Clinical governance: what does it mean for NHS Scotland?
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Humans↗
Biomedical subjects
S Downie
Publications and source records attributed to S Downie.
Unusual origin of the flexor digiti minimi brevis muscle.
An unusual origin of the flexor digiti minimi brevis muscle of the right hand was discovered during cadaveric dissection. The muscle originated from the anterior aspect of the transverse fibers of the distal antebrachial fascia and inserted onto the base of the fifth proximal phalanx. When traction was applied to the proximal portion of the muscle, flexion was produced at the fifth metacarpophalangeal joint. Other intrinsic muscles of the hand and the muscles of the flexor forearm compartment had normal morphology. Although muscular anomalies in the hypothenar region have been described, the muscular variant described here was distinct in its origin and size from those previously reported. Knowledge of anomalous muscles in the hand has important clinical significance in routine surgery and in determining associated pathology.
Aged↗
Web-based education and support for patients on the cardiac surgery waiting list.
We assessed the effectiveness of two methods of patient education, a printed manual and a Website, provided to patients waiting for cardiac surgery. The four-phase study was conducted over two and a half years, and included urban and rural subjects in Vancouver and the interior of British Columbia. The Website was based on the specially developed patient education manual. A pilot evaluation study was carried out to assess the features of the Website and to ensure it was 'user-friendly', after which it was revised. The two education methods were evaluated using both qualitative and quantitative studies. Findings supported the feasibility and viability of both formats. The Web-based format demonstrated two additional benefits over the print-based format, namely increased social support and decreased anxiety. Other findings included the perception of increased support, lifestyle changes and more positive attitudes towards the impending surgery.
Adult↗
Rates of small intestinal mucosal protein synthesis in human jejunum and ileum.
We investigated possible differences in the rates of mucosal protein synthesis between the proximal and distal regions of the small intestine. We took advantage of access to the gut mucosa available in otherwise healthy patients with ileostomy in whom the terminal ileum was histologically normal. All subjects received primed, continuous intravenous infusions of L-[1-(13)C]leucine after an overnight fast. After 4 h of tracer infusion, jejunal biopsies were obtained using a Crosby-Kugler capsule introduced orally; ileal biopsies were obtained via endoscopy via the ileostomy. Protein synthesis was calculated from protein labeling relative to intracellular leucine enrichment obtained by appropriate mass spectrometric measurements. Rates of jejunal and ileal mucosal protein synthesis were significantly different (P < 0.001) at 2.14 +/- 0.2 and 1.2 +/- 0.2 %/h (means +/- SD). These are lower than rates in normal healthy duodenum (2.53 +/- 0.25 %/h), suggesting a gradation of rates of synthesis along the bowel. Together with other data, these results suggest that mucosae of the bowel contribute not more than 10% to whole body protein turnover.
Adult↗
Small-intestinal mucosal protein synthesis and whole-body protein turnover in alcoholic liver disease.
We used stable-isotope-labelled amino acids to measure the effects of alcoholic liver disease (ALD) on whole-body protein turnover and small-intestinal mucosal protein synthesis. Groups comprising eight patients with ALD and eight healthy control subjects were studied. They received primed, continuous intravenous infusions of L-[1-(13)C]leucine after an overnight fast; after 4 h, duodenal biopsies were obtained via endoscopy. Protein synthesis was calculated from protein labelling relative to intracellular leucine enrichment. Rates of duodenal mucosal protein synthesis were 2. 58+/-0.32%.h(-1) (mean+/-S.D.) in the normal subjects and 2.04+/-0. 18%.h(-1) in the ALD patients (P<0.003), despite the fact that the protein synthetic capacity (microgram of RNA/mg of protein) was higher in ALD patients (160+/-14 compared with 137+/-6 microgram/mg; P<0.003). The mucosal cell size (protein/DNA ratio) was lower in ALD patients (9.23+/-0.91 compared with 13+/-2.2 microgram/mg; P<0.002). Although the mean rates of whole-body protein turnover were not significantly different between the two groups (204+/-18 and 196+/-44 micromol leucine.h(-1).kg(-1) for ALD and control subjects respectively), there was, in the ALD patients, an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the severity of ALD; furthermore, there was a direct relationship between the rate of whole-body protein turnover and the severity of ALD. Thus there was an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the rate of whole-body protein turnover in ALD patients, which was not seen in the normal subjects.
Adult↗
Effects of flooding amino acids on incorporation of labeled amino acids into human muscle protein.
