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Biomedical subjects

F L Ruben

Publications and source records attributed to F L Ruben.

At least 19 recordsLinked to original sources

Clinical infections in the noninstitutionalized geriatric age group: methods utilized and incidence of infections. The Pittsburgh Good Health Study.

Because noninstitutionalized senior citizens comprise over 95% of the population 65 years of age and older, their health needs are a major concern. Data regarding infections in this population including the epidemiology, morbidity, and mortality are lacking. The authors recruited a study population of 417 free-living persons, all 65 years of age or older, from two neighborhoods in Pittsburgh, Pennsylvania. After the collection of self-reported baseline information from these persons, they were monitored for all clinical infections for 2 years, beginning July 1986 and through June 1988, using clinic visits, hospitalizations, or phone calls when needed. The baseline information showed the study population of 417 persons to be comparable with a neighborhood comparison group and with established populations for epidemiologic studies of the elderly in three other states. The 24 months of infection surveillance yielded 494 diagnosed infections in 224 or 54% of the subjects. Respiratory infections were most frequent with 259 or 52% of the total, followed by genitourinary infections with 24%, skin infections with 18%, gastrointestinal infections with 4%, and other types of infection with 2%. By comparing 22 self-reported baseline conditions with the occurrence of infection, 10 historic factors were univariately significant for infection. Of these 10 factors, only history of a lung problem (relative risk = 1.7, 95% confidence interval (CI) 1.1-2.9) and history of difficulty controlling urination (relative risk = 2.7, 95% CI 1.3-4.9) were statistically significant in multivariate analysis. To our knowledge, this study represents the first prospective data on infections in the noninstitutionalized elderly. The data demonstrate the wide variety of infections that occurred in this population and suggest that persons with a history of any one of several medical problems were possibly at greater risk for infection.

Aged

Viral pneumonias. The increasing importance of a high index of suspicion.

Viral pneumonias account for at least 17% of cases of community-acquired pneumonia in children and in adults. Although patients with viral pneumonia appear less ill clinically than those with bacterial pneumonia, viral pneumonias can be fatal. Antiviral therapy is available for pneumonias caused by respiratory syncytial virus, influenza A virus, and cytomegalovirus. Several vaccines are important tools for the prevention of influenza A and B pneumonia.

Adult

Hemorrhagic cystitis with herpes simplex virus type 2 in the bladder mucosa.

A 67-year-old woman who had underlying rheumatoid arthritis and diabetes mellitus had an 8-year history of recurrent hemorrhagic cystitis. During her most recent episode of cystitis, a specimen of urine yielded herpes simplex virus type 2 in culture. A biopsy of the bladder mucosa revealed intranuclear inclusions in multinucleated and mononuclear giant cells that were positive for herpes simplex virus type 2 by immunoperoxidase staining. She had no evidence of infection with herpes simplex virus outside her bladder.

Aged

Viral pneumonitis.

Viral pneumonitis can affect all age groups and normal as well as compromised hosts. This article discusses salient features of pneumonitis caused by respiratory syncytial virus, adenoviruses, varicella-zoster virus, herpes simplex virus, influenza A and B viruses, and cytomegalovirus. The clinical picture, diagnosis, treatment and prevention for each agent are discussed.

Adenoviridae Infections

Antibody response to pneumococcal polysaccharide vaccine in myasthenia gravis: effect of therapeutic plasmapheresis.

The removal of specific antibody in experimental animals has been reported to result in a subsequent increase in antibody to levels equal to (rebound) or exceeding those existing prior to removal (overshoot). Anecdotal reports suggest that rebound antibody synthesis after plasmapheresis may occur in humans with autoimmune disorders. We measured the antibody response to 12 pneumococcal polysaccharide antigens in patients with myasthenia gravis (MG) receiving a variety of therapies in order to determine whether the T-cell-independent IgG response to these antigens was augmented by plasmapheresis. MG patients receiving no immunotherapy or receiving prednisone had pre- and post-immunization titers similar to those of control patients. MG patients receiving prednisone and chronic plasmapheresis had higher pre-immunization titers than did other patient groups and had significantly higher post-immunization titers against multiple pneumococcal serogroups. Aggregate post-immunization geometric mean titers were more than three-fold higher in the plasmapheresis group as compared with other MG treatment groups. Enhancement of antibody response by plasmapheresis was abolished by the concomitant administration of azathioprine. Antibody rebound and overshoot after antibody removal may have important implications for the therapy of immune disorders by plasmapheresis.

Adult

Now and future influenza vaccines.

