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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 253 records · Page 14Linked to original sources
PubMed1998

Continuous muscle fibre activity: description of neuroelectromyographic findings including single fibre EMG.

Four patients with continuous muscle fibre activity (Isaacs-Mertens syndrome) are reported in this communication. Electrophysiological evidence of peripheral neuropathy was present in two patients. Impulse induced repetitive CMAPs were noted in two patients. In one case the repetitive activity increased upon proximal stimulation. Single fibre EMG recordings of the spontaneous activity revealed pathological discharges with variable frequencies. Each pathological discharge comprised of a primary discharge and 1-4 extradischarges. There was marked variability of the interval between the primary discharge and subsequent extradischarges.

Adult↗
PubMed1998

NSAID induced gastrointestinal complications: the ARAMIS perspective--1997. Arthritis, Rheumatism, and Aging Medical Information System.

Gastrointestinal (GI) complications related to nonsteroidal antiinflammatory drug (NSAID) therapy are the most prevalent category of adverse drug reactions. Patients with arthritis are among the most frequent users of NSAID and are therefore particularly at risk for these side effects. To evaluate the nature of NSAID related GI complications and to determine how their frequency can be reduced, a series of studies of such complications in patients with rheumatic disease has been carried out based on data from the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). We review the literature and present findings from the ARAMIS studies. This report addresses whether GI side effects such as dyspepsia can serve as warning symptoms for serious GI complications and describes the risk factors for these life threatening complications. It also describes differences among NSAID with regard to their GI toxicity and describes a study that investigated whether H2-receptor antagonists and antacids affect the development of serious GI complications. In addition, ongoing research and topics to be addressed in future studies are described.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

The measurement of lipid peroxidation in vivo.

Tissue damage due to free radical activity may be a common mediator in pathology [Kehrer, Crit. Rev. Toxicol. 23 (1993) 21-48]. The confirmation that free radicals have a role in the disease process is hampered by the difficulty of their measurement, as free radicals are transient species present at low concentrations in tissue. Direct measurement of free radicals is confined to electron spin resonance, a specialised methodology not available in our laboratory. We have evaluated several indirect measures, namely, changes in antioxidant status, hydroxyl radical trapping assays and monitoring breakdown products of free radical attack. Here we describe a method from the latter category, monitoring lipid peroxidation. The measurement of lipid peroxidation has been favoured as the indicator of free radical activity in previous ex vivo and in vitro studies of oxidative stress, in particular by the measurement of malondialdehyde (MDA). There is an absence of reported measurements of MDA from in vivo preparations especially where samples are collected in situ. The method describes the combination of microdialysis sampling with high performance liquid chromatography coupled to ultraviolet spectroscopy, to measure MDA from in vivo preparations of rat brain. The methodology could equally be applied to other tissues.

Animals↗
PubMed1997

On Dimple Formation in Foam Films

Dimple formation has been studied numerically in foam films formed in the conventional Scheludko-Exerowa cell and in a miniature cell recently developed by O. D. Velev et al. (J. Colloid Interface Sci. 175, 68 (1995)). Results of the simulations provide a criterion for dimple formation in the conventional cell in the absence of disjoining pressure. Because the films in the miniature cell are very thin, disjoining pressure effects are important even during the liquid withdrawal step when the film is initially formed. If the disjoining pressure is repulsive, film thickness remains nearly uniform and constant as observed experimentally by the above authors. In other cases the simulations predict that dimple formation will occur in the miniature cell but that it will not be detectable by the usual interference techniques because film thickness is less than one-fourth the wavelength of visible light.

Journal Article↗
PubMed1997

Use of dot-immunobinding assay for visual detection of rinderpest antibodies in vaccinated cattle.

A dot-immunobinding (DIB) assay was used to detect rinderpest antibodies in cattle vaccinated with Kabete 'O' strain vaccine, using purified rinderpest virus. Of 120 serum samples from vaccinated and non-vaccinated animals, rinderpest antibodies were detected in 80%, 88.4% and 91.6% of samples at 2, 3 and 4 weeks postvaccination respectively. All the serum samples from non-vaccinated animals were negative. The DIB results had a good correlation with those of the micro neutralisation test. The technique is simple, easy to perform and suitable for routine use in detecting rinderpest antibodies following vaccination.

Animals↗
PubMed1997

Phase II clinical trial of a vas deferens injectable contraceptive for the male.