We investigated the effects of the nature of the flooding amino acid on the rate of incorporation of tracer leucine into human skeletal muscle sampled by biopsy. Twenty-three healthy young men (24.5 +/- 5. 0 yr, 76.2 +/- 8.3 kg) were studied in groups of four or five. First, the effects of flooding with phenylalanine, threonine, or arginine (all at 0.05 g/kg body wt) on the incorporation of tracer [13C]leucine were studied. Then the effects of flooding with labeled [13C]glycine [0.1 g/kg body wt, 20 atoms percent excess (APE)] and [13C]serine (0.05 g/kg body wt, 15 APE) on the incorporation of simultaneously infused [13C]leucine were investigated. When a large dose of phenylalanine or threonine was administered, incorporation of the tracer leucine was significantly increased (from 0.036 to 0. 067 %/h and 0.037 to 0.070 %/h, respectively; each P < 0.01). However, when arginine, glycine, or serine was administered as a flooding dose, no stimulation of tracer leucine incorporation could be observed. These results, together with those previously obtained, suggest that large doses of individual essential, but not nonessential, amino acids are able to stimulate incorporation of constantly infused tracer amino acids into human muscle protein.
Adult↗
Exposure of cats in southern Africa to Coxiella burnetii, the agent of Q fever.
Recently, the domestic cat has been implicated in numerous outbreaks of Q fever in humans. To determine if cats in southern Africa are infected with the agent of Q fever we tested sera from cats in South Africa and Zimbabwe by indirect fluorescence for antibodies reactive with phase II Coxiella burnetii antigen (Nine Mile strain). Reactive antibodies were detected at titres of > or = 1/40 in sera from cats in South Africa (1/52, 2%) and Zimbabwe (15/119, 13%). Our results indicate that cats in southern Africa are infected with C. burnetii and should be considered as sources of infection for humans.
Animals↗
Domestic cats as indicators of the presence of spotted fever and typhus group rickettsiae.
Using indirect immunofluorescence assays, sera from cats in Zimbabwe (n = 119) and South Africa (n = 52) were found to contain antibodies reactive with Rickettsia conorii (34% and 19% respectively) and R. typhi (7% and 10% respectively). These results indicate that cats may become infected with members of the spotted fever and typhus groups of rickettsiae and that cats can, therefore, be used as indicators of the presence of these organisms.
Animals↗
Correction of acidosis in hemodialysis decreases whole-body protein degradation.
Correction of acidosis in hemodialysis (HD) decreases protein degradation. The effect of the correction of chronic metabolic acidosis in chronic renal failure patients treated with HD was determined from the kinetics of infused L-[1-(13)C]leucine. Six HD patients were studied before (acid) and after (bicarbonate) correction of acidosis (pH: acid 7.36 +/- 0.01, bicarbonate 7.40 +/- 0.01, P < 0.005). Leucine appearance from body protein (PD) and leucine disappearance into body protein (PS) decreased significantly with correction of acidosis (PD: acid 180.6 +/- 7.3, bicarbonate 130.9 +/- 7.2 mumol.kg-1.h-1, P < 0.005; PS: acid 172.3 +/- 6.8, bicarbonate 122.0 +/- 6.8 mumol.kg-1.h-1, P < 0.005). There was no significant change in leucine oxidation or plasma amino acid concentrations. These results demonstrate that optimal correction of acidosis in HD is beneficial in terms of protein turnover and may improve long-term nutritional status in HD.
Acidosis↗
Presence of opiate alkaloid-selective mu3 receptors in cultured astrocytes and in brain and retina.
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Animals↗
Correction of acidosis in CAPD decreases whole body protein degradation.
Correction of acidosis in CAPD decreases protein degradation and synthesis but has no effect on leucine oxidation. The effect of the correction of metabolic acidosis in CRF patients treated with CAPD was determined from the kinetics of infused L-[1-13C]leucine. Seven CAPD patients were studied before (acid) and after correction of acidosis (bicarbonate) (pH:acid 7.39 +/- 0.01, bicarbonate 7.41 +/- 0.01, P = 0.005). Leucine appearance from body protein (PD) [corrected] and leucine disappearance into body protein (PS) [corrected] decreased significantly with correction of acidosis. (PS: acid 211.7 +/- 9.8, bicarbonate 142.3 +/- 4.2 micromol x kg-1 x hr-1, P < 0.001; PD: acid 200.6 +/- 8.5, bicarbonate 132.4 +/- 3.7 micromol x kg-1 x hr-1, P < 0.001). There was no significant change in leucine oxidation or plasma amino acid concentrations. These results demonstrate that optimal correction of acidosis in CAPD is beneficial in terms of protein turnover.
Acidosis↗
Increased rates of duodenal mucosal protein synthesis in vivo in patients with untreated coelia disease.
