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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 127 records · Page 7Linked to original sources

Epstein-Barr virus-related posttransplantation lymphoproliferative disorder involving pancreas allografts: histological differential diagnosis from acute allograft rejection.

The clinical and pathological features of acute pancreas allograft rejection and involvement of the graft by posttransplantation lymphoproliferative disorders (PTLD) overlap. Because the treatment is diametrically opposite in these two types of lesions, an accurate diagnosis is essential. The histological features in pancreas allograft needle biopsy specimens (n=7) and pancreatectomies (n=4) from four patients with Epstein-Barr virus (EBV)-related PTLD were compared with the material from 14 patients who did not develop PTLD after 12 to 58 months of follow-up and whose biopsy specimens (n=10) and pancreatectomies (n=10) showed rejection-related heavy or atypical inflammatory infiltrates. Features typical of rejection included most (>75%) being of mixed small and large, activated-appearing T lymphocytes, a smaller component of mature plasma cells, and variable numbers of eosinophils. Cytologically atypical cells were always a minority (< 10%). The inflammation involved the septal spaces with proportional involvement of the exocrine tissue, veins, ducts, and arteries. The inflammation was particularly targeted against the acini and was associated with acinar cell damage. Features characteristic of PTLD were nodular and expansile infiltrates, composed of a significant proportion of atypical, plasmacytoid B cells (40% to 70% of the infiltrate); Reed-Sternberg-like cells were noted in two patients. The infiltrates involved the parenchyma randomly with no apparent affinity for the acinar tissue. Extensive infiltration of the peripancreatic soft tissues was common. Arterial walls were not involved in PTLD unless there was concurrent acute vascular rejection. Features identified in both conditions were foci of necrosis and infiltration of venous walls with associated endotheliitis. Samples with concurrent PTLD and acute rejection showed combinations of these features. In situ hybridization for EBER (Epstein-Barr-encoded RNAs) was positive only in the samples from patients with PTLD. Based on the assessment of morphological differences and the selective use of relatively simple ancillary techniques, PTLD can be correctly diagnosed even in small tissue samples such as needle biopsy specimens. An early diagnosis will lead to the appropriate treatment.

Acute Disease↗

Genetic rearrangements leading to disruption of heterologous gene expression in mycobacteria: an observation with Escherichia coli beta-galactosidase in Mycobacterium smegmatis and its implication in vaccine development.

Different mycobacteria carrying cloned genes for heterologous protective antigens have been proposed as vaccine vehicles. In this study, the stability of the expression of beta-galactosidase was studied in Mycobacterium smegmatis using integrative (pMV361::lacZ) and replicative (pMV261::lacZ) vectors. Recombinant M. smegmatis forms blue colonies on X-gal plates. Occasional white mutants encountered while plating on X-gal plates were genetically analysed. The loss of lacZ phenotype was due to insertion of an IS element in lacZ gene of integrative vector whereas in case of replicative vectors, loss of lacZ phenotype was due to deletions of different sizes in the lacZ gene and the Phsp60 promoter region. The frequency of such events was rare, 1.7 x 10(-5) in integrative vector and 2 x 10(-3) in the case of replicative vector. The integrative vector seemed more stable in terms of expression of foreign genes in mycobacteria. Hence, the rearrangements reported in the present study warrant serious consideration before implementing mycobacteria as recombinant vaccines.

Bacterial Vaccines↗

Polymorphous low-grade adenocarcinoma of the sublingual gland.

A case of polymorphous low-grade adenocarcinoma occurring in the sublingual gland is described, followed by a brief discussion on the differential diagnosis. This is the first case ever reported of this entity occurring in the sublingual gland. This paper brings into question the early belief that this tumor is restricted to intraoral minor salivary glands.

Adenocarcinoma↗

Biliary lactoferrin concentrations are increased in active inflammatory bowel disease: a factor in the pathogenesis of primary sclerosing cholangitis?