Influenza is a modern day plague. In the young, the clinical picture is classical, but in the elderly, the disease may go unsuspected until complications such as pneumonia develop. Influenza A and B viruses are responsible, and these viruses mutate with great regularity. Antibodies to the HA and NA surface antigens of influenza viruses, both naturally and vaccine induced, are protective. The earliest influenza vaccines were crude, toxic, and ineffective. With modern purification techniques, the egg-grown viruses have been turned into safe, immunogenic, and effective killed-virus vaccines--whole virus and split virus. Surveillance permits the correct virus strains to be incorporated into each new vaccine. Those who have been experiencing the worst effects of influenza have been identified. These individuals need to be immunized each year. In the future, live influenza virus vaccines may offer the benefits of ease of administration and longer-lasting protection. Synthetic peptides, genetically engineered antigens, and even nonantigen (anti-idiotype) vaccines are possible, but such vaccines will require adjuvant enhancement. For the present, greater efforts must be made to use existing influenza vaccines.

Humans

The prevention of severe lower respiratory infections in chronic bronchitis.

Chronic bronchitis remains as a serious medical problem for many adults and a smaller proportion of children in the United States. The frequency of severe lower respiratory infections in patients with chronic bronchitis is quite variable. The infectious agents most likely responsible for severe lower respiratory disease include pneumococci, nontypable Haemophilus influenza, Mycoplasma pneumoniae, and Branhamella catarrhalis among the bacteria, and influenza A and B viruses, with parainfluenza and adenoviruses less common. Prophylactic antibiotics, particularly tetracycline and derivatives, were the only drugs suggesting efficacy in controlled trials for decreasing exacerbation, but many studies failed to show efficacy. Killed influenza vaccines should be used annually in any patient with chronic bronchitis. Pneumococcal vaccine has had questionable benefit for bronchitics but should nevertheless be considered for use because of its low cost and proven safety. The antiviral drug amantadine may be useful in bronchitics unable to take influenza vaccines.

Adult

Fatal adult respiratory distress syndrome in a patient with Lyme disease.

A dry cough, fever, generalized maculopapular rash, and myositis developed in a 67-year-old woman; she also had markedly abnormal liver function test results. Serologic tests proved that she had an infection of recent onset with Borrelia burgdorferi, the agent that causes Lyme disease. During a two-month course of illness, her condition remained refractory to treatment with antibiotics, salicylates, and steroids. Ultimately, fatal adult respiratory distress syndrome developed; this was believed to be secondary to Lyme disease.

Aged

Immune responses to killed influenza vaccine in patients with type 1 diabetes: altered responses associated with HLA-DR 3 and DR 4.

To assess the immunologic differences related to histocompatibility leukocyte antigen (HLA) haplotypes in patients with type 1 diabetes, trivalent killed influenza virus vaccine was given in the fall, when no influenza occurred, to 59 patients with diabetes (mean age 16 years) and 64 siblings without diabetes (mean age 36 years). All subjects had normal hemagglutination inhibition antibody responses at days 14 and 42 after vaccination, with no significant differences noted between patients with diabetes and those without diabetes. However, subjects with HLA haplotypes DR 3, DR 4, or both had lower antibody responses to influenza A/Chile and B/USSR at 14 days after vaccination (p less than 0.02) than DR x/x controls (who lacked 3 or 4). Lymphocyte transformation (LT) responses before and after vaccination were similar for patients with diabetes and those without diabetes. Of significance was that subjects with HLA haplotypes DR 3, DR 4, or both had 41.1% LT responders at 42 days after vaccination, compared with subjects with HLA-DR x/x (lacking 3 or 4) who had 22.6% responders (p less than 0.03), when influenza A/Chile was used as an antigen. Although not significant, influenza antigens A/Philippines and B/USSR each showed similar trends with increased postvaccine LT responses. The HLA associations were independent of sex, age, and the presence of diabetes. These studies suggest that HLA haplotypes DR 3 and DR 4, which were clearly linked to type 1 diabetes mellitus, were also associated with altered immune responsiveness to influenza viral proteins.

Adolescent

Prophylactic treatment of chronic bronchitis.

Exacerbations of chronic bronchitis may be caused by a variety of bacterial and viral agents. There is ample documentation of a role for Hemophilus influenza, Streptococcus pneumonia, Mycoplasma pneumoniae, influenza A and B viruses, and several other respiratory viruses in causing these exacerbations. Because of the lack of frequency of exacerbations (once every 20 to 78 weeks) and the wide range of pathogens, trials of prophylaxis with antibiotics have been difficult to conduct. Controlled trials conducted since the 1950s have shown mixed results, some demonstrating a reduction in the number of exacerbations and others failing to show efficacy. Of the antibiotics used, tetracycline seemed the most effective. Both the pneumococcal polysaccharide and killed influenza virus vaccines have been suggested for patients with chronic bronchitis. The antiviral drug amantadine has been recommended when vaccine cannot be used. This reviewer concludes that prophylactic antibiotics should be used in selected patients with one or more exacerbations yearly using a drug such as tetracycline. A one-time dose of pneumococcal vaccine and the annual use of killed influenza vaccine are also reasonable. During an influenza A epidemic, amantadine should be considered for unvaccinated patients. Future studies should study intermittent v chronic prophylaxis with cheap but appropriate antibiotics (chosen for their microbial spectrum), and should test newer antiviral vaccines and antiviral drugs as they become available.

