[On the Differential Diagnosis of Intractable Psychogenic Chronic Cough: Neuropathic Larynx Irritable - Gabapentin's Antitussive Action]. / Zur Differenzialdiagnose des quälenden psychogenen chronischen Hustens: neuropathischer Larynx irritable - Gabapentin als Antitussivum.

We present the case of a 76 year old female inpatient who suffered from a chronic intractable cough which arose simultaneously to a severe major depression and was secondary to an exorbitant psychological distress. Chronic cough had never been experienced before and was initially considered to have a mere psychogenic origin since a comprehensive and guideline-based diagnostic screening did not reveal any underlying somatic cause. However, several factors cast doubt on the solitary psychic genesis of the chronic cough: i) occurrence immediately after a penetrant cold, ii) embedding in other complaints of laryngeal hyperreagibility (larynx irritable), such as persistent globus pharyngeus sensation, throat clearing and episodic dysphonia, iii) first occurrence on old life, iv) erupting from sleep as well, v) persistence despite remission of the major depression, and v) no sustaining benefit from specific psychotherapy and speech therapy. Therefore, diagnostics were extended to apparative tools for objective evaluation of swallowing by using fiberoptic videoendoscopic (FEES) and videofluoroscopic (VFS) techniques, which revealed signs of laryngeal neuropathy but without evidence of penetration or aspiration. A co-existing small goiter and an impaired glucose tolerance along with a putative intracellular vitamin B12 or folate deficiency (as indirectly derived from an apparent hyperhomocysteinemia) were assumed to be responsible for the neuropathy and underwent specific treatments. The impaired glucose tolerance and putative vitamin deficit were compatible with a distal symmetric sensorimotoric, even subclinical polyneuropathy of the lower extremities. The larynx irritable improved under gabapentin being confirmed by drug removals several times, and finally calmed down almost completely under gabapentin, which was in line with the scant literature of this topic. Re-examination of the larynx per FEES nine months later showed no deficits any more under the well-tolerated treatment (gabapentin, levothyroxine, vitamin B12 and folic acid substitution, weight reduction and physical training). All in all, the larynx irritable as well as the chronic cough were most probably induced by a laryngeal neuropathy and were not solely of psychic origin. Due to good treatment options a larynx irritable should be regularly taken into consideration of the investigation of intractable chronic cough. Therefore, an apparative evaluation of deglutition is recommended in the diagnostic toolbox of chronic cough - even if embedded in a psychiatric disorder or distress - before diagnosing a sole psychic origin. An hypothetical scheme of the development of a larynx irritable caused by neuropathic and non-neuropathic ("nociceptive") conditions is proposed.

Alpha-N-acetylgalactosaminidase from marine bacterium Arenibacter latericius KMM 426T removing blood type specificity of A-erythrocytes.

An alpha-N-acetylgalactosaminidase IV able to remove blood type specificity of human A(II)-erythrocytes and not effecting B(III)-erythrocytes was isolated from the marine bacterium Arenibacter latericius KMM 426T. The alpha-N-acetylgalactosaminidase IV preparation exhibits high activity during inhibition of hemagglutination with blood group substance A containing determinants analogous to A-erythrocytes. The enzyme has a pH optimum from 7.0 to 8.0 and completely retains its activity during 30-min heating at 50 degrees C and for a week at 20 degrees C. The enzyme can be stored under the sterile conditions for any length of time at 4 degrees C, but it does not withstand freezing. The alpha-N-acetylgalactosaminidase is resistant to NaCl; for p-nitrophenyl-alpha-N-acetyl-D-galactosaminide, the Km is 0.38 mM. The molecular mass of the enzyme determined by gel filtration is 84 kD.

The European Service Mapping Schedule (ESMS): development of an instrument for the description and classification of mental health services.

