[Nationwide implementation of a hospital resource register for daily trauma care, mass casualties and disasters : Position paper of the German Trauma Society and the Federation of German Medical Directors of Emergency Medical Services]. / Bundesweite Einführung eines Krankenhauskatasters in den Klinikalltag und bei Großschadens- und Bedrohungslagen : Positionspapier der DGU und des BV-ÄLRD e. V.

The introduction of requirements for a minimum intake capacity of trauma patients by the German Trauma Society (DGU) into the so-called white book of treatment of seriously injured patients, is helpful for a sufficient preparation for threats and for dealing with mass casualties for trauma centers as well as for the emergency medical services (EMS). In the hospital information database provided by the Federation of German Medical Directors of Emergency Medical Services, more than 1300 hospitals are currently listed. This information supports the allocation of trauma patients from the field to the appropriate trauma center. Currently, without any coordination requirements, the current 626 trauma centers in Germany are able to immediately handle 6260 patients. This number could be doubled by activating the local hospital action plan, where a priority plan is set up. Additionally, the implementation of a nationwide flexible standardized communication structure between the dispatch center of the ambulance service and the hospitals, would improve daily care as well as the management of threats and mass casualties. It is the obligation of the local medical director of the EMS, to maintain and update the hospital database. Providing the information in the database with the hospital resources and the flexible standard communication structure, is appropriate to improve the daily collaboration and the preparation for mass casualties.

[On-scene times for helicopter services. Influence of central dispatch center strategy]. / Präklinische Versorgungszeiten bei Einsätzen der Luftrettung. Einfluss der Dispositionsstrategie der Rettungsleitstelle.

BACKGROUND: Previous studies have suggested that when using several emergency systems and air rescue prehospital and on-scene times are extended, depending on the dispatch strategy. Emergency medical services (EMS) in Germany are delivered by ambulances (AMB) staffed by paramedics alone or with physicians (EMD) and by helicopter emergency medical services (HEMS) always staffed by both. The advantages of HEMS in countries with short transport distances and high hospital density are controversial. The best dispatching strategy for HEMS has not been determined OBJECTIVE: The BoLuS study in the German state of Hessen was designed to evaluate the influence of dispatch strategy on prehospital times for responses involving both HEMS and EMS. METHODS: Rescue responses involving HEMS were prospectively evaluated in 12 regions of Hessen from July 2010 to September 2011. Although all regions had access to HEMS, only one had its own service. Data from both central dispatch centers and helicopter services were collected and combined to calculate the on-scene time (OST) and correlate it with dispatch strategy. RESULTS: A total of 2111 emergency interventions were evaluated. Internal medicine emergencies accounted for 42.9 % of cases and trauma for 36.7 %. Just one patient was involved in 87.9 % of rescues. Two services were involved in 65.3 % of rescues and three or more in 31.5 %. The most common dispatch categories were initial dispatch of EMS and HEMS (50.6 %), initial dispatch of EMS with later request for HEMS (19.7 %) and initial dispatch of both EMS and EMD with later request for HEMS (17.4 %). The OST for these categories were 31.0 ± 13.7 min, 43.7 ± 16.2 min and 54.6 ± 21.3 min (p < 0.01), respectively. CONCLUSION: OST varies significantly depending on the number of EMS involved and the dispatch strategy. Sequential dispatching of ground and later HEMS wastes time. Getting an emergency physician to the scene as quickly as possible, reducing transport time to an appropriate hospital and caring for more complex emergencies are the main indications for HEMS. If HEMS appears likely to be needed, it should be dispatched immediately.

The triple neurokinin-receptor antagonist CS-003 inhibits neurokinin A-induced bronchoconstriction in patients with asthma.

Neurokinin A (NKA) causes bronchoconstriction in asthmatic patients. In vitro both NK1 and NK2 receptors can mediate airway contraction. Moreover in guinea pigs, NK3 receptors facilitate cholinergic neurotransmission. Dual tachykinin NK1/NK2 receptor antagonism results in prevention of NKA-induced bronchoconstriction. We have now examined the effect of a single dose of the triple tachykinin receptor antagonist CS-003 on NKA-induced bronchoconstriction in asthmatics. A double blind, crossover, placebo-controlled trial in 16 mild asthmatics was performed. One single dose of CS-003 (200 mg, solution in distilled water) or matched placebo was given orally on the assessment days. NKA-provocation tests were performed pre-dose and 1, 8 and 24 h after dosing. There was a significant shift to the right of the dose-response curve at 1 and 8 h after intake of CS-003. PC20 was not reached in 12/16 patients at 1h post-dose and in 5/16 patients at 8 h post-dose. This did not occur under placebo treatment. A single dose of 200 mg CS-003 protected significantly against NKA-induced bronchoconstriction at 1 and 8h post-dose in mild asthmatics.

