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.     

Remission of Cushing's disease after administration of adrenocorticotropin

After receiving injections of ACTH, acute adrenal insufficiency developed in a patient with Cushing's disease presumably because of adrenal hemorrhage. The Cushing's disease remained in remission for 3 years and then recurred     

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.     

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.     

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.     

The superiority of the metyrapone test versus the high-dose dexamethasone test in the differential diagnosis of Cushing's syndrome

Differentiating the cause of Cushing's syndrome traditionally has depended upon measuring the response of 24-hour urine samples of cortisol or glucocorticoid metabolites to the high-dose (8 mg per day) dexamethasone test. The metyrapone test, however, is more convenient because it is a shorter test and requires the obtainment of serum samples, which can be collected more simply and more reliably than 24-hour urine samples. The usefulness of these two tests has not been adequately evaluated in a large series of patients with Cushing's syndrome. This study prospectively evaluated the accuracy of the dexamethasone and metyrapone tests in determining the cause of Cushing's syndrome in a series of 25 unselected patients. The diagnostic accuracy of these tests was calculated as follows: diagnostic accuracy = true positives and true negatives/study population X 100. Results of this study demonstrated that the metyrapone test was more accurate than the dexamethasone test in differentiating Cushing's disease from adrenocortical neoplasm (diagnostic accuracy, 100 percent versus 81 percent). All patients with Cushing's disease had a normal postmetyrapone 11-deoxycortisol concentration (greater than 10 micrograms/dl), while all patients with adrenocortical neoplasm had a suppressed 11-deoxycortisol concentration (less than 10 micrograms/dl). Thus, this study demonstrates that the metyrapone test is superior to the high-dose dexamethasone test in the differential diagnosis of Cushing's syndrome.     

Correction of infantile agranulocytosis (Kostmann's syndrome) by allogeneic bone marrow transplantation

Allogeneic bone marrow transplantation has been unsuccessful as therapy for genetically determined bone marrow disorders. In patients prepared for transplantation with drugs alone long-term hematopoietic engraftment is not achieved due to the overgrowth of the infused donor bone marrow cells by residual recipient hematopoietic stem cells. Utilizing a combination of total body irradiation and antihuman thymocyte serum, the successful eradication of the abnormal hematopoietic stem cells of patients with the Wiskott-Aldrich syndrome and now infantile agranulocytosis has been achieved. Following preparation with total body irradiation and antihuman thymocyte serum a 20 month old patient with infantile agranulocytosis has complete donor hematopoietic and lymphoid engraftment one year after a histocompatible allogeneic bone marrow transplant. Prior to transplantation, this patient had no circulating or bone marrow granulocytes; following transplantation he has normal numbers of circulating granulocytes with normal in vivo and in vitro function. This therapeutic result demonstrates that genetic disorders of myeloid function can be corrected by allogeneic bone marrow transplantation following preparation with total body irradiation and antihuman thymocyte serum, and suggests that infantile agranulocytosis is due to an intrinsic defect of the pluripotent hematopoietic stem cell and not to a micro-environmental defect.     

Primary empty sella syndrome, ACTH hypersecretion, and normal adrenocortical function. Report of two cases

Although the primary empty sella syndrome (PESS) is associated with normal endocrine function or subtle pituitary insufficiency, pituitary hormone hypersecretion associated with PESS has also been recognized. ACTH hypersecretion and primary empty sella syndrome have previously been reported in patients with either Cushing's disease or Addison's disease. This report describes two unique patients with ACTH hypersecretion, primary empty sella syndrome, and normal cortisol dynamics. The investigators speculate that this association may have resulted from infarction of hyperplastic adenohypophyseal corticotrophes due to production of an ACTH peptide with reduced biologic activity. These two cases emphasize that primary empty sella syndrome may be associated with ACTH hypersecretion and normal adrenocortical function.     