Following up on an earlier clinical trial demonstrating the safety of an intra-vas deferens injection of a contraceptive drug named Risug, comprised of styrene maleic anhydride (SMA) in a solvent vehicle of dimethylsulphoxide (DMSO), a study to assess the contraceptive effectiveness of a specific dose (60 mg) of SMA bilaterally was planned and implemented. Male subjects and their wives with normal reproductive profiles were the volunteer subjects. The wives were not using any contraceptives. The results reconfirm the safety and show that for a period of at least 1 year, the treatment leads to azoospermia in the male and gives pregnancy protection.

Adult↗
PubMed1997

Direct osteolysis induced by metastatic murine melanoma cells: role of matrix metalloproteinases.

We examined the osteolytic ability of metastatic cells and the role of tumour matrix metalloproteinases (MMPs) in bone degradation. The histomorphometry of experimental bone metastases of B16/F1 melanoma cells showed that osteolysis was associated with a 90% decrease in osteoclast number and predominance of cancer cells overlaying resorption pits. In vitro, B16/F1 cells and their conditioned medium (CM) degraded 3H-proline-labelled extracellular matrices from osteoblast-like cells and 45Ca-labelled calvariae. Using bone slices, we observed morphological evidence of degradation by B16/F1 cells. A role for tumour MMPs in bone degradation was supported by inhibition of degradation by 1,10-phenanthroline, collagen I degradation by tumour cells and the presence of TPA-inducible M(r) 90,000, 84,000 and 64,000 gelatinolytic, and 54,000 caseinolytic bands in B16/F1-CM. These studies indicate that metastatic cancer cells degrade bone matrix directly and that this is partially mediated by MMPs.

Animals↗
PubMed1997

Cross-resistance to photofrin-mediated photodynamic therapy and UV light and recovery from photodynamic therapy damage in Rif-8A mouse fibrosarcoma cells measured using viral capacity.

Photodynamic therapy (PDT) utilizes the localized delivery of light to activate a photosensitizing drug (such as Photofrin) which is selectively retained by the tumour tissues. The intrinsic in vitro sensitivity of tumour cells to PDT is thought to be an important determinant of clinical tumour response to PDT. In this work we show the feasibility of using a viral capacity assay for adenovirus (Ad) DNA synthesis as an indicator of cellular sensitivity to and recovery from Photofrin-mediated PDT. Rif-1 mouse fibrosarcoma cells and a PDT resistant derivative, Rif-8A, as well as Chinese hamster ovary (CHO) cells and CHO-MDR multi-drug resistant mutant cells were studied. Consistent with the clonogenic survival of these cells, the capacity of PDT-treated cells for Ad DNA synthesis was greater for Rif-8A compared to Rif-1 cells and for CHO-MDR compared to CHO-N cells. Delaying infection of the Rif cells from immediately after, to 6 hours after PDT, resulted in an increased capacity for Ad DNA synthesis, which was greater for Rif-8A compared to Rif-1 cells, suggesting that the increased resistance of Rif-8A cells to PDT results from an elevated recovery and/or repair of PDT damage. The capacity of UV-irradiated cells for Ad DNA synthesis was also greater for Rif-8A compared to Rif-1 cells indicating a cross-resistance of Rif-8A cells to UV. These results suggest some overlap in the types of cellular damage induced by UV and PDT and/or overlap in the pathways for the repair of UV and PDT damage in Rif cells.

Adenoviridae↗
PubMed1997

Transforming growth factor beta upregulates the integrin-mediated adhesion of human prostatic carcinoma cells to type I collagen.

Prostate cancer frequently metastasizes to bone, and we propose that this process may be facilitated by the adhesion of metastatic cells to bone-derived type I collagen. We examined collagen receptor function and regulation in osteotropic PC-3 human prostatic carcinoma cells. PC-3 cell adhesion to immobilized human type I collagen was promoted by Mn2+ and Mg2+ ions and was RGD-independent. Antibodies directed against beta1 or alpha2 integrin subunits inhibited adhesion to collagen by 90% and 53%, respectively, suggesting involvement of the alpha2 beta1 receptor. Anti-alpha1 or anti-alpha3 antibodies had no effect on adhesion. Flow cytometry and immunoprecipitation of [35S]methionine-labeled cells demonstrated that alpha2 beta1 was the major collagen receptor expressed by PC-3 cells. The pretreatment of PC-3 cells with transforming growth factor-beta1 (TGF-beta1), a major bone-derived growth factor, caused a rapid (2 h) 2-fold increase in the de novo synthesis of alpha2 and beta1 integrin subunits, and also increased by 2- to 3-fold the adhesion and spreading of PC-3 cells on collagen. We conclude that alpha2 beta1 is the major collagen receptor employed by PC-3 cells, and that alpha2 beta1 upregulation by TGF-beta is associated with an increased adhesion and spreading on collagen. The data suggest that exposure of metastatic PC-3 cells to the high levels of TGF-beta in bone may promote their ability to adhere to bone-derived collagen, which may thereby facilitate the localization of metastatic cells in the skeleton.