Typing and antimicrobial susceptibilities of methicillin resistant Staphylococcus aureus (MRSA) strains isolated in a hospital in Korea.

Methicillin-resistant Staphylococcus aureus (MRSA) strains may cause serious nosocomial infections, including pneumonia and septicemia. The rate of methicillin-resistance among S. aureus isolates in Korea is over 50%. In this study, 90 MRSA isolates from Kyung Hee University Hospital were characterized employing bacteriophage typing, pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. Eighty percent of the strains could be phage-typed. The largest group or 40% of the strains belonged to lyso group III, followed by 32% of the isolates which produced a reaction with regional additional phages. Phage type 83A was most frequently encountered, followed by phage type D11. PFGE patterns confirmed the presence of two major clusters, which comprise the isolates belonging to lyso group III and the strains that were typable with regional additional phages. The latter group also contained a number of strains that were nontypable with bacteriophages. The resistance rates to ciprofloxacin, erythromycin, tetracycline, gentamicin and clindamycin were over 94%. Strains with intermediate resistance to vancomycin strains or resistance to mupirocin were not found. In conclusion, this study demonstrates that the results of phage typing are confirmed and supplemented by PFGE data.

Evaluation of a sensitive colorimetric FXIII incorporation assay. Effects of FXIII Val34Leu, plasma fibrinogen concentration and congenital FXIII deficiency.

There is an increasing interest in the role of coagulation factor XIII (FXIII) in cardio- and cerebrovascular diseases. It has recently been reported that a common G-->T point mutation in the A-subunit gene of FXIII, which codes for a valine (val) to leucine (leu) change (FXIIIVal34Leu), is protective against thrombotic diseases but seems to increase the risk of intracerebral bleeding. We developed a colorimetric incorporation assay for detection of FXIII activity based on incorporation of 5-(biotinamido) pentylamine (BAPA) into fibrin or fibrinogen. With this new assay, we studied the effects of FXIIIVal34Leu mutation, plasma fibrinogen concentration and congenital FXIII deficiency on FXIII activity. There are no data available about the ability of different FXIII assays to detect altered activity in FXIIIVal34Leu genotypes. We therefore compared our results determined by the incorporation method with a commonly used photometric method based on ammonia release after cross-linking of glycine-ethylester to a specific glutamine containing peptide substrate. We also determined FXIII A-subunit antigen (Ag) levels using enzyme-linked immunosorbent assay (ELISA) technique. The FXIIIVal34Leu genotype could not be detected either by the photometric method nor by the FXIII A-subunit ELISA. The incorporation assay showed an increased specific FXIII activity in subjects possessing the leu allele. The photometric assay and ELISA gave similar results independent from genotype. In patients with congenital FXIII deficiency before and after substitution, however, ELISA and the incorporation assay gave similar results, whereas the photometric assay showed consistently higher values. Our results show that the incorporation assay, not the photometric assay based on ammonia release, can be used for detection of elevated activity in subjects with FXIIIVal34Leu. Because of specificity and over a wide range sensitivity, the assay can also be used for determination of FXIII deficiency and monitoring of FXIII substitution therapy.

Differential expression of functional guanylyl cyclases in melanocytes: absence of nitric-oxide-sensitive isoform in metastatic cells.

