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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 163 records · Page 9Linked to original sources
PubMed2000

Secretory immunoglobulin A in the vesical urothelium of patients with neuropathic bladder--an immunohistochemical study.

STUDY DESIGN: A pilot study was carried out on archival material of bladder biopsies taken during 1994 and 1995 from patients with neuropathic bladder. OBJECTIVES: To compare the pattern of immunostaining for sIgA in the urothelium of biopsies taken from neuropathic bladder with the biopsies obtained from patients with non-neuropathic bladders. SETTING: Regional Spinal Injuries Centre, Southport and Department of Pathology, Royal Liverpool University Hospital, Liverpool. METHODS: Formalin-fixed, paraffin-embedded biopsies of bladder mucosa taken from patients with neuropathic urinary bladder (n=43) during 1994 and 1995 were processed for immunostaining with rabbit polyclonal antibody for secretory component of IgA. Archival specimens of bladder biopsies from non-neuropathic bladder were stained as controls. All sections were stained contemporaneously. RESULTS: In all the control biopsies, strong immunostaining for sIgA was observed in the superficial cells of transitional epithelium. In the biopsies taken from patients with neuropathic bladder, immunostaining in the transitional epithelium was variable: strong in 14 cases; moderate in four; faint in 16; and absent in three. Immunostaining for sIgA was absent in all the five biopsies in which the urothelium had undergone squamous metaplasia. One biopsy showed intestinal metaplasia; immunostaining for sIgA was seen in the basal cells. CONCLUSION: Strong immunostaining for sIgA was observed in the urothelium of all biopsies taken from non-neuropathic bladder. In contrast to this, only 18 of 37 biopsies obtained from neuropathic bladder showed strong or moderate immunostaining for sIgA in the transitional epithelium. Spinal Cord (2000) 38, 378 - 381.

Archives↗
PubMed2000

Parathyroid hormone-related protein (1-34) and urothelial redifferentiation in the neuropathic urinary bladder.

STUDY DESIGN: A comparative study of immunostaining for parathyroid hormone-related protein (1-34) (PTHrP (1-34)) in the vesical epithelium of biopsies obtained from patients with non-neuropathic bladder and those with neuropathic bladder. OBJECTIVES: To investigate the immunostaining for PTHrP (1-34) in the control cases and in neuropathic bladders showing (1) normal transitional epithelium, (2) hyperplastic transitional epithelium, and (3) squamous metaplasia. SETTING: Regional Spinal Injuries Centre, and Department of Cellular Pathology, Southport & Ormskirk Hospitals NHS Trust, Southport, Department of Pathology, Royal Liverpool University Hospital and the Departments of Clinical Chemistry and Cell Biology, The University of Liverpool, Liverpool, England. METHODS: Cold cup biopsies of bladder mucosa were taken from patients suffering from neuropathic urinary bladder when they were undergoing a therapeutic procedure in the urinary tract. Immunohistochemistry was performed on these biopsy specimens using a rabbit polyclonal antibody raised to a synthetic peptide corresponding to human PTHrP (1-34). Control group (n=10) consisted of archival biopsies taken from non-neuropathic bladders. RESULTS: In the control group, the transitional epithelium showed no immunostaining, or at the most, very faint positive staining was seen in the transitional epithelium of non-neuropathic bladder. Positive immunostaining to PTHrP (1-34) was seen in the normal transitional epithelium of neuropathic bladder in nine of 13 cases. Hyperplastic transitional epithelium showed positive immunostaining for PTHrP (1-34) in 11 of 13 biopsies from patients with neuropathic bladder. Immunostaining for PTHrP (1-34) was observed in the metaplastic squamous epithelium in 14 of 17 cases with neuropathic bladder. CONCLUSION: The transitional epithelium of non-neuropathic bladder showed no immunostaining, or at the most, very faint positive staining for PTHrP (1-34). In contrast to this, positive immunostaining for PTHrP (1-34) was observed more frequently in the vesical epithelium of neuropathic bladder. This observation opens up avenues for innovative therapy with PTHrP or its analogues for possible modulation of urothelial differentiation in the neuropathic bladder.

