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Biomedical subjects

M Heckmann

Publications and source records attributed to M Heckmann.

At least 19 recordsLinked to original sources
PubMed2006

[A new breath actuated dry powder inhaler (Auto-Jethaler)].

BACKGROUND: The aim was to examine the handling of the recently developed breath actuated dry powder inhaler Auto-Jethaler (PulmoTec GmbH/Höchstädt, launch by Ratiopharm and CT Berlin). METHOD: 75 patients suffering from asthma, cystic fibrosis or primary ciliary dysfunction (age: 3 to 34 years; 29 female, 46 male) with mild or moderate bronchial obstruction took part in the study. Lung function testing including body plethysmography was performed to measure bronchial obstruction independent of effort. Peak Inspiratory Flow (PIF) was measured using a Fleisch pneumotachograph equipped with or without a Auto-Jethaler. Instead of the commercially available drug tablet a stainless steal ring device of equivalent resistance, easy to disinfect, was used. Actuation of the rotation mechanism which was triggered by inspiration at an inspiratory flow of about 40 L/min was accompanied by a rattling noise. Aims of the study were to examine, whether the subjects were able to handle the new device, and to measure PIF without and via Auto-Jethaler. RESULTS: Handling of the Auto-Jethaler was found to be easy. All patients managed to reach or surpass the critical value of 40 L/min, even those with mild to moderate bronchial obstruction. PIF without Jethaler was 85 to 599 L/min, via Auto-Jethaler 40 to 215 L/min. PIF was significantly age dependent (p<0.001). CONCLUSIONS: These findings suggest that the Auto-Jethaler will be an appropriate device for drug administration in children older than 3 years provided that they understand the inspiratory breathing manoeuvre.

Adolescent↗
PubMed2006

Active zone assembly and synaptic release.

Neurotransmitter release at chemical synapses occurs when synaptic vesicles fuse to the presynaptic membrane at a specialized site termed the active zone. The depolarization-induced fusion is highly dependent on calcium ions, and, correspondingly, the transmission characteristics of synapses are thought to be influenced by the spatial arrangement of voltage-gated calcium channels with respect to vesicle release sites. Here, we review the involvement of the Drosophila Bruchpilot (BRP) protein in active zone assembly, a process that is required for the clustering of presynaptic calcium channels to ensure efficient vesicle release.

Animals↗
PubMed2005

Psychosocial aspects of patients with focal hyperhidrosis. Marked reduction of social phobia, anxiety and depression and increased quality of life after treatment with botulinum toxin A.

BACKGROUND: Primary focal hyperhidrosis (PFH) is defined as excessive sweating typically localized to specific body areas such as axillae, hands and feet. An association between PFH and anxiety as well as depressive syndromes has been suggested. OBJECTIVES: To investigate a possible association between PFH and anxiety, depression, social phobia and quality of life, and to study the effect of treatment with botulinum toxin A on these factors. METHODS: PFH was confirmed clinically and by gravimetry. To measure anxiety and depressive syndromes several German versions of standardized questionnaires were used: State-Trait Anxiety Inventory G Form X2 (STAI), Social Phobia Scale (SPS), Symptom Checklist of Derogatis (SCL-90-R), subscales 'Social Insecurity', 'Depression', 'Anxiety' and 'Phobia', and Hospital Anxiety and Depression Scale (HADS-D). Quality of life was assessed using Skindex. Two analyses were performed. The first analysis included all patients with PFH, the second analysis only patients with PFH who were treated with botulinum toxin A. In the latter group the questionnaires were repeated 2-4 weeks after treatment. RESULTS: For the total group at baseline the values for STAI, SCL-90-R, HADS-D and SPS were well within the normal range. However, in the group of patients treated with botulinum toxin A, the mean +/- SD SPS score was 17.6 +/- 15.5, i.e. above the normal range. Quality of life was impaired, with a mean +/- SD Skindex score of 24.3 +/- 5.7 at baseline. Treatment with botulinum toxin A led to a significant reduction in all investigated symptoms. CONCLUSIONS: Despite an impaired quality of life, patients with PFH in general do not show increased symptoms of anxiety, depression or social phobia. Only in the subgroup of patients treated with botulinum toxin A was the SPS increased at baseline. Treatment with botulinum toxin A led to a marked improvement in all factors investigated.

