Clinical spectrum of postpartum renal failure

Four patients in whom renal functional abnormalities developed in the postpartum period are discussed. Two patients had a fulminant, fatal course, typical of most of the previously reported cases of postpartum renal failure. The other two patients, however, had only mild, transient renal abnormalities. Pathologically, all four patients showed changes suggestive of fibrin deposition in the renal vasculature. It is suggested that postpartum renal failure includes a spectrum of disease from fulminant renal failure with extensive fibrin deposition to minor renal dysfunction with minimal fibrin deposition.     

Insulin binding to monocytes and insulin sensitivity in anorexia nervosa

In six female patients with anorexia nervosa, we examined specific binding of ¹²⁵I-insuIin to monocytes and in vivo sensitivity to insulin before and after treatment. Insulin sensitivity was determined by the rate of glucose disappearance during an intravenous insulin tolerance test (K_ITT).In the untreated state, the patients with anorexia nervosa were 26 to 41 per cent below ideal weight and amenorrheic. Fasting plasma glucose and insulin levels were, respectively, 20 per cent and 55 per cent below those observed in healthy controls. Insulin binding to monocytes was 70 per cent greater than that in controls. Scatchard analysis of the insulin binding data revealed an increase in binding capacity with no change in binding affinity. During the insulin tolerance test, K_ITT (9.7 ± 0.7 per cent · min^?1) was 50 per cent greater in untreated patients than in healthy controls.Following treatment with behavior modification, there was a gain in body weight to within 2 to 11 per cent of ideal body weight, and menstrual function returned. Plasma glucose and insulin levels rose to values similar to those in healthy controls. Insulin binding declined by 40 per cent to values comparable to those in the controls. The decrease in insulin binding was due to a reduction in binding capacity. The plasma glucose response to the insulin tolerance test (K_ITT) fell 50 per cent below pretreatment values to levels comparable to those in healthy controls.Both before and after treatment, an inverse correlation was observed between plasma insulin concentration and insulin binding to monocytes whereas a direct correlation was demonstrable between insulin binding to monocytes and k_ITT.The data indicate that in anorexia nervosa insulin binding to monocytes and in vivo sensitivity to insulin are increased. The increase in insulin binding may be a consequence of a decrease in plasma insulin and may, in turn, be responsible for the increase in insulin sensitivity. The increases in insulin binding and insulin sensitivity return to normal following regain of body weight.     

New and traditional therapy of congestive heart failure. A European view

Our experiences with new drugs in the therapy of congestive heart failure indicate that nitroprusside infusion favorably influences acute left ventricular failure resulting from acute myocardial infarction. Although this vasodilator is beneficial in improving hemodynamic derangements in the acute phase, its effects on enhancing both short-term and long-term survival in myocardial infarction pump dysfunction remain to be ascertained. Concerning the oral vasodilators, of the agents we have evaluated, oral isosorbide dinitrate has been the most useful in achieving improved cardiac function in chronic hemodynamic overload. In contrast, although long-term administration of oral slow-release phentolamine in chronic ischemic heart disease has decreased, increased left ventricular filling pressure and tended to enhance an increase in cardiac output with exercise, serious side-effects obviate the use of the agent in longterm therapy of cardiac failure. Dobutamine infusion provides pronounced enhancement of abnormal hemodynamics in chronic coronary heart disease; however, its use appears to worsen the degree of myocardial aerobic metabolism in patients with active ischemic heart disease. Digitalis and diuretics still play an important role in the therapy of most instances of chronic congestive heart failure.     

Pharmacokinetics of digoxin and digitoxin in patients undergoing hemodialysis

The pharmacokinetics of digoxin and digitoxin in patients undergoing long-term hemodialysis were examined to determine which is the preferred cardiac glycoside in this patient population.Absorption curves from 0 to 24 hours after an oral dose of digitoxin were similar in dlalyzed patients and in control patients. Serum glycoside concentrations after an oral dose of digoxin were higher in dialyzed patients than in control patients, significantly so from 2 to 24 hours, reflecting the absence of the predominantly renal route of excretion of digoxin.When nine dialyzed patients were placed on a maintenance dose of digoxin, 0.125 mg 5 days a week, serum levels plateaued at 30 days at a mean concentration (± SE) of 0.84 ± 0.05 ng/ml. Maintenance therapy with 0.1 mg digitoxin 5 days a week resulted in stabilization of serum levels within 30 days at a mean concentration of 19 ± 1 ng/ml. Variability in the serum glycoside concentrations was determined after stabilization of levels during 2 to 19 week follow-up periods with each drug. Variability in serum levels was somewhat increased during maintenance therapy with digitoxin. On the basis of the pharmacokinetic data obtained in this study, no clear cut preference for one glycoside over the other could be established.     

