An erythematous nodule on the vulva.
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Female↗
Biomedical subjects
M Heckmann
Publications and source records attributed to M Heckmann.
Desensitization reduces amplitudes of quantal end-plate currents after a single preceding end-plate current in mouse muscle.
While in membrane patches nicotinic channels from end-plates desensitize with time constants of 10-100 ms and recover with time constants of 100-200 ms, doubts remain as to whether such rapid reactions are also found in intact neuromuscular junctions. Therefore, the desensitization effected by a single end-plate current (EPC) on monoquantal EPCs (qEPCs) was studied. Using a published reaction scheme for the adult end-plate receptor, the desensitizing effects of an EPC on a following one were simulated. Twenty milliseconds after an EPC, a subsequent qEPC was reduced to 90% of control, and to 70-80% if acetylcholine esterase (AChE) was blocked. EPCs were elicited and recorded through a macropatch electrode. Series of four EPCs (control qEPC, conditioning EPC, test qEPC 1 and 2) were repeated several thousand times and the amplitudes and decay time constants of the qEPCs were evaluated. A highly significant average depression of the qEPC to 96.4% of control was found 20 ms after the conditioning EPC; if the AChE was blocked the depression after 40 ms was to 76% of control. Under both conditions, the time constant of recovery from desensitization was below 100 ms. The time constant of decay of the qEPC, taudecay, tended to be slightly shortened during depression in the presence of AChE. If AChE was blocked, taudecay was lengthened to 130-140% of control after a preceding EPC, and this lengthening outlasted the depression of the EPC amplitude by a second. These changes in taudecay are not predicted by the channel reaction scheme, and possible additional modulatory effects are discussed.
Acetylcholine↗
Side-controlled intradermal injection of botulinum toxin A in recalcitrant axillary hyperhidrosis.
BACKGROUND: Although topical application of aluminium chloride is the most common measure against axillary sweating, severely affected patients often undergo surgical procedures that are expensive and may have considerable side effects. Recently botulinum toxin A (BT-A) has been reported as a potentially effective antihyperhidrotic agent. OBJECTIVE: Our purpose was to determine the therapeutic strength, safety, and mode of application of BT-A in severe axillary hyperhidrosis. METHODS: Intradermal injection of BT-A (Dysport) was given in an open left-versus-right side trial with each patient being his own control for initial efficacy, followed by treatment of the contralateral side. RESULTS: Seven days after initial treatment sweat production fell to below 10% of the untreated contralateral axilla as determined by gravimetry. Satisfaction was rated unanimously as "very good," the highest of 5 rankings. No side effects such as skin irritation or muscle weakness were noted in any patient. CONCLUSION: Intradermal injection of BT-A is a potent and well-accepted therapeutic option in patients with recalcitrant axillary hyperhidrosis.
Adult↗
Maintenance treatment with medroxyprogesterone acetate in patients with advanced breast cancer responding to chemotherapy: results of a randomized trial. Essen Breast Cancer Study Group.
The purpose of this randomized phase III trial was to study whether medroxyprogesterone acetate (MPA) maintenance treatment prolongs the time to progression in advanced breast cancer patients responding to an induction chemotherapy. Patients with progressive advanced breast cancer previously untreated with anthracylines and progestins were given epirubicin (30 mg/m2) and ifosfamide (2 g/m2) on days 1 and 8 at 3-weekly intervals. Patients without disease progression after 6 cycles of chemotherapy were randomly assigned to receive, until progression, either no treatment or MPA at a daily total dose of 500 mg. Ninety patients were randomized: 46 to the MPA arm and 44 to the observation arm. Median time to progression was longer in the MPA arm: 4.9 months versus 3.7 months in the intent-to-treat analysis (p = 0.02), and 4.9 months versus 3.0 months in the secondary efficacy analysis (p = 0.012). Seven patients were removed from MPA due to side effects. The changes in patient-rated quality of life scores were similar in both groups. The median length of survival from randomization was 17.4 months for patients receiving MPA and 18.3 months for patients randomized to observation (p = 0.39). In conclusion, in patients with advanced breast cancer achieving remission or non-progression with 6 cycles of epirubicin and ifosfamide chemotherapy, MPA maintenance treatment led to a significant, though modest, prolongation of the time to progression without affecting overall survival of the study patients.
Aged↗
Reference range for serum cortisol in well preterm infants.
