Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg

To cover intermediate sensitive Candida glabrata in ICU patients,fluconazole plasma peak levels at least in the range of 16–32µg/ml appear necessary for treatment. Previous studiesdid not reach these fluconazole levels under continuous veno-venoushaemofiltration (CVVHF) with dosages of 200–600 mg fluconzoledaily. In the present study, nine patients simultaneously requiringCVVHF for treatment of acute oligoanuric renal failure and antimycotictherapy of Candida septicemia received fluconazole 800 mg/day.Fluconazole plasma levels were determined to evaluate whetherthis dosage is adequate to reach the advised fluconazole levels.Patients were dialysed on two consecutive days with an ultrafiltrationrate (UF) of 1000 ml/h or 2000 ml/h, respectively, in a randomizedorder. The predilution was 800 ml/h and 1800 ml/h, respectively.The treatment was tolerated without adverse effects. All patientsreached plasma fluconazole concentrations between 16 and 32µg/ml, remaining in this range for a minimum of 1 up to24 h with a mean of 9.6 h and a UF rate of 2000 ml/h, and 15.7h with a UF rate of 1000 ml/h. So far, there are no in vivodata on the fluconazole plasma concentrations required for effectivetreatment. However, our data demonstrate, that at least thefluconazole concentrations desirable on the basis of in vitrosusceptibility testing can be reached in critically ill patientson CVVHF in an ICU setting. However, in these patients, 800mg fluconazole/day are necessary to achieve fungicidal drugconcentrations.     

Fatal craniocervical necrotizing fasciitis in an immunocompetent patient: A case report and literature review

Background. Craniocervical necrotizing fasciitis (CCNF) is a rapidly progressive, severe bacterial infection of the superficial fascial planes of the head and neck. Group A beta–hemolytic Streptococcus, staphylococcus aureus, and obligate anaerobic bacteria are common pathogens. The disease usually results from a dental source or facial trauma. Extensive fascial necrosis and severe systemic toxicity are common manifestations of CCNF. Recently the lay press has referred to necrotizing fasciitis in several articles about “flesh eating” bacteria, which have resulted in several deaths. Methods. We report the first case of a fatality in an otherwise immunocompetent patient. The patient was a 66-year-old black man with no identifiable source of infection and no history or evidence of immunocompromising disorders. Results. Despite aggressive surgical debridement and broad-spectrum antibiotic coverage, he died 30 hours after admission from multisystem organ failure secondary to overwhelming sepsis. Conclusion. Treatment consists of early recognition of CCNF combined with aggressive surgical debridement and drainage of the involved necrotic fascia and tissue along with broad-spectrum intravenous antibiotic coverage. Although 11 other fatal cases of CCNF have been previously reported, all had an underlying medical problem which created an immunocompromised state, usually diabetes mellitus or chronic alcoholism. We present a case report and literature review along with a discussion of the related anatomy. © 1995 Jons Wiley & Sons, Inc.     

Psychological factors in functional gastrointestinal disorders: characteristics of the disorder or of the illness behavior?

OBJECTIVE: This study examines factors affecting the frequency of physician consultations by individuals with functional gastrointestinal disorders (FGD) in a group of subjects with functional dyspepsia or irritable bowel syndrome. Systematic selection of persons who were already seeing a physician for one of these problems was avoided by conducting an epidemiological field study rather than a clinical study. METHODS: A representative sample of the German population (N=2201) completed a questionnaire that included, in addition to the criterion (number of physician visits in the past 12 months), items aimed at identifying the target group and questions about physical symptoms, illness behavior, living situation, personality features, and sociodemographic status (a total of 31 predictors). RESULTS: Individuals with functional gastrointestinal disorders who consulted a physician for their gastrointestinal disorders and those who did not differed significantly, especially on psychological measures. The differences between these individuals and the general population were greater for the consulters than for the nonconsulters. Multiple regression analyses yielded nine predictors that explained 40.2% of the variance of the criterion. The best predictors of frequency of physician consultations were the duration of periods with symptoms and psychological factors, such as the severity of depression and the patients' views on the cause of their illness. CONCLUSIONS: The psychopathology seen in people with functional gastrointestinal disorders is of two types: one is a characteristic of the illness itself and the other leads the individual to consult a physician. When gastroenterologists see patients with such disorders, they can assume that they may be dealing with a self-selected group of individuals with psychological stress. Psychological assessment would, therefore, be useful to determine whether a given individual with FGD might benefit from psychotherapy.     

Activated protein C resistance shows an association with pregnancy-induced hypertension

A common mutation in the factor V gene, the Leiden mutation, is the most frequent genetic cause of resistance to activated protein C (APC). Recent studies have shown that the prevalence of APC resistance is associated with severe pregnancy-induced hypertension (PIH). Our objective was to determine whether the factor V Leiden mutation is more prevalent in patients who developed severe PIH than in normotensive pregnant women. In 70 women with a history of severe PIH, of whom 15 had pre-eclampsia, we investigated common coagulation factors as well as APC resistance (factor V related). We found that seven of these 70 women showed low values for APC. Out of these, five were heterozygous and none was homozygous for factor V Leiden mutation. In a control group of normotensive pregnant women we found a 3.0% rate of APC resistance and a 3.0% rate of carriers of the Leiden mutation. These results indicate a significantly higher prevalence of both APC resistance and factor V Leiden mutation in women with severe PIH. Placental infarctions and micro-embolisms are considered to be one of the principle pathophysiological changes in severe PIH. Our results suggest that APC resistance is a risk factor for severe PIH, in addition to its well-known role in macrothrombo-embolism.     

