Aspiration of bile during laparoscopic cholecystectomy benefits surgeon and investigator.
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Biomedical subjects
Publications and source records attributed to J Morris.
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OBJECTIVE: To determine the increase in FEV1 associated with increasing doses of inhaled terbutaline and salbutamol, the reproducibility of the increase in FEV1, and the reproducibility of the associated optimal bronchodilator dose, in patients with chronic airflow limitation (CAL). DESIGN: Double-blind, randomized, controlled trial examining spirometric response to cumulative doses of bronchodilators. PATIENTS AND SETTING: Patients with clinical diagnosis of CAL, FEV1 below 70% predicted, and FEV1 to FVC ratio less than 0.7 after administration of bronchodilator recruited from secondary care respirology practices. MEASURES OF OUTCOME: The estimates of maximum and optimal bronchodilation, as well as the associated drug dosages, were established in each patient on three occasions (twice on terbutaline and once on salbutamol). The 'optimal' drug dose was defined as the lowest dose associated with an FEV1 not exceeded by 50 ml on any other dose. MAIN RESULTS: Thirty-five patients completed the trial. FEV1 improved from 0.93 to a maximum of 1.191 with terbutaline (average of the two administrations) and from 0.951 to 1.141 with inhaled salbutamol (difference in increase in FEV1 between terbutaline and salbutamol P = 0.006). In less than 50% of cases administration of more than four puffs of bronchodilator resulted in FEV1 increase by more than 50 ml. The average dose of salbutamol and terbutaline associated with optimal bronchodilation were 430 micrograms and 1160 micrograms respectively. Patients varied widely in the optimal dose. Estimates of optimal dose were not reproducible (intraclass correlation coefficient < 0.5). CONCLUSION: Substantial incremental increase in FEV1 in response to increasing doses of beta-agonists beyond those commonly used in clinical practice is restricted to a minority of patients. Lack of reproducibility limits the clinical usefulness of establishing the optimal dose of beta-agonist for a given patient.
Conservative surgery followed by a course of radiotherapy has been shown to be as effective as mastectomy in terms of survival and disease-free interval. This has led to an increase in the number of surgeons who undertake conservative surgery for early breast cancer. However, some studies have shown that, when offered a choice of surgery, some women elect mastectomy. Such results highlight the need for patients to be fully involved in the decision made about surgery, especially in the circumstances where there is more than one surgical option and a choice of surgery can be offered.
Arguments are being made more frequently to incorporate economic evaluations and quality of life assessments into clinical trials. Using a randomised, multicentre, phase 3 cancer clinical trial as an example, this paper outlines the importance of including such assessments; the practical considerations associated with the design of such trials; the methods for collecting such data; and, how such data can be used. Finally, it is emphasised that the anticipated benefits of collecting data relating to resource use and quality of life should outweigh the associated costs to research funding organisations.
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A case-control study has been undertaken in a rural area of The Gambia to evaluate risk factors for death from acute lower respiratory tract infections (ALRI) in young children. On the basis of a post-mortem interview 129 children aged < 2 years were thought to have died from ALRI. These cases were each matched according to age, sex, ethnic group, time and place of death with a child who had died from a cause other than an ALRI and with two live control children. Cases and controls were well matched. Comparison of cases and live controls suggested that exposure to smoke during cooking, parental smoking and exclusive, prolonged breastfeeding were associated with an increased risk of death from ALRI whilst sharing a bed with siblings, use of antenatal and welfare clinics and immunization were associated with a reduced risk of death from ALRI. No associations were found between mortality from ALRI and maternal education and literacy, socioeconomic status or with the age of the mother. Comparison of children who died from causes other than ALRI with the live controls showed a similar pattern of associations and no significant differences were found in any of the risk factors studied between children whose deaths were attributed to ALRI and those whose death was attributed to another cause. Association of death with exposure to smoke during cooking was the strongest risk factor identified. This risk might be altered by reducing smoke exposure during cooking.