Adult↗
PubMed2000

Xanthogranulomatous funiculitis and epididymo-orchitis in a tetraplegic patient.

STUDY DESIGN: A case report of xanthogranulomatous funiculitis and epididymo-orchitis. Xanthogranulomatous inflammation is an uncommon, non-neoplastic process characterised by destruction of tissue, which is replaced by a striking cellular infiltrate of lipid-laden macrophages. CASE REPORT: A 21-year male sustained complete tetraplegia at C-6 level, after a fall in 1998. The neuropathic bladder was managed with an indwelling urethral catheter. He had many unsuccessful trials of micturition. Sixteen months after the cervical injury, he noticed swelling of the left side of the scrotum following removal of a blocked catheter. He was prescribed antibacterial therapy. Four weeks later, physical examination revealed a hard and irregular swelling encompassing the testis, epididymis and spermatic cord. The clinical diagnosis was epididymo-orchitis progressing to pyocele. Through a scrotal incision, the swollen testis, epididymis and diseased segment of the spermatic cord were removed en masse. Histopathology showed extensive areas of necrosis, with xanthogranulomatous inflammation in the spermatic cord and to a lesser extent in the testis/epididymis. CONCLUSION: Repeated episodes of high-pressure urinary reflux along the vas deferens during dyssynergic voiding, and subsequent interstitial extravasation of urine together with chronic, low-grade, suppurative infection possibly led to development of xanthogranulomatous inflammation in the testis and the epididymis. Since tissue destruction is a feature of xanthogranulomatous inflammation, the definite and curative treatment is either complete (or, where applicable, partial) excision of the affected organ in most of the cases.

Adult↗
PubMed2000

Silent hydronephrosis/pyonephrosis due to upper urinary tract calculi in spinal cord injury patients.

STUDY DESIGN: A study of four patients with spinal cord injury (SCI) in whom a diagnosis of hydronephrosis or pyonephrosis was delayed since these patients did not manifest the traditional signs and symptoms. OBJECTIVES: To learn from these cases as to what steps should be taken to prevent any delay in the diagnosis and treatment of hydronephrosis/pyonephrosis in SCI patients. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: A retrospective review of cases of hydronephrosis or pyonephrosis due to renal/ ureteric calculus in SCI patients between 1994 and 1999, in whom there was a delay in diagnosis. RESULTS: A T-5 paraplegic patient had two episodes of urinary tract infection (UTI) which were successfully treated with antibiotics. When he developed UTI again, an intravenous urography (IVU) was performed. The IVU revealed a non-visualised kidney and a renal pelvic calculus. In a T-6 paraplegic patient, the classical symptom of flank pain was absent, and the symptoms of sweating and increased spasms were attributed to a syrinx. A routine IVU showed non-visualisation of the left kidney with a stone impacted in the pelviureteric junction. In two tetraplegic patients, an obstructed kidney became infected, and there was a delay in the diagnosis of pyonephrosis. The clinician's attention was focused on a co-existent, serious, infective pathology elsewhere. The primary focus of sepsis was chest infection in one patient and a deep pressure sore in the other. The former patient succumbed to chest infection and autopsy revealed pyonephrosis with an abscess between the left kidney and left hemidiaphragm and xanthogranulomatous inflammation of perinephric fatty tissue. In the latter patient, an abdominal X-ray did not reveal any calculus but computerised axial tomography showed the presence of renal and ureteric calculi. CONCLUSIONS: The symptoms of hydronephrosis may be bizarre and non-specific in SCI patients. The symptoms include feeling unwell, abdominal discomfort, increased spasms, and autonomic dysreflexia. Physicians should be aware of the serious import of these symptoms in SCI patients.

Adult↗
PubMed2000

Role of selective intra-operative cholangiography during cholecystectomy.