Hypertension corrected by discontinuing chronic sodium bicarbonate ingestion: Subsequent transient hypoaldosteronism

A 52 year old man with a long history of marked hypertension, peptic ulcer disease, nephrocalcinosis and intermittent hypercalcemia was referred to be evaluated for primary aldosteronism suspected on the basis of low plasma renin activity, hypokalemia and blood pressure responsive to spironolactone. Aldosterone excretion, however, was extremely low. Alkaluria, high urinary sodium excretion and hypercalciuria were observed. The patient admitted to chronic ingestion of large amounts of baking soda. Upon cessation of alkali abuse, his blood pressure fell dramatically; orthostatic hypotension, concomitant azotemia, hemoconcentration, hyperkalemia and weight loss occurred. Despite dramatic elevation in plasma renin activity, urinary aldosterone excretion remained low during this period. Adrenal glucocorticoid secretion was intact. All abnormalities of sodium, potassium and aldosterone subsequently returned to normal. A 10 day challenge with oral sodium bicarbonate was associated with a rise in blood pressure, but serum calcium remained normal. The patient remains normotensive 15 months after discontinuing alkali abuse.     

Bronchial component in chronic obstructive lung disease

Possible changes in the responsiveness of the airway to nebulized isoproterenol were studied in 69 patients evaluated retrospectively over an average period of 29 months and in 65 additional patients evaluated prospectively over a period of 6 months. Airway resistance (R_aw) decreased more than 15 per cent in 91 per cent of the patients studied retrospectively and in 97 per cent of the patients studied prospectively. Approximately 25 per cent of the group showed significant increases in vital capacity (VC) and maximum expiratory flow rate (EFR_max). Evidence of airway refractoriness was not observed. The variable physiologic response to isoproterenol suggests separation of patients into resistance-reactive, flow-reactive and vital capacity-reactive groups indicating differential response of the functional segments of the airway in chronic obstructive lung disease. Failure of EFR_max to increase after the inhalation of isoproterenol should not be taken as evidence of an unresponsive airway.     

Immunosuppressive therapy of chronic idiopathic thrombocytopenic purpura

The results of 17 courses of immunosuppressive therapy in 12 adult patients with chronic idiopathic thrombocytopenic purpura were compared to those reported in 94 patients in the literature. About 50 per cent of the reported patients with chronic idiopathic thrombocytopenic purpura treated with immunosuppressive drugs have had a successful response. In most of these, however, the idiopathic thrombocytopenic purpura was of short duration which suggests that many of the responses were spontaneous. The probability of response to immunosuppressive agents is much greater in the splenectomized patient than in the nonsplenectomized patient.Azathioprine and cyclophosphamide are the drugs of choice for the immunosuppressive therapy of chronic idiopathic thrombocytopenic purpura. The immunosuppressive effects of cyclophosphamide probably are better, but the potential complications of this drug in patients with chronic idiopathic thrombocytopenic purpura are more serious. Nonsteroidal immunosuppressive therapy should be used as the primary form of treatment only in patients with serious disease who fail to respond to corticosteroid therapy and who are poor risks for splenectomy. One or more courses of nonsteroidal immunosuppressive therapy may be indicated in patients with chronic refractory idiopathic thrombocytopenic purpura with life-threatening disease. It is expected that from 15 to 35 per cent of adults and probably more children with chronic refractory idiopathic thrombocytopenic purpura will have a successful response.The use of nonsteroidal immunosuppressive drugs in patients with chronic idiopathic thrombocytopenic purpura remains experimental and involves uncertain risks to the patient.     

Cellular immune findings in Lyme disease. Correlation with serum IgM and disease activity

Cellular immune findings were studied in 48 patients with various stages of Lyme disease. At each stage, some patients, particularly those with neuritis or carditis, had elevated serum IgM levels and lymphopenia. During early disease, mononuclear cells tended to respond normally to phytohemagglutinin, and spontaneous suppressor cell activity was greater than normal. Later, during active neuritis, carditis, or arthritis, the trend was toward heightened phytohemagglutinin responsiveness and less suppression than normal. By multiple regression analysis, serum IgM levels correlated directly with disease activity (p = 0.025) and inversely with the number of T cells (p = 0.02); during acute disease only, elevated IgM levels correlated with increased phytohemagglutinin responsiveness (p = 0.004) and decreased suppressor cell activity (p = 0.03). Decreased suppression, observed later in the disease, may permit damage to host tissues because of either autoimmune phenomena or a heightened response to the Lyme spirochete.     

