Recovery of adrenal reserve following treatment of disseminated South American blastomycosis

South American blastomycosis commonly involves the adrenal glands as proved in autopsy series, although clinical adrenocortical insufficiency is infrequently suspected. In 1972, an Ecuadorian man was seen with disseminated paracoccidioidomycosis and Addison's disease documented by low basal steroid levels and lack of response to ACTH therapy. The patient has since been treated with a total dose of 4,000 mg of amphotericin B. He discontinued all steroid replacement therapy for two years but remained asymptomatic. Recent evaluation documented improvement in basal steroid production, particularly mineralocorticoids. Adrenal reserve has also been demonstrated by the response of glucocorticoids to ACTH stimulation. This is the first well documented case in which adrenal reserve was recovered following treatment of granulomatous Addison's disease.     

Candida arthritis. A manifestation of disseminated candidiasis.

Fungal infections infrequently involve the joints. Review of the literature reveals that Candida arthritis is rare, that it is usually a complication of disseminated candidiasis and that it occurs as a primary joint infection without spread from adjacent osteomyelitis. In the patient we describe Candida arthritis and bursitis of separate joints developed as a late manifestation of disseminated infection following "transient" C. tropicalis fungemia. Treatment consisting of aspiration and parenteral amphotericin B eradicated the joint infection without the need for surgery. Bursectomy, however, was required to eradicate the bursal infection. Awareness of this as well as other late complications of candidemia which signify disseminated infection is important. Optimal therapy will be determined only by further clinical experience with this unusual manifestation of Candida infection.     

Disseminated paracoccidioidomycosis (South American blastomycosis) in the United States

Paracoccidioidomycosis or South American blastomycosis (SAB) is a systemic mycosis endemic to South America but rarely recognized in North America. Visceral dissemination has not been described in the eight cases previously reported from the United States. The patient we describe represents the first case of visceral disseminated SAB, with testicular, adrenal and probable hepatic involvement, diagnosed in the United States. The pathogenesis, clinicopathologic manifestations and therapy of SAB, with particular attention to disseminated paracoccidioidomycosis with adrenal insufficiency, is reviewed.     

Bacterial invasion of pulmonary vessels: Pseudomonas bacteremia mimicking pulmonary thromboembolism with infarction

Pseudomonas aeruginosa displays a curious propensity for invading blood vessels and causing vessel wall necrosis. This bacteremiarelated “vasculitis” is often associated with hemorrhagic necrosis and infarction of surrounding organ parenchyma. With the exception of skin lesions, however, clinical manifestations of Ps. aeruginosa vasculitis seldom occur. In the patient we describe, fatal Ps. aeruginosa bacteremia was first manifested by a syndrome indistinguishable from pulmonary thromboembolism with infarction.     

Eosinophilia,elevated immunoglobulin E level and chronic enteritis due to intestinal helminthiasis

Recurrent urticaria, abdominal pain, peripheral eosinophilia, hyperimmunoglobulin E and small bowel abnormalities on roentgenograms prompted evaluation of a 36 year old man for intestinal parasitism. Evidence for helminthiasis as the cause of his symptoms included changing antibody titers to helminth antigens and a dramatic response to therapy. Helminth larvae or eggs were not recovered. Diagnosis of strongyloidiasis, the most likely cause of the illness, is discussed.     

Interferons.

Only a generation ago, health conditions in China were similar to those found in the least developed nations; but today, Chinese mortality rates resemble those found in the most highly industrialized nations. The incidence of infectious diseases and other diseases associated with deprivation has decreased markedly, especially in urban areas, and degenerative diseases are now a major health concern in China. In Peking cardiac disease is the leading cause of death and 45% of these deaths are due to strokes. While China has made great strides in improving sanitation and hygiene standards, efforts to control chronic diseases have not been as effective. Little effort has been made to collect information on health problems at the national level, and this dearth of information prevents effective planning for the continuing services needed for the treatment of individuals with chronic disease. These observations on the state of public health in China were made by 2 groups of medical personnel who visited China for several weeks in 1978 and toured medical facilities in 7 cities and 3 communes. The visitors also noted that most deliveries of babies in rural areas are performed by trained midwives and that most urban women deliver at hospitals. In the urban areas many women are sterilized after the 2nd birth. Most childhood diseases are under control, but respiratory tract infections and mastoiditis are still common problems. Acupuncture as an anesthetic for major surgery is widely used. A table comparing cardiovascular and cancer mortality rates in China and the U.S. is included.     