BACKGROUND: The use of routine intra-operative cholangiography (IOC) remains controversial. This prospective study was carried out to determine whether to perform selective or routine IOC in patients undergoing cholecystectomy for gallstones. METHODS: All consecutive patients undergoing open cholecystectomy over a 16-month period were included in the present study. They were divided into two groups based on the absence (n = 79) or presence (n = 55) of indicators of choledocholithiasis. All patients were subjected to cholangiography. Each indicator, subsets of indicators and all indicators combined were evaluated for their ability to predict choledocholithiasis. RESULTS: There would be only two missed stones (1.5%) if selective cholangiography was to be practised. Intra-operative cholangiography had a positive predictive value of 100%. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of all the indicators combined were 93.5%, 84.6%, 74.5%, 97.5% and 88.0%, respectively. The best indicators in each subset were jaundice, common bile duct diameter as assessed by ultrasonography, and a palpable stone during surgery with NPV of 82.7%, 91.1% and 96.8%, respectively. CONCLUSION: Routine IOC during cholecystectomy is not essential for the prevention of retained stones. A combination of the various indicators of choledocholithiasis can be used to select patients for cholangiography.

Cholangiography↗
PubMed2000

Treatment of chronic contained spontaneous esophageal perforations.

Spontaneous esophageal perforations are associated with a high mortality and morbidity without surgery. The treatment mortality for early (<24) and late (>24 h) spontaneous esophageal perforations is reviewed as well as all recent cases of chronic spontaneous esophageal perforations. Chronic esophageal perforations with mediastinal cavities may be best treated by internal drainage of the cavity into the esophagus in order to convert the transmural perforation into an intramural esophageal dissection.

Chronic Disease↗
PubMed2000

Neonatal intestinal obstruction with isolated levocardia.

An unusual case of isolated levocardia, duodenal obstruction, and malrotation with volvulus is reported. Three cases of situs inversus abdominus with malrotation with volvulus have been reported to date. The current case is the fourth case and only the second survivor in the series. In cases of situs inversus abdominus, because of inversion of viscera, the volvulus may occur in an anticlockwise direction and, thus, should be derotated in a clockwise direction.

Humans↗
PubMed2000

Gastroesophageal reflux disease in patients with spinal cord injury.

Due to certain risk factors that pertain to patients with spinal cord injury (SCI), the prevalence and severity of gastroesophageal reflux disease (GERD) may be greater among patients with SCI than the general population. In this retrospective study, the prevalence of GERD in patients with SCI as compared with age- and sex-matched controls, using pharmacy data from a large health care system, and the adequacy of the diagnostic evaluation process are evaluated and the symptom and disease severity in patients with SCI who were treated for GERD are assessed. The findings show a 22% prevalence of GERD in patients with SCI versus 28% in General Medicine Clinic controls. Although the symptom severity is similar in patients with SCI and controls, patients with SCI who have GERD symptoms undergo endoscopy less frequently. Disturbingly, the prevalence of severe, stage IV esophagitis among patients with SCI is higher than controls (p = .03). These results should alert clinicians caring for patients with SCI to more aggressively evaluate and treat such patients with reflux symptoms of heartburn and regurgitation before the development of complications.

Adult↗
PubMed2000

Intratumoral therapy of cisplatin/epinephrine injectable gel for palliation in patients with obstructive esophageal cancer.

Obstructing esophageal cancer produces severe dysphagia with ensuing death within 90 days. Palliation is possible with modalities like stent placement, laser, and photodynamic therapy. However, these treatments have a high rate of complications, and the overall mortality is not altered. A new alternative treatment evaluated in this study is endoscopic intratumoral injection with cisplatin/epinephrine (CDDP/epi) gel. CDDP/epi gel injections were administered weekly for 3 to 8 weeks in nine patients, median age, 72 years; mean tumor volume (+/-SEM), 41.44 (+/-22.4) cm3. Eight patients had stage IV, and one had stage III esophageal carcinoma. The mean dysphagia score (+/-SEM) was 3.5 (+/-0.17). All patients were followed up until death. Dysphagia resolved in eight patients with reduction in mean dysphagia score (+/-SEM) from 3.5 (+/-0.17) to 0.75 (+/-0.28; p = 0.005). Tumor volume was reduced by 75% in one patient and by 50% in two patients. The median survival was 4 months. The longest follow-up has been 15 months (458 days). In this pilot study, intratumoral injection of CDDP/epi gel restored swallowing in eight of nine patients and was an effective and safe outpatient treatment in patients with obstructive esophageal cancer.

