Intrafamilial variation of the phenotype in Bardet-Biedl syndrome

AIMS—To describe the variation of the phenotype within families with several individuals with Bardet-Biedl syndrome.
METHODS—The phenotypes of affected siblings in 11 Scandinavian families were compared with two or more members who had at least three of the features: retinal dystrophy, polydactyly, obesity, hypogenitalism, and mental retardation. Individuals without retinal dystrophy were excluded.
RESULTS—Intrafamilial variation of expressivity of the features obesity, polydactyly, abnormal radiograms of the extremities, hypogenitalism, short stature, paraplegia, and dental abnormalities was found. The retinal dystrophy varied with respect to both the onset of symptoms and the course of the disease. The morphology of the fundus, however, was consistent within the families. The disorder showed statistically significant genetic linkage to the BBS4 locus on chromosome 15 in the affected siblings in two of the families, but the clinical features in these patients did not differ from the other cases of Bardet-Biedl syndrome.
CONCLUSION—Comparison of siblings with the Bardet-Biedl syndrome showed variation of the typical features. In addition, the course of retinal dystrophy varied. No distinctive clinical features were found to separate the BBS4 phenotype from the remaining patients.

     

Atrial natriuretic peptide and blood volume in patients with chronic glomerulonephritis: effects of albumin and frusemide administration

Blood volume, blood pressure, plasma concentrations of atrial natriuretic peptide (ANP), cyclic 3',5'-guanosine monophosphate (cGMP), angiotensin II, aldosterone, and arginine vasopressin (AVP), and urinary excretion rates of cGMP, sodium, and water were determined before and after infusion of human albumin 20%, 3.5 ml/kg body-weight to 12 patients with chronic glomerulonephritis and 19 healthy control subjects (Study 1); and before and after frusemide injection, 0.75 mg/kg to 15 patients with chronic glomerulonephritis and 19 healthy control subjects (Study 2). In Study 1 blood volume was expanded to the same degree in patients (8.8 and 7.5%, medians, after 90 and 180 min) and controls (8.6 and 6.1%). ANP was enhanced in the patients (5.9 to 11.0 pmol/l, P less than 0.01) and the controls (4.9 to 7.1 pmol/l, P less than 0.01), but the elevated level was protracted in the patients simultaneously with a delayed sodium excretion. Plasma cGMP increased, aldosterone decreased and AVP was unchanged in both groups, whereas angiotensin II decreased in the patients (P less than 0.01), but not in the controls. In Study 2 blood volume was reduced to a smaller extent in the patients than in the controls (8.9% versus 9.9%, P less than 0.05). ANP an cGMP decreased, and angiotensin II, aldosterone and AVP increased in both patients and controls. In conclusion, patients with glomerulonephritis respond to albumin- and frusemide induced changes in blood volume with essentially the same counter-regulatory changes in ANP, angiotensin II, aldosterone and AVP as do healthy subjects. The more protracted increase in ANP and the decrease in angiotensin II after albumin, and the smaller blood volume reduction after frusemide suggest an abnormal regulation of blood volume in glomerulonephritis.     

Amino acid sequences and structures of chicken and turkey beta 2-microglobulin

The complete amino acid sequences of chicken and turkey beta 2-microglobulins have been determined by analyses of tryptic, V8-proteolytic and cyanogen bromide fragments, and by N-terminal sequencing. Mass spectrometric analysis of chicken beta 2-microglobulin supports the sequence-derived Mr of 11,048. The higher apparent Mr obtained for the avian beta 2-microglobulins as compared to human beta 2-microglobulin by SDS-PAGE is not understood. Chicken and turkey beta 2-microglobulin consist of 98 residues and deviate at seven positions: 60, 66, 74-76, 78 and 82. The chicken and turkey sequences are identical to human beta 2-microglobulin at 46 and 47 positions, respectively, and to bovine beta 2-microglobulin at 47 positions, i.e. there is about 47% identity between avian and mammalian beta 2-microglobulins. The known X-ray crystallographic structures of bovine beta 2-microglobulin and human HLA-A2 complex suggest that the seven chicken to turkey differences are exposed to solvent in the avian MHC class I complex. The key residues of beta 2-microglobulin involved in alpha chain contacts within the MHC class I molecule are highly conserved between chicken and man. This explains that heterologous human beta 2-microglobulin can substitute the chicken beta 2-microglobulin in exchange studies with B-F (chicken MHC class I molecule), and suggests that the MHC class I structure is conserved over long evolutionary distances.     

