Pseudomonas aeruginosa endocarditis. Report of a case, with review of the literature

A 69 year old woman presented with malabsorption and steatorrhea. There was an M component of immunoglobulin M, (IgM) lambda (ι) type in the serum, an increase in lymphocytes and plasma cells in the bone marrow, and splenic enlargement, but no other features characteristic of Waldenstrom's macroglobulinemia were present. Repeat peroral intestinal biopsy specimens revealed infiltration of the intestinal mucosa by homogeneous extracellular material. Immunofluorescent and histochemical analysis showed it to be composed of monoclonal IgM (lambda) with an admixture of phospholipid. Marked dilatation of mucosal lymphatics and moderate numbers of plasmalymphocytic cells were also found.This appears to be the first case of malabsorption syndrome associated with monoclonal IgM, in which the immunoglobulin has been positively identified in the intestinal wall. Treatment with steroids resulted in remarkable clinical improvement.     

Benign hepatic tumors and oral contraceptive pills.

In order to consider possible environmental factors related to the development of benign hepatic tumors, all reports of this disorder in the case records of five different hospitals in Rochester, New York, during the past 10 years were reviewed. Seven patients with benign hepatic tumors of the liver and two with peliosis hepatis were identified. Among the seven with a benign hepatic tumor, four were women currently receiving oral contraceptives; one had been receiving this medication in the past, and two had no history of exposure to any steroid whatsoever. The two patients with peliosis hepatis were receiving long-term androgenic anabolic steroids. Dilated, thin-walled vessels and vascular spaces were a more prominent feature of the tumor seen in four patients receiving oral contraceptive pills. It is emphasized in this report that benign hepatic tumors do occur in men and in patients with cirrhotic liver without the use of any kind of steroids.     

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.     

Regression of atherosclerotic stenosing lesions of the renal arteries and spontaneous cure of systemic hypertension through control of hyperlipidemia

We describe a 49 year old woman with impressive regression of renal artery stenosing atherosclerotic lesions in response to sustained excellent control of hyperlipidemia.Initially, she had high blood pressure necessitating combined drug therapy with chlorothiazide, methyldopa and propranolol, with only moderately satisfactory control. Renal arteriography revealed a 90 per cent stenosing lesion of the right renal artery and 75 per cent narrowing of the left renal artery. Peripheral vein plasma renin was markedly increased at 32 ng/ml. With a combination of cholestyramine and clofibrate, serum lipids were maintained at normal values for several years. Increased blood pressure diminished spontaneously, and the patient has maintained normal blood pressures after discontinuation of antihypertensive therapy. Repeat renal arteriograms showed almost complete regression of the right renal artery lesion and a possible decrease in left renal artery disease. Peripheral vein plasma renin became normal at 3 ng/ml.This case illustrates that sustained control of hyperlipidemia could lead to regression of atherosclerotic nodules and impressive clinical improvement in certain patients.     

Usefulness and limitations of saralasin, a partial competitive agonist of angioten II, for evaluating the renin and sodium factors in hypertensive patients.

Saralasin was infused into 52 untreated hypertensive patients. Immediate, transient pressor responses occurred in 94 per cent followed by a more gradual sustained change in blood pressure reaching an apogee in about 20 minutes. Most (86 per cent) patients with high renin values had sustained depressor responses irrespective of sodium balance. In contrast, during a normal sodium intake, the drug produced a neutral (45 per cent) or mildly pressor (50 per cent) response in patients with normal renin and pressor responses in patients with low renin values. Sodium depletion abolished pressor responses and resulted in depressor responses in 64 per cent of the patients with normal renin values. The pretreatment angiotensin level appeared to determine direction and amplitude of the response to saralasin, since increases and decreases in diastolic pressure exhibited a highly significant relationship to the control renin lever (r = 0.80, p less than 0.001). Above a neutral range of control renin values, from 2 to 7 ng Al/ml/hour, depressor responses were the rule, and below it pressor responses were consistent. Sodium balance also appeared to determine the amplitude of the response. In a subset of patients with similar renin values (range 1.4 to 2.2 ngAl/ml/hour), the induced pressor responses correlated directly with the 24-hour sodium excretion (p less than 0.05). For all patients, the induced pressure change also was related to the rate of sodium excretion (r = 0.53, p less than 0.001). The data suggest that saralasin behaves as a partial competitive agonist of angiotensin II. For this reason, saralasin testing provided only a rough physiologic validation for renin profiling. Thus, depressor responses expose most patients with high renin values. Neutral responses occur in many patients with normal renin and intermediate renin values. But pressor responses occur in subjects with either low or normal renin levels and they may reflect sodium and volume excess associated with a partial or relative absence of renin. Accordingly, due to its partial agonism, saralasin testing under-estimates the renin factor. Hence, the drug cannot be used to identify or exclude renin involvement in the blood pressure in the large majority of hypertensive patients who do not exhibit depressor responses. For them an agent devoid of agonism is required. Moreover, prior sodium depletion as a device to increase the frequency of depressor responses to saralasin does not measure intrinsic renin dependency of the blood pressure but rather the reactivity of the system to sodium depletion.     

