Methadone dosing, heroin affordability, and the severity of addiction

OBJECTIVES: This study sought to track changes in US heroin prices from 1988 to 1995 and to determine whether changes in the affordability of heroin were associated with changes in the use of heroin by users seeking methadone treatment, as indexed by methadone dose levels. METHODS: Data on the price of heroin were from the Drug Enforcement Administration; data on methadone doses were from surveys conducted in 1988, 1990, and 1995 of 100 methadone maintenance centers. Multivariable models that controlled for time and city effects were used to ascertain whether clinics in cities where heroin was less expensive had patients receiving higher doses of methadone, which would suggest that these patients had relatively higher physiological levels of opiate addiction owing to increased heroin use. RESULTS: The amount of pure heroin contained in a $100 (US) purchase has increased on average 3-fold between 1988 and 1995. The average dose of methadone in clinics was positively associated with the affordability of local heroin (P < .01). CONCLUSIONS: When heroin prices fall, heroin addicts require more methadone (a heroin substitute) to stabilize their addiction--evidence that they are consuming more heroin.     

Cost-effectiveness analysis in anaesthesia

In order to preserve the quality of anaesthetic care under cost containment programmes, the concept of value-based anaesthesia was introduced. To achieve this goal, namely, the provision of the best possible care attainable at a reasonable cost, studies are necessary that compare anaesthetic techniques in terms of both quality and costs, e.g. by means of cost-effectiveness analyses.     

Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group

PURPOSE: We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques. MATERIALS AND METHODS: A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996. RESULTS: Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant). CONCLUSIONS: Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.     

Cell subsets responding to purified hepatocytes and evidence of indirect recognition of hepatocyte major histocompatibility complex class I antigen. I. The role of L3T4+ T cells in the development of allospecific cytotoxicity in hepatocyte-sponge matrix allografts.

The purpose of this study was to determine the role of L3T4+, Ly2- T cells in the development of allospecific cytolytic T cells in response to purified allogeneic MHC class I+, class II- hepatocytes in vivo in hepatocyte-sponge matrix allografts (HC-SMA). In previous studies we have shown that 99% pure murine hepatocytes stimulate the development of allospecific cytolytic T cells in vitro in mixed lymphocyte-hepatocyte culture (MLHC) and in vivo in HC-SMA. Furthermore, depletion of L3T4+, Ly2- T cells from responder splenocytes inhibits the development of allo-CTLs in response to purified hepatocytes in mixed lymphocyte-hepatocyte culture. Here, using an anti-L3T4 monoclonal antibody, we tested the effect of in vivo immunodepletion of L3T4+, Ly2- T cells on the subsequent development of allo-CTLs in HC-SMA. Sponge cells were harvested on day 4 and day 12 after grafting from control and treated groups and phenotypically analyzed by FACS and immunofluorescent labelling. Splenocytes from the same animals were similarly analyzed to assess for completeness of immunodepletion. Allospecific cytotoxicity was assessed on day 12 after grafting. We found that immunotherapy with anti-L3T4 mAb was effective in depleting L3T4+, Ly2- T cells from the spleen; however, a similar number of L3T4+ cells was isolated from the sponge between control and treated groups. Furthermore, the development of allo-CTLs in response to hepatocytes in HC-SMA was completely abrogated by both local and systemic immunotherapy with anti-L3T4 mAb. We conclude from these and previous data that host or responder L3T4+, Ly2- T cells and responder accessory cells in MLHC or host macrophages in HC-SMA may participate in "indirect" recognition of hepatocyte class I antigen both in vitro and in vivo.     

Ethical issues in health care institutions. Lesson three: Hospital ethics committees

The hospital ethics committee serves as the topic for this third lesson of a five-part WMU/AHRA magazine course on ethics. Proliferating during the last ten years and fostered by the Karen Ann Quinlan case, hospital ethics committees today function in three areas: education, development of guidelines and policies, and individual case consultation. Using specific examples in the discussion of each function, the authors give a detailed picture of the valuable contribution these committees make to the institutions they serve.     

Patterns of structural deterioration due to ischemia in Purkinje fibres and different layers of the working myocardium

Cellular and mitochondrial swelling are regarded as typical intra-ischemic alterations ("IIA"), contraction band lesions (CBL), in contrast, as products of post-ischemic reperfusion. The occurrence of both types of structural deterioration was investigated in Purkinje fibres and subendocardial and intramural working myocardium: initially after St. Thomas- or HTK cardioplegia, then during ensuing global ischemia up to the "practical limit of resuscitability", and following post-ischemic reperfusion. Generally, Purkinje fibres are not better preserved than neighbouring working myocardium. Comparing St. Thomas- and HTK cardioplegia, considerable quantitative, but not qualitative differences in the reaction patterns of different cell types or layers arise. Immediately after cardioplegia, CBL are completely lacking in both cell types. During ischemia, CBL occur occasionally in Purkinje fibres and seldom in subendocardial working myocardium, "IIA" predominate. During post-ischemic reperfusion "IIA" tend to reverse in all layers, whereas CBL are found to remain in the subendocardial cell types. In intramural layers, CBL occur only during reperfusion. Thus, we deduce that cardioplegia only modulates the severity of "IIA" and the frequency of CBL, but cannot abolish the particular sensitivity of subendocardial Purkinje fibres to global ischemia. Prerequisites for the development of irreversible CBL are on the one hand ischemic metabolic alterations and corresponding energy deficits, and, on the other hand, a supply of oxygen. The oxygen may be inadequately supplied via diffusion during ischemia or may be subsequently provided by reperfusion.     

Circadian rhythm of lithogenic substances in the urine

Summary After determination of the lithogenic and inhibitory substances in serum and urine of 18 healthy control subjects and 20 patients with calcium oxalate urolithiasis on an uncontrolled diet, the alteration of the parameters while taking a standard diet was investigated. After attainment of a steady state, the investigations were performed over 48h on 3-h aliquots of urine. Typical circadian rhythms were detected for all lithogenic parameters in the urine and normal ranges were established. This special investigation permits detection of peaks in the excretion of lithogenic substances which were masked in investigation of 24-h urine samples alone.     

Retroperitoneal mature teratoma 15 years after initial treatment of testicular mixed germ cell tumor

We present a patient with a retroperitoneal tumor noted 15 years after treatment of a testicular mixed germ cell cancer. The patient initially underwent right-sided orchiectomy and retroperitoneal lymph node dissection for clinical stage I disease. An early relapse indicated by increasing tumor markers shortly after retroperitoneal lymph node dissection was successfully treated with five cycles of combined chemotherapy. However, 187 months after completion of chemotherapy, a symptomatic right-sided iliac mass was diagnosed. Radical surgical excision of the mass was performed and histologic examination revealed differentiated mature teratoma. This represents the longest time interval reported in the literature for a mature teratoma following treatment of a testicular germ cell tumor.