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Biomedical subjects

M George

Publications and source records attributed to M George.

At least 91 records · Page 5Linked to original sources
PubMed1997

Candesartan cilexetil: safety and tolerability in healthy volunteers and patients with hypertension.

The tolerability and safety of candesartan cilexetil has been evaluated in over 5000 subjects enrolled into double-blind or open-label clinical studies. In double-blind clinical trials in patients with primary hypertension, candesartan cilexetil 2-16 mg once-daily was associated with a low incidence of adverse events and drug-related withdrawals, similar to placebo. The drug showed no evidence of dose-dependent adverse events and it was equally well tolerated by men and women and by elderly (> or =65 years) and younger (<65 years) patients alike. Candesartan cilexetil had no effect on blood glucose control or serum lipid profile in patients with type II diabetes. It was very well tolerated also when given in combination with hydrochlorothiazide or amlodipine and during long-term open-label therapy (up to 1 year). Candesartan cilexetil therefore possesses an excellent tolerability profile that extends to a wide variety of patients including the elderly and it does not aggravate co-existing risk factors such as hyperlipidaemia or glucose intolerance. It therefore appears to offer a better tolerated alternative to other commonly used antihypertensive agents.

Angiotensin Receptor Antagonists↗
PubMed1997

Evaluation of primers for PCR amplification of RNA polymerase gene sequences of foot-and-mouth disease virus.

Eight oligonucleotide primers in 7 different combinations were used to amplify 3D gene sequences of foot-and-mouth disease virus (FMDV) by reverse transcription-polymerase chain reaction (RT-PCR). Six of the primers were designed at this laboratory. All the primer combinations could specifically amplify 3D gene sequences of FMDV serotypes O, A, and C. The largest fragment amplified was of 1,393 bp and the smallest was of 208 bp in size. The 1,393 bp fragment included sequences from the preceeding P18 region of FMDV genome. The second largest fragment of 734 bp included sequences from the 3'-extracistronic region of viral genome. The remaining fragments were amplified either from the 3'- or 5'-half of the 3D gene. Specific amplification of the entire 3D gene in fragments of different size showed sequence conservation in the 3D genomic region of FMDV and usefulness of the primers reported in detecting inapparent or persistent FMDV infection in susceptible animals by RT-PCR.

Animals↗
PubMed1996

AIDS. Sharing knowledge.

There is a large and growing demand for HIV/AIDS services among residents of east London. Many of those infected or affected are refugees or asylum seekers who often fear statutory agencies.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The antidepressant drug phenelzine produces antianxiety effects in the plus-maze and increases in rat brain GABA.

Research on the effects of antidepressant/ antipanic drugs in animal models of anxiety has yielded equivocal results, even after chronic drug regimens. In contrast, we found that the antidepressant/antipanic drug phenelzine, given acutely, produced a clear anxiolytic effect in the elevated plus-maze, a widely-used animal model of "anxiety" that is primarily sensitive to benzodiazepine-type anxiolytics (e.g., diazepam). Furthermore, the effective dose of phenelzine (15 mg/kg) administered to rats was associated with more than a 2- fold increase in whole brain levels of gamma-aminobutyric acid (GABA), whereas an ineffective dose of phenelzine (5.1 mg/kg) did not significantly change GABA levels. The N-acetylated metabolite of phenelzine, N2-acetylphenelzine, produced neither an anxiolytic effect in the elevated plus-maze nor a significant change in whole-brain levels of GABA. However, both phenelzine and N2-acetylphenelzine potently inhibited monoamine oxidase, a mechanism commonly thought to be involved in the therapeutic effects of monoamine oxidase inhibitors such as phenelzine in the treatment of depression in humans. These results suggest that the mechanism whereby phenelzine produces anxiolytic effects in the plus-maze model is unique to a facilitatory action on brain levels of GABA, in contrast to classical benzodiazepines, which produce anxiolytic effects by enhancing the affinity of the GABAA-receptor for GABA.

Animals↗
PubMed1996

A district-wide examination of 75-year olds suggests discrimination in the provision of services.

The aim of this study was to assess the adequacy of existing services across a whole health district for those aged 75 years, in an attempt to detect shortfalls and biases in the provision of services. This study was carried out as a cross-sectional survey using community based nurses in the county of South Glamorgan. 1376 people in their 75th year who were registered with a general practitioner were visited, and their problems assessed by community based nurses. There was a marked difference in the results of the assessment for different services. It was estimated that 76% of the 75-year olds would benefit from additional health services, and 37% from social services. There was a striking difference between the services in the proportion of people whose problems were satisfactorily solved, according to the criteria used by the community nurses. The proportion of problems that were solved varied according to the degree of dependency of the individuals, and the service involved. Some services showed a clear trend to care more for dependent people; services with a relatively undeveloped home delivery system seemed likely to discriminate against people who were dependent.

