Nucleotide sequence of the leukotoxin genes of Pasteurella haemolytica A1.

A 4.4-kilobase-pair DNA fragment coding for the leukotoxin of Pasteurella haemolytica A1 has been isolated, and its nucleotide sequence has been determined. Two open reading frames, designated lktC and lktA, coding for proteins of 19.8 and 101.9 kilodaltons, respectively, were identified. Expression of the two genes in minicell-labeling experiments resulted in the production of the predicted proteins LKTC and LKTA. By using an antiserum against the soluble antigens of P. haemolytica A1 in Western blot (immunoblot) analysis of total cellular proteins from the Escherichia coli clones, LKTA was identified as an additional antigenic protein. Results from subcloning of the DNA fragment suggested that expression from both lktC and lktA is required for leukotoxin activity, indicating that the leukotoxin of P. haemolytica A1 is encoded by two genes. A comparison of the organization and the DNA sequence of the leukotoxin genes with those of the E. coli alpha-hemolysin genes showed a significant degree of homology between the two loci. This analysis suggested that the leukotoxin genes of P. haemolytica A1 and the E. coli alpha-hemolysin genes may have evolved from a common ancestor and that the two toxins may share similar activities or functional domains or both.     

Altered islet Beta-cell function before the onset of Type 1 (insulin-dependent) diabetes mellitus

Summary To define the glucose to insulin dose-response relationship before the onset of diabetes, we studied 22 nondiabetic co-twins of patients with Type 1 (insulin-dependent) diabetes mellitus and nine control subjects. All had intravenous glucose tests at 0.02, 0.1 and 0.5 g/kg and were followedup prospectively for at least 6 years. Seven twins developed diabetes a mean of 7 months later; the remaining 15 are now unlikely to develop diabetes. The seven pre-diabetic twins had higher fasting insulin levels than control subjects (4.2±2.0 vs 1.8±1.8 nmol/l; p<0.05); but lower glucose clearance (1.0±0.5 vs 1.9±0.7 %/min; p<0.05), first phase insulin response at 0.5 g/kg (21.1±23.2 vs 143±50 nmol/l; p<0.0001), and total insulin responses at 0.1 g/kg (p<0.05) and 0.5 g/kg (p<0.00005). Using a curve-fitting programme, the normal glucose to insulin relationship was lost in prediabetic twins who had lower coefficient of determination (R²) than control subjects (p<0.01). In contrast, 15 low-risk twins and their nine control subjects had similar fasting glucose and insulin levels, glucose clearance, R² and insulin secretory responses to different glucose loads. The positive predictive values of subnormal R² and subnormal first phase insulin response were 67 % and 58 % respectively. These observations demonstrate an altered glucose to insulin dose-response relationship and loss of maximum insulin secretory response to glucose before the onset of Type 1 diabetes.     

Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study

The pharmacokinetics and metabolism of 4-demethoxydaunorubicin (idarubicin, IDA) were studied in 21 patients with advanced cancer after i.v. (12 mg/m2) and oral (30-35 mg/m2) treatment according to a balanced crossover design. Patients were divided into four groups: subjects who showed normal liver and kidney function (group N), those who presented with normal kidney function and liver metastases (group L), those with kidney dysfunction (creatinine clearance, less than or equal to 60 l/h; group R), and those with both liver and kidney dysfunction (group LR). Five patients showed variations in liver or kidney function after the first treatment and were considered to be nonevaluable for the crossover study but evaluable for the liver/kidney function study; some of them appeared in different groups for the i.v. as opposed to p.o. treatments. After i.v. administration, IDA plasma levels followed a triphasic decay pattern. The main metabolite observed in all patients was the 13C-reduced compound (IDAol), which attained plasma levels 2-12 times higher than those of the parent compound. IDA pharmacokinetics was not dependent on the presence of liver metastases but was related to the integrity of kidney function. Analysis of variance indicated a significant correlation between IDA plasma clearance and creatinine clearance; it was also found that IDA plasma clearance was lower in patients whose creatinine clearance was less than 60 ml/min [group N, 122.8 +/- 44.0 l/h; group L, 104.4 +/- 27.7 l/h (P = 0.58) vs group R, 83.4 +/- 18.3 l/h (P = 0.037)]. The IDAol terminal half-life and mean residence time (MRT) were significantly increased in patients with impaired kidney function [MRT: group N, 63.6 +/- 10.8 h; group L, 69.9 +/- 10.2 h (P = 0.27) vs group R, 83.2 +/- 10.9 h (P = 0.025) and t1/2 gamma: group N, 41.3 +/- 10.1 h; group L, 47.0 +/- 7.4 h (P = 0.31) vs group R, 55.8 +/- 8.2 h (P = 0.025)]. After oral treatment, drug absorption occurred during in the first 2-4 h after IDA administration; a biphasic decay pattern was observed thereafter. The main metabolite observed in all patients was again IDAol. The AUC of IDAol was greater after oral administration than after i.v. treatment in proportion to the AUC of IDA (i.v.: AUC-IDAol/AUC-IDA, 2.4-18.9; p.o.: AUC-IDAol/AUC-IDA, 4.1-21.4). Following oral dosing, a substantial amount of 4-demethoxydaunomycinone (AG1) was found in 11/21 patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Adult-to-adult living donor liver transplantation using extended right lobe grafts.

