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Biomedical subjects

M H Ali

Publications and source records attributed to M H Ali.

At least 19 recordsLinked to original sources

Failure to implement hospital antimicrobial prescribing guidelines: a comparison of two UK academic centres.

BACKGROUND: Rational antimicrobial therapy should provide maximum benefit to patients while minimizing the development of resistant microorganisms. OBJECTIVES: The aim of this study was to investigate (i) which antimicrobial drugs were chosen by hospital doctors faced with two common infections [community-acquired pneumonia (CAP) and urinary tract infection (UTI)], (ii) whether these choices were compliant with local guidance and (iii) the factors that influenced antimicrobial choice. METHODS: A questionnaire based on two hypothetical clinical scenarios was distributed to 316 hospital doctors across four UK NHS hospitals in two cities (Newcastle and Edinburgh). RESULTS: Doctors in Newcastle were significantly more aggressive in their management: more patients were admitted (CAP: 78.9% versus 48.4%, P < 0.05) and given antimicrobials intravenously (CAP: 53.4% versus 21.2%, P < 0.05). Adherence to the local hospital guideline for CAP was significantly higher in Newcastle (83.3% versus 38.0%; P < 0.05). Fewer than half of the doctors surveyed used the local hospital guideline when choosing an antimicrobial, and the British National Formulary was the most frequently used resource (>90%). Junior doctors also identified medical school teaching and opinions of senior doctors as important influences. CONCLUSIONS: This study highlights inadequacies in the implementation and promotion of local guidelines, and demonstrates the potential for widely varying antimicrobial practices in two comparable UK cities.

Anti-Bacterial Agents↗

Evidence that the lizard helospectin peptides are O-glycosylated.

Six forms of helospectin (a vasoactive intestinal peptide analogue) were purified from the venom of the Heloderma horridum lizard. Their identification was performed by combining sequencing by automated Edman degradation and electrospray mass spectrometry analysis on the complete peptides and their tryptic fragments. The products resulting from the action of an O-glycosidase were also analysed. Two forms were identified as the previously named Hs1 and Hs2 of 38 and 37 amino-acid residues, respectively. Two forms corresponded to Hs1 and Hs2 O-glycosylated by a N-acetylhexosamine-hexose motif attached to the Ser32 residue. Two other forms were not completely characterized but might correspond to the O-glycosylated forms bearing a phosphate or a sulfate group. The glycosylation did not affect the capacity of the helospectins to recognize and to activate the human and the rat VPAC1 and VPAC2 receptors.

Adenylyl Cyclases↗

A single centre's 20 years' experience of columnar-lined (Barrett's) oesophagus diagnosis.

BACKGROUND: The pattern of oesophageal carcinoma type has been changing for some time in a number of countries, with adenocarcinoma becoming more frequent OBJECTIVE: To investigate the prevalence of columnar-lined (Barrett's) oesophagus and oesophageal adenocarcinoma in Barrett's oesophagus during a 20-year period in a single centre. METHODS: All upper gastrointestinal endoscopy and histology reports for the period January 1977 to December 1996 inclusive were reviewed. Data were analysed from patients who had histologically proven Barrett's oesophagus. The data were analysed as a single cohort and in five-year bands according to the date of diagnosis. RESULTS: Of 44,721 endoscopies, 636 Barrett's oesophagus cases were diagnosed; 508 (323 males 185 females; M:F ratio 1.7) were histologically proven. The frequency of Barrett's oesophagus detection increased steadily from 0.2% to 1.6% of all endoscopies per five-year band. The M:F ratio and the mean ages at diagnosis (61 years, range 60-63 for males and 69 years, range 68-79 for females) remained constant throughout. Barrett's oesophagus was diagnosed at a younger age in males (peak 60-69 years) compared to females (peak 70-79 years). The male oesophageal adenocarcinoma incidence (11.1%) was almost twice that in females (6.5%). In the majority (81%), the initial diagnosis of oesophageal adenocarcinoma and Barrett's oesophagus was made concurrently. CONCLUSIONS: The increasing Barrett's oesophagus frequency may reflect an increasing incidence or recognition of this condition or both. Barrett's oesophagus males are more likely to develop oesophageal adenocarcinoma than females.