A simplified statistical method for local INR using linear regression

A simplified method of International Normalized Ratio (INR) derivation using linear regression of certified INR plotted against local prothrombin time (PT) results has been compared with INR from conventional orthogonal regression. Linear regression assumes error only with the local PT results whereas orthogonal regression assumes error with both reference and local results. The reliability of local INR derivation using lyophilized plasmas has been assessed in a collaborative study. INR from conventional fresh plasma International Sensitivity Index (ISI) calibrations have been compared with INR from calibrations with two types of lyophilized plasma, artificially depleted and coumarin.
Although calibration slopes differed with the two types of analysis and the different lyophilized plasmas, both gave reasonable approximations to fresh plasma ISI calibrations. With orthogonal regression the overall percentage INR deviation was 5.25% with the artificially depleted plasmas and 6.85% for the results with lyophilized coumarins. With the linear regression, deviation was 8.40% for the artificially depleted plasmas and 5.05% for coumarin-treated patients' lyophilized plasmas. The simpler regression method appears to be worthy of further study as the present report has demonstrated that if the calibrant plasmas are accurately certified with the thromboplastin International Reference Plasma (IRP) results approximate to the conventionally determined INR using the manual PT technique. Coagulometers require further assessment.     

Occupational exposure of deck crews to carcinogenic agents on crude oil tankers

Occupational exposure to carcinogenic agents on the decks on six Norwegian crude oil tankers was examined in five harbors. The purpose of the study was to evaluate the need for improving the working environment on deck on these tankers. Technical arrangments and the work itself on the deck were observed during loading or unloading. Occupational monitoring was performed by active sampling of benzene, polyaromatic hydrocarbons, and some aldehydes. The crew answered a questionnaire concerning their work, use of protective equipment, and occurrence of acute symptoms. The levels of air-borne carcinogenic agents were low, probably due to closed loading systems on all tankers. However, the seamen reported discomfort during the work that may be related to other chemical agents in the cargo. The seamen were frequently painting with lead chromate paint without using personal protective equipment. This type of chemical exposure should be evaluated.     

Incidence of multiple sclerosis in Hordaland, western Norway: a fluctuating pattern

The incidence of multiple sclerosis (MS) was studied in the county of Hordaland, western Norway. A significant increase in incidence in the period 1958-1987, a decline followed by a gradual increase in mean age at onset, geographic differences in time trends and a biphasic pattern revealed by a birth cohort analysis support the theory of real time-space fluctuations in the incidence of MS over time.     

Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype

Mutations in the CLCN1 gene, encoding a muscle-specific chloride channel, can cause either recessive or dominant myotonia congenita (MC). The recessive form, Becker's myotonia, is believed to be caused by two loss-of-function mutations, whereas the dominant form, Thomsen's myotonia, is assumed to be a consequence of a dominant-negative effect. However, a subset of CLCN1 mutations can cause both recessive and dominant MC. We have identified two recessive and two dominant MC families segregating the common R894X mutation. Real-time quantitative RT-PCR did not reveal any obvious association between the total CLCN1 mRNA level in muscle and the mode of inheritance, but the dominant family with the most severe phenotype expressed twice the expected amount of the R894X mRNA allele. Variation in allelic expression has not previously been described for CLCN1, and our finding suggests that allelic variation may be an important modifier of disease progression in myotonia congenita.     

Sexual dysfunction in male and female patients with epilepsy: A study of 86 outpatients

Sexual dysfunction is a well-known complication of chronic somatic illness. Eighty-six consecutive epileptic outpatients, 38 men and 48 women, without accompanying disorders, were studied. The frequency and symptoms of sexual dysfunction were compared with results from previous studies using identical sexological methodology. The previous studies were of diabetic patients and healthy controls. Eight percent of the epileptic men reported a sexual dysfunction compared to 44% of the diabetics and 13% of the controls. Epileptic women, diabetic women, and controls showed no significant differences in sexual dysfunction (29%, 28%, and 25%, respectively). In both sexes, the sexual function measured by frequencies of coitus and masturbation was normal. Most patients had good control of epileptic attacks on a treatment of monotherapy. Hormonal status was generally within normal limits in both men and women; only a few minor differences were found and they showed no correlation with sexual dysfunction. Psychologically and socially the patients did not differ appreciably from normals, and they exhibited a high degree of disease acceptance. This study, using a biopsychosocial approach in understanding sexual dysfunctions, is in contrast with previous, mainly uncontrolled, studies of epileptic patients that reported high frequencies of hyposexuality in males. We conclude that epilepsy does not necessarily increase the risk of sexual dysfunction in male or female.     

Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy

Twenty patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction.