Antihypertensive Medications in End‐Stage Renal Disease

Hypertension is almost universal in end‐stage renal disease (ESRD) and contributes to the substantial cardiovascular (CV) morbidity and mortality observed in these patients. The management of blood pressure (BP) in ESRD is complicated by a number of factors, including missed dialysis treatments, intradialytic changes in BP, medication removal with dialysis, and poor correlation of BPs obtained in the dialysis unit with those at home and with CV outcomes. Control of extracellular volume with ultrafiltration and dietary sodium restriction represents the principal strategy to manage hypertension in ESRD, and antihypertensive medications are subsequently added if this strategy is inadequate. While reduction in BP with medication improves CV outcomes, few head‐to‐head clinical trials have been performed to firmly establish the superiority of one antihypertensive medication class over another. Therefore, individualization of therapy is necessary, and patient comorbidities must be considered. Angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta‐blockers are reasonable first‐line agents for most patients. ACE inhibitors and ARBs exert cardioprotective effects that are independent of BP reduction. Medications that are removed with dialysis may be preferred in patients who are prone to develop intradialytic hypotension. Intradialytic hypertension can be managed with challenging the patient's dry weight and using nondialyzable medications. Within a class of antihypertensive medications, there may be large variability in drug removal with dialysis, which must be considered upon medication selection. Studies demonstrate that even thrice‐weekly dosing of medication after dialysis has robust BP‐lowering effects, which may be a useful regimen in nonadherent patients.     

Hard superconducting nitrides

Detailed study of the equation of state, elasticity, and hardness of selected superconducting transition-metal nitrides reveals interesting correlations among their physical properties. Both the bulk modulus and Vickers hardness are found to decrease with increasing zero-pressure volume in NbN, HfN, and ZrN. The computed elastic constants from first principles satisfy c11 > c12 > c44 for NbN, but c11 > c44 > c12 for HfN and ZrN, which are in good agreement with the neutron scattering data. The cubic delta-NbN superconducting phase possesses a bulk modulus of 348 GPa, comparable to that of cubic boron nitride, and a Vickers hardness of 20 GPa, which is close to sapphire. Theoretical calculations for NbN show that all elastic moduli increase monotonically with increasing pressure. These results suggest technological applications of such materials in extreme environments.     

Transcatheter Valve Repair for Patients With Mitral Regurgitation: 30-Day Results of the CLASP Study

ObjectivesThe authors report the procedural and 30-day results of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences, Irvine, California) in patients with mitral regurgitation (MR) enrolled in the multicenter, prospective, single-arm CLASP study.BackgroundSevere MR may lead to symptoms, impaired quality of life, and reduced functional capacity when untreated.MethodsEligible patients had grade 3+ or 4+ MR despite optimal medical therapy and were deemed appropriate for the study by the local heart team. All outcomes were assessed through 30 days post-procedure. Major adverse events (MAEs) were adjudicated by an independent clinical events committee, and echocardiographic images were assessed by a core laboratory. The primary safety endpoint was the rate of MAEs at 30 days.ResultsBetween June 2017 and September 2018, 62 patients with grade 3+ or 4+ MR were enrolled. The mean age was 76.5 years, and 51.6% of patients were in New York Heart Association functional class III or IV, with 56% functional, 36% degenerative, and 8% mixed MR etiology. At 30 days, the MAE rate was 6.5%, with an all-cause mortality rate of 1.6% and no occurrence of stroke; 98% had MR grade ≤2+, with 86% with MR grade ≤1+ (p < 0.0001); and 85% were in New York Heart Association functional class I or II (p < 0.0001). Six-minute walk distance improved by 36 m (p = 0.0018), and Kansas City Cardiomyopathy Questionnaire and EQ-5D scores improved by 17 (p < 0.0001) and 10 (p = 0.0004) points, respectively.ConclusionsThe PASCAL repair system showed feasibility and acceptable safety in the treatment of patients with grade 3+ or 4+ MR. MR severity, irrespective of etiology, was significantly reduced and accompanied by clinically and statistically significant improvements in functional status, exercise capacity, and quality of life. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study; NCT03170349)     

