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Biomedical subjects

J T Li

Publications and source records attributed to J T Li.

At least 55 records · Page 3Linked to original sources

Sulbactam/cefoperazone versus cefotaxime for the treatment of moderate-to-severe bacterial infections: results of a randomized, controlled clinical trial.

We conducted a randomized, open-label, controlled, multicenter study to compare sulbactam/cefoperazone with cefotaxime in terms of efficacy and safety for the treatment of hospitalized patients with moderate-to-severe bacterial infections. More than two-thirds of the pathogens recovered from these patients produced beta-lactamase. Two hundred-seven (88.1%) of the 235 patients enrolled completed the study and were included in the efficacy and safety evaluations. One hundred-three patients received sulbactam/cefoperazone (2-4 g/d) administered in evenly divided doses every 12 hours by a 30-minute intravenous drip; 104 patients received cefotaxime (6-12 g/d) administered in evenly divided doses every 6 or 8 hours by a 30-minute intravenous drip. The overall efficacy rates (i.e., cure or markedly improved) were 95% for the sulbactam/cefoperazone group and 90% for the cefotaxime group (P = .186), whereas the bacterial eradication rates were 85% for the sulbactam/cefoperazone group and 81% for the cefotaxime group (P = .467). Both drug regimens were well tolerated. Sulbactam/cefoperazone is effective and safe for the treatment of moderate-to-severe bacterial infections caused mainly by beta-lactamase-producing organisms.

Adolescent↗

Mechanisms of asthma.

Understanding of the mechanisms of asthma has progressed in three areas: the genetics of asthma, the role of nitric oxide in asthma, and the role of neurokinins in asthma. Genes encoding for the high affinity IgE receptor, the beta 2-adrenergic receptor, and interleukin-4 have been linked to clinical characteristics of asthma. Exhaled nitric oxide may be a useful clinical marker for airway inflammation in asthma. Tachykinin receptors are present in human lung and may be differentially expressed in individuals with asthma.

Adolescent↗

Exercise-induced urticaria and anaphylaxis.

Exercise-induced urticaria and anaphylaxis have become increasingly recognized during the past 2 decades as more people participate in physical activities. These syndromes can be categorized as cholinergic urticaria or exercise-induced anaphylaxis based on the clinical manifestation. Newer subsets such as food-dependent and familial exercise-induced anaphylaxis have also been recognized. Further studies are needed to characterize the variables involved in mast cell activation and mast cell mediator release in these syndromes. The management strategy for patients who have exercise-induced syndromes with skin manifestations only differs from the management for those with systemic symptoms. Currently, antihistamines, as a single agent or in combination with other agents, may be helpful prophylactically in both groups. Avoidance of precipitating factors, modification of exercise, and use of a self-injectable epinephrine kit are recommended for patients with anaphylaxis.

Adolescent↗

Eosinophilic myocarditis manifesting as myocardial infarction: early diagnosis and successful treatment.

OBJECTIVE: To report a case of eosinophilic myocarditis with remarkable initial clinical manifestations and outcome. MATERIAL AND METHODS: A 67-year-old woman with hypertension and a history of asthma and drug hypersensitivity was referred to our institution with a diagnosis of acute myocardial infarction on the basis of severe chest pain, ST elevation on an electrocardiogram, and a slight increase in cardiac enzymes. Further diagnostic studies were performed. RESULTS: Echocardiography disclosed left ventricular dysfunction in conjunction with apical asynergy, thinning, and thrombus. The eosinophil count in the peripheral blood was increased only slightly. Coronary angiography showed normal arteries and prompted the performance of endomyocardial biopsy, which revealed active eosinophilic myocarditis. After corticosteroid therapy, global and regional left ventricular function returned to normal. CONCLUSION: This unusual clinical picture and outcome demonstrate that eosinophilic myocarditis may simulate acute myocardial infarction and should be considered in patients with a history of allergies or acute left ventricular dysfunction, even in the absence of pronounced eosinophilia in the peripheral blood. With appropriate medical therapy, recovery for these patients can be complete.

Acute Disease↗

Phase I clinical trial of cefditoren pivoxil (ME1207). Tolerance in healthy volunteers.

