Serologic diagnosis of access device-related staphylococcal bacteremia.

Staphylococcal bacteremia occurs frequently in patients undergoing long-term hemodialysis (dialysis patients). Although such bacteremia is frequently uncomplicated, it may be associated with endocarditis, metastatic infection or suppuration at the access site requiring excision of the access device for control of the infection (complicated bacteremia). To distinguish patients with uncomplicated bacteremia from those with complications, we measured staphylococcal teichoic acid antibodies by agar-gel diffusion and immunoglobulin G (IgG) antibodies by radioimmunoassay in 18 patients with staphylococcal bacteremia undergoing long-term hemodialysis. Although teichoic acid antibodies were not detected in five patients with uncomplicated bacteremia, they were observed in only three of 13 patients with complicated bacteremia. IgG staphylococcal antibodies were present in 10 of 13 patients with complicated bacteremia compared to none of five patients with uncomplicated bacteremia compared to none of five patients with uncomplicated bacteremia (p less than 0.05). Thus, radioimmunoassay was spuerior to agar-gel diffusion in identifying dialysis patients with complicated bacteremia. In patients with increased concentrations of IgG staphylococcal antibodies by radioimmunoassay, the diagnosis of endocarditis, metastatic infection and suppuration at the access site should be considered. Prolonged antibiotic therapy and/or operative removal of the access device may be necessary.     

Peripheral neuropathy presenting with respiratory insufficiency as the primary complaint. Problem of recognizing alveolar hypoventilation due to neuromuscular disorders

A 57 year old farmer, initially believed to have hypoventilation secondary to medullary respiratory insensitivity, died with a peripheral neuropathy and marked involvement of the phrenic nerves. Peripheral neuropathy has not previously been reported to present in this manner. Routine pulmonary function tests that would help to distinguish patients with hypoventilation due to neuromuscular disorders from patients with hypoventilation due to diseases of the lung parenchyma and depression of the medullary respiratory centers were investigated. Five subjects with severe neuromuscular disease were studied (arterial carbon dioxide tension [pCO₂]48 to 69 mm Hg, vital capacity [VC] 13 to 79 per cent of predicted and 1 second forced expiratory volume [FEV₁] 76 to 96 per cent of VC). The mean ratio of maximum mid-inspiratory flow (MMIF) to maximum mid-expiratory flow (MMEF) was 0.79. In age-matched control subjects this ratio was 1.41. In addition to observing the ratio of MMIF to MMEF other effective clinical screening procedures to distinguish patients with hypoventilation secondary to neuromuscular disorders from patients with medullary respiratory insensitivity include (1) identification of weakness of the muscles used for ventilation by measuring the static maximum inspiratory and expiratory airway pressures, (2) determination of ability to lower the arterial pCO₂ with voluntary hyperventilation, and (3) comparison of the maximum breathing capacity to the minute ventilation while breathing 7.5 per cent carbon dioxide for 3 minutes. The latter two measurements permit assessment of central hypoventilation in the presence of intrinsic lung disease.     

The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex

To determine the value of the electrocardiogram for differentiating aberrant conduction from ventricular ectopy, findings were retrospectively reviewed from patients with a widened QRS complex during tachycardia in whom the site of origin of tachycardia was determined by His bundle electrography. Seventy episodes of sustained ventricular tachycardia from 62 patients and 70 episodes of aberrant conduction during supraventricular tachycardia from 60 patients were available for study. Findings suggesting a ventricular origin of tachycardia were (1) QRS width over 0.14 sec, (2) left axis deviation, (3) certain configurational characteristics of QRS and (4) atrioventricular (A-V) dissociation. Capture or fusion beats resulting from A-V conduction of dissociated atrial complexes during ventricular tachycardia were seen during only four of 33 episodes of sustained tachycardia.     

Lung biopsy in immunocompromised hosts.