Aged↗
PubMed1996

Management of malignant biliary stricture with self-expanding metallic stent.

BACKGROUND: Self-expanding metallic mesh stents are designed to remain patent longer than polyethylene (PE) stents, which generally clog in 3 to 4 months. Though more expensive, metal stents may therefore be a better choice for malignant strictures. METHODS: From January 1991 to October 1995, we performed ERCP in 212 patients with malignant or benign strictures, and 34 ultimately had insertion of a metallic stent. These stents were placed by the percutaneous transhepatic route in 17 patients and endoscopically in 17. RESULTS: Metallic stent insertion was successful in each case and relieved the preoperative jaundice and cholangitis. There were no procedure-related deaths; complications were pancreatitis (one) and hemorrhage (one). Overall stent patency was 6.2 months. Three of 34 stents occluded due to tumor ingrowth at 3, 4.5, and 8 months and were treated by placing a new PE stent through the blocked metal stent. The remaining 31 stents remained patent until patient death (n = 15, mean survival = 4.9 months) or are still open (n = 16, mean patency = 12.2 months). CONCLUSIONS: Self-expanding metal stents provide effective palliation of malignant biliary strictures and should be considered an alternative to open surgery. Metal stents remain patent much longer than PE stents and usually a single session of metal stenting can palliate biliary obstruction for life.

Adult↗
PubMed1996

Responses to novelty stress in female F344 rats: effects of age and d-fenfluramine treatment.

To elucidate some of the mechanisms underlying the neuroendocrine and neurochemical changes associated with age in female rats, we administered the serotonin (5-HT) releaser and reuptake inhibitor, d-fenfluramine (d-FEN; 0.0 or 0.6 mg/kg/day, PO) for 30-38 days to young (4 month) and old (21 month) F-344 female rats. Animals were placed into a novel open field (OF) for 20 min before sacrifice. Control animals were sacrificed immediately upon removal from their home cage (HC). Old rats exhibited significantly (p < 0.05) less exploratory behavior and a smaller CORT response to OF than young animals. d-FEN treatment had no effect on plasma ACTH and CORT levels or exploratory behavior. The old HC rats had significantly (p < 0.05) higher plasma levels of prolactin (PRL) than the young HC rats. A stress induced increase in PRL secretion was observed in the old rats only, which was attenuated by d-FEN treatment. In the OF groups, both the young and old rats showed elevated medial frontal cortex (MFC) dopamine turnover (DOPAC/DA ratio), but only the young rats exhibited an elevation in norepinephrine (NE) turnover (MHPG/NE ratio). d-FEN treatment blocked the stress-induced increase in NE turnover in the young rats and the increase in DA turnover in the old rats. These data suggest that 5-HT activity could be involved in the age-related changes in the MFC catecholamine and PRL responses to stress in female rats.

Adrenocorticotropic Hormone↗
PubMed1996

Lack of requirement for prolonged incubation of Septi-Chek blood culture bottles in patients with bacteremia due to fastidious bacteria.

A questionnaire survey for which there were 538 respondents from American clinical microbiology laboratories was used to assess the need for prolonged incubation of Septi-Chek blood culture bottles for the recovery of HACEK bacilli, Brucella species, Francisella tularensis, and nutritionally deficient streptococci from blood. Among a total of 219 reported isolates of these bacteria, in only 6 cases (2.7%) was incubation longer than 7 days required. Only 2 of 136 patients (1.5%) were noted to be bacteremic exclusively following incubation of Septi-Chek blood culture bottles for periods of greater than 7 days. It appeared from the results of this study, that incubation of Septi-Chek blood culture bottles for 7 days is usually sufficient in patients suspected of having bacteremia due to fastidious bacteria.

Bacteremia↗
PubMed1996

Endoscopic management of benign and malignant biliary strictures.