Adult↗
PubMed2005

Misleading diagnosis of partial N-acetylglutamate synthase deficiency based on enzyme measurement corrected by mutation analysis.

UNLABELLED: N-acetylglutamate synthase (NAGS) deficiency is a rare urea cycle disorder. Most of the patients present in the early neonatal period with severe hyperammonaemia and marked neurological impairment. We report on a Turkish family with an index patient, who died due to hyperammonemia, and another three siblings, who received a prophylactic treatment consisting of arginine hydrochloride, sodium benzoate and phenylbutyrate directly after birth. Enzyme measurement in a liver biopsy suggested a diagnosis of partial NAGS deficiency in all three siblings. Thereafter, N-carbamylglutamate was added to the treatment. None of the patients developed hyperammonaemia. After the human NAGS gene was identified, mutation analysis revealed that the consanguineous parents and two siblings were heterozygous for a private mutation (W484R), whereas the wild-type gene was found in the eldest sibling. Therapy was stopped without any deterioration of urea cycle function. CONCLUSION: Diagnosis of partial NAGS deficiency based on enzyme measurement may be misleading and should be completed by mutation analysis.

Acetyltransferases↗
PubMed2003

Plasma arginine and urinary nitrate and nitrite excretion in bronchopulmonary dysplasia.

The aim of this prospective study was to determine whether preterm infants with bronchopulmonary dysplasia (BPD) and signs of increased pulmonary artery pressure have a deficiency of plasma arginine (ARG) and systemic nitric oxide (NO) synthesis. Plasma amino acid concentrations, Doppler pulmonary systolic time intervals (ratio of acceleration time and ejection time corrected for heart rate: AT/ET(C)) and urinary nitrate and nitrite concentrations were determined at the 28th day postnatal age and at 36 weeks postmenstrual age in 73 preterm infants less than 30 weeks gestational age. The AT/ET(C) ratios were significantly lower in infants with BPD (n = 32) compared to controls. However, total amino acid concentrations, ARG intake as well as plasma ARG concentrations were not different between groups (median (interquartile-range) micromol/l): control: 58 (42.5-75.5) and 54.5 (42-71) at day 28 and 36 weeks; BPD: 54.5 (31.5-70.5) and 43 (35-62), respectively. Urinary nitrate and nitrite concentrations, were not different between groups at day 28, but significantly higher in infants with BPD at 36 weeks (p = 0.014). In conclusion, plasma ARG concentrations and systemic NO synthesis were not deficient in preterm infants with BPD and signs of elevated pulmonary artery pressure.

Arginine↗
PubMed2003

Lung volume reduction surgery in bronchopulmonary dysplasia.

UNLABELLED: We report on a female preterm infant of 29 wk gestational age, who developed acquired lobar emphysema after prolonged artificial ventilation secondary to respiratory disease syndrome and bronchopulmonary dysplasia. The infant underwent atypical segmentectomy at the age of 12 mo because of life-threatening hypoxaemia with pulmonary hypertension and failure of conservative treatment. CONCLUSION: Lung volume reduction surgery (LVRS) dramatically improved the respiratory function and resulted in adequate weight gain and psychomotor development. In selected cases LVRS can be an option for lobar emphysema in premature infants with severe bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗
PubMed2002

Epinephrine treatment of hypotension in very low birthweight infants.