Nitric oxide (NO) is a reactive endogenous molecule with multiple functions and its cellular signaling activity is mainly mediated by activation of the soluble isoform of guanylyl cyclase, a heterodimeric (alpha/beta) hemeprotein. The expression of the NO-sensitive soluble isoform of guanylyl cyclase was studied in various cultured melanocytic cells by measuring the accumulation of guanosine 3',5'-cyclic monophosphate in the presence and absence of NO donors. Here we report that 3-morpholino-sydnonimine, a donor of NO redox species, and (Z)-1-[2- (2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, a direct NO donor, induced a 20-fold increase in intracellular guanosine 3',5'-cyclic monophosphate in nonmetastatic melanoma cells and normal melanocytes in culture that could be related to cellular melanin content in a concentration-dependent manner. The increased intracellular guanosine 3',5'-cyclic monophosphate was due to stimulation of the activity of soluble guanylyl cyclase as such increase was completely abolished by using a specific inhibitor of soluble guanylyl cyclase. The involvement of functional soluble guanylyl cyclase was further confirmed by the presence of alpha1 and beta1 subunits in these cells at both mRNA and protein levels. In contrast, none of the NO donors induced guanosine 3',5'-cyclic monophosphate production in metastatic melanoma cells, which could be attributed to the absence of the beta1 subunit that is essential for catalytic activity of the soluble isoform of guanylyl cyclase. Metastatic melanoma cells produced higher levels of intracellular guanosine 3',5'-cyclic monophosphate in response to natriuretic peptides than other cell types, however, due to upregulation of membrane-bound guanylyl cyclase activities, but they are less pigmented or unpigmented. The present finding suggests that NO signaling in association with melanogenesis is dependent on the soluble isoform of guanylyl cyclase, whereas absence of soluble guanylyl cyclase but the presence of membrane-bound guanylyl cyclase correlates with the metastatic behavior of melanoma cells.

[Molecular and phenotypic characterization of methicillin-resistant Staphylococcus aureus isolates. Studies at a traumatic surgery clinic, 1994-1997]. / Molekulare und phänotypische Charakterisierung von Methicillin-resistenten Staphylococcus-aureus-Isolaten. Untersuchungen an einer Unfallchirurgischen Klinik von 1994-1997.

Methicillin resistant Staphylococcus aureus-strains, isolated from 1994 to 1997 from patients of the traumatic surgery hospital Tübingen, were compared using lysotyping and pulsed-field gel electrophoresis. Both typing methods detected two clones causing an outbreak 1994 in 6 patients and a third endemic clone of MRSA, which was isolated from 5 patients (1995), 4 patients (1996), and 6 patients (1997). Additionally other MRSA-types were found in 6 cases of which transmissions occurred in up to three patients. An epidemiological connection to MRSA isolated from patients of the university hospital of Tübingen was made. Possible consequences for patient management and antibiotic strategies in MRSA-infections were discussed.

Presence of Staphylococcus aureus with reduced susceptibility to vancomycin in Germany.

A total of 457 Staphylococcus aureus strains from the culture collection of the National Reference Center for Staphylococci in Bonn, Germany, were screened for susceptibility to vancomycin because some Staphylococcus aureus strains are able to form subpopulations that show intermediate resistance to vancomycin. Two methicillin-resistant Staphylococcus aureus strains (isolated in 1993) exhibited intermediate resistance. One of these, Staphylococcus aureus 137-93, which displayed the genomic DNA fragment pattern of the northern German epidemic strain, appeared homogeneously resistant. Neither of these strains had been identified by routine susceptibility testing. The resistance of the German isolates was lower than that of the Japanese isolate Mu50. To determine whether a similar mechanism confers vancomycin resistance in Staphylococcus aureus Mu50 and 137-93, the intracellular cell wall precursor concentration was measured and was not found to be comparably increased in Staphylococcus aureus 137-93. In conclusion, strains showing intermediate resistance have been present in Germany for some time (at least since 1993), but the subpopulations with decreased sensitivity were overlooked during antibiotic susceptibility testing.

New type of synpolydactyly of hands and feet in two unrelated males.

An 18-year-old Japanese boy and a 10-year-old Chinese boy both had nearly complete cutaneous syndactyly of the fingers and toes, six diphalangeal fingers on each hand, six toes on each foot (except the right foot of patient 2), and short, deformed, and on occasion partially fused metacarpals and metatarsals. Neither had other malformations and were of normal intelligence. The accessory toes in patient 1 were mesoaxial, each situated between the hallux and the third toe, whereas those in patient 2 were postaxial. In view of these findings, the disorder in 2 individuals is likely to represent a hitherto undescribed type of nonsyndromic synpolydactyly.

[Hormone substitution after carcinoma]. / Hormonsubstitution nach Karzinom.

OBJECTIVE: The colorectal carcinoma is one of the most frequent malignomas in western countries. Therefore the gynecologist often will be confronted with the question whether a hormone replacement with sexual steroids is allowed after a curative operation. MATERIAL AND METHODS: Basing on the data of several international publications we have substituted in an own study from 1989 to 1997 42 women with colon and 10 with rectal cancer after successful operation with a combined preparation. RESULTS: In the meantime it could be proved that in the cells of colorectal carcinomas estrogen and progesterone receptors are absent or only existing in a low concentration. Thus analogous to the receptor positive breast cancer the hormone replacement therapy also after curative treatment of a colorectal cancer should be justified. Therefore the benefit of the individual hormone replacement therapy shouldn't be withheld from these women without worsening the prognosis. CONCLUSIONS: After palliative therapy and in the case of a relapse a combined hormone replacement can be an act for diminishing the disease and should be recommended after a corresponding clearing-up and weighing the risk.

