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Biomedical subjects

L Lai

Publications and source records attributed to L Lai.

105 records · Page 6Linked to original sources

Peripheral blood and bone marrow abnormalities in patients with HIV related disease.

Between February 1983 and April 1986 we studied peripheral blood and bone marrow samples from 20 patients with human immunodeficiency virus (HIV) related disease. 14 patients had AIDS, three had ARC, two had PGL and one had ITP as a sole manifestation of HIV related disease. Peripheral blood abnormalities included marked anisocytosis and poikilocytosis, rouleaux formation, neutropenia, lymphopenia, monocytopenia, a left shift in the granulocyte series and, in the patients with AIDS, vacuolated monocytes. The most frequent bone marrow abnormalities were reticuloendothelial iron block, dyserythropoiesis, megaloblastic change and erythroid hypoplasia. Excess histiocytes were noted in four marrows, one exhibiting haemophagocytosis. None of the bone marrows showed lymphopenia. Eight of the 20 marrows were difficult or impossible to aspirate. None of the trephine biopsies showed increased reticulin. The causes of these abnormalities are probably multiple and include opportunistic infections, drug therapy, immune mechanisms and possibly direct insult by the HIV virus.

AIDS-Related Complex↗

Thrombin-induced chemotaxis and aggregation of neutrophils.

Thrombin-induced neutrophil chemotaxis and aggregation were studied using cells isolated from either human or sheep blood. Sheep neutrophils (10(8) cells/ml) exhibited maximum chemotactic migration towards 10(-8)M human alpha-thrombin, 10(-8)M gamma-thrombin (which lacks the fibrinogen site), and 10(-12)MD-Phe-Pro-Arg-CH2-alpha-thrombin (catalytically inactive thrombin). Chemotactic responses of the same magnitude were obtained with human neutrophils (10(8) cells/ml). The chemotactic responses to thrombin were comparable to those obtained with diluted (1:200 v/v) zymosan activated serum (ZAS) and 10(-11)M FMLP. Premixing of the thrombin forms with hirudin in 1:1 stoichiometric amounts abolished the chemotaxis but not chemokinesis Aggregatory responses of human and sheep neutrophils were comparable for ZAS, alpha-thrombin, and gamma-thrombin. The responses of both human and sheep neutrophils to D-Phe-Pro-Arg-CH2-alpha-thrombin were attenuated, indicating that the proteolytic site may be involved in the aggregatory response. The results suggest that thrombin-induced neutrophil chemotaxis and aggregation are mediated by different mechanisms, since chemotaxis is a catalytically independent response whereas aggregation is an active site independent response.

Animals↗

Pulmonary hemodynamic effects of antisheep serum-induced leukopenia.

Antisheep antileukocyte serum (ALS) was produced in rabbits, purified, and adsorbed against erythrocytes and platelets. The ALS was infused intra-arterially over a 3-hour period into anesthetized sheep (n = 6) prepared with lung lymph fistulas. Pulmonary vascular resistance (PVR) and pulmonary lymph flow (Qlym) increased two- to threefold while the lymph-to-plasma protein concentration ratio (L/P) did not change from baseline, suggesting an increase in pulmonary vascular permeability to proteins. The arterial leukocyte count decreased from 4,935 +/- 840 to 1,385 +/- 325 cells/microliters, the neutrophil count decreased from 1,045 +/- 265 to 340 +/- 130 cells/microliters, and the platelet count decreased from 2.8 X 10(5) +/- 0.2 X 10(5) to 0.65 X 10(5) +/- 0.12 X 10(5) cells/microliters. ALS induced neutrophil aggregation in vitro, but not platelet aggregation. In the present study, we also examined the effects of ALS-induced leukopenia on the increase in pulmonary vascular permeability after intravenous alpha-thrombin challenge to assess the role of leukocytes in mediating the increased permeability response. Sheep (n = 5) were made leukopenic by an intramuscular injection of ALS; Qlym was in the normal range 4 to 5 hours after the ALS administration. In the leukopenic group, thrombin challenge caused an increase in Qlym from 7.8 +/- 0.7 to 12.9 +/- 1.9 ml/hr (a 64% increase) while L/P decreased from 0.86 +/- 0.04 to 0.70 +/- 0.05 (a 19% decrease). In contrast, thrombin-induced intravascular coagulation in control sheep (n = 5) produced a 250% increase in Qlym with an increase in L/P. The results indicate that leukocytes are required for the increase in lung vascular permeability after thrombin-induced intravascular coagulation.

Animals↗

Treatment of immune thrombocytopenic purpura in homosexual men.

