Biomedical subjects
Publications and source records attributed to A Watson.
We describe here the integration of image analysis and robotics to produce a fully automated colony picking/plate handling system. Biological tests were performed to verify its performance in terms of sterilisation and accuracy of picking. The machine was then used by a single operative to pick a 36,000 clone cDNA library in approximately 42 hrs over 5 days.
Forty-five patients with histologically proven Barrett's columnar-lined oesophagus (CLO) were treated in one unit over a 9-year period. Patients were studied prospectively as part of a surveillance programme; all initially received standard conservative treatment including high-dose H2-receptor antagonists. A satisfactory initial response was seen in 21 patients, but in 24 the symptoms were unchanged or progressed; 19 patients in the latter group were considered suitable for antireflux surgery and underwent fundoplication. Symptoms of heartburn or dysphagia persisted or recurred in 88 per cent of patients receiving medical treatment alone and complications developed in 38 per cent, including nine strictures and one adenocarcinoma. In patients undergoing antireflux surgery, symptoms persisted or recurred in 21 per cent and complications developed in 16 per cent (P < 0.01). Complete regression of Barrett's CLO occurred in two patients (11 per cent) after antireflux surgery. The results of this study suggest the superiority of antireflux surgery over pharmacological acid suppression in the control of symptoms and prevention of complications in patients with Barrett's CLO.
1. Intramuscular injection of the 5-HT agonist DL-fenfluramine increased the metabolic rate of mature cockerels by about 25% over the following 22 hr. The acute effect, over the 3 hr following injection, attained 40% at 10 degrees C, 35% at 20 degrees C and 25% at 32 degrees C. 2. Heat loss mechanisms (peripheral vasodilatation, postural change and panting) were also stimulated, to an extent which varied with ambient temperature. 3. Food intake, respiratory quotient and locomotor activity were significantly reduced by fenfluramine injection. 4. The opposing effects on heat production and heat loss had an influence on deep-body temperature which varied from a reduction of 0.5 degrees C at 10 degrees C ambient to an increase of about 0.5 degrees C at 32 degrees C. 5. The 5-HT blocker, methysergide, prevented the effects of fenfluramine on both heat production and heat loss for about 5 hr after injection. 6. The autonomic ganglion blocker, hexamethonium chloride, reduced the thermogenic but not the heat-loss effects of fenfluramine. 7. The results suggest that DL-fenfluramine has centrally-occurring but independent effects on heat production and a number of heat loss effectors, and that the heat production effect is mediated by the autonomic nervous system. The effect of fenfluramine on deep-body temperature appears to result from an altered equilibrium between heat production and heat loss.
Nine primary pulmonary carcinomas, one metastatic carcinoma, and two malignant pleural mesotheliomas have been analysed for the expression at the mRNA level of metalloproteinases (MPs) and tissue inhibitors of MPs (TIMPs). In situ hybridisation showed TIMP-1 and TIMP-2 transcripts predominantly over tumour stroma and gelatinases evenly distributed over both stromal and tumour cells. While both TIMP-1 and TIMP-2 were expressed in non-neoplastic lungs (NNL) as well as in carcinomas, stromelysin 3 (ST3), 92 kDa gelatinase and interstitial collagenase were expressed only by carcinomas. Expression of these MPs by carcinomas was independent of histologic type and such tumour features as fibrosis or necrosis. The consistent expression of ST3 by all of the carcinomas examined and absence of its expression in NNL indicates that ST3 production is likely associated with the malignant phenotype. However, since 92 kDa gelatinase and interstitial collagenase transcripts were found in some but not all tumour samples, their expression is not a uniform feature of pulmonary carcinomas. The possible prognostic significance of the expression of the latter two enzymes by carcinomas remains to be established.
A prospective study compared post-operative astigmatism and visual acuity (corrected and uncorrected) following phacoemulsification and extracapsular surgery. Fifty eyes had implantation of a 7 mm diameter optic intraocular lens (IOL) following conventional extracapsular cataract extraction (ECCE) with a 10 mm corneal incision. Forty-seven eyes were implanted with a 5 x 6 mm optic IOL through a 5 mm scleral incision after phacoemulsification. Uncorrected visual acuity of 6/9 or better was achieved in 25% of eyes on the first day following phacoemulsification, 36% at 1 week and 57% at 12 weeks. These results (and also the best corrected acuity) were significantly better than those following ECCE. Less astigmatism was induced by phacoemulsification than extracapsular surgery, measured at all post-operative time intervals.