Adenocarcinoma↗
PubMed1997

Mitochondrial contributions to cancer cell physiology: redox balance, cell cycle, and drug resistance.

Alterations in the biochemistry of mitochondria have been associated with cell transformation and the acquisition of drug resistance to certain chemotherapeutic agents, suggesting that mitochondria may play a supportive role for the cancer cell phenotype. Mitochondria are multifunctional organelles that contribute to the cellular adenosine triphosphate (ATP) pool and cellular redox balance through the production of reactive oxygen intermediates (ROI). Our laboratory has focused on these mitochondrial functions in the context of cancer cell physiology to evaluate the potential role of mitochondria as controllers of tumour cell proliferation. Low concentrations of ROI have been implicated as messengers in intracellular signal transduction mechanisms; thus an imbalance of ROI production from the mitochondria may support cancer cell growth. In addition, suppression of mitochondrial ATP production can halt cell cycle progression at two energetic checkpoints, suggesting that the use of tumor-selective agents to reduce ATP production may offer a therapeutic target for cancer growth control.

Antineoplastic Agents↗
PubMed1997

The female tetraplegic: an admission of urological failure.

OBJECTIVE: To present the long-term follow-up of female patients with tetraplegia managed in our unit, many of who require permanent indwelling catheters or urinary diversions that lead to significant complications and associated morbidity. PATIENTS AND METHODS: Eighty-four female tetraplegics (mean age 31 years, range 13-81) were followed for a mean of 9 years (range 2-30). Three groups of patients were identified, depending on their neurology; 27 patients had complete lesions (Frankel A), 20 had incomplete lesions with poor functional recovery (Frankel B/C) and 37 had incomplete lesions with good function (Frankel D/E). RESULTS: The patients with complete lesions (Frankel A) were difficult to manage, with 23 of the 27 (85%) treated using indwelling catheters. Three patients underwent diversion and for one patient, the carer performs clean intermittent catheterization (CIC). Of the 20 patients with Frankel B/C lesions, 14 have permanent indwelling catheters, three are able to perform CIC and three void by controlled triggering of detrusor contractions (reflex voiding). The 37 patients with Frankel D/E lesions fared better and only three (8%) require permanent catheters. Of the others, four (11%) use CIC (one following a cystoplasty) and most (30, 81%) use reflex voiding. Most of the 40 patients with permanent catheters had significant problems with bladder stones (55%), leakage and by-passing (35%), and recurrent symptomatic infections (33%). Patients performing CIC fared better, with most needing anticholinergic therapy or subtrigonal phenol; patients who used reflex voiding also needed these two treatments at some stage. Four patients (two with ileal loops and two with indwelling catheters) developed dilated upper tracts. CONCLUSIONS: The urological status of female patients following cervical cord injury depends on the level of injury and recovery. Most patients with Frankel A-C lesions have permanent indwelling catheters and most patients with Frankel D or E lesions void with controlled triggering or use CIC. Although upper tract dilation was seen in only 5%, patients had significant morbidity related to the bladder.

Adolescent↗
PubMed1997

Supravesical diversion for incontinence: a long-term follow-up.

OBJECTIVES: To report the long-term follow-up of patients with an ileal conduit urinary diversion, constructed for intractable incontinence in patients with benign disease where the native bladder was left in situ, and to determine the fate of the bladder and the effects on the upper tracts. PATIENTS AND METHODS: Ninety-three patients (mean age at operation 50 years, range 8-78) were followed for a minimum of 2 (mean 5) years after undergoing an ileal conduit urinary diversion. Seventy-one patients (76%) had neurological disease (18 traumatic and 53 non-traumatic) and the single largest group of patients (28) suffered from disseminated sclerosis. Twenty-two patients with no obvious neurological disease underwent the procedure for unmanageable incontinence or intractable bladder symptoms or for interstitial cystitis. The patients were assessed for problems in the bladder remnant, stomal problems and upper tract changes following surgery. RESULTS: Forty-eight patients (52%) had recurrent vesical infections and pyocystis and of these, 23 (48%) required admission for in-patient bladder irrigations. To control recurrent bladder problems, five patients required creation of a vesico-vaginal fistula; this did not suffice in two and they subsequently underwent cystectomy; in total, five patients underwent cystectomy. Twenty-nine patients (31%) had stomal problems, those with the skin being commonest. Parastomal hernia repair was required in 10 (10%) patients and three had further surgery for recurrence. Of 83 patients with normal upper tracts before diversion, post-operative radiological assessment showed upper tract dilatation in 28 (34%) and in 10 (12%) this was bilateral. In one patient with a neuropathic bladder, the ileal diversion resulted regression of the dilated upper tracts. CONCLUSIONS: Supravesical diversion is safe and well tolerated but assessing the long-term follow-up, the incidence of bladder problems in over half these patients and upper tract changes in over a third suggests an indefinite follow-up is mandatory. Despite these problems, most patients are delighted with the outcome of their surgery.

