Angioimmunoblastic lymphadenopathy with hypogammaglobulinemia. Possible role of monocyte suppression

A patient wit angioimmunoblastic lymphadenopathy had low serum immunoglobulin values and no antibodies to injected immunogens. This occurred despite the proliferation of polyclonal B cells. T cells were deficient in number and in lymphoproliferative responses, but their helper and suppressor functions were maintained. Ia-antigen bearing leukocytes from the patient stimulated poorly in mixed leukocyte culture. In vitro immunoglobulin synthesis by mononuclear leukocytes form the patient was severely impaired. These leukocytes actively suppressed immunoglobulin synthesis by normal cells from healthy subjects in co-culture. The responsible cell had characteristics of a monocyte. The suppression was selective for humoral immunity and was manifest despite normal numbers of monocytes. It appears that heterogeneous immunoregulatory abnormalities can underlie the syndrome of angioimmunoblastic lymphadenopathy. Furthermore, monocyte suppressor abnormalities may be implicated in clinical disease phenomena.     

Rhabdomyolysis in thyroid storm

This is the first reported case of thyroid storm complicated by rhabdomyolysis with acute reversible renal failure. The only possible causes for the rhabdomyolysis were inherent features of thyroid storm. Although hyperthyroid patients characteristically have normal or low serum levels of muscle enzymes, this case report demonstrates that rhabdomyolysis with elevated serum levels of muscle enzymes can occur with hyperthyroidism. An appreciation of the potential for rhabdomyolysis in hyperthyroidism should facilitate prompt initiation of aggressive therapy for myoglobinuria and thereby limit the severity of acute renal failure in these already very sick patients.     

Autoimmune hemolytic anemia and carcinoma: an unusual association.

Four patients with Coombs'-positive hemolytic anemia associated with carcinoma are presented and compared to 12 previously described patients. These patients commonly seek medical attention for symptoms of anemia rather than for complaints due to the tumor mass. The physician should particularly evaluate for an underlying carcinoma when a patient over the age of 60 years presents with autoimmune hemolytic anemia. Autoimmune hemolytic disease has been demonstrated in patients with a wide variety of tumors, including squamous cell carcinomas, adenocarcinomas, hypernephromas, oat cell carcinomas and a seminoma. Corticosteroid treatment is less effective in autoimmune hemolytic disease associated with carcinoma than in idiopathic autoimmune hemolysis. Tumor extirpation in patients with localized neoplastic disease may abolish the autoimmune hemolytic anemia. Control of the carcinoma through irradiation and chemotherapy together with corticosteroid therapy and/or splenectomy lessened the anemia in some patients. The positive Coombs' test may revert to negative with tumor excision or control. Subsequently, the positivity of the Coombs' reaction may provide a clue to recurrent neoplastic activity. The pathogenic mechanism underlying the association between carcinoma and autoimmune hemolytic disease is poorly understood.     

Changes in plasma potassium concentration during acute acid-base disturbances

It has been widely held that the changes in plasma potassium concentration observed during acute acid-base disorders are solely determined by the associated changes in blood acidity. However, a critical examination of the literature uncovers wide differences among the four cardinal acid-base disorders with respect to the associated changes in plasma potassium concentration. In fact, the data suggest that a host of factors other than the attendant changes in plasma hydrogen ion concentration may well modulate the intercompartmental distribution of body potassium during acid-base disorders. In this study we review the qualitative, quantitative and mechanistic aspects of the plasma potassium response to acute alterations in blood acidity.     

The influence of PEEP on survival of patients in respiratory failure: a retrospective analysis.

Positive end expiratory pressure breathing (PEEP) is used to decrease morbidity and mortality in patients who are hypoxemic despite breathing oxygen in concentrations potentially toxic to their lungs. We reviewed the hospital course of 78 patients whose arterial oxygen tension (PaO2) was less than 70 torr despite a fraction of inspired oxygen (FiO2) of 1.0. Only 60 per cent of these patients were treated with PEEP and their clinical illnesses and severity of cardiopulmonary dysfunction were similar to those in patients not treated with PEEP. PEEP increased the length of survival from 4.2 to 9.2 days (P less than 0.05) whereas over-all survival, defined as hospital discharge, was similar at 31 per cent with and 26 per cent without PEEP. An improvement in PaO2 and decrease in shunt fraction following a trial of PEEP portends a favorable outcome, but its continued use appears to prolong life for a few days without affecting hospital mortality. Survival appears related more to the maintenance of adequate tissue oxygenation as manifested by a high mixed venous oxygen than to improved gas exchange as reflected by an increase in PaO2.     

