Unchanged acetylation of isoniazid by alcohol intake.

SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid. DESIGN: In a crossover design, an oral dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS: Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake. CONCLUSION: Acute alcohol intake has no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics.     

Expression pattern of the CCAAT/enhancer-binding protein C/EBP-beta in gestational trophoblastic disease.

The CCAAT/enhancer-binding protein (C/EBP) family consists of several factors that are important regulators of intracellular processes and hormone action. C/EBP-beta, the most important member of the C/EBP family, was shown recently to be expressed in the normal human placenta where it is localized in villous syncytiotrophoblast and in the extravillous (intermediate) trophoblast but not the villous cytotrophoblast. The purpose of this study was to investigate the expression pattern of C/EBP-beta in gestational trophoblastic disease (GTD) which has not been studied so far. We used immunohistochemistry on a total of 15 cases of GTD including nine complete hydatidiform moles, one placental site nodule (PSN), one placental site trophoblastic tumor (PSTT), and four choriocarcinomas. All our tested specimens showed positivity for C/EBP-beta. The strongest C/EBP-beta expression could be observed in villous syncytiotrophoblast and in the trophoblast proliferations on the villous surface of hydatidiform moles; villous cytotrophoblast was negative. The PSN also showed positive nuclear staining but the expression was not as strong as it was in the hydatidiform moles and the total amount of stained cells was the lowest of all GTD. The PSTT also showed immunoreactivity but with a weaker and more heterogeneous staining than in the choriocarcinomas. The specific expression pattern of C/EBP-beta in GTD indicate that C/EBP-beta could potentially be an additional marker of such lesions.     

Treatment results of aseptic non-unions of long bones with medullary canal reaming followed by intramedullary nailing]

This paper presents results of treatment of 46 consecutive patients with pseudoarthroses of the long bones treated with closed intramedullary reaming followed by intramedullary nailing. There were 22 nonunions of the tibia, 15 of the femur, 3 of the humerus and 6 of the forearm. The union occurred in 40 cases, among them in 3 of 4 treated atrophic, that gives 87% success. None of treated pseudoarthrosis of the humerus united.     

Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.     

Osseous destruction and rupture of the extensor tendon caused by sarcoidosis of the finger.

We describe a woman with osseous destruction and rupture of the extensor tendon as a result of sarcoidosis in the left third finger with no evidence of systemic involvement. The tendon was repaired and she was successfully treated with prednisone.     

Inhaled steroid delivery from small-volume holding chambers depends on age, holding chamber, and interface in children.

The relationship between the amount of inhaled steroids delivered from pressurized metered-dose inhalers used with their recommended holding chambers and age of the patients using these devices was studied in an open randomised cross-over filter study. We recruited 1-2-month-old healthy infants (n = 21), 2-3-year-old asthmatics (n = 13), 4-6-year-old asthmatics (n = 15), and 10-15-year-old asthmatics (n = 20). Each child inhaled two puffs, administered by a single investigator, of both budesonide through Nebuchamber and fluticasone propionate through Babyhaler, on two occasions. Moreover, the 4-6-year-old group inhaled via both facemask and mouthpiece. Drug, collected on a filter interposed between holding chamber and patient, was analysed by high performance liquid chromatography. Filter dose, expressed in percent of the nominal dose, was analysed in a mixed effect linear regression model with age group, holding chamber and inhalation interface (facemask or mouthpiece) as fixed effects and subject as random effect. Filter dose from both holding chambers increased significantly with age, from 3% with Babyhaler and 7% with Nebuchamber in the youngest children, to 40-41% with both holding chambers in adolescents. Nebuchamber delivered more drug than Babyhaler (p = 0.002), but variability in drug delivery (about 11%) was similar between holding chambers. Filter dose decreased from 35% to 22% with Babyhaler, and from 42% to 27% with Nebuchamber when using a mouthpiece rather than a facemask (p < 0.0001). Delivery of inhaled steroids used with their recommended holding chambers depends from age and holding chamber, but also from the inhalation interface. Lung deposition and clinical studies comparing inhalation from holding chambers with mouthpiece and facemask are urgently required.     