Adenocarcinoma↗

Endothelial permeability and IL-6 production during hypoxia: role of ROS in signal transduction.

Prolonged hypoxia produces reversible changes in endothelial permeability, but the mechanisms involved are not fully known. Previous studies have implicated reactive oxygen species (ROS) and cytokines in the regulation of permeability. We tested whether prolonged hypoxia alters permeability to increasing ROS generation, which amplifies cytokine production. Human umbilical vein endothelial cell (HUVEC) monolayers were exposed to hypoxia while secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1alpha, IL-6, and IL-8 was measured. IL-6 and IL-8 secretion increased fourfold over 24 h in a pattern corresponding to changes in HUVEC permeability measured by transendothelial electrical resistance (TEER). Addition of exogenous IL-6 to normoxic HUVEC monolayers caused time-dependent changes in TEER that mimicked the hypoxic response. An antibody to IL-6 significantly attenuated the hypoxia-induced changes in TEER (86 +/- 4 vs. 63 +/- 3% with hypoxia alone at 18 h), whereas treatment with anti-IL-8 had no effect. To determine the role of hypoxia-induced ROS on this response, HUVEC monolayers were incubated with the antioxidants ebselen (50 microM) and N-acetyl-L-cysteine (NAC, 1 mM) before hypoxia. Antioxidants attenuated hypoxia-induced IL-6 secretion (13 +/- 2 pg/ml with ebselen and 19 +/- 3 pg/ml with NAC vs. 140 +/- 15 pg/ml with hypoxia). Ebselen and NAC prevented changes in TEER during hypoxia (94 +/- 2% with ebselen and 90 +/- 6% with NAC vs. 63 +/- 3% with hypoxia at 18 h). N-nitro-L-arginine (500 microM) did not decrease hypoxia-induced changes in dichlorofluorescin fluorescence, IL-6 secretion, or TEER. Thus ROS generated during hypoxia act as signaling elements, regulating secretion of the proinflammatory cytokines that lead to alterations of endothelial permeability.

Antibodies↗

Prolonged hypoxia alters endothelial barrier function.

BACKGROUND: It is well recognized that hypoxia/reoxygenation and exposure to inflammatory mediators such as cytokines and neutrophils alter the barrier function of the vascular endothelium. The experiments we conducted tested whether hypoxia alone could produce changes in permeability and whether a prolonged period of hypoxia alters the surface expression of cell adhesion molecules. METHODS: Endothelial cells were cultured from human umbilical vein endothelial cells (HUVECs). Hypoxia was created by isolating the cells in a chamber through which 1% 02, 5% CO2, and 94% N2 were insufflated (30 min at 1/min). Oxygen tension was measured through oxygen-quenching phosphorescence. Hypoxia was maintained for 24 hours. Changes in endothelial permeability were measured by transendothelial electrical resistance (TEER). Endothelial leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression were assessed by flow cytometry (mean +/ standard error of the mean [SEM]. RESULTS: Exposure of endothelial cells to hypoxia resulted in increased permeability between 6 and 24 hours, with the greatest decrease in TEER at 18 hours (63% +/ 3%; P < .05). Prolonged hypoxia produced no change in the surface expression of ELAM-1 or ICAM-1. CONCLUSIONS: Hypoxia alone produced a significant reversible alteration in endothelial permeability. However, this change was observed only under severe hypoxic conditions (eg, below 20 mm Hg); higher oxygen tensions (25 and 35 mm Hg) had no significant effect. Unlike observations made after cytokine exposure, hypoxic breakdown of endothelial barrier function was unassociated with up-regulation of either ELAM-1 or ICAM-1.

