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Biomedical subjects

J Kahn

Publications and source records attributed to J Kahn.

At least 55 records · Page 3Linked to original sources

Association between dental occlusal variables and intraarticular temporomandibular joint disorders: horizontal and vertical overlap.

STATEMENT OF PROBLEM: It has been suggested that dental occlusion may play a role in the development of intraarticular temporomandibular joint disorders. PURPOSE: This study evaluated the relationship between horizontal and vertical overlap and intraarticular temporomandibular joint disorders. MATERIAL AND METHODS: Vertical and horizontal overlap of the anterior teeth of 82 asymptomatic volunteers and 263 symptomatic patients were examined. RESULTS: Fifty-five (67%) of the asymptomatic volunteers had normal joints and 27 (33%) had disk displacement. Two hundred and twenty-one patients (84%) had disk displacement and 42 (16%) had bilateral symptomatic normal joints. Horizontal overlap equal to or greater than 4 mm was more prevalent in the symptomatic patient group as compared with the asymptomatic volunteer group (p < 0.05). Vertical overlap equal to or greater than 4 mm demonstrated no significant differences. CONCLUSION: Horizontal overlap equal to or greater than 4 mm was greater in symptomatic patients with intraarticular temporomandibular joint disorders.

Adult↗

Evolutionary pattern of human immunodeficiency virus (HIV) replication and distribution in lymph nodes following primary infection: implications for antiviral therapy.

Evolutionary patterns of virus replication and distribution in lymphoid tissue during the early phases of HIV infection have not been delineated. Lymph node (LN) biopsies were excised from patients at different times after the estimated time of primary infection. Within 3 months of the acute viral syndrome, HIV was mostly present in individual virus-expressing cells in LNs; trapping of virions in the follicular dendritic cell (FDC) network was minimal or absent, but was the predominant form of HIV detected in LNs of subjects with chronic infection, either recent (4-20 months after primary infection) or long-term (>2-3 years after primary infection). Plasma viremia was significantly higher in patients during the first 3 months than in those recently infected; however, there were no significant differences in the number of virus-expressing cells per square millimeter of LN tissue in these two groups. Numbers of virus-expressing cells in lymphoid tissue were significantly lower in the subjects with long-term infection than in the other two groups. Therefore, during the transition from primary to chronic HIV infection, the level of HIV replication in lymphoid tissue remains elevated despite the fact that viremia is significantly downregulated. These findings have implications for therapeutic strategies in primary HIV infection and in recent seroconvertors.

Acute Disease↗

The association of weapon carrying and fighting on school property and other health risk and problem behaviors among high school students.

OBJECTIVE: To examine the association between weapon carrying on school property and engaging in health risk and problem behaviors such as fighting and substance use on school property, fear of attending school, and victimization at school. DESIGN: A complex 2-stage probability survey (Massachusetts Youth Risk Behavior Survey). SETTING: High schools in Massachusetts. PARTICIPANTS: Three thousand fifty-four high school students. MAIN OUTCOME MEASURE: Number of days a weapon was carried on school property during the 30 days prior to the survey. RESULTS: The prevalence of self-reported weapon carrying on school property was 15% among male students and 5% among female students (P < .001). Weapon carrying on school property was significantly (P < .001) associated with frequency of physical fights on school property (r = 0.26), being a victim of threat or injury with a weapon on school property (r = 0.27), being a victim of stolen or damaged goods on school property (r = 0.14), not attending school owing to fear (r = 0.15), and substance use while at school, including smoking cigarettes (r = 0.20), using chewing tobacco (r = 0.18), smoking marijuana (r = 0.24), and using alcohol (r = 0.29). The association between weapon carrying and alcohol use in school was higher among students who were afraid to come to school (r = 0.49) than among students who were not afraid (r = 0.28). Students who had engaged in same-sex sexual activity (P < .001) or had been offered, given, or sold illicit drugs at school (P < .001) were more likely to carry a weapon at school. Multiple regression analysis showed that male sex and the frequencies of physical fighting, being a victim of a threat or injury, drinking alcohol, smoking cigarettes, and being offered or sold an illicit drug while on school property accounted for 21% of the variance in weapon carrying in school. When weapon carrying was dichotomized and analyzed with logistic regression, a model containing age, male sex, lower academic achievement, days not attending school owing to fear, times threatened or injured with a weapon at school, frequency of fighting at school, cigarette smoking, alcohol use, and being offered or sold illicit drugs on school property correctly classified 91.83% of the students who did or did not carry weapons. CONCLUSIONS: Weapon carrying at school was more strongly associated more with use of violence and the use of substances at school than with previous victimization and fear of attending school. However, there is a subgroup of students that seems to have been victimized at school, is afraid to come to school, is using alcohol at school, and is carrying weapons at school.

