Pneumococcal pericarditis: A persisting problem in contemporary diagnosis

We reviewed the clinical and laboratory features of six patients with pericarditis caused by Streptococcus pneumoniae who were admitted to Boston City Hospital. The diagnosis of pneumococcal pericarditis was delayed or missed entirely during life in all patients. The frequent absence of pericardial friction rubs and cardimegaly on chest roentgenograms contributed to the difficulty in recognizing this illness. Electrocardiograms and physical examinations of the heart almost always disclosed abnormalities, but they were not sufficiently specific to suggest pericarditis, and patients were often thought to have had an acute complication of arteriosclerotic heart disease. Review of the English literature since 1945 supports the recent experience in our hospital that the diagnosis of pneumococcal pericarditis may be elusive.     

Antibiotic susceptibility of gram-negative bacilli isolated from blood cultures. Results of tests with 35 agents and strains from 169 patients at Boston City Hospital during 1972

Gram-negative bacilli of several of the more common species grown from the blood of 169 patients hospitalized at Boston City Hospital during 1972 were tested with 32 antibiotics and with trimethoprim and sulfamethoxazole, alone and in combination. More than half of the agents are currently under clinical trial for efficacy and safety. Chemically related antibiotics were shown to differ in varying degrees in their activity against the different species, and even against different strains of the same species. The size of the inoculum affected the activity of the agents differently, depending on the antibiotic, the species and even the strain. Polymyxin B was generally the most active antibiotic against most species, but it was essentially inactive against Proteus mirabilis and Serratia marcescens. Trimethoprim alone, and particularly when combined with sulfamethoxazole, was even more active against most species, but it was essentially inactive against Pseudomonas aeruginosa.     

Management of infections in hospital employees

Hospital employees are often exposed to infectious diseases, both within and outside of the hospital. Susceptible personnel are at risk of acquiring infection and are a possible source of infection for patients, other employees and members of their households. In recent years epidemics in hospitals due to rubella, pertussis, hepatitis B and Legionnaires' disease have included infection transmitted to and from personnel. A comprehensive plan for management of hospital personnel exposed to communicable diseases should include the following: (1) protocols for the management of each of the common infectious diseases; (2) protocols for employees who are at special risk (pregnant women) and employees who work in areas of risk for certain infectious diseases (newborn nursery, clinical and pathology laboratories, hemodialysis unit); (3) assessment of infectious disease experience of new employees by history, skin test (tuberculosis) and serology (rubella, hepatitis B), and a plan for subsequent tests during employment; (4) continuous program of education of employees in infection control; and (5) coordination of policies among administration, employee health service and infection control officer and committee.     

Immunopathology of the nephrotic syndrome associated with renal vein thrombosis. Report of two cases and brief review of the literature

Renal tissue from two patients with the nephrotic syndrome and renal vein thrombosis was studied by immunofluorescence microscopy in addition to conventional histologic and electron microscopic technics. Granular deposits of immunoglobulins G (IgG), M (IgM) and beta₁ C/beta₁ A globulin (one case) were seen by fluorescence microscopy along the basement membranes in a pattern similar to that observed in patients with chronic membranous nephropathy and in the experimental model of chronic serum sickness. Renal vein thrombosis, associated with the nephrotic syndrome, is not clearly separated clinically or pathologically from primary glomerular disease with the nephrotic syndrome. In view of the lack of experimental evidence to show that either the glomerular lesion or the proteinuria is the result of elevated venous pressure alone, the pathogenesis of the lesion must remain in doubt.     

Hepatitis B exposure in emergency medical personnel: Prevalence of serologic markers and need for immunization

To assess the occupational risk of hepatitis B infection in emergency medical personnel, a seroepidemiologic survey of 87 emergency medical technicians and paramedics was conducted. Serologic markers indicating exposure to hepatitis B virus were detected in 18 percent. The prevalence of markers was associated with race (p = 0.006), with a relative risk of 3.5 (95 percent confidence interval 1.42 to 8.63) for nonwhites. Seropositivity was not associated with age, sex, previous clinical hepatitis, or blood transfusion. There was a suggestion that duration of employment as an emergency medical technician was related to the prevalence of hepatitis B markers (p = 0.11). Efforts to control the risk of hepatitis B infection in this profession are complicated by unique problems with postexposure prophylaxis and uncontrolled exposure to blood. Immunization with hepatitis B vaccine would be the optimal strategy to reduce infection in this high-risk occupation.     

