Popliteal pterygium syndrome: a clinical study of three families and report of linkage to the Van der Woude syndrome locus on 1q32

Popliteal pterygium syndrome (PPS) is a rare autosomal dominant disorder, thought to occur with an incidence of approximately 1 in 300 000 live births. The main clinical manifestations are popliteal webbing, cleft lip, cleft palate, lower lip pits, syndactyly, and genital and nail anomalies. This report describes the clinical features in two families with PPS and one isolated case, showing the range of anomalies found both within and between the families. PPS has some features in common with Van der Woude syndrome (VWS), also inherited as an autosomal dominant condition, with cleft lip/palate and, more distinctively, lower lip pits. Although the gene for VWS has not yet been identified, it has been localised to within 1.6 cM in the region 1q32-41. To determine whether PPS and VWS represent allelic forms of the same gene, three families were genotyped for markers flanking and within the critical region. A multipoint lod score of 2.7 was obtained, with no evidence of recombination, supporting the hypothesis that these two disorders are allelic.     

A randomised controlled trial of joint consultations with general practitioners and cardiologists in primary care.

BACKGROUND: Joint consultation sessions of a small group of general practitioners (GPs) and a specialist in orthopaedics proved to be an effective way of decreasing the referral rate of orthopaedic patients. Cardiac complaints comprise an important category of health problems with high referral rates. AIMS: To study the effects of joint consultation on the quality of care and referrals for patients with cardiac complaints. DESIGN OF STUDY: Randomised controlled trial. SETTING: Forty-nine GPs participated in 16 consultation groups, each with one of 13 cardiologists, in monthly joint consultations over a period of about 18 months. METHOD: The GPs selected patients about whom they were uncertain, and those needing urgent referral were excluded. Patients were randomly assigned to joint consultation or to usual care. After a follow-up period all patients had a joint consultation for outcome assessment. Referral data were provided by two regional health insurance companies and questionnaires were given to the patients, GPs, and cardiologists to gauge their opinion of the trial. RESULTS: One hundred and forty-eight patients in the intervention group and 158 patients in the control group fulfilled the whole protocol. The quality of care was similar in both groups. In the intervention group, 34% of the patients were referred, compared with 55% in the control group (P = 0.001), and fewer patients underwent further diagnostic procedures (7% compared with 16%, P = 0.013). Referrals to cardiology as a proportion of all referrals decreased in the practices of the participating GPs, compared with their reference districts (P = 0.024). CONCLUSION: Joint consultation is an effective method that provides a quality of care that at least equals usual care and that contributes to a better selection of patients who need specialist care.     

Outer membrane proteins from rough strains of four Brucella species.

Outer membrane proteins from 15 rough strains of Brucella abortus, B. ovis, B. canis, and B. melitensis were extracted with a dipolar detergent, and outer membrane proteins from selected strains were purified by anion exchange chromatography and gel filtration (Verstreate et al., Infect. Immun. 35:979-989, 1982). Outer membrane proteins produced two types of profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One type, demonstrated by B. abortus, B. ovis, and B. canis strains, contained the three predominant protein groups present in smooth B. abortus strains (Verstreate et al., Infect. Immun. 35:979-989, 1982): groups 1, 2 (porin [Douglas et al., Infect. Immun. 44:16-21]), and 3. B. melitensis strains demonstrated the second profile type, in which there was an additional band between groups 1 and 2. The relative proportion of porin was considerably lower in B. ovis, B. canis, and B. melitensis than in B. abortus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles could be used to distinguish B. abortus and B. melitensis from each other and from B. canis and B. ovis. The amino acid compositions of groups 2 and 3 from rough strains of B. abortus, B. canis, and B. melitensis were similar to those of corresponding proteins from smooth B. abortus strains. Zwittergent-soluble fractions from most rough strains contained antigen [b], which cross-reacted with group 2 from smooth B. abortus strains, and antigens [c] and [d], which cross-reacted with group 3 from smooth B. abortus strains. Antigen [a], shared by groups 2 and 3 (D. R. Verstreate and A. J. Winter, Infect. Immun. 46:182-187, 1984), was detected in most rough strains. None of these antigens were related to either rough or smooth lipopolysaccharide.     

Recombinant mouse monoclonal antibodies with single amino acid substitutions affecting Clq and high affinity Fc receptor binding have identical serum half-lives in the BALB/c mouse.

