Impact of the oil industry on malaria diagnosis and management in north-east Scotland (1992-99).

In order to assess the current pattern of malaria presenting to the Aberdeen Infection Unit a retrospective casenote review was undertaken of 110 patients admitted with that diagnosis between 1st January 1992 and 31st August 1999. Oil-related work was the reason for travel in 48 (43.6%) of the UK residents, holiday in 35 (31.8%), backpacking in 8 (7.3%) and other work in 5 (4.5%). Sixty-five patients (59.1%) had PL falciparum malaria (pure or mixed), 25 (22.7%) had PL vivax, 6 (5.4%) PL ovale and 3 (2.7%) PL malariae infection. No prophylaxis had been taken by 66% of the 47 UK-based oil workers and by 36% of the other 48 UK residents who had returned from Africa. There is a need for better education of oil workers and holidaymakers travelling to areas endemic for malaria. We are now setting up a travel advisory service in our Unit to address the problem.

A novel human gene similar to the protein kinase (PK) coding domain of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) codes for a serine-threonine PK and is expressed in melanoma cells.

The large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is a multifunctional protein that contains a serine-threonine protein kinase (PK) activity (Nelson, J. W., Zhu, J. , Smith, C. C., Kulka, M., and Aurelian, L. (1996) J. Biol. Chem. 271, 17021-17027). Phylogenetic analyses indicated that ICP10 PK belongs to a distinct subfamily of growth factor receptor serine-threonine PKs that are characterized by their ability to function with a limited number of conserved catalytic motifs (Hunter, J. C. R., Smith, C. C., and Aurelian, L. (1995) Int. J. Onc. 7, 515-522). Here, we report the isolation and characterization of a novel gene, designated H11, that contains an open reading frame of 588 nucleotides, which encodes a protein similar to ICP10 PK. The H11 protein has Mn(2+)-dependent serine-threonine-specific PK activity as determined with a GST-H11 fusion protein and by immununocomplex PK/immunoblotting assays of 293 cells transfected with a H11 eukaryotic expression vector. PK activity is ablated by mutation of Lys(113) within the presumtive catalytic motif II (invariant Lys). 293 cells stably transfected with H11 acquire anchorage-independent growth. Endogenous H11 RNA and the H11 phosphoprotein are expressed in melanoma cell lines and primary melanoma tissues at levels higher than in normal melanocytes and in benign nevi. Melanoma cell proliferation is inhibited by treatment with antisense oligonucleotides that inhibit H11 translation, suggesting that H11 expression is associated with cell growth.

Anxiety and endocrine responses to surgery: paradoxical effects of preoperative relaxation training.

It has been argued that surgery is a form of psychological stress, and that the response to it should therefore be modifiable by psychological means. To test this hypothesis, we assessed the effect of preoperative relaxation instructions on endocrine, cardiovascular, and subjective responses in 21 patients undergoing minor abdominal surgery. Controls (N = 19) received general procedural information. In the relaxation group only, there was a significant increase in cortisol and adrenaline concentration from immediately before induction of anesthesia to immediately after surgery. Noradrenaline values were unaffected by relaxation. In contrast, relaxation reduced state-anxiety on the preoperative day and the two postoperative days; maximal peroperative systolic and diastolic blood pressures were also reduced. The results are consistent with previous evidence that adrenaline and cortisol responses to surgery are greater in less anxious patients.

Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.

We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [3H]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (Bmax) than F344/N rats, but there were no differences in benzodiazepine binding affinities (Kd) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine Bmax to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hypothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary-adrenal axis function through differential sensitivity to GABA-mediated feedback.

An open study of teicoplanin in the treatment of gram-positive infections.

Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, was evaluated in treating 36 hospitalized patients suffering from various Gram-positive infections. The 36 patients received teicoplanin once daily as a mean intravenous injection of 550 mg/day (range 200-800 mg/day). Previous antimicrobial therapy was used in 28% of patients. The mean duration of therapy was 7.5 days (range 3-38 days). The overall clinical success rate was 94%. 24/36 patients (66%) had positive microbiology. Elimination of the pathogens was seen in 75% of all evaluable cases. Four patients with early prosthetic valve endocarditis due to coagulase negative Staphylococcus (3 patients) and Propionibacterium acnes (1 patient) had a favorable clinical and microbiological outcome. No adverse drug reactions were observed. Teicoplanin is safe and effective in the therapy of many different infections caused by Gram-positive bacteria.

Piperacillin/tazobactam in the treatment of serious acute soft tissue infection.

Twenty-five consecutive patients admitted to hospital with severe soft tissue infection were entered into an open trial designed to evaluate safety and efficacy of the drug combination tazobactam/piperacillin. The dosage regimen was 4 g piperacillin/500 mg tazobactam Q8H. There were twenty cases of uncomplicated cellulitis and five cases with associated abscess formation. These five cases required adjunctive surgical drainage. Mean duration of therapy was 7.6 days. No other antibiotics were administered unless treatment with the study drug failed. There were eight treatment failures, six related to the trial drug. Four patients developed an allergic response to the trial drug, necessitating a change of therapy. Three patients failed to respond; all three had acute cellulitis in association with peripheral vascular disease. Significant bacterial isolates were grown in thirteen patients; Group A streptococci in three, S. aureus in five, other pathogenic streptococci in four and coliforms or Ps. aeruginosa in five. The majority of isolates except the streptococci were resistant to piperacillin but all isolates except one strain of Ps. aeruginosa were susceptible to the combination. The combination is suitable for the treatment of serious soft tissue infection, but increased doses may be appropriate in infection at poorly perfused sites.

Treatment of symptomatic enteric aeromonas hydrophila infection with ciprofloxacin.

As a part of local sporadic outbreak of Aeromonas hydrophila gastroenteritis, 3 symptomatic patients required hospitalisation. Treatment with ciprofloxacin appeared to accelerate recovery from severe or persistent diarrhoea due to this organism. All the isolates from the outbreak were sensitive to this drug.

Amniotic fluid infection syndrome in private and non-private patients.

The incidence of placental histological evidence of amniotic fluid infection syndrome (AFIS) was studied in two groups of patients delivered at term. One group received private medical care during pregnancy, while the other patients were delivered at a midwife obstetric unit. There was no significant difference in histological evidence of AFIS in the private patient (22%) and non-private patient (28%) groups.

Glucose tolerance and plasma lipid distributions in rats fed a high-sucrose, high-cholesterol, low-chromium diet.

Male Sprague-Dawley rats were fed either a low-chromium (60 to 100 micrograms per kg of diet) or chromium-supplemented (5 mg per kg of diet), high-sucrose, high-cholesterol diet from weaning until age 18 months. Rats that were pair- and meal-fed the low-chromium diet had higher one-hour postprandial plasma glucose concentrations than their supplemented partners at ages 4 and 8 months (P less than 0.05), but not at age 12 months. One-hour postgavage (250 mg glucose/100 g body wt) glucose concentrations did not differ between dietary groups at 12 months. Plasma cholesterol concentrations increased up to age 12 months, but neither they nor postprandial triglyceride concentrations differed significantly between dietary groups. Ad libitum feeding of the low-chromium and chromium-supplemented diets was initiated at age 14 months in order to determine whether there were differences due to dietary chromium content which might not be manifest on the pair-feeding regimen. Animals of both dietary groups had significant weight gain by age 16 months, but their one-hour postgavage plasma glucose concentrations did not differ significantly. Plasma cholesterol concentrations increased significantly following institution of ad libitum feedings, but neither they nor lipoprotein cholesterol or triglyceride distributions differed significantly between dietary groups. Experimental conditions, methods, and results from this study and previous studies are compared and critically examined. We suggest that other factors in addition to dietary chromium content may contribute to the differences in glucose tolerance and plasma cholesterol concentrations described in such studies and that there is a need for improved documentation of glucose intolerance and tissue chromium concentrations in this animal model.

