Putting teeth into the developmental origins hypothesis: A longitudinal study of early childhood malnutrition, enamel hypoplasia and adolescent health in Amazonian Bolivia

Thesis (Ph.D.)--University of Washington, 2016-06

Relationships between sirolimus dosing, concentration and outcomes in renal transplant recipients

Aim To explore relationships between sirolimus dosing, concentration and clinical outcomes. Methods Data were collected from 25 kidney transplant recipients (14 M/11 F), median 278 days after transplantation. Outcomes of interest were white blood cell (WBC) count, platelet (PLT) count, and haematocrit (HCT). A naive pooled data analysis was performed with outcomes dichotomized (Mann-Whitney U-tests). Results Several patients experienced at least one episode when WBC (n = 9), PLT (n = 12), or HCT (n = 21) fell below the lower limits of the normal range. WBC and HCT were significantly lower (P < 0.05) when sirolimus dose was greater than 10 mg day(-1), and sirolimus concentration greater than 12 mu g l(-1). No relationship was shown for PLT and dichotomized sirolimus dose or concentration. Conclusions Given this relationship between sirolimus concentration and effect, linked population pharmacokinetic-pharmacodynamic modelling using data from more renal transplant recipients should now be used to quantify the time course of these relationships to optimize dosing and minimize risk of these adverse outcomes.

White blood cell count predicts reduction in coronary heart disease mortality with pravastatin

Background-Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. Methods and Results-We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1 X 10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2X10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased ( by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). Conclusions-These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

Serum procalcitonin, interleukin-6, soluble intercellular adhesin molecule-1 and IgG to short-chain exocellular lipoteichoic acid as predictors of infection in total joint prosthesis revision

The diagnosis of prosthetic joint infection and its differentiation from aseptic loosening remains problematic. The definitive laboratory diagnostic test is the recovery of identical infectious agents from multiple intraoperative tissue samples; however, interpretation of positive cultures is often complex as infection is frequently associated with low numbers of commensal microorganisms, in particular the coagulase-negative staphylococci (CNS). In this investigation, the value of serum procalcitonin (PCT), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) as predictors of infection in revision hip replacement surgery is assessed. Furthermore, the diagnostic value of serum IgG to short-chain exocellular lipoteichoic acid (sce-LTA) is assessed in patients with infection due to CNS. Presurgical levels of conventional serum markers of infection including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) is also established. Forty-six patients undergoing revision hip surgery were recruited with a presumptive clinical diagnosis of either septic (16 patients) or aseptic loosening (30 patients). The diagnosis was confirmed microbiologically and levels of serum markers were determined. Serum levels of IL-6 and sICAM-1 were significantly raised in patients with septic loosening (P=0.001 and P=0.0002, respectively). Serum IgG to sce-LTA was elevated in three out of four patients with infection due to CNS. In contrast, PCT was not found to be of value in differentiating septic and aseptic loosening. Furthermore, CRP, ESR and WBC were significantly higher (P=0.0001, P=0.0001 and P=0.003, respectively) in patients with septic loosening. Serum levels of IL-6, sICAM-1 and IgG to sce-LTA may provide additional information to facilitate the diagnosis of prosthetic joint infection.

Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone.

Leukemic B-chronic lymphoproliferative disorders (B-CLPDs) are generally believed to derive from a monoclonal B cell; biclonality has only occasionally been reported. In this study, we have explored the incidence of B-CLPD cases with 2 or more B-cell clones and established both the phenotypic differences between the coexisting clones and the clinicobiologic features of these patients. In total, 53 B-CLPD cases with 2 or more B-cell clones were studied. Presence of 2 or more B-cell clones was suspected by immunophenotype and confirmed by molecular/genetic techniques in leukemic samples (n = 42) and purified B-cell subpopulations (n = 10). Overall, 4.8% of 477 consecutive B-CLPDs had 2 or more B-cell clones, their incidence being especially higher among hairy cell leukemia (3 of 13), large cell lymphoma (2 of 10), and atypical chronic lymphocytic leukemia (CLL) (4 of 29). In most cases the 2 B-cell subsets displayed either different surface immunoglobulin (sIg) light chain (n = 37 of 53) or different levels of the same sIg (n = 9 of 53), usually associated with other phenotypic differences. Compared with monoclonal cases, B-CLL patients with 2 or more clones had lower white blood cell (WBC) and lymphocyte counts, more frequently displayed splenomegaly, and required early treatment. Among these, the cases in which a CLL clone coexisted with a non-CLL clone were older and more often displayed B symptoms, a monoclonal component, and diffuse infiltration of bone marrow and required early treatment more frequently than cases with monoclonal CLL or 2 CLL clones.

The effect of garlic extract on growth, haematology and cell-mediated immune response of newborn goat kids

The present study was carried out to evaluate the effect of different levels of garlic extract supplemented in milk on growth rate, haematology and cell–mediated immune response of Markhoz newborn goat kids. Twenty four newborn goat kids (aged 7+/-3days) were randomly assigned to four groups. The groups consisted of control (received milk without garlic extract), T1, T2 and T3 which received milk supplemented with 62.5, 125 and 250 mg aqueous garlic extract per kg live weight per day for 42 days, respectively. Body weights were measured weekly throughout the experimental period. At day 42, about 10 ml blood samples were collected from each kid via the jugular vein for haematological study. Cell–mediated immune response was evaluated through double skin thickness after intradermal injection of phyto-hematogglutinin (PHA) at day 21 and 42. Total gain was significantly higher for kids in T3 (P<0.05) compared with the control group. Average daily gain (ADG) in T3 group in week 4–5 was higher (P<0.05). Significant differences in globulin (P<0.01), hemoglobin (Hb; P<0.001), hematocrit (PCV; P<0.001), erythrocyte (RBC; P<0.001), neutrophil (P<0.001), lymphocyte (P<0.001) and leukocyte (WBC; P<0.001) were observed among groups. Hb, PCV, RBC, lymphocytes and WBC were higher in kids given garlic extract supplementation. There was a significant difference of double skin thickness among the groups at day 42 (P<0.01). In conclusion, this study indicated that milk supplemented with aqueous garlic extract improved growth rate and immunity of newborn goat kids.

