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.     

Studies of twins with systemic lupus erythematosus: A review of the literature and presentation of 12 additional sets

To assess the role of genetic factors in systemic lupus erythematosus (SLE), 12 twin pairs (seven definitely monozygotic, three definitely dizygotic) of which one or both twins had SLE, were studied and compared to 17 twin pairs (12 definitely monozygotic) previously described. In the present series, four of seven (57 per cent) definitely monozygotic pairs were clinically concordant for SLE, satisfying the preliminary criteria of the American Rheumatism Association (ARA). Concordance for the presence of antinuclear factor (ANF) and hypergammaglobulinemia was 71 and 87 per cent, respectively. These data closely agree with those on the 12 definitely monozygotic sets previously described. All three of the dizygotic sets in the present series were discordant for clinical SLE, although one clinically well twin had marked serologie abnormalities.Comparison of these data with those from other first degree relatives of our twins clearly suggests a strong genetic component in the pathogenesis of SLE. The relative contribution of nongenetic and environmental factors to the expression of the disease is discussed.     

Mycobacterium avium infections in man

A disseminated infection with Mycobacterium avium, serotype 1, is described in a 63 year old woman with reticulum cell sarcoma. The organism was demonstrated in vivo in lymph nodes, bone marrow, urine and sputum, and at autopsy within an intraocular abscess.Previous reports of human infections with Myco. avium describe cases of chronic, cavitary pulmonary disease, frequently occurring in patients with pneumoconiosis, cervical lymphadenopathy in children, and disseminated infection. Infected birds and mammals, and soil rich in bird droppings appear to constitute natural reservoirs of infection. However, extensive exposure to birds or the carcasses of slaughtered animals has been documented in only a minority of cases.Myco. avium can be reliably identified only by serotyping or by inoculation into chickens, rabbits and guinea pigs. Skin tests with avian purified protein derivative together with standard purified protein derivatives and antigens prepared from other mycobacteria may be helpful in diagnosis prior to isolation and identification of the organism. Although localized infections have apparently been cured by surgical excision, more extensive infections have been reported to be progressive or fatal and have responded poorly to chemotherapy.     

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.     

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.     

Elevated hemoglobin A1c and low-density lipoprotein cholesterol levels in thiazide-treated diabetic patients

Despite the well-known hyperglycemic effect of thiazide diuretics, these agents are often administered to diabetic patients. This study compared 89 insulin-treated diabetic patients receiving hydrochlorothiazide, 57 receiving furosemide, and 255 receiving no diuretic. Hemoglobin A1c level was 7.2 +/- 1.8 percent (mean +/- SD) with hydrochlorothiazide, significantly higher than the levels of 5.9 +/- 2.3 percent with furosemide and 6.4 +/- 2.0 percent with no diuretic. Low-density lipoprotein cholesterol level was 154 +/- 43 mg/dl with hydrochlorothiazide, but 134 +/- 42 mg/dl with furosemide and 130 +/- 42 mg/dl with no diuretic. Multivariate analysis showed that the associations remained significant after adjustment for age, sex, race, type and duration of diabetes, body mass index, blood pressure, serum potassium level, insulin dose, and treatment with other medications. These findings suggest that treatment with thiazide diuretics in the diabetic population may increase low-density lipoprotein cholesterol and hemoglobin A1c levels.     

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.     

Central nervous system disease in systemic lupus erythematosus: Therapy and prognosis

The effect of corticosteroid therapy in 28 patients with 52 episodes of neuropsychiatric disease in systemic lupus erythematosus (SLE) was evaluated. Categories of organic central nervous system disease were seizures (eight patients), organic brain syndromes (nine patients), aseptic meningitis (four patients) and a variety of focal neurologic findings (seven patients). Fourteen patients had 15 episodes of functional psychosis without other evidence of neurologic disease.Although there was a general correlation between clinical and serologic evidence of active SLE and the development of organic neurologic disease, there was no evidence that therapy with very large doses of corticosteroids was beneficial. Of the deaths in this series, two were due to probable active SLE involving the central nervous system whereas five were attributable to complications of therapy. The long-term morbidity, likewise, was high in the patients who received large doses of corticosteroids. In all, 12 patients had major complications of corticosteroid therapy.Functional psychosis was usually precipitated by corticosteroid therapy and responded to a reduction in steroid dosage and administration of psychotropic drugs.     

Clinical spectrum of infection due to Bacillus species

Bacillus species other than B anthracis were isolated from culture material and seen on gram-stained smear in 12 patients over a 6 year period in a hospital for patients with neoplastic diseases. In some cases Bacillus species were recovered repeatedly from an individual patient, occasionally from more than one site. Pulmonary and disseminated infection developed in two patients with acute leukemia who were under intensive chemotherapy, and they died following rupture of a brain abscess into the ventricular system. In both patients, Bacillus species were recovered from cultures of blood and sputum antemortem, and in the heart's blood after death, and seen in histopathologic sections of the lung and brain. These cases were similar to those few previously reported cases in that the usually nonpathogenic Bacillus disseminated in an immunologically compromised host. Nearly all the remaining isolates were from drainage from recent surgical wounds. Rarely was specific treatment given for the Bacillus, and they seemed to exert no definite influence on the patient's clinical course, although occasionally the character of a wound drainage altered after the Bacillus was no longer recovered on culture.     

