite the evaluation of several antiangiogenic genes.

Animals↗

Classic adamantinoma in a 3-year-old.

Classic adamantinoma of the long bones is a rare, low-grade malignant neoplasm arising most often in the tibia and usually in patients during the second to fifth decades. Although adamantinomas have been described in children, the histologic pattern in this age group is different from that seen in adults and resembles osteofibrous dysplasia. The usual pattern of adamantinoma in children has been termed "differentiated adamantinoma" and follows a benign course. We report a case of adamantinoma in the proximal tibia of a 3-year-old patient. The lesion had abundant epithelial component with formation of keratin pearls, a pattern that has been described only in classic adamantinoma occurring in adults. Since differentiated adamantinomas are essentially benign and classic adamantinomas are low-grade malignancies, the finding of a classic variant at this young age raised important therapeutic and prognostic issues.

Ameloblastoma↗

The role of oxidative stress in the genesis of heart disease.

Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery of superoxide dismutase in 1969. This antioxidant enzyme is responsible for the dismutation of superoxide radical--a free radical chain initiator. A fine balance between free radicals and a variety of endogenous antioxidants is believed to exist. Any disturbance in this equilibrium in favour of free radicals causes an increase in oxidative stress and initiates subcellular changes leading to cardiomyopathy and heart failure. Our knowledge about the role of free radicals in the pathogenesis of cardiac dysfunction is fast approaching the point where newer therapies employing antioxidants are in sight.

Cardiomyopathies↗