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.     

Self management of oral anticoagulation with the IN Ratio system: impact of a structured teaching program on patient's knowledge of medical background and procedures.

BACKGROUND: Self management of oral anticoagulation (OAC) decreases complication rates and improves quality of life. Manual and cognitive abilities of patients and patient training in a structured format are a precondition for this concept. Up to now, there is no evidence about knowledge increase from teaching programs. METHODS: Seventy-six patients (mean age, 57.4 years, 71% male) who started long-term OAC were included in the prospective multi-center study at three teaching centers representing different populations of anticoagulation patients: a department of cardiovascular surgery, an inpatient rehabilitation center and an anticoagulation clinic. The patients were trained in a structured education program for two days. For the evaluation, the patients performed standardized tests including 16 questions prior to start (T0), after each training unit (T1/T2) and 6 weeks later (T3). The primary endpoint was the percentage of > or =75% of patients who could answer > or =50% of questions correctly at T3. Secondary endpoints were the overall and item-specific percentages of correct answers at the end of each training unit (T1, T2) and at T3. In addition, the teaching program was rated by the patients on a six-point rating scale. RESULTS: Seventy-four out of 76 patients gave at least 50% correct answers at T3 (97.4%; 95% confidence interval, 90.8-99.7%). The average rates of correct answers developed from 40% (T0), 86% (T1), 94% (T2) to 96% (T3). The greatest increase of knowledge was observed with blood components, interpretation of International Normalized Ratio (INR) value, and the interaction of anticoagulation with other variables (e.g. drugs or infection). Patients rated the teaching program between 1 (best rating) and 2 at all time points. At T3, the patients reported less fear of complications and less limitations in their daily life than in earlier evaluations. CONCLUSION: The structured training program INRatio appears to be an appropriate instrument for instruction of INR self management. In comparison with baseline knowledge, the percentage of correctly answered questions was twice as high directly after the end of training and remained at a high level of >90% for at least 6 weeks.     

Lumbar spinal stenosis operative treatment--early results]

Early results (12 weeks after surgery) of the lumbar spinal stenosis operative treatment were assessed in the group of 36 patients (aged 40-65 years). In 72% of patients posterior fusion was applied. In the results evaluation lumbar pain, low extremities pain, neurogenic claudicat ion, sensory disturbances and functional status were taken in account. A significant decrease in low extremities and lumbar pain was observed. Some sensory disturbances after operative treatment did not affect general high patients assessment of the performed surgical procedures (positive 80.5% cases).     

Prevalence of impaired glucose tolerance 6 years after gestational diabetes.

AIM: Prevalence of glucose metabolism disorders in women six years after gestational diabetes in the index pregnancy (GDM). METHOD: 227 Caucasian women who developed GDM between 1995 and 1996 were investigated; 173 women (BMI 27.5+/-6.0 kg/m2) received 75 g oGGT on average 5.8+/-2.0 years after delivery. RESULTS: Impaired glucose metabolism was found in 31.2%, IGT or IFG 19.1%, diabetes mellitus type 2 (DM2) 9.2%, diabetes mellitus type 1 (DM1) 2.3%, second GDM 0.6%. 27.2% (BMI 25-29.9 kg/m2) were overweight, 23.1% suffered from obesity (BMI 30-39.9 kg/m2) and 5.2% morbid obesity (BMI>or=40 kg/m2). In comparison to a healthy control group, women with DM2 at re-examination were: older in age (32.1+/-5.9 vs. 29.1+/-4.8 years, p<0.05), had higher BMI (29.4+/-6.9 vs. 24.6+/-4.8 kg/m2, p<0.05), higher fasting blood glucose (6.5+/-1.9 vs. 5.2+/-0.9 mmol/l, p<0.05), earlier diagnosis of GDM (25+/-8 vs. 29+/-5 SSW, p<0.05), more frequent insulin therapy during pregnancy (75 vs. 24%) and had significantly higher insulin- and C-peptide for all measures of the oGTT, whereas HbA1c was not different (4.9+/-0.5 vs. 4.8+/-0.3%, n. s.). CONCLUSION: In an average of 5.8 years after the diagnosis of GDM, the majority of women still have chronic insulin resistance. One third has either IGT, IFG or diabetes mellitus. Therefore, a long term follow-up is strongly recommended for women diagnosed with GDM.     

Late diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Congenital adrenal hyperplasia results from 21-hydroxylase deficiency in more than ninety percent of cases. The classical form of 21-hydroxylase deficiency presents in the neonatal period with virilization or adrenal insufficiency, with or without concurrent salt wasting. We report on a rare case of classic 21-hydroxylase deficiency diagnosed in late adulthood. A 39-year-old male patient presented for workup of infertility. Urologic investigation revealed small testes, bilateral testicular masses, and asthenozoospermia. The patient's steroid metabolism showed markedly increased levels of adrenal androgens, in particular of 17-hydroxyprogesterone amd 21-deoxycortisol. The gas chromatographic-mass spectrometric (GC-MS) urinary steroid profile was dominated by metabolites of 17-hydroxyprogesterone, while the endogenous glucocorticoid production was subnormally low. ACTH levels in plasma were elevated. These hormonal findings were consistent with 21-hydroxylase deficiency. Therapy with dexamethasone was initiated. The CTP21A2 gene analysis revealed the mutation I172N (ATC --> AAC) in exon 4 of allele 1 and a large gene deletion in allele 2. Cases of 21-hydroxylase deficiency diagnosed in late adulthood are rare; however, clinicians should be alert of this possibility.