Tissue section image analysis: comparison of different software releases.
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Biomedical subjects
Publications and source records attributed to M Thomas.
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Anecdotal accounts suggest that colds and influenza may increase human error. This view is supported by laboratory studies of the effects of upper respiratory tract illnesses (URTIs) on performance efficiency, which have shown that both experimentally induced and naturally occurring URTIs reduce aspects of performance efficiency. The present research examined the relationship between accidents and URTIs by studying 923 patients attending an Accident and Emergency department at a time of year when upper respiratory tract viruses were circulating. The results revealed no significant associations between URTIs and workplace accidents, and, similarly, no significant associations emerged when all accidents were compared with other attenders. The only effect which was close to statistical significance was a protective effect of influenza against workplace accidents, which could be explained in terms of a person with influenza or who has recently had influenza being less likely to work and therefore less likely to be at risk of experiencing a workplace accident. Further research must examine this topic with different methodologies, such as selecting controls from fellow workers of the index case, and these studies will provide us with a clearer view as to whether or not there is an association between URTIs and workplace accidents.
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Hypercalcaemia is common in some lymphoproliferative disorders such as myeloma or T-cell leukaemia-lymphoma, but is rarely described in B cell chronic lymphocytic leukaemia (BCLL). We report the case of a patient with BCLL, hypercalcaemia and osteolytic bone lesions. Parathyroid hormone-related protein (PTHrP) mRNA was identified by Northern blot analysis of liver, spleen and lymph node tumour samples. Serum levels of tumour necrosis factor alpha (TNF alpha) were increased.
In order to produce a successful infection, Neisseria gonorrhoeae (GC) must attach to and invade mucosal epithelial cells. To identify GC gene products involved in this early interaction with host cells we constructed a gene bank derived from a clinical isolate of GC, and isolated a clone which had the capacity to adhere to the human endometrial adenocarcinoma tissue-culture line HEC-1-B. The cloned sequence was identified as a member of the opa gene family whose protein products have been associated with virulence. The GC chromosome contains numerous variant opa genes which, in MS11, are designated opaA-K. Previous work showed that expression of opaC confers a highly invasive phenotype upon strain MS11. When our cloned opa gene was mutated and returned to the GC MS11A chromosome by transformation and homologous recombination, we isolated one transformant that was significantly reduced in its invasive capacity. The locus mutated in this transformant was identified as opaH. Our results indicate that invasiveness of GC for human epithelial cells can be determined by more than one opa gene in strain MS11A.
A controlled study of different modes of acupuncture stimulation was conducted on patients fulfilling clinical criteria for chronic low back pain of nociceptive origin. Forty patients were randomly entered into the study. Thirty had three trial treatments with manual stimulation of needles (MS), electrical low frequency stimulation at 2 Hz (LF), and high-frequency stimulation at 80 Hz (HF), and then continued treatment with the mode they felt most benefitted them. Ten patients were put on the waiting list for treatment but served as the untreated control group. The results were evaluated after 6 weeks and at 6 months for: activity related to pain; mobility; verbal descriptors of pain and the patient's subjective assessment of his condition. After 6 weeks, patients receiving treatment showed significant improvement (P < 0.05 to P < 0.001) on three of the four measures compared to the untreated controls. After 6 months a similar measure of significant improvement was seen in patients continuing with low-frequency (LF) acupuncture, but not in those groups continuing with manual stimulation (MS) or high-frequency (HF) acupuncture. The results suggest that 2 Hz electrical stimulation is the mode of choice when using acupuncture in the treatment of chronic nociceptive low back pain.
The recognition of photosensitivity depends upon the finding of an abnormal EEG response to intermittent photic stimulation (IPS). Photosensitive epilepsy being the most common form of reflex epilepsy, has been studied most extensively and is reported to account for 5-10% of the epileptic population in general. One thousand unselected epileptics hailing from different parts of Northern India were screened for photosensitivity, both clinically and on a standard protocol of IPS-provoked EEG recordings. Six patients (mean age 14.5 +/- 3.56 yr) were found to be photosensitive: 4 had generalized, 1 had complex partial and 1 mixed seizures; 3 had history of seizures provoked by visual stimuli. The baseline EEG in 4 patients showed generalized and 2 partial, with secondary generalized, epileptiform discharges. On IPS, similar EEG findings were obtained with a wide range of stimulus frequency (6-60 cycles/s). There is a low incidence of photosensitivity in our epileptic population, for which we believe, genetic factors are responsible.
