Delta glycophorin (glycophorin B) gene deletion in two individuals homozygous for the S--s--U-- blood group phenotype

Blood cells from two unrelated individuals whose erythrocytes exhibit respectively N S-s-U- and MN S-s-U- blood group phenotypes were examined by immunoblotting, periodic acid-Schiff (PAS) staining, and Southern blotting. Protein bands characteristic of delta glycophorin (glycophorin B) were absent from the immunoblots of whole erythrocyte lysates when probed with polyclonal glycophorin antisera and from isolated erythrocyte membranes stained with PAS reagents. Genomic DNA from the two individuals' leukocytes was digested with a panel of restriction enzymes and probed with alpha M glycophorin cDNA obtained from human K562 leukemic cell line. The EcoRI, PstI, and KpnI restriction site patterns were identical to those of S+s+U+ controls in fragment numbers and relative size but differed from controls in band intensities. Restriction mapping with HindIII, PvuII, SacI, MspI, and BamHI revealed that S-s-U- individuals lack fragments that are reproducibly observed in S+s+U+ controls, and most likely encode delta glycophorin. Using truncated 5' and 3' cDNA segments as probes and comparing, in control individuals, hybridization intensities of fragments with amino acid sequence homologies, we have inferred the assignment of restriction fragments to the alpha and delta glycophorin genes. Our results suggest that the absence of delta glycophorin in the two S-s-U- individuals is a result of deletion of the entire delta glycophorin gene. This is the first report of a glycophorin gene deletion.     

Liver transplantation for hepatitis C-associated cirrhosis in a single Australian centre: Referral patterns and transplant outcomes

During the study period, 63 patients with hepatitis C virus (HCV) cirrhosis were referred to our unit for liver transplantation. All cases referred and transplanted were retrospectively examined. Eighty-six per cent of referred patients were male, 35% consumed alcohol in the harmful hazardous range, 13% were infected with hepatitis B and 7% had hepatocellular carcinoma. Patients with sporadic infection were more likely to be born outside Australia and were an average of 10 years older than those with HCV acquired via intravenous drug use (P< 0.001). However, patients were an average of 12 years younger at referral if they consumed harmful amounts of alcohol than if they abstained (P = 0.002). We examined the impact of HCV on the outcome of 28 patients who underwent liver transplantation (mean follow up 25 months; range 3–76 months). The use of OKT3, HCV genotype and hepatitis B status were examined for their effect on HCV-related graft dysfunction. Three year survival was 84%, equivalent to a control group. Chronic HCV-related graft dysfunction occurred in 15 (56%) patients, of whom 10 had an asymptomatic elevation in serum amino transferase, two had cholestatic hepatitis and three had severe hepatitis C that progressed onto chronic rejection. Hepatitis C virus genotype 1b tended to be associated with HCV graft dysfunction (5/6 type 1b vs 10/16 in non-type 1b). In conclusion, HCV is an increasingly common-indication for liver transplantation. Alcohol and hepatitis B were frequently occurring cofactors in the referral cohort. Most patients referred were male, although the reason why is not clear. Transplantation offers a good medium-term outcome, despite the high incidence of HCV-associated graft dysfunction.     

The Association between Latrine Use and Trachoma: A Secondary Cohort Analysis from a Randomized Clinical Trial

Latrine use has been promoted as a component of an integrated strategy for trachoma control. As part of a randomized trial in Ethiopia, 12 communities received a mass azithromycin distribution followed by a latrine promotion intervention. A random sample of children ages 0–9 years in each community was monitored longitudinally for ocular chlamydia. After latrine construction ended, those communities with a higher proportion of households using latrines were more likely to experience a reduction in the prevalence of ocular chlamydia. Specifically, for each 10% increase in latrine use, there was a 2.0% decrease (95% confidence interval = 0.2–3.9% decrease) in the community prevalence of ocular chlamydia over the subsequent year (P = 0.04).     

