Cocaine use in pregnancy in Amsterdam

To study the effects of cocaine use in pregnancy in Amsterdam, clinical data on cocaine-using pregnant women ( n = 21) and their offspring ( n = 23) were obtained retrospectively (1987–1994) at the Academic Medical Center, Amsterdam. Infants exposed to cocaine had a median gestational age of 39 weeks and a median birth weight of 3090 g. There were six preterm infants, two small-for-gestational-age infants and five infants with a small head circumference. Three infants had a congenital malformation. One infant (Potter's syndrome) died shortly before birth. One infant had congenital syphilis, four had intracerebral abnormalities on ultrasound and four had abnormal neurologic symptoms in the neonatal period. One infant died after 21 days of life. At follow-up four infants showed abnormal development. In 12 of the 23 infants (52%), one or more possible effects of cocaine were found.     

Substance use in pregnancy: do we care?

Two cohorts of substance-using women were compared retrospectively. From 1969 to 1979 a very high perinatal mortality rate (PMR 9.8%) was found among 92 polydrug-using women (1 twin excluded). Preterm delivery occurred in 25% of all pregnancies and in 30% of the children birth weight was below the 10th percentile. Nineteen women using heroin only had a worse fetal outcome (PMR 32%, preterm delivery in 47%, birth weight < 10th percentile in 42%). These results led to a strict surveillance system. In the period 1980–1989, 240 women (4 twins excluded) delivered after 16 weeks. Total fetal loss decreased to 2.1% and PMR to 0.4%, which was similar to results in controls. However, 22% of the women still delivered before 37 weeks and 27% delivered a child < 10th percentile. Methadone-using women were able to halve their dosage during pregnancy and 16 were detoxified. Multivariate analysis within the substance users of the second cohort showed that the neonatal abstinence syndrome, but not the (registered) amount of opiates used, was related to a lower birth weight. Not coping with prenatal care was related to a shorter pregnancy length. Multivariate analysis, including the controls, showed a significant relation of birth weight (345 g lower) with substance use. Also, head circumference was 0.8 cm smaller. Length of pregnancy however was related to smoking. This study shows that it is difficult to make substance users attend prenatal care, but also that women coping with prenatal care reduce substance intake. Opiate use might be responsible for lower birth weight, although not in a clear dose–response relationship, whereas lifestyle, as represented by not coping with prenatal care and the quantity of cigarette smoking, shortens the length of pregnancy.     

Rehabilitation outcomes of a psychosomatic clinic integrating fully inpatient and partial hospitalization rehabilitation approaches: a comparison

As publications from the domain of psychosomatic rehabilitation pertaining to the conceptual approaches and effects of partial-hospitalization rehabilitation have so far relied on very small case numbers, the effectiveness of partial-hospitalization rehabilitation was analysed in 318 patients in comparison to a large sample of rehabilitants who had participated in fully inpatient rehabilitation. No relevant differences were found among the groups studied in sociodemographic respects or range of diagnoses. The same was true concerning the level of complaints present at the onset of rehabilitation. Good rehabilitation outcomes were achieved in both groups, however, the effect sizes found for changes in depressiveness and indulgence to complaining ("Klagsamkeit") (GSI from the SCL-90) were lower in the partial-hospitalization group than in the patients in fully inpatient rehabilitation. Also, the relatively high share of partial-hospitalization patients discharged unable to return to work might be clinically significant. While our findings confirm the good results reported from other disciplines, they nevertheless are a reminder of the need for very careful selection of patients for partial-hospitalization rehabilitation, in order not to withhold "better" rehabilitation than could be provided on a partial-hospitalization basis from patients with special sociomedical problems. The best rehabilitation outcomes seem to be achieved by those patients who, towards the end of fully inpatient rehabilitation, were granted transition to the partial-hospitalization programme.     

Comparative in vitro activity of temocillin and other antimicrobial agents against Enterobacteriaceae isolated from patients admitted to five Belgian hospitals

Temocillin, a methoxy-derivative of the broad-spectrum penicillin, ticarcillin, has been introduced into clinical practice in Belgium in 1988. Since then, not many surveys of its in vitro activity have been published. This study addresses this issue in a prospective collection of 300 consecutive Gram-negative isolates originating from in-patients in five general hospitals throughout Belgium. In addition to temocillin, seven common antibiotics were tested: amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime, aztreonam, meropenem, ciprofloxacin and amikacin. Meropenem appeared to exhibit the best activity overall, whereas amoxicillin-clavulanate scored the worst. Cumulative MIC plot for two subsets of organisms are given: temocillin, meropenem and cefotaxime are the most active on E. coli and Klebsiella spp., while a significant percentage is resistant to ciprofloxacin and amoxicillin-clavulanate. In the group of inducible Enterobacteriaceae, temocillin, meropenem and amikacin are the most active drugs, while the activity of amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime and ciprofloxacin is largely decreased. Taking this well preserved in vitro activity of temocillin into account, and looking at its convenient pharmacokinetics and low cost of acquisition, this drug may prove a useful alternative in the treatment of severe nosocomial infections.     