UNLABELLED: The aim of this study was to examine the influence of a continuous infusion of epinephrine (adrenaline) on mean arterial blood pressure (MABP), heart rate, urine output and base deficit in very low birthweight infants (VLBWI) with systemic hypotension. In VLBWI who received an infusion of epinephrine for at least 12 h the mean urine output, administered fluid volume, base deficit and administered buffer 12 h before and 12 h during the infusion were recorded. If the infusion was shorter, but given for at least 2 h, the mean heart rate and MABP 2 h before and 2 h during the infusion were recorded. Thirty-one infants with a gestational age of 26 (23-30) wk [median (minimum-maximum)] and birthweight 690 (390-1310) g were included in this retrospective chart review. The patients received an infusion of epinephrine at a postnatal age of 3 (1-21) d. The doses ranged between 0.05 and 2.6 microg kg(-1) per minute within the first 24 h of administration. Three of 31 infants received epinephrine on 2 different occasions. The MABP [+7 (-1 to 13) mmHg, p=0.000001] and the heart rate [+10 (-10 to 42) bpm, p=0.000036] increased significantly (n = 34), whereas total volume administration and urine output remained the same between the 2 periods (Wilcoxon matched pairs test). The base deficit increased significantly [-3 (-10.2 to 2.6), p = 0.0014, n = 19] without a change in the administration of buffer. CONCLUSION: The infusion of epinephrine increased the MABP and the heart rate without decreasing urine output in VLBWI with hypotension not responding to a dopamine infusion up to 15 microg kg(-1) per minute. A potential adverse effect was an increase in metabolic acidosis.

Blood Pressure↗
PubMed2001

Botulinum toxin A for axillary hyperhidrosis (excessive sweating).

BACKGROUND: Treatment of primary focal hyperhidrosis is often unsatisfactory. Botulinum toxin A can stop excessive sweating by blocking the release of acetylcholine, which mediates sympathetic neurotransmission in the sweat glands. METHODS: We conducted a multicenter trial of botulinum toxin A in 145 patients with axillary hyperhidrosis. The patients had rates of sweat production greater than 50 mg per minute and had had primary axillary hyperhidrosis that was unresponsive to topical therapy with aluminum chloride for more than one year. In each patient, botulinum toxin A (200 U) was injected into one axilla, and placebo was injected into the other in a randomized, double-blind manner. (The units of the botulinum toxin A preparation used in this study are not identical to those of other preparations.) Two weeks later, after the treatments were revealed, the axilla that had received placebo was injected with 100 U of botulinum toxin A. Changes in the rates of sweat production were measured by gravimetry. RESULTS: At base line, the mean (+/-SD) rate of sweat production was 192+/-136 mg per minute. Two weeks after the first injections the mean rate of sweat production in the axilla that received botulinum toxin A was 24+/-27 mg per minute, as compared with 144+/-113 mg per minute in the axilla that received placebo (P< 0.001). Injection of 100 U into the axilla that had been treated with placebo reduced the mean rate of sweat production in that axilla to 32+/-39 mg per minute (P<0.001). Twenty-four weeks after the injection of 100 U, the rates of sweat production (in the 136 patients in whom the rates were measured at that time) were still lower than base-line values, at 67+/-66 mg per minute in the axilla that received 200 U and 65+/-64 mg per minute in the axilla that received placebo and 100 U of the toxin. Treatment was well tolerated; 98 percent of the patients said they would recommend this therapy to others. CONCLUSIONS: Intradermal injection of botulinum toxin A is an effective and safe therapy for severe axillary hyperhidrosis.

Adult↗
PubMed2001

Normalisation of blood pressure in hypertensive TGR(mREN2)27 rats by amlodipine vs. enalapril: effects on cardiac hypertrophy and signal transduction pathways.