Outcome from a rapid-assessment chest pain clinic

Chest pain accounts for much of the rising numbers of emergency admissions, but in-patient assessment is not necessarily the best way of dealing with these patients. We ran a 'rapid-assessment chest pain clinic' to provide an alternative route of assessment, and audited its outcome. General practitioners referred patients with recent-onset chest pain, increasing chest pain, chest pain at rest, or other chest pain of concern, on the understanding that they would be seen within 24 h. During 8 1/2 months, 334 patients were referred and 317 patients were seen, most of whom had exercise electrocardiography. A median of 6 months later, 278 patients were personally contacted to determine outcome. Of these, 18% had been admitted immediately with acute coronary syndromes, and 49% had been diagnosed as non-coronary chest pain (none of whom subsequently infarcted or died). Continuing symptoms were infrequent, and satisfaction was high, although 13% of patients had been revascularized. A significant number of patients required immediate admission and/or ultimate revascularization, but many more did not. The majority of these patients had non-coronary chest pain, and this diagnosis was substantiated by their excellent outcome and (in some cases) by further investigation.      

The nomenclature, definition and classification of hypoplastic left heart syndrome

The hypoplastic left heart syndrome encompasses a spectrum of cardiac malformations that are characterized by significant underdevelopment of the components of the left heart and the aorta, including the left ventricular cavity and mass. At the severe end of the spectrum is found the combination of aortic and mitral atresia, when the left ventricle can be close to non-existent. At the mild end are the patients with hypoplasia of the aortic and mitral valves, but without intrinsic valvar stenosis or atresia, and milder degrees of left ventricular hypoplasia. Although the majority of the patients are suitable only for functionally univentricular repair, a small minority may be candidates for biventricular repair. The nature of the syndrome was a topic for discussion at the second meeting of the International Working Group for Mapping and Coding of Nomenclatures for Paediatric and Congenital Heart Disease, the Nomenclature Working Group, held in Montreal, Canada, over the period January 17 through 19, 2003. Subsequent to these discussions, the Nomenclature Working Group was able to create a bidirectional crossmap between the nomenclature initially produced jointly on behalf of the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons, and the alternative nomenclature developed on behalf of the Association for European Paediatric Cardiology. This process is a part of the overall efforts of the Nomenclature Working Group to create a comprehensive and all-inclusive international system of nomenclature for paediatric and congenital cardiac disease, the International Paediatric and Congenital Cardiac Code. In this review, we discuss the evolution of nomenclature and surgical treatment for the spectrum of lesions making up the hypoplastic left heart syndrome and its related malformations. We also present the crossmap of the associated terms for diagnoses and procedures, as recently completed by the Nomenclature Working Group.     

Survival benefits of heart and lung transplantation.

OBJECTIVE: Heart and lung transplantation has gained acceptance as therapy for end-stage cardiac and pulmonary failure. The early and intermediate survival benefits of one center's 10-year experience with 177 patients undergoing thoracic transplantation were examined. SUMMARY BACKGROUND DATA: As experience in cardiac and pulmonary transplantation has increased, improvements in patient selection, organ preservation, preoperative support, and perioperative care have significantly reduced the early threats to patient survival. Graft dysfunction due to chronic rejection appears to be the main risk for longer-term survival, and data compiled by the United Network for Organ Sharing (UNOS) indicate a 70% 5-year survival for heart transplants and a 50% 5-year survival for lung transplant recipients. METHODS: The medical records of 120 heart recipients, 52 lung transplant recipients, and 5 heart-lung recipients were reviewed. Cumulative survival estimates were made using Kaplan-Meier analysis. The etiologies of operative and long-term mortality in each transplant population were identified. A comparison of long-term survival after heart transplantation versus coronary revascularization in a group of patients with ischemic cardiomyopathy was performed. RESULTS: Operative mortality in both the cardiac and pulmonary transplant recipients was 8%. From 1990 to 1995, 70 consecutive adult cardiac transplant procedures were performed without an operative mortality. Three of five patients survived heart-lung transplantation. The extended actuarial survival rate at 5 years was 80% for the cardiac transplant recipients. The 2-year actuarial survival rate for the lung transplant recipients was 88%. Graft dysfunction was the most common cause of operative mortality in the heart transplant group whereas infection was responsible for most of the operative mortality after lung transplantation. CONCLUSIONS: Cardiac and pulmonary transplantation can be applied to morbidly ill patients with excellent operative and intermediate-term survival.     

