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Biomedical subjects

M Rubin

Publications and source records attributed to M Rubin.

At least 163 records · Page 9Linked to original sources

Disorders of peripheral nerves associated with HIV infection.

The clinician with interest in neuromuscular disease must become familiar with the clinical manifestations of HIV infection. It is important to realize that not everyone who is infected with HIV will develop clinical AIDS. This includes patients with clinical manifestations related to HIV infection, for example, neuropathy. Thus, if treatment is successful, patients can continue a normal life. HIV infection should be considered in almost any neuromuscular syndrome, especially neuropathies with features of demyelination, which may be the first manifestation of HIV infection. Plasmapheresis may be the treatment of choice for these disorders. Steroids should be used with caution. AZT seems to be a promising new agent to combat AIDS.

Biopsy↗

Monotherapy for empirical management of febrile neutropenic patients.

New fever in a neutropenic patient mandates prompt institution of empirical broad-spectrum antibiotics. Traditional empirical regimens have relied on combinations that include an aminoglycoside. However, certain classes of newer antibiotics (e.g., third-generation cephalosporins, carbapenems, quinolones) include agents with a broad spectrum and high bactericidal activity that may provide therapeutic alternatives to combination regimens. We previously compared empirical monotherapy with ceftazidime to a combination regimen of cephalothin, gentamicin, and carbenicillin and found the regimens comparable with respect to percentage with success (survival without change of initial regimen; 62% vs 67%), success with modification (survival with additional antibiotics; 33% vs 29%) and failure (death; 5% vs 4%). Imipenem has a broader in vitro spectrum of activity than ceftazidime, particularly against gram-positive organisms and anaerobes, raising the possibility of equivalent or even improved efficacy as monotherapy. Accordingly, we are prospectively randomizing febrile, neutropenic patients to either empirical ceftazidime or imipenem therapy. Imipenem appears to be comparable to ceftazidime in this ongoing study but has not resulted in fewer modifications or secondary infections. Studies assessing the role of quinolones in the management of neutropenic patients are under way.

Agranulocytosis↗

Single application treatment of human papillomavirus infection of the cervix and vagina with trichloroacetic acid: a randomized trial.

Treatment of human papillomavirus (HPV) infection of the lower genital tract with trichloroacetic acid was evaluated in a randomized, double-blind fashion at the Hospital of the University of Pennsylvania. Thirty-four patients who had colposcopic and histologic evidence of HPV without dysplasia were entered into the study and randomly placed into either a treatment or placebo group. The treatment group received a single topical application of 50% trichloroacetic acid to the vagina and cervix on day 1. The placebo group was treated in the same manner using saline. The patients were evaluated at 4 and 16 weeks post-treatment for cytologic and histologic evidence of HPV. No differences between the treatment and placebo groups were found. Only one of 16 patients in the treatment group and three of 18 in the placebo group were free of HPV infection at the 4- and 16-week evaluations. Our data suggest that treatment of subclinical HPV infection with trichloroacetic acid is ineffective at this concentration.

Adolescent↗

Occupational cancer mortality in Illinois white and black males, 1979-1984, for seven cancer sites.

A death certificate mortality odds ratio study of seven cancer sites was conducted by using 1979-1984 data on Illinois deaths in white and black males. Cancer sites selected include stomach, pancreas, lung, prostate, bladder, brain, and non-Hodgkin's lymphomas. This surveillance study was undertaken to detect occupational associations that might suggest further avenues of research. Some of the occupations and industries found to have elevated cancer risks and that are consistent with previous studies include: brickmasons and stonemasons (stomach); metal workers (pancreas, lung); photoengravers and lithographers (pancreas); butchers (lung); locomotive operators and truck drivers (lung); farmers (prostate, brain, non-Hodgkin's lymphoma); mechanics and repairers, especially auto mechanics (prostate); physicians (brain); glass products manufacturing workers (brain); and communications industry (brain) and chemical plant workers (non-Hodgkin's lymphomas). It was also noted that for black males, the death certificate occupational data are of limited usefulness due to the high percentage of missing or inexact information. The Division of Vital Records in the State of Illinois should make an effort to improve the reporting of this data through additional training of the funeral directors and hospital clerks who collect this information and by follow-up of incomplete or missing data.