Amenorrhea and edema.

In a 22 year old woman extensive edema developed during evaluation for amenorrhea. It was learned then that she was consuming escessive amounts of a laxative daily. Balance studies were performed which demonstrated that she excreted large amounts of sodium in her liquid stools while taking the dose of laxative she had been using. The presence of increased plasma renin activity and increased urinary aldosterone suggest that in this patient the occurrence of the edema after she discontinued use of the laxative was due to secondary aldosteronism presumably caused by plasma volume depletion.     

Activation of Hageman factor in the nephrotic syndrome

The patient described had the nephrotic syndrome associated with decreased levels of plasma coagulation factors XI (35 per cent) and XII (15 per cent). The patient also had a decrease in concentration of prekallikrein and kallikrein inhibitor, suggesting that the kallikrein system was activated. Addition of purified factor XII did not correct this defect. The fibrinolytic system was activated as indicated by an increase in fibrinogen split products. Thus, it seems that three Hageman-dependent proteolytic pathways (coagulation, fibrinolysis and kallikrein) were activated in this patient with the nephrotic syndrome.Another possible cause of decreased factors XI and XII is urinary loss of these proteins. The urine did contain apparent activities of factors XI and XII. The finding of factor VIII in the urine in higher concentrations than XI or XII, however, as well as the inability to adsorb the activity with Celite®, suggested that the activity was due to a nonspecific urinary procoagulant. This hypothesis was confirmed by removal of the activity via adsorbtion of the urine with barium citrate.     

Low dose radioiodide thyroid ablation in postsurgical patients with thyroid cancer

Sixty-four patients with well-differentiated carcinoma of the thyroid were treated with initial high (80 to 100 mCi) or low (less than 30 mCi) doses of I¹³¹ after bilateral subtotal thyroidectomy. A total of 36 patients in the various histologic categories were initially treated with the low dose of I¹³¹ (group 1), and a total of 28 patients were treated with the higher dose (group 2). Disease-free criteria were no visible tissue in the neck or body, a protein-bound radioactive iodine (PBI¹³¹) of less than 0.005 per cent per liter at seven days and/or whole body retention of less than 3 per cent at seven days. Of the patients receiving less than 30 mCi (group 1), 56 per cent with papillary carcinoma, 67 per cent with follicular carcinoma and 56 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Of the patients receiving the higher dose of I¹³¹ (group 2), 67 per cent with papillary carcinoma, 50 per cent with follicular carcinoma and 67 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Disease-free mean follow-up time was 5.17 years (group 1) and 5.82 years (group 2). There was no statistical difference in these mean follow-up times, nor was there a statistical difference in the net (total minus initial) dose of I¹³¹ needed to render the patient disease-free. These data demonstrate that low dose I¹³¹ therapy is as effective as the larger more routine doses of I¹³¹ given in this disease.     

Anaplastic thyroid cancer presenting with hyperthyroidism

Primary thyroid malignancies typically do not interfere with thyroid function. A patient is reported with anaplastic thyroid carcinoma presenting with hyperthyroidism; this is believed to be the first such case described. Prior to the onset of the thyroidal process, the patient was clinically euthyroid. It is concluded that the mechanism of thyrotoxicosis is analogous to that of subacute thyroiditis: rapid tissue necrosis with resultant release of thyroid hormone.     

Prazosin and congestive heart failure: Short- and long-term therapy

Reviewed here are the data from 34 patients given prazosin for chronic intractable heart failure. In 13 patients in whom hemodynamics were measured after the fifth 3 mg dose of prazosin was given, no attenuation was found. The cardiac index increased from 1.77 ± 0.13 to 2.5 ± 0.13 liters/min/m² (p < 0.001), and the pulmonary capillary wedge pressure decreased from 31.46 ± 1.56 to 23.54 ± 1.11 mg Hg (p < 0.001).During long-term follow-up (15.9 ± 1.5 months) the administration of spironolactone proved to be very useful. Within three months of starting prazosin therapy, none of the 15 patients discharged on a regimen of spironolactone needed readmission for edema, but 11 of the 13 patients discharged without a spironolactone regimen did. The addition of spironolactone or an increase in furosemide to the therapeutic regimen was helpful but a change to hydralazine was not.We conclude that prazosin causes short-term hemodynamic and long-term clinical improvement in patients with intractable heart failure; that spironolactone helps to prevent clinical attenuation but that more detailed studies are required to better characterize the attenuation to vasodilators seen in patients with congestive heart failure.     

