Combining methods to identify new measures of women's drinking problems Part I: the ethnographic stage

In recent years, some researchers in the alcohol survey field have raised concerns about the shortcomings in severity/frequency scales for drinking and drinking problems used for both clinical and household survey purposes, especially with regard to women. This article reports on Part I of a two-part study that used ethnographic and survey methods to assess indicators of drinking problems among women across various US subcultures. Methodology for the ethnographic component consisted of three steps: analysis of findings in literature on indicators of women's drinking problems, and analysis of indicators addressed in the most commonly used standard instruments for alcohol assessment; semi-structured interviews with 12 specialists in treatment and/or research who focused on alcohol problems of women; and semi-structured interviews with 65 women from four ethnic populations who were clients in alcohol treatment centers. Analysis of these data from the ethnographic component produced a taxonomy of indicators of women' s drinking problems and fourteen novel indicators that are not included or are inadequately examined in the most commonly used alcohol assessment instruments. The novel indicators were then incorporated into a questionnaire used for a county-wide survey of men and women that assessed indicators of drinking problems. Report of findings from the survey are presented in the second paper of this series.     

In Vitro Fertilization and Embryo Transfer

The technique of in vitro fertilization and embryo transfer is explained, and nurses are given an overview of this new technique for treating infertility. The role of the nurse in each phase of the process is described, with emphasis on meeting the educational and emotional needs of couples.     

Follow-up at 11 years of 46 children with severe unilateral hearing loss at 7 years

SUMMARY In the ongoing NCDS, 44 children of the 46 identified at 7 years as having a serious unilateral hearing loss were followed up at 11 years. Half of them had recovered normal bilateral hearing, the remainder still had serious deafness in one ear. Although at 7 years the 46 children as a group had shown backwardness in oral ability, speech and reading, at 11 years both the 'recovered' and the 'persistent' were similar to their age peers in scholastic attainment. Despite their original apparent difficulty it was encouraging to find that several children in both subgroups were noted as possessing outstanding academic ability. It is concluded that with prompt follow-up by an alerted school doctor, children with unilateral deafness at age 7 years are likely to progress satisfactorily in later childhood.     

Synthesis of a cyclic fibrin-like peptide and its analysis by fast atom bombardment mass spectrometry

For immunochemical purposes, a cyclic 12-peptide was synthesized to model the γ-γ-chain cross-link site in human fibrin. The model was based upon the structure proposed by Chen & Doolittle (Biochemistry (1971) 10, 4486–4491) which is characterized by two reciprocating e -(γ-Glu)Lys bonds between adjacent fibrin γ-chains oriented in an antiparallel manner. To achieve the antiparallel orientation of the peptide backbone, Pro and Gly were inserted at positions 6 and 7 of the linear 12-peptide: acetyl-Gly-Glu-Gln-His-His-Pro-Gly-Gly-Gly-Ala-Lys-Gly-amide. The insertions were made to facilitate a reverse turn of the peptide during the last synthetic step, which was formation of the e -(γ-Glu)Lys bond between Glu at position 2 and Lys at position 11 with diphenylphosphorylazide. The resulting cyclic peptide represented half of the symmetrical cross-linked region in clotted fibrin. Following purification by HPLC, both linear and cyclic 12-peptides were analyzed by fast atom bombardment mass spectrometry. Abundant molecular protonated ions were observed for both peptides. In addition, the amino acid sequence of the linear peptide and the location of the e -(γ-Glu)Lys bond in the cyclized peptide could be verified.     