A tolerance study to ME1207 was conducted in healthy volunteers using five single doses administered before a meal (50, 100, 200, 300 and 500 mg), a single 200 mg dose administered after a meal, and 200 mg administered every 12 h for 7 days. No subjective symptoms or changes in haematological and biochemical examinations and urinalysis were observed after single administration of 50 to 500 mg Four subjects complained of minimal upper abdominal discomfort when 200 mg was administered every 12 h for 7 days, but this symptom disappeared without remedial action in all cases. Therefore ME1207 was thought to be safe when orally administered at the above-mentioned doses by the above-mentioned administration methods.

Administration, Oral↗

Phase I clinical trial of cefditoren pivoxil (ME 1207): pharmacokinetics in healthy volunteers.

Pharmacokinetics of ME1207 were evaluated in 5 groups of healthy adult male volunteers given single preprandial administration of 100, 200 and 300 mg; postprandial administration of 200 mg; and administration of 200 mg every 12 h for 7 consecutive days. Blood drug concentrations were determined by HPLC and bioassay after oral single administration of 100, 200 and 300 mg before meals. Serum concentrations and major pharmacokinetic parameters (Cmax, Tmax, AUC and T1/2 Ke) determined by these two methods were comparable. Cmax and AUC determined by bioassay after postprandial administration were greater than those determined after preprandial administration. Blood concentrations determined 1.5 and 12 h after each administration, during repeated administration of 200 mg every 12 hours for 7 days, were always about 2.5 and 0 mg/l, respectively, indicating that the drug is not accumulated in the body. Within 24 hours after administration of 100, 200 and 300 mg, 19.93 +/- 5.20, 20.24 +/- 3.72 and 21.29 +/- 5.47%, respectively, of the dose were excreted into urine in an unchanged form.

Absorption↗

Ragweed immunotherapy in adult asthma.

BACKGROUND: Although allergen immunotherapy is effective for allergic rhinitis, its role in treating asthma is unclear. METHODS: We examined the efficacy of immunotherapy for asthma exacerbated by seasonal ragweed exposure. During an observation phase, adults with asthma who were sensitive to ragweed kept daily diaries and recorded peak expiratory flow rates between July and October. Those who reported seasonal asthma symptoms and medication use as well as decreased peak expiratory flow were randomly assigned to receive placebo or ragweed-extract immunotherapy in doses that increased weekly for an additional two years. RESULTS: During the observation phase, the mean (+/- SE) peak expiratory flow rate measured in the morning during the three weeks representing the height of the pollination season was 454 +/- 20 liters per minute in the immunotherapy group and 444 +/- 16 liters per minute in the placebo group. Of the 77 patients who began the treatment phase, 64 completed one year of the study treatment and 53 completed two years. During the two treatment years, the mean peak expiratory flow rate was higher in the immunotherapy group (489 +/- 16 liters per minute, vs. 453 +/- 17 in the placebo group [P = 0.06] during the first year, and 480 +/- 12 liters per minute, vs. 461 +/- 13 in the placebo group [P = 0.03] during the second). Medication use was higher in the immunotherapy group than in the placebo group during observation and lower during the first treatment year (P = 0.01) but did not differ in the two groups during the second year (P = 0.7). Asthma-symptom scores were similar in the two groups (P = 0.08 in year 1 and P = 0.3 in year 2). The immunotherapy group had reduced hay-fever symptoms, skin-test sensitivity to ragweed, and sensitivity to bronchial challenges and increased IgG antibodies to ragweed as compared with the placebo group; there was no longer a seasonal increase in IgE antibodies to ragweed allergen in the immunotherapy group after two years of treatment. Reduced medication costs were counterbalanced by the costs of immunotherapy. CONCLUSIONS: Although immunotherapy for adults with asthma exacerbated by seasonal ragweed exposure had positive effects on objective measures of asthma and allergy, the clinical effects were limited and many were not sustained for two years.

Adult↗

Clinical evaluation of asthma.