Ninety-five lung biopsy procedures in 78 immunocompromised patients yielded treatable diagnoses in 35 per cent of the needle aspirates, 46 per cent of the cutting needle biopsies and 65 per cent of the open thoracotomies. Complication rates of bleeding or pneumothorax were comparable to those previously described in nonimmunocompromised patients. In patients with coagulation defects, the risk of having bleeding complications was high. Among 44 patients with primary lymphoma, 22 (50 per cent) had a lymphomatous infiltrate in the lung. Twenty-two patients with severe hypoxemia were studied and their mortality, although significantly greater than in the patients without hypoxemia, was marginally improved when a treatable lung lesion was found. The over-all recovery rate was 70 per cent when a treatable diagnosis was made in contrast to 25 per cent when there was no specific diagnosis. Hence lung biopsy, particularly by thoracotomy, appears to be a valuable procedure in immunocompromised patients who have otherwise undiagnosable lung lesions.     

Hypoglycemia and endogenous hyperinsulinism complicating diabetes mellitus. Application of the C-peptide assay to diagnosis and therapy.

Described here is a patient with insulin-requiring diabetes mellitus in whom spontaneous fasting hypoglycemia developed. Endogenous hyperinsulinism was considered after the systematic exclusion of other causes of hypoglycemia, and this possibility was confirmed by measurement of serum C-peptide reactivity (CPR), an indicator of beta cell secretory function. Subtotal pancreatectomy relieved the fasting hypoglycemia, and was associated with a marked decline in CPR levels. The pancreatic islets showed hyperplasia and the beta cells were degranulated.     

Leukemic reticuloendotheliosis. A clinicopathologic study with review of the literature

The salient clinical and pathologic features of leukemic reticuloendotheliosis are evaluated in our 13 patients and in 98 patients described in the literature. Leukemic reticuloendotheliosis affects mainly male adults whose chief clinical manifestations are related to pancytopenia and splenomegaly. Splenomegaly is nearly constant and frequently massive, whereas lymphadenopathy is infrequent and skin involvement rare. Characteristic pathologic changes are present in the bone marrow, spleen and liver. Splenectomy often leads to remission; chemotherapy is not beneficial in most cases and is probably to be discouraged. The entity deserves recognition because the optimal clinical management is different from that of other forms of leukemia and lymphoma.     

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.     

Fever in systemic lupus erythematosus.

The frequency, causes, clinical and laboratory features, and outcome of febrile episodes in 160 hospitalized patients with systemic lupus erythematosus were reviewed. Eighty-three febrile episodes were identified in 63 patients and were ascribed to active lupus erythematosus alone (60 per cent), infections (23 per cent) and miscellaneous causes (17 per cent). Bacteremia was present in nine of the 19 infectious episodes and resulted in a fatal outcome in a third of the patients. Leukocytosis, neutrophilia, shaking chills and normal levels of anti-DNA antibodies were associated with infection in febrile patients with lupus erythematosus.     

Cell wall-deficient bacterial variant cultural surveillance. A useful laboratory aid.

A cell wall-deficient variant of Corynebacterium species was isolated from the blood of a patient with a chronic febrille illness of unkown etiology. He was given antimicrobial therapy, to which both variant and reverted bacterial forms of this organism were sensitive, and he recovered. Cultural surveillance for cell wall-deficient organisms was not only helpful in confirming the presence of infection in our patient but also in following his clinical course once antimicrobial therapy had been instituted.     

Atypical lymphoma with prolonged systemic remission after splenectomy. Description of three cases

Three patients with an unusual clinicopathologic picture and a striking response to splenectomy are described. All three presented with fever and severe systemic symptoms, pancytopenia and splenomegaly. Two of the patients had hypogammaglobulinemia and absent delayed hypersensitivity. Atypical lymphohistiocytic proliferation consistent with lymphoma was present in the spleen in all three patients, and also in the bone marrow and abdominal lymph nodes in two. Splenectomy led to prompt and prolonged clinical remissions in all three patients, possibly of a permanent nature in one.     

Late onset systemic lupus erythematosus.