Plasma prorenin: cryoactivation and relationship to renin substrate in normal subjects.

We previously demonstrated an inactive form of renin, termed prorenin, in the plasma of normal, hypertensive and anephric patients. Prorenin activity can be determined in plasma from the total renin activity after activation, minus the prior endogenous plasma renin activity. In the present study, conditions for cryoactivation of prorenin have been defined. Plasma prorenin is slowly converted to active renin-like material at -5 degrees C at pH 7.4. Activation takes four days and does not occur at pH 5.0. The degree of activation increases above pH 5 and is greatest between pH 7 and pH 9. Thus, almost no cryoactivation of prorenin occurs at the pH optimum for renin (5.7) in contrast to maximum activation at pH 7.4. No activation has been observed in the frozen state, but it does occur with decreasing rapidity at temperatures from -5 degress to +4 degress C. Since blood samples obtained for the determination of plasma renin activity are routinely chilled upon collection by most laboratories, some activatin of prorenin most likely occurs in all routine renin assays. The pH optimum of the enzymatic reaction of the activated prorenin in plasma is 5.8, the same as for renal renin, and the shape of the pH optimum curve is similar to that of renal renin added to human plasma. In a group of 23 normal subjects with plasma renin activity of 3.5 +/- 2.9 (SD), the activated prorenin increment was found to be significantly higher, 6.3 +/- 5.0 (SD) ng/ml/hour. Unlike plasma renin activity, prorenin activity in these normal subjects was directly related to the concentration of renin substrate (p less than 0.001). When the actual "concentration" of prorenin was calculated using renal renin as the reference standard, a direct relationship was also found between the concentration of prorenin and renin substrate (p less than 0.01). The observed relationship between prorenin and renin substrate concentrations might be a consequence of their regulation by common factors.     

Analysis of the disturbance in oxygen transfer in hypoxic lung disease

Studies have been made to quantitate the disturbance of oxygen transfer in terms of the unevenness of ventilation, perfusion and diffusing capacity within diseased lungs. The technics used employ nitrogen washout studies coupled with other measurements including the use of Bohr integral isopleths. These isopleths are briefly explained. Four types of pulmonary disturbance are briefly presented: (1) Chronic obstructive pulmonary disease of type A, in which the slow space occupies a very large volume, is poorly ventilated and has a very low diffusing capacity and a moderate reduction in its ventilation perfusion ratio. (2) Chronic obstructive pulmonary disease of type B, in which the slow space is not as large, has a good diffusing capacity, a very low alveolar ventilation and a very low ventilation perfusion ratio. The syndrome of alveolar-capillary block also shows two patterns of disturbance. (3) Those with both unevenness of diffusing capacity and of ventilation perfusion ratios. (4) Those with disturbance in diffusing capacity but no unevenness in ventilation perfusion ratios. The existence of the latter type of patient is at variance with the assertion which is sometimes made that the disturbance of function in the alveolar-capillary block syndrome is purely a disturbance in ventilation perfusion ratios.     