Hydatidiform Mole Macromolecules Inhibit Interleukin-2-Mediated Murine Lymphocyte Proliferation In Vitro

ABSTRACT: Macromolecules extracted from hydatidiform mole trophoblast inhibit mitogen-induced lymphocyte proliferation. To characterize the mechanism of this immunomodulation, we determined the effects of hydatidiform mole vesicle fluid (HMF) and tissue extracts (HME) on lymphokine function in vitro. Utilization of interleukin-1 (IL-1) and interleukin-2 (IL-2) were determined by using a lymphoma cell line (LBRM-33-1A5) and a murine T cell line (CTLL2), respectively. HMF suppressed (P < .05) IL-2-dependent CTLL2 cell proliferation at 500 (36.4% of controls) and 50 (74.9% of controls) μg/ml. HME also suppressed CTLL2 proliferation (P < .05) at 500 (46.0% of controls), 100 (67.2% of controls), 50 (71.5% of controls), and 10 (85.4% of controls) μg/culture ml. In contrast, HMF exhibited no effect on IL-1-stimulated LBRM-33-1A5 production of IL-2. However, 500 μg/ml of HME inhibited (P < .05) IL-2 production (63.0% of controls) in the IL-1 utilization assay. This suppressive effect was probably due to a carry over of HME from the LBRM-33-1A5 culture to the target cells (CTLL2) used to measure IL-2 production. Molecular weight chromatography of an HME sample eluted an IL-2 inhibitor in a low molecular weight (35–50 kd) and high molecular weight (> 250 kd) fraction. These data suggest that one way in which macromolecules derived from hydatidiform mole could interfere with in vitro immunologic responses is by modulating interleukin-2 function.     

Dental agenesis in Kallmann syndrome individuals with FGFR1 mutations

International Journal of Paediatric Dentistry 2010; 20: 305–312 Background. Kallmann syndrome (KS) is a rare genetic disorder characterised by central hypogonadism with a lack of sense of smell and in some cases renal aplasia, deafness, syndactyly, cleft lip/palate, and dental agenesis. To date, five genes for KS have been identified: KAL1, located on the X chromosome, and FGFR1, PROKR2, PROK2 and FGF8, which are involved in autosomally transmitted forms of KS. Aim. The study characterised the dental ageneses of individuals with KS associated with mutations in the FGFR1 gene. Design. Six individuals displaying dental agenesis were included. Clinical and radiological dental evaluations as well as medical anamneses were carried out. Results. Microdontia, screwdriver‐shaped mandibular incisors, thin molar roots, and patterns of dental agenesis in both dentitions were observed. One to nine teeth were missing, most frequently, in descending order, lateral mandibular incisors, second premolars of upper and lower jaws, and lateral maxillary incisors. The pattern of dental agenesis is associated with four new mutations in the FGFR1 gene. Conclusion: Dental agenesis may be a clinical feature of Kallmann syndrome caused by a mutation in the FGFR1 gene. These findings highlight the role that odontologists can play in the early diagnosis and treatment of gonadotropic deficiency.     

New hydroxamate inhibitors of neurotensin-degrading enzymes Synthesis and enzyme active-site recognition

Selective and mixed inhibitors of the three zinc metallopeptidases that degrade neurotensin (NT), e.g. endopeptidase 24-16 (EC 3.4.24.16), endopeptidase 24-11 (EC 3.4.24.11 or neutral endopeptidase, NEP) and endopeptidase 24-15 (EC 3.4.24.15), and leucine-aminopeptidase (type IV-S), that degrades the NT-related peptides, Neuromedin N (NN), are of great interest. On the structural basis of compound JMV 390-1 (N-[3-[(hydroxyamino)carbonyl]-I-oxo-2(R)-benzylpropyl]-L-isoleucyl-L-leucine), which was a full inhibitor of the major NT degrading enzymes, several hydroxamate inhibitors corresponding to the general formula HONHCO-CH₂-CH(CH₂-C₆H₅)CO-X-Y-OH (with X-Y = dipeptide) have been synthesized. Compound 7a (X-Y = Ile-Ala) was nearly 40-times more potent in inhibiting EC 24-16 than NEP and more than 800-times more potent than EC 24-15, with an IC₅₀ (12 nM) almost equivalent to that of compound JMV 390-1. Therefore, this compound is an interesting selective inhibitor of EC 24-16, and should be an interesting probe to explore the physiological involvement of EC 24-16 in the metabolism of neurotensin. © Munksgaard 1996.