Adolescent↗
PubMed1997

Bowel problems after enterocystoplasty.

OBJECTIVES: To document the changes in bowel habit in patients who have undergone enterocystoplasty. PATIENTS AND METHODS: Sixty-nine patients with neuropathic (NP) and 44 with non-neuropathic (NNP) bladder dysfunction (mean age 26 years, range 13-61, 93.6% socially continent), followed for at least 36 months after cystoplasty, were assessed using a questionnaire addressing faecal frequency, consistency, method of evacuation and incontinence episodes before and after surgery. RESULTS: Of the patients with NP bladder dysfunction, 26 (38%) had more and seven (10%) less frequent bowel action after surgery, with 36 (52%) unchanged; 38 (55%) of patients had unchanged consistency, 26 (38%) were looser and five (7%) more constipated; 41 (59%) opened their bowels as before, 16 (23%) needed more help and 12 (17%) less help to evacuate; 16 (23%) patients had more and 17 (25%) less episodes of incontinence; 21 (30%) patients felt their bowels had not become normal after their operation and only 24 (35%) that they had returned to normal within 3 months of their operation. The bowel segment used was ileum in 44 patients, ileocaecal in 11 and sigmoid cystoplasty in 14. Patients with intact ileum did not have the same degree of diarrhoea, with only three of the 14 patients with a sigmoid cystoplasty being adversely affected. Of the patients with NNP bladder dysfunction, 18 patients (41%) had a more and five (11%) a less frequent bowel action; 20 (46%) had more loose and five (11%) less loose bowel action; similar numbers (five and four) needed either an increase or a decrease in laxatives or enemata: surprisingly, 12 patients (27%) felt they had an increase in the episodes of incontinence; 17 (39%) patients felt their bowels returned to normal within 3 months of surgery and 30% felt their bowels had not become normal after surgery. Only one patient in this group had a sigmoid cystoplasty and she did not find that the operation interfered with her bowel function. CONCLUSIONS: Ileal resection results in malabsorption of bile acids, maldigestion of fat and an imbalance of water and electrolytes. Patients with neurogenic bladders are finely balanced between acceptable bowel function and choas, and surgery often tips this balance the wrong way. In 30% of the present patients, bowel problems persisted after surgery, with 38% having increased frequency. 38% having looser consistency and 23% more incontinence episodes following surgery. More surprisingly, a high percentage of NNP patients had bowel problems after cystoplasty.

Adolescent↗
PubMed1997

Subcellular localization of Photofrin and aminolevulinic acid and photodynamic cross-resistance in vitro in radiation-induced fibrosarcoma cells sensitive or resistant to photofrin-mediated photodynamic therapy.

The subcellular and, specifically, mitochondrial localization of the photodynamic sensitizers Photofrin and aminolevulinic acid (ALA)-induced protoporphyrin-IX (PpIX) has been investigated in vitro in radiation-induced fibrosarcoma (RIF) tumor cells. Comparisons were made of parental RIF-1 cells and cells (RIF-8A) in which resistance to Photofrin-mediated photodynamic therapy (PDT) had been induced. The effect on the uptake kinetics of Photofrin of coincubation with one of the mitochondria-specific probes 10N-Nonyl acridine orange (NAO) or rhodamine-123 (Rh-123) and vice versa was examined. The subcellular colocalization of Photofrin and PpIX with Rh-123 was determined by double-label confocal fluorescence microscopy. Clonogenic cell survival after ALA-mediated PDT was determined in RIF-1 and RIF-8A cells to investigate cross-resistance with Photofrin-mediated PDT. At long (18 h) Photofrin incubation times, stronger colocalization of Photofrin and Rh-123 was seen in RIF-1 than in RIF-8A cells. Differences between RIF-1 and RIF-8A in the competitive mitochondrial binding of NAO or Rh-123 with Photofrin suggest that the inner mitochondrial membrane is a significant Photofrin binding site. The differences in this binding may account for the PDT resistance in RIF-8A cells. With ALA, the peak accumulations of PpIX occurred at 5 h for both cells, and followed a diffuse cytoplasmic distribution compared to mitochondrial localization at 1 h ALA incubation. There was rapid efflux of PpIX from both RIF-1 and RIF-8A. As with Photofrin, ALA-induced PpIX exhibited weaker mitochondrial localization in RIF-8A than in RIF-1 cells. Clonogenic survival demonstrated cross-resistance to incubation in PpIX but not to ALA-induced PpIX, implying differences in mitochondrial localization and/or binding, depending on the source of the PpIX within the cells.

