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Biomedical subjects

G Kaplan

Publications and source records attributed to G Kaplan.

At least 73 records · Page 4Linked to original sources

Polyarthralgia-arthritis syndrome induced by low doses of rifabutin.

We describe 2 cases of polyarthralgia-arthritis syndrome induced by rifabutin, an effective treatment for infections of Mycobacterium avium intracellulare complex. This syndrome has been reported with doses higher than 1 g per day when rifabutin is given in monotherapy. But our cases were treated with low doses, 300-450 mg per day, in combination with clarithromycin. The plasma concentration of rifabutin has been shown to be increased by clarithromycin, suggesting that co-prescription of clarithromycin could lead to development of rifabutin induced polyarthralgia-arthritis syndrome.

Anti-Bacterial Agents↗

Osteonecrosis-like syndrome of the medial tibial plateau can be due to a stress fracture. MR findings in 13 patients.

OBJECTIVE: To demonstrate the contribution of magnetic resonance imaging to the elucidation of mechanisms involved in "osteonecrosis-like syndrome of the medial tibial plateau". PATIENTS AND METHODS: A magnetic resonance study with sagittal and coronal sections was done in 13 patients (age range, 57-95 years) two weeks to four months into a painful syndrome meeting the definition of "osteonecrosis-like syndrome of the medial tibial plateau". Gadolinium injection was used in nine patients. Clinical symptoms resolved within a few weeks in all 13 cases. RESULTS: T1-weighted images without gadolinium showed diffuse low signal from the epiphysis (n = 12) containing an area of even lower signal seen either as a crescent-shaped subchondral image (n = 3/12) or as a linear image (n = 9/12). On postgadolinium images, the low signal was abolished except for a line of low signal parallel to the subchondral bone. T2-weighted images demonstrated diffuse high signal from the medial tibial plateau with persistence of the line of low signal (n = 8/12). CONCLUSION: Magnetic resonance imaging allows to analyze the anatomic lesion responsible for "osteonecrosis-like syndrome of the medial tibial plateau". Our magnetic resonance findings were similar to those seen in stress fractures at other sites.

Aged↗

Leadership 99. Interview by Terese Hudson.

Cost control, customer service and collaboration among health care sectors rank as top concerns with panelists in H&HN's annual Leadership Report. Efforts to improve community health are a priority, too, but are often frustrated by financial and other constraints. The 16 panelists represent managed care, physicians, and hospitals and health systems.

Attitude of Health Personnel↗

Parental knowledge of the treatment of fever in children.

BACKGROUND: Although the onset of fever in children often prompts parents to seek immediate treatment, the general level of parental knowledge on pediatric fever and administration of antipyretic medications is unknown. Parents without a basic understanding of treatment principles may give their children incorrect doses of medication. Overdosing may cause drug toxicity, while underdosing may lead to unnecessary, repeated clinic and/or emergency room visits. OBJECTIVES: To assess parental decision-making with regard to treating fever in children, and its effectiveness, and to suggest methods for improving the level of treatment. METHODS: In this cross-sectional self-reported survey, questionnaires were completed by 650 parents who sought medical assistance for a child under the age of 10 years. Parents represented various socioeconomic levels, educational backgrounds and religious affiliations. RESULTS: Ninety-six percent of parents treated fevers that reached 38.5 degrees C, and 77.6% treated fevers of only 38 degrees C. Acetaminophen was the treatment of choice for 96% and dipyrone for 4%. Parental sources of information for managing and administering antipyretic drugs were medical personnel (40.7%), mother's or grandmother's experience (30%), and the enclosed leaflet or instructions on the bottle (29.3%). Forty-three percent of the parents administered the recommended dosage (10-20 mg/kg), whereas 24.3% used less and 32.7% used more; 11% exceeded a daily dosage of 120 mg/kg. CONCLUSIONS: A total of 57% of parents treated children with incorrect doses of antipyretic drugs. In 11% of the children treated, the daily dose was at a level that could cause severe toxicity. Parental knowledge of the treatment of fever must be improved.

Acetaminophen↗

Geographic heterogeneity of 4 common worldwide cystic fibrosis non-DF508 mutations in Brazil.

Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 750 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The frequency of the most common mutation (DF508) in Brazilian patients of European origin is 47%. To determine the frequency of 4 other common CF mutations (G542X, G551D, R553X, and N1303K) in Brazilian patients of European origin, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards. The DNA came from 247 non-DF508 chromosomes from 172 Brazilian CF patients ascertained from 5 different states of Brazil. The results show that the 4 mutations account for 17% of the non-DF508 alleles and only 9% of the total number of Brazilian CF alleles. Overall, the frequency of each mutation is different from northern European and North American populations but similar to southern European populations, mainly the Italian and Spanish populations. When Brazilian patients of European origin are grouped according to state of birth, the frequencies of the mutations are significantly different between southern and southeastern states of Brazil. Therefore there are serious implication for risk assessment of DNA-based tests in heterogeneous populations such as Brazilians. Further studies are needed to identify the remaining 44% of CF mutations for the different populations and regions of Brazil.

Adolescent↗

Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset.

The efficacy of thalidomide (alpha-phthalimido-glutarimide) therapy in leprosy patients with erythema nodosum leprosum is thought to be due to inhibition of tumor necrosis factor alpha. In other diseases reported to respond to thalidomide, the mechanism of action of the drug is unclear. We show that thalidomide is a potent costimulator of primary human T cells in vitro, synergizing with stimulation via the T cell receptor complex to increase interleukin 2-mediated T cell proliferation and interferon gamma production. The costimulatory effect is greater on the CD8+ than the CD4+ T cell subset. The drug also increases the primary CD8+ cytotoxic T cell response induced by allogeneic dendritic cells in the absence of CD4+ T cells. Therefore, human T cell costimulation can be achieved pharmacologically with thalidomide, and preferentially in the CD8+ T cell subset.

Antibodies, Monoclonal↗

High anti-cytomegalovirus (CMV) IgG antibody titer is associated with coronary artery disease and may predict post-coronary balloon angioplasty restenosis.

Recent studies have demonstrated that cytomegalovirus (CMV) DNA was found in atherosclerotic coronary arteries in restenotic lesions, and prior infection with CMV could be a strong independent risk factor for restenosis after coronary atherectomy. We studied the correlation between anti-CMV antibody titer and coronary artery disease. Sixty-five patients (50 men and 15 women) with coronary artery disease were enrolled prospectively. All had symptomatic coronary artery disease with an angiographic documentation of a de novo single coronary lesion. All underwent balloon coronary angioplasty and were followed for 12 months with a thallium perfusion scan 3 months after angioplasty. Patients who had recurrent chest pain and/or a positive thallium scan had another coronary angiography. Blood samples were taken before angiography and 1 and 3 months later. Patients with high anti-CMV titer > or = 1:800 had a higher prevalence of coronary artery disease (p <0.001) than seropositive patients with a lower antibody titer (< or = 1:400); patients with high antibody titer (> or = 1:800) had a higher restenosis rate than seropositive patients with a low antibody titer (< or = 1:400) (p <0.05). High antibody titers against CMV (IgG) may be a strong marker for coronary artery disease, and might predict post-coronary angioplasty restenosis. These findings support the infectious theory of atherosclerosis (especially with prior CMV infection), and also suggest that a chronic immunologic response has a role in atherosclerosis and restenosis.

Adult↗

[Drowning in Israel--1990-1992].

There are no epidemiological studies of drowning in Israel in the scientific literature, despite prominent reports in the media. We analyzed the extent of mortality from drowning in Israel during 1990-92, attempting to identify and characterize groups at high risk, and to determine trends and differences between Israel and other countries. Computerized death certificate files were provided by the Israel government Central Bureau of Statistics; deaths from drowning were included among external causes codes E-830, 832, E-910, E-954, E-964, E-984. In Israel, as in the United States, mortality from drowning is the fourth cause of death among all unintentional causes, and the second cause in age-groups 1-24, ranking after transport accidents. During 1990-92 there were 1.2 drownings a year/100,000 population. The highest rates were found among young non-Jews 15-24 years old (7.8/100,000) and among elderly Jews (3.5/100,000). Unintentional drowning accounted for 89% of all deaths; while about 10% were defined as suicides. Males had a rate almost 3 times greater than females, and the among Arabs was 2.4 times greater than among Jews. The 1990-92 drowning rate was slightly lower than in previous years. Drowning rates in Israel are lower than in the United States, except in the elderly. Apparently the principal reason for this difference is difference in sites of drowning. In Israel most drownings occur in the sea, so site data are unavailable for international comparisons. Careful consideration of the categories (E-codes) included in the rates, and of local registration procedures, is necessary for international comparisons. Foreign workers, tourists and other nonresidents are not included in national vital statistics. But estimations based on Ministry of Interior sources show that foreign workers (most, recent arrivals) during the last few years are an extremely high risk group. Population-based drowning rates are not an accurate estimation of drowning risk, since universal exposure to the "opportunity to drown" is assumed.