OBJECTIVE: This paper describes the development of an instrument for description and classification of mental health services and for measurement of service use. Purposes to be served by the instrument include: (i) identification of gaps in the spectrum of services in a catchment area; (ii) obtaining background information which may be important to understanding why apparently similar interventions lead to different outcomes in different areas; (iii) investigating how introduction of a particular type of service influences use of other local services; and (iv) understanding the relationship between sociodemographic factors and service use. METHOD: The instrument was developed through meetings of an international expert panel and pilot stages in several European countries. RESULTS: Use of the European Mapping Service Mapping Schedule (ESMS) appears feasible in several countries and allowed description and classification of the full range of services identified within each of the study catchment areas. CONCLUSION: The ESMS promises to fill a gap in the technology available for mental health services research. Further practical experiences of its use for a variety of purposes in a variety of settings are now needed to indicate how far the ESMS does successfully generate data which are useful to researchers and planners.

Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.

Diamnionic monochorionic twin gestations: an overview.

Monochorionic (MC) twins account for about 20-30% of all twins, but contribute disproportionately to mortality, intrauterine growth restriction, and preterm delivery compared with dichorionic (DC) twins. This higher mortality in MC twins is likely due to the effects of placental morphologic characteristics, which include complex vascular communications between the twins associated with twin-twin transfusion syndrome (TTTS), and the tendency for the common placenta to be shared either symmetrically or asymmetrically. In assessment of clinical outcomes for TTTS, artery to vein anastomoses in the absence of artery to artery or vein to vein, especially if present with placental asymmetry, carry the worse prognosis. Chorion status in twins forms the basis for clinical risk assessment and can be determined by 7 menstrual weeks using transvaginal sonography. The variable results reported in the literature for intertwin umbilical artery Doppler findings in MC twins may be explained by differences between sonographic and clinical criteria (including differential hemoglobin concentrations) reported by various investigators. Antenatal fetal Doppler assessment of the umbilical artery and cerebral arteries can help distinguish between TTTS and placental insufficiency in MC twins. Significant restriction of fetal growth occurs in about 25% of multiple gestations, accounting for about 17% of all growth-retarded infants. Redistribution of fetal blood (brain-sparing effect), as determined by Doppler interrogation of fetal cerebral and umbilical arteries, occurs more commonly in MC twins compared to DC twins and in growth-restricted MC twins compared to nongrowth-restricted MC twins. Overall, the prognosis is poorer for the donor twins in TTTS and there is a greater prenatal death rate for the donor (18-35%), and a higher overall survival rate for recipients following fetoscopic laser treatment. Finally, the clinical and sonographic findings suggest that the polyhydramnios/oligohydramnios sequence seen in MC twins likely represents a spectrum strongly linked to placental variables.

Treating previable twin-twin transfusion syndrome with fetoscopic laser surgery: outcomes following the learning curve.

AIMS: We have performed fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) in previable pregnancies affected by twin-twin transfusion syndrome (TTTS) since 1988. Treatment outcomes obtained after the procedure's learning curve are presented and compared to those from other centers performing FLOC or other treatment methods. METHODS: A total of 100 cases of FLOC have been performed at our centers. The later 67 TTTS patients had a mean gestational age of 21.1 +/- 1.7 weeks (range 18-24.5) with a mean fundal height of 33.1 +/- 4.9 cm (range 27-44) when treated. Eighteen (27%) had failed another treatment method before FLOC. RESULTS: All 67 cases have delivered with 82% (55/67) having at least one surviving twin and 93/134 (69%) of the twins surviving overall. Thirty-eight have surviving twins, 17 have one survivor (5 neonatal and 12 fetal deaths), and 12 have none. The mean duration of pregnancy following FLOC was 9.9 +/- 5.5 weeks (range 1.0-19). Only 4 of 93 (4.3%) survivors have significant handicaps at a mean follow-up of 14.3 +/- 10.1 months (range 1.0-34). CONCLUSION: Fetoscopic laser occlusion of chorioangiopagous vessels within the vascular equator limits the duration of fetal pathophysiology in TTTS and results in neonatal outcomes superior to the modified procedure and other treatment methods.

