Pain remembered with a dash of humour.
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Biomedical subjects
Publications and source records attributed to S Hudson.
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Experimental studies have shown that administration of antilymphocyte serum combined with donor bone marrow cells can induce tolerance to allograft tissue. We have initially reported application of these protocols in clinical studies of cadaveric renal allograft recipients who were treated with MALG and donor-specific bone marrow cells. To evaluate the effectiveness of the donor marrow cells in the production of chimerism, a detection method based on 32P-incorporated PCR was established. The 32P PCR was utilized with primers specific for the HLA class II, VNTR (D17S5 and D1S111), and/or Y-chromosome genes to detect the presence of allogeneic chimerism in the recipients. Immediately posttransplant, 26.4% of marrow recipients demonstrated the presence of allogeneic chimerism prior to the marrow transfusion as did 18% in the untransfused controls. In transfused patients, chimerism was detected most frequently during the 1-3-month interval after marrow transfusion (65%), and then diminished to 50-56% at 3-12 months posttransfusion. In the control group the frequency of allogeneic chimerism was gradually decreased and was undetectable in the majority of the patients beyond 3 months posttransplant while marrow-transfused recipients were more likely to have chimeric cells detected consistently beyond 3 months. Rejection episodes were significantly effected by the presence of chimerism in the recipients. Of the transfused patients, 91.3% who demonstrated allogeneic chimerism were rejection-free as compared with 8.7% who experienced at least one rejection episode (P = 0.01). While the presence of allogeneic chimerism in the control group was correlated with rejection-free graft survival, this difference did not reach statistical significance.
Growth of bacteria within a biofilm, visible macroscopically as a yellow coating, was seen on the interior walls of semi-transparent plastic dialysis monitor fluid pipes. The level of bacterial growth along the water/dialysis fluid pathway, and the effect of in-line bacterial filters, on colony counts in reverse osmosis reject water and monitor effluent were examined. Little difference in colony counts was seen at either sampling point in monitors fitted with and without filters. Because of the increasing use of high-flux dialysis, and its potential for transmembrane transport of endotoxin and bacteria into patients, staff should be aware that dialysis fluid pathways may be colonized with viable bacteria, which are not readily killed by conventional heat and chemical cleaning processes.
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Flinders Island spotted fever (FISF), a spotted fever group (SFG) rickettsial disease first described in 1991, occurs in south-eastern Australia. The isolation of the aetiological agent is described for the first time having been obtained from the blood of two patients. An additional 22 cases are also reported. Of these patients four had positive initial serology, and 20 showed seroconversion (using Rickettsia australis as antigen). Acute phase blood specimens taken from seven patients caused neonatal mice to seroconvert to R. australis and a blood specimen from one of these patients (and one other) yielded rickettsiae. A field survey for possible reservoir and vector animals on Flinders Island, Tasmania and in Gippsland, Victoria (both in south-eastern Australia) yielded 217 vertebrates and 1445 invertebrate ectoparasites, mostly ticks. Ixodes cornuatus from humans and dogs in Gippsland produced seroconversion to SFG rickettsia when inoculated into mice but no invertebrate pools from Flinders Island produced seroconversion in mice. Haemolymph from an individual I. cornuatus removed from a human in Gippsland, yielded a SFG rickettsia on tissue culture. Sera from several species of native vertebrates, especially the bush rat, Rattus fuscipes, were positive for antibodies to SFG rickettsia.
BACKGROUND: Hypothermia develops rapidly during the 1st h of anesthesia and results in part from evaporative heat loss during surgical skin preparation. The authors tested the hypothesis that evaporation of skin preparation solution contributes significantly to hypothermia. METHODS: Five healthy, unanesthetized volunteers were studied in a 22 +/- 0.4 degrees C environment. One thigh of each volunteer was washed for 10 min, using each of the following representative solutions: (1) water; (2) 50% ethanol in water (EtOH/H2O; similar to tincture of iodine); and (3) povidone-iodine gel. Water and EtOH/H2O each were tested at ambient temperature (cold), warmed to 40 degrees C before application (warm), and with radiant heating of the skin, and gel only at ambient temperatures, resulting in seven study states. Heat loss and skin temperatures on the washed thighs were measured using thermal flux transducers, and values compared with the data obtained from the contralateral unwashed thighs. Change in mean body temperature (per 70 kg) due to washing was calculated by integrating measured heat loss over time and multiplying by the specific heat of human tissue. A mathematical model was developed to predict cutaneous heat loss using only skin temperature, independent of the type and temperature of skin-preparation solution or the use of radiant heating during preparation. RESULTS: Heat loss from the unwashed thigh was approximately 14 kcal/m2 during radiant warming and approximately 39 kcal/m2 without warming. Net heat loss (increment produced by washing) was approximately 30 kcal/m2 with water and gel without radiant warming, but loss was larger with EtOH/H2O than with water under all study conditions. Radiant warming reduced total heat loss (increment produced by washing and environment) during both the EtOH/H2O and water trials, compared with warm or cold EtOH/H2O and water alone. The calculated decreases in mean body temperature per 70 kg ranged from -0.2 to -0.7 degree C/m2. The smallest decrease occurred during radiant warming and washing with water, and the largest decreases during warm or cold EtOH/H2O. CONCLUSIONS: Heat loss was significantly less with water-based than with alcohol-based solutions. Though heating the solutions and radiant warming decreased heat loss, such loss under each tested condition, even per square meter of washed surface, was small compared to other causes of perioperative hypothermia. Consequently, the authors recommend that efforts to maintain intraoperative normothermia be directed elsewhere.