1. One hypothesis for the link between inflammatory bowel disease and primary sclerosing cholangitis is that neutrophil activators, such as bacterial chemotactic peptides or neutrophil granule products themselves, pass from the inflamed colon to the liver via an enterohepatic circulation. However, there are no data on biliary concentrations of neutrophil granule products in patients with active and inactive inflammatory bowel disease.2. Gall bladder bile was obtained at laparotomy from 42 patients with ulcerative colitis and 21 patients with Crohn's disease. Biliary lactoferrin and myeloperoxidase concentrations were quantified by ELISA.3. In active ulcerative colitis, the mean lactoferrin concentration in gall bladder bile of 2.8+/-0.40 mg/l was higher than that seen after colectomy (1.2+/-0.11 mg/l; P<0.0001) or in patients with pouchitis (1.8+/-0.34 mg/l; P=0.06). In active Crohn's colitis, the mean lactoferrin concentration was 3.7+/-0.9 mg/l, compared with 1.1+/-0. 24 mg/l in the post-colectomy group (P<0.05) and 3.1+/-0.71 mg/l in those with active ileitis or ileocolitis. In contrast, biliary myeloperoxidase concentrations were low and comparable in all groups, with a mean concentration in the 42 patients with ulcerative colitis of 11.2+/-1.9 microgram/l.4. In contrast to myeloperoxidase, biliary lactoferrin concentrations are increased in active ulcerative colitis and Crohn's disease, and fall with colectomy and with disease remission. These findings indirectly support the hypothesis that bacterial chemotactic peptides (which induce selective degranulation of neutrophil secondary granules), and/or lactoferrin itself, undergo an enterohepatic circulation.

Acute Disease↗

Abdominal ultrasonography in the diagnosis of colonic cancer.

BACKGROUND: Colonic cancer is normally diagnosed by barium enema or colonoscopy. Neither investigation is ideal, especially in the elderly patient. This study investigates the potential role of abdominal ultrasonography in the diagnosis of colorectal carcinoma. METHODS: Fifty-four patients with known or suspected colonic carcinoma were referred for abdominal ultrasonography. A single radiologist performed scans on these patients and the site of any colonic mass or wall thickening considered to be consistent with a colonic carcinoma was reported. All carcinomas were confirmed by histology on tissue obtained at colonoscopy or surgery against which the ultrasonographic diagnosis was compared. Colonic masses detected in patients undergoing routine abdominal ultrasonography for abdominal symptoms were also reported. RESULTS: Forty-five of the 54 patients referred had colonic carcinoma and abdominal ultrasonography detected 43 of the tumours and correctly identified the site of 41. The sensitivity, specificity and accuracy of abdominal ultrasonography in the detection of colonic tumours considered to be consistent with a colonic carcinoma was 96, 67 and 91 per cent respectively. Seven tumours were identified in patients referred before any other investigation had been carried out. CONCLUSION: Abdominal ultrasonography may detect a colonic mass or wall thickening consistent with a colonic carcinoma with a high degree of accuracy and may be useful when barium enema or colonoscopy is not possible.

Colonic Neoplasms↗

Adjuvant therapy for resectable rectal and colonic cancer.

BACKGROUND: Recurrence of rectal and colonic carcinoma remains substantial despite apparently curative surgery. Adjuvant therapy has been applied to improve prognosis. METHODS: This review evaluates the use of adjuvant therapy in the management of resectable rectal and colonic carcinoma. It assesses critically the evidence supporting the addition of radiotherapy, chemotherapy, chemoradiotherapy and other treatment modalities to optimal surgery. RESULTS: In the case of rectal tumours, preoperative is more effective than postoperative radiotherapy; It can significantly reduce the incidence of local tumour recurrence. A number of trials have tended towards showing a survival advantage and a recent large randomized trial has shown a significant improvement in survival in patients with Dukes C tumours. Postoperative chemoradiotherapy is associated with a survival benefit and is standard therapy in the USA, although it is associated with increased toxicity. The effectiveness of preoperative chemoradiotherapy is currently being investigated. Postoperative fluorouracil-containing chemotherapy has resulted in a survival advantage in patients with Dukes C colonic tumours; such therapy may be administered either systemically or intraportally. The evidence of benefit with rectal tumours is more limited. Immunotherapy has been studied to a limited extent and the use of a tumour-directed monoclonal antibody has produced a survival advantage in a single trial. CONCLUSION: Preoperative radiotherapy and postoperative chemoradiotherapy can produce a survival advantage in patients with Dukes C rectal carcinoma and reduce local recurrence. Postoperative fluorouracil-containing chemotherapy can produce a survival advantage in those with Dukes C colonic cancer. The optimal use and combination of adjuvant therapy remains uncertain.

