Phylogenetic analysis of partial L1 gene of 10 human papillomavirus types isolated most commonly from women with normal and abnormal cervical cytology in Kuwait

This study was undertaken to evaluate the presence of human papillomavirus (HPV) variants in cervical samples. L1 genetic variable region was studied in 10 HPV types: HPV 11, 16, 18, 33, 53, 54, 56, 61, 66 and 81. A total of 116 isolates were examined, including 47 HPVs isolated from women with normal cytology and 69 with abnormal cytology of different grades. HPV sequences were detected using MY09/MY11 consensus primers. Fifty silent and 65 missense mutations were detected. Two missense mutations were detected in HPV18, 3 in HPV56 and 17 in HPV61. The number of missense mutations per isolate ranged from 1 to 3, except in HPV54 and HPV61, where 7 and 11 missense mutations were found, respectively. Most of the isolates (52.3 %) with missense mutations were isolated from women with abnormal cervical samples. Low-grade squamous intraepithelial lesion cytology diagnosis dominated all cervical abnormalities. This study is the first on the identification of molecular variants in the Middle East and suggests the circulation of new HPV subtypes and variants in Kuwait, which needs to be confirmed by further analysis of the complete HPV genome.     

Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia

PURPOSE: High-risk human papillomavirus (HPV)-associated vulval intraepithelial neoplasia (VIN) is difficult to treat by excision or ablation because of high recurrence rates. Small studies of photodynamic therapy (PDT) and imiquimod treatments have shown some success and function at least in part through stimulation of local immune responses. Indeed, there is evidence that immunosuppressed individuals have higher rates of VIN, suggesting immune control is relevant. EXPERIMENTAL DESIGN: In the study, 20 women with high-grade VIN were treated with topical imiquimod and the PDT sequentially. Vulval biopsy and blood were taken pretreatment and, after imiquimod and PDT, with follow up for 1 year. Clinical response was assessed by measuring lesion size. Biopsies were analyzed for HPV DNA and tumor-infiltrating lymphocytes including T regulatory cells. RESULTS: The treatment was well-tolerated. There was an overall response rate of 55% by intention treat and 64% per protocol. The 52-week symptom response was 65% asymptomatic, compared with 5% at baseline. The nonresponders showed a significantly higher level of T regulatory cells in the lesions after imiquimod treatment. CONCLUSIONS: The response rates are clinically relevant, and the treatment regimen was feasible for the majority. Initial nonresponders to imiquimod seem to be relatively refractory, and this may derive from their unfavorable local immune environment, in particular, the increased proportions of T regulatory cells, possibly the limiting action and/or development of any HPV T-cell immunity. The potential benefit of this treatment is its ability to treat multifocal disease.     

Treatment related problems for outpatients with chronic diseases in Jordan: the value of home medication reviews

Background Research conducted in Jordan has shown that suboptimal use of medications by outpatients along with the suboptimal role played by community pharmacists is currently a big dilemma highlighting the need for the Home Medication Review (HMR) service in the country. Objectives To evaluate the prevalence and types of treatment related problems (TRPs) for outpatients with chronic diseases. Setting Patient interview was conducted at the patients’ community pharmacy initially, then at their home to collect required data. Methods 167 patients with chronic conditions (mean age 58.9 ± 13.54, 53 % males) were recruited. Data collected by the graduate pharmacists to conduct a HMR included patient’s demographics, income, laboratory data, medical history, medication record, and adherence. A HMR was conducted for each patient by the researchers (experienced clinical pharmacists) to identify the patients’ TRPs based on published literature. A focus group interview was conducted to elicit information regarding the feasibility of the HMR process and acceptability of the patient to the service. Main outcome measure Prevalence and nature of identified TRPs, associated diseases and drugs, and patients’ acceptability to the HMR service. Results The mean number of disease conditions per patient was 4.1 ± 1.7, and the mean number of medications taken by each patient was 8.1 ± 2.7. HMR results showed a mean number of TRPs per patient of 7.4 ± 2.8. TRPs prevalence: 34.7 % of patients were found to have unnecessary drug therapy; 68.3 % had untreated conditions, and 74.9 % had ineffective/incomplete drug therapy; 50.3 % had inappropriate dosage regimen; 10.2 % were found to have actual adverse drug effects. A significant correlation between the number of TRPs and the number of disease states the patient had (r = 0.311, p = 0.003; Pearson correlation) and the number of drugs the patient was taking (r = 0.443, p < 0.001) was found. Patients accepted the HMR service well including the home visiting part. Conclusion TRPs in Jordanian outpatients with chronic diseases visiting community pharmacies are of concern and this signifies the integral role of pharmacists to identify these TRPs and hence provide the HMR service in the country.     