Adolescent↗

Surveillance of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States in 1996-1997 respiratory season. The Laboratory Investigator Group.

A U.S. surveillance study of antimicrobial resistance in respiratory tract pathogens in the respiratory season (1996-1997) is reported that included 11,368 isolates from 434 institutions in 45 states and the District of Columbia. beta-lactamase was produced by 33.4% of Haemophilus influenzae and 92.7% of Moraxella catarrhalis. Of the 9,190 Streptococcus pneumoniae isolates tested, 33.5% were not susceptible to penicillin (MIC > or = 0.12 microgram/mL), with 13.6% having high-level resistance (MICs > 1 microgram/mL). For H. influenzae, the most active antimicrobials (based on percent of strains susceptible) were levofloxacin (100%) and ceftriaxone (99.9%); the least active were ampicillin (67.2%) and clarithromycin (58.1%). For M. catarrhalis, the most active drugs were amoxicillin-clavulanate, ceftriaxone, and levofloxacin (100%); the least active was ampicillin. The order of the activity of the drugs against S. pneumoniae were levofloxacin (97.3%) > ceftriaxone (87.1%) > amoxicillin-clavulanate (81.7%) = clarithromycin (80.9%) > cefuroxime (74.5%) > penicillin (66.5%). The activity of the beta-lactams and clarithromycin against isolates of S. pneumoniae was closely associated with the resistance to penicillin. Levofloxacin was more active against S. pneumoniae overall, because it exhibited no cross-resistance. These data indicate that the incidence of beta-lactamase production in H. influenzae (33.4%) and M. catarrhalis (92.7%) is similar to other recent studies, and that the incidence of penicillin-intermediate and -resistant S. pneumoniae is increasing, particularly the high-level penicillin-resistant (MICs > 1 microgram/mL) strains, which were often multi-resistant.

Amoxicillin-Potassium Clavulanate Combination↗

Low albumin gradient ascites complicating severe pseudomembranous colitis.

Pseudomembranous colitis (PMC) is a frequently severe, sometimes fatal iatrogenic disease that is antibiotic-associated in almost all cases. The most common clinical features of PMC include abdominal pain, watery diarrhea, fever, leukocytosis, hypoalbuminemia, and hypovolemia. Ascites, not considered a well-known feature of PMC, is fairly common, based on a review of the English language literature but has not been characterized fully. This case report describes 5 patients with PMC who presented with low serum-ascites albumin gradient (SAAG) and neutrocytic ascites, without evidence of infectious, malignant, or inflammatory peritoneal disease, which has not been reported previously. In 1 patient, massive low SAAG ascites was the presenting manifestation of PMC, a feature also not reported previously. Three of the 5 (60%) patients had acquired immunodeficiency syndrome. The characteristics of the fluid specimens in these 5 patients and the possible pathogenetic mechanisms are proposed. The findings suggest that PMC should be included in the differential diagnosis of low SAAG ascites, especially in patients with acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Neutralization of a clade B primary isolate by sera from human immunodeficiency virus-uninfected recipients of candidate AIDS vaccines.

The inability of antibodies induced by experimental human immunodeficiency virus type 1 (HIV-1) vaccines to neutralize HIV-1 primary isolates may be due to a failure to elicit such antibodies, antigenic differences between the vaccine and the strains tested, insensitivity of the assays used, or to a combination of factors. New neutralization assays were used to determine the ability of candidate AIDS vaccines to generate neutralizing antibodies for clade B primary isolate BZ167, which is closely related in portions of its envelope to the immunizing strains. Sera from HIV-uninfected volunteers in vaccine trials were tested, and neutralizing activity was found in recipients of recombinant (r) gp120MN or of rgp160MN-containing canarypox boosted with rgp120SF-2. Detection of antibodies that neutralize primary isolate BZ167 correlated with neutralizing activity for homologous vaccine strains. These data demonstrate that certain candidate AIDS vaccines can elicit antibodies that neutralize a primary isolate of HIV-1.