Antineoplastic Agents↗

Glutaraldehyde cross-linked collagen in the treatment of faecal incontinence.

BACKGROUND: The treatment of faecal incontinence secondary to internal anal sphincter dysfunction is unsatisfactory. The aim of the study was to evaluate the efficacy of anal glutaraldehyde cross-linked (GAX) collagen injections in patients with a surgically incorrectable disorder. METHODS: Seventeen patients were studied: nine had idiopathic faecal incontinence, three had incontinence following haemorrhoidectomy, two following internal sphincterotomy, two following an internal sphincter defect from obstetric injury and one following treatment for fistula in ano. All patients were refractory to conservative treatment and were unsuitable for surgical repair. All had anorectal physiology and endoanal ultrasonography before and after GAX collagen injections. RESULTS: All patients tolerated the injection without side-effects. All patients had an intact external anal sphincter. Following injection, 11 patients showed marked symptomatic improvement. One patient reported symptomatic improvement but remained in clinical grade 3, and two reported minimal improvement. There was no improvement in three patients, but one of these had a repeat injection and showed significant improvement subsequently. CONCLUSION: Injection of GAX collagen in the anal canal is a simple and well tolerated method of treating faecal incontinence due to internal sphincter dysfunction. Early results suggest it provides an easy and reliable alternative to the currently available methods that are often unsuccessful and at best unpredictable.

Adult↗

Ultrasonographically-guided fine-needle aspiration cytology in the diagnosis of colonic lesions.

BACKGROUND: The use of fine-needle aspiration cytology (FNAC) in the diagnosis of colonic lesions was investigated. METHODS: Some 22 patients (median age 71 years) with a colonic lesion identified on abdominal ultrasonography underwent ultrasonographically-guided FNAC using a 21-G needle. The sample was checked immediately by a cytopathologist for adequacy. RESULTS: Eighteen patients had colonic carcinoma; aspiration cytology detected malignant epithelial cells consistent with colonic carcinoma in 17 patients and severely dysplastic cells in one patient. The sensitivity and specificity of ultrasonographically-guided FNAC in the diagnosis of colonic carcinoma was 94 and 100 per cent respectively. The remaining four patients had a diagnosis of ileocaecal tuberculosis, ileocaecal Crohn's disease, and metastatic adenocarcinoma in the liver with no identifiable primary (two patients). One demonstrated granulomata, grew acid-fast bacilli and the patient was treated for tuberculosis. One had inflammatory cells and the patient was found to have Crohn's disease on histology. The remaining two patients had confirmed metastatic adenocarcinoma in the liver on aspiration cytology but suspected colonic lesions were found to be benign on cytological examination and no primary lesion was subsequently demonstrated. There were no complications of FNAC and patients complained of minimal discomfort. There has been no evidence of tumour recurrence with a median follow-up of 12 (range 1-25) months. CONCLUSION: Ultrasonographically-guided FNAC is a valid method for the diagnosis of colonic tumours.

Adult↗

Posttransplantation lymphoproliferative disorder associated with OKT3 and decreased antiviral prophylaxis in pancreas transplant recipients.

Between September 1994 and October 1995, we diagnosed and treated four cases of early onset posttransplantation lymphoproliferative disorder (PTLD) occurring within 62 days of pancreas transplantation. The development of PTLD was associated with both a significantly higher total muromonab-CD3 (OKT3) dose and a lack of ganciclovir/acyclovir prophylaxis, but it was not associated with the total dose of antithymocyte globulin or cytomegalovirus serostatus. All four patients were treated aggressively and survived without evidence of recurrent PTLD more than 1.5 years later. We conclude that the use of a high total dose of OKT3 puts pancreas transplant recipients at increased risk for early onset PTLD, while ganciclovir/acyclovir prophylaxis may help to prevent this disorder; however, if early onset PTLD does occur in these patients, aggressive therapy can lead to a favorable outcome.

Acyclovir↗

Variable phenotype in Kaufman-McKusick syndrome: report of an inbred Muslim family and review of the literature.