This study describes the clinical and laboratory features and the natural history of 31 patients with late onset (in the sixth decade or later) systemic lupus erythematosus (SLE). Patients with late onset SLE constitute a distinct subset of the general lupus population that accounts for approximately 12 per cent of the cases. Advanced age modifies the expression of SLE in terms of clinical presentation (pleuritis and/or pericarditis are the most common presenting manifestations) and pattern of organ involvement (pulmonary abnormalities are more common, whereas lymphadenopathy, Raynaud's phenomenon, neuropsychiatric disease, alopecia and skin rash are less common). Because SLE is not usually considered to be a disease that affects the elderly, and because the pattern of SLE in the older age group may differ substantially from the seen in younger patients, there is often a delay in diagnosis (median of 10 months, with a delay of over one year in 32 per cent of patients). In light of the high incidence of steroid complications in older patients (40 per cent in our series), and because these patients with SLE have a relatively good prognosis (five year survival of 92.3 per cent; nine year survival of 83.1 per cent), therapy should be more conservative in late onset SLE.     

Influence of the kidney upon urate homeostasis in health and disease

The role of the kidney in the maintenance of urate homeostasis is reviewed, with particular emphasis upon the major contributions of Dr. Alexander B. Gutman to our understanding in this area. Data in support of various models of renal urate transport are presented, in conjunction with a discussion of the pyrazinamide suppression test and its limitations as a means of characterizing urate transport. It is proposed that postsecretory reabsorption of urate, as well as the rate of urate secretion, controls and modulates the final rate of urate excretion in man.The renal basis for some of the disturbances of urate homeostasis encountered clinically is also considered. The role of the kidney in the pathogenesis of the hyperuricemia observed in hypertension, toxemia of pregnancy, gout and renal failure is discussed, as well as three apparently distinct defects in tubular reabsorption of urate which lead to hypouricemia. It is emphasized that the mechanisms of renal urate handling in health, and the pathogenesis of the disordered states of renal urate homeostasis which are discussed, remain partially within the realm of speculation. A clearer understanding of the pathophysiologic mechanisms underlying disordered urate balance awaits more complete knowledge of normal physiology.     

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.     

Chest pain with angiographically insignificant coronary arterial obstruction: Clinical presentation and long-term follow-up

Among 3,242 coronary angiograms performed from November 1972 through October 1975 at the Massachusetts General Hospital, 175 patients had normal coronary arteries or luminal narrowings of less than 30 per cent. All patients were studied for chest pain, and none had experienced prior myocardial infarction. Subsequent information was available in 159 patients over a mean follow-up period of 42.7 months. There were no deaths, and only one myocardial infarction occurred during this period. However, among the patients followed, continued chest pain with episodes occurring at least once monthly was present in 54 per cent. In addition, 17 per cent of all patients required subsequent hospitalization and 44 per cent continued to receive antianginal medication. Nearly half of the group (46 per cent) suffered some limitation of activity, and 22 per cent stated that they had either changed jobs or stopped work because of chest pain. Continuing chest pain was significantly more common in women and in patients who had experienced chest pain for more than one year before angiography. However, typicality of chest pain for angina or the occurrence of electrocardiographic changes of ischemia prior to angiography did not predict continued chest pain during the follow-up period. Thus, although mortality and morbidity are low in this group of patients, the syndrome of chest pain with angiographically insignificant coronary artery obstruction has an important impact on the lives of a majority of those affected.     

Double myeloma. Production of both IgG type lambda and IgA type lambda myeloma proteins by a single plasma cell line

Monoclonal immunoglobulins G (IgG) and A (IgA) of the lambda light chain type were present in the serum of a patient with multiple myeloma. Three populations of myeloma cells were seen by immunofluorescence of bone marrow; those containing either IgG or IgA and those staining for both IgG and IgA. Idiotypic determinants present on the variable regions of the two myeloma proteins were immunologically identical and all the myeloma cells contained the same idiotypic determinant. The idiotypic specificity was related more closely to the variable region of the heavy chain than to the light chain. Structural and electrophoretic analysis confirmed that the light chains of the two myeloma proteins were identical. The myeloma in this patient appears to have arisen from a single clone of cells that was capable of synthesizing the constant portions of both the IgG and IgA heavy chain but only a single light and heavy chain variable region. These findings suggest that current concepts of antibody synthesis involving the sequential production of immunoglobulin M (IgM) and IgG antibodies may apply to certain cell lines synthesizing IgG and IgA antibodies as well.     