A new HLA-B antigen, HLA-B7Qui that appears to be a variant of HLA-B7 has been identified. This antigen, which is HLA-Bw6 associated, reacts with approximately two-thirds of cytotoxic antisera stimulated by HLA-B7 or B27 that lack a B27 or B7 component, respectively. All anti-B7 + 27 antisera (stimulated by either B7 or B27) react with B7Qui as do most B22-stimulated sera possessing a B7 component. However, sera stimulated by B60, with or without a B7 component, fail to react with B7Qui. Family studies show the B7Qui allele to be unique to the haplotype-HLA-A32 CW6 B7Qui Bf*S C4A*6 C4B*1 DR11 DQ7 (GLO2). Six Caucasoid subjects on the panel of 6861 HLA-typed potential bone marrow donors have this antigen (phenotype frequency, 0.08745%; gene frequency, 0.04473%). Work undertaken during the 11th International Histocompatibility Workshop (Reekers et al., 1992) showed that B7Qui has the same isoelectric point as HLA-B702 and HLA-B703 (Bpot) and that B7Qui is distinct from the HLA-B7 variants B703, B7SL, BDT, B7 x 40, BRI, and B41v.
Factor B of human complement is encoded within the Major Histocompatibility Complex (MHC) and is polymorphic, with up to 30 alleles defined by electrophoretic mobility. One of the most common alleles, BF*F, is subdivided into the FA and FB subtypes, which differ at the gene level by non-synonymous base substitutions in the seventh codon. We have found at this position a new restriction site polymorphism, as a Bsl I site absent from the FB allele. Using this restriction polymorphism, we have developed a method for BF F subtype determination, based on amplification by polymerase chain reaction of the 5' end of the BF gene, and digestion with Bsl I. This new method has been applied to a panel of 29 selected BF F individuals. A single strand DNA conformation analysis of the same region of the gene allowed us to confirm the above DNA-based BF F subtyping. During this study, two BF*F1 alleles showed discrepancies between protein and DNA typing, which were confirmed by our sequencing data. These were identical, in the 5' region, to BF*S and BF*FB genes, respectively. In a comparison with two protein subtyping methods, identical results were found for only one third of the selected samples. The conflicting results may arise, in part, from previously undescribed molecular heterogeneity within BF F subtypes, or from the presence of a null allele. Our new method allows BF*F subtyping to be used with confidence in the definition of disease-associated MHC haplotypes.
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BACKGROUND: The contribution of nonangiotensinergic effects of converting enzyme inhibitors to their hemodynamic effects in patients with chronic heart failure is not clear. A comparison of the effects of renin and converting enzyme inhibition should help to clarify this issue. METHODS AND RESULTS: Thirty-six patients with chronic heart failure (New York Heart Association class II or III) were randomly assigned to receive double-blind either intravenous placebo, the renin inhibitor remikiren, or the converting enzyme inhibitor enalaprilat followed by coinfusion of a second placebo infusion, the addition of remikiren to enalaprilat, or the addition of enalaprilat to remikiren, respectively. Systemic hemodynamics (Swan-Ganz and radial artery catheters) were measured before (rest and submaximal recumbent bicycle ergometry), during (rest), and at the end (rest and exercise) of each 45-minute single- or combination-infusion period. Placebo did not change hemodynamics or renin activity. Effective inhibition of the renin-angiotensin system by remikiren and enalaprilat was indicated by increases of plasma immunoreactive renin together with rapid and complete inhibition of renin activity after remikiren and an increase after enalaprilat (all P < or = .05). Remikiren and enalaprilat rapidly and to a similar extent reduced resting blood pressure through a reduction of systemic vascular resistance, and these changes were significantly correlated to baseline plasma renin activity. Both compounds also decreased pulmonary artery, pulmonary capillary wedge, and right atrial pressures to a similar extent (P < .05). During exercise, pulmonary capillary wedge and right atrial pressures were equally reduced and stroke volume index was increased with remikiren and enalaprilat (P < .05) for both). The combination of converting enzyme with renin inhibition or vice versa did not cause additional hemodynamic changes. CONCLUSIONS: Specific renin inhibition in patients with chronic heart failure produces short-term hemodynamic effects that are almost indistinguishable from those of converting enzyme inhibition. This finding and the lack of additional effects of converting enzyme inhibition added to renin inhibition suggest that nonangiotensinergic effects of converting enzyme inhibitors do not play a significant role in their short-term hemodynamic effects in patients with chronic heart failure.
