Whites and African-Americans in headache specialty clinics respond equally well to treatment

This study sought to determine if Whites and African-Americans respond similarly to headache treatment administered in 'real-world' headache specialty treatment clinics. Using a naturalistic, longitudinal design, 284 patients receiving treatment for headache disorders completed 30-day daily diaries that assessed headache frequency and severity at pretreatment and 6-month follow-up and also provided data on their headache disability and quality of life at pretreatment and 1-, 2- and 6-month follow-up. Controlling for socioeconomic status and psychiatric comorbidity, hierarchical linear models found that African-Americans and Whites reported significant reductions in headache frequency and disability and improvements in life quality over the 6-month treatment period. African-Americans, unlike Whites, also reported significant decreases in headache severity. Nevertheless, Africans-Americans had significantly more frequent and disabling headaches and lower quality of life after treatment relative to Whites. Although Whites and African Americans responded favourably to headache treatments, more efficacious treatments are needed given the elevated level of headache frequency that remained in both racial groups following treatment.     

Pharmacokinetics and safety of bromotetrandrine (BrTet, W198) after single-dose intravenous administration in healthy Chinese volunteers

Objective: To investigate the safety and pharmacokinetics of bromotetrandrine (BrTet, W198), a novel inhibitor of P‐glycoprotein (P‐gp), after single‐dose i.v. infusion in healthy Chinese volunteers. Methods: We conducted a randomized, dose‐escalating, phase I clinical study for that purpose. Thirty healthy subjects received BrTet at the doses of 10, 20 or 30 mg/m² by i.v. infusion. Plasma and urine concentrations of bromotetrandrine were determined by using a liquid chromatography–tandem mass spectrometric (LC/MS/MS) method. AUC was calculated by the trapezoidal rule extrapolation method. C_max, T_max, t_1/2α, t_1/2β, Cl and V_d were compiled from the plasma concentration–time data. Results: Bromotetrandrine was generally well tolerated at all doses. No serious or severe adverse events were found in the study. The pharmacokinetic parameters of BrTet after single i.v. infusion doses of BrTet 10, 20 and 30 mg/m² were as follows: T_max were 1·5 h in three groups, C_max were 24·79, 39·59 and 64·31 μg/L, t_1/2α were 0·37, 0·29 and 0·30 h, t_1/2β were 62·88, 56·45 and 52·20 h. AUC_0–194h were 345·83, 688·15 and 1096·28 μg h/L, Cl were 23·68, 25·69 and 25·66 L h/m², V_d were 157·73,156·96 and 140·73 L/m². In urine, the total eliminate rate of originate compound was 0·61 ± 0·19%. Conclusions: This study suggested that bromotetrandrine was well tolerated in healthy volunteers within the dose range evaluated. The pharmacokinetics parameters of bromotetrandrine indicated that the compound was rapidly distributed and accumulated in the tissues, and slowly cleared from plasma, which supported the use of BrTet for a once or twice dosing per chemotherapy cycle.     

Synchronous Bilateral Breast Carcinoma in a Patient with Cowden Syndrome: A Case Report with Morphologic,Immunohistochemical and Genetic Analysis

Abstract: Synchronous bilateral breast carcinoma (SBBC) and early onset are important characteristics of hereditary cases. The lifetime risk for breast carcinoma in Cowden syndrome (CS) is estimated to be 25–50%. We reported a 44‐year‐old woman presenting SBBC and characteristic mucocutaneous lesions of CS, confirmed by PTEN gene mutation analysis. Bilateral modified mastectomy and axillary dissection were performed. Histopathologic examination revealed a moderate‐differentiated invasive ductal carcinoma with mixed features of luminal A immunophenotype (Estrogen and/or Progesterone Receptors >50% and/or Ki67 < 30% of positive cells). The skin lesions showed the characteristic findings of tricholemmoma. Lack of PTEN expression was observed in all specimens. Sequencing analysis confirmed the presence of PTEN splice‐acceptor site mutation in intron 8 (c.1027‐2A>G), a germline mutation which had not been previously reported in CS. The patient received adjuvant chemotherapy and tamoxifen for 5 years. After 5 years of follow‐up, she persists recurrence‐free. SBBC with early onset suggests a hereditary predisposition. Thus, analysis of PTEN expression abnormality, easily assessed by immunohistochemistry, may be of clinical value to screen those patients with CS.     

Minoxidil (Mx) as a prophylaxis of doxorubicin - induced alopecia

BACKGROUND: Minoxidil (Mx) is known to induce hair growth in men with male-patternbaldness. Based on this potential, the effectiveness of Mx 2%topical solution was evaluated in cancer patients (pts) to preventdoxorubicin-induced alopecia. PATIENTS AND METHODS: 48 female pts with different types of solid tumors treated withdoxorubicin-based chemotherapy in a dose range of 50–60mg/m²/cycle were randomly assigned to receive Mx 2% topicalsolution or placebo. RESULTS: 88% and 92% of pts in both arms showed severe alopecia (p –ns). No adverse effects were observed. CONCLUSIONS: In this study Mx 2% topical solution was non-toxic but was noteffective in the prevention of chemotherapy-induced alopecia. alopecia, minoxidil, doxorubicin, chemotherapy     