A large outbreak of infections caused by a strain of staphylococcus aureus resistant to oxacillin and aminoglycosides

An extensive outbreak of nosocomial infections caused by oxacillinand aminoglycoside-resistant Staphylococcus aureus (OARSA) occurred over a 16 month period. A total of 349 isolates of OARSA were obtained from 174 patients. Colonization with OARSA was found in 92 patients. There were 120 infections in 82 patients; 50 were surgical wound infections, 13 were nonsurgical wound infections, six were pneumonias, 15 were urinary tract infections, 12 were intravenous site infections, and there were 19 episodes pf bacteremia (seven transient, 12 persistent). In patients with persistent bacteremia, the mortality rate was 33 percent. In patients treated for persistent bacteremia with vancomycin, the survival rate was 80 percent. Infections were highly associated with the surgical intensive care unit, and 90 percent of the isolates of OARSA tested had the same phage-type. Elderly patients with significant underlying disease, a history of previous surgery or of prior antimicrobial therapy appeared to be at increased risk for OARSA infections. OARSA were resistant to multiple antibiotics besides oxacillin, but all isolates were sensitive to vancomycin and rifampin. Three surgical intensive care unit nurses were found to be nasal carriers of OARSA, and one nurse had dermatitis of both hands colonized with OARSA. Following the removal of these nurses from the surgical intensive care unit and the institution of strict infection control measures, the number of OARSA infections and colonizations decreased to less than one per month. OARSA produces serious nosocomial disease, and epidemiologic intervention was effective in controlling this outbreak.     

Contaminated medication nebulizers in mechanical ventilator circuits. Source of bacterial aerosols

The contamination rates of medication nebulizers inserted into mechanical ventilator circuits were studied. Semiquantitative techniques were used to sample the reservoir fluid from in-line nebulizers during the first 24 hours after a circuit change. In the initial survey, high levels of contamination (organism concentrations above 10(3)/ml) were present in 13 (68 percent) of the 19 nebulizer reservoirs, and bacterial aerosols were produced by 10 (71 percent) of 14 nebulizers. Gram-negative bacilli were the predominant organisms isolated. Nebulizer contamination originated primarily from reflux of contaminated condensate in the ventilator circuit. When nebulizers were cleaned after each treatment, a reduced rate of contamination was found. Small bacterial aerosols (less than 3 microns in size) were produced in vitro after inoculation of nebulizers with gram-negative bacilli in concentrations isolated from in-use nebulizers. Contaminated in-line medication nebulizers generate small-particle bacterial aerosols that may increase the risk of ventilator-associated pneumonia and therefore should be cleaned or disinfected after each treatment rather than every 24 hours.     

Gram-negative bacteremia: IV. Re-evaluation of clinical features and treatment in 612 patients