Detection of radiation cardiomyopathy by gated radionuclide angiography

Twenty-one asymptomatic adults underwent rest and exercise gated radionuclide angiography seven to 20 years after having received mediastinal radiation (2,000 to 7,600 rads) for Hodgkin's disease. None of these patients received cytotoxic chemotherapy. Twelve patients (57 percent) had abnormal left (less than 53 percent at rest and/or greater than 5 percent decrease at peak exercise) and/or right (less than 27 percent at rest and/or greater than 5 percent decrease at peak exercise) ventricular ejection fractions. Previous reports have described myocardial fibrosis occurring late after therapeutic mediastinal radiation; however, the incidence of this occurrence based on clinical follow-up has been low. Rest and exercise radionuclide angiography is a sensitive method for assessing systolic ventricular function and reveals a high prevalence of cardiomyopathy that can be linked to previous radiotherapy.     

Comparison of the effects of sleep, exercise and autonomic drugs on ventricular extrasystoles, using ambulatory monitoring of electrocardiogram and electroencephalogram.

Ambulatory monitoring of the electrocardiogram (ECG) and the electroencephalogram (EEG) in 12 untreated patients with frequent ventricular extrasystoles showed a significant decrease in both ventricular extrasystoles and heart rate during sleep. The decrease in ventricular extrasystoles correlated more closely with the change in heart rate than with the level of arousal. During wakefulness, similar changes in ventricular extrasystoles and heart rate could be produced by the intravenous administration of propranolol and, to a lesser extent, by phenylephrine. Exercise produced an initial increase in ventricular extrasystoles, with suppression at higher levels in most patients. Thus, the frequency of ventricular extrasystoles is usually reduced at both extremes of heart rate, and the changes that occur during sleep can be explained by autonomic mediation, with the sympathetic limb of the autonomic nervous system having a greater effect than the vagus.     

A prospective controlled investigation of prophylactic trimethoprim/sulfamethoxazole in hospitalized granulocytopenic patients.

Oral trimethoprim/sulfamethoxazole (TMP/SMZ) therapy was investigated in the prophylaxis of infections in granulocytopenia. Hospitalized granulocytopenic patients were allocated at random to receive TMP/SMZ (group 1) or to a control group (group 2). The percentage of febrile granulocytopenic days was significantly reduced in group 1, 19 per cent compared to 39 per cent in group 2 (P less than 0.01). In group 1, there were no bacteremias in 59 episodes of granulocytopenia (909 days). In group 2, there were nine bacteremias in 52 episodes of granulocytopenia (796 days)(P = 0.001). Disseminated candidiasis developed in two patients in each group. Candida occurred in similar numbers in surveillance cultures in both groups; Staphylococcus aureus and Pseudomonas aeruginosa were slightly decreased, and Enterobacteriaceae resistant to TMP slightly increased in group 1. This study suggest that oral prophylactic TMP/SMZ therapy is an effective, well tolerated, easily administered alternative to "gut sterilization" with nonabsorbable antibiotics.     

Granulocytopenia in hospitalized patients: I. Prognostic factors and etiology of fever

The clinical course of 126 hospitalized patients during 192 episodes of granulocytopenia and fever was studied. Fever was a regular accompaniment of granulocytopenia, occurring in 94 per cent of granulocytopenic episodes. The mean duration of granulocytopenia (less than 1,000/mm3) was 18 days, with fever (temperature greater than 38 degrees C) being present during 44 per cent of those days. Fever was present during 69 per cent of days with a granulocyte count less than 10/mm3. A presumed infection was present in 86 of 128 febrile granulocytopenic episodes in adults and in 19 of 64 febrile granulocytopenic episodes in children. A fungal infection was found in 11 patients; a viral infection in 23 patients. Bacteremia occurred during 44 granulocytopenic episodes with 16.8 bacteremias/1,000 days of granulocytopenia in adults and 12.7 bacteremias/1,000 days in children. The mortality was 33 per cent per granulocytopenic episode in adults and only 8 per cent per episode in children.     