Acute promyelocytic leukemia. A review of literature.

Acute promyelocytic leukemia is a form of acute myeloblastic leukemia characterized by hemorrhagic episodes, severe thrombocytopenia and infiltration of the marrow with "hypergranular" promyelocytes, often with multiple Auer bodies. Ultrastructurally. the promyelocytes show many splinter granules and Auer bodies with characteristic hexagonal arrangement of tubules with a periodicity of 250 A. Serum vitamin B12 and B12-binding proteins, in particular, transcobalamin I, are abnormally high. Karyotypic abnormalities include pseudodiploidy and partial deletion of the long arm of chromosome 17. Coagulation profile during bleeding episodes is usually consistent with disseminated intravascular coagulation. Greatly improved prognosis in recent years as a result of aggressive chemotherapy and anticoagulation emphasizes the need of early recognition of this clinical entity.     

A randomized study of carbenicillin plus cefamandole or tobramycin in the treatment of febrile episodes in cancer patients.

Patients were randomly assigned to receive carbenicillin plus tobramycin by continuous infusion (C+T), carbenicillin plus cefamandole by continuous infusion (C+CC) or carbenicillin plus cefamandole by intermittent infusion (C+IC) during 490 febrile episodes. Carbenicillin was administered over 2 hours every 4 hours. The per cent of cures achieved during the 235 documented infections was 65 per cent for C+CC, 57 per cent for C+IC and 54 per cent for C+T. Among those infections caused by single gram-negative bacilli, C+CC produced a higher cure rate than C+IC or C+T(74 per cent versus 59 per cent versus 50 per cent). C+CC was significantly more effective than C+IC among patients with persistent severe neutropenia of less than 100 neutrophils/mm3 (65 per cent versus 21 per cent, p = 0.03). If the infecting organism was sensitive to both antibiotics, the cure rate which occurred during 12 per cent to 13 per cent of the febrile episodes, regardless of antibiotic regimen. However, it occurred significantly more often during documented infections than during fevers of unknown etiology (20 per cent versus 6 per cent, p less than 0.001). C+CC appears to be the most effective of the three regimens for the treatment of infections in patients with persistent severe neutropenia.     

Nitroprusside therapy in acute and chronic coronary heart disease

To elucidate the effects of nitroprusside on the relations between systemic pressure, coronary blood flow and regional myocardial ischemia, dogs were subjected to constriction of the proximal left anterior descending (LAD) artery to induce ischemia determined by intramyocardial S-T segments and intramyocardial mass spectrometric oxygen tension (PO₂) and carbon dioxide tension (PCO₂). Nitroprusside was infused to incrementally lower mean blood pressure from 137 to 62 mm Hg. A decrease in mean blood pressure to 87 mm Hg lowered (p < 0.05) intramyocardial S-T segment elevations and diminished left ventricular filling pressure, but it did not alter (p > 0.05) poststenotic flow in the LAD artery, intramyocardial PCO₂ and PO₂, and cardiac oxygen uptake. With a further decrease in systemic arterial blood pressure below normal, S-T segments rose, LAD artery flow decreased, intramyocardial PCO₂ increased and intramyocardial PO₂ decreased. In addition, 12 patients with acute anterior infarction had 35-lead S-T segment maps before and after a 10 minute infusion of nitroprusside. Heart rate was unchanged, left ventricular pressure decreased from 139/19 to 115/11 mm Hg (p < 0.01), cardiac index was maintained, S-T segment sum was lowered from 42 to 29 mm (p < 0.001) and mean S-T segment elevation declined from 1.6 to 1.2 mm/lead (p < 0.001). Thus, modest nitroprusside-induced reduction in blood pressure has beneficial effects on multiple indices of experimental and clinical regional ischemia. In contrast, a further decrease in blood pressure below normal lowers poststenotic coronary blood flow and thereby ischemia worsens.     

