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.     

Markers of Inflammation,Endothelial Activation and Autoimmunity in Adolescent Female Gymnasts

High levels of physical activity have been linked to benefits in cardiovascular and bone health by affecting, in part, changes in proinflammatory profile. Therefore, we have aimed to assess the effects of intensive training on markers of inflammation, endothelial activation and auto-immunity in the absence of the potential confounding effects of incident atherosclerosis. The subjects comprised 25 competitive gymnasts and 19 healthy sedentary adolescent females, aged 8-17 years. Serum soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hsCRP), heat shock protein 27 (Hsp27) and Hsp27 antibody titres were measured by ELISAs in a sample of adolescent girls who were either physically active (competitive gymnasts) or sedentary. The association between age, body mass index (BMI), dietary intake, serum hsCRP, sICAM-1 and Hsp27 antigen and antibody titres were determined. The mean serum sICAM-1 concentrations were significantly higher in the gymnasts compared to the sedentary females (0.29 ± 0.02 versus 0.23 ± 0.01 mg·L^-1, p < 0.01). In contrast serum hsCRP concentrations were substantially lower in the gymnasts compared to the sedentary adolescent females (0.49 ± 0.03 versus 1.38 ± 0.19 mg·L^-1, p < 0.001). Differences remained significant after adjustment for anthropometric factors. We also found that serum Hsp27 antigen concentrations were determined by dietary saturated fat intake (p < 0.001), and antibody titres to Hsp27 were determined by dietary PUFA (p < 0.001) after adjustment for BMI. Our findings show that young female gymnasts have an altered profile of inflammatory markers and endothelial activation compared to their less physically active peers.

Key points

• Results showed that adolescent young female gymnasts have an altered serum inflammatory markers and endothelial activation, compared to their less physically active peers.
• Physical activities improved immune system.
• Differences in these biochemical data kept significant after adjustment for body weight and height.

Key words: Physical activity,; dietary intakes,; hsCRP,; sICAM-1,; Hsp27,; antibodies     

Predictors of duration of postoperative hospital stay in patients undergoing advanced laparoscopic surgery

The expansion of the indications for laparoscopic surgery to include high-risk patient, acute and malignant pathology, and more complex procedures may prolong the hospital stay. Cox multiple stepwise regression analysis model was employed to determine independent predictors of prolonged postoperative hospital stay (more than 3 days) following advanced laparoscopic procedures among 10 variables. Some 130 patients had undergone advanced laparoscopic surgical procedures between November 2000 and August 2003. The median postoperative hospital stay was 3 days (interquartile range 2-5), and 81 patients (62.3%) were discharged within 3 days of surgery. The independent predictors of prolonged postoperative hospital stay were ASA score of 3 or 4 (odds ratio [OR] = 4.610, P = 0.0002) and preoperative hospital stay (OR = 0.151 per day, P = 0.001). Independent predictors of duration of preoperative hospital stay were emergency admission to hospital (OR = 9.516, 95% CI 5.770-13.261, P < 0.0001) and an underlying malignant pathology (OR = 7.948, 95% CI 3.623-12.273, P = 0.0004). Advanced laparoscopic surgery is associated with a short postoperative hospital stay in the majority of patients. Prolongation of the postoperative hospital stay (more than 3 days) may be expected if the patient had been in the hospital with an acute or malignant disease for more than 6 days prior to surgery and in patients with high comorbidity. The duration of surgery has no impact on the duration of the postoperative hospital stay.     

Dissection of coronary artery: A clinical overview

Spontaneous coronary artery dissection (SCAD) is a rare but life-threatening disorder. SCAD is gaining importance as an emerging cause of acute coronary syndrome (ACS), especially in otherwise healthy young women. While SCAD and ACS show similarity in presentation, the management of SCAD differs to that of ACS. If not managed properly SCAD can lead to sudden death. This review examines the pathophysiology, clinical presentation, diagnostic algorithms, and the current and future management of SCAD.     

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.