Cure of cryptococcemia and preservation of graft function in a renal transplant recipient.

Disseminated cryptococcosis with cryptococcemia occurred in a renal transplant patient in whom immunosuppression was continued throughout antifungal therapy in an effort to ensure graft viability. Despite the initial presence of positive fungal cultures of blood, urine, and CSF, infection cleared rapidly, and there has been no evidence of recurrence. Throughout this period, renal function remained unaltered. This favorable outcome suggests that the prognosis for the renal transplant recipient with disseminated cryptococcosis may be improved.

Influence of renin levels on the treatment of essential hypertension with thiazide diuretics.

Initial plasma renin activity (PRA) was measured in 213 patients with untreated hypertension before beginning thiazide (chlorothiazide and hydrochlorothiazide) therapy alone to test whether patients with low-renin hypertension exhibited a greater response to diuretic therapy. Diastolic blood pressure response to treatment in the low, mid-range, and high PRA groups did not differ significantly (delta diastolic blood pressure, -13.6 +/- 1.6, -11.6 +/- 1.5, and -10.8 +/- 2.6 mm Hg, respectively). Moreover, eight subjects with the highest PRA values exhibited the same magnitude of decrease in diastolic blood pressure as did the low PRA group (15.0 +/- 4.2 vs 13.6 +/- 1.6, respectively). This study thus provides no evidence for increased sensitivity to diuretic therapy among patients with low-renin essential hypertension.

Side effects of calcium channel blockers.

Calcium channel blocking drugs are a chemically heterogenous group, so it might be expected that their effects on vascular smooth muscle, cardiac contractility, and conduction tissue may differ. However, the majority of adverse reactions are predictable from their pharmacological actions and may be conveniently grouped in the following categories: 1) vasodilatation, 2) negative inotropic effects, 3) conduction disturbances, 4) gastrointestinal effects, 5) metabolic effects, and 6) drug interactions. Vasodilatory symptoms, namely, dizziness, headaches, flushing sensation, and palpitation, are more likely with nifedipine. Peripheral edema is also common with nifedipine, but the mechanism is uncertain. For a given degree of vasodilation, the greatest negative inotropic effect is seen with verapamil first, diltiazem second, and nifedipine last. Calcium channel blocking drugs are contraindicated in hypertensive patients with second and third degree heart block, sick sinus syndrome, and severe heart failure. Verapamil and diltiazem have a significant effect on cardiac conduction, whereas nifedipine, in therapeutic doses, does not. Local gastrointestinal symptoms, such as nausea and constipation, are common with verapamil. None of the calcium channel blocking drugs have been reported to adversely affect lipid or protein metabolism. However, nifedipine, verapamil, and diltiazem in high doses may inhibit liberation of insulin. The significance of this finding needs to be explored further in hypertensive diabetics. Serum digoxin levels have been shown to increase after administration of verapamil and nifedipine, but there is no evidence that this change has any clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between blood pressure and renin, renin substrate, angiotensin II, aldosterone and urinary sodium and potassium in 574 ambulatory subjects.

Five hundred and seventy-four ambulatory subjects with blood pressures ranging from 94/58 to 250/145 mm Hg were studied on their usual dietary and sodium intake. Renin, renin substrate, angiotensin II, aldosterone and urinary sodium and potassium were compared with blood pressure to access the contribution of these variables to the blood pressure variance. Our analyses revealed that renin substrate was highly and positively correlated with diastolic blood pressure (r = +0.39; p < 0.00001) but all other components of the renin-aldosterone system exhibited a significant negative correlation with blood pressure. A highly significant relationship between potassium, the renin-aldosterone system and blood pressure was found but no such relationship could be demonstrated for sodium. Subjects with higher blood pressures had lower urinary potassium concentrations and lower potassium/creatine ratios. These findings raised the possibility of a significant pathogenetic relationship between potassium and high blood pressure. Multiple linear regression reveals that influences of the renin-angiotensin-aldosterone system can only account for less than 20% of the variance exhibited by the blood pressure in these subjects.

Hypertension following coronary artery bypass surgery. Role of preoperative propranolol therapy.

