Topically applied treatments for external genital warts in nonimmunocompromised patients: a systematic review and network meta-analysis.

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02-3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12-0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents.

Molecular cytogenetic studies towards the full karyotype analysis of human blastocysts and cytotrophoblasts.

Numerical chromosome aberrations in gametes typically lead to failed fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means of preimplantation genetic diagnosis (PGD), we now can screen human embryos in vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us to select unaffected embryos for transfer and increases the implantation rate in in vitro fertilization programs. Molecular cytogenetic analyses using multi-color fluorescence in situ hybridization (FISH) of blastomeres have become the major tool for preimplantation genetic screening of aneuploidy. However, current FISH technology can test for only a small number of chromosome abnormalities and hitherto failed to increase the pregnancy rates as expected. We are in the process of developing multi-color FISH-based technologies to score all 24 chromosomes in single cells within a three-day time limit, which we believe is vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at the fetal-maternal interface acquire aneuploidies as they differentiate to an invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated pregnancies were found to be aneuploid, suggesting that the acquisition of aneuploidy is an important component of normal placentation, perhaps limiting the proliferative and invasive potential of CTBs. Since most invasive CTBs are interphase cells and possess extreme heterogeneity, we applied multi-color FISH and repeated hybridizations to investigate the feasibility of a full karyotype analysis of individual CTBs. In summary, this study demonstrates the strength of Spectral Imaging analysis and repeated hybridizations, which provides a basis for full karyotype analysis of single interphase cells.

Measuring the indirect and direct costs of acute otitis media.

OBJECTIVES: To test a method of measuring the related cost of acute otitis media (AOM) and to provide a preliminary calculation of the indirect and directs costs associated with a single, medically treated episode of AOM. DESIGN: The Otitis Media Diary was used to measure indirect and direct costs associated with AOM in a prospective cohort study. Measured values included the parental time spent in otitis-specific child care and the number and type of medications used. A previously developed economic model was used to calculate the monetary costs associated with the value of caregiver time and the total opportunity cost of AOM. SETTING: The pediatric clinic of Madigan Army Medical Center, Tacoma, Wash. PATIENTS: A cohort of 25 children (12 with AOM and 13 controls) aged 1 to 3 years. MAIN OUTCOME MEASURES: Caregiver time and medication use. RESULTS: The total cost attributable to AOM in the 3-month period following diagnosis was $1330.58 (95% confidence interval, $1008.75-$1652.43), with the majority of that cost stemming from the indirect, rather than direct, costs of illness. After conservative estimates of unmeasured expenses, such as clinic visits and transportation, were accounted for, indirect costs, accrued primarily by parental time, accounted for nearly 90% (95% confidence interval, 87.1%-92.3%) of the total 3-month cost associated with AOM and its medical treatment. The cost items of the Otitis Media Diary were also highly correlated with each other and with other measures of clinical and functional health status. CONCLUSIONS: Otitis Media Diary measures of parental time and medication use appear to provide a more accurate means of calculating the real social costs attributable to the AOM disease process in this cost-effectiveness analysis.

Otitis media health status evaluation: a pilot study for the investigation of cost-effective outcomes of recurrent acute otitis media treatment.

There are no reliable and valid instruments that measure otitis media clinical or functional health status in children ages 1 to 3 years. This study develops and tests three new instruments of clinical and functional otitis health status: the Otitis Media Clinical Severity Index (OM-CSI), the Otitis Media Functional Status Questionnaire (OM-FSQ), and the Otitis Media Diary (OMD). The OM-CSI was found to be a reliable measure of clinical acute otitis media (AOM) severity, with high internal consistency (Cronbach's alpha) scores, as well as an accurate indicator of AOM severity. The OM-FSQ and OMD were demonstrated to be reliable and valid measures of otitis-specific functional health status, with reproducible scores over time, high internal consistency alpha scores, and high correlation with measures of AOM clinical severity and other functional health status instruments. These three new instruments were also sensitive and specific indicators of AOM episodes.

Synthesis and gastric antisecretory properties of 15-deoxy-16-hydroxyprostaglandin E analogues.

The preparation and gastric antisecretory activity of a series of 15-deoxy-16-hydroxyprostaglandin analogues are described. The compounds were tested intravenously in histamine-stimulated Heidenhain pouch dogs in relation to the reference standards PGE1 and PGE1 methyl ester (PGE1ME). The parent compound of this seris, (+/-)-15-deoxy-16alpha,beta-hydroxyprostaglandin E1 methyl ester (3), was found to be equipotent to the reference standard PGE1ME. Methylation at C-16 of 3 produced 8 which was found to be some 40 times more potent than PGE1. In sharp contrast, addition of two methyl groups to 3 at C15 or C17 markedly reduced the antisecretory action. The 16-ethyl analogue of 3 also showed reduced potency. Removal or epimerization of the C-11 hydroxy group of 8 reduced the activity. Likewise, hydrogenation or changing the stereochemistry of the 13,14 double bond from trans to cis decreased the activity. On the other hand, omega-homologation of 8 or the introduction of a cis-5,6 double bond did not affect the potency. From these studies, it appears that 8, 16, and 17 possess optimum gastric antisecretory effects in this series.

Sickle cell trait and hematuria associated with von Willebrand syndromes.

A von Willebrand syndrome was present in four patients with sickle cell trait and hematuria. The first two patients had severe anemia and active bleeding and received cryoprecipitate, with prompt cessation of hemorrhage. All of the patients had repetitive laboratory and clinical features; that is, reduced, but detectable, factor VIII-related antigen, heterogeneity of, and incongruities within, the coagulation studies performed by consistently defective platelet aggregation to ristocetin correctable only with normal plasma. Bleeding outside the genitourinary tract never was observed. Because of the focal nature of the hemorrhage, the hematuria may not have been perceived as part of a general hemorrhagic disorder and the diagnosis not pursued. These observations suggest that when sickle cell trait and hematuria occur together, a von Willebrand syndrome should be a major diagnostic consideration that ultimately may point toward a rational, effective, easily administered, and clinicially acceptable form of treatment with cryoprecipitate.

Prostaglandin studies: the total synthesis of DL-prostaglandin B1.

PIP: An 11-step process for total synthesis of dl-PGB1 (prostaglandin B1) is described. The chemical structure of each interim step in the process is presented. The following analytical data were obtained for each new compound in the process: 1) ultraviolet absorption spectra in methanol; 2) infrared absorption spectra in chloroform; and 3) NMR spectra in deuterochloroform.^ieng