Bicarbonate and the regulation of ventilation

The regulation of ventilation involves a multifactorial control system with several feedback loops transmitting deviations from normal in pH, carbon dioxide tension (pCO₂) and oxygen tension (pO₂) to the control area. Variations in the size of the bicarbonate pool, caused by ventilatory or metabolic disturbances, can be expected to modify resting ventilation if hydrogen ion activity is the ultimate stimulus of the regulation of ventilation. A relationship between serum bicarbonate and resting ventilation can be identified in patients with stable acid-base disturbances including those in whom correction of the arterial blood pH was not achieved by respiratory adaptation. Why the pH in arterial blood is rarely returned to the normal range is not well understood. It may be an inadequacy of the control system, a “compromise” solution avoiding hypoxia in metabolic alkalosis or increasing work of breathing in metabolic acidosis, or a consequence of discrepancies in hydrogen ion activity in body fluids adjacent to and remote from the control site.Additional information about the role of bicarbonate in the control of ventilation may be obtained by measuring the response to carbon dioxide inhalation at varying extracellular bicarbonate concentrations. The increments in ventilation during inhalation of carbon dioxide are within individual limitations, inversely and exponentially related to the bicarbonate concentrations in blood.These observations are in accord with the concept that the extracellular bicarbonate concentration modulates resting ventilation and the ventilatory response to inhalation of fixed concentrations of carbon dioxide by acting as a determinant for the hydrogen ion activity within or adjacent to the central chemosensitive control area.     

Fever and pulmonary thromboembolism.

Fever patterns associated with pulmonary thromboembolism have not been well characterized. Upon review of 35 consecutive patients with angiographically documented pulmonary emboli, fever was present in 24 patients; and in 20, it was attributed solely to pulmonary thromboembolism. Analysis of these cases indicates that high fever (temperature greater than 39 degrees C) due to pulmonary thromboembolism may occur early, and low-grade fever may continue for a week or more. Fever persisting beyond six days, however, especially with temperatures over 38.5 degrees C, should not be ascribed to pulmonary thromboembolism unless other causes have been carefully excluded. If the clinical setting and patient's findings are consistent with pulmonary thromboembolism, one should not be deterred from presumptively making this diagnosis and initiating therapy because of the presence of high fever.     

Methyldopa hepatitis: A report of six cases and review of the literature

Six cases of methyldopa hepatitis, including two in which the patients died are reported; and 77 cases from the literature are reviewed. Patients in whom severe hepatotoxic reactions to methyldopa develop usually complain of prodromal symptoms typical of hepatitis, often with fever, one to four weeks after therapy is initiated. Jaundice, when it occurs, is usually manifest within three months.

Asymptomatic, transient elevations of serum transaminase levels may occur in patients receiving methyldopa. However, since the clinical and histologic features of hepatic injury from methyldopa are indistinguishable from viral hepatitis, it is suggested that the incidence of this iatrogenic disease is higher than generally appreciated.

Serum transaminase levels should be determined at the initiation of therapy with methyldopa and four weeks later. Moreover, any patient who has unexplained fever or the prodromal symptoms of hepatitis should undergo liver chemistry studies immediately.     

Estimating renin participation in hypertension: superiority of converting enzyme inhibitor over saralasin.

This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 addtional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p less than 0.001) and with the pretreatment plasma renin levels (p less than 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but but converting enzyme inhibitor produced changes of greater amplitude (p less than 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade preduced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 +/- 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was -10.2 +/- 1.2 per cent, p less than 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.     

Delayed hyperacute rejection in recipients of kidney transplants from HLA identical sibling donors.

Delayed hyperacute rejection, with its characteristic clinical course and histopathologic findings, occurred within one month after transplantation in five recipients of kidney transplants from HLA-A, B and D identical sibling donors. In all cases, unidirectional mixed lymphocyte cultures and immunologic studies to detect cytotoxic antibodies in the recipients against their respective donors, before kidney transplantation and after transplant nephrectomy, were unresponsive or negative. Onset of delayed hyperacute rejection was preceded by bacteremia in two of these patients. Two of these received second kidney transplants, three to six months later, from HLA-A, B and D identical sibling donors again. Although both have had an episode of acute rejection in the early postoperative period, the grafts have maintained excellent function for 21 and 25 months, respectively. Irreversible forms of transplant rejection, such as delayed hyperacute rejection, do occur even in recipients of kidney transplants from HLA-A, B and D identical sibling pairs, indicating that genetic determinants other than HLA-A, B and D loci, and perhaps other nongenetic immune mechanisms, play an important role in the ultimate results of kidney transplantation.