Regulation of natriuretic peptide (urodilatin) release in a human kidney cell line.

BACKGROUND: To identify the molecular mechanisms underlying the release of a renal natriuretic peptide (NP) we selected a human kidney cell line (HEK 293) that displays several characteristics of distal tubular cells. METHODS: Cells were exposed to different extracellular and intracellular stimuli, and the effect on NP release was measured with a specific urodilatin radioimmunoassay, as well as with an atrial NP (ANP) radioimmunoassay. RESULTS: In the absence of stimuli, HEK 293 cells showed a basal release of urodilatin immunoreactivity and ANP immunoreactivity. Raising the osmolality of the secretion medium with sodium chloride and various other osmolytes rapidly increased cellular NP secretion. Elevation of intracellular cAMP levels by forskolin plus 3-isobutyl-1-methylxanthine and administration of phorbol-12-myristate-13-acetate together with the calcium-ionophore A23187 also resulted in respective increases in the amount of secreted peptide. HEK 293 cells exhibit the endogenous expression of both particulate and soluble guanylyl cyclases. In the presence of 8-Br-cGMP, cell cultures showed the enhanced secretion of an ANP immunoreactive peptide only, indicating that guanylyl cyclase activation provoked the secretion of ANP immunoreactivity but not of urodilatin immunoreactivity. CONCLUSIONS: The human embryonic kidney cell line HEK 293 represents a renal cellular model system in which we have identified a rapid and regulated release of NPs in response to the osmotic effect of increased extracellular sodium chloride and various intracellular stimuli.

The renal natriuretic peptide urodilatin is present in human kidney.

BACKGROUND: The natriuretic peptide urodilatin was first isolated from human urine and may be one of the important mediators of natriuresis, while the atrial natriuretic peptide alpha-ANP, the circulating member of the family, rather seems to play a role in cardiovascular regulation. Although the renal expression of the common propeptide for urodilatin and alpha-ANP has been detected in rat and pig, it is not yet shown that urodilatin is synthesized in human kidney. METHODS: Immunohistochemically we localized urodilatin with an urodilatin-antibody, which does not cross-react with alpha-ANP, the ANP propeptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Radiolabelled urodilatin binding was examined autoradiographically. RESULTS: We could demonstrate that urodilatin is present in human distal tubular cells, in which we could also localize propeptide immunoreactivity. The glomeruli, the cells of the proximal tubule, and the collecting duct did not show any urodilatin immunoreactivity. In human kidney homogenate the urodilatin content was 4600 + 520 fmol/g protein (n = 6). The renal concentration of BNP and CNP, mainly localized in the distal tubule, was much lower at 40 + 8 and 400+/-50 fmol/g protein (n=6) respectively. Furthermore the autoradiographic examinations showed that radiolabelled urodilatin binds to natriuretic peptide receptors in the glomeruli, blood vessels, and collecting ducts. CONCLUSIONS: Our data suggest that urodilatin may be the predominant representative of natriuretic peptides in human kidneys. Urodilatin being synthesized in the distal tubular region may be transported as a paracrine factor to the collecting duct, where it exerts its suppressing effect on the sodium reabsorption by stimulating the guanylyl cyclase A.

European multicentre evaluation of a commercial system for identification of methicillin-resistant Staphylococcus aureus.

A commercial system for the rapid detection of methicillin-resistant Staphylococcus aureus, the BBL Crystal MRSA test (C-MRSA ID; Becton Dickinson, USA), was evaluated prospectively and compared with a polymerase chain reaction test for the presence of the mecA gene. Ten European centres tested a total of 676 isolates of Staphylococcus aureus from blood cultures. The system correctly identified 661 (97.8%) isolates within 4 h. All but three mecA gene-negative isolates (99.4% specificity) yielded a negative C-MRSA ID reaction, and 158 of 170 mecA gene-positive isolates were accurately detected (92.9% sensitivity). After repeated testing of discrepant results, sensitivity and specificity increased to 99% and 100%, respectively.

Receptor internalization delays m4 muscarinic acetylcholine receptor resensitization at the plasma membrane.