Severity in biliary peritonitis

Objective. To analyze clinical and laboratory findings in order to find variables predictive of severity of Biliary Peritonitis (BP). Patients and methods. Physical findings, course of illness, imaging and laboratory data were evaluated in 42 patients with BP, and statistically analysed to assess their prognostic significance. Results. Serious illness and worse outcome were associated with: age ≥ 60 years (P=0.034), long time between onset of symptoms and treatment (P=0.025), fever > 38°C (P=0.009), WBC count > 17,000 cell/mm³ (P=0.043), diffuse abdominal pain (P=0.034), and infected bile (P=0.048). Conclusions. Most patients become severely ill due to supervening infection, while early bile drainage avoids serious complications. In addition, abdominal pain, fever and WBC count are also predictive of severity of BP.

Evaluation of the protective effects of kolaviron on Kolanut-induced oxidative stress in developing rat brain

The brain is exposed throughout life to oxidative stress, and certain diseases of the brain and nervous system are thought to involve free radical processes and oxidative damage. This study is aimed at evaluating the effect of kolaviron on kolanut-induced oxidative stress in developing rat brain. Twenty-five adult pregnant Wistar rats weighing between 160 and 180g were used for the experiment. They were randomly divided into five groups of five animals each. The animals were fed with standard diets of mice cubes and water provided ad libitum. The control rats received water and cornoil, while the experimental animals received 200 mg/kg body weight of kolanut (kn), 200 mg/kg of kolaviron (kv), and 200 mg/kg body weight of vitamin E which served as a standard antioxidant with cornoil as vehicle orally in pre- and post-natal life. After birth, gross morphometry and behavioural changes of the pups of days 1, 7, 14, 21 and 28 postpartum were evaluated. Blood samples were collected from pups of day 21 for hematological, liver and renal function analyses, while the brains of pups of day 21 postpartum were preserved in phosphate buffer at a temperature of 4oC and pH 7.4 for biochemical analysis. There were significant alterations in the gross morphometry and behavioural parameters studied in the treated animals compared with the control at p< 0.05. There were elevated levels of RBC, WBC and platelets in the treated group compared with the control at p< 0.05. However, no significant change was observed in the PCV, Hb, liver and renal function parameters studied at p>0.05. A non-significant increase in levels of malondialdehyde, MDA, a bye-product of lipid peroxidation in the kolanut group was observed. However, administration of kolaviron and vitamin E non-significantly (p>0.05) reversed these changes. In conclusion, maternal consumption of kolanut induced mild oxidative stress and the administration of kolaviron and vitamin E decreased the rate at which kolanut induced oxidative stress in developing rat brain.

Efeitos da terapia periodontal na contagem de leucócitos e níveis do fator de crescimento transformador beta no soro de indivíduos com periodontite severa

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2015.

Therapeutic effects of ciprofloxacin/bushenhuazhuo combination on chronic prostatitis

Purpose: To evaluate the clinical effect of bushenhuazhuo (a Chinese traditional medicine) in combination with ciprofloxacin (an orthodox medicine) in chronic prostatitis (CP) therapy. Methods: A total of 160 patients who suffered from CP and received treatment in the People’s Hospital of Zhengzhou between April 2012 and June 2014 were selected and divided randomly into treatment and control groups, with 80 patients in each group. Control group was given 0.25 g ciprofloxacin hydrochloride tablets twice a day for 4 weeks. In addition to ciprofloxacin administration, patients in the treatment group also received a dose of bushenhuazhuo preparation twice daily for 4 weeks. Clinical outcomes, quality of life as well as lecithin body and white blood cell (WBC) count in expressed prostatic secretions (EPS-WBC) were evaluated. Results: Cure rates in the treatment and control groups were 90 and 72.50 %, respectively; this difference was significant (p < 0.05). Scores for National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), WBC, and lecithin bodies in the treatment group (8.20 ± 2.20 points, 4.50 ± 1.20 points, and 28.10 ± 2.10 points, respectively) were higher (p < 0.05) than for the control group (12.20 ± 2.20, 6.30 ± 2.20, and 23.30 ± 2.90 points, respectively). The levels of interferon (IFN)-γ and tumour necrosis factor (TNF)-α in the treatment group (26.20 ± 3.30 and 33.80 ± 5.40 mg/L, respectively) were lower than those in the control group (37.70 ± 3.90 and 48.40 ± 3.70 mg/L, respectively), whereas the level of interleukin (IL)-10 in the treatment group (292.60 ± 23.70 mg/L) was higher (p < 0.05) than that in control group (235.80 ± 25.90 mg/L). Conclusion: Ciprofloxacin combined with the Chinese traditional medicine, bushenhuazhuo preparation, demonstrates a marked therapeutic effect in CP. Its mechanism of action may be related to decreased levels of IFN-γ and TNF-α and increased IL-10.