Oral trimethoprim/sulfamethoxazole in attempt to prevent infection after induction chemotherapy for acute leukemia

The efficacy of orally administered trimethoprim/sulfamethoxazole for infection prevention following induction chemotherapy was evaluated in 43 patients with acute leukemia. Twenty patients were randomly assigned to treatment with trimethoprim/sulfamethoxazole during 20 episodes of profound granulocytopenia; 23 patients in the control group were followed through 25 granulocytopenic episodes. The incidences of superficial skin and overall infections were significantly lower in those patients with multiple relapses who received trimethoprim/sulfamethoxazole (p = 0.008); however, there was no difference between the groups in regard to days of fever, days of antibiotic administration, days of hospitalization, or gram-negative rod bacteremia. As a result of this study, this regimen cannot be unequivocally recommended for infection prevention in neutropenic patients with acute leukemia undergoing induction or reinduction chemotherapy.     

Infectious complications of neoplastic disease

Progress has been made in the diagnosis and treatment of infection in patients with neoplastic disease. Among the advances is the appreciation that certain opportunistic infections occur in association with particular host immune defects and epidemiologic factors. Such immune defects are seen secondary to or as a consequence of treatment for the patient's basic disease. Improved methods such as serology, open lung biopsy, and fiberoptic bronchoscopy have allowed for earlier diagnosis and treatment of opportunistic infections. The development of empiric antibiotic regimens, particularly aminoglycosides and the antipseudomonal penicillins, have improved the outcome in the febrile neutropenic patient. The benefits of protective environments have been challenged; prophylactic antibiotics and various forms of immunotherapy are of interest but remain investigational.     

Severe<Emphasis Type="Italic"> Chlamydia pneumoniae</Emphasis> infection in a patient with mild neutropenia during treatment of Hodgkin’s disease

Chlamydia pneumoniae is known to cause acute respiratory tract infections in the non-immunocompromised population. So far, no data about the incidence of chlamydial infections in neutropenic patients are available. Macrolide antibiotics are not considered to be first-line treatment options in neutropenic patients. We report the case of a patient with Hodgkins disease who developed C. pneumoniae pneumonia during mild neutropenia. C. pneumoniae should be considered as a causative agent of pneumonia in neutropenic patients.     

Accidental hypothermia in an alcoholic population

Thirty-nine cases of accidental hypothermia are reviewed. Data indicate that mortality varies with the presence of underlying disease rather than with the degree of hypothermia or the methods of rewarming. In 31 patients with hypothermia alone (average temperature 85 °F) mortality was 6.25 per cent. In eight patients with hypothermia and another primary condition (average temperature 84 °F) mortality was 75 per cent.Intractable cardiac arrhythmia has been reported as the primary cause of death in hypothermia. In these patients, death during hypothermia resulted from pulmonary complications. Ventricular arrhythmias, when they occurred, were responsive to routine measures such as electrical cardioversion and myocardial suppressant drugs. Methods of treatment are discussed.     

Analysis of T cell subsets in cancer patients treated with interferon

T cell subsets were analyzed in 33 patients with advanced cancer who were treated with either of two interferon preparations: a partially purified human leukocyte interferon (HulFN-alpha (Le] and a highly purified recombinant interferon (lFLrA). Included in the lFLrA-treated group were eight patients with immunodeficiency and Kaposi's sarcoma. The OKT4+/OKT8+ ratio was used to define the balance between helper/inducer and suppressor/cytotoxic T cell subsets. With both interferon preparations, the mean OKT4+/OKT8+ ratio decreased 24 hours after the first interferon dose. Within the HulFN-alpha (Le) group, the decrease in ratio was related to an increase in OKT8+ cells; in the lFLrA group, it was accompanied by a small decrease in the proportion of OKT4+ cells that was greater than the decrease in OKT8+ cells. Patients treated with lFLrA were followed for the first three weeks of therapy. Most patients treated with lFLrA at all dose levels, ranging from 1 X 10(6) to 54 X 10(6) units per day, had a decrease in OKT4+/OKT8+ ratio on Day 1. No substantial change in the ratio was observed on Days 7, 14, and 22. Patients with immunodeficiency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with lFLrA. In conclusion, although both HulFN-alpha (Le) and lFLrA induce immediate decreases in the OKT4+/OKT8+ ratio, the T cell subset(s) primarily responsible for the decrease varies with the source of interferon.     