AIM: To establish a reference range for serum cortisol concentrations in preterm infants with a gestational age of less than 30 weeks during the first two weeks of life. METHODS: Infants were prospectively classified by the following exclusion criteria: surfactant administration, arterial hypotension, acute or uncontrolled infection, ventricular haemorrhage II degrees or above, serum glucose < 2.2 mmol/l, exchange transfusion, stress as a result of any kind of examination or nursing for at least 4 hours before blood sampling. The cortisol value was measured once using radioimmunoassay in each infant. RESULTS: In appropriate for gestational age (AGA) infants (n = 37, median gestational age 27.7 weeks, median birthweight 1030 g) the distribution of the cortisol concentrations was non-Gaussian. These had a nearly normal distribution, when log(10) values of the data were used. The points determined by mean (2 SD) on the logarithmic scale were transformed back to the original units to provide a reference range: 73-562 nmol/l. Gestational age was significantly (p = 0.033) associated with cortisol values (log(10)) with a regression coefficient (standard error) of -0.045 (0.020). Small for gestational age (SGA) infants (n = 8) had significantly higher cortisol values (median 357 nmol/l) than AGA infants (median 199 nmol/l) (p=0.028). CONCLUSIONS: There is a strictly defined reference range of serum cortisol concentrations in AGA preterm infants.
Gestational Age↗
Effects of postnatal estradiol and progesterone replacement in extremely preterm infants.
The fetus is supplied from the placenta with estradiol (E2) and progesterone (P) in increasing amounts during gestation. After delivery of a premature infant, placental supply is disrupted, resulting in a rapid decrease in E2 and P. Replacement of these placental hormones may restore intrauterine conditions and may be beneficial for bone mineral accretion, clinical course, and outcome. Thirty female infants with a median gestational age of 26.6 weeks (between 24.1-28.7) and a birth weight of 675 g (370-990) were randomized to receive E2 and P replacement, aiming to maintain plasma levels equaling the intrauterine levels, or no replacement. The E2 and P replacement was started iv and was followed by transepidermal administration for a total duration of 6 weeks. Repeated measurements included plasma levels of E2, P, FSH, and LH; uterine volume; calcium and phosphorus in spot urine specimens; and bone mineral accretion by single photon absorption densitometry. Further, the incidence of chronic lung disease and various clinical outcome data were recorded. The plasma levels of E2 and P were within the intrauterine range with median replacements of 2.30 mg/kg x day E2 (1.13-6.23) and 21.20 mg/kg x day P (11.23-27.36), iv. Three- and 6-fold higher doses of E2 and P were needed via the transepidermal route. The uterine volumes increased, and FSH and LH as indicators for biological effectiveness were significantly lowered with replacement. The bone mineral accretion rates tended to be higher, and the incidence of chronic lung disease tended to be lower (0% vs. 29%; P = 0.097). E2 and P replacement via iv and transepidermal routes is capable of maintaining plasma levels as high as those in utero with biological effectiveness. Trends toward improved postnatal bone mineral accretion and less chronic lung disease were found with the hormone replacement. Further and more extensive studies are warranted to address the role of this new approach in the care of extremely premature infants.
Birth Weight↗
Evoked quantal currents at neuromuscular junctions of wild type Drosophila larvae.
Evoked excitatory postsynaptic currents (EPSC) were recorded with an extracellular macropatch electrode from glutamatergic neuromuscular junctions of Drosophila larvae. At 20 degrees C quantal current amplitude was about -400 pA and the 10-90% rise time was slightly below 0.2 ms for the fastest rising events and on average 0.3+/-0.1 ms in our best recordings. The quantal currents often had 'shoulders' but decayed approximately monoexponentially from half amplitude. The time constant of the exponential fit varied with mean values ranging from 2.5 ms to 7.7 ms in 13 experiments and an average value of 4.4+/-1.6 ms. Comparison of these results with data obtained earlier with outside-out patches of larval muscle membrane (Heckmann, M. and Dudel, J., Biophys. J., 72 (1997) 2160-2169) leads us to conclude that glutamate has to reach a saturating peak concentration of at least 10 mM in the synaptic cleft to allow the observed short quantal current rise times. To account for the time course of the quantal current decay one has to assume that the glutamate concentration in the synaptic cleft remains in the millimolar range for more than a millisecond and that the time course of the decay of the quantal currents is in part due to desensitization of the postsynaptic receptor channels.