We analyzed the role of receptor internalization and recycling in muscarinic acetylcholine receptor (mAChR) desensitization and resensitization. Incubation of Chinese hamster ovary cells stably expressing the m4 mAChR with 1 mM carbachol for 1 hr reduced cell surface receptor number by 50-60% with no change in total receptor number. Pretreatment of the cells with 450 mM sucrose, which did not affect the ability of m4 receptors to inhibit forskolin-stimulated cAMP accumulation, completely blocked receptor internalization. On the other hand, the carbachol treatment reduced the ability of m4 receptors to inhibit cAMP accumulation in both sucrose-treated and untreated cells, with a similar onset and to a similar extent. The EC50 value for carbachol was increased approximately 10-fold, and maximal inhibition determined at 100 microM carbachol was reduced approximately 50%. In contrast, thrombin-induced inhibition of cAMP accumulation was not affected. Recycled receptors in cells not treated with sucrose remained refractory to carbachol stimulation for > or = 2 hr after agonist removal, even though cell surface receptor number had recovered completely within 1 hr. In contrast, resensitization of receptor function was very rapid in cells treated with sucrose. Ten minutes on removal of agonist, mAChRs in the plasma membrane of sucrose-treated cells were fully resensitized. Also, an internalization-defective m4 mAChR mutant, T399A, that was found to desensitize similar to the wild-type receptor, resensitized more rapidly than the wild-type receptor. We conclude that desensitization and resensitization of m4 mAChRs in Chinese hamster ovary cells can occur at the plasma membrane and that receptor internalization strongly delays the process of resensitization of desensitized receptors.

Staphylococcal scalded skin syndrome in an immunocompromised adult.

Staphylococcal scalded skin syndrome, a generalized exfoliative dermatitis complicating infections by exfoliative toxin-producing strains of Staphylococcus aureus, is rarely observed in adults. In contrast to mortality in infants, mortality in adults is usually high. A case of generalized staphylococcal scalded skin syndrome in an immunocompromised woman is reported. Culture of skin biopsy and pleural fluid yielded identical strains of staphylococcus aureus belonging to phage group II. Exfoliative toxins A and B were detected in both isolates. As far as can be determined, this is the first reported case of generalized staphylococcal scalded skin syndrome in an adult with detection of exfoliate toxins A and B in which the patient was treated successfully.

[Typing, resistance behavior and occurrence of methicillin-resistant Staphylococcus aureus strains in a surgical intensive care unit]. / Typisierung, Resistenzverhalten und Häufigkeit Methicillin-resistenter Staphylococcus aureus-Stämme einer chirurgischen Intensivstation.

Over a period of three years, the frequency of the appearance of methicillin-resistant S. aureus strains (MRSA) was observed on a surgical intensive care unit. During this above-mentioned period of investigation it came to a heaped occurrence of nosocomial infections on this ICU with altogether 332 S. aureus-stems being isolated from different patient specimen. 204 (61.5%) of these were resistant against methicillin and could be divided into 48 first- and 156 follow-up-isolates. The thereupon accomplished differentiation of the 48 MRSA-first isolates by means of lysotyping and the pioneered GenePath Strain Typing System for a standardized pulsed-field-gel-electrophoresis (PFGE) gave the proof of 7 different MRSA-types. Around 7 different, in part parallel chains of infection on this ICU were observed, which could be led back to different strains. In reference to all analyzed S. aureus, an especially high rate (90%) of MRSA on this ICU could be isolated in taken wound-swabs, followed by 83.3% MRSA at catheter tips and 71,9% in tracheal and bronchial secretion. A consideration of the antibiotic susceptibility yielded, that also gentamicin and the quinolones showed an in-vitro resistance against MRSA, while fosfomycin, fusidic acid, chloramphenicol and trimethoprim/sulfamethoxazole reached positive responding rates between 80 and 100%. On the other hand, presently still 100% of the explored MRSA-strains are susceptible for glycopeptides such as vancomycin and teicoplanin. Because of intensive hospital hygienic measures the number of newly isolated MRSA could be reduced clearly on this ward.

The role of membrane proximal threonine residues conserved among guanine-nucleotide-binding-protein-coupled receptors in internalization of the m4 muscarinic acetylcholine receptor.