Outbreak of Kaposi's sarcoma with cytomegalovirus infection in young homosexual men

Kaposi's sarcoma, a multicentric malignant neoplasm, occurs in certain geographic areas in the world. It is most common in Equatorial Africa and Eastern Europe. The annual incidence of Kaposi's sarcoma in the United States is between 0.021 and 0.061 per 100,000 persons. The appearance of an outbreak of Kaposi's sarcoma in young homosexual men in New York and California is a new and unique phenomenon. Certain differences are already recognized between the disease in these young men and the ordinary Kaposi's sarcoma. Herein we report our observations of the first 10 cases of Kaposi's sarcoma in young homosexual men. In these patients, the disease follows an aggressive clinical course characterized by widespread skin lesions with early involvement of the lymph nodes. In some of these patients, the result was death in a short period of time after initial diagnosis. In addition, cytomegalovirus infections were seen in these patients, which suggests at least a possible association between this viral and the disease.     

Therapeutic neutrophil transfusions: Are controlled studies no longer appropriate?

The aim of this review is to determine whether sufficient data have been reported to completely define the role and/or efficacy of neutrophil transfusions in the treatment of specific types of infections in neutropenic patients. Data were collected from the literature pertaining to the use of therapeutic neutrophil transfusions. When only the controlled studies are analyzed, a significant therapeutic advantage for neutrophil transfusions plus antibiotics can be demonstrated when this treatment is compared to treatment with antibiotics alone. However, the controlled studies are vulnerable to critical analysis, and several points argue against applying data from these studies indiscriminately to all infected, neutropenic patients encountered in practice. Moreover, it is apparent when all of the data (controlled and uncontrolled studies) are tabulated, that information is insufficient to establish the efficacy of neutrophil transfusions as treatment for most types of specific bacterial infections. Several problems exist in the wholesale acceptance of liberal transfusion policies, and the benefits that justify continued controlled studies deserve emphasis.     

Long-term antiarrhythmic therapy with acetylprocainamide

Nineteen patients whose arrhythmias were initially suppressed with acetylprocainamide underwent long-term treatment with this drug. Eleven patients were still taking the drug at the end of 12 months. Drug withdrawal with substitution of a placebo caused an increase in ventricular premature beats. Thus, suppression of ventricular premature beats persisted for 1 year. The eight withdrawals from the study were due to death during the year (n = 6) or recurrence of arrhythmias. The deaths occurred in patients who were in New York Heart Association functional class II (one patient), III (three patients) and IV (two patients). Ventricular performance, assessed from systolic time intervals, improved with drug therapy and declined during drug withdrawal. Symptomatic effects were common, with seven patients requiring a reduction in dosage or discontinuation of therapy. Three patients treated for 3 years continued to show drug suppression of ventricular premature beats compared with the level during placebo substitution. Small amounts of procainamide were present in all patients because of in vivo deacetylation of acetylprocainamide. Many patients with good initial responses to this drug had recurrent arrhythmias during long-term therapy. For this reason, the usefulness of acetylprocainamide as an antiarrhythmic drug appears to be limited.     