Animals↗
Single channel currents at six microsecond resolution elicited by acetylcholine in mouse myoballs.
1. A patch-clamp set-up was optimized for low noise and high time resolution. An Axoclamp 200B amplifier was modified to incorporate a Teflon connector to the electrode. An electrode puller was equipped with a hydrogen-oxygen burner to produce quartz-glass pipettes with optimally 0.2 micron openings and 20 MOmega resistance. 2. The r.m.s. (root mean square) noise of sealed pipettes in the bath ranged from 3.6 fA with 100 Hz filter cut-off to 1.5 pA with 61 kHz filter cut-off. At these extremes currents of 17 fA and more than 3 ms, or 9 pA and more than 6 micros could be resolved with a negligible error rate. 3. The system was tested on mouse myoballs, recording 9-10 pA single channel currents on-cell at -200 mV polarization which were elicited by 0.1-5000 microM acetylcholine (ACh). 4. Distributions of open and closed times and of correlations of open times to the preceding closed time defined several open states: single openings with mean durations of 1.2 and 25 micros, from single-liganded receptors, and bursts of 10 ms mean duration containing on average 800 micros openings and 16 micros closings, from double liganded receptors. Above 0.1 mM ACh these openings are interrupted increasingly by on average 18 micros and 72 micros channel blocks by ACh.
Acetylcholine↗
Vascular activation of adhesion molecule mRNA and cell surface expression by ionizing radiation.
During cutaneous inflammatory reactions the recruitment of circulating leukocytes into the tissue critically depends on the regulated expression of endothelial cell adhesion molecules (CAMs). Various proinflammatory stimuli upregulate endothelial CAMs, including cytokines and UV irradiation. We have investigated the effects of ionizing radiation (IR) on endothelial CAM expression. Organ cultures of normal human skin as well as cultured human dermal microvascular endothelial cells (HDMEC) were exposed to IR. Expression of three major endothelial CAMs was studied in skin organ cultures by immunohistochemistry and in cell culture by Northern blot analysis and flow cytometry. In skin organ cultures vascular immunoreactivity for ICAM-1, E-selectin, and VCAM-1 was strongly induced 24 h after exposure to 5 or 10 Gy of IR, while immunoreactivity for CD31/PECAM-1, a constitutively expressed endothelial cell adhesion molecule, remained unchanged. In cultured HDMEC IR upregulated ICAM-1, VCAM-1, and E-selectin mRNAs and cell surface expression in a time- and dose-dependent fashion. Cellular morphology and viability remained unaltered by IR up to 24 h postirradiation. This study characterizes microvascular activation of adhesion molecule expression in response to ionizing radiation in a clinically relevant IR dose range. The findings also underscore the ability of endothelial cells to integrate environmental electromagnetic stimuli.
Antigens, CD↗
Follow-up of patients with axillary hyperhidrosis after botulinum toxin injection.
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Botulinum Toxins, Type A↗
[Botulinum toxin A in dermatology].
Based on its unique botulinum toxin is referred to as the most poisonous poison. Its specific inhibition of the acetyl-cholin-dependent neuromuscular transmission is used by ophthalmologists and neurologists for the relaxation of spastic or dystonic muscles, preferably in muscle groups in the head and neck area. Analogously, it is being used by dermatologists to remove facial wrinkles by paralyzing mimic muscles which account for mechanically induced wrinkling. Apart from this purely cosmetic use, botulinum toxin has gained recent attention in dermatology as a potent treatment modality for circumscribed hyperhidrosis.
Botulinum Toxins, Type A↗
[Axillary hyperhidrosis: successful treatment with botulinum toxin A].
Severe hyperhidrosis may present as a vexing condition for the patient and a therapeutic challenge for the physician. As botulinum toxin-A (BT-A) can potently block cholinergic sympathic innervation of sweat glands it was used in an open trial for controlling severe axillary hyperhidrosis. After visualization of hyperhidrosis using the iodine-starch-test BT-A (Dysport, 400 Units) was injected intradermally in one axilla. One week later gravimetric quantification of sweat secretion revealed a reduction of sweating to 4-9% of initial values. In order to rule out daily variations as well as other factors interfering with sweat production BT-A treatment was restricted to only one axilla in each individual clearly demonstrating extensive anhidrotic efficacy on the treated side only. The treatment was well tolerated without side-effects and was assessed as 'completely satisfying' by all patients. BT-A may offer a fast, safe and highly effective therapeutic option for severe hyperhidrosis.