Adolescent↗

Recombinant interleukin 2 adjunctive therapy in multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis patients respond poorly to antituberculosis therapy and therefore require new modalities of treatment to overcome the infection. Administration of low dose recombinant human interleukin 2 (rhuIL-2) in combination with chemotherapy to multidrug-resistant tuberculosis patients resulted in reduced or cleared sputum acid-fast bacilli in about 60% of the patients in association with enhanced activation of the immune system. Daily rhuIL-2 administration for 30 days induced increases in CD25+ and CD56+ cells in the blood. rhuIL-2 therapy also resulted in increased expression of gamma-interferon and IL-2 mRNA at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin. Differential display reverse transcriptase PCR revealed several genes expressed at the DTH skin test site that were up- or down-regulated during rhuIL-2 treatment. The differentially regulated genes included components of endocytic vacuoles, enzymes of the respiratory pathway and other regulators of cellular function. The physiological importance of the differential expression of these genes is under investigation to determine their roles in leukocyte activation and in the development of an antimycobacterial response.

Adjuvants, Immunologic↗

Serum amyloid type A may be a predictor of restenosis.

BACKGROUND: Elevation of acute phase proteins [C-reactive protein (CRP) and serum amyloid type A (SAA)] has been demonstrated in unstable angina with an adverse clinical prognosis. HYPOTHESIS: The study was undertaken to determine the effect of angioplasty on the levels of SAA and the correlation with postangioplasty restenosis. METHODS: In a university-affiliated tertiary medical center, a prospective case study was undertaken in 55 patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) of a single coronary lesion for angina pectoris. Three groups of patients were clinically characterized according to Braunwald's classification of anginal syndrome: Group A: class III; Group B: class I; Group C: stable angina. Serum amyloid type A was measured by an ELISA method before PTCA and after 24 h, 1, and 3 months. Patients were followed clinically for 12 months. A thallium stress perfusion scan was performed 3 months after PTCA and coronary angiography was repeated in patients with an abnormal thallium perfusion scan. RESULTS: Serum amyloid type A levels > 100 micrograms/ml could identify Group A patients with a high sensitivity and specificity (r = 0.85 and 0.86, respectively). Of the patients studied, 75% increased their SAA level 24 h after angioplasty. An increase of SAA by > 100% was associated with an increased risk of restenosis, with a relative risk of 6.4 (p < 0.05). CONCLUSION: Increased levels of SAA characterize patients with unstable angina pectoris with a high specificity and sensitivity. Levels of SAA that increase > 100% 24 h after angioplasty may serve as a marker of restenosis.

Adult↗

Degradation of hammerhead ribozymes by human ribonucleases.

Hammerhead ribozymes were used as substrates to examine endoribonucleolytic activities in cell extracts and cultured human cells. Primer-extension analyses showed that ribozymes directed against tumor necrosis factor-alpha mRNA and human immunodeficiency virus type 1 tat mRNA were cleaved at UA and CA dinucleotides by extracts. Preferred cleavage sites were similar to those observed following digestion with RNase A, and cleavage was blocked by RNasin, an inhibitor of pyrimidine-specific ribonucleases. Removal of UA and CA dinucleotides rendered ribozymes more stable when incubated in cell extracts that were not significantly contaminated by extracellular nucleases. Placement of UA dinucleotides adjacent to a ribozyme in mRNA led to excision of the ribozyme from long transcripts during incubation in extracts. UA dinucleotides also made mRNA more labile than a control RNA when expressed from an endogenous plasmid gene in the human myeloid cell line U937. Similarly, UA and CA dinucleotides caused ribozymes to have a shorter half-life when delivered to U937 cells by lipofectin-mediated transformation. Taken together, these data indicate that one or more members of the pyrimidine-specific ribonuclease family is involved in the intracellular degradation of RNA, and they explain the paucity of UA dinucleotides in eukaryotic mRNA. Judicious manipulation of preferred target sequences of pyrimidine-specific ribonucleases may be useful in designing effective hammerhead ribozymes.

