Blood pressure independent effects of nitrendipine on cardiac structure in patients after renal transplantation

Left ventricular hypertrophy is well established as a blood pressure independent cardiovascular risk factor in patients on renal replacement therapy. The effects of antihypertensive treatment on myocardial structure and function in renal transplant recipients have been so far only rarely investigated. In a double-blind, placebo-controlled study patients were randomized to the calcium channel blocker nitrendipine or placebo if the transplanted kidney had developed a stable phase. Normotensive patients received nitrendipine 2 x 5 mg daily or placebo, hypertensive patients received 2 x 10 mg up to 2 x 20 mg nitrendipine daily or placebo. To achieve adequate blood pressure control, all patients with still elevated blood pressure on study medication received antihypertensive drugs other than calcium channels blockers. Ambulatory blood pressure recording and 2D-guided M-mode echocardiography were performed at baseline and upon completion of the study. In addition, laboratory workup (including serum creatinine and lipids) was done, and serum aldosterone, plasma renin activity, plasma angiotensin II and blood glucose levels were measured in all patients at baseline and after at least 12 months of therapy. Ambulatory blood pressure was almost identical between both groups at study baseline and follow-up. In renal transplant patients on nitrendipine, posterior wall thickness (-0.10 +/- 1.77 mm) and septal wall thickness (-0.83 +/- 2.23 mm) did not change significantly from baseline. In contrast, posterior wall thickness (0.71 +/- 0.92 mm, P < 0.01) and septal wall thickness (0.97 +/- 2.20 mm, P < 0.05) increased in patients on placebo, which differed from the observed changes on nitrendipine (ANOVA: P = 0.093 and P = 0.048, respectively). Relative wall thickness, a parameter for concentric left ventricular hypertrophy, became numerically smaller on nitrendipine therapy from 0.46 +/- 0.07 to 0.44 +/- 0.09 (-0.02 +/- 0.09, NS) but increased from 0.42 +/- 0.08 to 0.48 +/- 0.08 in the placebo arm (+0.04 +/- 0.08, P < 0.02), which was also significant between the two groups (ANOVA: P = 0.036). Endocrine parameters, lipids and blood glucose were not different between the two groups. We conclude from these data that the calcium channel blocker nitrendipine exerted beneficial effects on cardiac structure in patients after renal transplantation independent of blood pressure.     

Donor treatment with the lazeroid U74389G reduces ischemia-reperfusion injury in a rat lung transplant model

BACKGROUND: Antioxidant treatment with lazeroids has proven beneficial for the amelioration of reperfusion injury in experimental lung transplantation. This study compares the effect of donor versus recipient treatment on immediate postoperative graft function. METHODS: A model of acute double-lung transplantation in rats was used to assess graft function. Transplanted controls after 2 (group I) and 16 hours of ischemia (group II) were compared to a recipient (group III; 16-hour ischemia) and a donor treatment group (group IV; 16-hour ischemia) using the lazeroid U74389G (6 mg/kg). Serial assessment of alveolar-arterial oxygen difference, dynamic lung compliance, airway and pulmonary vascular resistance was obtained during a 2-hour reperfusion period. Final analysis included survival, weight gain, and histologic examination. RESULTS: Graft function was significantly better after 2 hours of ischemia than in any of the three 16-hour ischemia groups (II, III, IV). After 16 hours of ischemia, donor treatment provided superior graft function with respect to dynamic lung compliance, airway resistance, and alveolar-arterial oxygen difference when compared with groups II and III. The pulmonary vascular resistance was significantly higher in group III when compared with groups II and IV. Graft weight increase reflecting edema was highest in groups III (104%) and II (98%). CONCLUSIONS: After prolonged ischemia only donor treatment with the lazeroid U74389G was able to significantly reduce ischemia-reperfusion-related graft dysfunction.     