Over a 9-month period, the incidence and characteristics of hypertension following coronary artery bypass surgery were studied in a group of 52 patients. Hypertension occurred in 61% of the patients and was characterized by an increase in arterial blood pressure of 35 +/- 2 mm Hg mean +/- SEM during the early postoperative period. Preoperative blood pressures and hemodynamic variables were similar in those who developed hypertension of those who remained normotensive. Ninety-four percent of those who developed hypertension as compared to only 40% of those who remained normotensive received propranolol during the 24 hours preceding surgery (x2 = 15.4; p less than 0.001). Maximal blood pressures during the first 5 hours following the termination of cardiopulmonary bypass were significantly positively correlated with preoperative propranolol dosage (p less than 0.01). Hypertension was not associated with significant changes in plasma renin activity or angiotensin II levels, but concomitant plasma catecholamine concentrations were elevated significantly (p less than 0.005). However, a similar rise in plasma catecholamine concentrations was found in those who remained normotensive. Hypertension was associated with an increase in systemic vascular resistance (p less than 0.001) and left ventricular stroke work index (p less than 0.05), and a fall in stroke volume (p less than 0.005) and cardiac index (p less than 0.001). These studies suggest that hypertension following coronary artery bypass surgery is common, results from an increase in systemic vascular resistance, is not renin-angiotensin mediated, and may, in part, be related to preoperative propranolol administration.

Patterns of care for hypertension among hospitalized patients.

In a sample of 19,210 adult inpatients discharged from Maryland community hospitals in 1978, 1 in 4 had either an elevated diastolic blood pressure greater than or equal to 100 mmm Hg (3,338) or a diagnosis of hypertension (1,233). Among the patients with elevated blood pressure, hypertension was disgnosed in 44 percent, and 48 percent received advice concerning followup care. Likewise, of the patients with diagnosed hypertension, 72 percent were treated in the hospital, and 70 percent received advice concerning followup care. Age, race, and sex differences were significant. White male were least likely to have hypertension diagnosed, to be treated for it, or to receive instruction about it. The survey results were used to the Maryland State Department of Health and Mental Hygiene to formulate a statewide high blood pressure coordination plan and to construct modules for the education of professional in high blood pressure treatment and control. A followup survey is planned to evaluate the effect of these efforts.

Renal artery angioplasty. Technical considerations and results.

Renal angioplasty was attempted on 38 renal arteries in 34 patients and was technically successful in 84.2%. Twenty-four patients were followed for 1 to 36 months (mean 15.3 months). The hypertension was cured or improved in 18 (75%), unchanged in 2 and recurrent after an initial period of improvement in four. Six patients were not available for further evaluation as five had additional renovascular surgery and one was lost to followup. Four patients had major complications; loss of the kidney occurred in one patient (2.9%). Respiratory renal mobility, predilatation with tapered teflon catheters and the contralateral femoral approach were found to be important technical aids for successful renal artery angioplasty.

Collaborative development for setup, execution, sharing and analytics of complex NMR experiments.

Factory settings of NMR pulse sequences are rarely ideal for every scenario in which they are utilised. The optimisation of NMR experiments has for many years been performed locally, with implementations often specific to an individual spectrometer. Furthermore, these optimised experiments are normally retained solely for the use of an individual laboratory, spectrometer or even single user. Here we introduce a web-based service that provides a database for the deposition, annotation and optimisation of NMR experiments. The application uses a Wiki environment to enable the collaborative development of pulse sequences. It also provides a flexible mechanism to automatically generate NMR experiments from deposited sequences. Multidimensional NMR experiments of proteins and other macromolecules consume significant resources, in terms of both spectrometer time and effort required to analyse the results. Systematic analysis of simulated experiments can enable optimal allocation of NMR resources for structural analysis of proteins. Our web-based application (http://nmrplus.org) provides all the necessary information, includes the auxiliaries (waveforms, decoupling sequences etc.), for analysis of experiments by accurate numerical simulation of multidimensional NMR experiments. The online database of the NMR experiments, together with a systematic evaluation of their sensitivity, provides a framework for selection of the most efficient pulse sequences. The development of such a framework provides a basis for the collaborative optimisation of pulse sequences by the NMR community, with the benefits of this collective effort being available to the whole community.

