Bromocriptine-desipramine protocol in treatment of cocaine addiction

Thirty-six male cocaine abusers, in withdrawal, were studied for 99 days in a double-blind design. Treatment with bromocriptine was significantly more effective than placebo in alleviating withdrawal symptoms. Adding desipramine to the bromocriptine regimen was significantly more effective than either placebo or bromocriptine alone. The authors hypothesize that these results support a model of dopamine depletion and receptor supersensitivity in cocaine withdrawal.     

Inter-NICU variation in rates and management of thrombocytopenia among very low birth-weight infants.

OBJECTIVES: To investigate variation among neonatal intensive care units (NICUs) in prevalence and management of thrombocytopenia in infants <1500 g. STUDY DESIGN: In total 1283 infants &<1500 g admitted to six NICUs over 21 months were prospectively analyzed. Illness severity was measured by the Score for Neonatal Acute Physiology (SNAP). Platelet counts in the first 12 hours after birth and on day 3 of life were abstracted from the infants' medical records. Thrombocytopenia was determined from the lowest platelet count in each of these time periods. RESULTS: There was variability in rates of thrombocytopenia among NICUs, even after controlling for risk factors (e.g., SNAP, small for gestational (SGA) age and maternal hypertension). One site had a high prevalence of thrombocytopenia, but the lowest percentage of infants with thrombocytopenia who received platelet transfusions. After controlling for SNAP, GA, SGA, Apgar score and incidence of thrombocytopenia, the odds of receiving platelets at this site, relative to the site with the highest transfusion rate, was 0.10 (95% CI 0.02 to 0.43). CONCLUSIONS: This multicenter study finds a 10-fold variation among NICU in the administration of platelets to their thrombocytopenic infants that cannot be explained by presence of thrombocytopenia or illness severity.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.     

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced thoracic cavity. In the most common subtype (TD1), femurs are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were identified in both subtypes. While TD2 was accounted for by a single recurrent mutation in the tyrosine kinase 2 domain, TD1 resulted from either stop codon mutations or missense mutations in the extracellular domain of the gene. Here, we report the identification of FGFR3 mutations in 25/26 TD cases. Two novel missense mutations (Y373C and G370C) were detected in 8/26 and 1/26 TD1 cases respectively. Both mutations created cysteine residues in the juxta extramembrane domain of the receptor. Sixteen cases carried the previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically homogeneous condition and give additional support to the view that newly created cysteine residues in the extracellular domain of the protein play a key role in the severity of the disease.      

Association study of dopamine D3 receptor gene and schizophrenia

Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. © 1995 Wiley-Liss, Inc.     

Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture

We have recently shown using dansyl-L-lysine exclusion studies that the release of human chorionic gonadotrophin (HCG) in conjunction with L- lactate dehydrogenase (LDH) from first trimester villi during organ culture is symptomatic of syncytiotrophoblast degeneration. The purpose of this study was to examine chorionic villi at the ultrastructural level in order to determine events occurring during organ culture. The tissue was sampled after 0, 24, 48 and 120 h in culture and processed for electron microscopy. In addition to confirming the previously recorded syncytial degeneration, the electron micrographs showed clearly the generation of a new syncytiotrophoblast layer. The new layer, derived from differentiating cytotrophoblast cells, was largely formed by 48 h and was maintained for at least 120 h in culture. This study demonstrates a model which provides an opportunity to study the differentiation of cytotrophoblast cells whilst they retain their anatomical relationships within the villous structure.