It is still a controversial issue whether different classes of antihypertensive drugs are equally effective in the regression of cardiac hypertrophy and associated complications. The present study compared the effects of prolonged treatment with the Ca2+-channel blocker amlodipine and the ACE inhibitor enalapril, respectively, in TGR(mREN2)27 rats (TGR), an animal model of renin-dependent hypertension. TGR were divided into three groups and received either amlodipine, enalapril or drinking water without addition, Sprague-Dawley rats (SPRD) served as normotensive control group. Cardiovascular parameters were monitored by radiotelemetry, and drug doses were titrated until 24-h blood pressure was reduced to approximately 140/90 mmHg in both active treatment groups. After 8 weeks of treatment left ventricular (LV) hypertrophy was completely reversed in both treatment groups despite a tenfold increase in plasma angiotensin II in amlodipine-treated TGR. In untreated TGR LV catecholamines were depleted, and beta1-adrenergic stimulation of adenylyl cyclase was blunted. Treatment of TGR with enalapril prevented both the depletion of tissue catecholamines and the desensitisation of LV beta1-adrenoceptors. Amlodipine had no effect on cardiac adrenergic signal transduction. Basal activity of LV soluble guanylyl cyclase was not different between TGR and SPRD, but its sensitivity to stimulation by nitric oxide was slightly reduced in TGR. Treatment had no effect on basal and stimulated guanylyl cyclase activity. The present study in an animal model of renin-dependent hypertension suggests that blood pressure reduction per se is sufficient for a regression of cardiac hypertrophy. However, beta-adrenergic desensitisation was prevented only in the enalapril-treated group, supporting a blood pressure-independent contribution of the renin-angiotensin system to the regulation of beta-adrenergic signal transduction.

Adenylyl Cyclases↗
PubMed2001

Evaluation of renal Kt/V as a marker of renal function in predialysis patients.

BACKGROUND: The use of renal Kt/V (r-Kt/V) as an indicator for the need of dialysis initiation has been recommended in the NKF-DOQI guidelines. In analogy to clinical practice in peritoneal dialysis, a fall of r-Kt/V below a threshold of 2.0 per week may indicate inadequate renal toxin elimination. However, there are no studies linking r-Kt/V with other parameters of glomerular filtration rate (GFR) in predialysis patients, and the validity of r-Kt/V as parameter for timing of dialysis initiation is unknown. METHODS: Renal function was assessed repeatedly in 125 patients (N = 465 measurements). In predialysis patients (r-Kt/V <2.5 per week) r-Kt/V was compared with creatinine [CCr], urea [CUr], averaged creatinine/urea clearance [CCr/Ur], Cockcroft-Gault formula [CCG], and MDRD prediction equation 6 (MDRD6-GFR). The diagnostic performance of r-Kt/V as a parameter for timing the initiation of dialysis was evaluated. RESULTS: Renal Kt/V <2.5 was prevalent in 24.9% of cases (N = 116, mean 1.92 +/- 0.34). In this group mean CCr was 13.8 +/- 4.9, mean CUr 6.7 +/- 1.3, and CCr/Ur 10.2 +/- 2.9 mL/min/1.73 m2. There was no correlation of r-Kt/V with serum creatinine and MDRD6-GFR, but a significantly positive correlation with CCr/Ur (r2 = 0.3382, P < 0.001). Sensitivity of r-Kt/V to detect CCr/Ur < 10.5 mL/min/1.73 m2, defined as the threshold for dialysis initiation, was 73.6% with a specificity of 91.9%. CONCLUSIONS: These results suggest that r-Kt/V is a parameter of acceptable specificity but poor sensitivity for the timing of dialysis initiation. Additional measures of renal function, such as the average of measured creatinine and urea clearance, also should be taken into consideration when deciding on the timing of dialysis initiation prior to the development of clinical signs of uremia and malnutrition.

Adult↗
PubMed2001

Quantification of the efficacy of botulinum toxin type A by digital image analysis.