OBJECTIVE: The purpose of this article is to review the medical history and physical examination of the asthmatic patient. DATA SOURCES: English references identified from relevant articles and book chapters, experts, and MEDLINE search, using "asthma," "physical diagnosis," and "medical history." STUDY SELECTION: Clinical studies of the medical history or physical examination in subjects with respiratory disease were selected for review. RESULTS: Symptoms such as wheezing, chest tightness and difficulty in taking a deep breath suggest asthma, while symptoms such as gasping, smothering or air hunger suggest alternative diagnoses. Symptoms of asthma correlate poorly with airway obstruction in one-third to one-half of asthmatic patients. Respiratory signs such as wheezing, breath sound intensity, forced expiratory time, accessory muscle use, respiratory rate and pulsus paradoxus correlate roughly with airway obstruction. However, clinicians disagree on the presence or absence of respiratory signs 55% to 89% of the time. Furthermore, physicians correctly predict pulmonary function based on history and physical examination only about half the time, and correctly diagnose asthma based on the clinical examination 63% to 74% of the time. CONCLUSIONS: The medical history and physical examination are moderately effective in diagnosing asthma and estimating its severity. Objective measures of lung function are necessary for the accurate diagnosis of asthma.

Asthma↗

A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys.

The utility of the simian immunodeficiency virus of macaques (SIVmac) model of AIDS has been limited by the genetic divergence of the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and the SIVs. To develop a better AIDS animal model, we have been exploring the infection of rhesus monkeys with chimeric simian/human immunodeficiency viruses (SHIVs) composed of SIVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rev. SHIV-89.6, constructed with the HIV-1 env of a cytopathic, macrophage-tropic clone of a patient isolate of HIV-1 (89.6), was previously shown to replicate to a high degree in monkeys during primary infection. However, pathogenic consequences of chronic infection were not evident. We now show that after two serial in vivo passages by intravenous blood inoculation of naive rhesus monkeys, this SHIV (SHIV-89.6P) induced CD4 lymphopenia and an AIDS-like disease with wasting and opportunistic infections. Genetic and serologic evaluation indicated that the reisolated SHIV-89.6P expressed envelope glycoproteins that resembled those of HIV-1. When inoculated into naive rhesus monkeys, SHIV-89.6P caused persistent infection and CD4 lymphopenia. This chimeric virus expressing patient isolate HIV-1 envelope glycoproteins will be valuable as a challenge virus for evaluating HIV-1 envelope-based vaccines and for exploring the genetic determinants of HIV-1 pathogenicity.

Acquired Immunodeficiency Syndrome↗

An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys.

To explore the roles played by specific human immunodeficiency virus type 1 (HIV-1) genes in determining the in vivo replicative capacity of AIDS viruses, we have examined the replication kinetics and virus-specific immune responses in rhesus monkeys following infection with two chimeric simian/human immunodeficiency viruses (SHIVs). These viruses were composed of simian immunodeficiency virus SIVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rep. Virus replication was assessed during primary infection of rhesus monkeys by measuring plasma SIVmac p27 levels and by quantifying virus replication in lymph nodes using in situ hybridization. SHIV-HXBc2, which expresses the HIV-1 env of a T-cell-tropic, laboratory-adapted strain of HIV-1 (HXBc2), replicated well in rhesus monkey peripheral blood leukocytes (PBL) in vitro but replicated only to low levels when inoculated in rhesus monkeys. In contrast, SHIV-89.6 was constructed with the HIV-1 env gene of a T-cell- and macrophage-tropic clone of a patient isolate of HIV-1 (89.6). This virus replicated to a lower level in monkey PBL in vitro but replicated to a higher degree in monkeys during primary infection. Moreover, monkeys infected with SHIV-89.6 developed an inversion in the PBL CD4/CD8 ratio coincident with the clearance of primary viremia. The differences in the in vivo consequences of infection by these two SHIVs could not be explained by differences in the immune responses elicited by these viruses, since infected animals had comparable type-specific neutralizing antibody titers, proliferative responses to recombinant HIV-1 gp120, and virus-specific cytolytic effector T-cell responses. With the demonstration that a chimeric SHIV can replicate to high levels during primary infection in rhesus monkeys, this model can now be used to define genetic determinants of HIV-1 pathogenicity.

Animals↗

Use of an objective structured clinical examination to determine clinical competence.