BACKGROUND AND AIMS: A robust, reproducible method for the measurement of protein synthesis in the gastrointestinal mucosa was applied to investigate possible differences between the rate of duodenal mucosal protein synthesis in coeliac patients and normal control subjects. PATIENTS AND METHODS: Eight patients, means (SD) (51 (10) years, 57 (11) kg, 160 (6) cm) with newly diagnosed untreated coeliac disease and seven control subjects (48 (11) years, 71.5 (12) kg, 172 (10) cm) received primed, continuous, intragastric (IG) and intravenous (i.v.) infusions of L-[1-13C]leucine and L-[1-13C]valine after an overnight fast. Distal duodenal biopsy specimens were obtained at endoscopy performed after 240 minutes of infusion. Protein synthesis was calculated from protein labelling relative to intracellular free amino acid enrichment, after appropriate mass spectrometric measurements. RESULTS: Rates of duodenal protein synthesis were significantly greater in coeliac patients than in control subjects (i.v. tracer, coeliac v control, 3.58 (0.45) v 2.26 (0.22)%/h, p< 0.05; IG tracer, 6.25 (0.97) v 2.34 (0.52)%/h respectively, p < 0.01). The rates of mucosal protein synthesis calculated on the basis of the tracer infused via the intragastric route were higher in patients with coeliac disease than in control subjects. Tissue protein/DNA ratios were significantly reduced in coeliac patients (coeliac v control, 9.2 (1.6) mg/micrograms v 13.0 (2.2) mg/micrograms respectively, p < 0.05) suggesting smaller mucosal cell size in coeliac patients. CONCLUSIONS: Despite the villous atrophy and reduced cell size observed in coeliac disease, the rates of mucosal protein synthesis are considerably increased. These results suggest that a high rate of protein synthesis may be adaptive to a high rate of protein breakdown or mucosal cell loss in coeliac patients.
Adult↗
Exposure of cats in southern Africa to Coxiella burnetii, the agent of Q fever.
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Animals↗
Gut mucosal protein synthesis measured using intravenous and intragastric delivery of stable tracer amino acids.
We measured the rates of mucosal protein synthesis during the simultaneous delivery of [1-13C]leucine and [1-13C]valine delivered either intragastrically or intravenously to investigate any influence of the route of supply of the tracers. Dependent on the route, there were marked differences in the gradient of labeling between the plasma and intramucosal leucine and valine; i.e., for intravenous tracers the ratio was 1.73 +/- 0.16, but for intragastric tracers it was 0.65 +/- 0.12 (P < 0.05). Incorporation of intravenous tracer into mucosal protein was linear with time, and irrespective of tracer route, the calculated fractional rates of protein synthesis were identical when based on the intracellular labeling of the leucine or valine tracer, i.e., with intravenous 2.58 +/- 0.32%/h and with intragastric 2.45 +/- 0.36%/h. The results demonstrate that a robust and reproducible method of measurement of gastrointestinal mucosal protein synthesis has been developed and that use of either intragastric or intravenous routes of tracer administration gives comparable results. The high rates measured suggest that the gastrointestinal mucosa contributes substantially to whole body protein synthesis in normal healthy subjects.
Adult↗
Effect of a flooding dose of leucine in stimulating incorporation of constantly infused valine into albumin.
Recently, we demonstrated increased incorporation of [13C]valine tracer into muscle protein after administration of a flooding dose of L-leucine. We have now investigated the possibility of a similar effect on albumin synthesis in the same group of volunteers. We gave L-[1-13C]leucine (20 atom%, 0.05 g/kg) during the final 90 min of a 7.5-h primed constant infusion of L-[1-13C]valine (99 atom%, 1.5 mg/kg prime constant infusion of 1.5 mg.kg-1.h-1) in healthy male volunteers in the postabsorptive state. Blood samples, taken at 0.5- to 1-h intervals during the constant infusion and at 5- to 30-min intervals during the application of the flooding dose, were analyzed for the concentration and 13C enrichment of leucine, valine, and their ketoacids. Albumin was isolated and hydrolyzed, and the enrichments of incorporated valine and leucine were compared with the mean enrichment of various possible precursor pools to calculate the apparent rate of albumin protein synthesis according to the standard procedures. During constant infusion of [13C]valine tracer the rate of albumin synthesis (measured using alpha-ketoisovalerate labeling as a surrogate for the true precursor) was 0.250 +/- 0.041%h (SD), a value identical to that routinely obtained using constant leucine tracer infusion and alpha-ketoisocaproate labeling. During the application of the flooding dose of leucine, the rate of incorporation of tracer [13C]valine into albumin increased by 73% to 0.433 +/- 0.129%/h (P < 0.05); the apparent protein synthetic rate calculated from the incorporation of leucine applied during the flood was 0.402 +/- 0.057 (P < 0.001). These results raise further doubts about the validity of the flooding dose method for the measurement of rates of human protein synthesis.
Adult↗
Lithium effects on neuroendocrine function.
We studied growth hormone and prolactin responses to insulin hypoglycemia and TSH response to TRH in symptom-free bipolar patients and healthy controls. There were no significant differences in prolactin and growth hormone responses to hypoglycemia between stabilized bipolar patients and healthy controls, both tested medication-free. When lithium was administered to both groups, only bipolar patients showed a dramatic reduction in prolactin and growth hormone responses. Both bipolar patients in remission and healthy controls showed an increase of TSH response to TRH when treated with lithium in comparison with the testings before lithium administration. The subjects, both patients and volunteers, showed a comparable degree of hypoglycemia on and off lithium. The observed difference in responsiveness of bipolar patients warrants further systematic investigation and offers interesting possibilities for practical utilization.
Adolescent↗