1 A questionnaire about undergraduate teaching on antimicrobial chemotherapy was sent to academic Departments of Clinical Pharmacology, Pharmacology and Medical Microbiology throughout the UK. 2 Questionnaires about postgraduate lectures and information circulated to doctors about antimicrobial chemotherapy were sent to Drug Information Centres and Postgraduate Tutors throughout the UK. Review articles and editorials in general medical journals were assessed. 3 The median amount of core undergraduate teaching on antimicrobial chemotherapy was 13.5 h but the range was from 9.0 h to 102.0 h. Content was predominantly oriented towards drugs rather than diseases and towards prescribing in hospital rather than in the community. Most teaching was by formal lecture as part of a core programme. On a scale from 0 to 5 the median emphasis given to individual topics ranged from 2.50 to 3.75 but the range of emphasis given by individual medical schools was wide, for example from 1.00 to 4.50 for teaching on pharmacokinetics. 4 Postgraduate tutors identified advice from local specialists and requests from local practitioners as the most important determinants of content of continuing medical education. Material from drug information centres was predominantly oriented towards discussion of individual drugs rather than management of specific diseases and even this limited survey found evidence of duplication. The UK general medical literature contained a total of 112 reviews or editorials on antimicrobial chemotherapy covering a wide range of topics but these were not, and should not be assumed to be comprehensive. 5 Almost all doctors regularly prescribe antimicrobials and require education about the subject. Wide variations in current medical practice should be addressed explicitly through more extensive use of problem solving. The literature suggests that knowledge is most effectively disseminated through local networks of practitioners. There should be more national co-ordination of the content of information to be disseminated through the existing drug information networks.
The authors tested the hypotheses that isoflurane anesthesia increases the threshold for sweating but minimally decreases the gain (sensitivity) or maximum intensity of this response and that thermoregulatory responses to hyperthermia are similar in anesthetized men and women. Sweating in response to core hyperthermia was studied in five men and five women during 0, 0.8, and 1.2% end-tidal isoflurane anesthesia. Thigh sweating was quantified by measuring gas flow, relative humidity, and temperature passing over a known surface area. The distal esophageal temperature triggering sweating was considered the sweating threshold, and gain was defined as the core temperature increment required to increase sweating rate from 25 to 75% of maximum observed intensity. The sweating threshold increased linearly with isoflurane concentration from 36.6 +/- 0.1 to 38.1 +/- 0.1 degrees C in the men and from 37.1 +/- 0.3 to 38.3 +/- 0.2 degrees C in the women. The thresholds were significantly higher in women than in men. Gain and maximum sweating intensities were similar at each anesthetic concentration and in men and women. These data indicate that isoflurane anesthesia significantly increases the threshold triggering thermoregulatory sweating but that gain and maximum sweating rate are relatively well preserved.
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We have investigated the action of the chemotherapeutic agent Fe(II)-bleomycin on yeast tRNA(Phe), an RNA of known three-dimensional structure. In the absence of Mg2+ ions, the RNA is cleaved preferentially at two major positions, A31 and G53, both of which are located at the terminal base pairs of hairpin loops, and coincide with the location of tight Mg2+ binding sites. A fragment of the tRNA (residues 47-76) containing the T stem-loop is also cleaved specifically at G53. Cleavage of both the intact tRNA and the tRNA fragment is abolished in the presence of physiological concentrations of Mg2+ (> 0.5 mM). Since Fe(II) is not displaced from bleomycin under these conditions, we infer that tight binding of Mg2+ to tRNA excludes productive interactions between Fe(II)-bleomycin and the RNA. These results also show that loss of cleavage is not due to Mg(2+)-dependent formation of tertiary interactions between the D and T loops. In contrast, cleavage of synthetic DNA analogs of the anticodon and T stem-loops is not detectably inhibited by Mg2+, even at concentrations as high as 50 mM. In addition, the site specificities observed in cleavage of RNA and DNA differ significantly. From these results, and from similar findings with other representative RNA molecules, we suggest that the cleavage of RNA by Fe(II)-bleomycin is unlikely to be important for its therapeutic action.
The accumulation of microorganisms embedded in biofilm within the drainage pipework leading from individual dialysis monitors in a renal dialysis centre, represents a significant threat to the safe operation of the whole centre due to blockage of the pipes and overflow of waste water. Attempts to disperse the growth with chemicals and disinfectants have been unsuccessful. Only mechanical rodding has removed the deposit, and regrowth has occurred. Those planning new dialysis centres should ensure that effluent pipework is readily accessible with multiple rodding eyes and is made of material able to withstand rodding and chemicals.