Fifty-eight back pain patients and 21 entry-level Postal Service workers without low-back pain were evaluated using a variety of lumbar function measures. Isolated trunk strength and full lifting strength were gauged with isokinetic and isometric methods. Lumbar range-of-motion was computed using toe-touch and goniometers. Conventional clinical techniques such as toe touch and straight leg raise were effective in distinguishing back-injured from normal subjects. Isometric and isokinetic peak force and torque tests failed to show significant differences between low-back pain and job applicant groups. When compared with published norms, our job applicant group was significantly deconditioned. Our data suggest that asymptomatic, deconditioned subjects could be mistaken for back-impaired patients or symptom magnifiers.
It has been suggested that T lymphocytes expressing gamma delta T-cell receptors could play an important role in defence against some intracellular infectious pathogens. The present study was undertaken to characterize the occurrence and variable delta gene expression of T lymphocytes expressing the gamma delta T-cell receptor in oriental cutaneous leishmaniasis. Eleven cases of oriental cutaneous leishmaniasis were investigated by immunohistological analysis using an alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. In three cases, we observed an increased percentage of gamma delta T cells (about 20% of CD3+ cells). In these cases gamma delta T cells generally expressed the V delta 2 segment, and only rarely the V delta 1 gene product. V delta 2+ cells were predominantly localized in the dermis, and were virtually absent in the epidermal compartment. The rare gamma delta T cells observed in the epidermis were almost exclusively V delta 1+. This study demonstrates that an increase of gamma delta T cells may be found in oriental cutaneous leishmaniasis, although it is not a constant feature of the disease. The finding of a preferential expansion of the V delta 2 subset suggests that this subpopulation of gamma delta T cells might be selectively involved in the recognition of Leishmania antigens. The distinct compartmentalization of gamma delta T-cell subpopulations indicates that these subsets may recognize distinct sets of antigens.
The extent of diversity of the gamma delta T-cell receptor (TCR) in normal human skin and Oriental Cutaneous Leishmaniasis (OCL) was examined by molecular analysis of the variable (V) delta gene segment, junctional (J) delta gene segment and junctional regions. To examine the expression of TCR delta genes, segments of gamma delta T lymphocytes, DNA isolated from normal human skin and from OCL were subjected to enzymatic gene amplification by the polymerase chain reaction (PCR) method using TCR V delta- and J delta-specific oligonucleotides as primers. PCR amplification using these primers indicated that the V delta 2 gene segment was predominantly used by gamma delta T lymphocytes in both normal human skin and OCL. To determine the extent of junctional diversity in the delta gene of gamma delta T cells in normal human skin and OCL, we sequenced the nucleic acid sequences corresponding to the V delta 2/J delta 1 junctional regions. Sequence analysis of junctional regions demonstrated broad junctional diversity in normal skin but only limited diversity in OCL. Our findings support the hypothesis that skin gamma delta T lymphocytes may derive from a fetal subset of gamma delta T lymphocytes that leaves the thymus early and colonizes the periphery. The limited junctional diversity demonstrated in OCL lesions indicates that gamma delta T cells can undergo oligoclonal expansion following recognition of a specific ligand and supports the idea that junctional regions are important in the recognition of antigenic determinant.
The transforming function of human papillomavirus type 16 (HPV16) E7 has been shown to depend on activities additional to the ability to bind RB. In this paper we describe two further properties of E7 which may also contribute to transformation, an association with a histone H1 kinase at the G2/M phase of the cell cycle and an ability to bind the RB-related protein p107. The region of E7 identified previously as important for RB binding was found to be involved in the association with the kinase and complex formation with p107, although analysis of E7 point mutants within this region revealed a difference in the precise sequence requirement for RB and p107 binding. Association with the kinase activity correlated with the ability to bind RB, but the restriction of the kinase association to the G2/M phase of the cell cycle implies that this activity might not be directly mediated by RB binding. Since kinase-binding-deficient E7 mutants are also transformation defective, this may represent an independent function of E7 which plays a role in the G2/M phase of the cell cycle.