PURPOSE: To describe the performance of second-year internal medicine residents on an objective structured clinical examination (OSCE) and to analyze the role of the OSCE in the evaluation of clinical competence. METHOD: In 1993-94, 51 second-year residents in an internal medicine training program at the Mayo Clinic participated in an OSCE. The OSCE was administered in four sessions, with 12 or 13 students in each session. The OSCE was composed of nine physical diagnosis stations, with two or three test-interpretation stations per session. Student's t-test and one-way analysis of variance were used to compare scores on the basis of the residents' gender, medical school training (international medical graduates versus those trained in the United States and Canada), and OSCE session. In addition, the residents' scores were correlated with scores on the American Board of Internal Medicine's in-training exam (ITE) and with the training program's clinical rotation scores (CRSs). RESULTS: The residents' scores were significantly higher for test interpretation stations than for physical diagnosis stations (p < .0001). There was no significant difference in average scores based on gender, medical school training, or OSCE session. The OSCE scores correlated with the ITE scores (r = .30) and the CRSs (r = .40). CONCLUSION: The OSCE's moderate correlation with the ITE and CRS suggests that the OSCE, which consists largely of physical diagnosis stations, may test a component of clinical skills not evaluated by the other measures. Thus, the OSCE is an important addition to the assessment of clinical competence.

Analysis of Variance↗

Persistent infection of macaques with simian-human immunodeficiency viruses.

Chimeric simian-human immunodeficiency viruses (SHIV) containing the human immunodeficiency virus type 1 (HIV-1) tat, rev, env, and, in some cases, vpu genes were inoculated into eight cynomolgus monkeys. Viruses could be consistently recovered from the CD8-depleted peripheral blood lymphocytes of all eight animals for at least 2 months. After this time, virus isolation varied among the animals, with viruses continuing to be isolated from some animals beyond 600 days after inoculation. The level of viral RNA in plasma during acute infection and the frequency of virus isolation after the initial 2-month period were higher for the Vpu-positive viruses. All of the animals remained clinically healthy, and the absolute numbers of CD4-positive lymphocytes were stable. Antibodies capable of neutralizing HIV-1 were generated at high titers in animals exhibiting the greatest consistency of virus isolation. Strain-specific HIV-1-neutralizing antibodies were initially elicited, and then more broadly neutralizing antibodies were elicited. env sequences from two viruses isolated more than a year after infection were analyzed. In the Vpu-negative SHIV, for which virus loads were lower, a small amount of env variation, which did not correspond to that found in natural HIV-1 variants, was observed. By contrast, in the Vpu-positive virus, which was consistently isolated from the host animal, extensive variation of the envelope glycoproteins in the defined variable gp120 regions was observed. Escape from neutralization by CD4 binding site monoclonal antibodies was observed for the viruses with the latter envelope glycoproteins, and the mechanism of escape appears to involve decreased binding of the antibody to the monomeric gp120 glycoproteins. The consistency with which SHIV infection of cynomolgus monkeys is initiated and the similarities in the neutralizing antibody response to SHIV and HIV-1 support the utility of this model system for the study of HIV-1 prophylaxis.

Acquired Immunodeficiency Syndrome↗

Home peak expiratory flow rate monitoring in patients with asthma.

OBJECTIVE: To describe how the peak expiratory flow rate (PEFR) is measured, review published studies of the accuracy in which patients and physicians can estimate the severity of asthma by clinical observations only, and review published studies of the benefits of home PEFR monitoring. DESIGN: A review of home PEFR monitoring and its associated benefits for both the physician and the patient is presented. RESULTS: An accurate assessment of the severity of asthma is crucial for the optimal treatment of the patient with asthma; however, patients and their physicians are often unable to estimate correctly the degree of airway obstruction. Peak flow measurement is a simple, inexpensive method of objectively determining airflow obstruction. Management of asthma based on home PEFR measurements can result in early recognition and prompt treatment of asthma exacerbations. Home PEFR monitoring in the setting of a comprehensive self-management program can lead to fewer symptoms of asthma, fewer days absent from work or school, fewer emergency examinations, fewer hospitalizations, lower requirements of inhaled beta-antagonists and oral corticosteroid therapy, and better pulmonary function. CONCLUSION: For best results, home PEFR monitoring should be coupled with a thorough educational program on asthma and periodic office spirometry.

Asthma↗