Circadian rhythms in the Zucker obese rat: assessment and intervention

The proximate determinants of fertility framework, developed in its current form by Bongaarts, has been used extensively by researchers for the past 20 years. Since the initial framework was developed, a wealth of new survey data on the proximate determinants has become available. This article reviews the new data and past experiences and suggests modifications to the framework that would take advantage of this experience. The major modifications suggested are (1) the use of sexual activity rather than marriage to indicate exposure to pregnancy; (2) a revision of the sterility index to measure infecundity from all causes; (3) a revised index of contraception that accounts for the fact that users of sterilization may become infecund before age 49; and (4) a revised definition and estimate of total fecundity.     

Responsiveness of the adult male rat reproductive tract to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1 induction, and Ah receptor down-regulation

Cardiovascular diseases (CVD), principally coronary heart disease (CHD), stroke, and congestive heart failure, continue to be the leading cause of death claiming nearly 1,000,000 lives annually and accounting for more than 40% of the deaths in the United States (American Heart Association). While cardiovascular disease is often viewed as a problem of the elderly, 45% of heart attacks occur among individuals less than 65 years old. Moreover, CVD is the second leading cause of death for those 45 to 64 years of age and the third leading cause of death for those 25 to 44 years old. In economic terms, the annual direct and indirect costs of heart attack and stroke are approximately $259 billion or $492,444/second, in the United States alone. Thus, from a human and economic perspective, heart and vascular diseases are an enormous burden worthy of significant attention. This review is not intended to ignore the 50% decline in age-adjusted rates for heart attack and stroke events over the preceding three decades, as summarized by the recent report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI). However, progress has halted as coronary heart disease and stroke mortality rates have reached a plateau in recent years and appear to be rising. Consequently, this is an excellent time for re-examining our approach to the prevention and treatment of CVD. In this article, readers will find an overview of the CVD prevention and treatment topics and not an in-depth analytical or epidemiological assessment of risk factors and outcomes. First, a macroscopic approach to reducing CVD is presented, followed by a discussion emphasizing the critical importance of public health and community-based programs in the effort to significantly reduce the burden of hypertension and related cardiovascular morbidity and mortality. Effective public health programs can play a pivotal role in raising awareness, and more importantly, in facilitating lifestyle change, entry and retention in the healthcare system, and compliance with non-pharmacological as well as drug therapy.     

Every sperm is sacred--or is it?

We have the opportunity to present a rare case of late local recurrence after treatment of intrascrotal extratesticular malignant schwannoma with rhabdomyoblastic features in an adult man. As our case is the first in the literature, we want to inform the reader about the long-term follow-up of our patient and suggest that these tumors may have a long survival and late recurrences may occur even after 5 years postoperatively.     

Application of automatic image segmentation to tibiae and vertebrae from ovariectomized rats

Aqueous extracts from various crude drugs showing a selective inhibition on the induction or effector phase of delayed-type hypersensitivity (DTH) reaction were applied to the new model of liver injury induced in mice by picryl chloride(PCl)-induced DTH. The inhibiting drugs to the induction phase of DTH, Fructus Triburi (FT) and Er-Miao-San (EMS), showed a remarkable improvement against the elevation in serum transaminase levels as well as in histopathological changes when given during this phase. The administration in the effector phase by Rhizoma Smilacis Glabrae (RSG) and Cortex Dictamni (CD), selectively inhibiting the phase of DTH, also significantly improved the liver damage. In addition, RSG and CD showed an almost complete recovery of serum alkaline phosphatase from a persistent decrease in the sustaining process of liver injury when given consecutively for 4 weeks after the elicitation of liver injury. Cyclophosphamide, an immunosuppressive agent, significantly inhibited the enzymatic elevation given in either phase, while it did not affect the ability to sustain liver injury. When the above extracts were given in a combined manner to the same mouse during these two phases, respectively, FT with RSG and EMS with CD showed a distinct synergism against the liver injury. RSG or CD also enhanced the activity of prednisolone in suppressing PCl-induced ear contact sensitivity. These findings suggest that this immunological liver injury may be regulated by a set of selective suppressants to DTH reaction and the suitable application of such agents may pave the way for a new strategy in treating liver damage.     