Clinical features and specific aspects of treatment were evaluated in 612 patients with gram-negative bacteremia observed over a 10 year period. Coagulation abnormalities or thrombocytopenia were observed in 64 per cent of the patients. Evidence of disseminated intravascular coagulation (DIG) was found in approximately 10 per cent of them but was of sufficient severity to be associated with subcutaneous or visceral bleeding in 3 per cent of them. The frequency of coagulation abnormalities, other than DIC, was greater in patients with more severe underlying disease but DIC occurred with similar frequency irrespective of the severity of underlying host disease. Coagulation abnormalities of all types were associated with increased fatality rates. Hypothermia was noted in 13 per cent of the patients at the onset of bacteremia but was transient and was not associated with increased fatality. Failure to mount a febrile response >99.6 °F within the first 24 hours of bacteremia was associated with a significant increase in fatality rates. Prior corticosteroid therapy diminished the febrile response to bacteremia. Age, underlying host disease, granulocytopenia, congestive heart failure, diabetes mellitus, renal insufficiency, nosocomial infections, and antecedent treatment with antibiotics, corticosteroids, and antimetabolites significantly increased fatality rates. Appropriate antibiotic treatment reduced the fatality rate of those with bacteremia by approximately one-half among patients in each category of severity of underlying host disease. In addition, it was shown that early appropriate antibiotic therapy also reduced the frequency with which shock developed by one half. Even after development of shock, appropriate antibiotic therapy significantly reduced fatality rates. The use of combinations of antibiotics could not be demonstrated to significantly improve survival rates. Minimal differences in therapeutic efficacy could be demonstrated between individual antibiotics and various combinations of antimicrobials. Shock occurred in approximately 40 per cent of the patients and its frequency was not influenced by the species of etiologic agent. Contrary to previous reports, corticosteroid therapy in patients with shock did not enhance survival and treatment with an average of 4.0 g/day of hydrocortisone or its equivalents was associated with a significant increase in fatality rates.     

Tuberculous arthritis: A report of two cases with review of biopsy and synovial fluid findings

Two cases of tuberculous arthritis with synovial fluid findings are presented, and the major series with culture results and synovial fluid analyses are reviewed. Synovial fluid cultures are positive for tuberculosis in almost 80 per cent of proved cases. Specimens obtained by open synovial biopsy are positive by histology or culture in over 90 per cent of proved cases. Little experience with closed needle biopsy has been published. About one-fifth of the patients with tuberculous arthritis will have a positive synovial fluid acid-fast smear for tubercle bacilli. The tuberculous synovial effusion invariably has an elevated protein level, fair to poor mucin clot formation and usually a low joint fluid sugar level. The synovial fluid white cell count is usually in the range of 10,000 to 20,000 cells/ mm³, but it varies widely. Most fluids exhibited a predominance of polymorphonuclear leukocytes. The importance of bacteriologic or histologic study of synovial fluid and membrane in establishing the diagnosis is emphasized. In general, this disease is different from tuberculous involvement of serous membranes both in the frequency of positive cultures and in the difference in cellular response.     

Severe intrahepatic cholestasis in primary amyloidosis: a report of four cases and a review of the literature.

Liver involvement occurs frequently in patients with systemic amyloidosis, but jaundice is rare. The clinical and histopathologic features are described in four of 78 patients (5.3 per cent) with primary amyloidosis in whom severe intrahepatic cholestasis developed. The data on an additional eight patients recorded in the literature were reviewed. Criteria for inclusion were a tissue diagnosis of amyloidosis, a serum bilirubin level greater than 5 mg/100 ml, histopathologic evidence for cholestasis and no extrahepatic biliary obstruction. Hepatomegaly was present in 12 patients (100 per cent), ascites in nine (75 per cent) and pruritus in eight (67 per cent). The serum bilirubin ranged from 9 to 44 mg/100 ml, the serum alkaline phosphatase was markedly increased in 10 patients (83 per cent) and hypercholesterolemia occurred in seven (58 per cent). Microscopic examination of the liver revealed diffuse amyloid deposition and compression atrophy in 12 patients (100 per cent). The amyloid was prominent in the periportal regions, and some sparing of the centrilobular areas was observed. Bile thrombi and bilirubin staining of hepatocytes were predominantly in the centrilobular zones. Liver cell necrosis, fibrosis or nodularity was uncommon.The pathogenesis of intrahepatic cholestasis in these patients is probably related to the deposition of amyloid in a manner that interferes with the passage of bile from the canaliculi and/or the small intrahepatic bile ducts to the septal bile ducts. Obstructive jaundice carries a poor prognosis. Nine of 12 patients (75 per cent) died of renal failure three weeks to two months after the onset of jaundice. Amyloidosis should be considered in the patient with unexplained intrahepatic cholestasis, and liver tissue should be stained with Congo red and viewed under polarized microscopy.     