The nucleus basalis in Alzheimer's disease: cell counts and cortical biochemistry.

The cell density in the Nucleus Basalis in six patients with clinical and histological evidence of Alzheimer's disease and reduced choline acetyltransferase activity in frontal and temporal cortex was found to be in approximately 50% of the cell count in five control subjects.

Choline acetyltransferase activity and histopathology of frontal neocortex from biopsies of demented patients.

Cortical biopsies were taken from the frontal lobe of 25 patients with presenile dementia. Choline acetyltransferase (ChAT) activity, and in some specimens the high affinity uptake of choline, was used to estimate loss of cholinergic nerve terminals. Of the 15 samples with varying degrees of histological evidence of Alzheimer's disease (AD) 14 were from clinically suspected examples of the disease. There was significant loss of ChAT in 10 of the 15 compared with control and the mean activity was also highly significantly reduced (to 41% of control). The deficit was found in patients examined within a year of onset of symptoms. In 6 biopsies from clinically suspected cases of AD without diagnostic histological features there was loss of activity in only one, subsequently shown to have Jakob-Creutzfeldt disease. The remaining samples were two of vascular dementia (no loss of ChAT), one probable disorder of white matter (no loss of activity) and one undiagnosed disorder (with loss of ChAT activity). Thus most patients without histologically demonstrated AD had no evidence of a presynaptic cholinergic defect. It was concluded that suspected cases of AD particularly suitable for putative cholinergic therapy were those with an onset of the disease at 55 to 65 and an absence of family history.

Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities.

We have examined the choline acetyltransferase [CAT] activity in autopsy samples of frontal and temporal lobe cortex from 47 patients (31 with Alzheimer's disease, 4 with dementia due to cerebrovascular disease and 12 undemented controls) and compared it with the severity of dementia during life and with the numbers of argyrophilic plaques and neurofibrillary tangles in the corresponding areas of cortex in the contralateral cerebral hemisphere. CAT activity was significantly reduced, most severely in the temporal lobe, in patients with Alzheimer's disease but not in patients with a cerebrovascular cause for their dementia, and CAT activity showed no significant reduction with age in the undemented control patients. In the patients with Alzheimer's disease the reduction in CAT activity was significantly correlated with the severity of dementia and with the numbers of neurofibrillary tangles, but not argyrophilic plaques, present in the corresponding contralateral cortex.

The effect of dietary ascorbic acid and alpha-tocopherol on fecal mutagenicity.

The effect of supplemental ascorbic acid and alpha-tocopherol on fecal mutagenicity was examined in 2 studies involving 20 healthy human donors aged 22-55 years. The vitamins were given at a dose of 400 mg daily each. The mutagen was extracted from individual frozen feces samples with dichloromethane, and assayed with Salmonella Typhimurium tester strain TA100 without microsomal activation. In the first study, with a single donor on a controlled diet, the fecal mutagenicity decreased (P less than 0.001) on treatment to 21% of control. In the second study, with 19 donors on free-choice diets, the mutagenicity in producers on treatment decreased (P less than 0.01) to 26% of control. Addition of ascorbic acid and alpha-tocopherol directly to feces led to no change in mutagenicity. Antioxidants in the diet may have a role in lowering the body's exposure to endogenously produced mutagens.

Non-mutagenicity for Salmonella of the chlorinated hydrocarbons aroclor 1254, 1,2,4-trichlorobenzene, mirex and kepone.

A polychlorinated biphenyl mixture, Aroclor 1254, two commercial grade insecticides, mirex and kepone, and a pesticide breakdown product, 1,2,4-trichlorobenzene were evaluated for mutagenicity and hepatic enzyme induction potential in the Salmonella/microsomal assay. None was found to revert strains TA1535, TA1537, TA98 or TA100 when tested with or without metabolic activation. Liver microsomal extracts (S9) from rats induced with 1,2,4-trichlorobenzene were shown to differ from S9 of either control or Aroclor 1254-induced rats in the capacity to activate 2-aminoanthracene mutagenesis.