Female pelvic floor. Descriptive anatomy and clinical exploration by transvaginal ultrasound

In order to assess the state and pathology of the woman's pelvis minor, a number of methods are commonly used among practitioners, encompassing clinical exploration, radiology, MRN, urodynamics, endoscopy and echography.

Echography has been poorly used in clinical pelvic exploration and its reliability is actually a matter of controversy 1. However, echographic surveys can provide us with valuable gynecological data on the state and pathologies of the soft pelvis, within the genital regions or even going beyond them, i.e. the rectal channel, bladder, urethra, anus, vascular plexuses, and all of their supporting tissues.

At our research unit, we have been employing Transvaginal Ultrasound echography (TVU) for a long time in conjunction with other pelvis-focused methods in order to study different kinds of pelvic alterations. TVU has proven to be friendly to use, fast, harmless and inexpensive, allowing serial explorations and producing high-quality dynamic images (loop-cinema, video-tape). Furthermore, this method is fairly aseptic in that the occurrence of faeces in the rectal ampolla is not a nuisance but a bonus in tracking the contours of the rectum walls and other topographical features which would be otherwise difficult to survey.

A complete pelvic floor TVU may add no longer than 5-8 minutes to a routine gynecological examination, can be implemented by the general gynecologist and generates data that can be further studied by the appropriate specialist for a more insightful evaluation 2.     

Evaluation of a radioimmunologic technique for the detection of anti-native DNA antibodies

The anti-native DNA antibodies were measured by a radioimmunoassay (RIA) type Farr assay in the sera from 648 patients: 108 with active or inactive systemic lupus erythematosus (SLE), 181 with clinical symptoms of another connective tissue disease, 171 with liver diseases, 29 with different pathology and 159 normal sera were obtained from a blood bank. The anti-DNA kit has been calibrated against the first international units/ml. This assay has proved to be sensitive and specific, and appears to be reliable for the diagnosis and follow-up of SLE patients. The authors propose a new reference cut-off level higher than producer's one.     

Error rate for HLA-B antigen assignment by serology: implications for proficiency testing and utilization of DNA-based typing methods

Until recently, the majority of HLA class I typing has been performed by serology. Expensive commercial typing trays are frequently used for testing non-Caucasian subjects and new strategies using DNA-based methods have been adopted for improving clinical histocompatibility testing results and adapted as supplements in proficiency testing. A double-blind comparison of the typing of HLA-B specificities in 40 samples was carried out between serology and two polymerase chain reaction (PCR) methods, PCR amplification with sequence-specific primers (PCR-SSP) and PCR amplification and subsequent hybridization with sequence-specific oligonucleotide probes (PCR-SSOP). The results demonstrated 22.5% misassignments of HLA-B antigens by serology. There was complete concordance between the results obtained with the two PCR based typing methods. A second panel of 20 donor samples with incomplete or ambiguous serologic results was analyzed by PCR-SSP and SSOP. Both PCR methods identified correctly the HLA-B antigens. Our results suggest that more accurate typing results can be achieved by complementing serologic testing with DNA-based typing techniques. The level of resolution for HLA-B antigen assignment can be obtained by this combination of serology and limited DNA-based typing is equivalent to the HLA-B specificities defined by the WHO-HLA Committee. This level of resolution cannot routinely be achieved in clinical histocompatibility testing or in proficiency testing using serologic reagents only.     

Immunogenicity of multiple antigen peptides (MAP) containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite protein.