PD98059 is an equipotent antagonist of the aryl hydrocarbon receptor and inhibitor of mitogen-activated protein kinase kinase

Striatal dopamine transporter function and dopamine D2 receptor status were evaluated in 15 patients with early untreated Parkinson's disease using single photon emission tomography (SPECT) with 123I-Iodo-2beta-carboxymethoxy-3beta-(4-idiophenyl)tropane (beta-CIT) and 123I-Iodobenzamide (IBZM) as pre- and postsynaptic ligands. Symptoms were unilateral in five patients and bilateral but asymmetric in 10 patients. Patients with bilateral symptoms had significantly lower 18-hour striatal/cerebellar beta-CIT binding ratios (3.59 +/- 0.79) than hemiparkinsonian patients (5.76 +/- 1.48, p < 0.05) reflecting more advanced disease in this subgroup. Patients with bilateral parkinsonism were also found to have a significant side-to-side difference in striatal beta-CIT binding with more marked reduction contralateral to the presenting limb (18-hour striatal/cerebellar ratio: 4.13 +/- 0.78 [ipsilateral] versus 3.59 +/- 0.79 [contralateral], p < 0.05). Dopamine D2 receptor binding as measured by IBZM was significantly elevated contralateral to the affected side in hemiparkinsonian patients (striatal/cerebellar ratio: 2.42 +/- 0.90 [contralateral] versus 2.19 +/- 0.80 [ipsilateral], p < 0.05). This asymmetric upregulation was absent in the patients with bilateral parkinsonism (striatal/cerebellar ratio: 1.85 +/- 0.43 [contralateral to more severely affected side] versus 1.83 +/- 0.34 [ipsilateral], p > 0.05). Our data suggest that postsynaptic dopamine receptor upregulation contralateral to the presenting side occurs in untreated unilateral PD and disappears in untreated bilateral (asymmetric) PD despite a greater loss of dopamine transporter function. Combined beta-CIT and IBZM SPECT studies may be helpful to monitor the progression of nigrostriatal dysfunction in early PD.     

Association of parvovirus B19 genome in children with myocarditis and cardiac allograft rejection: diagnosis using the polymerase chain reaction

BACKGROUND: Inflammatory diseases of the heart, including myocarditis and cardiac transplant rejection, are important causes of morbidity and mortality in children. Although viral infection may be suspected in either of these clinical conditions, the definitive etiology is often difficult to ascertain. Furthermore, the histology is identical for both disorders. Coxsackievirus has long been considered the most common cause of viral myocarditis; however, we previously demonstrated by polymerase chain reaction (PCR) analysis that many different, and sometimes unexpected, viruses may be responsible for myocarditis and cardiac rejection. In this study, we describe the association of parvovirus genome identified through PCR analysis of cardiac tissue in the clinical setting of myocarditis and cardiac allograft rejection. METHODS AND RESULTS: Myocardial tissue from endomyocardial biopsy, explant, or autopsy was analyzed for parvovirus B19 using primers designed to amplify a 699-base pair PCR product from the VP1 gene region. Samples tested included those obtained from patients with suspected myocarditis (n=360) or transplant rejection (n=200) or control subjects (n=250). Parvoviral genome was identified through PCR in 9 patients (3 myocarditis; 6 transplant) and no control patients. Of the 3 patients with myocarditis, 1 presented with cardiac arrest leading to death, 1 developed dilated cardiomyopathy, and the other gradually improved. Four of the 6 transplant patients had evidence of significant rejection on the basis of endomyocardial biopsy histology. All transplant patients survived the infection. CONCLUSIONS: Parvovirus is associated with myocarditis in a small percentage of children and may be a potential contributor to cardiac transplant rejection. PCR may provide a rapid and sensitive method of diagnosis.