Multiple congenital anomalies (MCA) in two siblings and digit abnormalities in four related individuals from a large highly inbred Muslim family are described. The pattern of MCA is consistent with the autosomal recessive Kaufman-McKusick syndrome [MIM 236700]. The present report reviews the previously published reports on this uncommon MCA dysmorphic syndrome and draws attention to the marked variation in the phenotype.

Abnormalities, Multiple↗

Antibiotic use, childhood affluence and irritable bowel syndrome (IBS).

BACKGROUND: Antibiotics cause well defined short-lived disturbances in bowel habit. There is evidence to suggest that antibiotics may play a role in the pathogenesis of IBS. Atopy has been associated with small household size in childhood and could also play a role in IBS. We conducted a survey examining the relation of drug use and other epidemiological correlates of IBS. SETTING: General practice health screening clinic. SUBJECTS AND METHODS: 421 subjects (46% male, mean age 47 years (range 18-80 years) attending a general practice health screening clinic were interviewed by a research nurse and completed a previously validated questionnaire. Symptoms of IBS were said to be present if abdominal pain with 2 or more Manning criteria symptoms occurred more than once per month over the previous 6 months. RESULTS: 48 subjects had symptoms of IBS. The following were strongly related to its presence: antibiotic use [adjusted OR 3.70 (1.80-7.60)], female sex and childhood living density < 1 person per room [OR 3.47 (1.57-7.64)], manual father's occupation [OR 0.35 (0.16-0.76)]. The use of NSAIDS, H2 antagonists or other types of medication was not greater in this group. CONCLUSION: Antibiotic use is associated with IBS. The association with antibiotic use requires testing in prospective studies. Privileged childhood living conditions were also an important risk factor which is consistent with an allergic aetiology for IBS.

Adolescent↗

Regional and transmural density of interstitial cells of Cajal in human colon and rectum.

The interstitial cells of Cajal (ICC) are thought to play an important role in the control of gut motility. The regional and transmural pattern of distribution of ICC in the normal human colon and rectum was evaluated with immunohistochemistry using an anti-c-kit antibody. The transmural distribution of ICC was constant throughout the whole colon, the density of ICC was significantly greater at the myenteric plexus than at either the longitudinal or circular muscle layers, and in the rectum the transmural distribution was more even. Regionally, at the myenteric plexus, the transverse colon had a significantly greater density of ICC compared with the right colon (P = 0.038), left colon (P = 0.006), and rectum (P = 0.008). The pattern of distribution of ICC identified in this study is consistent with the proposed roles of ICC as colorectal pacemakers, intermediaries of the neural control of muscle activity, and coordinators of colorectal muscle activity. The highest density of ICC was at the myenteric plexus of the transverse colon, which is the proposed region of pacemaking activity.

Adult↗

Apocrine metaplasia: mammographic and sonographic appearances.

OBJECTIVE: Our objective was to evaluate the mammographic and sonographic appearances of apocrine metaplasia and correlate imaging and histopathologic findings. MATERIALS AND METHODS: Retrospective review of 408 lesions in 318 consecutive patients undergoing core needle biopsy (n = 370) or fine needle aspiration (n = 38) revealed 46 cases of apocrine metaplasia. In 17 of these cases, apocrine metaplasia represented more than 50% of the lesion sampled; these 17 lesions formed the basis for analysis. RESULTS: On mammography, all 17 cases appeared as new or enlarging equal-density (n = 15) or low-density (n = 2) masses with an average size of 12.8 mm. Borders were microlobulated in 59% (10/17), macrolobulated in 29% (5/17), and circumscribed or oval in 12% (2/17). Sonography revealed a lobulated mass containing a cluster of small (2- to 5-mm) anechoic foci and intervening septae in 77% (10/13) of cases. A discrete hypoechoic solid component was seen in 23% of cases (3/13). Posterior acoustic enhancement was seen in 85% of cases (11/13). In 65% of lesions (11/17), we noted a decrease in size or total resolution during biopsy or fine needle aspiration. Histopathologic examination showed the typical appearance of dilated cystic acini lined by apocrine metaplastic epithelium. CONCLUSION: On mammography, the combined findings of an equal- or low-density microlobulated or lobulated mass that corresponds on sonography to a cluster of small (2- to 5-mm) anechoic foci with intervening septae should suggest the diagnosis of focal apocrine metaplasia. With radiologists' increasing experience, follow-up, rather than biopsy, of such typical-appearing lesions may be adequate.

