The hereditary spastic paraplegias

The hereditary spastic paraplegias are a complex group of neurodegenerative conditions which are characterised by slowly progressive lower limb spasticity. This article describes the main clinical features of pure and complicated hereditary spastic paraplegias and summarises recent advances in our understanding of the molecular genetics of these conditions. Received: 2 June 1999 Accepted: 7 August 1999     

Rapid repeat pregnancy and experiences of interpersonal violence among low-income adolescents

CONTEXT: Rapid repeat pregnancy (RRP) among adolescents, usually defined as pregnancy onset within 12-24 months of the previous pregnancy outcome, has frequently been the target of public health interventions, due to the exacerbation of negative consequences associated with recurrent adolescent pregnancy (and more specifically with childbearing). OBJECTIVE: To examine what, if any, relationship exists between RRP and the experience of interpersonal violence and abuse among low-income adolescents at one semi-urban health center. DESIGN: Case-control study using retrospective chart review. PARTICIPANTS AND SETTING: 100 women aged 13-21 who received prenatal care at one independent nonprofit health center that serves adolescents and their children from June 1994 through June 1996. MAIN OUTCOME MEASURES: Number and timing of pregnancies, occurrence of physical or sexual abuse; other psychosocial risk factors were evaluated. RESULTS: In this population, the experience of any form of physical or sexual violence during the study interval was associated with RRP within 12 months (p = 0.01, OR = 3.46) and 18 months (p = 0.013, OR = 4.29). Other previously reported predictors of RRP, including family stress, financial stress, and other environmental stressors did not reach statistical significance at either 12 months or 18 months in this sample. Of additional note, young women who experienced any form of abuse during the 12-month study interval were substantially more likely to miscarry than were their nonabused peers, and spontaneous abortion was also very strongly associated with RRP (p < 0.00001; OR = 22.6). CONCLUSIONS: The experience of interpersonal violence is correlated with rapid repeat pregnancy among low-income adolescents. This study strongly suggests a need for both extensive screening for partner and family violence among pregnant and postpartum adolescents, and follow-up safety planning support in combination with family planning interventions.     

Effects of Extracorporeal Shock Wave Lithotripsy to One Kidney on Bilateral Glomerular Filtration Rate and PAH Clearance in Minipigs

Purpose

This study examined the acute time course of effects of extracorporeal shock wave lithotripsy (ESWL)¹ on renal hemodynamics in anesthetized minipigs with and without pretreatment with verapamil.

Materials and Methods

We applied ESWL (2000 shocks, 24 kV, unmodified Dornier HM3), to the right kidneys of isoflurane-anesthetized female pigs. Urine flow and renal hemodynamics were monitored from each kidney via ureteral balloon catheters. Arterial blood pressure and bilateral urine flow, glomerular filtration rate (GFR, inulin clearance) and renal plasma flow (RPF, para-aminohippurate clearance) were monitored for 45 minutes before ESWL, and at 1, 4 and 24 hours after ESWL.

Results

Treatment with ESWL consistently caused unilateral hematuria and subcapsular renal hematomas in the shocked kidneys and significantly reduced GFR and RPF in those kidneys at 1 and 4 hours after ESWL. Urine flow was reduced through 24 hours in the shocked kidneys. Renal plasma flow, but not GFR, was significantly reduced in the contralateral (unshocked) kidneys at 1 and 4 hours after ESWL to the other kidneys. Verapamil blunted the ESWL-induced reductions of urine flow, GFR and RPF in the shocked kidneys and eliminated the reduction of RPF in the unshocked kidneys.

Conclusions

These experiments demonstrate that ESWL to 1 kidney acutely impaired hemodynamics in both kidneys and that verapamil attenuated the response in the shocked kidneys and eliminated it in the contralateral unshocked kidneys.     

Primary cutaneous mucoepidermoid carcinoma: report of a case

Primary mucoepidermoid carcinomas of the skin are extremely rare tumors. We describe a primary cutaneous mucoepidermoid carcinoma arising in the right ear (posterior mid helix) of a 66-year-old white man. The tumor was 0.6 cm in diameter, ulcerated and nonencapsulated. No other tumors were found in the patient. Histologically the tumor showed the characteristics of a "low grade" mucoepidermoid carcinoma, consisting of lobules of polygonal cells with vesicular nuclei. In the center of the lobules were large vacuolated cells (goblet cells). Transitions between the two cell populations were present throughout the tumor. An epidermal attachment of the tumor, as well as epidermal dysplasia, predominantly at the acrosyringium was present, consistent with the theory of sweat duct histogenesis of these tumors. Immunoperoxidase staining showed positivity for epithelial membrane antigen, keratin and carcinoembryonic antigen. The latter was predominantly positive in the goblet cells. Cutaneous metastasis of mucoepidermoid carcinomas with epidermal attachment has been reported. Our case showed only ear involvement and follow-up at 8 months has revealed no evidence of recurrence. These findings are consistent with the diagnosis of primary cutaneous mucoepidermoid carcinoma.     

Comparison of in vitro and in vivo inhibition potencies of fluvoxamine toward CYP2C19.

A previous study suggested that fluvoxamine inhibition potency toward CYP1A2 is 10 times greater in vivo than in vitro. The present study was designed to determine whether the same gap exists for CYP2C19, another isozyme inhibited by fluvoxamine. In vitro studies examined the effect of nonspecific binding on the determination of inhibition constant (K(i)) values of fluvoxamine toward CYP2C19 in human liver microsomes and in a cDNA-expressed microsomal (Supersomes) system using (S)-mephenytoin as a CYP2C19 probe. K(i) values based on total added fluvoxamine concentration (K(i,total)) and unbound fluvoxamine concentration (K(i,ub)) were calculated, and interindividual variability in K(i) values was examined in six nonfatty livers. K(i,total) values varied with microsomal protein concentration, whereas the corresponding K(i,ub) values were within a narrow range (70-80 nM). In vivo inhibition constants (K(i)iv) were obtained from a study of the disposition of a single oral dose (100 mg) of the CYP2C19 probe (S)-mephenytoin in 12 healthy volunteers receiving fluvoxamine at 0, 37.5, 62.6, and 87.5 mg/day to steady state. In this population, the ratio of (S)-4-hydroxy-mephenytoin formation clearances (uninhibited/inhibited) was positively correlated with fluvoxamine average steady-state concentration with an intercept of 0.85 (r(2) = 0.88, p < 0.001). The mean (+/-S.D.) values of K(i)iv based on total and unbound plasma concentrations were 13.5 +/- 5.6 and 1.9 +/- 1.1 nM, respectively. Comparison of in vitro and in vivo K(i) values, based on unbound fluvoxamine concentrations, suggests that fluvoxamine inhibition potency is roughly 40 times greater in vivo than in vitro.     

Summary of findings from the evaluation of a pilot medically supervised safer injecting facility

In many cities, infectious disease and overdose epidemics are occurring among illicit injection drug users (IDUs). To reduce these concerns, Vancouver opened a supervised safer injecting facility in September 2003. Within the facility, people inject pre-obtained illicit drugs under the supervision of medical staff. The program was granted a legal exemption by the Canadian government on the condition that a 3-year scientific evaluation of its impacts be conducted. In this review, we summarize the findings from evaluations in those 3 years, including characteristics of IDUs at the facility, public injection drug use and publicly discarded syringes, HIV risk behaviour, use of addiction treatment services and other community resources, and drug-related crime rates. Vancouver's safer injecting facility has been associated with an array of community and public health benefits without evidence of adverse impacts. These findings should be useful to other cities considering supervised injecting facilities and to governments considering regulating their use.