A convenient approximation of life expectancy (the “DEALE”): II. Use in medical decision-making

We show how to use a bedside approximation of life expectancy in quantitative decision-making. This method, the declining exponential approximation of life expectancy (DEALE), enables the physician to collate various survival data with information on morbidity to determine a quality-adjusted expected survival for a potential management plan. The keystone in the DEALE approach is the approximation of survival by a simple exponential function. This approximation makes it possible to translate data from various literature sources (life expectancy tables, five-year survival rates, survival curves, median survival) into a single, unified mortality scale. In this paper, we use the DEALE method to obtain approximations of quality-adjusted life expectancy and illustrate the application of the method in a quantitative analysis of a clinical decision.     

Metastatic infection secondary to genitourinary tract sepsis

Metastatic infections arising from sepsis in the genitourinary tract are reviewed in 175 cases, including five in which we treated the patients. The skeleton was the most common site of metastasis (59 per cent). The endocardium was next most frequently involved (28 per cent). Gram-negative organisms were implicated in less than two-thirds of the cases (59 per cent). Impaired host defense mechanisms were noted in 25 per cent of the patients experiencing metastatic infections.The lower urinary tract was the source of metastasis in 75 per cent of the patients, particularly after urologic manipulation in men. Women were more likely to experience metastatic infection from the upper urinary tract. Anatomic and pathologic considerations explaining these sex differences are presented.     

Glomerular deposition of tumor antigen in membranous nephropathy associated with colonic carcinoma

Renal biopsy in a 60 year old man with idiopathic nephrotic syndrome revealed the characteristic light, immunofluorescent and electron microscopic features of membranous nephropathy. Elevated serum levels of carcinoembryonic antigen (CEA) were present, and a colonic carcinoma was found and resected. CEA could not be demonstrated in the glomerular immune deposits. An antibody was demonstrated in the patient's serum 1 week after resection of the tumor which was reactive with an antigen deposited on the glomerular basement membrane. This reactivity was specifically abolished by absorption of the serum with homogenates of the patient's tumor, but it was not altered by absorption with normal colon, colonic polyps, liver or spleen. The nephrotic syndrome persisted after resection of the tumor. A renal biopsy 4 months later showed evidence of complex resolution, and the tumor-associated antigen was no longer detectable in glomeruli.The nephrotic syndrome associated with colonic carcinoma in this patient appeared to be mediated by glomerular deposition of immune complexes containing a tumor antigen. Apparent complete removal of the source of antigen was followed by evidence of complex resolution but had no effect on the nephrotic syndrome.     

Capturing clinical expertise. A computer program that considers clinical responses to digitalis

The administration of digitalis by experienced cardiologists has been examined and a prototypical computer program has been developed which captures portions of their expertise. The new program first constructs a patient-specific model upon which to base the determination of dosage and then uses feedback information about a variety of clinical aspects of the patient's response to modify its recommendations. The model reflects both the program's knowledge of pharmacokinetics and those special features of the patient's condition which may alter his response to therapy. The program makes assessments of the therapeutic and the toxic effects of digitalis on the patient, and bases its subsequent recommendations on the "therapeutic-toxic" state which best describes the evolving clinical situation. A clinical trial was performed in which the program "followed" a series of patients managed by clinicians on a cardiology service. That trial demonstrated the feasibility of this type of program in dealing with acutely ill patients, even those who have increased sensitivity to the toxic effects of digitalis. Each patient in the trial in whom toxicity developed had received more digitalis than would have been recommended by the program. This approach to automated clinical consultation should eventually provide a technology for the distribution of clinical expertise.     

Ocular and pericardial involvement in Legionnaires' disease

Legionnaires' disease can exhibit protean extrapulmonary manifestations. Pericardial involvement is rare and has been described in three case reports. A patient is described with Legionnaires' disease and pericardial and ocular involvement, an entity that has not been reported previously. This patient was successfully treated with intravenous erythromycin with resolution of his pericardial effusion and ophthalmologic findings.     

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.     

