Buschke-Ollendorff syndrome: a novel case series and systematic review.

Buschke-Ollendorff syndrome (BOS) is a rare, often benign, autosomal skin disorder. BOS commonly presents with nontender connective tissue naevi and sclerotic bony lesions (osteopoikilosis [OPK]). Herein, we summarize the presenting features of BOS and potential associations by conducting a systematic review of the literature and summarizing a cohort seen at the Hospital for Sick Children (HSC), Toronto, Canada. PubMed was searched using the following terms: 'BOS'; 'dermatofibrosis lenticularis'; 'OPK'; 'LEMD3'; 'elastoma'; 'collagenoma'. Only case reports were included, without date or language restrictions. Cases were further narrowed to those where patients or their families had a combination of skin and bony lesions, or a positive genetic test. Data were summarized using frequencies. In total, 594 reports were discovered, of which 546 (92%) were excluded. The remaining 48 accounted for 164 cases. Skin lesions were noted in 24% of cases and bony lesions in 20%, while 54% of patients had both. In 1% of cases the diagnosis was made on genetic testing alone. A family history was noted in 92% of cases. All patients with spinal stenosis (2%) or shortened status (7%) had OPK. Six per cent of patients had neurological problems. However, 50% of the cohort from HSC had cognitive delays, and only cases from 2007 onwards reported cognitive delays (the prevalence was 17% among those cases). This review confirms the classical diagnostic features of BOS. In addition, it highlights a previously unreported association between a shortened stature and OPK, as well as a possible association with cognitive delays.

MPT64 patch test for the diagnosis of active pulmonary tuberculosis: a randomised controlled trial in Peru.

SETTING: There remains a lack of effective and inexpensive diagnostic tools for active tuberculosis (TB) disease. Testing immune responses to proteins secreted by Mycobacterium tuberculosis, such as MPT64, may be a diagnostic option. OBJECTIVE: To evaluate the sensitivity and specificity of a patch test using MPT64 for the diagnosis of active TB disease. DESIGN: This randomised, double-blind, placebo-controlled, prospective study in Lima, Peru, involved 55 healthy controls and 457 symptomatic individuals referred for routine TB testing by the National TB Control Programme. All subjects underwent a comprehensive diagnostic workup, and received an active patch on one arm and a placebo patch on the opposite arm, which were read after 4 days. RESULTS: Eighty-one (18%) of the symptomatic participants were classified as having definite TB, while an additional 98 (21%) had probable TB. The patch tests performed the same in both groups, with a sensitivity of 27% and specificity of 74%. The area under the receiver operating characteristic curve was 0.495 (95%CI 0.425-0.565). CONCLUSIONS: Contrary to existing literature, the MPT64 patch was not sensitive and specific to detect active TB. Given the potential of the test, understanding possible differences in the protein source or underlying genetic factors should be explored further.

Blinded proficiency testing of FTA-ABS test.

In 1976 and 1977, 28 state laboratories participated in a blinded proficiency testing study of syphilis serologic tests. The test considered of a battery of 50 duplicate reagin-positive sera; 12 specimens were obtained from syphilitic patients. The median reproducibility scores for the VDRL and FTA-ABS tests were the same, 92%, and the scores for the two tests were correlated. Given the relatively low prevalence of untreated syphilis in the United States today, serologic results that are highly predictive of syphilis are obtainable only from the most proficient laboratories, if unselected sera are tested. Reactivity in the VDRL and FTA-ABS tests does not prove the diagnosis of syphilis. Physicians must use clinical judgment to preselect patients for serologic testing.

Controlled-release delivery systems for hormones. A review of their properties and current therapeutic use.

Biomedical engineering approaches used to develop controlled-release delivery systems for hormones are here reviewed regarding system design and therapeutic applications. The biomedical engineering approach uses a system of non-drug components to control the rate and duration of hormone delivery. The non-drug components vary from system to system, but generally include: a reservoir for the hormone; a barrier or regulator to contain the hormone within the reservoir and to control its release; an energy source to remove the hormone from the reservoir; and a pathway for egress of the hormone from the system. Controlled-release delivery systems for hormones discussed in this review include mechanical and osmotic pumps; intraocular, intravaginal and intrauterine platform devices; biodegradable and non-biodegradable subcutaneous implants; and small particulate systems including microcapsules, microspheres and liposomes. Examples of the therapeutic application of the various systems are given along with a discussion of design factors and pharmacological aspects relevant to their clinical use.

SP-I secretion by baboon embryos in vitro.