Adult↗

Dystrophin immunocytochemistry in muscle culture: detection of a carrier of Duchenne muscular dystrophy.

Dystrophin is the gene product which is affected in Duchenne muscular dystrophy (DMD). We studied differentiating clonal muscle cultures derived from normal muscle and from the mother of a DMD patient by immunocytochemistry, using anti-dystrophin antibody. While clonal cultures derived from normal muscle expressed dystrophin in all myotubes, two populations of myogenic cells could be demonstrated in muscle from this possible DMD carrier; in 13 clones the myotubes expressed dystrophin and in 7 clones dystrophin was undetectable. No DNA deletion, duplication or rearrangement was detected by Southern blot analysis of DNA from this family using cDNA probes. Thus, immunocytochemical analysis of clonal muscle cultures may be a useful method to determine whether mothers of DMD patients are carriers of the DMD mutation, especially in the absence of demonstrable gene defects.

Adult↗

Stage II papillary clear cell adenocarcinoma of the vagina during observation in a diethylstilbestrol-exposed daughter.

Although many cases of Diethylstilbestrol (DES)-associated clear cell adenocarcinoma (CCA) of the cervix and vagina have occurred, few have arisen in patients whose initial gynecologic evaluation has revealed only nonmalignant DES-related changes. We report a case of a 32-year-old lady who developed a stage II CCA after 8 years of thorough gynecologic examinations. This case substantiates the need for long-term gynecologic assessment in DES daughters.

Adenocarcinoma, Papillary↗

Pharmacokinetics and tissue penetration of Sch 39304 in granulocytopenic and nongranulocytopenic rabbits.

We studied the plasma pharmacokinetics and tissue penetration of Sch 39304 (SCH), a new antifungal triazole, in granulocytopenic [G(+)] and nongranulocytopenic [G(-)] rabbits. Five female New Zealand White G(-) rabbits were given a single oral dose of 2 mg of SCH per kg of body weight. Levels in plasma, determined by gas-liquid chromatography-electron capture, were obtained for 6 days. This procedure was repeated 2 weeks later with the same rabbits, which were induced and maintained G(+) with cytosine arabinoside. There were no significant differences between the pharmacokinetic parameters of G(+) and G(-) rabbits. Among all animals studied, the maximum concentration of the drug in plasma was 1.4 +/- 0.11 micrograms/ml at 4 +/- 0.5 h, the half-life was 25 +/- 1.4 h, the volume of distribution at steady state was 3.8 +/- 0.3 liters, and the area under the concentration-time curve was 44 +/- 3.4 micrograms.h/ml. SCH was detectable in plasma up to day 6. Levels of SCH in tissue were studied at steady state in six G(+) and six G(-) rabbits receiving 2 mg of the drug orally per kg per day for experimental disseminated candidiasis. Tissue SCH levels equalled or exceeded those in plasma (at steady state) at all sites examined, and these ratios were similar in both G(+) and G(-) rabbits. Thus, plasma pharmacokinetics of orally administered SCH were similar for G(+) and G(-) rabbits, and SCH achieved high levels of penetration into multiple tissues, including the liver and the central nervous system.

Agranulocytosis↗

Purification, toxicity, and antiendotoxin activity of polymyxin B nonapeptide.