Cytoadhesins of Mycoplasma hominis.

The mechanism of Mycoplasma hominis adherence to host cells of the urogenital tract was investigated with monoclonal antibodies (MAbs) directed against antigenic surface-localized polypeptides P50, P60, P80, and P100 of cytoadherent M. hominis FBG. A cell enzyme-linked immunosorbent assay was established allowing quantification of cytoadherent mycoplasmas detected by one of the following MAbs: four MAbs directed against P100 (molecular weight, about 100,000), three MAbs against P80, one MAb against P60, and three MAbs against P50. MAb binding to one of the surface proteins resulted in a decrease of mycoplasmal adherence to HeLa cells. To exclude the thesis that this is caused by nonspecific blocking of adherence, P100 and P50 were purified by affinity chromatography and tested instead of intact mycoplasmas in the cell enzyme-linked immunosorbent assay for cytoadherence. Both proteins bound to the surface of the eukaryotic cells. MAb binding to single epitopes of these proteins resulted in inhibition of protein adherence. These experiments strongly suggest that of the four surface-localized proteins at least P100 and P50 are adhesins of M. hominis FBG.     

Two-Generation Reproductive Toxicity Study of Dietary Tributyl Phosphate in CD Rats

Tributyl phosphate (TBP) was tested for reproductive toxicityin rats. Thirty weanlings/sex (F0) were exposed to TBP in thediet ad libitum at 0, 200, 700, or 3000 ppm for 10 weeks andthen randomly mated within groups for 3 weeks with continuedexposure. F0 parents and 10 F1 weanlings/sex/dose were necropsied,and adult reproductive organs, urinary bladders (both sexes),kidneys (males), and livers (females) were evaluated histologically.Thirty F1 weanlings/sex/dose continued exposure for 11 weeksand were bred as described above. F1 parents and P2 weanlings,10/sex/dose, were then necropsied as described above. Adulttoxicity was observed in both sexes and generations at 700 and3000 ppm; observations included reduced body weights, weightgain and feed consumption, urinary bladder epithelial hyperplasia(both sexes), renal pelvis epithelial hyperplasia only at 3000ppm (male kidneys), and centrilobular hypertrophy (female livers).At 200 ppm, transient reductions in body weight were observedin F0 and F1 females, with urinary bladder epithelial hyperplasiain F0 males and females and in F1 males. There was no evidenceof reproductive toxicity, of reproductive organ pathology, orof effects on gestation or lactation at any dose tested. Postnataltoxicity was evidenced by consistent reductions in F1 and F2pup body weights at 3000 ppm and by occasional weight reductionsin F2 litters at 700 ppm, and was associated with maternal toxicityobserved at these doses and times. Under the conditions of thisstudy, a NOAEL was not determined for adult toxicity; the NOAELfor reproductive toxicity was at least 3000 ppm and the NOAELfor postnatal toxicity was approximately 200 ppm.     

Beta-oxidation of 1-[14C]-17-[131I]-iodoheptadecanoic acid following intracoronary injection in humans results in similar release of both tracers

Radioiodine labelled 17-iodo-heptadecanoic acid (IHA) is used for non-invasive study of myocardial metabolism in coronary heart disease and cardiomyopathy. Yet in the interpretation of in vivo myocardial tracer kinetics, it is controversial whether the intracellular degradation of IHA or the removal of iodide across cellular membranes is the rate-limiting step in iodide release from the myocardium. In five patients undergoing coronary sinus catheterization, a mixture of about 40 kBq of [¹²³I] NaI was injected into the left coronary artery. During the following 15-min period, frequent blood samples were taken from the aorta and the coronary sinus. In the aqueous phase of the venous blood, ¹⁴CO₂ and inorganic ¹³¹I appeared nearly in parallel, with a peak time of 4–5 min. Moreover, as shown by the AV difference, there was no significant back diffusion of IHA and no significant non-specific deiodination detectable over the period of observation. There was myocardial retention of inorganic iodide (¹²³I) injected into the left coronary artery. The data strongly support the premise that lipid turnover through -oxidation is the rate-limiting step in the externally measured release of iodide after IHA injection, provided that recirculating inorganic radioactive iodide is corrected for. In addition, 15 volunteers were studied using [¹¹C]palmitic acid and [¹²³I]IHA using PET and dynamic planar camera scintigraphy with iodide correction. There was no significant difference between the mean values of the elimination half-times, and also no significant correlation between half-times of both fatty acids for single individuals.     

Analysis of the S810L point mutation of the mineralocorticoid receptor in patients with pregnancy-induced hypertension.

OBJECTIVE: A missense mutation at codon 810 (Ser --> Leu) of the mineralocorticoid receptor was recently observed in a family with early manifestation of hypertension. Our objective was to determine if this mineralocorticoid receptor alterations is prevalent in patients with pregnancy-induced hypertension. METHODS: Thirty-eight women with hypertension during pregnancy were tested for the mineralocorticoid receptor gene mutation. DNA was extracted out of blood leucocytes. PCR and automated DNA sequencing were used to analyze exon 6 for the S810L missense mutation. Anamnestical data concerning cardiovascular risk factors and family history were evaluated with a questionnaire. Pregnancy course and outcome were documented in all cases. RESULTS: In 33 patients with pregnancy-induced hypertension and in five patients with exacerbation of preexisting hypertension in pregnancy no point mutations were found at codon 810 in exon 6. CONCLUSIONS: Our data suggest that the S810L missense mutation of the mineralocorticoid receptor does not play a major role in the etiology of pregnancy-induced hypertension in a German /Turkish population.