OBJECTIVE: The authors report their experience with living donor liver transplantation (LDLT) using extended right lobe grafts for adult patients under high-urgency situations. SUMMARY BACKGROUND DATA: The efficacy of LDLT in the treatment of children has been established. The major limitation of adult-to-adult LDLT is the adequacy of the graft size. A left lobe graft from a relatively small volunteer donor will not meet the metabolic demand of a larger recipient. METHODS: From May 1996 to November 1996, seven LDLTs, using extended right lobe grafts, were performed under high-urgency situations. All recipients were in intensive care units before transplantation with five having acute renal failure, three on mechanical ventilation, and all with hepatic encephalopathy. The median body weight for the donors and recipients was 58 kg (range, 41-84 kg) and 65 kg (range, 53-90 kg), respectively. The body weights of four donors were less than those of the corresponding recipients, and the lowest donor-to-recipient body weight ratio was 0.62:1. The extended right lobe graft was chosen because the left lobe volume was <40% of the ideal liver mass of the recipient. RESULTS: Median blood loss for the donors was 900 mL (range, 700-1600 mL) and hospital stay was 19 days (range, 8-22 days). Homologous blood transfusion was not required. Two donors had complications (one incisional hernia and one bile duct stricture) requiring reoperation after discharge. All were well with normal liver function 5 to 10 months after surgery. The graft weight ranged from 490 g to 1140 g. All grafts showed immediate function with normalization of prothrombin time and recovery of conscious state of the recipients. There was no vascular complication, but six recipients required reoperation. One recipient died of systemic candidiasis 16 days after transplantation and 6 (86%) were alive with the original graft at a median follow-up of 6.5 months (range, 5-10 months). CONCLUSIONS: When performed by a team with experience in hepatectomy and transplantation, LDLT, using an extended right lobe graft, can achieve superior results. The technique extends the success of LDLT from pediatric recipients to adult recipients and opens a new donor pool for adults to receive a timely graft of adequate function.     

Attitudes towards mental illness: testing the contact hypothesis among Chinese student nurses in Hong Kong

This study investigated whether previous contact with mental illness affected the attitudes to mental illness (AMI) of general student nurses in Hong Kong — the contact hypothesis. We employed a quasi-experimental design. We compared the attitudes to mental illness of students who had previous contact with mental illness through having taken a psychiatric secondment with those who had not taken a psychiatric secondment. Also, we compared the AMI of: students who had taken other courses related to mental illness with those who had not; those who had a family history of mental illness with those who had not; and those who lived with a mentally ill relative with those who did not. We found that previous contact with mental illness had no significant effect on the attitudes to mental illness of the students. In other words our findings do not support the contact hypothesis. Our sample expressed positive general attitudes to mental illness when presented with general issues about mental illness. However, their attitudes were less positive when presented with specific issues about mental illness that might impinge upon their daily lives. We discuss the implications of these findings for mental health nursing practice, education and research.     

Posterior beam-stop method for scatter fraction measurement in digital radiography.

The authors presented a new posterior beam-stop (PBS) technique for measuring the ratio of scattered to total-detected photon flux (scatter fraction) in a radiographic examination while preserving the diagnostic quality of the image. The scatter measurement was made using a standard imaging geometry with both beam stops and an additional x-ray detector placed behind the standard imaging detector. This PBS geometry differs from the standard beam-stop (SBS) technique for scatter measurement. With SBS, a beam-stop shadow appears on the image. To evaluate the PBS technique, scatter fraction measurements were performed on an anatomic phantom using both the PBS and SBS techniques. When compared with the standard technique, PBS provided accurate estimation of scatter fractions. Since the measurement can be performed without degrading a standard clinical radiographic examination, the PBS technique allows simultaneous acquisition of scatter measurements from human patients in combination with a standard radiographic examination.     

Effect of cyclosporin A and analogues on cytosolic calcium and vasoconstriction: possible lack of relationship to immunosuppressive activity.

1. The full therapeutic potential of the main immunosuppressive drug, cyclosporin A (CsA), is limited because of its side effects, namely nephrotoxicity and hypertension. Several lines of evidence suggest that the origin of both side effects could be CsA-induced vasoconstriction. However, the underlying molecular mechanisms are not well understood. 2. Diameter measurements of rat isolated mesenteric arteries showed an increase in noradrenaline- and [Arg]8vasopressin-induced vasoconstriction when arteries were pretreated with CsA. 3. Measurements in cultured vascular smooth muscle cells (VSMC) of either cytosolic calcium concentration or of 45Ca2+ efflux showed that CsA potentiated the calcium influx to several vasoconstrictor hormones: [Arg]8vasopressin, angiotensin II, endothelin-1 and 5-hydroxytryptamine. On the other hand, 45Ca2+ efflux in response to thapsigargin, which depletes calcium from intracellular pools, was not potentiated by CsA. 45Ca2+ uptake was not altered by CsA or by any of the analogues tested. 4. Time-course studies in cultured VSMC showed that maximal CsA-induced Ca2+ potentiation occurred after ca. 20 h and this effect was reversed over approximately the next 20 h. 5. To investigate the possible role played by the known intracellular targets of CsA, namely cyclophilin and calcineurin, CsA derivatives with variable potencies with respect to their immunosuppressive activity, were tested on the calcium influx to [Arg]8vasopressin. Derivatives devoid of immunosuppressive activity (cyclosporin H, PSC-833) potentiated calcium signalling, while the potent immunosuppressant, FK520, a close derivative of FK506, and MeVal4CsA, an antagonist of the immunosuppressive effect of CsA did not. The latter compound was unable to reverse the calcium potentiating effect of CsA. 6. Our results show that CsA increases the calcium influx to vasoconstrictor hormones in smooth muscle cells, which presumably increases vasoconstriction. Loading of the intracellular calcium pools appears not to be involved. Experiments with derivatives of CsA and FK520 suggest that interactions with cyclophilins and calcineurin are not the mechanism involved. This indicates, for the first time, that the immunosuppressive activity can be dissociated from the calcium potentiating effect of CsA in vascular smooth muscle.     

Effect of exercise on repetitive nerve stimulation studies: new appraisal of an old technique.

Repetitive nerve stimulation (RNS) is a simple and rapid method for evaluation of neuromuscular transmission defects. Although the effect of exercise in conjunction with RNS is well recognized, it has not been standardized in actual patient and control groups. In a prospective study over a period of 1 year, the authors evaluated the effect of exercise in conjunction with RNS in comparison with conventional 3-Hz RNS at rest in the clinical setting. Fifty-four patients who were referred for possible neuromuscular transmission disorders, in addition to 35 healthy control subjects, were studied. Amplitude and area decremental responses with RNS at rest and after 20 seconds of maximal exercise at 1-minute intervals up to 3 minutes were evaluated. The use of RNS with exercise resulted in additional diagnostic yield of up to 36.4% compared with conventional 3-Hz RNS at rest. The standardized use of exercise with RNS is advocated for increasing its diagnostic yield in the neurophysiologic laboratory.     

Acute pseudo-obstruction of the colon following partial splenic artery embolization: report of a case.

This is a case of a 45-year-old woman suffering from liver cirrhosis with hypersplenism who received a partial splenic artery embolization with gelfoam pieces. Thrombocytopenia and leukopenia improved immediately after treatment. Marked abdominal distention, metallic bowel sounds and combined small and large bowel distension with air-fluid levels as shown on a plain abdominal X ray were noted on the fifth day after the embolization procedure. Laparotomy was performed. No mechanical obstruction was found during surgery. Acute pseudo-obstruction of the colon (Ogilvie's syndrome) was diagnosed. This condition was considered to be a complication of the partial splenic artery embolization and has not hitherto been reported.