Outpatient treatment of juvenile-onset diabetes with a preprogrammed portable subcutaneous insulin infusion system

Seven patients with juvenile-onset, insulin-dependent diabetes (aged 13 to 32 years) were continuously treated for 12 to 32 weeks while out of the hospital in their usual environment with a portable, batterypowered infusion pump which delivers insulin subcutaneously in basal (between-meal) doses with pulse dose increments before meals. Mean blood glucose levels (237 ± 28 mg/dl during conventional insulin therapy) fell to 105 ± 5 mg/dl after four weeks of pump treatment (p < 0.01) and were maintained at 80 to 104 mg/dl as pump treatment was continued beyond eight weeks. Glycosylated hemoglobin levels (16.0 ± 1.5 per cent before pump therapy) also fell within two weeks (p < 0.01) reaching normal values (9.9 ± 0.3) after eight weeks of pump therapy. Mean plasma cholesterol and triglyceride levels were elevated during conventional therapy and fell to normal after pump treatment. After the first month of pump treatment, only minor adjustments in insulin dose (< 5 per cent of total daily dose) were made. No episode of mechanical pump failure occurred during the 1,110 patient-days of treatment. Overinsulinization and underinsulinization due to human error were relatively rare (four and six episodes, respectively) and failed to result in symptoms of hypo- or hyperglycemia. All patients performed their usual home, work or school activities during pump treatment. We conclude that normalization or near normalization of blood glucose levels can be achieved with a portable subcutaneous insulin infusion system when continuously used to treat patients with juvenile-onset, insulindependent diabetes outside the hospital for three to eight months.     

Nonpharmacologic therapy for hypertension.

Nonpharmacologic treatment for hypertension, including behavioral therapy, weight and/or salt reduction and exercise has been proposed as an alternative or as an adjunct to accepted drug therapy. Behavioral technics, especially the relaxation response, a modification of transcendental meditation, have successfully lowered blood pressure ($\text{10}\text{5}$ mm Hg) in small numbers of highly motivated patients, but the general applicability and success of these technics have been questioned. Biofeedback uses complex instrumentation to inform the patient of his or her moment-to-moment blood pressure and can assist the patient in voluntarily learning to lower it. In studies carried out with biofeedback, small reductions in blood pressure have been achieved. Substantial weight and salt reduction will lower blood pressure, and recent studies suggest that even modest reductions in weight (averaging 9.5 kg on a 800 to 1,200 calorie diet) or salt intake (157 meq/day) may be adequate antihypertensive therapy for many patients. Regular exercise has also been advocated, but data are too fragmentary to draw any firm conclusions as to its efficacy for the general hypertensive population. Long term follow-up of all of these nonpharmacologic methods of treatment has not yet been reported, and only preliminary information is available on simultaneous use of several methods to see if synergy occurs. Patient adherence to these life-style modifications is uncertain, and no data demonstrating the reduction of cardiovascular mortality and morbidity have been obtained as yet Since nonpharmacologic treatment for hypertension is inexpensive and probably safe, the time is right for extensive research to determine the efficacy, applicability, patient compliance and safety of this approach.     

Atypical lymphoma with prolonged systemic remission after splenectomy. Description of three cases

Three patients with an unusual clinicopathologic picture and a striking response to splenectomy are described. All three presented with fever and severe systemic symptoms, pancytopenia and splenomegaly. Two of the patients had hypogammaglobulinemia and absent delayed hypersensitivity. Atypical lymphohistiocytic proliferation consistent with lymphoma was present in the spleen in all three patients, and also in the bone marrow and abdominal lymph nodes in two. Splenectomy led to prompt and prolonged clinical remissions in all three patients, possibly of a permanent nature in one.     

A familial glucagonoma syndrome: Genetic,Clinical and Biochemical Features

A family with multiple endocrine neoplasia type I (MEN-I) is described in which three members had A-cell pancreatic tumors. Two of these members had classic glucagonoma syndromes. The proband, a 62 year old woman, had a high (≤9.2 ng/ml) basal plasma glucagon level, most of which eluted in the 3,500 dalton fraction. Plasma glucagon increased following the ingestion of mixed meals and arginine. Secretin, which, in the dog, has been reported to inhibit normal glucagon secretion, provoked a twofold increase in 3,500 dalton plasma glucagon concentration. Increased plasma glucagon in the proband was associated with mild hyperglycemia and insulin resistance. Somatostatin infusion suppressed peripheral glucagon and insulin levels, and increased blood glucose levels. The unique responses to secretin and somatostatin observed in this patient may be diagnostically important in syndromes of inappropriate or autonomous glucagon secretion.