BACKGROUND: It is now possible to manage most extrahepatic bile duct strictures, benign or malignant, using endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic dilatation and stenting. METHODS: Over a 5-year period we treated 218 patients with strictures of extrahepatic bile ducts. Eighty-six patients had benign biliary stricture. Endoscopic treatment was performed in 67 (78%) of these patients. Open surgical biliary drainage was preferred in 12 patients (14%), and 7 patients (8%) were managed conservatively without stenting or surgery. One hundred and thirty-two patients had malignant biliary stricture. One hundred and one patients (77%) underwent endoscopic stent placement. Thirty-one patients (23%) underwent surgery for potential curative resection after diagnostic ERCP. The average life span in the malignant stricture group was 5 months (range 0.1 to 25 months) after the initial endoscopic procedure. RESULTS: Altogether 313 endoscopic procedures in 218 patients were performed for benign and malignant bile duct strictures. Complications included hemorrhage in 8 (3%), pancreatitis in 10 (3%), and suspected retroperitoneal perforation in 2 (0.6%). There were no ERCP related deaths; one patient died of uncontrolled bleeding from transhepatic stenting. In benign strictures, there has been no recurrence of strictures after the last stent removal with a mean followup of 21 months (range 0.1 to 31 months). All complications were successfully treated conservatively. CONCLUSIONS: Endoscopic management of benign and malignant biliary stricture is possible with minimal morbidity and mortality and should be considered an acceptable option to surgical management.

Bile Duct Diseases↗
PubMed1996

Synthesis and structure determination of the adducts formed by electrochemical oxidation of 1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene in the presence of deoxyribonucleosides or adenine.

Study of DNA adducts formed with aromatic hydrocarbons is part of the strategy to elucidate the mechanisms of tumor initiation by these compounds. 1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene (THDMBA) is of special interest because it allows discrimination between the pathways of bioactivation by one-electron oxidation and monooxygenation. To study and identify adducts formed biologically, synthetic adducts are needed as reference standards. THDMBA was electrochemically oxidized in the presence of deoxyadenosine (dA), adenine (Ade), deoxyguanosine (dG), or deoxycytidine (dC). In the presence of dA, four adducts were isolated: 7-methyl-1,2,3,4-tetrahydrobenz[a]anthracene-12-CH2-N7Ade (7-MTHBA-12-CH2-N7Ade, 3.6%), 12-MTHBA-7-CH2-N7Ade (4.2%), 7-MTHBA-12-CH2-N6dA (5.8%), and 12-exo-methylene-7-MTHBA-7-N6dA (22.8%); a dehydrogenated product, 7,12-di-exo-methylene-THBA (44.2%), was also obtained. In the presence of Ade, nine adducts were synthesized: 7-MTHBA-12-CH2-N7Ade (1.1%), 12-MTHBA-7-CH2-N7Ade (2.4%), 7-MTHBA-12-CH2-N1Ade (10.2%), 12-MTHBA-7-CH2-N1Ade (13.2%), 7-MTHBA-12CH2-N3Ade (1.7%), 12-MTHBA-7-CH2-N3Ade (1.7%), 7-exo-methylene-12-MTHBA-12-N3Ade (11.2%), 12-exo-methylene-7-MTHBA-7-N3Ade (27.9%), and 12-exo-methylene-7-MTHBA-7-N6Ade (12.1%), as well as the dehydrogenated product 7,12-di-exo-methylene-THBA (16.7%). In the presence of dG, three adducts were produced: 7-MTHBA-12-CH2-N7Gua (24.2%), 12-MTHBA-7-CH2-N7Gua (12.2%), and 7-MTHBA-12-CH2-N2dG (3.7%), as well as the dehydrogenated product 7,12-di-exo-methylene-THBA (38.9%). Anodic oxidation in the presence of dC yielded a large amount of 7,12-di-exo-methylene-THBA (80.4%), but no adducts. The structure of the adducts was elucidated by using UV, NMR, and MS. The N-7 positions in dG, dA, and Ade, the 2-NH2 in dG, and the N-1 position in Ade form exclusively methyl-linked adducts. In contrast, the 6-NH2 group of dA and Ade and the N-3 of Ade prefer to attack the meso-anthracenic positions rather than the methyl groups. The order of reactivity of dG and dA in the formation of methyl-linked THDMBA adducts agrees well with that previously found for 7,12-dimethylbenz[a]anthracene [RamaKrishna et al. (1992) J. Am. Chem. Soc. 114, 1863-1874.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

The relationship between tumour glutathione concentration, glutathione S-transferase isoenzyme expression and response to single agent carboplatin in epithelial ovarian cancer patients.