Many guanine-nucleotide-binding-protein-coupled receptors contain consensus sequences for phosphorylation by cAMP-dependent protein kinase (PKA), often located in the membrane proximal regions critically important for receptor signalling. In the present study, we have evaluated by site-directed mutagenesis the role of the putative PKA phosphorylation sites in the m4 muscarinic acetylcholine receptor (mAChR), i.e. Thr145 in the second cytoplasmic loop and Thr399 in the third cytoplasmic loop, and the influence of PKA on m4 mAChR function and internalization. Antagonist binding was unaltered by any of the mutations studied, while the agonist-binding affinity was either not affected (Thr145 alanine), increased (Thr399 alanine) or decreased (Thr399 serine or aspartic acid). m4 mAChR-mediated inhibition of adenylyl cyclase was unaltered by the mutations, except for an approximately tenfold reduced agonist potency of the Thr399 aspartic acid mutated receptor. Agonist-induced receptor internalization was unaltered with Thr399 serine or aspartic acid mutations of the receptors, but was strongly decreased in its rate and extent upon replacement of Thr399, Thr145 or both of these residues with alanine. These mutational effects could not be reproduced by treatment of wild-type receptor-expressing cells with the PKA inhibitor H-8. Furthermore, maximal stimulation of cellular PKA neither affected receptor internalization nor signalling measured as receptor-mediated Ca2+ mobilization. We conclude that the membrane proximal threonine residues of the m4 mAChR are not required for receptor signalling, but replacement by alanine residues can significantly affect receptor internalization, independently of PKA phosphorylation. Sequence comparisons suggest that threonine residues at corresponding positions may be relevant to internalization of other guanine-nucleotide-binding-protein-coupled receptors.

Granulomatous dermatitis and mastitis in two SPF rats associated with a slowly growing Staphylococcus aureus--a case report.

An isolated occurrence of multifocal severe granulomatous dermatitis and mastitis accompanied by extensive calcifications is described in 2 female Sprague-Dawley, SPF breeding rats. Poorly growing Staphylococcus aureus of uncertain lysotype (probably lysotype II) was isolated from the lesions of both rats. The source of infection could not be determined. No further cases in the closed barrier maintained breeding colony occurred in the following 7 months. Difficulties in interpreting these findings and the practical consequences relating to the hygienic status of the barrier breeding colony are discussed.

Agonist-induced down-regulation of the m4 muscarinic acetylcholine receptor occurs without changes in receptor mRNA steady-state levels.

The regulation of m4 muscarinic acetylcholine receptor mRNA expression by receptor activation was studied in N1E-115 neuroblastoma and AtT-20 pituitary cells that endogeneously express the m4 muscarinic receptor. Receptor concentration was measured by binding of the muscarinic receptor radioligand [3H]quinuclidinyl benzilate, and RNA-RNA solution hybridization/RNase protection assay with a m4 receptor-specific [32P]-cRNA probe was used to evaluate the levels of receptor mRNA. Treatment of both cell lines with a receptor-saturating concentration of the agonist carbachol decreased receptor number. However, there was no change in steady-state levels of m4 mAChR mRNA in both cell lines. Determination of mRNA stability in the presence of the transcription blocker actinomycin D revealed that carbachol treatment increased half-life of receptor mRNA in N1E-115 cells, but not in AtT-20 cells, suggesting that receptor activation can regulate m4 receptor mRNA stability dependently on cell type. Analysis of receptor degradation kinetics in the presence of the protein synthesis inhibitor cycloheximide showed that receptor down-regulation in N1E-115 and AtT-20 cells is sufficiently accounted for by increased receptor degradation. These results indicate than m4 muscarinic receptor down-regulation is substantially different from that of the muscarinic receptor subtypes m2 and m3 which is reported to be associated with agonist-induced reduction in receptor mRNA.

Smoking during pregnancy and congenital limb deficiency.

OBJECTIVE: To examine genetic and environmental factors in the origin of isolated congenital limb deficiencies. DESIGN: Case-control study with questionnaire at a family interview of cases of isolated congenital limb deficiencies (six types), negative controls (matched for age, sex, and place of residence), and positive controls (cases of sentinel anomalies). SETTING: The database of the Hungarian Congenital Abnormality Registry, 1975-84, complemented by three other sources of ascertainment (1,575,904 births). SUBJECTS: 537 case-control pairs; 392 positive controls. MAIN OUTCOME MEASURES: Smoking during pregnancy, congenital limb deficiencies. RESULTS: The adjusted rate of smoking during pregnancy was significantly higher in the mothers of cases of terminal transverse defect (relative odds 1.48; 95% confidence interval 0.98 to 2.23; P = 0.017). This finding supports the hypothesis of vascular disruption as a cause of congenital limb deficiency. CONCLUSIONS: Maternal smoking during pregnancy raises the relative odds for terminal transverse limb deficiencies.