AIDS Vaccines↗

The safety and efficacy of adefovir dipivoxil, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults: a randomized, double-blind, placebo-controlled trial.

Adefovir dipivoxil is a novel nucleotide analogue with several promising in vitro anti-human immunodeficiency virus (HIV) characteristics. To evaluate the safety and efficacy of adefovir dipivoxil monotherapy, a randomized, double-blind, placebo-controlled study was initiated involving 72 subjects with moderately advanced HIV disease. Subjects were randomly assigned in a 2:1 ratio to receive adefovir dipivoxil or placebo as a once-daily oral dose for 6 weeks, followed by 6 weeks of open-label adefovir dipivoxil. Two dose levels were studied (125 mg and 250 mg). Adefovir dipivoxil was determined to be safe and well-tolerated when administered for 12 weeks. At week 6, changes in absolute CD4 T cell levels and HIV-1 RNA levels were significantly greater with adefovir dipivoxil than with placebo. These effects were sustained through 12 weeks of treatment. As determined by standard RNA sequencing techniques, only 1 of the 24 subjects who received adefovir dipivoxil (125 mg/day) developed any genotypic change from baseline.

Adenine↗

The role of reader age and focus of attention in creating situation models from narratives.

We examined adult age differences in the mental representation of situations and how readers update this representation during narrative comprehension. Older and younger adults memorized a building layout and then read narratives about a protagonist's actions in this building. The narratives contained critical sentences that described the protagonist moving from one room (the "source room") into another (the "goal room"), through an unmentioned path room. Each critical sentence was followed by a target sentence referring to an object in one of these rooms. Half of the target sentences explicitly mentioned the room containing this object and half did not. Reading time increased when the target object was more distant from the protagonist and when the room containing the object was not mentioned, suggesting that readers tracked the protagonist's location in the layout and allocated resources in order to maintain coherence in the situation model. Older adults' reading times differentially slowed with distance, and older readers who more accurately understood the narrative differentially slowed when the location of the target object was not mentioned. Finally, the more accurate readers (older and younger) slowed primarily when updating was most difficult (i.e., both when the room containing the object was not mentioned and for more distant objects). While these findings reveal qualitative similarity in how older and younger readers update spatially organized situation models, they also suggest that older readers must sometimes allocate more resources to this updating process in order to maintain comprehension.

Adult↗

Meta-analysis of five randomized controlled trials comparing continuation of zidovudine versus switching to didanosine in HIV-infected individuals.

A meta-analysis of the original data from 2411 patients in the ACTG 116A, ACTG116B/117, ACTG175, BMS010 and CTN002 trials was conducted to improve the estimate of the effect of switching from zidovudine to didanosine on rates of clinical progression, to better quantify the rates of neurological events (including AIDS dementia and peripheral neuropathy) and to examine the effects of switching from zidovudine to didanosine among women and racial subgroups. In total, 1012 patients received zidovudine therapy, 557 received high-dose didanosine and 842 received didanosine. The median duration of follow-up was 15 months. Ninety-one percent of patients were male, 78% were white, mean age was 36.5 years. The median CD4 count was 195 cells/mm3 (range: 0-762) and the median duration of prior zidovudine therapy was 14 months (range: 0.1-94). There were 336 deaths and 686 new AIDS-defining illnesses (ADIs) or deaths. After stratification by study and adjusting for baseline CD4 count and presence of an AIDS diagnosis prior to baseline, the relative risks of death associated with switching from zidovudine to high-dose didanosine or to didanosine were 0.94 (P = 0.64) and 0.77 (P = 0.07), respectively. The relative risks of a new ADI or death associated with switching from zidovudine to high-dose didanosine and didanosine were 0.78 (P = 0.01) and 0.66 (P = 0.0001), respectively. There were 21 documented cases of AIDS dementia complex (ADC) during the entire follow-up period. The rates per 100 person years of follow-up were 0.70, 0.65 and 0.41 for the zidovudine, high-dose didanosine and didanosine arms, respectively. There were no significant differences in risks of ADC between treatment arms (zidovudine versus high-dose didanosine: P = 0.30, zidovudine versus didanosine: P = 0.97, didanosine versus high-dose didanosine: P = 0.41). Our data confirm a clinical benefit and CD4 increase associated with a switch from zidovudine to didanosine therapy. No statistical differences were detected between doses of didanosine with respect to survival or progression to a new ADI or death. Furthermore, there was no statistical difference in the frequency of ADC between treatment arms.