The serum half-lives of three recombinant mouse monoclonal antibodies, differing radically in their ability to bind to Clq or FcRI but only minimally in structure, were determined in the BALB/c mouse following intravenous administration. The wild-type antibody, a chimaeric antibody comprising variable domains binding 3-iodo-4-hydroxy-5-nitrophenylacetate and constant domains of the mouse IgG2b isotype, was eliminated from the bloodstream with biphasic kinetics: alpha-phase, 0.5 days; beta-phase, 7.0 days. The alpha- and beta-phase half-lives of mutant recombinant antibodies with single amino acid substitutions, either Glu 235-Leu allowing binding to the mouse FcRI, or Lys 322-Ala reducing Clq binding 30-fold, were indistinguishable from those of the wild-type antibody demonstrating that the biological half-life of intact mouse IgG is independent of the ability to bind Clq or FcRI. The major implication of the present study is that IgG molecules which have been genetically engineered to eliminate interaction with other components of the immune system should retain the long half-life typical of natural antibodies.     

Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve

The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.      

HLA diversity, differentiation, and haplotype evolution in Mesoamerican Natives

Genetic variation of the Human Leukocyte Antigen region (HLA) in three Amerindian populations from the Southern Mexican state of Oaxaca, the Zapotec, Mixtec and the Mixe is examined. Individuals were typed using PCR-SSOP for four class II loci (DRB1, DQA1, DQB1, DPB1) and three class I loci (HLA-A, -B, and -C). Based on known HLA distributions, European admixture ranged from 1% to 10%. Individuals with European alleles were excluded from subsequent analysis. New alleles were revealed at each of the class I loci. In general, genotype frequencies were in Hardy-Weinberg equilibrium, although some deviations were detected. Allele frequency distributions at the DRB1, DQA1, DQB1 and HLA-A loci in all populations were more even than expected under neutrality, supporting a model of balancing selection at these loci. A history of directional selection for DPB1 in all three populations was indicated, as homozygosity values were significantly above expected values. Allele frequency distributions at HLA-B and HLA-C did not differ significantly from neutrality expectations. The data also provide evidence from linkage disequilibrium that strong haplotypic associations are present across the entire HLA region in each of the populations. Significant overall linkage disequilibrium exists between all pairs of loci typed in these populations, except those which include the DPB1 locus. These associations exist despite the fact that the recombination fraction between HLA-A, in the class I region, and DQB1, in the class II region, may exceed 0.02. One explanation is that selective pressures are maintaining the relationships between particular alleles at these loci in these populations. These relationships are maintained in general across the entire HLA region in the Oaxacan Amerindians, with the exception of DPB1.     

Damaged chromatin does not prevent the exit from metaphase I in fused mouse oocytes

The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.      

Location decisions made easier

"Should we have a facility at XYZ location?" Location plays an important role, though perhaps not a dominant one, in determining consumer patronage, and many healthcare providers are now facing major location decisions. Some of the subjectivity can be taken out of these decisions through the use of readily available demographic data from the US Census Bureau and the National Center for Health Statistics, along with a program designed for microcomputers.     

The perception of problem drinkers by general hospital staff, general practitioners and alcoholic patients

A sample of 275 subjects (general hospital staff, general practitioners and alcoholic patients) was investigated regarding their perception of problem-drinkers. A set of semantic differential scales was used, and subjects were asked to evaluate the concepts of "problem drinker," "self" and "ideal self." Psychological distance was measured in terms of bipolar personality constructs between each of the above concepts. Significant differences were found between the groups in terms of concept evaluation and psychological distance. The implications of these findings for both research and treatment are discussed.     

Respiratory effects in two-dimensional Fourier transform MR imaging

Respiratory and other regular motions during two-dimensional Fourier transform magnetic resonance imaging produce image artifacts consisting of local blurring and more or less regularly spaced "ghost" images propagating along the direction of the phase-encoding magnetic field gradient. The patterns of these ghost artifacts can be understood in terms of the technique of image production and basic properties of the discrete Fourier transform. This understanding permits, without respiratory gating, production of images of improved quality in body regions in which there is significant respiratory motion. In particular, the ghosts can be maximally separated from the primary image by choosing intervals between phase-encoding gradient pulse increments that are equal to one-half the respiratory period; they can be minimally separated by choosing an interval equal to the respiratory period. Increasing the number of signal averages between each phase-encoding increment decreases the intensity of the ghosts.