The immunogenicity of multiple antigen peptides (MAP) constructs containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite (CS) protein was examined in vitro, using a human T cell clone, and in vivo, using four different strains of mice. All the MAP constructs that contained the T cell epitope, (DPNANPNVDPNANPNV), stimulated proliferation and interferon-gamma production by a human T cell clone specific for this epitope which is located in the 5' end of the repeat region of the P. falciparum CS protein. These human T cells did not recognize MAP that contained only the B cell epitope, (NANP)3, which is located in the 3' repeat region. Optimal antibody responses were obtained in mice immunized with MAP containing four copies of tandemly arranged T and B cell epitopes, (TB)4. The murine immune response to the MAP constructs was genetically restricted. Mice of a high responder strain, C57BL, recognized both the 5' and 3' repeat sequences in the MAP as T, as well as B, cell epitopes and developed very high anti-MAP and anti-sporozoite antibody titers. A/J and C3H mice, which were intermediate responders, developed lower antibody titers which varied according to the orientation of the T vs. the B cell epitopes within the MAP constructs. BALB/c mice were nonresponders and did not develop antibodies following immunization with any of the MAP constructs containing the 5' and 3' repeats of the P. falciparum CS protein.     

Generating new evidence,improving clinical practice and developing research capacity: the benefits of recruiting to the U.K. Dermatology Clinical Trials Network's STOP GAP and BLISTER trials

Clinical trials may benefit clinical practice in three ways: firstly, clinicians may change their practice according to the new trial evidence; secondly, clinical processes can improve when working on a trial; and thirdly, research capacity is increased. We held a meeting to present and discuss the results of two large multicentre randomized controlled trials delivered through the U.K. Dermatology Clinical Trials Network. Investigators gave reflections on how the trials had changed their clinical practice. The STOP GAP trial showed that prednisolone and ciclosporin are equally effective as first‐line systemic treatment for pyoderma gangrenosum. The final decision of which treatment to use should be based on the different adverse event profiles of the two drugs in relation to comorbidities, along with age, disease severity and patient preference. The BLISTER trial showed that starting people with pemphigoid on doxycycline produces acceptable short‐term effectiveness and a superior safety profile to oral corticosteroids. Recruiting to these trials has led to the development of new specialist clinics with improved documentation. It has increased the profile of participating departments and embedded research in the department's activities. Helping to design and run these trials has also allowed trial staff to develop new skills in research design, which has been beneficial for career development. These and other benefits of recruiting to the trials are summarized here. We hope that these reflections will inspire wider involvement in clinical research.     

The response of γ vitamin E to varying dosages of α vitamin E plus vitamin C

Vitamin E has been studied extensively in the prevention of atherosclerosis. Cross-sectional population studies as well as randomized controlled intervention trials have demonstrated conflicting results. A recent meta-analysis of these trials has emphasized the ineffectiveness of vitamin E in atherosclerosis prevention, with a possibility of harm at higher dosages. However, vitamin E has several isomers, with the α form being available via dietary supplements and the γ form being available via dietary foodstuffs. The γ form of vitamin E demonstrates several superior properties (such as trapping reactive nitrogen species and detoxifying nitrogen dioxide) compared with α vitamin E. All clinical trials have used the α isomer, with little concern that this isomer of vitamin E may actually suppress the γ isomer of vitamin E. We undertook a dose-response study in volunteers with type 2 diabetes mellitus to include all the dosages of α vitamin E that have been used in cardiovascular prevention trials to determine the effect of α vitamin E on γ vitamin E. We also assessed the effect of α vitamin E on several traditional markers of atherosclerotic risk. We added vitamin C to the vitamin E because several clinical trials included this vitamin to enhance the antioxidant effects of α vitamin E. Volunteers received, in randomized order for a 2-week period, one of the following vitamin dosage arms: (1) no vitamins, (2) low-dose supplemental vitamins E plus C, (3) medium-dose supplemental vitamins E plus C, and (4) high-dose supplemental vitamins E plus C. Blood levels of both α and γ vitamin E were measured as well as surrogate markers of oxidative stress, hypercoagulation, and inflammation during a high-fat atherogenic meal (to increase the ambient oxidative stress level during the study). The results demonstrate that α vitamin E levels increased in proportion to the dose administered. However, at every dose of α vitamin E, γ vitamin E concentration was significantly suppressed. No beneficial changes in surrogate markers of atherosclerosis were observed, consistent with the negative results of prospective clinical trials using α vitamin E. Our results suggest that all prospective cardiovascular clinical trials that used vitamin E supplementation actually suppressed the beneficial antioxidant γ isomer of vitamin E. No beneficial effects on several potential cardiovascular risk factors were observed, even when the vitamin E was supplemented with vitamin C. If a standardized preparation of γ vitamin E (without the α isomer) becomes available, the effects of γ vitamin E on atherosclerotic risk will warrant additional studies.     