The renal circulation in hypertensive disease

The pivotal role of the kidney in sustaining hypertension from any source or etiology is becoming increasingly clear. The possibility that the renal vasculature participates not only in the pathogenesis of renal vascular hypertension, but also in that of essential hypertension, has been the subject of continuing interest for 40 years. Evidence that a functional abnormality resulting in increased renal vascular tone is present in about two-thirds of patients with uncomplicated essential hypertension is reviewed, along with more circumstantial evidence that sympathetic nervous system activity operating on the renal vasculature is responsible. Two additional groups of patients in whom a characteristic abnormality of the renal vasculature is present have also been identified. In one group there is severe hypertension which is resistant to most forms of antihypertensive therapy but which is especially responsive to propranolol. In these patients renal blood flow and glomerular filtration rate are reduced, renin secretion rate is increased and the renal vessels are resistant to vasodilators, suggesting the presence of advanced organic arteriolonephrosclerosis, as a complication of long-standing, severe hypertension. The renal lesion, in turn, contributes to the increasing severity of the process. In a second group of patients, generally young and with uncomplicated hypertension, renal blood flow is inappropriately increased. In these patients a number of observations on their renal vasculature, renin and aldosterone responses to a volume challenge suggest an abnormality in the perception of extracellular fluid volume. A perfectly normal renal arterial tree, free of organic abnormality or an increase in tone due to active vasoconstriction, is distinctly unusual in essential hypertension.     

Steroid myopathy in connective tissue disease

In eight women with polymyositis (three patients), systemic lupus erythematosus (SLE) (three patients), rheumatoid arthritis (one patient) and shoulder-hand syndrome (one patient), weakness developed during high dose prednisone therapy. These women were studied using serial functional and manual muscle tests, determination of serum glutamic oxaloacetic transaminase (SGOT), creatinine phosphokinase (CPK) and serum aldolase levels, and urinary excretion of creatine. Insidious onset of weakness was characteristic. Myalgias were seen in five patients and unusual sudden weakness in two. Weakness was always most severe in the pelvic girdle muscles; there was a lesser involvement of shoulder girdle and distal muscles.Serum muscle enzyme levels were normal in all cases, but urinary creatine excretion was invariably increased and proved to be the most sensitive laboratory indicator for clinical diagnosis and for monitoring patient improvement. Serial urinary creatine excretion and serum enzyme studies were of value in differenting steroid myopathy from a flare of myositis in patients with connective tissue disease. Diagnosis and effective management were achieved by the use of readily available laboratory and clinical procedures without resorting to muscle biopsy.     

1,25-dihydroxyvitamin D3: a kidney-produced steroid hormone essential to calcium homeostasis

Principal among the many relationships involving the metabolism and function of vitamin D is the central role of the kidney in the production of the biologically active steroid, 1,25-dihydroxychole-calciferol. Three important topics under intensive investigation in many laboratories are (1) the role of the kidney as an endocrine organ producing the biologically active form of vitamin D, (2) the regulation of the endocrine organ and its integration in the process of calcium homeostasis, and (3) reevaluation of the wide variety of vitamin D-related disease states as they relate to the central role of the kidney in vitamin D action.     

Bacteremia due to Fusobacterium species

Twenty-six patients were identified as having bacteremia with Fusobacterium species over a five-year period at Boston City Hospital. They represented 0.9 percent of bacteremic patients and were equally divided as to sex. Bacteremia with Fusobacterium occurred primarily in young adults and in patients over 60 years of age and was not observed in children. In 16 patients (62 percent), Fusobacterium was the only blood culture isolate. The most common primary foci of infection were the female genital tract, the upper respiratory tract, the oral cavity, and the lower respiratory tract. Five patients had primary foci of infection that were initially occult. Three of these patients were found to have unappreciated oral and pharyngeal lesions, and one had a liver abscess; no primary infection was established in the remaining patient. Shock related to bacteremia developed in six patients (23 percent), four of whom had Fusobacterium species as the only blood culture isolate. Death occurred in three patients (12 percent), all of whom were over 60 years old. Metastatic infection occurred in only one patient in whom hematogenous osteomyelitis developed. Postpartum fusobacterial bacteremia was uniformly benign. Evaluation of bacteremia with Fusobacterium species in nonpostpartum patients, without an overt focus of infection, should be directed to a search for occult abscess, especially of the upper respiratory tract and oral cavity.     