Adult↗

Predictive value of specimen radiography for core needle biopsy of noncalcified breast masses.

OBJECTIVE: Our objective was to determine the predictive value of specimen radiography for large core (14-gauge) needle biopsy of noncalcified breast masses. SUBJECTS AND METHODS: Eighty-four biopsies of 83 breast masses yielded 403 specimens. Specimens showing dense material on specimen radiography were predicted to be diagnostic; specimens showing intermediate- or low-density material were predicted to be nondiagnostic. Specimen radiographic and histopathologic findings were correlated for each specimen using vital dyes to mark individual specimens. RESULTS: Of the 403 specimens, 307 (76%) contained diagnostic material representative of the lesion, with a specific diagnosis achieved for 82 (99%) of 83 lesions (62 benign, 20 malignant). Of the 293 passes containing dense material, 268 (91%) proved to be diagnostic; 11 (18%) of 62 specimens containing only low-density material proved to be diagnostic. Of the 25 (9%) of 293 specimens containing radiographically dense but nondiagnostic material, 18 (72%) showed focal fibrosis and had missed the lesion; 15 (83%) of 18 such specimens were obtained in dense parenchyma. The positive predictive value of specimen radiography was 13 (100%) of 13 in fatty breasts; 77 (96%) of 80 in breasts with minimal scattered fibroglandular elements; 91 (94%) of 97 in heterogeneously dense breasts; and 35 (70%) of 50 in breasts with extremely dense parenchyma. Of the 16 lesions sampled stereotactically, specimen radiography helped assess the inadequacy of initial sampling in three (19%). In six (9%) of 68 sonographically guided biopsies, only one or two specimens could be obtained; specimen radiography helped us predict whether material was adequate for diagnosis. CONCLUSION: Radiography of core specimens obtained from noncalcified breast masses accurately reveals the adequacy of sampling unless the breast parenchyma is extremely dense. Such immediate assessment can help ensure adequate material from lesions that are difficult to biopsy and can thereby improve the diagnostic yield of large core needle breast biopsy.

Adolescent↗

Diabetic peripheral neuropathy. Effectiveness of electrotherapy and amitriptyline for symptomatic relief.

OBJECTIVE: To evaluate the efficacy of combining electrotherapy with amitriptyline for the management of chronic painful peripheral neuropathy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients (n = 26) with peripheral neuropathy were treated with amitriptyline. After 4 weeks, those patients (n = 23) who failed to respond to amitriptyline or who only had partial relief were randomized between a sham treatment group (control) or an electrotherapy group. Transcutaneous electrotherapy was given for 12 weeks by a portable unit (H-wave machine) that generated a biphasic exponentially decaying waveform (pulse width 4 ms, 25-35 V, > or = 2 Hz). The degree of pain and discomfort was graded on a scale of 0-5. An analog scale was used to record the overall change in symptoms. RESULTS: Amitriptyline produced some degree of symptomatic relief in 15 (60%) of the 26 patients by the 4th week; pain scores decreased from 3.8 +/- 0.1 to 2.9 +/- 0.2 (P < 0.1) and the overall reduction in pain was 26 +/- 5% on an analog scale. In the amitriptyline plus sham treatment group (n = 9), pain scores declined from 2.8 +/- 0.3 to 1.9 +/- 0.5 (P < 0.03) and the overall reduction in pain was 55 +/- 12%, suggesting a procedure-related placebo effect. In the group receiving combined electrotherapy and amitriptyline (n = 14), symptomatic improvement occurred in 12 (85%) patients. Five (36%) of the patients in this group became asymptomatic. Pain scores declined from 3.2 +/- 0.2 to 1.4 +/- 0.4 (P < 0.01) and the overall reduction in pain was 66 +/- 10%. The degree of reduction in pain scores and the incremental relief (above the amitriptyline effect) were significantly greater (P < 0.03) with electrotherapy as compared with sham treatment. The outcomes indicate a substantial beneficial effect of electrotherapy over and above any placebo influence. CONCLUSIONS: Our clinical observations suggest that transcutaneous electrotherapy is effective in reducing the pain associated with peripheral neuropathy. This form of therapy may be a useful adjunctive modality when it is combined with a pharmacological agent, such as amitriptyline, to augment symptomatic relief.

Adult↗