Cell Hypoxia↗

Invasive carcinoma in juvenile polyposis--report of a case in an African patient.

Since the 1980s it has been recognized that the polyps of juvenile polyposis have malignant potential. Since the introduction of colonoscopy this syndrome has been redefined and the hamartoma-adenoma-carcinoma sequence recognized. We believe this case is the first report of an invasive carcinoma associated with juvenile polyposis to be described in an African patient.

Adenocarcinoma, Mucinous↗

Cytokines and the malnutrition of chronic renal failure.

Malnutrition in uremic patients remains one of the major causes of morbidity and mortality. Its mediators remain largely unknown. Uremia is characterized by changes in circulating levels of catabolic cytokines and anabolic growth factors. The aim of this study was to investigate whether these changes are associated with the malnutrition of patients with chronic renal failure (CRF). We have studied the prevalence of malnutrition in a small group of patients (n = 20) with CRF (serum creatinine = 551 +/- 105 mumol/l, mean +/- SD) and 25 age-matched controls. Nutritional status was assessed by dietary diaries, subjective global assessment (SGA), and by measurement of anthropometric parameters. Regression analysis was applied to examine the relationship between biochemical and anthropometric parameters. Simultaneously, we have investigated changes in the circulating levels of catabolic cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6] and an anabolic growth factor [insulin-like growth factor-I (IGF-I)]. We observed a high prevalence of malnutrition as judged initially by SGA: 50% moderately malnourished and 15% severely malnourished. This was confirmed by anthropometric measurements. We noted a significant reduction in both triceps skinfold thickness (TST; 35% of patients < 25th centile) and midarm muscle circumference (MAMC, 65% of patients < 25th centile). We also noted a reduction in serum IGF-I in malnourished patients (IGF-I in well-nourished patients = 207 +/- 48 micrograms/l, in malnourished patients = 133 +/- 33 micrograms/l, p < 0.01). IGF-I correlated with TST (r = 0.71, p < 0.001) and MAMC (r = 0.47, p < 0.05). IGF-I had a high predictive value for TST (R2 = 51%, p < 0.001). In contrast, TNF-alpha levels were higher in malnourished patients: 19.5 +/- 30 pg/ml compared to 3.9 +/- 8 pg/ml in healthy patients (p < 0.001) and TNF-alpha showed a negative correlation with MAMC (r = -0.69, p < 0.01; R2 = 47%, p < 0.01). IL-1 beta levels were higher in CRF than in controls but did not correlate with nutritional parameters. No significant changes could be detected in serum IL-6. A significant percentage of predialysis patients with CRF suffer from some degree of malnutrition. This may be attributed in part to a fall in circulating anabolic growth factors and an increase in catabolic cytokines.

Adult↗

Community-acquired bacteremia in human immunodeficiency virus-infected children in Harare, Zimbabwe.

BACKGROUND: HIV infection is common in mothers and their children in Zimbabwe, and HIV-infected children are particularly susceptible to bacterial infections. There is little information on the etiology and outcome of HIV-related bacteremia in African children. METHODS: Blood cultures from 309 hospitalized children in Zimbabwe, of whom 168 were diagnosed as having HIV, were examined for pathogens. The association among significant bacteremia, HIV infection and mortality was assessed in these children. RESULTS: The most common isolates were coagulase-negative staphylococci (31 children, 25 clinically significant), Staphylococcus aureus (22 children) and Streptococcus pneumoniae (20 children). Nontyphoidal Salmonella (10 children), Escherichia coli (4 children) and Klebsiella sp. (4 children) were the most frequent Gram-negative bacteria. Two children had Rhodococcus equi pneumonia. HIV-infected children showed increased risk of bacteremia (odds ratio (OR) = 2.68), especially if younger than 18 months of age (OR = 2.94), and high risk of enterobacteremia (OR = 15.76). There was no significant association of bacteremia with nutritional status. Mortality was 17% overall but was higher in HIV-infected children up to 6 months of age (OR = 2.81) and in bacteremic children of any age (OR = 2.03). CONCLUSIONS: Prompt recognition of pathogens and early administration of appropriate antimicrobials is important in reducing the morbidity and mortality associated with bacteremia in HIV-infected children in Africa.

