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Biomedical subjects

B Singh

Publications and source records attributed to B Singh.

At least 289 records · Page 16Linked to original sources
PubMed1998

Impact of comorbidity on outcome of young patients with head and neck squamous cell carcinoma.

BACKGROUND: Comorbid conditions have a significant impact on the actuarial survival of patients with head and neck cancer. However, no studies have evaluated the impact of comorbidity on tumor- and treatment-specific outcomes. This study was performed to evaluate the impact of comorbidity, graded by the Kaplan-Feinstein comorbidity index (KFI) on the incidence and severity of complications, disease-free interval, and tumor-specific survival in patients undergoing curative treatment for head and neck cancer. METHODS: A multi-institutional, retrospective cohort of 70 patients 45 years of age and under with head and neck squamous cell carcinoma (SCC) presenting over an 11-year period was studied. RESULTS: Advanced comorbidity (KFI grade 2 or 3) was present in 21 patients (30%). Patients with advanced comorbidity did not differ from patients with low-level comorbidity (KFI grades 0 or 1) in sex distribution, race, presence of human immunodeficiency virus (HIV) infection, tobacco use, location of primary lesion, stage at presentation, pathologic differentiation of the tumor, or type of initial treatment. The overall incidence of treatment-associated complications was similar between the groups (57% versus 49%; p > 0.05), but a higher proportion of patients with advanced comorbidity developed high-grade complications (24% versus 6%; p = .04). The median disease-free interval (11.1 months versus 21.6 months; p = .045) and tumor-specific survival (13.7 months versus 57.6 months; p = .03) was poorer for patients with advanced comorbidity. The effects of comorbidity on survival remained significant even after adjusting for the confounding effects of HIV status and tumor stage (p = .05). CONCLUSIONS: The presence of comorbid conditions has a significant impact on tumor- and treatment-specific outcomes. Although the presence of advanced comorbid conditions is not associated with an increase in the rate of treatment-associated complications, complications tend to be more severe in this population. More importantly, advanced comorbidity has a detrimental effect on the disease-free interval and tumor-specific survival in patients with head and neck cancer, independent of other factors. This suggests that comorbidity may impact on tumor behavior, presumably by altering the host's response to cancer. Accordingly, to be more predictive and reliable, the current staging system for head and neck cancer should include a description of the patient's comorbidity.

Adult↗
PubMed1998

Development of an I-Ag7-expressing antigen-presenting cell line: intrinsic molecular defect in compact I-Ag7 dimer generation.

Insulin-dependent diabetes mellitus (IDDM) results from chronic, T-cell dependent, autoimmune destruction of the insulin-producing beta-cells in the Langerhans' islets of the pancreas. Non-obese diabetic (NOD) mice spontaneously develop IDDM that resembles human type I diabetes. The susceptibility to diabetes in the NOD strain is a complex polygenic trait that determines a phenotype of immune alterations. The unique MHC class II molecule expressed by NOD mice (I-Ag7) plays a major role in the development of disease. Recently, it has been reported that I-Ag7 molecules generate a lower proportion of compact alphabeta heterodimers, compared to other haplotypes. However, it is not clear whether this reflects an intrinsic defect of this molecule to bind peptide stably or is the result of abnormal processing and/or peptide loading into the I-Ag7 molecule. Our aim was to develop and characterize a suitable antigen-presenting cell (APC) that expressed I-Ag7 in the context of a non-diabetes-prone antigen processing and presentation machinery. Here, we report the generation of a mouse DAP.3 fibroblast cell line (DAP.3Ag7) that constitutively expresses high levels of I-Ag7. Using DAP.3 cells transfected with I-Ag7 or I-Ak, we show that the expression of compact dimers in the same cell type is proportionally less for I-Ag7 molecules than for I-Ak molecules, implying an intrinsic defect of the I-Ag7 molecule as the cause for the low generation of compact dimers. However, DAP.3Ag7 cells are able to process and present antigen, as indicated by I-Ag7-dependent IL-2 production by a GAD67-specific NDO T-cell hybridoma after stimulation with GAD and live, but not fixed, DAP.3Ag7 cells. The IL-2 response to GAD when presented by DAP.3Ag7 was significantly higher than the response to GAD presented by NOD splenocytes. Based on these data, we conclude that the low generations of compact dimers is an intrinsic feature of I-Ag7 molecules and not affected by other genes in the NOD background. The DAP.3Ag7 cell line should be a valuable tool with which to dissect the role of the I-Ag7 molecule in antigen presentation and T-cell activation in NOD mice, which clearly contributes to the development of IDDM.