BACKGROUND: Botulinum toxin type A (BT-A) is increasingly being used by dermatologists for correction of frown lines. Because objective measurements of clinical results appear to be difficult, several different treatment protocols have been issued purely empirically or on the basis of subjective ratings. OBJECTIVE: Our purpose was to establish objective parameters to measure the efficacy of BT-A for correction of hyperkinetic facial lines. METHODS: Thirty consecutive patients received BT-A injections for correction of facial expression lines. For each patient a full range of facial expressions was recorded by means of a digital imaging system that allowed identical positioning and illumination before and after treatment. Computer-assisted measurements of brow mobility were used to measure muscular paralysis. RESULTS: Reproducibility of serial photographs by means of a digital overlay technique was confirmed by 4 independent observers. Upward mobility of brows was decreased to 35% at 2 weeks and 71% at 12 weeks after treatment. In contrast, inward mobility (frowning) was decreased to 7% at 2 weeks and 57% at 12 weeks. Brow-to-brow distance in repose increased with treatment by 13% and displayed a negative correlation with age. CONCLUSION: The effects of BT-A on upper face muscular activity can reproducibly be measured by digital image analysis; this is a valuable tool for clinical documentation and evaluation of treatment efficacy. Onset and offset of the effects of BT-A display a longer time course than previously assumed. Tissue qualities such as elasticity contribute measurably to smoothing facial expression lines after BT-A treatment and correlate inversely with age.

Adult↗
PubMed2000

Quartz glass pipette puller operating with a regulated oxy-hydrogen burner.

Quartz glass electrodes are superior to conventional glass electrodes for low-noise recording. They have better electrical characteristics and hydrophobic surfaces which resist creeping of salt solutions. We used oxy-hydrogen heating with program-controlled gas pressure to melt quartz glass capillaries. Usually, the relative wall thickness (the quotient of the outer and inner diameters do/di) of capillaries is, at best, maintained up to the electrode tip. If tips with thicker walls can be produced, coating and other surface treatments can be avoided. We found that programmed heating periods without pull allowed an fivefold increase of do/di in the tip region. Since do/di is inversely proportional to input capacity, the recording noise was minimized and became insignificant relative to amplifier and holder noise. A sample patch-clamp recording is shown.

Animals↗
PubMed2000

Serum cortisol concentrations in ill preterm infants less than 30 weeks gestational age.

Adrenal insufficiency is suspected in some ill preterm infants. The aim of this prospective study was to compare serum cortisol concentrations during the first 2 wk of life of well preterm infants (group A) less than 30 wk of gestational age with the cortisol concentrations of ill preterm infants whose arterial hypotension-a potential sign of adrenal insufficiency-had been treated with catecholamine (group B), and the cortisol concentrations of ill preterm infants who had not been so treated (group C). Cortisol concentrations did not differ significantly between group A (240 nmol/l, 58-659; n = 46) (median, minimum-maximum) and group C (268 nmol/l, 58-1007; n = 25). Group B had a double-peaked distribution of cortisol. Two subgroups were formed by taking the highest cortisol level of group A as a threshold: group B1 (110 nmol/l, 41-378; n = 20) and group B2 (1200nmol/l, 764-1482; n = 8). The cortisol concentrations of group B1 were significantly lower (p = 0.00097) compared to the cortisol concentrations of the well preterm infants (group A). The severity of illness, which was quantified by two scoring systems, differed significantly among the groups (p < 0.003 for all comparisons) with the following sequence: A < C < B, but not between B1 and B2, as clinical variables were not different between the subgroups.

Female↗
PubMed1999

Glutamate receptor expression regulates quantal size and quantal content at the Drosophila neuromuscular junction.

At the Drosophila glutamatergic neuromuscular junction, the postsynaptic cell can regulate synaptic strength by both changing its sensitivity to neurotransmitter and generating a retrograde signal that regulates presynaptic transmitter release. To investigate the molecular mechanisms underlying these forms of plasticity, we have undertaken a genetic analysis of two postsynaptic glutamate receptors that are expressed at this synapse. Deletion of both genes results in embryonic lethality that can be rescued by transgenic expression of either receptor. Although these receptors are redundant for viability, they have important differences. By transgenically rescuing the double mutant, we have investigated the relationship of receptor gene dosage and composition to synaptic function. We find that the receptor subunit composition regulates quantal size, Argiotoxin sensitivity, and receptor desensitization kinetics. Finally, we show that the activity of the receptor can regulate the retrograde signal functioning at this synapse. Thus, the diversity of receptors expressed at this synapse provides the cell with mechanisms for generating synaptic plasticity.

Animals↗