To determine the thermoregulatory effects of propofol and nitrous oxide, we measured the threshold for peripheral vasoconstriction in seven volunteers over a total of 13 study days. We also evaluated the effect of vasoconstriction on oxyhemoglobin saturation (SpO2). Anesthesia was induced with an intravenous bolus dose of propofol (2 mg/kg), followed by an infusion of 180 micrograms.kg-1 x min-1 for 15 min, and maintained with 60% nitrous oxide and propofol (80-160 micrograms.kg-1 x min-1). Central and skin surface temperatures and SpO2 (using two different pulse oximeters) were measured continuously; plasma propofol concentrations and arterial PO2 were measured at 15-min intervals. Volunteers were cooled with a circulating water blanket until definitive peripheral vasoconstriction was detected. The tympanic membrane temperature triggering vasoconstriction was considered the thermoregulatory threshold. Vasoconstriction developed on seven study days during propofol/nitrous oxide anesthesia at a central temperature of 33.3 +/- 1.0 degrees C (mean +/- SD) and plasma propofol concentration of 3.9 +/- 1.1 micrograms/mL. The thresholds during anesthesia were significantly lower than those during the control period (36.7 +/- 0.3 degrees C), but the correlation between plasma propofol concentrations and vasoconstriction thresholds was poor. On the remaining six study days, vasoconstriction did not develop despite central temperatures ranging from 32.1 to 32.7 degrees C. Corresponding propofol concentrations were 4.1-10.9 micrograms/mL. These data suggest that anesthesia with propofol, in typical clinical concentrations, and 60% nitrous oxide substantially inhibits thermoregulatory vasoconstriction. Vasoconstriction increased SpO2 by approximately 2% without a significant concomitant change in PO2. The observed increase in SpO2 probably reflects decreased transmission of arterial pulsations to venous blood in the finger.
This study reports results from experiments designed to test common, clinically useful anti-convulsants for their effectiveness, if any, against the high pressure nervous syndrome (HPNS) in rats. Phenytoin, carbamazepine, phenobarbitone, or diazepam were administered orally to rats before compression. Endpoints used to assess the progression of the HPNS were T1, T3, and T5 (onset of, continuous, and severe tremor), myoclonus, and seizures. Of the four drugs tested, only phenobarbitone increased the onset pressure for tremor and seizures by: T1 33%; T3 11%; T5 14%; seizures 10%. Neither phenytoin, carbamazepine, nor diazepam had any significant effect on any of the endpoints studied. High dose chronic pretreatment with phenytoin also had no effect on the HPNS. These data suggest that conventional anticonvulsant treatment would be of limited value for HPNS in man, and the lack of effect also suggests that HPNS seizures are of an unusual type.
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The effects of high helium pressure on the subsequent acquisition of spatial memory were studied in male rats. Thirty-two rats were exposed to 65 ATA helium-oxygen pressure for 4.2 days, decompressed (total time in chamber 5 days), and then tested in an eight-arm radial maze. Thirty-two control rats were exposed in the chamber to 1 ATA air. Each rat had 20 sessions in the maze (2 sessions/day for 10 days), and the number of correct (visiting an arm not previously visited to obtain the reward pellet) and incorrect choices (visiting a previously visited arm) were recorded. Statistical analysis showed that the rats exposed to 65 ATA performed significantly better than 1-ATA controls during the first 8 of 20 sessions. This effect was most pronounced in sessions 5-8. Results for sessions 9-20 showed that the pressure-treated rats still made more correct choices but to an extent that did not always reach statistical significance. Possible explanations include the pressure-treated rats performing better because of hunger after a lower food consumption at pressure. Alternatively, pressure itself may enhance proposed mechanisms of spatial memory such as long-term potentiation.
Daily injection of ovine and bovine somatotropin (oST and bST, respectively) has been shown to improve performance and carcass quality of finishing lambs. To evaluate responses to continuously released bST and porcine ST (pST), which have 99 and 91% sequence homology with oST, respectively, finishing lambs were implanted with 2-wk Alzet pumps containing bST or pST, which was released at rates of 2 or 4 mg/d. Six-week growth rate and feed efficiency responses to bST were greater than those to pST (P less than .05). Overall feed efficiency was improved 15% and growth rate was increased 16% in lambs treated with 4 mg/d of bST compared with control lambs and neither trait was affected in pST-treated lambs. Performance responses were reflected by changes in circulating glucose, blood urea nitrogen, and insulin-like growth factor I (IGF-I) concentrations. Scatchard analysis of sera with relative binding of greater than 30% revealed that average binding capacities and affinities of pST-treated lambs were 7.0 mg/liter and 6.0 x 10(9) liters/mol, respectively, and of bST-treated lambs were .8 mg/liter and 1.3 x 10(9) liters/mol, respectively. In addition, lambs with high-capacity pST antibodies had lower 6-wk IGF-I concentrations than those of controls, suggesting that these antibodies may have been attenuating responsiveness to pST. It is concluded that continuously released bST, but not pST, improves performance of finishing lambs.