Animals↗
PubMed1998

Characterization of novel T-cell epitopes on 65 kDa and 67 kDa glutamic acid decarboxylase relevant in autoimmune responses in NOD mice.

It has recently been shown that the T-cell mediated immune responses to glutamic acid decarboxylase (GAD) play an important role in insulin-dependent diabetes mellitus (IDDM) in NOD mice. However, specific epitopes responsible for eliciting these responses remain unresolved. In this study, the T-cell epitopes involved in GAD-specific immune responses in NOD mice were characterized. By priming NOD mice with GAD65, three new GAD65 epitopes (GAD65 78-97, GAD65 202-221, GAD65 217-236) distinct from those previously reported were found. Furthermore, our investigations into the fine determinant specificity of GAD67 revealed two additional GAD67-specific peptide epitopes (GAD67 28-47, GAD67 42-61). Two of the GAD65 epitopes (GAD65 202-221 and GAD65 217-236) are shared between GAD65 and GAD67. Spontaneous immune responses to these peptides were found in pre-diabetic and diabetic mice and differential patterns of responses to these peptides were observed depending on the age of the mice, disease status, or if the mice were protected from diabetes by adjuvant immunotherapy. Characterization of these new epitopes will help in the elucidation of autoimmune responses to GAD in IDDM.

Age Factors↗
PubMed1998

Endogenous immune response to glutamic acid decarboxylase (GAD67) in NOD mice is modulated by adjuvant immunotherapy.

We have shown that immunization of non-obese diabetic (NOD) mice with adjuvants (CFA or BCG) prevents the onset of diabetes by induction of regulatory cells. Since autoimmune responses to glutamic acid decarboxylase (GAD) are up-regulated in insulin-dependent diabetes mellitus (IDDM), in this study GAD67-specific antibody, T cell proliferation and lymphokine production patterns were analysed in the adjuvant-treated mice to characterize the regulatory mechanisms underlying the protection. We used both spontaneous diabetes and syngeneic islet transplantation models in NOD mice. Protection against spontaneous diabetes and prevention of syngeneic islet graft rejection by CFA or BCG treatment was found to be accompanied by the production of long lasting and high titre anti-GAD67 antibody of IgG1 isotype in the sera. Upon in vitro stimulation with GAD67, draining lymph node and spleen cells from CFA-immunized NOD mice or syngeneic islet-grafted and BCG-protected NOD mice produced much more IL-4, whereas there was no significant change in IFN-gamma production. The strong early T cell proliferative response to GAD67 in CFA or BCG-immunized NOD mice was followed by a low or unresponsiveness state. Taken together, these results suggest a shift in Th1/Th2 balance in the GAD67-specific endogenous immune response to a change in Th2 levels after adjuvant treatment. We postulate that the protective effect of CFA or BCG is due to the diversion of GAD-specific endogenous cellular immune response to a non-pathogenic humoral response.

Adjuvants, Immunologic↗
PubMed1998

Protective and destructive effects of microbial infection in insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) is a T-cell mediated autoimmune disease, which results in the destruction of the islet beta-cells. The major histocompatibility complex (MHC) encodes the major susceptibility gene in IDDM. The concordance rate for diabetes in identical twins is 30-50% and in inbred animal models of disease the incidence rate is 20-80%. These results emphasize a role for environmental factors in the disease process. It has long been suggested that IDDM in humans may be caused by-viral infections. While considerable progress has been made in defining the genetics of IDDM, our understanding of the role of environmental factors, which might provide a more direct approach to therapy is considerably lacking. We suggest that (1) the density and affinity of epitopes derived from microbial antigens that bind to MHC molecules; (2) their cross-reactivity with beta-cell antigens; and (3) the nature of immunoregulatory cytokines induced by the microbial infections are the primary factors in the induction of either effector or protective T cells in IDDM.

Animals↗
PubMed1998

Membranous fat necrosis in appendices epiploicae. A clinicopathological study.

Membranous fat necrosis (MFN) is a degenerative process involving mature systemic adipose tissue. It is characterised by the presence of membranocystic foci surrounded by a lipophagic fibro-inflammatory reaction typical of fat necrosis. Membranocystic foci are cysts lined by an eosinophilic membrane with pseudopapillary infoldings having the histochemical staining profile of ceroid. Although MFN is described in an increasing number of adipose tissue sites, it has not been described as a distinct entity in appendices epiploicae (AE). Macroscopically, MFN in AE mimics nodal tuberculosis or metastatic tumour with necrosis and cystic change. Ischaemia, which can be secondary to physiological or pathologic processes, is crucial in the pathogenesis of MFN in AE. Heightened awareness of MFN as a distinct entity in AE is essential for accurate diagnosis and establishment of the pathogenesis of this enigmatic pathological process.