There is evidence to suggest that glutathione (GSH) and glutathione-S-transferases (GST) are important factors in determining sensitivity to cytotoxic drugs in vitro and in preclinical in vivo model systems. To define the relationship between tumour GSH concentration, GST isoenzyme expression and response to carboplatin in epithelial ovarian cancer (EOC), tumour samples from 39 patients with assessable disease after primary surgery were analyzed for GSH content and GST expression. Response was assessed after completing six courses of single agent carboplatin therapy. GSH was measured by high performance liquid chromatography (HPLC) in fresh tumour samples taken at primary laparatomy. GST isoenzyme expression was assessed by immunohistochemistry of fixed tumour material using antibodies specific for pi, alpha and mu classes. GST isoenzyme expression was defined as positive if the staining intensity was strong and more than 10% of tumour cells were involved. The mean GSH concentrations were: 8351 +/- 4496, 7211 +/- 5026, 6559 +/- 4573 and 3758 +/- 1885 (nmol g-1 tissue dry weight mean +/- s.d.) for tumours from patients who subsequently achieved a complete response (CR, n = 18), partial response (PR, n = 10) or who had static disease (SD, n = 7) or progressive disease (PD, n = 4) respectively. There was no relationship between GSH concentration and response (ANOVA, P = 0.32). There were also no relationship between GST isoenzyme expression and response (P Fisher's exact test 0.51-0.55 and chi-squared test 0.98-0.99). In conclusion, there was no association between the concentration of GSH or expression of GST isoenzymes and response to single agent carboplatin in primary previously untreated EOC.

Antineoplastic Agents↗
PubMed1996

Faecal microflora and urease activity during the first six months of infancy.

Gastrointestinal degradation of urea might, according to a new hypothesis, have consequences for the regulation of acid-base balance as well as control of breathing during infancy. Thirteen infants were investigated from their first few days of life to the age of 6 months by collecting faecal samples at the age of 3 days, 2, 3, and 6 months, respectively. The faecal microflora was determined after aerobic and anaerobic cultivation and the faecal urease activity was assessed after 36 h aerobic and anaerobic preincubation. The infants were mostly breast fed and had a faecal microflora containing anaerobic bacteria such as Bifidobacteria, Bacterioides and Lactobacilli but also aerobics such as Escherichia coli, Enterococci and sometimes Klebsiella. The faecal pH increased from approximately 5.30 to 5.90, the pH after anaerobic preincubation being on an average 0.2 pH units lower than after aerobic preincubation. Simultaneously the nitric oxide production of the faecal specimens increased approximately 10-fold and the urease activity decreased by a factor of 3 to 5. We also found an inhibitory action of nitrate, nitrite (in mumolar concentration) and nitric oxide (in parts per million concentration) on the faecal urease activity. Hence, the present results warrant further research in order to determine more precisely the action of different concentrations of various nitrous oxides on individual bacterial species, and furthermore, to assay the faecal urease activity in victims of sudden infant death syndrome as well as in infants dead due to other causes.

Bacteria, Aerobic↗
PubMed1996

Recombinant human interleukin-3 (rhIL-3) enhances the mobilization of peripheral blood progenitor cells by recombinant human granulocyte colony-stimulating factor (rhG-CSF) in normal volunteers.

To identify a precisely timed and safe protocol for progenitor cell mobilization, we studied the effects of rhIL-3 and rhG-CSF administration to normal volunteers. rhG-CSF 5 micrograms/kg/d was administered subcutaneously (s.c.) for 7 consecutive days either alone or preceded by rhIL-3 5 micrograms/kg/d s.c. for 4 consecutive days in sequential or partially overlapping schedules. The combined cytokines were well-tolerated--adverse effects were similar to those of the individual agents. Total white blood cell (WBC) and neutrophil counts rose briskly in response to rhG-CSF, and peak mean values were similar between treatment cohorts. Mean platelet counts were modestly elevated during rhG-CSF treatment only in the cohorts receiving rhIL-3 and rhG-CSF. Mean circulating CD34+ cells peaked on day 5 in the rhG-CSF group (38.9+/-14.3/microliter), day 6 in the sequential rhIL-3/rhG-CSF group (56.4+/-12.4/microliter), and day 6 in the partial overlap group (46.1+/-10.9/microliter). On day 3, mean CD34+ cell counts of the subjects who received sequential treatment were markedly higher than observed in the other groups (p<0.05) and were estimated to have been sufficient for collection of adequate grafts by single 10-L leukapheresis procedures in 60% of subjects. Circulating clonogenic cells (CFU-GM and/or BFU-E) were substantially higher in the sequential group than the rhG-CSF group on days 3-6 but were only minimally elevated above baseline in the partial overlap group. The numbers of circulating CD34+/Lin-/Thy-1+ cells (putative stem cells) were increased substantially, especially in the sequential group. On the basis of this pilot trial, we conclude that priming with rhIL-3 is a safe and well-tolerated method for enhancing the mobilization of human blood progenitors and stem cells by rhG-CSF.

Adult↗