The effect of nitroglycerin on atrioventricular conduction in man

His bundle electrograms were performed on 10 patients with organic heart disease. Six patients had had a recent myocardial infarction. Recordings were made at various rates utilizing right atrial pacing. Nitroglycerin, $\text{1}\text{150}$ gr, was administered to all 10 subjects, and the P-A, A-H, H-Q and H-S intervals were determined before, and immediately after the disappearance of the sublingually administered nitroglycerin. A significant decrease in the A-H interval occurred with negligible effects on the P-A, H-Q and H-S intervals. At the atrial pacing rate of 100/min, the average A-H interval fell from the control value of 152 msec to 129 msec after the administration of nitroglycerin (p < 0.02); at the pacing rate of 130/min, the A-H interval decreased from 194 to 133 msec (p < 0.05). Second degree heart block occurred at higher pacing rates in six patients after nitroglycerin administration as compared to the control value. The average postsuppression sinoatrial recovery time control value of 1,083 msec decreased to 906 msec after nitroglycerin administration (p < 0.01). These findings demonstrate that nitroglycerin can improve conduction through the A-V node.     

Induction of clinical ventricular tachycardia using programmed stimulation: value of third and fourth extrastimuli

Initiation of ventricular tachycardia (VT) by right ventricular extrastimulation was analyzed in 142 consecutive patients, 53 with electrocardiographically documented episodes of spontaneous VT or ventricular fibrillation (VF) and 68 with no spontaneous VT or VF; 21 patients with a history of sudden death but no documented arrhythmia were excluded from further analysis. All patients received 1 to 4 extrastimuli (S2, S3, S4 and S5) during pacing at fixed cycle lengths of 600 or 500 msec at 1 or 2 right ventricular sites. Clinical VT was reproduced by extrastimulation in 28 of 43 patients (65%) with sustained VT and in 0 of 10 patients with nonsustained VT. Clinical VT was induced by S2 or S3 in 16 patients and by S4 or S5 in 12 patients. Ventricular burst pacing reproduced clinical VT in 3 other patients. Nonclinical VT, which was most often polymorphic and nonsustained, was induced in 24 of 121 patients (20%), in 11 by S2 or S3 and in 13 by S4 or S5. Ventricular burst pacing induced nonclinical VT in 4 other patients. In patients with spontaneous sustained VT, the use of S4 and S5 in the right ventricle increases the yield of inducible clinical VT compared with use of S2 and S3 alone, but at a cost of increased induction of nonclinical VT. Frequent induction of nonclinical VT limits the interpretation of the results of such stimulation in patients without previously documented VT.     

Anaerobic bacterial meningitis.

Anaerobic meningitis occurred in four patients in whom anaerobic bacteria had not been suspected as a possible cause. The predisposing conditions were typical of those seen in patients previously reported to have this infection and included chronic otitis media with mastoiditis, chronic sinusitis, recent craniotomy and abdominal trauma. Two of the patients had undergone immunosuppression (immunosuppressed patients); a compromised immune system may facilitate the development of anaerobic meningitis in patients with the appropritate underlying conditions. Head and neck neoplasms, head trauma, suppurative pharyngitis and laminectomy wounds are additional situations in which anaerobic meningitis occurs. Anaerobic bacterial meningitis probably occurs more often than is recognized. The cerebrospinal fluid should be transported and cultured anaerobically when meningitis develops in a patient with a predisposing condition.     

A nationwide outbreak of Reye's syndrome: Its epidemiologic relationship to influenza B

Between December 15 and June 30, 1974, 379 cases of confirmed Reye's syndrome were reported to the Center for Disease Control. Of these, 316 occurred during February and March 1974. A simultaneous surveillance system for influenza B indicated that this clustering of cases of Reye's syndrome correlated both temporally and geographically with influenza B outbreaks. The incidence of Reye's syndrome was higher in rural than in urban centers. Epidemiologically, two groups of cases of Reye's syndrome emerge: those which occur in older children (median age 11 years), cluster in time and geographic region, and are associated with antecedent influenza B infection; and those which occur sporadically throughout the year, are isolated in occurrence, occur in younger children (median age 6 years), and are associated with a wide variety of antecedent viral illnesses.     

Efficacy of intravenous vancomycin in the treatment of gram-positive peritonitis in long-term peritoneal dialysis

Peritonitis is the major complication of long-term peritoneal dialysis. Gram-positive bacteria are responsible for two thirds of the total number of peritonitis episodes. Conventional therapy consists of daily administration of antibiotics, either parenterally or intraperitoneally. Vancomycin, an antibiotic with a prolonged half-life in renal failure, has a wide spectrum of activity against gram-positive bacteria and diffuses readily across the peritoneal membrane. In the present study, 82 percent of gram-positive peritonitis episodes were cured following the intravenous administration of vancomycin at weekly intervals. This cure rate compares favorably with that obtained following conventional therapy of peritonitis. It is concluded that intravenous vancomycin is an effective treatment for gram-positive peritonitis in patients undergoing long-term peritoneal dialysis. This form of therapy is convenient, reduces hospitalization, minimizes cost, and avoids possible contamination of the peritoneal dialysate used during the intraperitoneal administration of antibiotics.     