Active tuberculosis undiagnosed until autopsy

In this report 21 patients in whom tuberculosis was the primary cause of death, but which was not diagnosed until necropsy, are reviewed. Of the 21 deaths, 11 were due to pulmonary tuberculosis and 10 to miliary tuberculosis. Proper evaluation of the following factors might have led to the correct diagnosis in many of the patients: A family history of tuberculosis, prior pleurisy, a gastrectomy, diabetes mellitus or end-stage renal failure; all can be associated with an increased incidence of tuberculosis. A negative tuberculin skin reaction does not exclude the presence of active tuberculosis. In the search for Mycobacterium tuberculosis, the examination of just one or two sputum specimens is not an adequate bacteriologic investigation. A positive gastric smear can have diagnostic importance. Ascitic fluid findings can be characteristic of tuberculous peritonitis. A negative bone marrow aspirate for acid-fast bacilli does not exclude miliary tuberculosis. Significant anemia, high fever and leukopenia increases the possibility of tuberculosis. The persistence and/or progression of lung infiltration, irrespective of supposedly specific antibiotic therapy, strongly suggests tuberculosis. Miliary tuberculosis can present as an adult respiratory distress syndrome. All but one patient in this series had fever. The failure to diminish the pyrexia believed due to specific lung infections with presumably effective antibiotics, and the inability of therapy to control other conditions thought to cause the fever indicate the presence of tuberculosis. Tuberculosis, especially miliary disease, should be considered as a possible etiology of fever of unknown origin.If the diagnosis of tuberculosis is highly suggestive, even without bacteriologic confirmation, a therapeutic trial of antituberculosis drugs should be given.     

Infection and diabetes: The case for glucose control

This review summarizes data concerning the host resistance to infection in diabetes and the influence of an acute infection upon the endocrinologic-metabolic status of the diabetic patient. While it is well known that acute infections lead to difficulty in controlling blood sugar levels and that infection is the most frequently documented cause of ketoacidosis, controversy persists as to whether or not patients with diabetes mellitus are more susceptible to infection than age- and sex-matched nondiabetlc control subjects. Our data obtained from the charts of 241 diabetic patients who were being followed as outpatients show a striking direct correlation between the overall prevalence of infection (p < 0.001) and the mean plasma glucose levels (representing three or more fasting glucose determinations taken at times when no evidence of infection existed). There is a significant diminution in intracellular bactericidal activity of leukocytes with Staphylococcus aureus and Escherichia coli in subjects with poorly controlled diabetes in comparison with the control group. Serum opsonic activity for both Staph. aureus and E. coli were significantly lower than in the control subjects. Taken together, the results from published reports as well as our data suggest to us that good control of blood sugar in diabetic patients is a desirable goal in the prevention of certain infections (Candida vaginitis, for example) and to ensure maintenance of normal host defense mechanisms that determine resistance and response to infection.     

Repeated 1 hour electrocardiographic monitoring of survivors of myocardial infarction at 6 month intervals: Arrhythmia detection and relation to prognosis

In a study of the relation between ventricular premature beats and sudden death among 1,739 male survivors of myocardial infarction enrolled in the Health Insurance Plan of Greater New York (HIP), patients underwent 1 hour of electrocardiographic monitoring at a baseline examination. During follow-up periods of up to 5 1/2 years, survivors underwent repeated monitoring at 6 month intervals for a maximum of four monitorings. At each monitoring a constant proportion of the men—25 percent—showed complex ventricular premature beats (runs of two or more, R on T phenomenon, bigeminal or multiform beats) during the hour. In comparison with men free of such arrhythmia, those demonstrating these complex forms in a given hour were three times as likely to show such beats in a subsequent monitoring hour. The mortality risk over 3 1/2 years after each of the four monitoring observations was in all cases elevated among men with complex ventricular premature beats. The risk of sudden death over this period was 6 percent for men without and 13 to 17 percent for men with such complexes. A study of the 1,445 men who underwent monitoring both at baseline examination and 6 months later identified the presence of runs of ventricular premature beats in either observation as a particularly important harbinger of sudden death.     

Deaths from nosocomial infections: Experience in a university hospital and a community hospital

To assess the importance of nosocomial infections as a contributory cause of death in patients who die in the hospital, we studied the hospital course of 100 consecutive patients who died at Columbia-Presbyterian Medical Center and 100 consecutive patients who died at Hackensack Hospital. The epidemiologic patterns of infection were similar although the institutions provide care for different types of patients. There were 88 nosocomial infections in 63 patients. When the nosocomial infection was causally related or contributed to death, infection of the lower respiratory tract was predominant in 31 of 52 (60 per cent) instances. When the nosocomial infection was unrelated to death, urinary tract infection was predominant in 13 of 36 (36 per cent) infections. Among those who died with nosocomial infection, 42 of 63 (67 per cent) patients were terminal on admission and were typically in their 60's with metastatic carcinoma. The 21 patients who were not terminal on admission were typically in their late 70's and had complications of arteriosclerotic cardiovascular disease. Pneumonia was the most frequent nosocomial infection related to death. There is need to devise a pneumonia prevention program that identifies those at high risk and reduces the chance of aspiration of pharyngeal secretions and spread of virulent bacteria from person to person.     

