Spectrin-alpha I/61: a new structural variant of alpha-spectrin in a double-heterozygous form of hereditary pyropoikilocytosis

Recent biochemical studies have led to the identification of abnormal spectrins in the erythrocytes of patients with hereditary pyropoikilocytosis (HPP) and hereditary elliptocytosis (HE). In this report we describe the biochemical characterization of the erythrocytes from a proband with severe HPP who is doubly heterozygous for two mutant spectrins (Sp): Sp alpha I/74 and a new, previously undetected, mutant of alpha-spectrin designated Sp alpha I/61. The proband's erythrocytes are unstable when exposed to 45 degrees C, and her membrane skeletons exhibit instability to shear stress. The content of spectrin in the proband's erythrocyte membranes is decreased to 75% of control values. The amount of spectrin dimers in crude 4 degrees C spectrin extracts is increased (58%) as compared with control values (6% +/- 4%). Limited tryptic digestion reveals a marked decrease in the normal 80,000-dalton alpha I domain, an increase in the 74,000-dalton fragment that is characteristic of Sp alpha I/74, and an increase in a series of new fragments of 61,000, 55,000, 21,000, and 16,000 daltons. Both parents are asymptomatic, but they have increased amounts of spectrin dimers (17% to 25%). Limited tryptic digestion of the father's spectrin demonstrates the presence of a previously identified abnormal spectrin (Sp alpha I/74) that is characterized by a decrease in content of the 80,000-dalton peptide and an increase in concentration of the 74,000-dalton peptide. The mother's spectrin digests show a decrease in the amount of 80,000-dalton peptide and the formation of new peptides of 61,000, 55,000, 21,000, and 16,000 daltons. The data indicate that this severe form of HPP is due to the inheritance of two distinct abnormal spectrins, Sp alpha I/74 and a new spectrin mutant, Sp alpha I/61.     

Specificity of autoantibodies in autoimmune thrombocytopenia

In 42 patients with autoimmune thrombocytopenia (AITP) and a positive direct platelet suspension immunofluorescence test (PSIFT), the antigenic specificity of the autoantibodies was studied. Because the autoantibodies were often not detectable in the serum and additional HLA antibodies may disturb the reaction pattern with the platelet panel, we used eluates prepared from the patients' platelets for this study. Thirty-five patients had antibodies equally reactive with normal platelets, irrespective of their antigenic make-up, but not with the platelets from two Glanzmann's disease patients. Absorption and elution experiments in two patients showed that his was probably not due to the presence of a combination of anti-Zwa and anti-Zwb antibodies. Thus, the majority of autoantibodies against platelets seems to be directed against antigenic determinants not present on Glanzmann's disease platelets, but perhaps located on the platelet-membrane glycoproteins IIb and/or IIIa. In ten patients, antibodies of no, or still unknown, specificity were detected. Three of these had additional antibodies not reactive with the platelets of the two Glanzmann patients.     

A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12)     

Factors influencing marital stability among HIV discordant couples in northern Thailand

The burden of HIV in stable relationships places emotional, economic and physical stresses on families. We compared the influence of HIV notification on marital partnerships in northern Thailand among a cohort of HIV discordant couples, and identified factors associated with marital disruption. Data were collected using in-depth interviews with both members of six separated or divorced couples and 13 couples whose relationship remained intact. Five factors influenced marital stability following HIV notification: longer duration of relationship; economic constraints, extended family members' opinions, especially parents; the existence of children from the marriage; and fear of stigmatization by community members. Social influences, both overt and perceived, are important in shaping marital behaviour and decision-making in HIV epidemic areas. HIV counselling needs to be extended beyond the individual seeking testing to include stable partners (and perhaps further, to include the extended family), although it is recognized that this is not the norm for most HIV testing centres.     

Clinic and ambulatory pulse pressure segregate a cluster of cardiovascular risk factors

Office pulse pressure (PP) has been found to be independently associated with cardiovascular morbidity and mortality. While there is evidence that 24 h blood pressure (BP) is a better marker of the cardiovascular complications of hypertension than office BP, this information is still lacking in regard to PP. The aim of the present study was, therefore, to evaluate possible differences between office and 24 h PP in their relationship with cardiovascular risk profile. This cross-sectional study was performed in a group of 175 (104 M, 71 F) hypertensives (43 never treated before the study) free of clinical evidence of target organ disease. BP was measured at rest and during 24 h monitoring; cardiac structure and function was studied by ultrasounds; biochemical analyses were performed to evaluate some parameters of lipid and carbohydrate metabolism. Patients were divided into tertiles of office PP and of 24 h PP. Those in the highest tertile of PP had a significantly higher office and 24 h systolic BP along with a reduction in peripheral insulin sensitivity. Regarding cardiac structure and function, a significantly higher prevalence of concentric left ventricular hypertrophy (23 vs 55%; P=0.05) and an initial impairment of diastolic function with increase of the A wave was detected in hypertensives with higher PP. No difference between office and 24 h PP in detecting patients at higher cardiovascular risk was observed. In conclusion, office and 24 h pulse pressures were both able to segregate patients with a cluster of cardiovascular risk factors.     

