Polynucleotide Immune Complexes in Serum and Glomeruli of Patients with Systemic Lupus Erythematosus

Several types of antipolynucleotide antibodies were eluted by acid buffer or deoxyribonuclease treatment of glomeruli obtained from nine kidneys from patients with systemic lupus erythematosus (SLE). Anti-SDNA antibodies were found concentrated over serum levels in eight eluates, anti-NDNA in six eluates and anti-RNA Pr in four eluates; anti-DSRNA antibodies were not demonstrable in any eluate tested. Deoxyribonuclease treatment eluted a high incidence and greater quantity of anti-NDNA and anti-SDNA antibody, whereas anti-RNA Pr antibody was mainly eluted by acid buffer. Simultaneous studies of antibody and antigen in serial serum specimens and in glomeruli suggested that complexes of SDNA antibody or antigen excess were frequently deposited in SLE kidneys, in addition to complexes containing anti-NDNA and anti-RNA Pr. It was observed that studies of antibody titers alone were inadequate for predicting the types of complexes deposited in the kidney. Either antigen excess could obscure detection of humoral antibody or extremely high titers of antibody as observed for RNA Pr are not conducive to the formation of kidney localizing immune complexes in the absence of antigen. Immunofluorescence studies demonstrated the presence of SDNA antigen in most cases from which anti-SDNA antibody was eluted providing direct evidence for the presence of SDNA-anti-SDNA complexes in renal glomeruli. A study of complement components indicated that Clq was absent from cases in which little or no SDNA was deposited in renal glomeruli; although all nephritic kidneys demonstrated C3 deposits. Several hypotheses accounting for this observation are discussed, including the probable utilization of the alternate pathway by certain types of complexes and a direct reaction between C1q and circulating or tissue-bound NDNA or SDNA.     

Echocardiographic comparison of black and white hypertensive subjects

Echocardiography was used to compare cardiac structure and function in 35 pairs of hypertensive blacks and hypertensive whites matched for age, sex, level and known duration of hypertension, treatment status, and renin level.     

Chronotherapeutic oral drug absorption system verapamil is effective in reducing morning blood pressure in African Americans: a post hoc analysis of the chrono trial

Results of several clinical trials have shown that verapamil is effective in reducing blood pressure (BP) in African Americans, a population at high risk for hypertension and target-organ damage. Nonetheless, adequate control of BP is perceived as difficult to achieve in this population. A post hoc analysis of data from the community-based CHRONO trial (Controlling Hypertension in the moRning with a ChrONO medication) was undertaken to assess racial/ethnic differences in the safety and efficacy of the Chronotherapeutic Oral Drug Absorption System (CODAS) formulation of verapamil in a real-world setting. Once-daily administration of the CODAS formulation of verapamil significantly reduced morning BP (P<0.0001) regardless of race or ethnicity. In the African-American population (N=466), the response rate for systolic BP (<140 mmHg or > or =10% reduction from baseline) and diastolic BP (<90 mmHg or reduction > or =10 mmHg from baseline) combined was 70.8%, and 60% of those individuals responded at the lowest (200 mg) dose. Of the 59.7% of African Americans who reached the target BP of <140/90 mmHg, 64% did so at the 200-mg dose. Response rates were not affected by gender, age or treatment history, and CODAS-verapamil was well tolerated in all ethnic/racial treatment groups. In a trial conducted in actual clinical practices, the CODAS formulation of verapamil was shown to be safe and effective in African Americans, Caucasians, Hispanics and Asians.     

Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas

The 40-kilodalton processed glycoprotein, mesothelin, is highly expressed in epithelial mesotheliomas and adenocarcinomas of the ovary (serous papillary) and pancreas, but its expression in a large series of other common carcinomas has not been completely explored. In the present study, we used oligonucleotide and tissue microarrays to profile the expression of the mesothelin gene (MSLN) and encoded protein, respectively. Among 150 carcinomas of multiple anatomic sites, we found the highest average expression of MSLN in serous carcinomas of the ovary and adenocarcinomas of the pancreas, consistent with previous reports, as well as measurable but less-striking expression in pulmonary, gastric/esophageal, and colorectal adenocarcinomas. On tissue microarrays containing 621 carcinomas derived from the same and additional sites as those profiled by gene expression, mesothelin immunoreactivity was highest in cancers of the ovary (serous papillary, endometrioid, and undifferentiated) and pancreas, with less frequent staining seen in adenocarcinomas of the endometrium, lung, and stomach/esophagus. Some immunopositivity was observed in 42% of pulmonary adenocarcinomas, including 18% that had >50% of tumor cells that were immunoreactive. Some 14% of breast and 30% of colorectal adenocarcinomas showed immunopositivity, but no case contained >50% tumor cells that were immunoreactive. Mesothelin was either entirely absent or present in <5% of carcinomas of the prostate, bladder/ureter, liver, kidney, and thyroid. Overall, we observed good concordance between the results obtained by oligonucleotide and tissue microarrays. This large study of the MSLN gene and protein expression in common carcinomas provides data for future investigations that evaluate the utility of mesothelin/megakaryocyte potentiating factor as a potential serum tumor marker or target of immunotoxin-based therapy in human cancers.     