Fatal disseminated adenovirus infection in a renal transplant recipient.

A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.     

Macroglobulinemia-myeloma double gammopathy. A study of four cases and a review of the literature

The coexistence of macroglobulinemia and myeloma type M components in the same serum is very rare. The following features were observed in four patients with this condition: (1) Hyperviscosity syndrome with widespread amyloidosis and foci of calcification; the serum contained an IgG4(κ), 7S and 17S IgM(κ) M components. (2) Polyarthritis, high fever, lymphadenopathy, hepatosplenomegaly and skin rash; IgA(λ) cryoglobulin and IgM(λ) pyroglobulin were found in the serum. (3) Plasmacytoma of the liver; IgG(λ) and IgM(λ) were detected. (4) Malignant lymphoma of a diffuse histiocytic type; IgG(κ) and IgM(κ) were present in the serum. A review of the literature disclosed 26 other examples of macroglobulinemia-myeloma type double gammopathy. The clinical picture, well described in 17 of these, was heterogeneous and not necessarily typical of either condition. Whereas some investigators stated that each M component was produced by a distinct population of malignant cells, others presumed that the same clone was capable of synthesizing more than one immunoglobulin.     

Staphylococcus aureus bacteremia. Current clinical patterns.

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.     

Occult dental infection as a cause of fever of obscure origin.

Three patients with prolonged unexplained fevers were ultimately found to have deep-seated dental infection. After initial examination failed to elicit symptoms or signs of dental infection, and extensive in-hospital evaluation was nonproductive, dental consultation with roentgenograms provided the diagnosis. All three patients underwent dental extractions with periapical or peridontal debridement; following a brief postoperative febrile period, all three responded with defervescence, without subsequent recurrence of fever. These cases emphasize the importance of periapical and peridontal infection as causes of fever of obscure origin. The pathogenesis, characteristics and bacteriology of periapical abscess are discussed.     

Cushing's disease with cure by resection of a pituitary adenoma. Evidence against a primary hypothalamic defect

A patient with Cushing's disease was treated by transphenoidal resection of a pituitary adenoma. Pituitary-adrenal suppressibility, responsiveness to metyrapone and circadian rhythm were observed postoperatively. Reversion to physiologic regulation after resection of an adenoma implies that the lesion secreted ACTH autonomously (primary hyperpituitarism). Current evidence favors the pituitary adenoma, when present, as the primary etiologic factor in pituitary-dependent Cushing's syndrome. Since adenomas occur in a majority of cases, initial therapy is best directed at the pituitary.     

Granulocytopenia in hospitalized patients: II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients

The results of empiric antibiotic therapy in 126 hospitalized patients with fever during 192 episodes of granulocytopenia were studied. Febrile granulocytopenic patients were randomly allocated to receive either carbenicillin, methicillin and gentamicin, or carbenicillin and cephalothin. The response rate for the two antibiotic regimens was similar, 49 (60 per cent) of 81 responded to the former and 42 (54 per cent) of 78 to the latter. The response rate in patients receiving other antibiotics because of specific indications or counterindications was 19 (58 per cent) of 33. Thirty-nine (35 per cent) of 110 patients who responded to initial antibiotic therapy had an increase in circulating granulocytes of one log₁₀ or more compared to only 10 (12 per cent) of 79 nonresponders with such an increase. The mortality rate in adult patients receiving carbenicillin, methicillin and gentamicin was eight (16 per cent) of 51, compared to 18 (37 per cent) of 49 in those receiving cephalothin and carbenicillin (P < 0.05). The significance of this difference in mortality rate is uncertain, as there was no difference in the initial response rate or mortality rate between patients treated with the two antibiotic regimens when only patients with documented bacterial infection were considered. Patients who responded to their initial antibiotic regimen, and patients for whose fever no explanation was found, had the best prognosis.     

Emphysematous pyelonephritis. A report of two cases

Emphysematous pyelonephritis is a suppurative infection of the renal parenchyma characterized by the production of gas by bacteria through fermentation. Although seemingly rare, this condition occurred in two diabetic patients on general medical wards over a two year period. Diagnosis, in an appropriate clinical setting, is confirmed roetgenologically. Escherichia coli is the most common etiologic organism. Despite appropriate medical and surgical intervention, this severe form of renal parenchymal infection carries a high mortality.     