myf5 is one of a family of four myogenic determination genes that control skeletal muscle differentiation. To study the role of myf5 in vivo, we generated transgenic mice harboring the bovine homolog, bmyf, under control of the murine sarcoma virus promoter. Ectopic expression of the full-length bmyf transgene was detected in brain and heart tissue samples of F1 progeny from transgenic founder mice. Ectopic bmyf expression activated endogenous skeletal myogenic determination genes in the hearts and brains of transgenic animals. Incomplete skeletal myogenesis in most hearts gave rise to cardiomegaly and focal areas of cardiomyopathy. In brains in which ectopic expression led to a more complete myogenesis, focal areas of multinucleated, striated myotubes containing actin, desmin, and myosin were observed. These unexpected results show that myf5 can initiate myogenic differentiation in vivo, supporting the hypothesis that myf5 is responsible for determination of cells to the myogenic lineage in normal embryogenesis.
An enema that contained a complex of bismuth citrate and polyacrylate was compared with 5-aminosalicylic acid (5-ASA) enemas for treatment of distal ulcerative colitis. The multicentre trial involving 63 patients was randomised and double blind with enemas given over four weeks; clinical, sigmoidoscopic, and histological assessments were made. Improvements were seen in both treatment groups. Clinical remission was seen in 18 of 32 patients treated with 5-ASA and 12 of 31 patients treated with bismuth citrate-carbomer (chi 2 1.94; p = 0.16). Sigmoidoscopic remission occurred in 20 of 32 patients in the 5-ASA group and 15 of 31 patients given bismuth (chi 2 1.27; p = 0.26). Improvement of rectal biopsy histology by at least one grade was seen in 16 of 32 patients in the 5-ASA group and 14 of 31 patients with bismuth (chi 2 0.15; p = 0.70). Analysis of covariance gave no significant difference between groups, although there was a trend favouring 5-ASA. There was no evidence of bismuth accumulation during the trial. Bismuth enemas may offer a new therapeutic option in distal ulcerative colitis.
AIMS: To compare the International Normalised Ratio (INR) obtained directly with the two types of WHO plain International Reference Preparation for thromboplastin in patients treated with coumarin. METHODS: Prothrombin times were performed in parallel at four centres using WHO human plain IRP (BCT/253) and rabbit plain IRP (RBT/79). Sixty patients and 20 normal controls were tested at each centre. Differences in INR among the centres were assessed by one factor, analysis of variance. The bias for each centre was assessed by the t test. RESULTS: At all four centres higher INRs were consistently found with the rabbit plain reagent. Two of the centres showed significantly greater bias. CONCLUSIONS: There was a small but significant difference in INR results obtained directly with these two reference reagents at all four centres (mean 7.35%). This in part may result from the different responsiveness of the two IRP to the coumarin defect or to imprecision of the original ISI calibrations of the two plain WHO IRP. The findings support the adoption of a single master IRP, in accord with WHO recommendations, which would resolve the present anomalous situation.
