Pre-treatment of bupivacaine-induced cardiovascular depression using different lipid formulations of propofol.

BACKGROUND: Pre-treatment with lipid emulsions has been shown to increase lethal doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine-induced cardiotoxicity. The aim of this study is to investigate the effects of propofol in intralipid or medialipid emulsions on bupivacaine-induced cardiotoxicity. METHODS: Rats were anaesthetised with ketamine and were given 0.5 mg/kg/min propofol in intralipid (Group P), propofol in medialipid (Group L), or saline (Group C) over 20 min. Thereafter, 2 mg/kg/min bupivacaine 0.5% was infused. We recorded time to first dysrhythmia occurrence, respective times to 25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time to asystole and total amount of bupivacaine consumption. Blood and tissue samples were collected following asystole. RESULTS: The time to first dysrhythmia occurrence, time to 25% and 50% reductions in HR, and time to asystole were longer in Group P than the other groups. The cumulative bupivacaine dose given at those time points was higher in Group P. Plasma bupivacaine levels were significantly lower in Group P than in Group C. Bupivacaine levels in the brain and heart were significantly lower in Group P and Group L than in Group C. CONCLUSION: We conclude that pre-treatment with propofol in intralipid, compared with propofol in medialipid or saline, delayed the onset of bupivacaine-induced cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies are needed to explore tissue bupivacaine levels of propofol in medialipid and adapt these results to clinical practice.

Natural killer cell activity in multidrug-resistant pulmonary tuberculosis.

BACKGROUND: Multidrug-resistant pulmonary tuberculosis (MDRTB), a major problem in developing countries, may result from either insufficiency of host cellular immune response or mycobacterial mechanisms which has been more intensively investigated so far. OBJECTIVES: The aim of the study was to investigate natural killer cell activity (NKA) and T lymphocyte subsets in HIV- patients with secondary MDRTB. METHODS: 20 male patients with MDRTB (mean age 38 +/- 8 years), 15 nonresistant tuberculosis male patients (NRTB) (mean age 36 +/- 11 years) and 12 healthy male controls (mean age 35 +/- 8 years) were included. The percentages of CD3+, CD4+, CD8+, CD25+, CD11b+ and CD16+56+ cells were measured by flow-cytometric analysis of peripheral blood lymphocytes (PBL). NKA was evaluated using the anticandidal index method. RESULTS: The mean tuberculin response was higher in MDRTB and NRTB patients compared to controls (15.4 +/- 3.8, 15.1 +/- 3.3 and 10.9 +/- 2.8 mm, respectively; p < 0.001). There was no significant correlation between PPD response and PBL subsets or NKA. The percentages of both CD3+ and CD3+CD4+ T lymphocytes were significantly lower in MDRTB (62.4 +/- 12.1 and 33.9 +/- 9.0%) compared to NRTB (70.8 +/- 7.5 and 42.9 +/- 8.6%; p < 0.05). Patients with MDRTB had significantly lower NKA compared to NRTB and controls (30.9 +/- 11.3, 49.7 +/- 15.5 and 40.0 +/- 8.5%, respectively; p < 0.01). CONCLUSION: This reduction in NKA may suggest a role for impaired NK function in the pathogenesis of MDRTB in HIV- patients.

The value of DNA content in predicting the prognosis of thyroid carcinoma in an endemic iodine deficiency region.

DNA content of tumour was found to correlate with various prognostic factors and survival, especially in well differentiated thyroid carcinoma. The aim of this investigation was to evaluate the correlation between the DNA ploidy and the prognosis as well as the survival in thyroid carcinoma in our country, being an endemic iodine deficiency region. DNA flowcytometry was performed on paraffin embedded archival tissue blocs of 74 patients with thyroid carcinoma (70 well differentiated, 3 anaplastic and Hurthle cell carcinoma) and 12 patients with multinodular goitre. DNA ploidy was defined as diploidy or aneuploidy. Aneuploidy was detected in 5 (6.8%) patients with thyroid carcinoma (3 anaplastic, 1 papillary and 1 Hurthle cell carcinoma). Aneuploidy was significantly more frequent in patients with anaplastic carcinoma (n: 3/3, 100%) compared to well differentiated thyroid carcinoma (n: 1/70, 1.4%) (p < 0.0001). Aneuploid DNA content significantly correlated with advanced age (p < 0.01), large tumour size (p < 0.001), and low survival (p < 0.01). Mean survival period of patients with anaplastic carcinoma in whom aneuploidy was frequently encountered, was shorter compared to patients with diploid well differentiated tumours (p < 0.01). In conclusion, although anaplastic and follicular carcinoma are more frequently diagnosed in endemic areas, the rate on aneuploidy was found to be lower in thyroid carcinoma in our country compared to data reported to nonendemic areas. As the prognostic predictive value of DNA ploidy is reliable in well differentiated thyroid carcinoma, DNA measurement of FNA biopsy may influence the extent of surgery. Thyroid carcinoma, other than well differentiated types, require radical operations independent of the DNA content. However, adjunctive treatment methods may be used earlier postoperatively according to quantitative DNA measurement.