Healthcare use by varied highly active antiretroviral therapy (HAART) strata: HAART use, discontinuation, and naivety

OBJECTIVES: Prior reports have found a temporal association between the introduction of highly active antiretroviral therapy (HAART) and population rates of health service use among persons living with HIV. Our objective was to explore further the effect of HAART by comparing healthcare use among persons who use HAART and persons who discontinue HAART to that among HAART-naive and HIV-negative persons. METHODS: Longitudinal analyses of 1485 women with and at-risk for HIV who contributed data to the Women's Interagency HIV Study between April 1997 and March 2000. RESULTS: Compared with HAART-naive women, those using HAART had a higher probability of more than three primary care visits per 6 months [odds ratio (OR), 1.38; 95% confidence interval (CI), 1.16-1.65), a lower probability of more than one emergency room visit per 6 months (OR, 0.75; CI, 0.59-0.95), and a lower probability of more than one hospitalization per 6 months (OR, 0.67; CI, 0.51-0.88). Compared with HAART-naive women, women who had discontinued HAART had a higher frequency of primary care visits (OR, 1.57; CI, 1.26-1.97) but did not demonstrate a significant change in emergency room or hospital use. Modeling of a standardized population HIV-positive women without AIDS indicated hospitalization and emergency room use among HAART users was equivalent to that among HIV-negative women. CONCLUSIONS: HIV-positive HAART users (without AIDS) exhibited emergency room and hospitalization use patterns equivalent to those of HIV-negative women. Furthermore, the discontinuation of HAART was associated with a loss of the reduction in hospital use that was achieved with HAART.     

Somatomedin binding proteins in GH-deficient children with normal plasma somatomedin levels

The major portion of circulating somatomedin (SM) is specifically carried by a large molecular weight binding protein of 150,000 (150K BP). There also exists a species of unsaturated binding protein in plasma of 40,000 mol wt that binds radiolabeled SM more avidly than the 150K complex. Patients with GH deficiency appear to have higher levels of this smaller BP while exhibiting decreased tracer binding and endogenous SM in the region of the 150K BP when compared to normals. This suggests the GH dependence of the 150K BP. We report studies on four GH-deficient children who had normal growth and normal SM levels after intracranial surgery. All were hyperphagic and obese at the time of study and were on replacement medications with the exception of GH. Endocrine evaluation revealed mild hyperprolactinemia in three patients and high insulin levels in three. SM-C/insulin-like growth factor I (IGF-I) levels by RIA and IGF-II by radioreceptor assay were normal for age. Sephacryl-200 column chromatography on plasma samples from these patients revealed patterns of tracer binding and endogenous SM migration similar to those of normal and GH-treated hypopituitary patients. The chromatograms were different from those usually seen in untreated GH-deficient patients. SM binding in whole serum was also similar to that observed in normal children (38 +/- 7% [125I]IGF-II bound for patients compared to 39 +/- 3% for controls) and less than that observed in GH-deficient children (48 +/- 5%). These data suggest that the characteristics of SM binding in our patients are similar to those of normal subjects. The regulation of the 150K BP is not accomplished by GH in these patients, although the exact mechanism for the maintenance of serum SM is unclear.     

Exclusion of cardiac myosin heavy chain and actin gene involvement in hypertrophic cardiomyopathy of several French families.

Familial hypertrophic cardiomyopathy (FHC) is characterized by idiopathic myocardial hypertrophy, which often and predominantly involves the interventricular septum. The disease is transmitted as an autosomal dominant trait, and its major risk is sudden death. It was recently demonstrated that this disease is genetically heterogeneous and that in 13 of 18 unrelated families the morbid locus, termed FHC-1, maps to chromosome 14q11-12 in and/or very near the cardiac beta-myosin heavy chain gene. We have performed linkage analysis with five chromosomal markers detecting polymorphisms in either the cardiac beta-myosin heavy chain gene or the cardiac actin gene (located on chromosome 15q) on eight families from different regions of France. We show that 1) it is possible to analyze medium-sized families by using highly informative microsatellite markers located in these genes and 2) the disease is not linked to the two contractile protein genes in any of these families. Moreover, 10-20% of chromosome 14 and 20-40% of chromosome 15 in the vicinity of the respective markers were excluded as possible locations for the morbid locus. These results provide new insights into the identification of the genes responsible for FHC.     