Aminolevulinic Acid↗
PubMed1997

Interactions between heterologous FtsA and FtsZ proteins at the FtsZ ring.

FtsZ and FtsA are essential for cell division in Escherichia coli and colocalize to the septal ring. One approach to determine what regions of FtsA and FtsZ are important for their interaction is to identify in vivo interactions between FtsA and FtsZ from different species. As a first step, the ftsA genes of Rhizobium meliloti and Agrobacterium tumefaciens were isolated and characterized. In addition, an FtsZ homolog that shared the unusual C-terminal extension of R. meliloti FtsZ1 was found in A. tumefaciens. In order to visualize their localization in cells, we tagged these proteins with green fluorescent protein (GFP). When R. meliloti FtsZ1-GFP or A. tumefaciens FtsZ-GFP was expressed at low levels in E. coli, they specifically localized only to the E. coli FtsZ ring, possibly by coassembly. When A. tumefaciens FtsA-GFP or R. meliloti FtsA-GFP was expressed in E. coli, they failed to localize detectably to the E. coli FtsZ ring. However, when R. meliloti FtsZ1 was coexpressed with them, fluorescence localized to a band at the midcell division site, strongly suggesting that FtsA from either A. tumefaciens or R. meliloti can bind directly to its cognate FtsZ. As expected, GFP-tagged FtsZ1 and FtsA from either R. meliloti or A. tumefaciens localized to the division site in A. tumefaciens cells. Therefore, the 61 amino acid changes between A. tumefaciens FtsA and R. meliloti FtsA do not prevent their direct interaction with FtsZ1 from either species, suggesting that those residues are not essential for protein-protein contacts. Moreover, the failure of the two non-E. coli FtsA derivatives to interact strongly with E. coli FtsZ in this in vivo system unless their cognate FtsZ was also present suggests that FtsA-FtsZ interactions have coevolved and that the residues which differ between the E. coli proteins and those of the two other species may be important for specific interactions.

Agrobacterium tumefaciens↗
PubMed1997

Role of ET and NO in resuscitative effect of diaspirin cross-linked hemoglobin after hemorrhage in rat.

Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based therapeutic agent that produces significant cardiovascular effects, possibly due to its actions on vasoactive substances, such as endothelin (ET) and nitric oxide (NO). We have studied the modulation of cardiovascular effects of DCLHb by an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and an ETA-receptor antagonist, FR-139317, in hemorrhaged rats. Control rats resuscitated with vehicle [Ringer lactate (RL), 4 ml/kg iv] did not show any improvement in O2 consumption, base deficit, systemic hemodynamics, or regional blood flow after hemorrhage, and the rats survived for < 70 min. Administration of DCLHb (400 mg/kg iv) significantly improved O2 consumption, base deficit, systemic hemodynamics, and regional blood circulation after resuscitation, and the rats survived for > 120 min after hemorrhage. Plasma ET-1 and guanosine 3',5'-cyclic monophosphate (cGMP) concentrations increased after hemorrhage. DCLHb produced an increase in ET-1 and decreased cGMP concentrations in plasma. Pretreatment with L-NAME (10 mg/kg iv) or FR-139317 (4 mg/kg iv) attenuated the DCLHb-induced improvement in survival time, base deficit, systemic hemodynamics, and regional blood circulation. L-NAME (10 mg/kg iv) per se did not produce any resuscitative effect; therefore the NO mechanism may not be contributing toward the efficacy of DCLHb in hemorrhaged rats. However, FR-139317 attenuated the efficacy of DCLHb; therefore an increase in plasma ET-1 concentration by DCLHb may be contributing toward the efficacy of DCLHb in hemorrhage. Hemorrhage-induced increase in cGMP levels could be attenuated by L-NAME, but L-NAME was not effective in resuscitation of hemorrhaged rats, indicating a lack of role of NO in resuscitation. It is concluded that the ET mechanism is more important in the beneficial effect of DCLHb than the NO mechanism in hemorrhage.

Animals↗