Effects of zinc supplementation on the immune system and on antibody response to multivalent influenza vaccine in hemodialysis patients.

The depression of the immune system in chronic uremia is a well-known phenomenon but the role of serum zinc (Zn) levels on both cell-mediated and humoral immunity is still controversial. The aim of this study was to investigate the effect of Zn supplementation on the immune system and on antibody response to multivalent influenza vaccine (MIV) in hemodialysis patients (HP). Twenty-six HP and 11 healthy subjects (HS) were vaccinated with MIV. Hemodialysis patients were randomly divided into two groups. Group I (13 HP) was supplemented with 120 mg ZnSO4 after each dialysis session. Group II (13 HP) and Group III (11 HS) were given placebo. In all cases, the serum Zn levels, CD3, CD4, CD8, CD19, HLA-DR+ cell percentages, CD4/CD8 ratio and CD3+ HLA-DR+ cell percentages were determined before and 30 days after vaccination. Antibody levels to subgroups of MIV were also measured. All the baseline parameters studied were not statistically different between Group I and II. However, there was a significant difference between the basal parameters of Group III and the other two groups, except for CD3 and CD4 cell percentages. Serum Zn, CD19 cell percentage and antibody levels to MIV subgroups were significantly increased in Group I at the end of the first month of the study (p<0.01, p<0.05, p<0.001, p<0.001, and p<0.01, respectively), but the other parameters showed no significant changes. The only significant change observed in Groups II and III was an increase in antibody levels to MIV subgroups one month after vaccination. Antibody levels to MIV subgroups, were not statistically different between Groups I and II, but in Group III they were strikingly higher than those of HP (p<0.001). These results led us to conclude that Zn supplementation could not restore the immune parameters and enhance antibody response to MIV in HP.

Analysis of peripheral blood leukocytes in patients with cyclosporine A-induced gingival hyperplasia.

BACKGROUND: Gingival overgrowth is one of the major adverse effects of the immunosuppressive drug cyclosporine A (CsA). Although several studies have attempted to determine the immunological mechanisms of gingival hyperplasia (GO) due to CsA therapy, the pathogenesis remains unclear. In this study, the distribution of the peripheral blood leukocytes in a group of renal transplant patients undergoing CsA therapy was analyzed and possible correlations of periodontal and pharmacological variables to lymphocyte subpopulations, natural killer cells, and monocytes investigated. METHODS: Thirty-six patients were classified into 2 groups of 18 each according to the degree of gingival overgrowth. The periodontal evaluation included plaque index (PI), gingival index (GI), gingival overgrowth (GO), calculus index (CI), and probing depth (PD). The pharmacological variables of current doses of the therapeutic serum levels of CsA were investigated. The peripheral blood leukocytes were studied by 2-color flow cytometric analysis using anti-human CD2, CD3, CD4, CD8, CD11b, CD11c, CD16, CD19, HLA-DR, and CD3+HLA-DR+ monoclonal antibodies. RESULTS: Statistical evaluation revealed that none of the pharmacological variables varied between the 2 groups. Responders (GO >30%) had significantly higher GI, PD, and GO scores compared to nonresponders (GO < or =30%). Of the immunological parameters studied, only CD2 was higher in the responder group. None of the clinical parameters correlated to the immunological values. CONCLUSIONS: The results of this study may be useful in explaining the underlying mechanisms of drug-induced gingival overgrowth. Several previously unsuspected cells and accessory activation mechanisms for T lymphocytes could play a role in the pathogenesis.

Generalized prepubertal periodontitis. A report of 4 cases with the immunological findings.

The clinical and immunological data from 4 patients with generalized prepubertal periodontitis are presented. The peripheral blood neutrophil chemotaxis was measured using zymosan activated sera as the chemoattractant. All of the 4 patients have shown depressed neutrophil chemotaxis compared to those of the healthy controls. Peripheral blood lymphocyte subpopulations were analysed by double-coloured flow cytometry using monoclonal antibodies for the receptors CD2, CD3, CD4, CD8, CD19, CD29, CD45RA+, 34,29dK, CD56. CD11b/CD18. Lymphocytes bearing CD3 receptors showed a significant decrease compared to those of the controls. Natural killer cells were lowered in 3 of the 4 cases. All of the patients showed a higher increase in CD11b/CD18 expression. The evaluation of CD11b/CD18 receptor in peripheral blood leukocytes may be of help explaining the rôle of neutrophils in the pathogenesis of the disease.