Acute infectious arthritis: A review of patients with nongonococcal joint infections (with emphasis on therapy and prognosis)

The clinical course of 59 patients with acute nongonococcai septic arthritis has been reviewed with special emphasis on the changing bacterial spectrum in recent years. The results of treatment were dependent on various factors, including the specific microbial agent and host defenses. Treatment should include parenteral antibiotics and drainage with needle aspfratton, except in hips which should be surgically drained. Successful therapy requires rapid initiation of treatment and ongoing assessment of adequacy of response.     

Towards the simulation of clinical cognition: Taking a present illness by computer

Remarkably little is known about the cognitive processes which are employed in the solution of clinical problems. This paucity of information is probably accounted for in large part by the lack of suitable analytic tools for the study of the physician's thought processes. Here we report on the use of the computer as a laboratory for the study of clinical cognition.Our experimental approach has consisted of several elements. First, cognitive insights gained from the study of clinicians' behavior were used to develop a computer program designed to take the present illness of a patient with edema. The program was then tested with a series of prototypical cases, and the present illnesses generated by the computer were compared to those taken by the clinicians in our group. Discrepant behavior on the part of the program was taken as a stimulus for further refinement of the evolving cognitive theory of the present illness. Corresponding refinements were made in the program, and the process of testing and revision was continued until the program's behavior closely resembled that of the clinicians.The advances in computer science that made this effort possible include “goal-directed” programming, pattern-matching and a large associative memory, all of which are products of research in the field known as “artificial intelligence.” The information used by the program is organized in a highly connected set of associations which is used to guide such activities as checking the validity of facts, generating and testing hypotheses, and constructing a coherent picture of the patient. As the program pursues its interrelated goals of information gathering and diagnosis, it uses knowledge of diseases and pathophyslology, as well as “common sense,” to dynamically assemble many small problem-solving strategies into an integrated history-taking process.We suggest that the present experimental approach will facilitate accomplishment of the long-term goal of disseminating clinical expertise via the computer.     

Metabolic alkalosis due to absorption of “nonabsorbable” antacids

In a patient with end-stage renal disease undergoing long-term maintenance hemodialysis, moderately severe metabolic alkalosis developed in the absence of vomiting or gastric drainage. The cause of the acid-base disorder was exogenous alkali administration, in the form of combined ingestion of “nonabsorbable” antacids (aluminum hydroxide and magnesium hydroxide), neutral phosphate, and a cation-exchange resin (sodium polystyrene sulfonate). In this report, the relevant data of this patient are detailed, and the literature on this well-documented, albeit poorly recognized, acid-base derangement is summarized.     

Outbreak of pyrogenic reactions at a dialysis center. Association with infusion of heparinized saline solution

Twenty-three pyrogenic reactions occurred in 16 patients undergoing hemodialysis at a private dialysis center in the south central United States between November 23 and December 2, 1978. No deaths were attributed to reactions; however, 10 patients were hospitalized for observation after experiencing a reaction. Cultures of all blood specimens obtained from the patients gave negative results. Chills (75 percent), nausea and/or vomiting (30 percent), and fever (90 percent) were the most common signs and symptoms, with mean times of onset after starting dialysis of 1.1, 1.6, and 3.6 hours, respectively. An epidemiologic and laboratory investigation documented that reactions occurred only in patients who had anticoagulation with a dilute solution of heparin. Analyses of heparinized saline solution used during the outbreak revealed a bacterial count of 7.4 X 10(5)/ml and a bacterial endotoxin level of 1,300 ng/ml. Acinetobacter calcoaceticus var. Iwoffi was isolated from the solution. Diluted heparin solution was prepared at the dialysis center by adding commercially supplied sodium heparin to 0.9 percent sodium chloride infusion fluid. Bacteria and endotoxin were not detected in vials of stock heparin and bags of unopened 0.9 percent sodium chloride infusion fluid. We concluded that contamination of the solution occurred at the dialysis center. After changes in the preparation and use of heparin were instituted on December 4, 1978, no pyrogenic reactions occurred in more than 400 subsequent dialyses.