Coronary artery calcification,atherogenic lipid changes,and increased erythrocyte volume in black injection drug users infected with human immunodeficiency virus-1 treated with protease inhibitors

Background Protease inhibitors (PIs) may be associated with accelerated atherosclerosis in individuals infected with human immunodeficiency virus (HIV). We assessed the effects of HIV PIs on subclinical atherosclerosis. Methods The lipid profiles, C-reactive protein (CRP) levels, coronary artery calcification (CAC) scores, and blood cell morphologic changes were quantified in 98 black adult participants, aged 25 to 45 years, with HIV-1 infection in Baltimore, Md. Fifty-five participants (56.1%) were taking PIs; 43 participants (43.9%) were not. The Student t and χ² tests were used as a means of detecting the between-group differences. Results Participants in both the PI and non-PI groups were similar in age, sex, body mass index, blood pressure, heart rate, and red and white blood cell counts. Compared with the non-PI group, the PI group had significantly higher serum total cholesterol (4.8 ± 1.0 vs 3.8 ± 0.7 mmol/L, P < .001) and LDL cholesterol (2.9 ± 0.8 vs 2.1 ± 0.7 mmol/L, P < .001) levels and red blood cell mean corpuscular volume (92.2 ± 9.3 vs 86.8 ± 7.2 μm³, P = .048). The CAC scores in the PI group were also higher than those in the non-PI group (11.0 ± 28.6 [n = 43] vs 1.7 ± 5.8, P = .043). CAC scores were marginally associated with log-transformed duration of the PI therapy (P = .055). Serum CRP levels remained unchanged (5.5 ± 13.6 mg/L [n = 45] vs 3.9 ± 5.5 mg/L, P = .467). Serum total cholesterol level, LDL cholesterol level, red blood cell mean corpuscular volume, and CAC scores were indicated by means of regression analyses to be associated with log-transformed duration of the PI therapy. Conclusions The use of PIs is associated with coronary artery calcification, atherogenic lipid changes, and increased erythrocyte volume in individuals infected with HIV-1. (Am Heart J 2002;144:642-8.)     

Undiagnosed migraine headaches. A comparison of symptom-based and reported physician diagnosis.

BACKGROUND--Although migraine headaches are a common cause of temporary disability, many people with migraine have not been diagnosed. In a sample of the US population, we sought to determine the proportion of migraineurs diagnosed by a physician and to identify the headache characteristics and sociodemographic profiles associated with undiagnosed migraine. METHODS--A mail questionnaire survey was sent to 15,000 US households, selected from a panel to be representative of the US population. Of a total study base population of 23,611, excluding 3043 subjects less than 12 years of age and respondents with unreported gender, we analyzed data for 20,468 subjects aged 12 to 80 years. Migraine diagnoses were assigned on the basis of reported symptoms by means of operational diagnostic criteria. Physician diagnosis of migraine was ascertained on the basis of self-report. RESULTS--Forty-one percent of female and 29% of male migraineurs reported having been diagnosed by a physician. Diagnosis was more likely in females, in people with high income levels, and in individuals who reported migraine associated with aura, vomiting, or disability. Of the undiagnosed subjects, 80% experienced at least some headache-related disability. CONCLUSIONS--Results of this survey indicate that the majority of people with migraine in the United States do not report having been diagnosed by a physician. Given the high proportion of undiagnosed subjects with headache-related disability, efforts to improve the diagnosis and treatment of migraine are recommended.     

Duodenal hematoma: the ring sign in MR imaging

Proper management of duodenal hematoma requires that an accurate diagnosis be made using noninvasive radiological methods. Conventional imaging may be nonspecific if there is no history of trauma or coagulopathy. Two cases of duodenal hematoma that were imaged by magnetic resonance (MR) and computed tomography (CT) are described. In both cases the hematoma had a well-defined concentric ring configuration on MR images, a finding which helped establish the diagnosis. MR imaging may provide tissue-specific characterization of duodenal hematomas.     

Biliary stricture dilatation: multicenter review of clinical management in 73 patients

Eighty-nine biliary strictures in 73 patients who had undergone percutaneous balloon dilatation were reviewed to determine long-term patency rates and clinical management problems. The majority of dilatations were performed in patients with anastomotic strictures (n = 44), iatrogenic strictures (n = 28), and strictures associated with sclerosing cholangitis (n = 17). Patency rates after 36 months or more were 67%, 76%, and 42%, respectively. Complications, mostly minor, occurred in less than 7% of patients. Of patients with significant biliary obstruction, 15% had little or no intrahepatic biliary duct dilatation demonstrated by cross-sectional imaging and/or direct cholangiography. No definite conclusions could be drawn about the utility of long-term internal/external stenting.