The calcineurin inhibitor cyclosporine A improves lipopolysaccharide-induced vascular dysfunction but does not rescue from cardiovascular collapse in endotoxemic mice

The calcineurin inhibitor cyclosporine A (CsA) improves survival in endotoxemic mice. It was hypothesized that CsA counteracts the bradycardia and hypotension characteristic of endotoxemia. Vascular reactivity was determined in lipopolysaccharide (LPS; 50 μg/mL)-treated mouse aortic rings suspended in a myograph. Arterial blood pressure and heart rate were measured continuously with indwelling catheters in conscious mice treated with CsA and a bolus injection of LPS (2 mg/kg). The α₁-adrenoceptor agonist phenylephrine induced stable tension of aortic rings that were attenuated significantly by LPS. Co-incubation of rings with LPS and CsA (1?×?10^?7 mol/L–1?×?10^?5 mol/L) restored vascular reactivity to phenylephrine. Intravenous administration of CsA (20 and 40 mg/kg/day) to mice induced a significant increase (by approximately 10 mmHg) in mean arterial blood pressure (MAP), with no effect on heart rate. An LPS bolus led to significant decreases in MAP (by approximately 30 mmHg) and heart rate (to 50 % of baseline). CsA-treated LPS-mice exhibited higher MAP at some (20 mg/kg) or all (40 mg/kg) time points after LPS. The decrease in MAP (Δ pressure) was similar between vehicle- and CsA-treated groups. The 50 % decrease in heart rate was not affected by CsA. Inducible nitric oxide synthase (iNOS) mRNA and protein levels in LPS-treated mice organs and plasma NO _x concentration were significantly reduced by CsA. It is concluded that in a murine model of endotoxemia, increased peripheral vascular resistance and suppression of systemic NO formation by cyclosporine A are not sufficient to prevent cardiovascular collapse, which is caused primarily by compromised cardiac function.     

Missed isolated volar dislocation of the scaphoid.

A patient presented with volar dislocation of the scaphoid, the diagnosis of which had been missed for two weeks. He was treated with open reduction through a combined volar and dorsal approach with decompression of the median nerve, internal fixation, and a cast for eight weeks. One year postoperatively the functional result was good. A radiograph showed no sign of avascular necrosis.     

Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction.

AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995 and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials, and dosages did not increase during the observation period. Patients who did not start treatment shortly after discharge had a low probability of starting treatment later. CONCLUSION: The main problem with underuse of recommended treatment after AMI is that treatment is not initiated at an appropriate dosage shortly after AMI. A focused effort in the immediate post-infarction period would appear to provide long-term benefit.     

Drug abuse treatment outcome study of adolescents: a comparison of client characteristics and pretreatment behaviors in three treatment modalities.

OBJECTIVES: The present study presents background and pretreatment characteristics of adolescent substance abuse treatment clients, and it provides a mechanism for describing perhaps the largest research sample of adolescents who were in drug treatment in this decade. METHODS: The sample was 3382 subjects who presented for treatment from 1993 to 1995 in 37 programs in Pittsburgh. Pennsylvania: Miami, Florida; Minneapolis, Minnesota; Chicago, Illinois; Portland, Maine; and New York City, New York. Informed permission for the youth to participate was obtained from the subject's custodial parent/guardian, and both the youth and the youth's parents or guardians provided informed assent if they agreed to participate as subjects. Adolescents then were interviewed privately and confidentially by a trained professional interviewer who was independent of the treatment programs. The interviews queried subjects about their background, including education and employment; physical and mental health; use of tobacco, alcohol, and other drugs; sexual experiences; legal problems: religious beliefs; and treatment experience. RESULTS: The long-term residential treatment modality was the least gender balanced of the modalities and had the most African-American and Hispanic clients. This modality was distinguished by the proportion of clients who were referred to treatment by the juvenile or criminal justice system. Compared with other clients in other modalities, short-term inpatient clients were more likely to be female and white. Inpatient clients also reported more indicators of psychiatric impairment. Outpatient clients were slightly younger than clients in the other modalities, and more of them were attending school at the time of admission to treatment. Outpatient clients had the least criminally involved lifestyles, their rates of (regular daily or weekly) drug use were also the lowest of the three modalities for all drugs assessed, and they had the least drug treatment experience. CONCLUSIONS: These results merit several recommendations. One is the need for more community-based adolescent substance abuse treatment programs. An additional recommendation is for more substance abuse treatment programs in facilities that serve incarcerated youth. Finally, and perhaps most critically, it is recommended that programs be designed to address such specialized issues as comorbid substance abuse and psychiatric problems, family dysfunction, physical and sexual abuse, gender and ethnic differences, and academic performance.     

Lengthening of the tibia over an intramedullary nail, using the llizarov external fixator: Major complications and slow consolidation in 9 lengthenings

We lengthened 9 tibial segments over a nail to reduce the time in the external fixator in 5 patients with constitutional shortness. The median lengthening was 7 (5.5-7.3) cm and the external llizarov frame was removed after median 99 (63-125) days. In spite of a short time in the external fixator, consolidation was slow, with a median lengthening index of 4.4 (2.4-6.1) months/cm. The procedure resulted in 3 fatigue fractures of the intramedullary nail or interlocking screws that needed revision and bone grafting. In 1 patient, a deep intramedullary infection occurred. After the experience of these major complications we have returned to the traditonal callotasis lengthening method described by llizarov.