Diffuse pulmonary infiltrates in immunosuppressed patients. Prospective study of 80 cases.

Over a two year period, we studied prospectively 80 cases of diffuse pneumonia at Memorial Sloan-Kettering Cancer Center. In 72 per cent of these, the patient had leukemia or lymphoma. Diagnostic procedures consisted of extensive serologic testing for antibody to known respiratory pathogens, including the agent of Legionnaire's disease, and culturing of biopsy specimens for bacteria, viruses, mycoplasmas and fungi. Of 44 cases in which open lung biopsy was performed, a specific cause was found in 61.4 per cent: Pneumocystis carinii in 38.6 per cent, other infections in 9.1 per cent and tumor involvement in 13.7 per cent. There were nonspecific pulmonary changes in 38.6 per cent. Of the 56 cases in which biopsy, autopsy or both were performed, a specific diagnosis was made in 69.7 per cent: P. carinii infection in 37.5 per cent and other infections in 12.5 per cent. In cases in which neither biopsy nor autopsy was performed, a specific infection was diagnosed in 33 per cent; no specific diagnosis was made in the remainder. One patient in the entire group had a significant antibody titer for Legionnaire's disease. Although diagnostic in some cases, extensive serologic testing proved relatively unfruitful. Pneumocystosis was the most frequent diagnosis in this study. The cause of some cases remained obscure, even after lung biopsy.     

Opportunistic fungal infections in patients with neoplastic disease

Opportunistic infections with yeast and molds are increasingly common in patients with neoplastic diseases. Candida species, Aspergillus species, Phycomyctes, and Cryptococcus neoformans remain most common, but other organisms are being encountered as pathogens. With the exception of Cryptococcus, most opportunistic fungal infections are difficult to diagnose. New diagnostic tests for these diseases are being evaluated. Amphotericin B remains the antifungal agent of choice. In certain patients, the addition of 5-flurocytosine may improve the outcome. Experience with cryptococcosis in severely immunocompromised cancer patients at Memorial Sloan-Kettering Cancer Center suggests that those who are treated with amphotericin B intravenously and intraventricularly via an Ommaya reservoir along with 5-flurocytosine do better than those treated with amphotericin B alone.     

Serious infections caused by Streptococcus milleri

Viridans streptococci continue to be the most common etiologic agents in bacterial endocarditis. The spectrum of diseases other than endocarditis caused by these organisms, however, has received sparse attention. Moreover, little clinical information is available concerning the individual viridans streptococcal species. During the 16 months of this study, one species of viridans streptococci, Streptococcus milleri, caused a surprising number of clinically significant suppurative infections. Clinical syndromes included the following: abscesses, 10 cases; peritonitis, four cases; endocarditis, three cases; cholangitis, empyema and cellulitis, one case each. A gastrointestinal source was apparent in eight of these 20 cases. Review of 58 cases of viridans streptococcal endocarditis demonstrated that although Strep. milleri was an infrequent cause of endocarditis, this species was associated with an unusual frequency of suppurative complications. Our experience suggests that Strep. milleri may be more commonly associated with serious suppurative infections than other viridans streptococci and that species identification may be a clinically useful procedure.     

Infection and chronic rheumatic disease in children

It is clear that various microbial agents can cause acute and chronic rheumatic disease by several mechanisms, that different agents, some perhaps yet unknown, may cause the same disease in different patients, and that genetic factors are important, perhaps crucial, to this host response. In trying to elucidate how microbe-host interactions result in chronic rheumatic disease, interest currently centers on the roles of genetic factors, of bacterial infections including endogenous flora, of cross-reactive microbial and host antigens, and of the immune response to them. As in the past, progress in understanding these complex interactions will probably be incremental and intermittent.     