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.     

Waldenström's macroglobulinemia in a patient with a chronic biologic false-positive serologic test for syphilis

Acute and chronic biologic false-positive serologie reactions for syphilis (VDRL) have been associated with a variety of diseases. Several investigators emphasize that false-positive VDRL titers are usually very low. This report describes a 73 year old man with Waldenström's macroglobulinemia. The biologic false-positive serologic test for syphilis was recognized 33 years before the diagnosis of Waldenström's macroglobulinemia was made. VDRL titers were as high as 1:8192 and 1:32,000 during exacerbations of the macroglobulinemia. A biologic false-positive serologic test for syphilis is frequently associated with an elevated immunoglobulin M (IgM) level. It would be interesting to search for a relation between biologic false-positive serologic tests for syphilis and diseases characterized by monoclonal gammopathies.     

Hepatocellular carcinoma, transfusion-induced hemochromatosis and congenital hypoplastic anemia (Blackfan-Diamond syndrome)

A 25 year old patient with congenital hypoplastic anemia (Blackfan-Diamond syndrome) is described. This patient was hepatitisantigen negative, had not received androgens and had a hepatoma develop in a transfusional hemochromatotic liver. Since androgens have been associated with hepatocellular carcinoma, the use of androgenic steroids for other than life-threatening symptoms in this disease should be avoided.     

Toxicity of D-penicillamine in rheumatoid arthritis: A report of 63 patients including two with aplastic anemia and one with the nephrotic syndrome

To assess toxicity of D-penicillamine a retrospective chart review was performed on 63 patients with rheumatoid arthritis receiving penicillamine. These patients had a total of 83 courses of therapy.The mean age of patients was 52 years and the mean duration of disease was 10.07 years. Laboratory data showed an increase in hematocrit values from 36 per cent to 40 per cent and a decrease in the erythrocyte sedimentation rate from an average of 50 to 29 mm/hour. The platelet count also decreased with treatment from 394,000 to 267,000/mm³.The over-all complication rate was 53 per cent. Life-threatening complications occurred in two patients including one case of aplastic anemia and one case of nephrotic syndrome. One additional patient was referred with aplastic anemia. Minor complications include rash in 18 per cent, loss of taste in 6 per cent, dyspepsia in 11 per cent, oral ulceration in 7 per cent and proteinuria of less than 3 g/day in 8 per cent.In summary, 53 per cent of the courses of penicillamine were associated with toxicity including one episode of aplastic anemia and one case of nephrotic syndrome. Therapy was stopped due to complications in 39 per cent of the patients in this series.     

Acute respiratory failure in scoliosis or kyphosis: prolonged survival and treatment

Acute respiratory failure (ARF) in adults with severe thoracic spinal deformity is said to be a preterminal event with a median survival of one year. Twenty patients with ARF (mean +/- S.D., arterial oxygen tension [PaO2] 35 +/- 7 mm Hg, arterial carbon dioxide tension [PaCO2] 63 +/- 9 mm Hg, pH 7.34 +/- 0.08) due to severe scoliosis or kyphosis (spinal curve 113 +/- 28 degrees ) were seen between 1965 and 1980. All 20 survived the initial episode of ARF and during the follow-up period (median, six years) experienced 2.4 additional episodes of ARF. The age at presentation was 52 years (mean, range 13 to 78), and the cause of spinal deformity was idiopathic (seven patients), poliomyelitis (seven), tuberculosis (five), and arthrogryposis multiplex congenita (one). ARF was treated with controlled low dose oxygen by Venturi mask and intensive general measures in 13 patients and by mechanical ventilation in seven. Of the latter seven patients, ventilatory failure was treated in two with a tank respirator and a cuirass, avoiding endotracheal intubation. Outpatient management was similar to conventional therapy for chronic obstructive pulmonary disease (COPD). Severe restrictive ventilatory impairment characterized the group after recovery from the first episode of ARF: vital capacity (VC) 906 +/- 362 ml (31 percent predicted) and FEV1 589 +/- 197 ml (23 percent). During follow-up, the VC decreased by 1.5 ml/year and the FEV1 by 13.9 ml/year. The PaO2 increased by 2.6 mm Hg/year and the PaCO2 increased by 1.7 mm Hg/year. Successful management of ARF due to severe scoliosis or kyphosis is possible in the great majority of patients, and long-term survival may be expected. Unlike COPD, pulmonary function following ARF in kyphosis or scoliosis deteriorates at a slower than expected rate and, in fact, may improve with treatment over many years.