Evaluation of flow hemodynamics by color-Doppler following two different brachial arterial repair techniques.

OBJECTIVES: We compared the clinical and hemodynamic results following surgical repair of traumatic brachial artery injury using two different techniques micro- and macrovascular repair. MATERIALS AND METHODS: This was a retrospective study of 27 patients who had sustained penetrating, clean cut injuries of the brachial artery. Macrovascular techniques and a saphenous vein graft was used in 13 patients, while 14 patients were treated by primary microsurgical technique. Postoperatively, patients were followed for a mean of 26 months. All patients had color Doppler examination of the brachial artery, digital artery pressures and transcutaneous oxygen saturation determined. RESULTS: Clinical results based on distal pulses, Allens test and digital pressures were similar in the two groups. Color Doppler showed 8/13 anastomotic stenoses in macrovascular vein grafted repairs and 2/14 in microvascular repairs (p<0.05). The ratio of flow velocity proximal compared distal to the injury was significantly decreased in patients who had macrovascular repairs. CONCLUSION: Using ratio between proximal and distal site of anastomosis maximal peak systolic velocity as a objective color Doppler parameter, we were able to demonstrate differences in the hemodynamic status following macrovascular repair with vein grafts and microvascular primary repair. The results emphasize the importance of using a standard repair technique for similar injuries rather than the preference of the surgeon.     

Tremor analysis in two normal cohorts.

OBJECTIVE: Quantitative tremor analyses using almost identical methods were compared between two independent large normal cohorts, to separate robust measures that may readily be used diagnostically from more critical ones needing lab-specific normalization. METHODS: Hand accelerometry and surface EMG from forearm flexors and extensors were recorded with (500 and 1000 g) and without weight loading under postural conditions in 117 and 67 normal volunteers in two different specialty centers for movement disorders in Germany. RESULTS: Tremor amplitude (total power) and frequency fell within a similar range but differed significantly. A significant reduction of tremor frequency under 1000 g weight load (>1 Hz), and a lack of rhythmic EMG activity at the tremor frequency in around 85-90% of the recordings were robust findings in both centers. CONCLUSIONS: The differences in frequency and total power indicate that these measures critically depend on the details of the recording conditions being slightly different between the two centers. Thus each lab needs to establish its own normative data. We estimate that at least 25 normal subjects have to be recorded to obtain normal values. The reduction of tremor frequency under load and lacking tremor-related EMG activity were well reproducible allowing a differentiation of physiological from low amplitude pathological tremor. SIGNIFICANCE: This study provides a framework for more standardized tremor analyses in clinical neurophysiology.     

Effects of human amniotic fluid on cartilage regeneration from free perichondrial grafts in rabbits.

After the chondrogenic potential of free grafts of perichondrium was shown in several experimental studies, perichondrium has been used to reconstruct cartilage tissue in various clinical situations. This study investigates the effects of human amniotic fluid on neochondrogenesis from free perichondrial grafts in a rabbit model. Since this fluid contains high concentrations of hyaluronic acid, hyaluronic acid-stimulating activator, growth factors, and extracellular matrix precursors during the second trimester, it may have a stimulating effect on neochondrogenesis. Perichondrial grafts, measuring 20 x 20 mm2 were obtained from the ears of 144 New Zealand young rabbits and were sutured over the paravertebral muscles. The rabbits were randomly divided into three groups with 48 rabbits per group. In group 1, 0.3 ml human amniotic fluid, and in group 2, 0.3 ml saline were injected underneath the perichondrial grafts. Group 3 formed the control group in which no treatment was given. Histologically, neochondrogenesis was evaluated in terms of cellular form and graft thickness at 2, 4, 6, and 8 weeks after surgery. In group 1, the mature cartilage was generated quickly and the cartilage plate in this group was significantly thick and extensive when compared with groups 2 and 3 at 8 weeks ( p<0.05 ANOVA). In conclusion, our study shows that human amniotic fluid enhances neochondrogenesis from free perichondrial grafts. The rich content of hyaluronic acid and growth factors possibly participate in this result.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.