Extra-intestinal manifestations of salmonella infections

While salmonellosis is often considered to affect primarily the gastrointestinal tract, infection at other sites may occur, producing characteristic clinical syndromes. We reviewed cases from our institutions and the literature on focal manifestations of salmonella infections. In the past, most extra-intestinal salmonella infections were caused by S. choleraesuis; however, we found S. typhimurium to be the predominant serotype. The mortality rate for patients in our series was considerably lower than the rate described for focal infections in other reviews. This may in part be due to lower proportion of infections due to S. choleraesuis, improved microbiologic and diagnostic techniques, increased use of ampicillin, and improved surgical techniques. Salmonella endocarditis usually occurs in patients with preexisting heart disease. Unlike other salmonella infections, S. choleraesuis is the most frequent serotype. Salmonella endocarditis is often very destructive, with a fatality rate of 70%. Nonvalvular (mural) endocarditis occurs in one-fourth of patients and survival has not been reported. While antibiotic therapy should be tried initially, if response is not prompt the clinician should look for an associated site of infection (intra- or extra-cardiac abscess), which will often require surgery. Salmonella pericarditis often presents with cardiac or pulmonary symptoms, but typical signs of pericardial disease (pulsus paradoxus, friction rub) or characteristic electrocardiographic changes (low voltage, elevated ST segments) are uncommon. Early diagnosis, before infection involves other areas of the heart, is crucial for survival. In addition to antibiotic therapy, pericardiocentesis or pericardiectomy is required. Salmonella may infect the peripheral or visceral arteries, but the abdominal aorta is the most frequent site of vascular infection. Most patients are men over age 50 with preexisting atherosclerosis of the aorta who do not have a previous history of gastroenteritis. About one-fourth of patients have associated lumbar osteomyelitis. No patients have been reported to survive with medical therapy alone. Specific guidelines for surgical removal of infected aneurysms have been proposed and these (in addition to increased use of ampicillin) may be responsible for higher survival rates in recent years. Due to the high incidence of relapses, postoperative blood cultures should be done routinely. Arterial infection should be considered in any elderly patient with salmonella bacteremia especially with prolonged fever or bacteremia after an "adequate course" of antibiotic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis.

A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-probe analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.     

Polymyalgia rheumatica

Polymyalgia rheumatica is a syndrome that occurs in the elderly and is characterized by pain and stiffness involving the neck, the shoulder girdle, and the hip girdle. The aching should be present for greater than one month. Polymyalgia rheumatica may be more common than reported. The etiology remains unknown. There is generally little found pathologically in this disease. The physical examination is often not impressive. Synovitis may be a main contributing factor to many of the symptoms seen in patients with polymyalgia rheumatica. Symptoms often do not correlate with physical findings. Polymyalgia rheumatica must be differentiated from many conditions since the diagnosis remains entirely clinical. Osteoarthritis, flu syndromes, inflammatory myopathies, fibromyalgia, and depression all have features that may mimic polymyalgia rheumatica. Malignancies and infections may also be difficult to separate from polymyalgia rheumatica. Polymyalgia rheumatica may also be extremely difficult to differentiate from seronegative rheumatoid arthritis in patients older than 50 years. Although some patients with polymyalgia rheumatica have underlying giant cell arteritis, the majority apparently do not. The distinction between polymyalgia rheumatica and giant cell arteritis cannot be made on the basis of laboratory studies and relies solely on clinical symptoms and physical findings. Although nonsteroidal antiinflammatory medications may control symptoms in patients with mild disease, most patients with polymyalgia rheumatica require low-dose corticosteroids. The tapering schedule for the corticosteroids is contingent upon the response of symptoms and laboratory parameters. Polymyalgia rheumatica usually follows a benign course with almost complete response to an adequate treatment program. Recently, there have been several studies suggesting that the course of polymyalgia rheumatica may not be as short and simple as once proposed. Nevertheless, many patients may be completely weaned from corticosteroids. Other agents have been used in this disease, but for the most part their use remains somewhat controversial. Patients must be monitored carefully. Most patients do well, and treatment is effective.