Adult↗
PubMed1998

Kaposi's sarcoma associated herpesvirus deoxyribonucleic acid sequences: lack of detection in prostatic tissue of human immunodeficiency virus-negative immunocompetent adults.

PURPOSE: A recent study argued that Kaposi's sarcoma associated herpesvirus is ubiquitous, as reflected by the frequent detection of its deoxyribonucleic acid (DNA) sequences in the prostatic tissue of healthy Italian men. Because these findings are discordant with serological data, our objective was to reassess the prevalence of this virus in prostate tissue from immunocompetent men. MATERIALS AND METHODS: Normal tissue samples from 45 human immunodeficiency virus-negative men undergoing radical prostatectomy for prostate carcinoma were snap frozen. DNA was extracted from normal noncancerous tissue. DNA was confirmed to be polymerase chain reaction amplifiable. Then, using multiple primer sets, extracted prostatic DNA was blinded, polymerase chain reaction amplified and screened for Kaposi's sarcoma herpesvirus by Southern blot. RESULTS: Kaposi's sarcoma herpesvirus DNA sequences were not detected in either the 45 prostatic DNA or in blinded internal negative controls, but they were consistently identified in all positive internal controls. CONCLUSIONS: Since Kaposi's sarcoma herpesvirus was undetectable in any of the prostatic samples despite high assay sensitivity, it is unlikely that the prostate serves as a reservoir for this virus in immunocompetent North American men. These findings also suggest that Kaposi's sarcoma herpesvirus is not ubiquitous.

Adult↗
PubMed1998

Isolated cervical tuberculosis in patients with HIV infection.

OBJECTIVE: Tuberculosis isolated to the head and neck region is common in patients with HIV infection. However, the management of isolated head and neck tuberculosis has not been reported in the literature. This study was done to describe the characteristics of tuberculosis isolated to the head and neck region in patients infected with HIV and to detect differences in presentation and diagnostic management based on the status of HIV infection at presentation. METHODS: A retrospective study was performed including 38 patients infected with HIV who were seen with tuberculosis isolated to the head and neck region at two tertiary care centers during a 10-year period. These patients were divided into two groups on the basis of the HIV status at presentation, which indirectly reflects the level of immunosuppression. Group 1 included 11 patients (29%) with AIDS at presentation. Group 2 included 27 patients (71%) with HIV infection but not AIDS. RESULTS: The cervical lymphatics were the most common site for isolated head and neck tuberculosis (89%), with the supraclavicular nodes most often involved (53%). Extralymphatic involvement was less common (11%), but involved a variety of anatomic locations (skin, spinal cord, larynx, parotid). The presenting history and physical examination had a low sensitivity for tuberculosis in patients with HIV infection, mainly because of the presence of multiple confounding factors. Purified protein derivative testing was highly sensitive for tuberculosis in patients with HIV infection alone (61 %); however, its usefulness was diminished in patients with AIDS (14%; p=0.03). Fine-needle aspiration biopsy was 94% sensitive for diagnosing tuberculosis and was not affected by the status of HIV infection. Surgical biopsy was the gold standard for diagnosing tuberculosis but was associated with chronically draining fistulas in a significant number of cases (14%). CONCLUSIONS: These data suggest that tuberculosis should be considered in the differential diagnosis of all head and neck lesions in patients infected with HIV, even in the absence of pulmonary involvement. Purified protein derivative testing should be done liberally in these patients, with realization that the sensitivity of purified protein derivative testing is reduced in patients with AIDS. Fine-needle aspiration biopsy should be the key diagnostic test in this patient population, with open surgical biopsy reserved for highly suspicious cases in which other measures were not diagnostic.

Adult↗
PubMed1998

Effectiveness of a medicament containing silicon dioxide, aloe, and allantoin on aphthous stomatitis.