Serum estrogen levels in men with acute myocardial infarction

Serum estradiol and serum estrone levels were assessed in 29 men with acute myocardial infarction; in 17 men with unstable angina; in 14 men in whom myocardial infarction was ruled out; in 12 men without apparent coronary heart disease but hospitalized in an intensive care unit; and in 28 men who were not hospitalized and who acted as control subjects. (The 12 men who were hospitalized but who did not have coronary heart disease were included to control for physical and emotional stress of a severe medical illness.) Ages ranged from 21 to 56 years. Age, height, and weight did not differ significantly among groups. Blood samples were obtained in the patient groups on each of the first three days of hospttalization. The serum estrone level was significantly elevated in all four patient groups when compared with that in the control group. Estrone level, then, did not differentiate patients with and without coronary heart disease. Serum estradiol levels were significantly elevated in the groups with myocardial infarction, unstable angina, and in the group in whom myocardial infarction was ruled out. However, estradiol levels were not significantly elevated in the group in the intensive care unit without coronary heart disease when compared to the level in the normal control group. Serum estradiol levels, then, were elevated in men with confirmed or suspected coronary heart disease but were not elevated in men without coronary heart disease even under the stressful conditions found in an intensive care unit. Serum estradiol levels were significantly and positively correlated (p < 0.03) with serum total creatine phosphokinase levels in the patients with myocardial infarction. The five patients with myocardial infarction who died within 10 days of admission had markedly elevated serum estradiol levels. The potential significance of these serum estradiol elevations is discussed in terms of estradiol's ability to enhance adrenergic neural activity and the resultant increase in myocardial oxygen demand.     

Normal chemoreceptor function in obesity before and after heal bypass surgery to force weight reduction

Ventilatory responses to progressive isocapnic hypoxia and rebreathing of carbon dioxide in oxygen were determined in four obese women before and approximately 1 year after ileal bypass surgery to force weight reduction. None of the patients was hypoventilating and all had normal pulmonary function tests. The ventilatory responses to hypoxia were normal before surgery and were not effected by weight reduction. The ventilatory responses to hypercapnia did not change in slope but a shift of the carbon dioxide response line toward a lower arterial carbon dioxide tension occurred in two subjects after weight reduction. We conclude that obesity per se does not necessarily cause loss of hypoxic ventilatory drive.     

Enhanced in vivo platelet release reaction and malondialdehyde formation in patients with hyperlipidemia

Plasma level of beta-thromboglobulin (beta TG), a useful marker of in vivo platelet "release reaction,"was determined by radioimmunoassay in 69 patients, with three types of primary hyperlipidemia (IIa, IIb, IV) and compared with the findings in age- and sex-matched healthy controls and 57 patients with established atherosclerosis and peripheral vascular disease. Malondialdehyde (MDA) formation, used for assessment of prostaglandin synthesis, was determined in 51 and plasma platelet factor 4 (PF4), measured by radioimmunoassay, in 48 of the patients with hyperlipidemia. Results were correlated to five serum lipids and lipoprotein levels in the patients with hyperlipidemia. beta TG was significantly increased in the patients with hyperlipidemia and peripheral vascular disease, compared to those in the controls (p < 0.001); it was significantly higher in the patients with hyperlipidemia than in those with peripheral vascular disease. PF4 and MDA formation were also increased in the patients with hyperlipidemia, and significantly higher levels of MDA were obtained in patients with type IIb and type IV hyperlipidemia than in those with type IIa hyperlipidemia (p < 0.02). beta TG and MDA correlated weakly with total serum cholesterol triglycerides and very low density lipoprotein-triglyceride. There was also a significant correlation between beta TG and PF4, and MDA production. These results indicate that in vivo platelet "release reaction" and MDA formation are increased in hyperlipidemic patients. The release reaction is more enhanced in those with hyperlipidemia than in the patients with peripheral vascular disease. They suggest that the abnormal platelet function is related to the elevated levels of serum lipids and lipoproteins in the hyperlipidemic patients and not only to the atherosclerotic changes associated with hyperlipidemia.     

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.