Alpha-galactosidase of the marine bacterium Pseudoalteromonas sp. KMM 701.

An alpha-galactosidase that inactivates the group specificity of B erythrocytes (group III) of human blood and does not affect A erythrocytes (group II) was isolated from the marine bacterium Pseudoalteromonas sp. KMM 701. The enzyme preparation did not contain lectin, hemolytic, sialidase, endoglycanase, or glycosidase activities. The enzyme is stable at 20 degreesC for 24 h, has pH optimum for catalysis within the range of 6.7-7.7, and is stable to high concentrations of NaCl. It is 4-fold more efficient than the alpha-galactosidase from green coffee beans. At pH 7.0 the Km for p-nitrophenyl-alpha-D-galactopyranoside is 0.29 mM. The molecular weight of the enzyme determined by gel-filtration is 195 +/- 5 kD. The alpha-galactosidase is denatured by urea and guanidine hydrochloride. Its activity does not depend on the presence of metal ions. It contains a sulfhydryl group essential for its catalytic activity.

Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome.

OBJECTIVE: We undertook a pilot study to determine the feasibility and efficacy of fetoscopic laser occlusion of chorioangiopagous vessels in severe previable twin-twin transfusion syndrome. STUDY DESIGN: A total of 35 patients were referred to the investigators with ultrasonographic findings consistent with twin-twin transfusion syndrome, posterior placental implantation, gestational age < 25 weeks, and clinical hydramnios. Placental vessel occlusion was performed with a rigid 2.9 x 3.85 mm dual-channel fetoscope and neodymium:yttrium-aluminum-garnet laser light. RESULTS: Of the original 35 patients, 5 were eliminated preoperatively and 4 intraoperatively for various factors. The 26 treated patients had a mean gestational age of 20.8 weeks (range 18 to 24) and a mean fundal height of 36.1 cm (range 29 to 44). One patient has surviving triplets, 8 have surviving twins, 9 have a single survivor (2 neonatal and 7 fetal deaths occurred in this group), and 8 have no survivors (all had pregnancy loss within 3 weeks of treatment). The cases with survivors were delivered for obstetric indications at a mean of 32.2 weeks (range 26 to 37), having gained a mean of 11.7 weeks (range 6 to 17) in utero. Fifty-three percent (28/53) of the fetuses survived with 96% (27/28) developing normally at a mean age of 35.8 months (range 1 to 68). Thirty-three of 35 placentas were monochorionic with chorioangiopagous vessels on gross and microscopic evaluation. CONCLUSIONS: Fetoscopic laser occlusion of chorioangiopagous vessels is technically feasible and improves the course and outcome of severe twin-twin transfusion syndrome in previable fetuses.

Validation of an in vivo wound healing model for the quantification of pharmacological effects on epidermal regeneration.

BACKGROUND: Non-invasive assessment methods such as measurement of the transepidermal water loss (TEWL) allow a continuous follow-up of cutaneous processes with impairment of the epidermal barrier function. OBJECTIVE: The aim of the trial was to establish an in vivo model for the assessment of drug effects on epidermal regeneration. METHODS: Twenty healthy volunteers were included in this double-blind randomized trial. After setting four suction blisters on the volar aspect of the forearm, the epidermis was removed to create a standardized subepidermal wound. Thereafter the wounds were treated topically for 6 h daily during 14 days. The following treatments were to be compared: a clobetasol 17-propionate preparation under occlusion, a corticoid-free cream under occlusion, no treatment and occlusion (aluminium chamber), no treatment and no occlusion. Daily measurement of TEWL above the wounds was performed. RESULTS: The 0.05% clobetasol 17-propionate preparation caused a dramatic delay in TEWL decrease, whereby the untreated unoccluded field showed a continuous decrease over the observed period of 14 days. Occlusion and corticoid-free treatment led to a weak but significant delay of TEWL decrease when compared to the untreated unoccluded test field. CONCLUSION: This model seems to describe re-epithelialization in a reliable manner and can be used for in vivo assessment of drug effects on migrating and proliferating epithelial cells.