AIDS Dementia Complex↗

Ethical issues in genetic testing for Alzheimer's disease.

The discovery of genetic mutations that increase the risk of developing Alzheimer's disease (AD) brings new promise of predictive testing for the disease. But the quality of information yielded by genetic tests for AD and the implications of this information raise serious questions about the use of such tests. This article examines some of the ethical issues related to predictive genetic testing for AD by examining the interpretation and potential misuses of such data, as well as the factors affecting the development and use of such testing technology. Finally, it poses some recommendations for how genetic testing for AD and the information it yields should be used.

Alzheimer Disease↗

Phase 1 study of combination therapy with L-697,661 and zidovudine. The ACTG 184 Protocol Team.

We performed a pilot study that examined the clinical and pharmacokinetic interactions between zidovudine (ZDV) and a pyridinone derivative, L-697-661. The results indicate that the drugs were well tolerated, with no important pharmacokinetic interactions, when administered concomitantly for as long as 8 weeks. Although the number of study participants was small, we noted rapid emergence of resistance to L-697,661 among ZDV-naive study subjects who were administered L-697,661 as monotherapy but did not observe isolates of human immunodeficiency virus type 1 (HIV-1) resistant to L-697,661 among those who were administered concomitant ZDV. These results suggest a potential interaction between development of resistance to L-697,661 and ZDV. Although the clinical development of L-697,661 has been halted, our results support the need for further studies to test whether specific interactions among antiretroviral agents administered in combination and the molecular target can delay the emergence of isolates that exhibit resistance to all drugs in the regimen.

Adult↗

Patterns of opportunistic infections in patients with HIV infection.

The pattern of the development of opportunistic infections (OIs) in HIV-infected patients was evaluated, based on a cohort of 1,530 patients enrolled in two AIDS Clinical Trials Group anti-retroviral studies. We quantified the increase in risk of OIs associated with the occurrence of a previous OI. This assessment was based on the observed event rates of the more common AIDS-defining OIs: Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), cytomegalovirus (CMV), and a systemic mycosis. Additionally, for each OI, we assessed the relative risks associated with a history of prior OIs, changes in CD4 levels, and baseline prognostic factors. We found that the occurrence of each of these OIs increased the risk of subsequent OIs, even after adjusting for the CD4 count. Specifically, the occurrence of PCP significantly increased the risk of MAC and CMV, and somewhat increased the risk of systemic mycoses. Diagnosis with MAC was associated with an increased risk of subsequent CMV, whereas the occurrence of CMV increased the risk of MAC. Finally, once patients were diagnosed with a systemic mycosis, they were at a somewhat increased risk of subsequently developing MAC or CMV. Although current practice for determining the timing and initiation of prophylactic therapies relies chiefly on CD4 count, the occurrence of specific AIDS-defining OIs in patients with HIV infection should also be taken into account in making decisions regarding prophylaxis strategies.

AIDS-Related Opportunistic Infections↗

Neutrophil rolling altered by inhibition of L-selectin shedding in vitro.