Clinical and immunological findings in 2 siblings with Papillon-Lefèvre syndrome.

Rapid and severe destruction of periodontal tissues in early childhood has been reported both in systemically healthy children and in children with systemic disorders. In this study, the clinical and immunological findings of two siblings in a family with Papillon-Lefèvre syndrome are presented. The peripheral blood lymphocytes were analyzed using a double colored flow cytometry and adequate monoclonal antibodies to CD2, CD3, CD4, CD5, CD8, CD11b, CD16, CD19, and HLA-DR receptors. CD11b expression was found to be higher in both siblings (35% and 37%). The elevated CD11b expression may be related to a defect in neutrophils. The expression of natural killer cells was found to be higher in one patient but the results were in normal range. The CD2+, CD3+, CD4+, CD5+, CD8+, and CD19+ lymphocytes were in normal range in both patients. We think that the depressed chemotaxis of peripheral neutrophils, and higher expression of HLA-DR and CD11b molecules in peripheral leukocytes were useful in explaining the pathogenesis of the Papillon-Lefèvre syndrome.

Papillon-Lefèvre syndrome. Analysis of peripheral blood lymphocyte subsets.

We have studied the peripheral blood lymphocyte populations in our 6 patients (2 female and 4 male) with a mean age of 11.19 with Papillon-Lèfevre Syndrome (PLS) using adequate monoclonal antibodies and double coloured flow cytometry. Total B, T, CD4, CD8, CD29, CD45RA, NK, HLA-DR cells were studied. Total B, T, CD4 and CD8 lymphocytes were within normal limits. We have observed an increase in the CD29 lymphocytes and NK cells and a decrease in CD45RA lymphocytes. We think that these findings are important in explaining B lymphocyte activation and in the pathogenesis of the PLS.

Immunoprotection in spontaneous remission of type 1 diabetes: long-term follow-up results.

This prospective pilot study was undertaken to test the efficacy of oral methyl-prednisolone (MP) therapy at spontaneous remission phase of type 1 diabetes in intervening the course of the disease. Twenty-five type 1 diabetic patients who were classified as having a spontaneous remission (honeymoon) were divided into treatment and non-treatment groups on voluntary basis. Fifteen patients thus making up the treatment group (13 males and 2 females, mean age 23.8 +/- 6.2 years) received 0.7-1.0 mg/kg/day of MP p.o. for 2 weeks. The dose of the drug was then gradually diminished every week until 5 mg/day (approx. 0.1 mg/kg/day) and discontinued at 10 +/- 2 weeks. In case of hyperglycemia occurring in 12 of 15 patients due to the administration of steroid, insulin was used to normalize blood glucose levels (average 0.47 +/- 0.21 IU/kg/day). The non-treatment group (8 males and 2 females, mean age 21.8 +/- 8.9) did not receive any special medication or placebo except for insulin whenever necessary to regulate glycemia. Upon completion of protocol, all patients in treatment group displayed clinical remission with 10 still in non-insulin requiring remission for follow-up periods ranging between 16 and 91 months. The remaining 5 patients relapsed within 3-15 months of therapy. Other metabolic (including basal and stimulated C-peptide levels) and immunological indices that have spontaneously ameliorated with the occurrence of honeymoon were also maintained within normal range in the NIR patients. Meanwhile, natural remission in the non-MP-treated group terminated at 3.4 +/- 0.6 months with deterioration of all metabolic and immunological markers as well as increasing requirements for insulin. In conclusion, the spontaneous remission of the patients could be prolonged significantly by MP therapy as opposed to no therapy (P < 0.001). These results suggest that the spontaneous remission phase may be a crucial point of intervention in immunotherapy of type 1 diabetes and that randomized trials with MP at this particular phase would be worthwhile.

Psoriasis-like lesions in guinea pigs receiving propranolol.

BACKGROUND: beta-Blockers cause a psoriasiform eruption. We investigated the skin effects of systemic propranolol in a formal protocol. METHODS: Propranolol, 0.1 mg/day, was used systemically by gavage in eight albino guinea pigs. Normal saline was given to another group of seven guinea pigs. RESULTS: Propranolol produced psoriasiform lesions in five of seven guinea pigs on the 30th day. Biopsies showed acanthosis, parakeratosis, microabscesses, and cellular infiltration of upper dermis. Topical application of propranolol did not produce clinical psoriasiform changes, while acanthosis and papillomatosis was observed in six of the six guinea pigs.