Cardiovascular teratogenicity of terbutaline and ritodrine in the chick embryo.

OBJECTIVE: We determined the teratogenic effects of terbutaline and ritodrine, both beta 2-sympathomimetic agonists, on the stage 24 (4-day) chick embryo. STUDY DESIGN: We used a topical method of application of terbutaline or ritodrine to the stage 24 chick embryo in ovo. Doses of terbutaline ranged from 5.5 x 10(-10) to 6.5 x 10(-9) mol per embryo, and ritodrine doses ranged from 4.6 x 10(-11) to 4.6 x 10(-8) mol per embryo. To further determine the pharmacologic nature of the teratogenic potential of terbutaline or ritodrine, the experiments were repeated after pretreatment with butoxamine hydrochloride, a preferential beta 2-antagonist, or metoprolol tartrate, a preferential beta 1-antagonist, 4 hours before application of terbutaline or ritodrine. RESULTS: Terbutaline treatment was associated with significantly higher rates of anomalies than in controls at all dosages used, whereas ritodrine induced significantly more anomalies at or above doses of 4.6 x 10(-9) mol per embryo. At an equimolar dose pretreatment with butoxamine hydrochloride significantly reduced the cardiovascular teratogenic effects of terbutaline and ritodrine. Pretreatment with metoprolol tartrate at any dose did not significantly reduce terbutaline's potential. Metoprolol, at doses tenfold or 100-fold higher than ritodrine, was able to significantly reduce the teratogenic effects of ritodrine. CONCLUSIONS: Our data suggest that terbutaline and ritodrine are teratogenic in the chick and that these agents exert their teratogenic effects primarily through stimulation of the beta 2-adrenergic receptor.

Treatment of venous leg ulcers with topical iloprost: a placebo controlled study.

The disturbed microcirculation is seen as a causative factor in provoking venous leg ulcers. The stable prostacyclin analogue iloprost has shown beneficial effects on the disturbed microcirculation after intravenous infusions. In this study the topical route was chosen in order to facilitate handling and to reduce the possibility of systemic adverse reactions. The aim of this study was to assess the efficacy and tolerability of two concentrations of iloprost solutions (0.0005% and 0.002%). The trial design was a randomized, double-blind, placebo controlled study in 11 centres in Germany with 49 patients allocated to treatment 1 (placebo solution); 49 patients to treatment 2 (0.0005% iloprost solution) and 50 patients to treatment 3 (0.002% iloprost solution). The study solutions were applied twice weekly for a period of eight weeks on the ulcer edge and ulcer surrounding. This study failed to show any statistically significant reduction in the ulcer size as a result of the iloprost treatment compared to the placebo treatment. Possible reasons for the findings are discussed.

Comparison of the local and systemic side effects of methylprednisolone aceponate and mometasone furoate applied as ointments with equal antiinflammatory activity.

BACKGROUND: The therapy for skin diseases with topical glucocorticoids is limited by their local and systemic side effects. A glucocorticoid with an improved benefit-to-risk ratio is desirable. OBJECTIVE: A new topical corticoid, methylprednisolone aceponate (MPA) 0.1% ointment, was compared with the same formulation of mometasone furoate. METHODS: The two ointments were compared with respect to suppression of UVB light-induced erythema (n = 20) and with respect to atrophogenicity and appearance of telangiectasia (n = 20) in two double-blind trials with intraindividual comparisons in healthy volunteers. In a third trial, serum cortisol levels were measured in volunteers receiving extensive (60% of body surface) cutaneous application of MPA (n = 10) or mometasone furoate (n = 11). RESULTS: MPA and mometasone furoate were equally effective in suppressing UVB light-induced erythema. Atrophogenicity, as well as the incidence and severity of telangiectasia, were significantly more pronounced with mometasone furoate than with MPA. Both ointments decreased serum cortisol levels and did not differ significantly in this respect. However, the incidence of serum cortisol level suppression was higher in the mometasone furoate group than in the MPA group. CONCLUSION: MPA ointment has equal antiinflammatory activity and similar cortisol suppression but significantly fewer local side effects than mometasone furoate.

