Allan B. Schwartz

Antihypertensive Effect of Clonidine

Clonidine hydrochloride is a sympathetic inhibitor with central site of action. The antihypertensive effect in man in the supine position is associated with a decrease in cardiac output and no consistent changes in total peripheral resistance. In the standing position, however, in addition to the decrease in cardiac output, a fall in total peripheral resistance becomes evident. The fall in blood pressure results in no significant alteration in renal blood flow or glomerular filtration rate in the supine position. In the standing position a consistent decrease in renal vascular resistance is seen. In the anesthetized dog the intravenous administration of clonidine produces a significant reduction of renal vein plasma renin activity. Similarly, in patients with essential hypertension oral administration of the drug results in a decrease in peripheral plasma renin activity. In ambulatory essential hypertensive patients treated with clonidine alone in doses of 400 to 900 μg per day, a modest antihypertensive effect is achieved. When clonidine is used with a diuretic, antihypertensive efficacy is achieved in 80% of the patients treated. In higher doses (up to 3,600 μg per day) and in combination with a diuretic, the antihypertensive effect appears to be superior to that of many of the standard agents. Drowsiness and dryness of the mouth are the most frequent and serious side effects with the higher doses.

Hemodynamics of Hypertension in Chronic End-Stage Renal Disease

This study was undertaken to define the hemodynamic changes in hypertension of chronic end-stage renal disease. Mean cardiac index in 75 uremic patients was higher (P < 0.001) than that of 42 normal volunteers while stroke index was not different from normals. The higher cardiac indices of uremic patients were accounted for by increased heart rates. Despite the significantly higher blood pressure in the uremics, their mean total peripheral resistance index was not different from that of normals.The total group of 75 patients included 52 hypertensive and 23 normotensive uremics. Cardiac index, heart rate, and stroke index were the same in 52 hypertensive and 23 normotensive uremics while mean total peripheral resistance index of hypertensive uremics was higher (P < 0.001) than normotensive uremics. Therefore, the hypertension in end-stage renal disease is sustained by a high total peripheral resistance.Bilateral nephrectomy in 12 hypertensive uremics resulted in no changes in cardiac index; a consistent decrease in blood pressure (P < 0.001) and a decrease in total peripheral resistance index (P < 0.001) occurred. Bilateral nephrectomy in eight additional uremics with malignant hypertension resulted in an actual increase in cardiac index (P < 0.001) with a consistent reduction in blood pressures (P < 0.001) and an even more dramatic decrease in total peripheral resistance (P < 0.001).These findings imply that a vasopressor substance of renal origin increasing peripheral resistance is the major factor in the pathophysiology of renal hypertension in the late stage of its natural history.

Pharmacodynamic Effects of a New Antihypertensive Drug, Catapres (ST-155)

Catapres is a new imidazoline compound with potent antihypertensive properties. Significant reduction in blood pressure occurs between 1 and 4 hours after oral administration, with the peak effect occurring at 2 to 4 hours and the antihypertensive effect extending for 6 to 10 hours. Blood pressure is reduced in both the supine and erect positions, although the orthostatic response is the more prominent.Cardiac output is reduced moderately in both the supine and erect positions. Peripheral vascular resistance is also reduced, particularly in the erect posture. Accordingly, the cardiac hemodynamic findings suggest that the antihypertensive effect of Catapres is related to the combination of reduction in cardiac output plus decrease in peripheral resistance. Renal blood flow and glomerular filtration rate are preserved in both the supine and erect positions following Catapres administration. Contrasting with the preservation of renal blood flow and glomerular filtration rate, however, is the marked reduction in sodium chloride excretion which follows acute administration of the drug.The clinical utility of the drug was demonstrated in the chronic outpatient study. Although Catapres administered alone exerted only modest antihypertensive effects, a markedly enhanced antihypertensive response was achieved when the drug was combined with a potent oral diuretic, with 80% of patients so treated achieving significant blood pressure reduction in both the supine and erect positions.

Potassium-Related Cardiac Arrhythmias and Their Treatment

Severe abnormalities of potassium balance constitute medical emergencies. Symptoms of hypokalemia are vague between 3.5 and 3.0 mEq/liter. Clinical problems can occur with the plasma potassium value lower than 2.7 mEq/liter. Hypokalemia and digitalis glycosides share electrophysiologic actions. Hypokalemia is both synergistic and potentiating for digitalis. In the presence of a normal amount of digitalis, toxicity may be prompted by coexisting hypokalemia. Hyperkalemia does not threaten life until plasma potassium values are greater than 7.0 mEq/liter. The immediate suspicion and recognition of hypokalemia or hyperkalemia in various clinical situations is imperative. Once suspected, confirmation of the diagnosis should follow immediately. Probably the single most useful diagnostic aid is the electrocardiogram, especially in critical situations with hyperkalemia. Prompt intravenous infusion of a calcium preparation, sodium bicarbonate, glucose, and insulin will provide rapid relief from serious hyperkalemia. The appropriate administration of these readily available drugs may obviate an otherwise critical situation.

Predicting success of intensive dialysis in the treatment of uremic pericarditis.