Adenocarcinoma↗
PubMed2000

Gastrointestinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, Rheumatism, and Aging Medical Information System.

More than 30 million people worldwide consume prescription nonsteroidal anti-inflammatory drugs (NSAIDs) on a daily basis. Gastrointestinal (GI) toxicity owing to the use of NSAIDs is a well-recognized clinical problem, with approximately 25% of all reported adverse drug reactions being attributed to prescription NSAID use. In addition to prescription NSAIDs, the use of over-the-counter (OTC) formulations of these products is common. Although it has been suggested that OTC doses of NSAIDs may not lead to significant GI toxicity, the data confirming this have been lacking. Data on the GI risks of OTC doses of aspirin, ibuprofen, naproxen, paracetamol, and no drug from 4164 consecutively diagnosed patients with rheumatoid arthritis from eight ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers in North America are presented. Serious GI events were defined as GI bleeds and other clinically significant GI events requiring hospitalization. Relative risks were standardized for potential demographic confounders using Cox proportional hazard models. Although the relative risk of OTC doses of NSAIDs (3 to 4) is less than the previously published risk of prescription doses (6 to 7), it remains clinically significant and a matter of serious concern because of the widespread use of these medications and an underappreciation of the true risk. Paracetamol was not associated with increased risk of GI complications and should be considered first-line therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Focal cortical-subcortical calcifications (FCSCs) and epilepsy in the Indian subcontinent.

PURPOSE: A focal cortical-subcortical calcification (FCSC) is a common finding on computed tomography (CT) in individuals with focal or generalized seizures in the Indian subcontinent. We sought to determine the relation of FCSCs to epilepsy by comparing the lobe of seizure origin by electroclinical and CT evaluations and to study the nature and severity of epilepsy associated with FCSCs. METHODS: The relation of these FCSCs to epilepsy/seizures was studied in 40 patients, seen for the first time to the neurology outpatient department of a tertiary care hospital. An attempt was made to classify seizures and determine their lobe of origin based on clinical-electroencephalographic (EEG) criteria of the International League Against Epilepsy (ILAE). The clinical lobe of origin was compared with the location of the FCSC on CT scan. In addition, records of the CT unit of the same hospital were reviewed retrospecitvely, to identify cases with an FCSC and their referral diagnoses. RESULTS: Thirty-one (77.5%) patients with FCSCs were considered to have localization-related epilepsy (frontal lobe epilepsy, 20; temporal lobe epilepsy, three; parietal lobe epilepsy, one; occipital lobe epilepsy, three; and definitely localization related but having ambiguous localization features, four) based on ictal semiology and EEG studies. Other ILAE categories in the cohort included epilepsy without unequivocal focal or generalized features (four patients; 10%), isolated seizures (one patient; 2.5%), juvenile absence epilepsy (one patient; 2.5%), and insufficient data to classify epilepsy (three patients; 7.5%). Radiologic sites for FCSCs included frontal (20; 50%), temporal (six; 15%), parietal (seven; 17.5%), and occipital (seven; 17.5%). Electroclinical and radiologic data were congruent in localizing and lateralizing seizures in 22 (55%) patients. The FCSC was truly incidental in one patient with juvenile absence epilepsy. Discordance between the clinical and radiologic localizations was noted in five (12.5%) instances. Magnetic resonance imaging (MRI) did not reveal additional lesions corresponding to lobes of origin as determined by electroclinical analysis. Discordance was surmised to be a result of seizure spread from a silent region to symptomatic cortex. In 12 (30%) patients, electroclinical and radiologic congruence could not be ascertained because ictal descriptions were either inadequate or ambiguous, and EEG findings were noncontributory. Review of 4,452 CT scans of brain performed in the CT unit revealed 29 (0.65%) cases with FCSCs in individuals with nonseizure disorders, that could be labeled as incidental. CONCLUSIONS: An FCSC is an important radiologic finding in localization-related epilepsy in the Indian subcontinent. The severity of epilepsy ranges from asymptomatic cases to daily seizures.