Over the past 3 yr we have treated 6 homosexual men (age 22-55 yr) with immune thrombocytopenic purpura. 4 of the 6 have antibody to HTLV-III in their serum, 1 of these patients has the acquired immune deficiency syndrome (AIDS), 1 has AIDS-related-complex (ARC), and a 3rd has persistent generalised lymphadenopathy (PGL). The platelet count at presentation was between 2 and 35 X 10(9)/l and in each case a bone marrow confirmed active platelet production. Antiplatelet antibodies were demonstrated in 3 of 4 patients tested. 3 of the 6 patients showed a partial response to prednisolone, 2 showed little or no response and the 6th showed a good response. 2 patients received high dose i.v. immunoglobulin - 1 had an excellent response prior to splenectomy, the other showed no response. 5 of the 6 patients had a splenectomy. 3 had a lasting remission (12-27 months after splenectomy), 1 of these has HTLV-III antibodies; 1 had a remission lasting 1 yr, followed by fluctuating thrombocytopenia (21-130 X 10(9)/l) and 1 showed no response.

Adult↗

Incidence and risk of transmission of HTLV III infections to staff at a London hospital, 1982-85.

In 1982 only two cases of acquired immune deficiency syndrome (AIDS) and one case of persistent generalized lymphadenopathy (PGL) were diagnosed at St Stephen's hospital in central London. By 31 July 1985, the numbers of cases with these conditions had increased to 41 and 185 respectively and a total of approximately 400 patients had been recognized as having HTLV III infection. A large increase in the numbers of cases of AIDS was noted between July 1984 and July 1985. Over 80 patients with HTLV III infection were admitted to hospital and had surgery or other invasive procedures carried out. Approximately 3000 blood samples from HTLV III antibody positive patients were processed by the pathology department--mainly by the microbiology and haematology laboratories. Hospital and laboratory staff observed hepatitis B precautions. In spite of regular contact with patients with HTLV III infection and their samples, serological studies on 150 hospital staff showed no evidence of spread of HTLV III from patients to staff.

Acquired Immunodeficiency Syndrome↗

Sensitivity of the slow component of the delayed rectifier potassium current (IKs) to potassium channel blockers: implications for clinical reverse use-dependent effects.

The slow delayed rectifier potassium current (I(Ks)) is unique in its slow activation and deactivation kinetics. It is important during cardiac repolarization, especially when the heart rate is fast. We compared the effects of quinidine, procainamide, sotalol, and amiodarone on I(Ks) and correlated the findings with the clinical reverse use-dependent effects of potassium channel blockers. Human minK RNA was obtained by reverse transcription-polymerase chain reaction using explanted human heart. The RNA was injected into Xenopus oocytes for heterologous expression of I(Ks). A two-electrode voltage clamp technique was performed to investigate the I(Ks). We demonstrated that quinidine, sotalol and procainamide had no effects on I(Ks) up to a concentration of 300 microM while amiodarone inhibited I(Ks) in a concentration-dependent manner starting from 10 microM. The inhibition by amiodarone was state-dependent with gradual unblocking after depolarization. The degree of inhibition was 53% immediately after depolarization and 19% at the end of a 5-second depolarization. I(Ks) is 30 times more sensitive to amiodarone than to quinidine, sotalol, and procainamide. Quinidine, sotalol and procainamide have reverse use-dependent effects while amiodarone does not. This is compatible with the hypothesis that no inhibition of I(Ks) at clinical concentrations contributes to the clinical reverse use-dependent effects.

Amiodarone↗

RASSE: a new method for structure-based drug design.

A novel method, RASSE, has been developed to suggest reasonable structures which can fit well to the binding sites of receptors. Molecules are generated by an iterative growing procedure in which atoms are added to existing fragments. Potential ligands are then picked out by special scoring rules. This atomgrowing based method is characterized by combinatorial searching of atom types and conformations. To some extent, it is the computer simulation of combinatorial chemistry. This method has been applied to the design of inhibitors for E. coli dihydrofolate reductase and human phospholipase A2. The results demonstrate that this program is capable of generating reasonable structures, thus proving its power in drug design.

Binding Sites↗

Structural features of toxic chemicals for specific toxicity.

We have studied the structural features of toxic chemicals from the RTECS database associated with specific toxicity. The frameworks, functional groups, and structure patterns of molecules are taken into account. Potential active frameworks, groups, and structure patterns for specific toxicity are gained by computational chemistry approaches. These structural features of toxic chemicals will be helpful in understanding activities of toxic chemicals and useful in predicting the toxicity of chemicals, especially in the early stage of drug design.