Iso-renin of extrarenal origin: The tissue angiotensinogenase systems

Enzymes, similar to kidney renin, are present in extrarenal tissue of most mammals; they hydrolyze angiotensinogen to form angiotensin I. We suggest that these enzymes be called angiotensinogenases. Angiotensinogenase concentrations in extrarenal tissue can exceed those in the kidney. The enzyme has been obtained in pure crystalline form. Angiotensinogenases are part of a complex enzyme system which leads to local production of angiotensin. Results indicating a biologic role of the angiotensinogenase system in brain, adrenal gland, uterus and tissue culture are discussed.     

A new clinical index of growth rate in the staging of breast cancer

The clinical rate of growth in patients with breast cancer can be auxometrically classified by identifying the first clinical manifestation observed by the patient (or physician) and by then noting the progression interval that elapsed before treatment and the occurrence of prognostically unfavorable transition events during that interval. These two features can be used to demarcate slow, intermediate and rapid auxometric stages, which approximate the cancer's rate of progression. A fourth stage consists of patients who have systemic or metastatic symptoms before treatment.Within any TNM (tumor-nodes-metastases) stage, degree of nodal involvement or treatment, these four auxometric stages delineate patients with distinctly different prognoses. In particular, the slow auxometric stage can be used to identify a subgroup of patients with excellent 10 year survival and other patients who have good outcomes despite an anatomically unfavorable status. Conversely, the rapid and systemic-metastatic stages identify patients with relatively poor prognoses despite an apparently favorable anatomic status. The auxometric classification is easily used, readily available and involves no technologic expense or risk. By improving the accuracy of anatomic staging, auxometry adds an important refinement to the estimation of prognosis and the evaluation of therapy for patients with breast cancer.     

A histologic evaluation of mixed connective tissue disease in childhood

Mixed connective tissue disease (MCTD) includes features of scleroderma, dermatomyositis and systemic lupus erythematosus (SLE), and has speckled antinuclear antibodies (ANA) and high titers of anti-RNP antibodies. There are no comprehensive investigations of its histopathology. We have followed 15 children with MCTD, of whom four have died (mean disease duration prior to death 5.4 years). The immediate causes of death were pneumococcal sepsis (two patients), meningococcal sepsis (one patient) and uncontrollable thrombocytopenia (one patient). Material from the three available autopsies and five renal biopsies was reviewed.The most prominent histopathologic feature was widespread proliferative vascular lesions including intimai vascular change in 31 of 58 organs (53 per cent) and medial vessel wall thickening in nine organs (16 per cent). Systemic hypertension was absent; the normal vascular responses to aging could be excluded. Inflammatory infiltrates, often with prominent plasmacytosis, were present in 26 of 58 organs (45 per cent), but fibrinoid vascular change (9 per cent) and fibrosis (14 per cent) were rare. Eight renal specimens all showed some degree of glomerulonephritis; membranous change was present in three, and six showed significant vascular sclerosis.The histopathology of MCTD is superficially similar to systemic sclerosis, but it may be distinguished by less frequent fibrosis, the frequency of organs with intimal vascular change, and a predilection for intimai thickening of large arteries including coronary, pulmonary, renal and aortic. A distinctive replacement of muscle layers by hyaline in the gastrointestinal tract, and an unusual nodular hyperplasia of the thymic medulla were also observed and may be unique features of MCTD. The findings from this study suggest an immunologic basis for MCTD different from those postulated for other rheumatic diseases, and strongly suggest that adjustment of morbidity and mortality expectations for MCTD are necessary.