Polymyxin B, a relatively toxic antibiotic, has potent endotoxin-neutralizing properties that may be beneficial as adjunctive therapy in gram-negative sepsis. Polymyxin B nonapeptide (deacylated polymyxin B) is devoid of antibiotic activity but retains the capacity to disorganize the outer membrane of gram-negative bacteria. To evaluate the potential therapeutic usefulness of this derivative, we produced purified polymyxin B nonapeptide, tested its in vivo toxicity in animals, and evaluated its in vitro antiendotoxin activity. Effectiveness as an antiendotoxin agent was assessed by examining the ability of polymyxin B nonapeptide to block the enhanced release of toxic oxygen radicals induced by lipopolysaccharide in human neutrophils (priming). In vivo, at doses of 1.5 and 3.0 mg/kg, polymyxin B nonapeptide did not exhibit the neuromuscular blocking, neurotoxic, or nephrotoxic effects that were observed with polymyxin B sulfate. Both polymyxin B and polymyxin B nonapeptide inhibited lipopolysaccharide-induced neutrophil priming in a concentration-dependent manner, but the parent compound, polymyxin B, was 63 times more effective on a weight basis. The inhibitory activity of both compounds, however, diminished rapidly when they were added after the start of the lipopolysaccharide-neutrophil incubation. We conclude that polymyxin B nonapeptide is less toxic than polymyxin B and, at the doses tested, lacks the neurotoxicity and nephrotoxicity of the parent compound. Polymyxin B nonapeptide retains the antiendotoxin activity of polymyxin B but is much less potent. The findings suggest that these compounds block an early step in the neutrophil priming process, possibly lipopolysaccharide attachment to or insertion into the neutrophil membrane.

Animals↗

Another look at psychologic complications of hysterectomy.

As with any surgical procedure, hysterectomy has associated physiological and psychological complications. While the picture of physiological complications has changed markedly over the past 45 years in response to research findings and medical advances, there seems to have been little change in the perception and treatment of psychological complications. Textbooks in medicine and nursing remain close to the current research when citing physiological complications, their diagnosis and treatment. However, in these same texts, sections concerning psychological complications continue to cite very early studies linking hysterectomy and depression. Current research has failed to support this link between hysterectomy and depression.

Anxiety↗

Developing a program grant for use in model testing.

Early discharge is becoming a practice as well as a goal for the acute care institution. It is essential that nursing investigate the effects of this shift in the care delivery site from the acute care institution to the home and community. Brooten et al. describe a research model designed to do just that. Transitional care, as this team calls it, may soon become familiar jargon in community health care.

Clinical Nursing Research↗

Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection.

To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition of the replication of human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging in age from 14 months to 12 years who had acquired HIV infection through transfusions or perinatally. All patients were symptomatic before AZT treatment (Class P2 of the Centers for Disease Control); 13 (62 percent) had evidence of neurodevelopmental abnormalities. The mean CD4/CD8 ratio was 0.18; 11 patients had CD4 counts below 0.2 x 10(9) per liter. We administered AZT at four dose levels: 0.5, 0.9, 1.4, and 1.8 mg per kilogram of body weight per hour. The plasma drug concentrations achieved at the respective dose levels were 1.9 +/- 0.3, 2.8 +/- 1.4, 3.1 +/- 1.1, and 4.5 +/- 1.0 microM. The steady-state cerebrospinal fluid:plasma ratio was 0.24 +/- 0.07. The only evidence of toxicity was bone marrow suppression. Transfusion was required in 14 patients because of low levels of hemoglobin (5 mmol per liter [less than 8 g per deciliter]). Dose-limiting neutropenia (less than 0.5 x 10(9) polymorphonuclear leukocytes per cubic millimeter) occurred in most patients who received doses of 1.4 mg per kilogram per hour or more. Improvement in neurodevelopmental abnormalities occurred in all 13 children who had presented with encephalopathy before treatment. Serial measurements of IQ before therapy and after three and six months of continuous therapy with AZT showed that IQ scores, including those for verbal and performance IQ, rose in these 13 patients and in 5 other children who had no detectable evidence of encephalopathy before treatment. Most patients also had increased appetite and weight, decreased lymphadenopathy and hepatosplenomegaly, decreased immunoglobulin levels, and increased numbers of CD4 cells. In some patients the improvement in the features of encephalopathy occurred despite the absence of immunologic improvement. We conclude that AZT is beneficial in children with symptomatic HIV infection, especially those with encephalopathy (which may be subclinical), and that the optimal continuous intravenous dose of AZT in children is between 0.9 and 1.4 mg per kilogram per hour.