Fifty normal subjects were studied comparing objective autorefraction using the Allergan Humphrey 570 (AH 570) and Canon RK-1 autorefractors in terms of ease of operation, the time taken and their accuracy compared with clinical refraction. Both the autorefractors were equally easy to operate but the AH 570 was quicker. Objective autorefraction with the AH 570 was more accurate than using the Canon RK-1 especially with respect to spherical equivalence, sphere power and cyclinder axis: approximately 80% of the values were within 0.51 dioptres or 11 degrees of clinical refraction compared to approximately 60% for the Canon RK-1. The possible reasons for the superior performance of the AH 570 are discussed.
Fifty patients (50 eyes) with posterior chamber intraocular lenses and a best corrected visual acuity of at least 6/12 were studied. The Allergan-Humphrey 570 (AH-570) and Canon RK-1 autorefractors were compared in terms of ease of operation, time taken and their accuracy relative to clinical refraction. Both the autorefractors were equally easy to operate but the AH-570 was quicker. The AH-570 had a higher percentage of eyes within 11 degrees of clinically determined cylinder axis while the Canon RK-1 had a higher percentage of patients within 0.51 diopters of spherical equivalence, sphere power and cylinder power as determined by clinical refraction. This difference in the accuracy of objective autorefraction was not statistically significant; the clinical significance is uncertain.
We measured Snellen visual acuity under standard and glare conditions using the Allergan Humphrey 570 autorefractor in 46 pseudophakes (46 eyes) undergoing Neodymium-YAG laser posterior capsulotomy before and after treatment. All the patients studied had a best corrected vision of at least 6/12 but complained of visual disability and had clinically observable posterior capsule opacification. The patients did not have other known causes of glare disability. Following posterior capsulotomy, 30 (65%) patients showed an improvement in standard Snellen visual acuity and 44 (97%) an improvement in Snellen visual acuity under glare conditions. This difference was statistically significant (p < 0.001). Of the 16 patients whose standard Snellen visual acuity did not improve after posterior capsulotomy, 14 showed a reduction in glare disability. Glare testing was clinically useful in evaluating pseudophakes with posterior capsule opacification who complained of visual disability in spite of good Snellen visual acuity under standard testing conditions.
Pseudomonas pseudomallei, which causes melioidosis, is most commonly associated with pulmonary infection. We describe seven patients who developed a neurological syndrome as the predominant manifestation of melioidosis: this syndrome was characterized by peripheral motor weakness (mimicking Guillain-Barré syndrome), brain-stem encephalitis, aseptic meningitis, and respiratory failure. Neurological melioidosis occurred in the absence of demonstrable foci of infection in the central nervous system (CNS) in five of six patients whose cerebrospinal fluid was available for culture. Computed tomography and magnetic resonance imaging of the brain and spinal cord of these patients were not suggestive of pyogenic infection, although the latter procedure detected brain-stem encephalitis. Autopsy findings in one case confirmed brain-stem encephalitis without evidence of direct bacterial infection. The clinical presentation of neurological melioidosis includes features of an exotoxin-induced neurological syndrome, with profound neurological disease occurring in the absence of apparent direct infection of the CNS. This syndrome appears to be a newly recognized clinical presentation of melioidosis.