AIDS-Related Opportunistic Infections↗

Are junior doctors taught to use problem lists?

One hundred junior doctors were asked to complete a questionnaire about the training they had received in the use of problem lists. A questionnaire was sent about the training in the use of problems lists at their medical school to the Deans in all 27 British medical schools. Of the 100 junior doctors, 57 reported that problem lists 'had hardly been mentioned' at their medical school. In contrast only one of the 24 Deans who responded thought that problems lists were 'likely to be hardly mentioned' at his medical school. After graduation only 35 junior doctors had worked for a consultant who had demanded the use of problem lists and only 17 of these had worked for more than one such consultant. Most junior doctors have received little training in the use of problem lists as undergraduates and even fewer as postgraduates. Few consultants demand the use of problem lists.

Academic Medical Centers↗

The polymerase chain reaction can reveal the occurrence of naturally mixed infections with Leishmania parasites.

On isolation and characterization of Leishmania parasites from Sudanese patients with visceral leishmaniasis (VL), four cases of mixed infections were found. Three of those cases were from the Eastern Sudan focus of VL. In one case the patient was found to be concomitantly infected with Leishmania donovani and Leishmania aethiopica, while the remaining three patients possessed mixed infections of Leishmania donovani and Leishmania major. Mixed infections were identified by PCR amplification of Leishmania kinetoplast DNA (kDNA) from parasites in culture or in original patient aspirate material and, additionally in the former cases by isoenzyme electrophoresis. In those cases where parasite culture was successful, PCR also demonstrated the rapidity with which one Leishmania species was eliminated from culture during continuous passage.

Animals↗

Characterization of a variant tandem repeat from Sudanese Onchocerca volvulus.

Strategies for detection and control of onchocerciasis in Africa have included identification of DNA probes and PCR target sequences for sensitive and specific detection of parasites. To evaluate the applicability of published PCR and DNA probe based methods for the study of onchocerciasis in Sudan, we collected adult O. volvulus from geographically distinct regions of Sudan (700 miles apart), Abu Hamed (northern desert) and Raja (southwestern savannah), and we examined the similarities between Sudanese O. volvulus repeats and published versions of the repeat from West African O. volvulus. Amplification of DNA extracted from the Raja O. volvulus strain predictably generated a ladder of products, multiples of the base 150 bp repeat, as has been reported from West Africa. However, amplification of DNA from the Abu Hamed O. volvulus isolate resulted in a series of doublets. The unexpected DNA fragments thus amplified differed in size from the base 150 bp unit by approximately 50 base pairs and was most clearly visualized at 150-200 base pairs. DNA sequence analysis of the amplified repeats in the isolate of O. volvulus from Abu Hamed revealed a variant of the 150 bp tandem repeat which contained an extra 49 bp. The additional 49 bp contained two short repeats of 21 bp and 10 bp, corresponding to bases 99-119 and 128-137 respectively, of the known 150 bp O. volvulus repeat. This work demonstrates a variant of the O. volvulus 150 bp tandem repeat, which easily distinguishes Raja and Abu Hamed isolates of O. volvulus, and which has potential value for differentiating Abu Hamed strains of O. volvulus from other strains in East Africa.

Animals↗

Vaginal and cervical abnormalities associated with trichomonal infection.

Cytological changes were studied among 393 women, reporting to Samir Health Centre, Khartoum (Sudan), using Papanicolaou staining. Vaginal trichomoniasis was confirmed by wet-mounts and cultural methods. Non-specific inflammatory changes were prominent (17.4%). In 33.5% of parasitised patients, the cervix was found healthy. Cancer of the cervix was not detected in patients investigated.

Adolescent↗