Acquired Immunodeficiency Syndrome↗

Adult onset motor neuronopathy in the juvenile type of hexosaminidase A and B deficiency.

Two sisters presented with progressive muscle cramps, as well as wasting and weakness of the legs with onset after age 20. They also showed intention tremor of the upper extremities and dysarthria starting during the first decade. The older patient also had fasciculations; the younger, hyperreflexia. Total plasma beta-hexosaminidase (Hex) activity with 4-methylumbelliferyl-acetyl-glucosamine as substrate was reduced to 1.4% and 2.7% of the control in the 2 patients, respectively. Hex A activity measured by 4-methylumbelliferyl-N-acetylglucosamine-6-O-sulphate as substrate was 9.9% and 12.8% of the mean control value in the 2 patients, respectively. Hex B activity was undetectable in both patients. Leukocyte total Hex activity was 7-8% of normal; residual Hex A activity in the 2 patients was 17.8% and 16.3% of normal controls, respectively. Fibroblastic residual Hex A activity in the 2 patients was 9.6% and 22% of normal mean value, respectively. Appendiceal ganglion cells contained membranous cytoplasmic bodies in the younger patient. Thin layer chromatography of the appendiceal extract from one patient (III/2) showed a marked increase of GM2 ganglioside, and some increase of GM3 ganglioside. Northern blots performed on fibroblast cell lines from both patients for the demonstration of alpha and beta locus messenger RNA showed no difference between patients and control. These patients have a rare form of adult-onset progressive motor neuron disease presumably due to abnormal beta subunits, causing severe deficiency of both Hex A and Hex B. The phenotypic expression of this disease is similar to motor neuron disease due to alpha locus mutations, which suggests that the Hex A deficiency, even though only a partial one, may be the important pathogenic factor.

Adult↗

Gram-positive infections and the use of vancomycin in 550 episodes of fever and neutropenia.

STUDY OBJECTIVE: To determine the appropriate role for vancomycin in neutropenic patients with cancer. To review the incidence, types, and outcome of gram-positive infections in a series of neutropenic patients with cancer. DESIGN: Retrospective review. SETTING: Inpatient units of the Medical and Pediatric Oncology Branches of the National Cancer Institute. PATIENTS: Five hundred and fifty consecutive episodes of fever and neutropenia in patients with cancer randomized prospectively on another study to receive either ceftazidime alone or combination antibiotics for initial empirical therapy. INTERVENTION: Intravenous vancomycin (dosage adjusted by serum levels). MEASUREMENTS AND MAIN RESULTS: Gram-positive organisms were the commonest of the bacterial pathogens isolated (63%). Of the 53 gram-positive organisms accounting for primary infections (isolated at initial presentation), there were 36 staphylococcal isolates (19 coagulase-negative and 17 coagulase-positive), 13 streptococcal isolates (8 non-group D and 5 group D), and 4 polymicrobial isolates. Of the 22 secondary gram-positive infections (occurring after institution of initial antibiotics), there were 10 streptococcal isolates (9 group D and 1 non-group D), 7 staphylococcal isolates (6 coagulase-negative and 1 coagulase-positive), and 5 polymicrobial isolates. Vancomycin was used to treat 26 of the 53 primary infections, but was begun only after knowledge of the isolate in 25. Vancomycin was used to treat 17 of the 22 secondary infections, and begun only after knowledge of the isolate in 14. This approach resulted in no treatment failures for the primary infections, and a single microbiological failure for the secondary infections. There was a tendency towards a greater proportion of secondary gram-positive infections in the monotherapy group compared to the combination therapy group (16 of 282 compared with 6 of 268 respectively, P2 = 0.04 by the chi-squared test); but all were treated successfully. CONCLUSION: Vancomycin need not be included in routine empirical therapy for febrile neutropenic patients, but should be added when clinical or microbiological data suggest the need.

Agranulocytosis↗