A small molecule that displays marked reactivity toward copper- versus zinc-amyloid-ß implicated in Alzheimer's disease.

Alzheimer's disease (AD) is a complex, multifactorial, neurodegenerative disease that poses tremendous difficulties in pinpointing its precise etiology. A toolkit, which specifically targets and modulates suggested key players, may elucidate their roles in disease onset and progression. We report high-resolution insights on the activity of a small molecule (L2-NO) which exhibits reactivity toward Cu(II)-amyloid-ß (Aß) over Zn(II)-Aß.

Benchmarking NMR experiments: a relational database of protein pulse sequences.

Systematic benchmarking of multi-dimensional protein NMR experiments is a critical prerequisite for optimal allocation of NMR resources for structural analysis of challenging proteins, e.g. large proteins with limited solubility or proteins prone to aggregation. We propose a set of benchmarking parameters for essential protein NMR experiments organized into a lightweight (single XML file) relational database (RDB), which includes all the necessary auxiliaries (waveforms, decoupling sequences, calibration tables, setup algorithms and an RDB management system). The database is interfaced to the Spinach library (http://spindynamics.org), which enables accurate simulation and benchmarking of NMR experiments on large spin systems. A key feature is the ability to use a single user-specified spin system to simulate the majority of deposited solution state NMR experiments, thus providing the (hitherto unavailable) unified framework for pulse sequence evaluation. This development enables predicting relative sensitivity of deposited implementations of NMR experiments, thus providing a basis for comparison, optimization and, eventually, automation of NMR analysis. The benchmarking is demonstrated with two proteins, of 170 amino acids I domain of alphaXbeta2 Integrin and 440 amino acids NS3 helicase.

Iatrogenically induced hypertensive encephalopathy.

A 49-year-old female with a 30-year history of untreated essential hypertension was noted to have a blood pressure of 290/175 mmHg during evaluation for elective gynecological surgery. At the time of hospitalization she complained chiefly of chronic frontal headaches. Physical examination revealed grade two hypertensive retinopathy, and laboratory studies showed left ventricular hypertrophy. Over the next 12 days the patient's blood pressure was successfully lowered to 178/106 mmHg. During revision of her therapy her mean blood pressure rose to 244/144 mm Hg (88% of the admission level) over 36 hours and she developed hypertensive encephalopathy with papilledema, headaches and projectile vomiting. Concomitant resolution of neurological symptoms and control of blood pressure occurred over the next nine days. The course of this patient suggests that autoregulation of cerebral blood flow may be acutely reversed and that the occurrence of hypertensive encephalopathy depends not only on the magnitude and duration of the blood pressure elevation but, more important, on the rate at which that blood pressure is attained.

Cyproheptadine in the control of Cushing's disease.

A patient with Cushing's disease was treated with cyproheptadine with concomitant remission of the disease for 60 months. Despite clinical improvement and achievement of normal levels of cortisol excretions, her menstruation-related cyclic surge of cortisol secretion was supranormal. The mode of action of cyproheptadine was studied by the administration of metyrapone. Long-term administration of cyproheptadine appeared to normalize excessive adrenocorticotropic hormone (ACTH) production by reducing the frequency and the peak levels of episodic secretion of ACTH.

Cure of cryptococcal infection during continued immunosuppressive therapy.

Cryptococcus neoformans is a significant pathogen in immunosuppressed patients. In renal transplant recipients receiving prednisone, the development of cryptococcosis is associated with a poor prognosis. When such patients develop cryptococcosis they pose a particularly difficult clinical dilemma since withdrawal of prednisone, to facilitate cure of their fungal infection, may predispose to loss of their transplanted kidney. We report our experience with cryptococcal infection in 13 renal transplant patients. In 11 of these patients maintenance immunosuppression was cautiously continued to preserve allograft function. The results of our study suggest that maintenance immunosuppressive therapy may be continued throughout the period of antifungal therapy and does not preclude eradication of the infecting organisms. Our experience indicates that the prognosis for the renal transplant patient who has cryptococcosis can be improved.