Database Management Systems↗

Differences in skin flora between inpatients and chronically ill outpatients.

BACKGROUND: Changes in skin flora have been reported among hospitalized and critically ill patients, but little is known about whether these changes are associated with hospitalization or with chronic, serious illness. The purpose of this survey was to compare skin flora of chronically ill outpatients and inpatients. METHODS: Aerobic skin flora of forearm and midsternum of 250 patients in an intensive care unit and 251 outpatients was sampled by contact plates. RESULTS: Mean colony-forming units were 160.6, forearm; 229. 4, sternum (P <.000). In logistic regression analysis, patients in the medical intensive care unit were significantly more likely to have high counts on the arm (odds ratio, 2.48; 95% confidence interval: 1.34-4.43; P =.004), and blacks were significantly more likely to have higher counts on the sternum when compared with other ethnic groups (odds ratio, 1.92; confidence interval: 1.18-3.11; P =. 009). No differences were noted between inpatients or outpatients in prevalence of methicillin-sensitive Staphylococcus aureus, but inpatients were more likely to carry methicillin-resistant Staphylococcus aureus (arm, P =.007; sternum, P =.02). Outpatients had a higher prevalence of micrococci and gram-negative bacteria at both skin sites (all P <.01) and yeast at the sternal site (P =.007). CONCLUSIONS: This comparison provides data to differentiate between effects of hospitalization and effects of chronic illness on skin flora.

Aged↗

Assessment of alternative hand hygiene regimens to improve skin health among neonatal intensive care unit nurses.

OBJECTIVE: The frequent handwashing and gloving required in high-risk, high-volume patient care areas such as critical care units damages skin of the hands. The purpose of this exploratory study was to compare 2 hand care regimens (traditional antiseptic wash with chlorhexidine-containing detergent versus mild soap wash with subsequent alcohol-based rinse for degerming as necessary) in a neonatal intensive care unit (NICU). DESIGN: Prospective, quasi-experimental, random assignment. SETTING: One NICU (47 beds) in a New York City children's hospital. SUBJECTS: Sixteen full-time NICU nurses. OUTCOME MEASURES: Microbial flora and skin condition of hands. INTERVENTION: Nurses were randomly assigned to one of the 2 hand care regimens. RESULTS: No significant differences in microbial counts or types of organisms from hands of staff were found, but after 2 weeks nurses in the mild soap and alcohol group had significant improvements in their skin condition (P =.005). CONCLUSIONS: Use of a mild soap for cleaning and an alcohol-based product for degerming may offer an acceptable alternative to the traditional antiseptic handwash and may reduce skin damage to health care professionals' hands.

2-Propanol↗

Quantitative analysis of epidermal growth factor in human benign prostatic hyperplasia and prostatic carcinoma and its prognostic significance.

The incidence of prostatic carcinoma (PC) is increasing worldwide. Despite the discovery by Huggins in 1941 of the hormone dependency of this tumour, the overall prognosis and survival for patients with advanced disease has not changed. The prognosis for individual patients with PC cannot be accurately predicted by factors such as clinical stage and histological differentiation of the tumour. There is therefore a need to investigate new prognosis factors to assess their role.

Aged↗

[Evaluation of the efficacy and tolerability of quinapril monotherapy in mild and moderate arterial hypertension].

The aim of this single blind, placebo controlled study is to evaluate the efficacy and safety of quinapril in mild to moderate hypertension. Thirty-six patients (from 32 to 64 years old, mean 54.8 +/- 8.84) with diastolic blood pressure (DP) greater than or equal to 96 mmHg and less than or equal to 114 mmHg were enrolled. After a two week wash-out, a placebo was administered for two weeks and than for 12 weeks 20 mg of quinapril u.i.d. At the eighth week if DP was not less than less than or equal to 94 mmHg 40 mg of quinapril was administered. Blood pressure was evaluated at the onset of the study, at the beginning of every step and every 4 weeks. Mean DP and systolic pressure were respectively 159.17 +/- 11.43 and 101.14 +/- 4.39 at the enrolling time, 159.72 +/- 9.41 and 101.86 +/- 3.45 after the wash-out period, 152.78 +/- 9.22 and 98.33 +/- 2.9 after the placebo period, 150 +/- 9.34 and 95.28 +/- 3.52, 144.72 +/- 8.89 and 92.22 +/- 4.32, 140.25 +/- 8.21 and 88.24 +/- 5.27 after 4, 8, 12 weeks of treatment.

Adult↗