Baboon embryos cultured to postimplantation stages have been shown to secrete the placental protein SP-I into the culture medium in quantities of up to almost 5 micrograms/day, based on a rhesus monkey standard. Twelve embryos, for which spent media samples have been assayed, have been shown to secrete this protein, with measurable quantities usually being present on day four following attachment of the zonaless embryo to the culture dish. Secretion has continued for up to 14 days, with over 26 micrograms total SP-I secretion from one embryo. These observations further enhance the utility of the baboon embryo culture system as a model for studying early placental development in the primate.

Demonstration of an early abortifacient effect of norethisterone (NET) in the primate (baboon).

A long-acting injectable contraceptive which provides continuous controlled release of norethisterone (NET) for three months following a single intramuscular injection was tested for antifertility effects in baboons using a low dose of microcapsules (total NET dose 2.5 mg; daily dose approximately 0.03 mg/day) which has no effect on ovarian function or ovulation. The continuous administration of NET during the cycle of conception had no effect on ovulation, fertilization or implantation as evidenced by the occurrence of nine pregnancies following 23 test matings. Pregnancy was diagnosed by the measurement of baboon chorionic gonadotropin hormone and the maintenance of elevated serum progesterone levels past the normal time of menstruation. Six of the nine pregnancies, however, ended in abortion between days 27 and 35 of pregnancy. The remaining three pregnancies continued to term and normal, healthy babies were delivered. Five control baboons included in this study became pregnant and all delivered normal, healthy infants. The results of this study demonstrate that early abortion should be considered as a mechanism of antifertility action of NET when administered continuously in low doses. These findings are contrary to the generally accepted explanation that low-dose synthetic progestins exert their contraceptive effect by inhibiting sperm transport and/or preventing implantation.

The abortifacient effect of synthetic androstane derivatives in the baboon.

Synthetic androstane derivatives have been tested for their ability to induce abortion during early pregnancy in primates. Two compounds were studied following intramuscular (IM) and oral treatment in fourteen baboons. A five-day treatment regimen was started at approximately day 20 of pregnancy in 12 baboons, with treatment delayed until after day 40 in two baboons. All seven baboons treated IM with either compound aborted following intramuscular treatment, although three required a second treatment series beginning on approximately day 40 of pregnancy. Two of five baboons treated orally aborted following the single treatment series initiated around day 20 of pregnancy. The two baboons treated only after day 40 continued to term and delivered healthy infants. These compounds are therefore effective at terminating pregnancy when given around the time of the missed menstrual period. Further studies are necessary to determine optimal dose and treatment schedule.

A 4-year summary of the nonsurgical recovery of baboon embryos: A report on 498 eggs.

A nonsurgical embryo recovery procedure, developed to allow the economical acquisition of cleavage stage baboon embryos, has been successfully used for 4 years. With this technique, 498 eggs have been recovered from 979 uterine flushes (50.9%) on 71 baboons. Of 467 eggs recovered from mated baboons, 290 (62.1%) were fertilized. Papio anubis females provided a higher percentage of fertilized eggs (75.3%) than did Papio hamadryas (47.8%) or Papio cynocephalus (44.3%) females following exposure to males during estrus, although sexual preference may be responsible for the reduced fertilization rate in the P. cynocephalus females. Recovery rates from individual baboons ranged from 0% (n = 11) to between 66% and 93% for ten baboons from each of which 12-33 eggs have been recovered. Fertilized eggs were at the two-cell (n = 23) to blastocyst (n = 53) stage at recovery 1-6 days postdeturgescence (PD) of the sex skin, with morulae (n = 84) being the most frequent cell stage recovered (30%). The optimum time for performing the procedure was the third day PD, when 113 (40%) embryos were recovered. The abilities of baboons to become pregnant and to provide fertilized embryos were significantly related (P < 0.005), allowing the embryo recovery technique to be used as a screening procedure for evaluating baboon fertility.

Prevalence of childhood and adolescent sexual abuse among sex offenders.

A simple nonstandardized questionnaire was developed and administered to 150 men convicted of various sexual offenses currently on probation or parole, living in the community, admitting their offenses and attending treatment. The hypothesis that men who engaged in sexual activity as adolescents with women would be at a higher risk of committing statutory rape-type sexual offenses was not substantiated.

The personal characteristics of effective counselors: what 10 experts think.

The counseling professional has called for the use of personal characteristics to be used for admissions to counseling programs as well as in the evaluation of counseling students. 10 expert counselors ranked 22 personality characteristics of potential students for importance and responsiveness to training. The most important include empathy, acceptance, and warmth, while the least important include resourcefulness, sympathy and sociability.

The Met Office Hadley Centre climate modelling capability: the competing requirements for improved resolution, complexity and dealing with uncertainty.