To identify predictors of the success or failure of daily intensive dialysis in uremic pericarditis, a retrospective examination was made of initial clinical, laboratory, and echocardiographic data in 97 patients using univariate and multivariate statistical analysis. In this group, 67 patients showed response to intensive dialysis, and 30 patients did not (22 required surgery and eight died). By univariate analysis, nine factors correlated with intensive dialysis failure (p less than 0.10): admission temperature over 102 degrees F, rales, admission blood pressure under 100 mm Hg, jugular venous distension, peritoneal dialysis treatment only because of severe hemodynamic instability, white blood cell count over 15,000/mm3, white blood cell count left shift, large effusion by echocardiography, and both anterior and posterior effusion by echocardiography. Echocardiographic left ventricular size and function were not useful predictors of success or failure; there was no difference in response to hemodialysis in patients with pericarditis before dialysis (69 percent) versus patients with pericarditis during a maintenance program (67 percent). By discriminant analysis, a seven-variable function was constructed that divided the patients into three groups: (1) those likely to show response to intensive dialysis (48 patients, predictive value of 98 percent), (2) those with an intermediate (38 percent) chance of showing response to intensive dialysis (30 patients), and (3) those unlikely to show response to intensive dialysis (14 patients, predictive value of 100 percent). When the function was applied prospectively to 12 patients (eight with success and four with failure), all were classified correctly. Thus, discriminant analysis of patients with uremic pericarditis allows improved selection of patients with uremic pericarditis likely to have response to daily intensive dialysis and early consideration of alternative forms of treatment in patients unlikely to show response to intensive dialysis. However, the model should be validated in the particular institution where it is to be used before its application.

Myelolipoma in a heterotopic adrenal gland. Light and electron microscopic findings

A symptomatic myelolipoma of the heterotopic adrenal gland was diagnosed as the cause of nephrotic syndrome and was surgically removed. Remission of the nephrotic syndrome promptly ensued. Ultrastructurally, the tumor consisted of well‐differentiated cells resembling adrenal cortical cells, bone marrow cells in various stages of differentiation, and lipid cells. Some cells that contained fat were of adrenal cortical origin, but the derivation of most lipid cells and of bone marrow elements could not be deduced from the present ultrastructural findings.

Surgical Correction of Uremic Constrictive Pericarditis

Abstract Constrictive pericarditis developed in two patients on home hemodialysis. Diagnosis in each case was confirmed by cardiac catheterization, and both patients were successfully treated by pe...

Pulmonary hemorrhage in renal disease: Goodpasture's syndrome and other causes.

Pulmonary hemorrhage is generally due to neoplasm, tuberculosis, necrotizing pneumonia, or bronchiectasis. If these are not found, kidney diseases, including anti-glomerular basement membrane antibody-induced bleeding (Goodpastures syndrome), should be considered. Hemoptysis in renal disease is more often due to azotemic hypervolemia than immune reaction. Typically linear immunofluorescent patterns along the glomerular and pulmonary alveolar basement membranes must be demonstrated to confirm the diagnosis of Goodpastures syndrome.

Expertise: No longer a sine qua non for guideline authors?

: Several sets of guidelines have been published recently and more are in the works. The very recent American College of Physicians/American Academy of Family Practitioners guidelines were put together by a set of authors and consultants without any expertise in the topic under discussion, that is, hypertension. Although we are not maintaining that all guidelines should be written exclusively by experts, complete lack of expertise among guideline authors is not acceptable.

Expertise: No Longer a Sine Qua Non for Guideline Authors?

See Related Editorial, pp 238–239 > Quis custodiet ipsos custodes?—Who will guard the guards themselves? > > —Decimus Iunius Iuvenalis (Juvenal), 1st–2nd century AD, Satire VI, lines 347–348 Guidelines are traditionally scripted by a panel of experts who are intimately familiar with the topic in question. Practicing physicians inherently trust guideline authors and rarely ever question their expertise, especially when guidelines are endorsed by such venerable societies as the American College of Physicians (ACP) and the American Academy of Family Practitioners (AAFP) and are published in high-impact journals, such as the Annals of Internal Medicine . The >250 000 members of the ACP and AAFP have come to expect that any set of clinically meaningful guidelines has been put together by authors who were selected because of their outstanding skills and expertise pertaining to the topic in question. Thus, there is little if any reason to voice doubt as to the validity of published guidelines The Free Dictionary defines expertise as special skills or knowledge acquired by a person through education, training, or experience. For a physician unfamiliar with the experts, there are several simple ways to get a grasp on the quality and quantity of expertise: 1. One can scrutinize the publication list of the experts to assess how often they have been involved with the guideline topic. Any expert is expected to be well published in the specific area of the expertise. 2. One may take into account an expert’s membership in professional organizations pertaining to the subject matter. Obviously, membership and participation in annual meetings demonstrates an ongoing interest in the guideline topic. 3. One may examine whether the physician/scientist has been invited to serve on editorial boards of journals dealing with the topic in question. Being a member of an editorial board and peer reviewing submissions attest to some expertise pertaining to the …