Differentiating normal from abnormal rates of genital epithelial findings in vaginal microbicide trials

BACKGROUND: Candidate vaginal microbicides could cause genital irritation, which in turn could facilitate HIV transmission instead of preventing it. While genital epithelial findings are documented in a standardized manner in most microbicide trials, little is known about background rates and predictors for many types of genital findings. STUDY DESIGN: A secondary analysis was conducted using data from a Phase II expanded safety study of the candidate microbicide Carraguard gel (Population Council, NY, USA) in Thailand. Genital findings were identified by visual inspection of the cervix, vaginal walls and external genitalia during pelvic exams prior to gel use (screening and enrollment) and during gel use (at 2 weeks and Months 1-12). Women were interviewed about potential risk factors for genital findings at every visit and tested routinely for sexually transmitted and vaginal infections. RESULTS: A total of 258 genital findings were identified in 152 woman-years of follow-up. Genital findings were positively associated with older age, increased parity, self-report of genital symptoms, positive HSV-2 serology, bacterial vaginosis by Nugent scoring and the presence of a genital finding at baseline. Furthermore, vaginal findings were positively associated with vaginal practices and yeast infections. Genital findings were negatively associated with use of hormonal contraception, inconsistently associated with frequency of sex and applicator use, and not associated with condom use. CONCLUSIONS: Several factors that are common in women of reproductive age account for the background rate of genital epithelial findings in this population.     

A randomized, placebo-controlled trial to assess the safety and acceptability of use of carraguard vaginal gel by heterosexual couples in Thailand

OBJECTIVES: To determine the safety and acceptability of use of Carraguard, a carrageenan-derived candidate microbicide gel, during sexual intercourse in women and men. STUDY DESIGN: We conducted a 6-month randomized, placebo-controlled trial among sexually active, couples at relatively lower risk for HIV infection in northern Thailand. METHODS: Women inserted 1 applicator of study gel vaginally every time the couple had sex. Safety was assessed by symptom report and genital examination of both partners and by changes in vaginal flora. Acceptability was assessed by participant interview. RESULTS: Overall, 55 couples were randomized, 28 to Carraguard use and 27 to the methyl-cellulose placebo gel group. Retention and study gel use were similarly high in both study groups; use of gel without condoms was reported in more than 95% of vaginal sex acts. The 2 study groups were similar in the proportions of women and men with symptoms or with genital findings without epithelial disruption, of men with findings with epithelial disruption, and of women with abnormal genital flora, whereas more women in the placebo group had findings with epithelial disruption. Women and men in both groups reported that the gel and applicator were acceptable. CONCLUSIONS: Carraguard can safely be used an average of 2 to 3 times per week during sex and is acceptable to Thai women and men.     

Laser Acupuncture Improves Memory Impairment in an Animal Model of Alzheimer’s Disease

The burden of Alzheimer’s disease is continually rising globally, especially in the Asia-Pacific region. Unfortunately, the efficacy of the therapeutic strategy is still very limited. Because the effect of acupuncture at HT7 can improve learning and memory, the beneficial effect of laser acupuncture, a noninvasive form of acupuncture, at HT7 on memory improvement in patients with Alzheimer’s disease has been a focus of research. To elucidate this issue, we used AF64A, a cholinotoxin, to induce memory impairment in male Wistar rats, which weighed 180–220 g. Then, the animals were treated with laser acupuncture either at HT7 or at a sham acupoint once daily for 10 minutes for a period of 14 days. Spatial memory assessments were performed at 1, 7, and 14 days after AF64A administration and at the end of the experiment, and the changes in the malondialdehyde (MDA) level and in the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in the hippocampus were recorded. The results showed that laser acupuncture significantly suppressed AChE activity in the hippocampus. Although laser acupuncture enhanced SOD and CAT activities, no reduction in MDA level in this area was observed. Therefore, laser acupuncture at HT7 is a potential strategy to attenuate memory impairment in patients with Alzheimer’s disease. However, further research, especially on the toxicity of laser acupuncture following repetitive exposure, is essential.     

HPV genotyping in cervical cancer in Northern Thailand: adapting the linear array HPV assay for use on paraffin-embedded tissue

ObjectiveThe objective of this study was to review our experience with abdominal radical trachelectomy in patients with early-stage cervical cancer.MethodsWe performed a retrospective review of all patients who underwent an abdominal radical trachelectomy at the Instituto de Cancerologia—Clinica las Americas in Medellin, Colombia, between April 2002 and January 2008. Data collected included age, stage, histopathologic subtype, tumor size, evidence of lymph-vascular space invasion, estimated blood loss, number of perioperative blood transfusions, number and disease status of lymph nodes removed, disease status of surgical specimen, length of hospital stay, intraoperative and postoperative complications, follow-up time, and fertility outcomes.ResultsFifteen patients underwent an abdominal radical trachelectomy during the study period. The median patient age was 30 years (range, 25–38). Three patients had stage IA2 and 12 had stage IB1 cervical cancer. Eleven patients had squamous cell carcinoma and 4 had adenocarcinoma. Thirteen patients were diagnosed by cervical conization and 2 by colposcopically directed biopsy. All patients had tumors smaller than 2 cm. The median estimated blood loss was 400 ml (range, 200–1000). The median surgical time was 265 min (range, 210–330). The median number of units of packed red blood cells transfused per patient was 2. The median number of lymph nodes removed was 26 (range, 11–48). The median length of hospitalization was 3 days (range, 2–7). The median follow-up time was 32 months (range, 5–32). There was 1 intraoperative complication and 6 postoperative complications in 4 patients. No patient has had a recurrence. Three patients were able to conceive spontaneously; 1 delivered at 31 weeks' gestation, and 2 delivered at term.ConclusionAbdominal radical trachelectomy is feasible and can be performed safely in a developing country in well-selected patients with early cervical cancer who wish to preserve their fertility.     

Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract

Kratom (Mitragyna speciosa Korth.) is an indigenous plant of Thailand used traditionally in folk medicine although it is claimed to cause addiction. It is used to treat diarrhea, however, there is no scientific evidence to support the use. The aim of this study is to investigate the effect of methanolic extract of kratom leaves on the rat gastrointestinal tract. Kratom extract at 50, 100, 200 and 400 mg/kg (p.o.) caused a dose dependent protection against castor oil-induced diarrhea in rats and also inhibited intestinal transit. The antidiarrheal effect was not antagonized by naloxzone. The inhibition of intestinal transit by kratom extract was significantly different from the control when treated with a single dose for 1 day. For longer-term treatments of 15 and 30 days, kratom extract did not decrease the intestinal transit time indicating that adaptation had occurred. Kratom extract at a dose level of 200 and 400 mg/kg for 30 days and morphine at 3 mg/kg (i.p.) caused a decrease in the increment of body weight that was significantly different from the control and kratom extract at lower doses (50 and 100 mg/kg). However it had no effect on the level of plasma cholecystokinin. The results suggested that methanolic kratom extract exhibited its antidiarrheal effect on rat gastrointestinal tract. The effects may occur via pathways in addition to the action on opioid receptors. High does of kratom extract decreased the increment of body weight similar to the effect of morphine.     

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity

Background: To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X‐linked familial exudative vitreoretinopathy (FEVR), Coat’s disease and retinopathy of prematurity (ROP). Methods: A dataset comprising 13 Norrie‐FEVR, one Coat’s disease, 31 ROP patients and 90 ex‐premature babies of <32 weeks’ gestation underwent an ophthalmologic examination and were screened for mutations within the NDP gene by direct DNA sequencing, denaturing high‐performance liquid chromatography or gel electrophoresis. Controls were only screened using denaturing high‐performance liquid chromatography and gel electrophoresis. Confirmation of mutations identified was obtained by DNA sequencing. Results: Evidence for two novel mutations in the NDP gene was presented: Leu103Val in one FEVR patient and His43Arg in monozygotic twin Norrie disease patients. Furthermore, a previously described 14‐bp deletion located in the 5′ unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14‐bp deletion was detected in an unaffected ex‐premature girl. Only two of the 13 Norrie‐FEVR index cases had the full features of Norrie disease with deafness and mental retardation. Conclusion: Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non‐coding region was associated with only mild‐regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full‐term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long‐term outcome.     

Combination chemotherapy as induction therapy for advanced resectable head and neck cancer

Fifty-four previously untreated patients with locally advanced resectable squamous cell carcinoma of the head and neck (SCCHN) were enrolled into a prospective randomized controlled trial to evaluate whether induction chemotherapy improves the disease-free survival compared to the standard treatment (surgery + radiation). Thirty patients received chemotherapy, which consisted of cisplatin 20 mg/m² day 1–5, bleomycin 10 mg/m², continuous infusion from day 3–7, and methotrexate 40 mg/m² given on day 15 and day 22. The cycle was repeated on day 29 for two cycles. Twenty patients completed chemotherapy courses. Overall response rate was 77% (23 of 30). No survival improvement was observed. Kaplan-Meier analysis indicated survival (and 95% confidence interval) at 3 years was 57% (29%-84%) for the control group and 60% (34%-87%) for the chemotherapy group, and 57% (29%-84%) and 45% (12%-78%) at 4 years (P = 0.736). However, patients who had a complete response were significantly better in terms of long-term survivors (5 of 7 patients were still alive), in contrast to patients who had partial responses among whom only 4 of 16 were alive. Toxicities of this induction protocol are tolerable; one chemotherapy-related death occurred from profound thrombocytopenia. If efforts in determining a chemotherapy-sensitive patient were successfully established, along with a better sequence and the discovery of new and safter drugs, survival of SCCHN should be much improved.     

Outcomes and risk factors of ventilator-associated pneumonia in neonates

Background:Ventilator-associated pneumonia (VAP) in neonates has been associated with high mortality and poor outcome.This study aimed to compare the incidence,risk factors,and outcomes of VAP and nonVAP conditions in neonates.Methods:We performed a prospective cohort study in a neonatal intensive care unit (NICU) in Thailand from January 2014 to December 2014.All neonatal patients who were ventilated more than 48 hours were enrolled.Results:There were 128 enrolled patients.The median (inter quartile range) gestational age and birthweight were 35 (30.2,37.8) weeks and 2380 (1323.8,3020.0) g.There were 17 VAP patients (19 episodes) and 111 non-VAP ones.The VAP rate was 13.3％ or 10.1 per 1000 ventilator days.According to the multivariate analysis,a birthweight less than 750 g [adjusted odds ratio (aOR)=10.75,95％ confidence interval (CI)=2.35-49.16;P=0.002] and sedative medication use (aOR=4.00,95％ CI=1.23-12.50;P=0.021)were independent risk factors for VAP.Compared with the non-VAP group,the median difference in the VAP group yielded a significantly longer duration of NICU stay (18 days,P=0.001),total length of hospital stay (16 days,P=0.002) and higher hospital costs ($5113,P=0.001).The inhospital mortality rate in the VAP and non-VAP groups was 17.6％ and 15.3％ (P=0.73),respectively.Conclusions:A neonatal birthweight less than 750 g and sedative medication use were independent risk factors for VAP.Our VAP patients experienced a longer duration of both NICU and hospital stay,and incurred higher hospitalization costs.