Frontal and parietal lobe activation during transitive inference in humans

Cortical areas engaged in knowledge manipulation during reasoning were identified with functional magnetic resonance imaging (MRI) while participants performed transitive inference (TI) on an ordered list of 11 items (e.g. if A < B and B < C, then A < C). Initially, participants learned a list of arbitrarily ordered visual shapes. Learning occurred by exposure to pairs of list items that were adjacent in the sequence. Subsequently, functional MR images were acquired as participants performed TI on non-adjacent sequence items. Control tasks consisted of height comparisons (HT) and passive viewing (VIS). Comparison of the TI task with the HT task identified activation resulting from TI, termed 'reasoning', while controlling for rule application, decision processes, perception, and movement, collectively termed 'support processes'. The HT-VIS comparison revealed activation related to support processes. The TI reasoning network included bilateral prefrontal cortex (PFC), pre-supplementary motor area (preSMA), premotor area (PMA), insula, precuneus, and lateral posterior parietal cortex. By contrast, cortical regions activated by support processes included the bilateral supplementary motor area (SMA), primary motor cortex (M1), somatic sensory cortices, and right PMA. These results emphasize the role of a prefrontal-parietal network in manipulating information to form new knowledge based on familiar facts. The findings also demonstrate PFC activation beyond short-term memory to include mental operations associated with reasoning.     

Estimates of the chromium(VI) reducing capacity in human body compartments as a mechanism for attenuating its potential toxicity and carcinogenicity

Estimates of the overall reducing capacity of hexavalent chromium(VI) in some human body compartments were made by relating the specific reducing activity of body fluids, cell populations or organs to their average volume, number, or weight. Although these data do not have absolute precision or universal applicability, they provide a rationale for predicting and interpreting the health effects of chromium(VI). The available evidence strongly indicates that chromium(VI) reduction in body fluids and long-lived non-target cells is expected to greatly attenuate its potential toxicity and genotoxicity, to imprint a threshold character to the carcinogenesis process, and to restrict the possible targets of its activity. For example, the chromium(VI) sequestering capacity of whole blood (187-234 mg per individual) and the reducing capacity of red blood cells (at least 93-128 mg) explain why this metal is not a systemic toxicant, except at very high doses, and also explain its lack of carcinogenicity at a distance from the portal of entry into the organism. Reduction by fluids in the digestive tract, e.g. by saliva (0.7-2.1 mg/day) and gastric juice (at least 84- 88 mg/day), and sequestration by intestinal bacteria (11-24 mg eliminated daily with feces) account for the poor intestinal absorption of chromium(VI). The chromium(VI) escaping reduction in the digestive tract will be detoxified in the blood of the portal vein system and then in the liver, having an overall reducing capacity of 3300 mg. These processes give reasons for the poor oral toxicity of chromium(VI) and its lack of carcinogenicity when introduced by the oral route or swallowed following reflux from the respiratory tract. In terminal airways chromium(VI) is reduced in the epithelial lining fluid (0.9-1.8 mg) and in pulmonary alveolar macrophages (136 mg). The peripheral lung parenchyma has an overall reducing capacity of 260 mg chromium(VI), with a slightly higher specific activity as compared to the bronchial tree. Therefore, even in the respiratory tract, which is the only consistent target of chromium(VI) carcinogenicity in humans (lung and sinonasal cavities), there are barriers hampering its carcinogenicity. These hurdles could be only overwhelmed under conditions of massive exposure by inhalation, as it occurred in certain work environments prior to the implementation of suitable industrial hygiene measures.      

Effect of proton pump inhibitors on the detection of Helicobacter pylori in gastric biopsies.

BACKGROUND: Proton pump inhibitors are known to decrease the activity of Helicobacter pylori organisms within the stomach and to shift their distribution proximally. This effect may reduce the sensitivity of histological examination and rapid urease testing for H. pylori on biopsies taken from recommended sites. It is of particular relevance if a proton pump inhibitor has been prescribed before the patient has undergone diagnostic endoscopy. METHODS: We studied patients referred to our open-access upper gastrointestinal endoscopy service who had either been on no medication (controls) or were already taking proton pump inhibitors. Biopsies taken from the gastric antrum and corpus were used for rapid urease testing and for histological examination. Sera, taken from patients who had no evidence of H. pylori in biopsies, were tested for IgG H. pylori antibodies as an alternative indicator of infection. RESULTS: H. pylori organisms were detected by histological examination in 27 of 40 controls (68%) and in 13 of 25 patients taking proton pump inhibitors (52%). Among patients with positive histology (organisms detected in either antral or corpus biopsies, or both), only the sensitivity of the antral urease test read at 1 h was significantly lower in patients taking proton pump inhibitors than in controls, with no significant difference in sensitivities of the antral urease test at 24 h, of the corpus urease test at 1 or 24 h, or of histology from the antrum or corpus. Of patients with negative histology, none of 13 controls compared with six of 12 patients taking proton pump inhibitors (50%) had positive serology (P = 0.005). Five (83%) of the six histology-negative, seropositive patients taking proton pump inhibitors had histological changes consistent with H. pylori gastritis even though no organisms were detected. CONCLUSIONS: Treatment with a proton pump inhibitor before endoscopy reduces the sensitivity of antral and corpus biopsies for H. pylori detection, both by urease testing and histological examination. If proton pump inhibitors already prescribed cannot be discontinued for an adequate period before endoscopy, patients should have biopsies taken from the corpus as well as from the antrum, and serum should be tested for H. pylori.     

Oxidative stress in term small for gestational age neonates born to undernourished mothers: a case control study

Background  

The objective of this study was to assess the status of oxidative stress in term small for gestational age (SGA) newborn infants born to undernourished mothers by estimating levels of erythrocyte superoxide dismutase (SOD), catalase, reduced glutathione, and serum malondialdehyde (MDA) in cord blood and comparing them to healthy appropriate for gestational age (AGA) controls. This was done in a case control design at a tertiary level teaching hospital.