OBJECTIVES: To determine the pattern, obstetric outcome and factors that predispose to pregnancies in young teenagers in Hull. DESIGN: Retrospective study of case records of pregnancies from 1977 to 1988 in girls aged 16 years or less and in a control group of nulliparous women aged 20-24 years. SETTING: Hull health district hospitals. SUBJECTS: 1,660 pregnant teenagers and 3,576 nulliparas aged 20-24 years. MAIN OUTCOME MEASURES: Ages at pregnancy, number of pregnancies per year, gestational age at booking and delivery, antenatal complications, mode of delivery, utilization of contraceptives and some social factors. RESULTS: Of the 1,660 pregnancies in the young adolescents, 59-6% were terminations. The youngest girl was 11. The average annual incidence of early teenage pregnancies was 10.5 per 1,000 girls aged 10-16 compared to 6.4 per 1,000 in England and Wales. Physical characteristics and pattern of antenatal care were similar in the study and control groups. Anaemia was 2.53 times as common in teenagers (95% CI 2.19-2.9; P < 0.0001) while hypertension alone was 1.7 times as frequent (95% CI 1.28-2.4; P = 0.002). Pre-eclampsia and proteinuric disorders were similar in the two groups. Apart from prolonged pregnancy, which was significantly less common in the index group, other gestational ages at delivery and birthweights were the same in both groups. The caesarean section rate in the index group was 0.56 times that in the control group (95% CI 0.4-0.75; P < 0.0001) but forceps deliveries were 2.37 times as common in the index group (95% CI 1.80-3.12; P < 0.0001). The uncorrected perinatal mortality rates were 13.6/1000 and 15.7/1000 in the index and control groups respectively. CONCLUSION: Early teenage pregnancies are common in Hull and, contrary to previous reports, are physically well tolerated by the early adolescents who book early and attend antenatal clinics regularly. Ineffective utilization and ignorance of contraceptive methods are contributory factors. We recommend that emphasis should be placed on providing contraceptive services for teenagers and adopting a more purposeful and holistic approach to sex education.
Cholestyramine is a nonabsorbable anion exchange resin that is used predominantly for the treatment of hypercholesterolemia in adults and the management of acute diarrhea in children. The authors report two cases of severe hyperchloremic nonanion gap metabolic acidosis associated with the use of cholestyramine therapy. The authors recommend that patients taking cholestyramine who have concomitant renal insufficiency or who are volume depleted or who are taking spironolactone be monitored carefully for the emergence of a hyperchloremic metabolic acidosis.
We have compared the effects of three-month periods of treatment with an inhaled corticosteroid, budesonide 600 micrograms twice daily and with placebo on bronchial responses to inhaled histamine and to bronchodilators in a double-blind crossover trial in 14 middle-aged male smokers (mean age, 59.6 years) with mild airways obstruction (mean FEV1 2.42 L, 80 percent predicted [range, 48 to 110 percent]). Responsiveness to inhaled histamine was assessed monthly by the provocative concentration (mg/ml) reducing FEV1 by 20 percent (PC20). Bronchodilator response to a combination of inhaled salbutamol (5 mg) and ipratropium (0.5 mg) was assessed before and after three months' treatment. Compliance with treatment was checked by weighing aerosol canisters, and by measuring plasma budesonide and metabolites. There was no significant change in FEV1 (budesonide mean 2.38 L [SEM 0.17] vs placebo 2.40 L [0.17]), vital capacity (budesonide mean 3.69 L [0.17] vs placebo 3.81 L [0.17]) or in bronchodilator responsiveness (mean increase over baseline FEV1, budesonide 11.6 [2.7] percent vs placebo 10.5 [3.2] percent). There was a small overall reduction in bronchoconstrictor responsiveness over the period of the trial, but there was no effect of 12 weeks of budesonide treatment compared with 12 weeks of placebo treatment (mean log PC20 during budesonide 0.595 [SEM 0.063], placebo 0.591 [SEM 0.055]). Following the three-month crossover trial, six men continued for nine more months to receive budesonide in a single-blind trial and the results were compared with those in six men who took no active treatment for the subsequent nine months. No improvements in baseline spirometry, home peak flow measurements, bronchoconstrictor or bronchodilator responsiveness were observed after 12 months of budesonide treatment. Thus, a regimen of budesonide treatment that consistently attenuates bronchial responsiveness in asthmatic subjects had no effect in these men; larger and longer trials will be required to establish whether a subgroup of smokers shows a favorable response.