Isolation of embryonic chick myosatellite and pluripotent stem cells

Summary The current study outlines the isolation and culture of two populations of cells derived from Day 11 embryonic chick leg muscle and associated connective tissues. The two populations consisted of myogenic lineage-committed stem cells (myosatellite stem cells) and lineage-uncommitted stem cells (pluripotent stem cells). After long-term culture the lineage-uncommitted stem cell population displayed differentiated phenotypes suggestive of the following adult tissues, fibroblasts, muscle, fat, cartilage, and bone.     

Migraine: epidemiological data, repercussions on daily life and socioeconomic cost

Studies made on the basis of IHS criteria on the prevalence of migraine show relatively homogeneous results, that is to say about 12% of the adult population is prone to migraine attacks, with a marked female bias (female/male ratio, 3.7:1). Migraine-associated comorbidity has not been extensively researched due to significant methodological problems. Migraine as a risk factor in relation to cardiovascular disease remains a subject of discussion, and migraine with aura appears to present a cerebral infarct risk in young women taking oral contraception. There is an established and significant association between migraine, anxiety and depressive disorders. Certain studies have determined the important repercussions of migraine on the quality of life. Some subjects are reluctant to contact a doctor, and therefore voluntarily deny themselves access to medical treatment to relieve their condition. The socioeconomic cost of migraine attacks is high, and the direct cost in France is estimated at about 4 billion French francs. It is quite probable that the indirect costs (e.g., absenteeism, reduced efficiency at work) are even higher.     

Ileal bypass for hyperlipidemia

Partial ileal bypass (PIB) is a safe, effective, and lasting therapy for the reduction of lipids and lipoproteins in patients with hyperlipidemia. Following PIB, circulating plasma and low-density lipoprotein (LDL) cholesterol fall markedly, while high-density lipoprotein (HDL) cholesterol rises. The average plasma cholesterol lowering is 25% after diet, with a 40% reduction in the LDL-cholesterol fraction; concurrently, the HDL-cholesterol rises about 8%. These effects have been demonstrated to be maintained for up to 20 years. Currently, PIB is being used in the Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized controlled clinical trial designed to assess the effects of lipid reduction on mortality and morbidity in a postmyocardial infarction population with arteriographically demonstrated coronary atherosclerosis.

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Resumen La derivación (bypass) ileal parcial (DIP) es una modalidad terapéutica segura, efectiva y durable para la reducción de los lípidos y lipoproteínas en pacientes con hiperlipidemia. Después de la DIP, los niveles de colesterol plasmático y de colesterol de baja densidad descienden en forma marcada, en tanto que los de colesterol de alta densidad ascienden. El promedio de reducción del colesterol plasmático es de 25% después de dieta, con una reducción de 40% de la fracción del colesterol de baja densidad; al mismo tiempo, el colesterol de alta densidad asciende alrededor de un 8%. Se ha demostrado que tales efectos perduran hasta por 20 años. Actualmente se utiliza la DIP en el Programa de Control QuirÚrgico de la Hiperlipidemia (POSCH), un ensayo interinstitucional prospectivo y aleatorizado diseñado para evaluar los efectos de la reducción de los niveles de lípidos sobre la mortalidad y la morbilidad en la población que ha sufrido infarto miocárdico con arteriosclerosis coronaria arteriograficamente demostrada.

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Résumé L'opération décrite par l'auteur en 1963, le courtcircuit partiel d l'iléon représente une méthode thérapeutique dénuée de danger, efficace et durable pour obtenir la réduction des lipides et des lipoprotéines chez les malades qui présentent une hyperlipidémie. A la suite de l'intervention la fraction du cholestérol lipoprotéique de haute densité s'élève. La chute moyenne du cholestérol plasmatique est de l'ordre de 25%: la réduction est de 40% en ce qui concerne la fraction LDL du cholestérol (la fraction athérogène) alors que la fraction HDL (la fraction protectrice) s'élève environ de 8%. Ces effets se maintiennent depuis plus de 20 ans. Actuellement, le court-circuit iléal partiel est soumis à un essai clinique randomisé de contrôle destiné à apprécier les effets de la réduction des lipides sur la morbidité et la mortalité chez des malades qui ont subi un infarctus et chez qui l'artériographie a démontré une athérosclérose coronarienne.

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Supported in part by National Heart, Lung, and Blood Institute, NIH, grant #R10 HL15265.     

Nosologic framework of mental deterioration in aged subjects. From clinical practice to epidemiology

The difficulty of defining a precise nosologic framework for mental decline is linked, on the one hand, to the contradictions surrounding the term normalcy as age increases, and, on the other, to the fact that mental decline has been mired for years under a term that must be definitively proscribed: "psycho-compartmental disorders of senescence". In this catch-all++ proscribed: "psycho-compartmental disorders of senescence". In this catch++-all it is, in fact, essential to identify diseases whose nature, prognosis and, above all, therapeutic approaches differ fundamentally one from the other; to confuse them is to risk dramatic consequences. Standardization of diagnostic criteria through the combined use of clinical data, the DSM III classification, scored tests (MMS, Hachinsky, etc.), as well as scannography, presently makes it possible to arrive at the diagnosis of dementia with reasonable accuracy. This standardization++ has its limits and is not necessarily useful in atypical cases. It is nevertheless an indispensable tool for epidemiological studies and therapeutic trials.     

Prognostic performance of clinical assessment tools following hip fracture in patients with chronic kidney disease

International Urology and Nephrology - People living with chronic kidney disease (CKD) are at a higher risk of hip fracture with an associated increased mortality risk compared to individuals...