Fractionated doses of oral etoposide in the treatment of patients with aids-related kaposi sarcoma: a clinical and pharmacologic study to improve therapeutic index

The purpose of this study was to examine the antitumor activity, toxic effects, and plasma pharmacokinetics of fractionated doses of oral etoposide aiming at the achievement of prolonged safe and active plasma drug levels in patients with AIDS-related Kaposi sarcoma (KS). This was designed as a phase II trial in which consecutive patients with progressing AIDS-KS after at least 3 months of active antiretroviral therapy received oral etoposide at the dose of 20 mg/m2 every 8 hours daily for 7 days every 21 days, with the study of its plasma pharmacokinetics. Eligible patients were 18 to 60 years old, with a histopathologically confirmed diagnosis of AIDS-related KS, human immunodeficiency virus-positive test, progressing after at least 3 months of active antiretroviral therapy, World Health Organization (WHO) performance status 0 to 3, New York University staging IIA or greater, no active infection except oral candidiasis, normal bone marrow, liver, and renal function, and who signed an informed consent. Objective tumor responses were evaluated after at least one full treatment course according to a modified WHO criteria, and toxicity was evaluated weekly and graded using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) criteria. For the pharmacokinetic study, plasma was obtained from patients during the first drug administration immediately before and at various time points thereafter. Etoposide was measured after extraction from plasma by a standard high-performance liquid chromatography. Twenty-one patients were accrued for the study, and 18 of them met the eligibility criteria. They were all men, with median age of 36 years old (range: 25-50 years), median WHO performance status 0 (range: 0-3) median CD4+ count (cells/mm3) 67 (range: 8-443), prior AIDS diagnosis in 10 of 18 cases, NYU staging IIA (1 patient), IIB (1), IIIA (7), IIIB (1), IVA (4), and IVB (4) sites of disease: mucocutaneous only (5), mucocutaneous/lymph nodes (5), mucocutaneous/lung (5) and mucocutaneous/lymph nodes/lung (2); and prior cytotoxic treatment in two patients. Seventy-two percent of cases presented some form of toxic effect (NCI-CTC). Leukopenia was documented in 50% of cases, anemia occurred in 61%, whereas thrombocytopenia was documented in 17% of the patients. The main nonhematologic toxicities were nausea and vomiting in 17% of cases and alopecia in 44%. The overall objective response rate was 83%, with 2 complete remissions documented (11%). The median duration of responses was 12 weeks (range: 3-45 weeks). The median t1/2 of etoposide in plasma was 4.11 hours (range: 1.95-9.64), area under the curve was 13.51 microg/h/ml (range: 7.12-24.42), Cmax was 2.17 microg/ml (1.40-4.41), tmax (1.00-2.00), mean residence time 4.62 hours (range: 3.75-5.20 hours), CIt (total clearance) 3.13 l/m2/h (range: 1.49-5.20 l/m2/h), Vd 13.08 l/m2 (range: 6.23-19.65 l/m2), and the median etoposide plasma concentration time greater than 1 microg/ml was 3.69 hours (range: 1.00-6.80 hours). The use of fractionated oral daily doses of etoposide produced significant antitumor activity with manageable clinical toxicity in the individuals with AIDS-KS included in this trial. This more favorable therapeutic index of etoposide could be due to the achievement of more sustained plasma levels of the drug within safe but active concentrations.     

添加谷氨酰胺的全胃肠外营养对造血干细胞移植术后常见并发症的防治作用

目的:严重的黏膜损伤是诱发造血干细胞移植后出现并发症的一常见原因,已有证据显示谷氨酰胺能降低接受化疗患儿黏膜炎的发生率。观察谷氨酰胺对异基因外周造血干细胞移植患者并发症及恢复的影响。方法:选择于2002-03/2006-11在河南省血液病研究所接受同胞异基因外周造血干细胞移植的48例血液系统肿瘤患者。所有患者及其家属对治疗和实验均知情同意,并经医院伦理委员会批准。所有患者移植前均处于完全缓解状态,营养中等或良好,心、肝、肾功能正常,将48例患者随机分为标准化全胃肠外营养液组(标准组,n=13)和加用谷氨酰胺的全胃肠外营养液组(谷氨酰胺组,n=35)。待患者中性粒细胞升至1.0×109L-1,且无任何感染指征,进行异基因外周造血干细胞移植。造血干细胞输注后第1天开始给予全胃肠外营养与胃肠外营养联合谷氨酰胺双肽,至中性粒细胞≥1.0×109L-1,且无消化道症状时停用。观察两组患者中性粒细胞恢复时间、出层流室时间以及关于感染、急性移植物抗宿主病等情况有无差异。结果:48例患者均进入结果分析。两组患者营养物质的摄入基本相同,谷氨酰胺组有6例发生黏膜炎,标准组有11例,差异显著(P<0.05);谷氨酰胺组有1例发生严重腹泻,标准组有5例,差异显著(P<0.05);谷氨酰胺组有3例发生临床感染,标准组有7例,差异显著(P<0.05);标准组中性粒细胞≥0.5×109L-1的持续时间短于谷氨酰胺组(P>0.05);谷氨酰胺组抗生素治疗时间及无菌病房居住时间较标准组短(P<0.05);两组急性移植物抗宿主病发生率差异无统计学意义(P>0.05)。结论:添加谷氨酰胺的全胃肠外营养可改善异基因造血干细胞移植患者的营养状态,减少感染及肠损害,减少急性移植物抗宿主病的发生,有利于异基因移植患者恢复。