Predictions of future climate change require complex computer models of the climate system to represent the full range of processes and interactions that influence climate. The Met Office Hadley Centre uses 'families' of models as part of the Met Office Unified Model Framework to address different classes of problems. The HadGEM family is a suite of state-of-the-art global environment models that are used to reduce uncertainty and represent and predict complex feedbacks. The HadCM3 family is a suite of well established but cheaper models that are used for multiple simulations, for example, to quantify uncertainty or to test the impact of multiple emissions scenarios.

Excellence in sexually transmitted infection (STI) diagnostics: recognition of past successes and strategies for the future.

Diagnostic advances do not generally receive the recognition given to prevention and treatment contributions, for the control and management of infectious diseases including sexually transmitted infections (STIs). In order to identify seminal diagnostic contributions over a half century (1950-2000), the Editorial Board of the WHO Sexually Transmitted Diseases Diagnostics Initiative (SDI) Publication Review or "electronic journal club" were asked to nominate their choices of peer-reviewed publications for special recognition. From 43 nominations, 13 were voted by a panel of 25 "experts" as having made the most significant contributions. The 1964 article by Thayer and Martin, which identified a selective media for gonococcal culture, was chosen unanimously by all panel members and is identified as the classic STI diagnostic article for this era.

A multi-centre evaluation of nine rapid, point-of-care syphilis tests using archived sera.

OBJECTIVES: To evaluate nine rapid syphilis tests at eight geographically diverse laboratory sites for their performance and operational characteristics. METHODS: Tests were compared "head to head" using locally assembled panels of 100 archived (50 positive and 50 negative) sera at each site using as reference standards the Treponema pallidum haemagglutination or the T pallidum particle agglutination test. In addition inter-site variation, result stability, test reproducibility and test operational characteristics were assessed. RESULTS: All nine tests gave good performance relative to the reference standard with sensitivities ranging from 84.5-97.7% and specificities from 84.5-98%. Result stability was variable if result reading was delayed past the recommended period. All the tests were found to be easy to use, especially the lateral flow tests. CONCLUSIONS: All the tests evaluated have acceptable performance characteristics and could make an impact on the control of syphilis. Tests that can use whole blood and do not require refrigeration were selected for further evaluation in field settings.

Replacement for 30-milliliter flat-bottomed, glass-stoppered, round bottles used in VDRL antigen preparation.

When the flat-bottomed, glass-stoppered, round bottle traditionally used to make VDRL antigen was discontinued, an appropriate substitute was needed. Although many laboratories have switched to one of the other nontreponemal tests for syphilis serology screening, the VDRL test remains the only approved procedure for testing spinal fluids of patients with possible neurosyphilis. We tested 25-ml glass-stoppered, convex-bottomed Erlenmeyer flasks to determine if these could be used as appropriate substitutes. We tested 52 reactive sera and 54 nonreactive sera by using one reference antigen prepared in the traditional flat-bottomed bottles and five antigens prepared in the Erlenmeyer flasks. Results with all serum samples were comparable. We also tested two lots of a commercial antigen plus an additional lot of reference antigen. Again there was no difference in the reactivity of the antigens. Therefore, we conclude that 25-ml glass-stoppered Erlenmeyer flasks can be used as an appropriate substitute for glass-stoppered, flat-bottomed, round glass bottles in the making of VDRL antigen.

Effect of heat or formalin treatment of leptospires on antibody response detected by immunoblotting.

Leptospira interrogans serovar icterohaemorrhagiae RGA (RGA), live or heated at 56 degrees C for 15 min or treated with Formalin, was injected into rabbits to prepare hyperimmune serum. The pathogens L. interrogans serovars icterohaemorrhagiae RGA, icterohaemorrhagiae 1, canicola Moulton, grippotyphosa Andaman, hardjo Hardjoprajitno, and pomona Pomona and the nonpathogen Leptospina biflexa serovar patoc Patoc 1 were processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and after electrophoresis they were then transferred to nitrocellulose paper. Antiserum against RGA (live, heat killed, or Formalin killed) was used on one of each of the three blots. Formalin appeared to completely eliminate antibody response to antigens with the molecular weight of 14,000 to 20,000 (14K to 20K) but did expose an antigen at approximately 23K in the pathogens only. This same band had only slight reactivity when antiserum against heat-killed RGA was used. Heating also eliminated cross-reactivity in the 19K to 30K range and partially degraded bands in the 14K to 20K region so that one broad band rather than several discrete bands appeared. The three antiserum specimens cross-reacted with all of the serovars tested, but fewer antigens of grippotyphosa and hardjo reacted with the antisera. Against patoc, reactivity was limited primarily to the flagellar region. The most cross-reactivity was with the antiserum prepared by using live leptospires.