Adolescent↗
[Basalioma terebrans of trunk skin. A neglected tumor].
Small basal cell carcinomas of the trunk are usually regarded as relatively harmless. In contrast, large and ulcerating basal cell carcinomas may become a therapeutic challenge with a less favourable prognosis and high risk of recurrence. The development of mutilating giant basal cell carcinomas appears less due to the biological aggressive character of the tumors, but rather to the patients' attitude of neglect. The case of a 62-year-old patient, featuring such attitude, demonstrates how a common basal cell carcinoma of the trunk can grow over a period of years to a troublesome ulcerating tumor.
Basal Cell Carcinoma↗
IL-10 inhibits ICAM-1 expression on human Langerhans cells but not on keratinocytes, dermal endothelial cells or fibroblasts.
Intercellular adhesion molecule-1 (ICAM-1) is regularly expressed or inducible on all major cutaneous cell populations including Langerhans cells, keratinocytes, endothelial cells and dermal fibroblasts. ICAM-1 is induced in the skin under inflammatory conditions and plays an important role in the activation of T cells. Interleukin-10 (IL-10) is a pluripotent immunosuppressive cytokine that inhibits proliferation of T cells via inhibition of antigen-presenting cells including Langerhans cells. We demonstrates that IL-10 inhibits baseline and also cytokine-stimulated ICAM-1 expression on human Langerhans cells, which has previously been shown in the murine system. No effect of IL-10 was seen on human dermal vascular endothelial cells, which like Langerhans cells are also able to present antigen. Additionally, no inhibitory effect of IL-10 was observed on the ICAM-1 expression of keratinocytes and dermal fibroblasts. As IL-10 only weakly suppresses MCH II on human Langerhans cells, inhibition of ICAM-1 and other accessory molecules by IL-10 seems to be an important mechanism inhibiting the antigen-presenting function of human Langerhans cells.
Dermis↗
Granulocytes enhance adhesion of peripheral blood mononuclear cells to dermal endothelial cells.
Interactions of all major peripheral blood leukocytes were studied during adhesion to human dermal microvascular endothelial cells (HDMEC). Simultaneous quantification of distinct leukocytic cell populations was carried in a recently established adhesion assay followed by FACS analysis. Adhesion of stimulated peripheral blood mononuclear cells (PBMC) was enhanced in the presence of granulocytes compared to adhesion of PBMC alone. This effect required direct cell-cell contact as granulocyte supernatant in the absence of granulocytes failed to yield the same extent of PBMC adhesion. Quantification of the common leukocyte beta2-integrin subunit (CD18) and the common leukocyte beta1-integrin subunit (CD29) as well as blocking with anti-CD18 antibodies revealed no differences between PBMC adhering alone or in company of granulocytes to HDMEC. Blocking E-selectin, however affected 'mixed' (i.e., PBMC in the presence of granulocytes) adhesion more profoundly than 'single' adhesion of PBMC. HDMEC subjected to 'mixed' leukocyte cell adhesion expressed E-selectin at 24 h after cytokine stimulation, while HDMEC without contact to leukocytes did no longer express E-selectin at this time. In conclusion, functionally diverse peripheral blood leukocytes can interact in order to enhance cell adhesion without up-regulation of leukocytic integrin expression via an E-selectin dependent mechanism.
Cell Adhesion↗
Optimizing botulinum toxin therapy for hyperhidrosis.
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Botulinum Toxins↗
Tension pneumopericardium in a preterm infant without mechanical ventilation: a rare cause of cardiac arrest.
A preterm infant with a gestational age of 32 weeks developed a tension pneumopericardium during the second day of life. The infant was treated with nasal continuous positive airway pressure and was not mechanically ventilated before pneumopericardium occurred. After emergency pericardiocentesis, two recurrences of pneumopericardium without clinical deterioration were diagnosed by X-ray during a 2-d observation period. A continuous pericardial drainage was positioned and was successfully removed on the seventh day of life after weaning from the ventilator. Tension pneumopericardium may occur even in non-ventilated newborns and should be considered as a rare but important differential diagnosis of cardiac arrest.
Disease-Free Survival↗
Complications in patients with palmar hyperhidrosis treated with transthoracic endoscopic sympathectomy.
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Endoscopy↗