Pharmacokinetics of ofloxacin in healthy subjects and patients with varying degrees of renal impairment.

The pharmacokinetics of the new fluoroquinolone antimicrobial ofloxacin were studied in 18 subjects with normal renal function or varying degrees of renal impairment, including patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis. Apparent total body and renal clearances declined and elimination half-life increased with decreasing creatinine clearance. CAPD and haemodialysis removed clinically insignificant fractions of ofloxacin body burden over the study period (6-15% and 9-11% of the dose, respectively). The apparent volume of distribution, peak concentration, time to peak concentration, and non-renal clearance were not altered significantly by renal insufficiency. An extended dosing interval of 24-48 h is recommended, depending upon the degree of renal impairment, when creatinine clearance falls below 50 mL/min. In addition, supplemental doses would not appear to be necessary during CAPD and following haemodialysis.     

Unusual presentation and clinical variability in Belgian pedigrees with progressive external ophthalmoplegia and multiple deletions of mitochondrial DNA

We studied 14 patients from three unrelated Belgian pedigrees with a familial mitochondrial disorder and multiple deletions of mitochondrial DNA (mtDNA). In one family with an oculopharyngeal presentation there is a clear autosomal dominant inheritance. Progressive external ophthalmoplegia (PEO), “ragged red fibres” (RRF) and multiple deletions of mtDNA are common to all three families. Therefore a diagnosis of autosomal dominant progressive ophthalmoplegia with multiple deletions of mtDNA (adPEO) was made in one family at least. Our data confirm the previous observations that adPEO is a systemic disorder rather than a pure myopathy. In our pedigrees frequently associated features include axonal peripheral neuropathy, dysphagia, psychiatric illness, and sudden death. Mild ataxia, pes cavus and mitral valve prolapse with associated mitral insufficiency also occur. In some cases onset is atypical with neuropathy, adolescent onset myopathy or psychiatric illness. In such cases the common features of PEO and muscle weakness always complete the clinical phenotype later during the course of the disease. Biochemical studies on mitochondrial fractions prepared from one patient's muscle, revealed no abnormalities of respiratory chain enzyme activities.     

Results of intensive care treatment in patients with hematologic malignancies; relation to infections]

In a retrospective study we determined the factors that influence the outcome of patients requiring intensive care (IC) for the complications of the treatment of haematological malignancies. All consecutive patients suffering from haematological malignancy admitted to the IC unit of the University Hospital Nijmegen over a 4 year period (1986-1989) were studied; 39 patients (21 female, 18 male) with a median age of 41 year (range 18-71). Various clinical variables were assessed at admission and related to the outcome of IC treatment in terms of death or survival. Previously, 33 patients had undergone chemotherapy. Eight (21%) survived. One of a subgroup of 13 bone marrow transplantation patients survived. Hypoxaemic respiratory failure requiring mechanical ventilation was the most frequent reason for admission (20 patients of whom four recovered). The second most frequent reason was combination of respiratory failure and septic shock (eight patients, none recovered). Three out of five patients admitted with septic shock survived. The need for mechanical ventilation had the highest predictive power for a poor prognosis (p = 0.002). Mortality increased with increasing APACHE II score (p = 0.03). When more than four major organ systems were affected (seven patients), mortality was 100%. Granulocytopenia (leucocyte count less than 1 x 10(9)/l) at admission turned out to be of no prognostic significance, but absence of leucocyte recovery was a prognostically bad sign (p = 0.05). A considerable number of patients (20) suffered from a non-bacterial (opportunistic) infection, carrying a high mortality (only two patients survived: one with candida, one with a cytomegalovirus infection).(ABSTRACT TRUNCATED AT 250 WORDS)     

功能性消化不良的突出症状与临床特征及病理生理学机制的关系

背景与目的：功能性消化不良（FD）被认为是一类由不同病理生理原因导致的多种机能紊乱而促发的症状。Rome Ⅱ委员会建议将具有同种病理生理学及临床特征的FD患划分为感觉明显疼痛组和感觉不适组两个亚组。该研究旨在分析显疼痛或感觉不适与病理生理学机制间的关系，评价是否考虑到个体的显性症状将会产生更好的结果。方法：持续性FD患（n=720；489例女性；年龄41．3±0．6岁）填写消化不良调查问卷并确定出最令人烦恼的症状。分析此显症状在人口统计学、临床、病理生理学特点上的相互联系（研究592例患幽门螺杆菌感染、胃排空情况，对332例患行胃敏感性、顺应性试验）。结果：根据Rome Ⅱ标准，22％疼痛明显，78％不适感明显。疼痛明显的患超敏性的发生率较高（44％ vs 25％），且在这些病例中观察到的胃排空迟缓较少出现（16％ vs 26％），但是有较多的重叠。详细分析表明可能有8种消化不良症状其中之一较为突出。