Hepatitis C virus (HCV) genotype analysis in apparently healthy anti- HCV-positive Parisian blood donors

BACKGROUND: As only a few studies have examined the prevalence of various hepatitis C virus (HCV) subtypes in blood donors, information about the variability and route of infection in apparently healthy persons is limited. STUDY DESIGN AND METHODS: Blood donations collected at a large Parisian hospital (52,441) were investigated for antibodies to HCV. Serum samples were screened with an enzyme immunoassay. All HCV- positive donations were retested with a second enzyme immunoassay and confirmed by immunoblot. The HCV genotype was determined for all polymerase chain reaction-positive subjects. Untypable genotypes were sequenced in the NS5B region. RESULTS: In total, 83 (0.26%) blood donors were anti-HCV positive. Men (0.34%) were significantly more likely to be infected (p < 0.001) than women (0.19%). Prevalence rates in men between 20 and 39 years of age were higher than those in similar women (p = 0.01), but greater in women aged from 50 to 65 years (p = 0.05). Fifty-five sera were viremic, of which 49 could be genotyped by a line probe assay. One new HCV type 1 subtype and three new HCV type 2 subtypes were discovered. In total, 28, 10, 11, 5, and 1 serum samples were grouped into HCV types 1 through 5, respectively, involving a total of 13 subtypes. The mean age of HCV type 2-infected donors was 42 +/− 11 years, but that for type 3-infected subjects was only 30 +/− 4 years (p = 0.0048). Forty-nine subjects showed elevated alanine aminotransferase levels; 39 (80%) of these subjects were viremic (p < 0.05). CONCLUSION: Among the sampled population, an HCV prevalence rate of 0.26 percent was found, with the five most common European genotypes causing the infections. Four new subtypes were discovered. Correlation between genotype and risk factors was not apparent, but links with age, sex, and ethnic origin emerged.     

Primary colorectal sarcoma. A retrospective review and prognostic factor study of 50 consecutive patients

Fifty patients were admitted to Memorial Hospital, Memorial Sloan-Kettering Cancer Center, New York, NY, with primary colorectal sarcoma between 1948 and 1987. Thirty-one patients (62%) presented with a high-grade tumor, 37 patients (74%) with a tumor larger than 5 cm, and 12 patients (24%) with metastasis. The median survival of the whole group was 33 months, and the median survival of patients who underwent curative operation was 174 months. Nineteen of 32 patients who underwent curative operation were observed to develop distant metastasis after 3 to 209 months. The dominant sites of metastatic disease were the liver and peritoneal cavity. In a multivariable analysis, noncurative treatment and high-grade tumor were the only prognostic factors unfavorably affecting tumor-related mortality. If the type of treatment received was not considered, presentation with metastatic disease and a high-grade tumor were the two unfavorable characteristics that had independent prognostic value. Patients with a tumor that was larger than 5 cm or that was located in the colon had a greater likelihood of having a palliative procedure or high-grade tumor.     

Virus inactivation by pepsin treatment at pH 4 of IgG solutions: factors affecting the rate of virus inactivation

BACKGROUND: IgG preparations have rarely transmitted infectious diseases; however, because such transmission has occurred a few times, manufacturers are required to present experimental proof that their specific production process removes and/or inactivates viruses that may be present in the starting material. STUDY DESIGN AND METHODS: The kinetics of virus inactivation mediated by pepsin treatment at pH 4 during the production of intravenous immunoglobulin was assessed with spiking experiments using human immunodeficiency virus, bovine viral diarrhea virus, Semliki Forest virus, and pseudorabies virus. The influence of various factors on the rate of virus inactivation also was studied by modifying the composition of the IgG solutions with respect to IgG, sucrose, and NaCl content. RESULTS: Virus inactivation at 37 degrees C was extremely rapid and resulted in a complete loss of infectivity within 5 minutes to 1 hour. Inactivation was much slower at lower temperatures. Furthermore, inactivation was dependent on the solute composition. Increasing the sucrose content from 0 to 15 percent reduced the rate of inactivation of pseudorabies virus but did not affect the rate of inactivation of Semliki Forest virus. In contrast, increasing the NaCl content from 0 to 150 mM resulted in a reduction in the rate of inactivation of Semliki Forest virus, whereas the rate of inactivation of pseudorabies virus remained unaffected. Moreover, increasing the IgG concentration from 0 to 10 percent resulted in an increased rate of inactivation of pseudorabies virus but a decreased rate of inactivation of Semliki Forest virus. CONCLUSION: Inactivation of viruses by pepsin treatment at pH 4 essentially is temperature- dependent, and the reaction rate is selectively influenced by the solute composition of the IgG solution. This has to be taken into account when safety data for different products are compared.