This study was conducted to compare the effects of omega 3 fatty acids, taken as fish or fish-oil supplements in the setting of a high- or low-fat dietary background, on blood pressure and heart rate in men with moderate cardiovascular risks. One hundred twenty men were randomly allocated to five high-fat (40% of daily energy) and two low-fat (30% of energy) groups to undertaken a 12-week dietary intervention period involving fish, fish oil, or a combination of these. Sodium intake was restricted to less than 90 mmol/d. The five high-fat groups were assigned to take either 6 or 12 fish-oil capsules daily, fish or a combination of fish oil and fish, or placebo capsules. The two low-fat groups took either fish or placebo capsules. Fish meals were devised to provide 1.3 g of eicosapentaenoic acid daily, equivalent to that contained in 6 fish-oil capsules. Subjects were instructed to eat a selection of fish that provided an average of 3.65 g/d (range, 3.2 to 4.1 g/d) of total omega 3 fatty acids. Subjects were seen at regular intervals during the baseline and dietary intervention periods for measurement of weight, blood pressure, heart rate, dietary compliance, urinary electrolyte excretion, platelet phospholipid fatty acids, blood glucose, and insulin concentration. There was a greater fall in both systolic and diastolic blood pressures in subjects allocated fish or fish oil, particularly in the low-fat groups, compared with control subjects. However, there was no significant group effect.(ABSTRACT TRUNCATED AT 250 WORDS)
A myofiber hyperplastic quail line P has been developed through selection for heavy body weight. Since the number of muscle fibers is determined early in development and skeletal muscle originates from somites, we compared somite formation and muscle-specific gene expression in P- and control C-line quail embryos. At 47 hours of incubation, C embryos had 18 somite pairs and P embryos had 14.3. By 72 and 120 hours, both lines appeared to be at the same stage of somite development. To determine whether the delay in the formation of the brachial somites was accompanied by alterations in muscle-specific gene expression, we conducted whole-mount in situ hybridization and immunofluorescence studies. At 47 hours of incubation, C embryos were expressing qmf1 in the first 12 somites, while in P embryos only the first 7 somites showed qmf1 activation. Delays in expression were also observed for qmf3 at 43 hours and for all three myogenic factors (qmf1, qmf2 and qmf3) at 60 hours. At 65 hours, C embryos expressed myosin heavy chain in the first 15 somite pairs and P embryos in the first 7. At 72 hours, the transient delay in somite formation had disappeared and there was no lag in myosin heavy chain expression between the lines. The phase delay in brachial somite formation, myogenic factors and myosin heavy chain expression may be associated with the observed myofiber hyperplasia in P-line quail by allowing an increase in the muscle stem cell population.
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We surveyed varsity athletes at a Big East university to assess attitudes toward a mandatory drug education and testing program and examined whether there were differences in drug-related attitudes and behaviors based on gender or varsity sport. We found no statistically significant differences in personal drug use behaviors based on gender or team affiliation. Attitudes about drug use and knowledge of a teammate using drugs did show significant differences based on varsity sport. Tennis players were most likely to agree that drug use by college athletes is socially acceptable. Lacrosse players were most likely to know of atleast one teammate using drugs. Overall, attitudes towards the mandatory drug education and testing program were ambivalent. About half of our responding athletes believed drug testing was necessary and discouraged drug use. Only 17% believed that the program was an invasion of privacy.
We examined a series of 2-aminochromone analogs typified by U-84569 [8-methyl-2-(4-morpholinyl)-7-(1-naphthylenylmethoxy)-4H-1- benzopyran-4-one] as potential antithrombotic agents. U-84569 proved to be a potent inhibitor of human platelet aggregation regardless of the agonist used. Subsequent experiments showed that U-84569 increased platelet cyclic AMP (cAMP) levels in intact cells, but U-84569 did not directly stimulate adenylate cyclase. Our experiments showed that U-84569 was a potent inhibitor of the low Km cAMP-dependent phosphodiesterase with an IC50 of 300 nM in platelet cytosol. Isobutylmethylxanthine had an IC50 of 10 microM in the same system. Although U-84569 elevated cAMP by inhibiting cAMP metabolism, we were interested in the mechanism by which cAMP blocked aggregation. Our first experiments showed that U-84569 concentration-dependently blocked agonist-stimulated, but not phorbol myristate acetate-dependent, phosphorylation of the 47 kDa protein kinase C substrate in platelets. These data suggested that U-84569 could interrupt receptor-mediated signal transduction. In support of this hypothesis, U-84569 proved to be a potent inhibitor of thrombin-stimulated inositol phosphate synthesis, diacylglycerol formation and Ca++ mobilization in intact cells. These data indicate that agonist-stimulated phospholipase C activity was reduced in U-84569-treated cells. There was no direct influence of U-84569 on either basal or thrombin-stimulated phospholipase C activity in broken cells, suggesting that U-84569 (by inhibiting phosphodiesterase and elevating cAMP), indirectly blocked receptor-mediated phospholipase C activation and aggregation in platelets. The 2-aminochromones represent a new class of potent antithrombotic agents.