Dynamic vascular factors in the genesis of myocardial ischemia

While fixed atherosclerotic and thrombotic lesions have long been known to cause myocardial ischemia and cardiac pain, the various transient or dynamic events that may also cause ischemia and pain have become better understood in the past 15 years. These can be classified into two broad categories: those that cause a dynamic reduction in the caliber of the coronary arteries and those that reduce the coronary vasodilatory reserve capacity. In the first group are myocardial compression or "bridging" of an artery; coronary vasoconstriction due to frank spasm or generalized arterial hypertonus, particularly at the site of atherosclerotic lesions; reduced arterial distending pressure and platelet aggregation which may transiently occlude a diseased arterial segment. The causes of inadequate coronary vascular reserve flow capacity can be either anatomic or functional. Among the former, the increased muscle mass to blood vessel ratio occurring in myocardial hypertrophy is most important. The functional causes of limited coronary vascular reserve include diastolic transmural compression and coronary "steal," both of hemodynamic origin. In addition, arteriolar "unresponsiveness" or dysregulation caused by smoking, drugs or other unknown conditions may adversely affect coronary vascular reserve. Hence, myocardial ischemia may result from conditions that limit potential for increase in flow or from conditions that reduce flow from a preexisting level. These conditions, which are transient and dynamic in nature, may modify the threshold for ischemia, particularly in patients with fixed coronary obstructive disease.     

Characterization of the ischemic process by regional metabolism.

The myocardial cell requires energy for contractile activity and for the work of internal maintenance. With the onset of ischemia mechanical performance is compromised. If the ischemia is severe and persistent, the energy necessary to maintain the internal millieu proves inadequate and cell death ensues. Ischemic heart disease is a regional phenomenon with normal and abnormal cell metabolism occurring side by side. The ischemic cell demonstrates hemodynamic, electrical and biochemical instability; its passage from a state of reversible to irreversible injury may persist for as long as 7 days and offers an opportunity to introduce interventions that may protect it and reduce ultimate infarct size. There is as yet no adequate objective means for predicting the mass of infarcted tissue. However, studies of regional metabolism, if properly conducted, may help define the adequacy of coronary vascular reserve and characterize the ischemic process. Current techniques utilize a myocardial pacing stress to induce an ischemic response. Although virtually every metabolic pathway is disrupted by severe ischemia, the assay of selected metabolities in arterial and coronary venous blood samples has provided information of diagnostic significance.     

Clinical potential of DAS181 for treatment of parainfluenza‐3 infections in transplant recipients

Parainfluenza virus (PIV) infections can cause serious respiratory infections and death in immunocompromised patients. No antiviral agents have proven efficacy against PIV, and therapy generally consists of supportive care. DAS181, a novel sialidase fusion protein that temporarily disables airway epithelial PIV receptors by enzymatic removal of sialic acid moieties, has been shown to inhibit infection with PIV strains in vitro and in an animal model. We describe here the clinical course of 2 immunocompromised patients with PIV‐3 infection, one with a history of lung transplantation and the other neutropenic after autologous hematopoietic stem cell transplantation for multiple myeloma. Both patients had substantial clinical improvement in respiratory and systemic symptoms after a 5‐day DAS181 treatment course, although the clinical improvement in the autologous stem cell transplantation patient also paralleled neutrophil engraftment.     

Parasitic diseases in immunocompromised hosts

In patients with compromised host defenses, diseases caused by protozoans and nematodes appeared, a few years ago, to be declining in importance. However, the outbreak of the acquired immunodeficiency syndrome (AIDS) among homosexual men, parenteral drug abusers, and other groups has made it necessary for physicians to familiarize themselves again with the manifestations of these diseases in abnormal hosts. The groups of patients at greatest risk, the usual clinical syndromes in abnormal hosts, and current approaches to diagnosis, treatment, and prevention of infections due to Pneumocystis carinii, Toxoplasma gondii, Strongyloides stercoralis, and organisms of the genus Cryptosporidium are reviewed. Because so many cases of these infections have recently occurred among patients with AIDS, recent experience with these diseases in AIDS patients at Memorial Sloan-Kettering Cancer Center is summarized.