Avascular necrosis of bone complicating treatment of malignant lymphoma

Over a 15-year period, 12 patients were seen at the Ontario Cancer Institute in whom avascular necrosis of bone developed after or during treatment for malignant lymphoma. All but one were treated with systemic chemotherapy that included high-dose intermittent corticosteroids. The average time to onset of symptoms was 34 months (range, eight to 72 months) after an average of 9.0 g of prednisone (range, 1.4 to 18.75 g). The one exception was a patient with Hodgkin's disease treated by pelvic radiation alone who had development of avascular necrosis of the femoral head within one month of irradiation. More than one joint was involved in 58 percent of patients. Six patients required surgery (usually hip replacement) but two patients had no evidence of deterioration over many years (average, seven years) and three patients had minimal symptoms easily controlled by mild analgesics up to six years after diagnosis. The evidence implicating corticosteroids in the development of avascular necrosis is presented and the various hypotheses of pathogenesis are reviewed, The predominance of Hodgkin's disease over non-Hodgkin's lymphomas (5:1) in this and other series and the identification of one patient with Hodgkin's disease with development of avascular necrosis within one month of radiotherapy treatment suggests that Hodgkin's disease itself may predispose to this condition.     

Simultaneous infection with multiple herpesviruses.

Active dual infection with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was observed in four otherwise healthy persons with mononucleosis syndromes. A secondary serologic response to EBV occurred in three patients as determined by the presence of antibodies to EBV-induced nuclear antigen (EBNA) early in the illness. All four patients lacked heterophil antibodies; in the one case tested, immunoglobulin M (IgM) antibodies specific for EBV viral capsid antigen (VCA) were absent as well. The Guillain-Barré syndrome occurred in one patient, who also had active infection with herpes simplex virus 1 (HSV-1). In a fifth patient, herpes zoster developed complicating heterophil-positive infectious mononucleosis due to primary infection with EBV.These five cases demonstrate that mononucleosis syndromes may occur in association with dual or multiple herpesvirus infections and that reactivation of EBV may be common during heterophil-negative mononucleosis. Reactivation of latent virus is most likely related to depressed cellular immunity due to a primary infection with another herpesvirus. An alternate hypothesis is that viral DNA polymerase induced by infection with one herpesvirus might simultaneously permit the productive replication of a second herpesvirus previously latent within the same cell. Thus, reactivation may result from molecular interactions between viruses at the cellular level.The possibility of multiple infections must be considered whenever determining the specific viral etiology of heterophil-negative mononucleosis.     

Effect of long-term thiazide therapy on intestinal calcium absorption in patients with recurrent renal calculi

Recurrent calcium-containing renal calculi are a common and poorly understood problem. Thiazide diuretics decrease urinary calcium excretion but their effect on other parameters of calcium metabolism is not established. The purpose of this study was to determine the effect of chronic administration of thiazide diuretics on intestinal calcium absorption, skeletal calcium turnover, and urinary calcium excretion, and to use this information to attempt to clarify the pathogenesis of idiopathic hypercalciuria. Forty-one patients with recurrent calcium-containing renal calculi were studied; 73% had hypercalciuria, 44% had increased intestinal absorption, and 7% had increased bone turnover. Thiazide diuretics given to 22 patients for 3–16 mo resulted in a consistent reduction in urinary calcium excretion, while calcium absorption was unchanged (< 6%) in 12 patients and significantly decreased (by 20%) in ten patients. Decreased intestinal absorption appeared to be a secondary effect of thiazides, presumably due to reduced urinary calcium losses. Bone turnover was significantly decreased by thiazides in each case in which it had been elevated and was unchanged in patients with initially normal values. These results indicate that increased bone turnover is probably not the primary defect in idiopathic hypercalciuria. The effects of long-term thiazide diuretic therapy on intestinal calcium absorption suggest that there may be two different subpopulations of patients with hypercalciuria, one with primary intestinal hyperabsorption which persists despite correction of urinary losses, and one with primary renal loss of calcium.     

Upward subluxation of the axis in ankylosing spondylitis. A clinical pathologic report.

Upward subluxation of the axis associated with cord compression and death was noted in a patient with a long history of idiopathic ankylosing spondylitis. Upward subluxation of the axis has been recognized in up to 8 per cent of patients with rheumatoid arthritis but it is an exceedingly rare complication of ankylosing spondylitis. In this patient psoriasis and then psoriatic dactylitis developed 26 years after the onset of his ankylosing spondylitis. It is tempting to speculate that the unusual destruction of the joints around the atlas might be due to an added effect of psoriasis on idiopathic ankylosing spondylitis.