Base Sequence↗

Surgical considerations in the contemporary management of biliary tract disease in the postpartum period.

BACKGROUND: Excluding sterilization procedures, no experience with laparoscopic procedures in the postpartum period has been reported. The postpartum patient may have unique characteristics that must be recognized for safe management. METHODS: The authors prospectively studied 1,100 consecutive biliary patients in a private surgical practice since the introduction of laparoscopic cholecystectomy (LC). The group includes 34 patients who presented with biliary tract disease and were operated upon within 6 weeks of obstetrical delivery. Laparoscopic procedures were performed on these 34 patients 1 to 42 days following vaginal (26) or Cesarean (8) deliveries. RESULTS: All patients had calculous cholecystitis. Choledocholithiasis was documented in 10 (29%) patients, including 3 patients (9%) with missed common duct stones, and strongly suggested in 5 (15%) others. Open biliary procedures were required for 2 patients. One patient returned to surgery for an ERCP-related complication. Follow up is known for all patients. There were no delayed complications. CONCLUSIONS: The laparoscopic approach to biliary tract disease in the postpartum period is safe. Recent vertical Cesarean incisions can withstand the strain of a reduced pneumoperitoneum. The high incidence of choledocholithiasis calls for routine cholangiography in the postpartum patient.

Adolescent↗

The distinctive features of influenza virus infection of dendritic cells.

CD8+ cytolytic T lymphocytes (CTLs) are considered to be critical mediators for resistance to influenza virus infection. We have previously demonstrated that dendritic cells are potent antigen presenting cells in the development of anti-influenza CTLs. Here we identify distinctive features of the interaction of influenza virus with dendritic cells. Exposure of dendritic cells to influenza virus at MOIs of 2-4:1 leads to > 90% infection, as manifested by the expression of the viral proteins HA and NS1. The infection is non-toxic as viral protein expression is sustained for > 2 days with retention of viability, but little infectious virus is produced. Substantial induction of the anti-viral cytokine IFN-alpha also occurs. Influenza infection of macrophages also results in viral protein expression in a majority of cells, and synthesis of IFN-alpha. In contrast to dendritic cells, macrophages display evidence of apoptosis within 10-12 hours, and the majority of cells die within 24-36 hours. During this interval macrophages synthesize > 10-fold higher levels of virus than dendritic cells. Infected dendritic cells but not macrophages, can induce substantial CTL responses from purified blood CD8+ T cells in the absence of exogenous cytokines such as IL-2. Low levels of infection (MOIs of 0.02) are sufficient to generate potent CTL responses. Influenza virus expressing non-cleaved HA does not elicit CTLs indicating that virus must access the cytoplasm of dendritic cells to utilize traditional class I processing pathways. These observations indicate that DCs are distinct in their handling of influenza virus and for the induction of anti-viral immunity.

Animals↗

Teat preference for suckling in common marmosets: relationship to side of being carried and hand preference.

Mother-infant interaction in common marmosets ( Callithrix jacchus jacchus ) was scored for the first 60 days post parturition. Teat preference was compared to hand preference for picking up and holding food over the same ages and at 18 months. All infants, except one, exhibited strong preferences for one of the mother's teats. Preference for a teat was maintained when twins suckled separately as well as together. Infants suckled separately for a mean 42% of the time of all suckling bouts being observed. There was a significant correlation between teat preference and the side of being carried by the mother. This correlation was maintained despite the fact that the father also carried the infants. There was no significant relationship between teat preference and hand preference from 0 to 2 months or later life.

Journal Article↗

A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death.

Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs predominantly in children and in immunocompromised adults. To study the pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system infection was set up (8-day study). Inoculation of live Mycobacterium bovis Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells), high protein levels, and release of tumor necrosis factor-alpha (TNF-alpha) into the cerebrospinal fluid within 1 day. Histologically, severe meningitis with thickening of the leptomeninges, prominent vasculitis, and encephalitis was apparent, and mortality was 75% by day 8. In animals treated with antituberculous antibiotics only, the inflammation and lesions of the brain persisted despite a decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was combined with antibiotics, there was a marked reduction in TNF-alpha levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived, suggesting a potential clinical use for thalidomide in TBM.

Animals↗