Anti-Bacterial Agents

Prevention and control of influenza. Role of vaccine.

A major component in the prevention and control of influenza should be the use of killed influenza vaccines. These vaccines became possible after the first discovery of human strains of influenza virus in the 1930s. The ensuing decades have seen marked improvement in the available inactivated vaccines. Current vaccines have excellent reliability and assured potency, and they contain the proper antigens to match the frequent changes in circulating influenza viruses. Killed vaccines work by inducing serum antibodies against the hemagglutinin and neuraminidase of the vaccine strains, with sufficient antibodies ensuring protection against infection. The antibody responses to current vaccines appear to be adequate in all age groups. Although antibody responses are depressed in patients receiving chemotherapy or immunosuppressants, current vaccines do provide protection for most populations. Vaccines prevent the manifestations of disease by about 30 to 70 percent in all populations, and they reduce deaths in high-risk individuals by about 60 to 87 percent. Local adverse reactions to vaccine are quite common, but not severe. Fever, also somewhat common, usually does not last beyond 48 hours. Neurologic complications have not been observed since the use of the swine influenza vaccine of 1976. Killed vaccines should be given annually in the fall, but they can be given up to and during an outbreak. Target groups for vaccines have been defined by the Centers for Disease Control. In recent years, these groups have included physicians and nurses who give care to patients at risk for complications of influenza.

Child

Antibody responses after influenza and pneumococcal immunization in HIV-infected homosexual men.

We conducted a study to assess the effect of human immunodeficiency virus (HIV) infection on humoral immunity. Fifty-five homosexual men and 19 heterosexual men had four- to six-week postimmunization antibody responses measured to trivalent influenza vaccine and 23-valent pneumococcal vaccine. The homosexual men were divided into three groups: 20 asymptomatic HIV-seronegative men, 10 asymptomatic HIV-seropositive men, and 25 HIV-seropositive men with persistent generalized lymphadenopathy. Antibody responses to influenza antigens in the subgroups of homosexual men did not significantly differ from those of heterosexual controls. The IgG antibody responses to pneumococcal capsular types 9N and 18C in men with lymphadenopathy, and type 18C in HIV-seronegative homosexual men, were lower than those of heterosexual controls. Otherwise, responses to other ten capsular types showed no significant differences. There was no evidence of an immunosuppressive effect of vaccination on T-cell numbers, or deterioration of clinical status associated with vaccination. This study demonstrates that HIV-infected homosexual men, asymptomatic or with persistent generalized lymphadenopathy, are able to mount appropriate antibody responses to two commonly used vaccines.

Acquired Immunodeficiency Syndrome

Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease.

Although pneumococcal vaccine has been recommended for patients with chronic obstructive pulmonary disease (COPD), its efficacy in this population has not been shown. A double-blind randomized controlled trial of 14-valent pneumococcal vaccine was carried out in 189 men and women aged 40 to 89 years with a clinical diagnosis of COPD and a forced expiratory volume in 1 second of less than 1.5 L. Of the 189, 92 received the vaccine and 97 received saline placebo. In a randomly chosen subsample of those who received the vaccine the mean titres of specific IgG antibody to selected pneumococcal polysaccharide serotypes increased two- to threefold by 4 weeks after vaccination. Over a 2-year period the rates of death, hospital admissions and emergency visits and the mean length of hospital stay were not significantly different in the two groups. Although a protective effect of 14-valent pneumococcal vaccine could not be shown, the small size of the sample and the relatively low follow-up rates preclude firm conclusions about efficacy from these data alone. The elevated antibody levels before vaccination in some of the patients, suggesting prior infection with Diplococcus pneumoniae, may partly explain the findings.

Aged

Tobramycin and ticarcillin as empiric therapy for febrile patients with granulocytopenia: a reevaluation.

The combination of tobramycin and ticarcillin is an established regimen used to empirically treat patients with granulocytopenia and fever. However, the clinician now has a plethora of newer alternative antibiotic combinations from which to choose. In this retrospective study of 25 granulocytopenic patients recently treated with tobramycin and ticarcillin, a combined favorable or partial response rate of 78% was achieved, without loss of efficacy over time as a result of emerging resistance of organisms. Our reevaluation of this antibiotic regimen emphasizes that it continues to be as efficacious and safe as newer antibiotic combinations, and supports its continued use until a newer regimen is shown to have significant advantages. This study also emphasizes the significance of staphylococci as pathogens in granulocytopenia, and suggests the need to add specific antistaphylococcal coverage whenever catheter-related infection is suspected.

Adolescent