While rare, mycotic aneurysms of the aorta have a high mortality rate from immediate rupture and late complications. The case of a patient with a ruptured mycotic aneurysm is presented, and the important role of scintigraphic studies in the early detection of complicating extensive soft-tissue infection and osteomyelitis is demonstrated.
We present a method allowing intra-operative monitoring of the common peroneal nerve during total knee arthroplasty using a magnetic stimulator. Previous reports have shown no pre-operative method successful in selecting those patients prone to develop a post-operative palsy. The device, placed beneath the lumbar spine, stimulates the cauda equina; common peroneal nerve function is assessed via the response in extensor digitorum brevis. There is a loss of signal from the nerve with the use of a tourniquet 25 min following its application. The protocol therefore requires that a tourniquet is used at least only for fixation of the prosthetic components. The method is quick, safe, non-invasive and reproducible, and is of use both in at-risk patients and in research work.
Alterations of PTH secretion in patients with mild to moderate chronic renal failure were evaluated using an oral calcium suppression test. Ionized calcium and PTH were measured at 0, 30, 60, 120, and 180 min after ingestion of 2 g elemental calcium in 18 patients and 15 control subjects. The mean glomerular filtration rate was significantly lower in the patients compared to the controls (58 +/- 18 vs. 100 +/- 12 mL/min, P < 0.01) but the basal ionized calcium and PTH were not significantly different. After ingestion of calcium there was a similar rise in ionized calcium with time in both patients and controls. However the mean PTH concentration in the patients was significantly higher than the controls at all equivalent ionized calcium concentrations. Overall the patients showed significantly less percentage suppression of PTH compared to control subjects, 63 +/- 10% vs. 74 +/- 9%, P < 0.01. The minimum PTH value was also higher in the patients than the controls, 1.2 +/- 0.7 vs. 0.7 +/- 0.3 pmol/L, P < 0.01. Thus although the majority of patients had PTH levels within the conventional reference range they demonstrated abnormal suppression of PTH secretion. The data from this study would further support the view that treatment for secondary hyperparathyroidism should be started early on in the course of chronic renal failure.
Changes in thyroid status have a major effect on the GH/insulin-like growth factor (IGF) axis. The majority of IGF in the circulation is bound to specific IGF-binding proteins (IGFBPs) of which six have been cloned and sequenced. We have studied changes in hepatic gene expression of IGFBP-1, -2 and -3, in male Wistar rats rendered hyperthyroid (thyroxine, 200 micrograms/kg per day) or hypothyroid (propylthiouracil, 0.1% daily). Littermates of the same age were used as controls (n = 6 in each group). Thyroxine was measured by radioimmunoassay, and hepatic IGFBP-1, -2 and -3 mRNA levels by Northern blot analysis using specific rat cDNA probes with a 28S ribosomal probe as a loading control. Mean +/- S.E.M. thyroxine levels were 247.0 +/- 44.5 (hyperthyroid group), < 9.0 (hypothyroid group) and 76.0 +/- 4.5 nmol/l (control group). IGFBP-1 and -2 mRNA levels in the hypothyroid animals compared with the controls were significantly increased, but similar levels of expression were found in thyrotoxic and control rats. IGFBP-3 mRNA levels in hypothyroid animals were decreased, and increased in thyrotoxic animals. Thus, in the adult rat, hypothyroidism is associated with increased hepatic IGFBP-1 and -2 gene expression, but decreased IGFBP-3 gene expression, while in thyrotoxicosis there are normal IGFBP-1 and -2 mRNA levels but increased IGFBP-3 gene expression. These results suggest that there is specific and different transcriptional regulation for IGFBP-1, -2 and -3 in hypo- and hyperthyroid rats.
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