The L-selectin adhesion molecule is involved in guiding leukocytes to sites of inflammation. L-selectin is cleaved by an unusual proteolytic activity at a membrane-proximal site resulting in rapid shedding from the cell surface. Although it has been demonstrated that L-selectin mediates, in part, the early event of leukocyte rolling under hydrodynamic flow, the contribution of shedding to L-selectin function has remained unknown. Here we show that hydroxamic acid-based metalloprotease inhibitors block L-selectin downregulation from the cell surface of stimulated neutrophils, without affecting Mac-1 mobilization or general neutrophil activation, and inhibit cleavage of L-selectin in a cell-free system. Unexpectedly, the hydroxamic acid-based inhibitors reduced neutrophil rolling velocity under hydrodynamic flow, resulting in increased neutrophil accumulation. These results suggest that L-selectin is cleaved in seconds--much faster than previously suspected--during the process of rolling under hydrodynamic flow, and that shedding of L-selectin may contribute significantly to the velocity of leukocyte rolling. L-selectin shedding during rolling interactions may be physiologically important for limiting leukocyte aggregation and accumulation at sites of inflammation.

Cell Adhesion↗

Shedding of the lymphocyte L-selectin adhesion molecule is inhibited by a hydroxamic acid-based protease inhibitor. Identification with an L-selectin-alkaline phosphatase reporter.

Expression of the L-selectin adhesion molecule can be rapidly down-modulated by regulated proteolysis at a membrane-proximal site. The L-selectin secretase has remained undefined, and the secretase activity is resistant to a broad panel of common protease inhibitors. We have developed an L-selectin-alkaline phosphatase reporter, consisting of the ectodomain of human placental alkaline phosphatase fused to the membrane-proximal cleavage, transmembrane, and cytoplasmic domains of L-selectin, to aid in the screening for L-selectin secretase inhibitors. A hydroxamic acid-based metalloprotease inhibitor, KD-IX-73-4, inhibited release of the L-selectin-alkaline phosphatase reporter in a dose-dependent manner. The hydroxamic acid-based peptide was also found to inhibit wild type L-selectin down-regulation from the surfaces of phorbol myristate acetate-activated peripheral blood lymphocytes and phytohemagglutinin-stimulated lymphoblasts. Analysis of the proteolytic cleavage fragments of L-selectin confirmed that KD-IX-73-4 inhibited L-selectin proteolysis. Lymphocyte L-selectin was not down-regulated when co-cultured with formylmethionylleucylphenylalanine-stimulated neutrophils, suggesting that the putative secretase acts in cis with the membrane-bound L-selectin. These results suggest that the L-selectin secretase activity may involve a cell surface, zinc-dependent metalloprotease, although L-selectin shedding is not affected by EDTA and may be related to the recently described activity involved in processing of membrane-bound TNF-alpha.

Alkaline Phosphatase↗

Pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor: the effects of zidovudine.

Recombinant human granulocyte-macrophage colony-stimulating factor (rHu GM-CSF) enhances bone marrow production of and stimulates granulocytes, macrophages, and eosinophils. Granulocyte-macrophage colony-stimulating factor may be used concomitantly with zidovudine in human immunodeficiency virus (HIV)-positive patients to minimize zidovudine-associated neutropenia. This open-label, randomized, placebo-controlled study was performed to evaluate the pharmacokinetic disposition of rHu GM-CSF in HIV-positive, asymptomatic patients in the absence and presence of concomitant zidovudine administration. Eight participants received rHu GM-CSF (5 micrograms/kg subcutaneously) daily for 4 days in combination with placebo or zidovudine (200 mg orally every 8 hours) in a randomized, crossover fashion, with each study period separated by a 3-day washout phase. Pharmacokinetic blood sampling was performed over 16 hours on days 1 and 4 of both treatment periods, and subsequent analysis of serum was performed using an enzyme-linked immunosorbent assay. Pharmacokinetic results of rHu GM-CSF at steady state (days 4 of periods I and II) in the absence (placebo) and presence of zidovudine included apparent total body clearance, half-life, and apparent volume of distribution, all of which were not significantly altered with concomitant administration of zidovudine. Mean pharmacokinetic results of rHu GM-CSF after the first dose (days 1 of periods I and II) were similar to steady-state values; however, total body clearance was significantly increased at steady state compared with the results of the first dose. Concurrent administration of zidovudine does not influence the pharmacokinetic disposition of rHu GM-CSF after single or multiple doses.

Adult↗

Stress and the boards.

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Education, Medical, Graduate↗