Adolescent↗
PubMed2000

Clara cell proteins.

Clara cells are nonciliated, nonmucous, secretory cells of the pulmonary airways. These cells are known to secrete a variety of proteins, including Clara cell 10-kDa protein/uteroglobin. This protein consists of a homodimer of 70-77 amino acid polypeptides arranged in antiparallel fashion. In vitro testing suggests that the protein suppresses inflammation. The physiologic role of the protein remains to be determined.

Animals↗
PubMed2000

Chronic continuous cocaine infusion in rats: effect on urine cocaine, ecgonine methylester and benzoylecgonine concentrations and bolus-dose cocaine pharmacokinetics.

The aim of this study was to determine the effect of chronic cocaine infusion on urine cocaine, ecgonine methylester and benzoylecgonine concentrations to establish if they varied with dose and duration of cocaine administration. Male rats were continuously infused with cocaine at either 6 or 18 mg kg(-1) daily for 13 days. Three urine samples taken over the course of the infusion period showed that cocaine, ecgonine methylester and benzoylecgonine concentrations varied with the dose administered and the duration of administration. Cocaine, ecgonine methylester and benzoylecgonine concentrations were 2-3 times greater in the high-dose group than the low-dose group at each sampling time point. These decreased, respectively, from 7.0+/-1.1, 26.7+/-4.5 and 29.5+/-5.4 microg mL(-1) to 2.5+/-0.5, 10.5+/-1.8 and 11.8+/-1.5 microg mL(-1) in the high-dose group and from 1.0+/-0-2, 7.8+/-1.5 and 6.3+/-0.1 microg mL(-1) to 0.5+/-0.1, 4.0+/-0.6 and 3.1+/-0.4 microg mL(-1) in the low-dose group (P < 0.05) over the infusion period. We also studied the pharmacokinetic and metabolic profile of an intravenous bolus dose of 2.5 mg kg(-1) cocaine hydrochloride after a similar cocaine infusion in rats. Cocaine pharmacokinetics and the profile of ecgonine methylester, benzoylecgonine and norcocaine were no different from rats chronically infused with saline for the same period. Altered cocaine metabolism could not explain the effect of the duration of cocaine infusion on altered metabolite concentrations in urine. Ecgonine methylester/benzoylecgonine urine concentration ratios did not alter with duration of infusion (1.2+/-0.2 and 1.1+/-0.2 in the high-dose group at the first and last time point) and were not affected by the dose of cocaine (1.3+/-0.6 and 1.2+/-0.1 at corresponding times in the low-dose group (P > 0.05)). We conclude that chronic cocaine infusion does not alter cocaine metabolism. This was not reflected by absolute cocaine metabolite urine concentrations, which varied with time, but was represented by urine ecgonine methyl ester/benzoylecgonine concentration ratios.

Anesthetics, Local↗
PubMed2000

Factors influencing delay in treatment seeking by first-time attenders at a genitourinary clinic.

We examined treatment-seeking behaviours amongst a consecutive sample of 188 first-time attenders at a busy genitourinary (GU) clinic in a general hospital. Participants were interviewed and completed a battery of questionnaires prior to receiving diagnosis or treatment. Delay in treatment seeking was measured in 3 ways: utilization delay, illness behaviour delay and appraisal delay. Appraisal delay and illness behaviour were significantly related, but were unrelated to utilization delay. Substantial delays were reported before seeking treatment, with a median of 30 days elapsing between first noticing symptoms and attending the clinic. Analysis of age groups indicated that the oldest groups--45 and above were likely to delay longest, on all 3 measures of delay.