Pleural involvement in sarcoidosis

A review of the records of 227 patients with biopsy proved sarcoidosis disclosed roentgenographic evidence of pleural reactions (pleural effusion and/or pleural thickening) in 23 (10.1 per cent). Pleural effusions were noted in 15, and in all of these the disease process showed signs of progression to stage 2 or beyond. Transudative effusions were found in eight patients. Pleural biopsies in seven patients with effusion disclosed noncaseating granulomas consistent with sarcoidosis. An extensive evaluation for other underlying disease processes, in all cases was negative. The effusions resolved, but in two patients serial roentgenographic studies showed progression to chronic pleural thickening. Pleural thickening was observed initially in eight patients and was always associated with an advanced stage of sarcoidosis. Biopsies performed in five of these patients showed thickened fibrotic pleura interspersed with noncaseating granulomas. On review of lung biopsy specimens from 11 patients with no roentgenographic indication of pleural reactions, noncaseating granulomas in simultaneously obtained pleura were found in four.The pleura is affected in sarcoidosis more frequently than has been recognized. The occurrence of pleural involvement and reaction is a consequence of sarcoidosis and appears to be associated with the progression of the disease process.     

Occult Cushing's disease presenting with acute psychosis

A 37-year-old woman presented with acute psychosis and cognitive impairment. Skull x-ray showed an enlarged sella turcica with erosion of the floor. Endocrinologic workup suggested the diagnosis of Cushing's disease and hyperprolactinemia. She had no cushingoid feature, and the only physical sign was mild generalized obesity. She showed a paradoxic response to dexamethasone suppression, and underwent trans-sphenoidal resection of a pituitary macroadenoma. Electron microscopy showed the tumor to be a Crooke's cell adenoma. Results of immunohistochemical staining were positive only for ACTH and beta-endorphin. The neuropsychiatric manifestations resolved after surgery.     

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.     

Association of a chromosomal abnormality with lymphocytes having both T and B markers in a patient with lymphoproliferative disease.

The lymphocytes of a patient with leukemic lymphosarcoma were found to have an unusual surface phenotype in that they bound both sheep erythrocytes (a T cell marker) and complement-coated erythrocytes (a B cell marker) but lacked other B cell surface characteristics. Marker chromosomes were present in these cells, but not in other, phenotypically normal cells from the same patient. This case may provide a clue to the chromosomal origin of some lymphocyte surface markers in man.     

Response of Paget's disease to porcine and salmon calcitonins: effects of long-term treatment

Multiple clinical, biochemical and immunologic variables were measured in 49 patients with Paget's disease during 4 to 41 months (mean, 25 months) of treatment with porcine (PCT) or synthetic salmon calcitonin (SCT) or both. Mild nausea and dermal reactions occurred in 20 per cent of the patients and were generally transient. Skeletal and radicular pain, and overt neurologic deficits were moderately to dramatically relieved in 75 per cent of the patients. Maximal clinical benefits were achieved during the first 6 to 12 months of treatment, with only one fifth of the patients experiencing intermittent exacerbations of pain during the 2nd and 3rd years of treatment. Three examples of dramatic roentgenologic improvement were observed. SCT doses of 50 MRC units three times a week generally were as effective as 100 MRC units three times a week or daily. Dissociation among the clinical effects, the decrease in serum alkaline phosphatase and the decrease in urinary hydroxyproline were common.Binding antibodies developed in 60 per cent of the patients treated with PCT and in 30 per cent of those treated with SCT; however, SCT-binding antibodies usually were present in higher titer and with a greater frequency of SCT neutralization activity. No correlations were present between the development of antibodies and the incidence of biochemical rebounds or the failure of increased doses of SCT to renew biochemical effects. No evidence of increased secretory activity of the parathyroid glands was observed in 10 patients with biochemical rebounds.These data demonstrate the feasibility and efficacy of continuous long-term therapy with calcitonin on an outpatient basis, and SCT may be the treatment of choice for Paget's disease.