An "all 5-mm ports" selective approach to laparoscopic cholecystectomy, appendectomy, and anti-reflux surgery

Laparoscopic appendectomy, cholecystectomy, or anti-reflux procedures are conventionally performed with the use of one and often two 10/12-mm ports. While needlescopic or micropuncture laparoscopic procedures reduce postoperative pain, they invariably involve the use of one 10/12-mm port and the instruments applied have their ergo-dynamic shortcomings. Between September 2002 and March 2003, we have attempted an "all 5-mm ports" approach in 49 laparoscopic procedures, which included 18 of 59 laparoscopic cholecystectomies (31%), 26 diagnostic laparoscopies for suspected appendicitis (of which we proceeded to a laparoscopic appendectomy in 17 patients), and in the last 5 of 9 laparoscopic Nissen fundoplications. Conversion of one of the 5-mm ports to a 10-mm port was required in 5 of the 18 (28%) laparoscopic cholecystectomies and in 6 of the 17 (35%) laparoscopic appendectomies to facilitate organ retrieval in patients with large gallstones (>5 mm in diameter) and in obese patients with fatty mesoappendix. There were no conversions to open surgery. No significant differences in the operating time between the laparoscopic procedures performed by the all 5-mm ports approach or the conventional approach were observed. No intraoperative or postoperative complications occurred in this series. The "all 5-mm ports" approach to laparoscopic cholecystectomy and appendectomy in selected patients and to laparoscopic fundoplication appears feasible and safe. A randomised comparison between this approach and the conventional laparoscopic approach to elective cholecystectomy and fundoplication in which two of the ports employed are of the 10-mm diameter is warranted.     

Prevalence and determinants of PTSD among Palestinian children exposed to military violence

Abstract. The prevalence and determinants of PTSD were assessed among 121 Palestinian children (6–16 years; 45% girls and 55% boys) living in the area of bombardment. The mothers (21–55 years) and the children themselves reported their exposure to military violence (being personally the target of violence or witnessing it towards others) and symptoms of posttraumatic stress disorders (PTSD: intrusion, avoidance and hypervigilance). The results showed that 54% of the children suffered from severe, 33.5 % from moderate and 11 % from mild and doubtful levels of PTSD. Girls were more vulnerable; 58% of them suffered from severe PTSD, and none scored on the mild or doubtful levels of PTSD. The childs gender and age, mothers education and PTSD symptoms were significant, and the exposure to traumatic experiences marginally significant determinants of childrens PTSD symptoms. The most vulnerable to intrusion symptoms were younger girls whose mothers showed a high level of PTSD symptoms, whereas those most vulnerable to avoidance symptoms were children who had personally been targets of military violence and whose mothers were better educated and showed a high level of PTSD symptoms. The results are discussed in the context of military violence interfering with the protective function of family and home.     

Electrical stimulation of the cochlear nerve in rats: analysis of c-Fos expression in auditory brainstem nuclei

We investigated functional activation of central auditory brainstem nuclei in response to direct electrical stimulation of the cochlear nerve using c-Fos immunoreactivity as a marker for functional mapping. The cochlear nerve was stimulated in the cerebellopontine angle of Lewis rats applying biphasic electrical pulses (120-250 muA, 5 Hz) for 30 min. In a control group, bilateral cochlectomy was performed in order to assess the basal expression of c-Fos in the auditory brainstem nuclei. The completeness of cochlear ablations and the response of auditory brainstem nuclei to electrical stimulation were electrophysiologically verified. C-Fos immunohistochemistry was performed using the free floating method. In anaesthetized animals with unilateral electrical stimulation of the cochlear nerve, increased expression of c-Fos was detected in the ipsilateral ventral cochlear nucleus (VCN), in the dorsal cochlear nucleus bilaterally (DCN), in the ipsilateral lateral superior olive (LSO) and in the contralateral inferior colliculus (IC). A bilateral slight increase of c-Fos expression in all subdivisions of the lateral lemniscus (LL) did not reach statistical significance. Contralateral inhibition of the nuclei of the trapezoid body (TB) was observed. Our data show that unilateral electrical stimulation of the cochlear nerve leads to increased expression of c-Fos in most auditory brainstem nuclei, similar to monaural auditory stimulation. They also confirm previous studies suggesting inhibitory connections between the cochlear nuclei. C-Fos immunoreactivity mapping is an efficient tool to detect functional changes following direct electrical stimulation of the cochlear nerve on the cellular level. This could be particularly helpful in studies of differential activation of the central auditory system by experimental cochlear and brainstem implants.