This research protocol was designed to test the effectiveness of a gel containing silicon dioxide, aloe vera, and allantoin in the healing of recurrent aphthous ulcers. The subjects were patients with histories of developing multiple ulcers on the oral mucosa during a 3-to-4-month period. The parameters used to evaluate healing were number of lesions during a 3-to-4-month period, length of the interval between ulcers, size of ulcers, and pain from ulcers. An approach was used in which data were accumulated from diaries maintained by the subjects throughout the study intervals. Because 3 active substances were present in the gel, a preliminary study (study I) was performed to indicate the effect of each active substance and each combination. In this phase, different combinations of the substances were compared with the use of the 2(3) factorial experimental design. The results of this study demonstrated that statistical differences in the durations of lesions (P = .017) were present when all 3 substances were included in the gel. In the next study (study II), which was initiated to test the results of study I, additional subjects were divided into 2 groups; one used a control gel with silicon dioxide, and the other a gel with all 3 active substances. Study II found no statistical differences in the parameters when the 2 groups were compared. In study III, a modified crossover design was used with the subjects of study II, and a significant difference was found in lesion-free intervals (P = .0335) and length of time for the study (P = .0001). The differences in lesion intervals may have been caused by the differences in study length. Alteration in the occurrence of aphthous ulcers was demonstrated by the reduction in numbers of lesions in study I and by the increase in length of intervals between lesions in study III. However, a consistent pattern was not present; this indicated a lack of effect of the gel on aphthous ulcers.

Adult↗
PubMed1998

Haematological and biochemical studies in broiler chicks fed ochratoxin and inoculated with inclusion body hepatitis virus, singly and in concurrence.

Day-old broiler chicks, which had been shown to be negative for maternal antibodies against inclusion body hepatitis (IBH) virus and for viral antigen in cloacal swabs, were divided into four groups of 20 chicks each. One group was fed ochratoxin-A at 0.5 ppm from 3 to 38 days of age, another group was inoculated with 1 ml of IBH virus containing 10(6.5) EID50 per 0.2 ml. A third group was given both ochratoxin-A and infected with IBH virus. The fourth group served as the control. Anaemia was observed in all three treated groups but the changes were more pronounced in the combined group. The biochemical changes also suggested a cumulative damaging effect by ochratoxin-A and IBH virus.

Adenoviridae Infections↗
PubMed1998

Microbial degradation of tannins--a current perspective.

Tannins are water-soluble polyphenolic compounds having wide prevalence in plants. Hydrolysable and condensed tannins are the two major classes of tannins. These compounds have a range of effects on various organisms--from toxic effects on animals to growth inhibition of microorganisms. Some microbes are, however, resistant to tannins, and have developed various mechanisms and pathways for tannin degradation in their natural milieu. The microbial degradation of condensed tannins is, however, less than hydrolysable tannins in both aerobic and anaerobic environments. A number of microbes have also been isolated from the gastrointestinal tract of animals, which have the ability to break tannin-protein complexes and degrade tannins, especially hydrolysable tannins. Tannase, a key enzyme in the degradation of hydrolysable tannins, is present in a diverse group of microorganisms, including rumen bacteria. This enzyme is being increasingly used in a number of processes. Presently, there is a need for increased understanding of the biodegradation of condensed tannins, particularly in ruminants.

Animals↗
PubMed1998

Comparing survival times for treatments with those for a control under proportional hazards.

Inferences for survival curves based on right censored data are studied for situations in which it is believed that the treatments have survival times at least as large as the control or at least as small as the control. Testing homogeneity with the appropriate order restricted alternative and testing the order restriction as the null hypothesis are considered. Under a proportional hazards model, the ordering on the survival curves corresponds to an ordering on the regression coefficients. Approximate likelihood methods, which are obtained by applying order restricted procedures to the estimates of the regression coefficients, and ordered analogues to the log rank test, which are based on the score statistics, are considered. Mau's (1988) test, which does not require proportional hazards, is extended to this ordering on the survival curves. Using Monte Carlo techniques, the type I error rates are found to be close to the nominal level and the powers of these tests are compared. Other order restrictions on the survival curves are discussed briefly.

Controlled Clinical Trials as Topic↗
PubMed1998

Transient complete atrioventricular block following radiofrequency ablation of left free wall accessory pathway.

We report the case of a forty-six-year-old female with symptomatic WPW syndrome. The accessory pathway was located on the left free wall, for which ablation was attempted from the retrograde aortic approach. The ablation catheter was positioned at the appropriate site on the mitral anulus. A single radiofrequency energy application resulted in complete AV block with no escape rhythm, necessitating ventricular pacing. The AV conduction soon resumed with no evidence of pre-excitation. This phenomenon was thought to be related to trauma to the AV node during catheter entry in to the left ventricle.

Atrioventricular Node↗
PubMed1998

Dynamic assessment of parathyroid function in acute malaria.

OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers. DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to 'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min. SUBJECTS: Six Malaysian patients aged 17-42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19-36 years. MAIN OUTCOME MEASURES: Whole-blood ionised calcium and serum intact PTH concentrations. RESULTS: The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/- 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment. CONCLUSIONS: There is a decreased ionised calcium 'set point' for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products.

Acute Disease↗
PubMed1998

Ultrastructural and cytochemical evaluation of sepsis-induced changes in the rat pulmonary intravascular mononuclear phagocytes.

Sepsis stimulates an increase in the number and activity of mononuclear phagocytes in systemic host-defence organs. The present study was conducted to define the ultrastructural and cytochemical characteristics of the mononuclear phagocytes that sequester in the lung microvasculature of septic rats. Fourteen rats were challenged with a single intraperitoneal injection of saline (0.5 ml/100 g), E. coli (2 x 10(7)/100 g) or glucan (4 mg/100 g), and euthanased 2, 4, or 7 d later. The lungs were inflation fixed and processed for transmission electron microscopy. Cellular morphology was used to identify the intravascular mononuclear phagocytes and acid phosphatase (AcPase) expression was monitored as an index of cellular differentiation and activation. Control rats contained a limited number of monocytes in the pulmonary vasculature. In contrast, large numbers of activated mononuclear phagocytes were seen in the microvasculature within 48 h of treatment with either microbial product. The recruited pulmonary intravascular mononuclear phagocytes (PIMP) exhibited AcPase-reactive Golgi complexes, accumulation of secretory vesicles and other features of cell activation consistent with enhanced biosynthetic activity. Subsequent electron microscopy, conducted 4 and 7 d posttreatment, suggested that a progressive decline in the number and activity of PIMPs then occurred. In order to quantify the sepsis-induced accumulation of AcPase-positive PIMP, the experimental challenges were repeated in 11 rats and, 48 h later, tissue samples were evaluated by light microscopy for tartrate-insensitive acid phosphatase. Control rats exhibited 0.148 +/- 0.107 AcPase-positive PIMP/alveoli. E. coli and glucan challenged animals exhibited significant (P < 0.01) increases in AcPase-positive mononuclear phagocytes, with 0.782 +/- 0.073 and 0.636 +/- 0.170 PIMP/alveoli respectively. The results demonstrate that focal sepsis stimulates a significant, but transient, recruitment of activated mononuclear phagocytes into the rat pulmonary microvasculature.

Acid Phosphatase↗
PubMed1998

Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells.

Increased soy consumption in Asian diets, resulting in increased serum isoflavone levels, has been associated with a decreased risk for prostate adenocarcinoma (PCa). The isoflavone genistein is believed to be the anticancer agent found in soy, and significant levels of genistein have been detected in human prostatic fluid, implicating the role of genistein in PCa prevention. Recent studies have demonstrated genistein's ability to inhibit cell growth and induce apoptosis in several cell lines; however, the molecular mechanisms of genistein's effect are not known. We have evaluated the mechanism by which genistein may inhibit PCa cell growth. Here we report that genistein inhibits PCa cell growth in culture in a dose-dependent manner, which is accompanied by a G2/M cell cycle arrest. Cell growth inhibition was observed with concomitant downregulation of cyclin B, upregulation of the p21WAF1 growth-inhibitory protein, and induction of apoptosis. Collectively, these results provide experimental evidence for a novel effect of genistein on cell cycle gene regulation, resulting in the inhibition of cell growth and ultimate demise of tumor cells.

Adenocarcinoma↗
PubMed1998

The effect of delta rays on the ionometric dosimetry of proton beams.

The interface effects arising in the measurement of absorbed dose by ionization chambers, owing to the inhomogeneity between the walls and the gas, have been evaluated by an analytical model. The geometrical situation considered here is appropriate for representing the behaviour of a plane-parallel ionization chamber exposed to a radiotherapeutic beam of protons. Two gases, dry air and tissue equivalent gas (methane based), as well as six materials commonly used in ionization chamber walls, i.e. graphite, A-150 tissue equivalent plastic, C-522 air equivalent plastic, nylon type 6, polymethyl methacrylate and polystyrene, have been examined. The analysis of the results shows that, within the limits of the detector dimensions and proton energies commonly used in the dosimetry of radiotherapeutic beams, these effects, if not taken into account in the measurement interpretation, can entail deviations of up to about 2% with respect to the correct absorbed dose in gas.

Biophysical Phenomena↗