Activity of topically applied methylprednisolone aceponate in relation to other topical glucocorticosteroids in healthy volunteers.

Topical glucocorticosteroids are useful in the treatment of various skin diseases. Although there are already many corticosteroids available, there is still need for highly potent and well tolerated ones. The anti-inflammatory activity of methylprednisolone aceponate (MPA, CAS 86401-95-8) has been investigated in 165 healthy volunteers of either sex. UV-B irradiation or cellophane tape stripping has served to produce erythema. First, the dose response relationship of MPA ointment (0.01%, 0.05%, 0.1% and 0.5%) has been evaluated. MPA effects have been related to those of the vehicle and difluocortolone 21-valerate 0.1% (DFV) ointment. Then the activity of 0.1% MPA (cream, ointment and fatty ointment) has been related to those of the respective vehicles as well as commercially available preparations of five corticosteroids: betamethasone 17,21-dipropionate 0.64% (BDP), betamethasone 17-valerate 0.1% (BV), clobetasol 17-propionate 0.05% (CP), hydrocortisone 17-butyrate 0.1% (HCB), prednicarbate 0.25% (P). In each experiment, MPA activity significantly exceeded that of the respective vehicle (p < or = 0.05). MPA 0.01-0.5% ointment exhibited strong anti-inflammatory activity, at least corresponding to that of 0.1% DFV ointment. A dose-dependent activity could only be observed in the UV-B-erythema test using 3 fold MED (minimal erythema doses) for irradiation, a test model differentiating strong corticosteroids. The comparison of 0.1% MPA formulations with respective reference preparations showed the following results: On stripped skin no significant differences could be detected which is demonstrated in the example of cream formulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of specific enzyme-linked immunosorbent antibody assay systems for the detection of chicken immunoglobulins G, M, and A using monoclonal antibodies.

The aim of the present study was the development of a sensitive and specific ELISA system for the quantitative and qualitative assay of chicken Ig Isotypes G, M, and A using monoclonal antibodies. Five hybridoma cell lines were developed that synthesized specific antibodies against chicken IgG and three lines each producing specific antibodies against IgM or IgA. Using an immunodiffusion test, the subclasses were determined. Isolation of monoclonal antibodies from ascites was carried out by way of affinity chromatography with protein G sepharose. The purity of the eluates were determined by both SDS-PAGE and HPLC. A Sandwich ELISA was found to be the most suitable technique for the assay. Specificity testing was carried out by Western blotting. An epitope analysis was also carried out. By variation of the single steps concerning incubation times, quantities, and concentrations of the substances to be applied, the whole procedure was optimized. Assay limits for individual Ig isotypes were determined. The limits were 20 ng/mL for IgG, 80 ng/mL for IgM, and 160 ng/mL for IgA.

Dose-response relationship of topically applied methylprednisolone aceponate (MPA) in healthy volunteers.

Topical glucocorticosteroids are useful in the treatment of various skin diseases. Although many corticosteroids are available today, there is still a need for highly potent compounds with minimal adverse effects. Methylprednisolone aceponate (MPA) has recently been synthesized. Its activity has been evaluated using the vasoconstrictor assay and the poison ivy test (rhus dermatitis) in 19/20 healthy volunteers of either sex. Comparable blanching was found with MPA in a cream vehicle, in an ointment and a fatty ointment. Vasoconstriction and suppression of experimentally-induced poison ivy contact dermatitis were dose-dependent in the concentration range 0.01% to 0.5% MPA. Concentrations of MPA of at least 0.05% were significantly active. Following the highest dose, blanching was close to the maximum which can be obtained. This finding, and the improvement of rhus dermatitis, suggest that MPA belongs to the highly potent local glucocorticosteroids.