Adolescent↗
PubMed2000

The role of the p53 tumor suppressor in the response of human cells to photofrin-mediated photodynamic therapy.

Although there is evidence that the p53 tumor suppressor plays a role in the response of some human cells to chemotherapy and radiation therapy, its role in the response of human cells to photodynamic therapy (PDT) is less clear. In order to examine the role of p53 in cellular sensitivity to PDT, we have examined the clonogenic survival of normal human fibroblasts that express wild-type p53 and immortalized Li-Fraumeni syndrome (LFS) cells that express only mutant p53, following Photofrin-mediated PDT. The LFS cells were found to be more resistant to PDT compared to normal human fibroblasts. The D37 (LFS cells)/D37 (normal human fibroblasts) was 2.8 +/- 0.3 for seven independent experiments. Although the uptake of Photofrin per cell was 1.6 +/- 0.1-fold greater in normal human fibroblast cells compared to that in LFS cells over the range of Photofrin concentrations employed, PDT treatment at equivalent cellular Photofrin levels also demonstrated an increased resistance for LFS cells compared to normal human fibroblasts. Furthermore, adenovirus-mediated transfer and expression of wild-type p53 in LFS cells resulted in an increased sensitivity to PDT but no change in the uptake of Photofrin per cell. These results suggest a role for p53 in the response of human cells to PDT. Although normal human fibroblasts displayed increased levels of p53 following PDT, we did not detect apoptosis or any marked alteration in the cell cycle of GM38 cells, despite a marked loss of cell viability. In contrast, LFS cells exhibited a prolonged accumulation of cells in G2 phase and underwent apoptosis following PDT at equivalent Photofrin levels. The number of apoptotic LFS cells increased with time after PDT and correlated with the loss of cell viability. A p53-independent induction of apoptosis appears to be an important mechanism contributing to loss of clonogenic survival after PDT in LFS cells, whereas the induction of apoptosis does not appear to be an important mechanism leading to loss of cell survival in the more sensitive normal human fibroblasts following PDT at equivalent cellular Photofrin levels.

Cell Line↗
PubMed2000

Mechanisms of tumor metastasis to bone.

Bone metastases occur in approximately 80% of patients with advanced cancer. They are characterized by cancer cell growth and bone destruction that cause pain, fractures, anemia, and hypercalcemia. At diagnosis, bone metastases are usually incurable owing to their advanced development. However, the early stages in their formation are asymptomatic and begin as single micrometastatic cells from the blood stream. These cells can be detected by molecular analysis of bone marrow in approximately 30% of patients at the time of cancer diagnosis, but not all single micrometastatic cells develop into clinically significant bone metastases. A synergistic relationship exists between the micometastasis and the bone environment creating favorable conditions for the development and growth of disseminated tumor cells. Such bone metastases induce osteolysis or new bone formation, releasing growth factors and cytokines, which in turn amplify this pathological mechanism. The underling hypothesis, first proposed by Paget in 1889, is that the growth of disseminated tumor cells in bone is dependent on the fertility of the soil or bone itself. This article explores the most current opinions in this area of study and presents a comprehensive summary of the major factors involved.

Bone Neoplasms↗
PubMed2000

Species-dependent pharmacological properties of the melanocortin-5 receptor.

The genes encoding the melanocortin-3 receptor and melanocortin-5 receptor have been cloned from rhesus monkey. Heterologous expression in CHO cells indicated species dependent in vitro pharmacological properties for the human and rhesus melanocortin-5 receptors. Several peptides including NDP-alpha-MSH, alpha-MSH, MT-II and ACTH1-24 are more potent at the rhesus melanocortin-5 receptor than the human melanocortin-5 receptor by more than 10-fold. In contrast, we found no species difference in pharmacological properties between the human and rhesus melanocortin-3 receptors. Such a species-dependent pharmacological difference for melanocortin-5 receptor appears to be an exception compared to other G protein-coupled receptors from human and rhesus monkey.

Amino Acid Sequence↗