Comparison of paclitaxel-eluting stent and sirolimus-eluting stent expansion at incremental delivery pressures

OBJECTIVES: We sought to compare the adequacy of paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) expansion based on intravascular ultrasound (IVUS) imaging criteria at conventional delivery pressures. METHODS: Forty-six patients underwent SES implantation and 42 patients underwent PES implantation for de novo native coronary lesions<33 mm in length with reference lumen diameters of 2.5-3.5 mm. Stents were serially expanded with gradual balloon inflations at 14 and 20 atm. IVUS imaging was performed prior to intervention and after each balloon inflation. Stent expansion (minimal stent cross-sectional area/reference lumen cross-sectional area) was measured. Inadequate stent expansion was defined using the MUSIC criteria (all struts apposed, no tissue protrusion, and final lumen cross-sectional area>80% of the reference or >90% if minimal lumen cross-sectional area was <9 mm2). RESULTS: The baseline characteristics of the two groups were similar except for shorter lesion length, larger mean lumen cross-sectional area, larger lumen diameter, and lower plaque burden in the PES group. Stent expansion was inadequate in 80% of patients with SES versus 63% of patients with PES at 14 atm, although this was not statistically significant. After 20 atm, 48% of patients with SES remained underexpanded as compared with 35% of patients with PES. CONCLUSION: Drug-eluting stents showed significant underexpansion by MUSIC criteria at conventionally used inflation pressures. Higher balloon inflations are required especially during deployment of a SES. IVUS guidance is recommended to ensure optimal results and outcomes with both stents.     

Dysregulation of glucose metabolism in HIV patients: epidemiology, mechanisms, and management

HIV-infected patients on highly active antiretroviral therapy (HAART) have increased prevalence of a number of chronic metabolic disorders of multifactorial but unclear etiology. These include disorders of lipid metabolism with or without lipodystrophy, insulin resistance, and an increased prevalence of impaired glucose tolerance, diabetes mellitus, and cardiometabolic syndrome. While much attention has been focused on the lipid and cardiovascular disorders, few investigations have attempted to characterize the prevalence, incidence, etiology, mechanisms, and management of glycemic disorders in HIV patients. In this review, we have focused specifically on a comprehensive assessment of dysglycemia in the context of HIV infection and HAART.     

Heat‐related changes in skin tissue dielectric constant (TDC)

The impact of 20 min of whole‐body heating (WBH) on the tissue dielectric constant (TDC) of forearm and hand skin was evaluated in 24 young adults. TDC was measured in triplicate at 300 MHz using an open‐ended transmission line method in which the effective measurement depth was about 2 mm. TDC measurements are an effective way to assess and track localized oedema and lymphoedema. The underlying hypothesis was that heat‐induced eccrine gland activation would increase TDC values via an increase in fluid within the TDC measurement volume. The goal was to test this concept and to determine the magnitude of the change when environmental temperatures were elevated to near 42°C and to estimate TDC recovery time. The practical aspect of this research is motivated by the fact that patients in whom such measurements are made may arrive at the clinic in various states of sweat gland activation. Thus, knowledge of the effect of such activation on measured TDC values permits better understanding of possible relationships between such activation and TDC values. Results showed that increasing environmental temperature from 23·3 ± 1·6 to 41·5 ± 1·3°C increased forearm and thenar eminence skin temperatures to 37·8 ± 0·5 and 37·9 ± 0·4°C, respectively. These changes were associated with increases in TDC at arm from 30·7 ± 4·6 to 36·3 ± 5·7 (18·2%) and at hand from 34·7 ± 4·9 to 45·1 ± 5·5 (30%). Based on calculated TDC recovery rates, it is concluded that temperature‐related TDC variability can be minimized using a wait time of at least 15 min after bandage removal prior to TDC measurements in affected limbs.