The T84 colonic cell line, a cultured Cl- secretory cell, elevates intracellular free Ca2+ [( Ca2+]i) in a concentration-dependent manner when exposed to carbachol or histamine. As determined with a fluorescence microscope imaging system, exposure of T84 cells to 100 microM carbachol or histamine resulted in an immediate [Ca2+]i rise of approximately 50-80 nM in all cells. Preincubation of monolayers for 1 h or longer with 0.4 microM phorbol 12,13-dibutyrate (PDB) reduced the number of cells which responded to histamine or carbachol and reduced the magnitude of the increase in the responding cells. This effect reached its maximum after 2 h and persisted for at least 24 h of PDB incubation. Binding of quinuclidinyl benzilate, a cholinergic receptor antagonist, indicated that down-regulation of external receptors was not an explanation for this effect. Examination of phospholipase C activity in T84 cell membranes showed increased basal activity in PDB-treated compared with control cells. Measurement of inositol phosphates generated by intact cells using myo-[3H]inositol incorporation or receptor binding assays showed that 2 h of incubation with PDB elevated basal levels of inositol 1,4,5-trisphosphate and prevented any further carbachol-induced generation of inositol trisphosphate. Probably as a consequence, both total cell calcium and Ca2+ ionophore-releasable calcium were decreased after 2 h of PDB incubation. Membrane-associated protein kinase C activity was elevated after a 2 h exposure to PDB but was below the level of detection after 24 h with PDB. Protein kinase C antagonists neither duplicated nor blocked the uncoupling of carbachol receptors induced by long term treatment with PDB. The results suggest that prolonged PDB incubation caused uncoupling and elevation of phospholipase C activity from cholinergic and histaminergic receptor regulation resulting in increased basal levels of inositol 1,4,5-trisphosphate. Protein kinase C apparently is not involved directly in the mechanism that leads to these effects.
Because nosocomial infection rates vary by hospital area and service, most infection control programs calculate area-specific rates to augment the reporting of their hospital-wide data. Rate development is often limited by the availability of appropriate specific denominator data to support important comparisons. Our university hospital reports a 20 month experience in which numerator data was collected as per the National Nosocomial Infections Surveillance System criteria for hospital-wide, high-risk nursery and ICU surveillance. These data were then combined with data in our hospital's patient-specific denominator file. This has enabled the development of risk-specific infection rates based on the analytic control of important variables available in both the numerator and denominator files. We found rate differences that were length of stay cohort specific, hospital day specific, age specific, birthweight specific, and survival cohort specific when examining our data by both the cumulative incidence and incidence density methods.
Infection with the human immunodeficiency virus (HIV-1) often produces a set of neuropsychiatric dysfunctions which have been termed the AIDS dementia complex. This complex appears due to the infection of brain cells by HIV-1. If so, brain cells might be expected to contain a binding site for the same viral envelope glycoprotein that enables HIV-1 to bind to other cells (e.g. CD4+ T-cells), gp120. The present study shows that the cells of the brain-derived U-138MG, U-373MG, SK-N-MC and SK-N-SH cell lines bind gp120 in an inhibitable fashion. Binding of gp120 to these cells is inhibited by the dyes Aurintricarboxylic acid (ATA) and Evans blue (EB), which are known to inhibit specific gp120 and HIV-1 binding, and block HIV-1 infection, in CD4-expressing cells. Binding is not inhibited by Aurin, a dye related to ATA but lacking its anti-HIV effects. As expected, anti-CD4 antibodies are ineffective in blocking gp120 binding to brain-derived cells. These results suggest that human brain-derived cells possess a specific binding site for gp120 that is not the CD4 antigen.
Ubiquitin-protein conjugates are found in the primary (azurophilic) lysosome-related granules but not in the secondary (specific) granules in mature polymorphonuclear neutrophils prepared from bone marrow. This is the first reported demonstration of ubiquitin-protein conjugates in lysosome-related membrane-bound vesicles in granulocytes and complements our previous findings of ubiquitinated proteins in lysosomes of fibroblasts. The significance of the selective presence of conjugates in only one of the two main types of neutrophil granules remains to be elucidated but may relate to the presence of the complement of acid hydrolases, including proteases, in the azurophilic granules compared to the specific granules. Ubiquitin-protein conjugates may enter the primary granules during neutrophil maturation by an autophagic process or by a heterophagic process during the fusion of phagosomes with primary granules. Alternatively protein ubiquitination may be involved in granule biogenesis.
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