Review of non-invasive vulvovaginal rejuvenation.

Vulvovaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) may affect up to 90% of menopausal women. Features include vulvovaginal atrophy, vulvovaginal laxity, vulvovaginal dryness and irritation, dyspareunia, anorgasmia and urinary symptoms. The vulva, vagina and bladder are oestrogen-responsive tissues, but oestrogen replacement therapy is not possible in women who have hormone-responsive cancers or normal oestrogen levels. Therefore, there is a role for alternative treatments. To date, three non-surgical energy-based therapies have been proposed: fractional microablative CO2 laser, erbium:YAG laser and temperature-controlled radiofrequency (RF). Our objective was to assess the available evidence for the safety and efficacy of erbium:YAG laser, microablative fractional CO2 laser and RF in the treatment of VVA/GSM. The authors reviewed the current published literature evaluating these therapies. All three therapies appear safe; however, all the studies were uncontrolled and used different protocols and outcome measurements. Therefore, comparison of treatments is difficult. It appears that there is more evidence in favour of the CO2 laser than the erbium:YAG laser. Both lasers have more evidence than RF. In conclusion, microablative CO2 laser, erbium:YAG laser and RF may be offered to patients suffering from VVA/GSM as an alternative or adjunct to conventional therapies. Further well-conducted controlled studies are needed.

Temporal variability of readmission determinants in postoperative vascular surgery patients.

INTRODUCTION: Clinical information continues to be limited regarding changes in the temporal risk profile for readmissions during the initial postoperative year in vascular surgery patients. We set out to describe the associations between demographics, clinical outcomes, comorbidity indices, and hospital readmissions in a sample of patients undergoing common extremity revascularization or dialysis access (ERDA) procedures. We hypothesized that factors independently associated with readmission will evolve from "short-term" to "long-term" determinants at 30-, 180-, and 360-day postoperative cutoff points. METHODS: Following IRB approval, medical records of patients who underwent ERDA at two institutions were retrospectively reviewed between 2008 and 2014. Abstracted data included patient demographics, procedural characteristics, the American Society of Anesthesiologists score, Goldman Criteria for perioperative cardiac assessment, the Charlson comorbidity index, morbidity, mortality, and readmission (at 30-, 180-, and 360-days). Univariate analyses were performed for readmissions at each specified time point. Variables reaching statistical significance of P< 0.20 were included in multivariate analyses for factors independently associated with readmission. RESULTS: A total of 450 of 744 patients who underwent ERDA with complete medical records were included. Patients underwent either an extremity revascularization (e.g. bypass or endarterectomy, 406/450) or a noncatheter dialysis access procedure (44/450). Sample characteristics included 262 (58.2%) females, mean age 61.4 ± 12.9 years, 63 (14%) emergent procedures, and median operative time 164 min. Median hospital length of stay (index admission) was 4 days. Cumulative readmission rates at 30-, 180-, and 360-day were 12%, 27%, and 35%, respectively. Corresponding mortality rates were 3%, 7%, and 9%. Key factors independently associated with 30-, 180-, and 360-day readmissions evolved over the study period from comorbidity and morbidity-related issues in the short-term to cardiovascular and graft patency issues in the long-term. Any earlier readmission elevated the risk of subsequent readmission. CONCLUSIONS: We noted important patterns in the temporal behavior of hospital readmission risk in patients undergoing ERDA. Although factors independently associated with readmission were not surprising (e.g. comorbidity profile, cardiovascular status, and graft patency), the knowledge of temporal trends described in this study may help determine clinical risk profiles for individual patients and guide readmission reduction strategies. These considerations will be increasingly important in the evolving paradigm of value-based healthcare.

Stereotactic ablative radiotherapy with CyberKnife for advanced thymic carcinoma: a case report.

Thymic carcinoma is a rare but lethal mediastinal cancer. The optimal treatment for advanced thymic carcinoma is not yet established. This report is the first known of stereotactic ablative radiotherapy (sabr) with CyberKnife (Accuray, Sunnyvale, CA, U.S.A.) as definitive therapy for thymic carcinoma. The patient, a 70-year-old woman with thymic carcinoma, invasion into neighboring organs, and pleural metastases-underwent CyberKnife sabr at 40 Gy in 5 fractions for two lesions, one in the thymus and one in the right paraspinal pleura. After 61 months of observation, a partial response was observed in the irradiated fields. However, disease progression in the non-irradiated pleura was noted. The patient underwent salvage CyberKnife sabr for the four initially nonirradiated pleural lesions. Computed tomography images obtained 10 months after the salvage therapy revealed a partial response. The patient is living, with progression-free irradiated lesions and no radiation-related toxicity. CyberKnife sabr is feasible for patients who are unable to undergo either surgery or conventionally fractionated radiation therapy.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 µM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 µM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 µM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 µM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 µM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 µM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts.

Are wider surgical margins needed for early oral tongue cancer?

BACKGROUND: Traditionally, a 1-cm surgical resection margin is used for early oral tongue tumours. METHODS: All tumour stage one (n = 65) and stage two (n = 13) oral tongue cancers treated between January 1999 and January 2009 were followed for a median of 38 months (minimum 12 months). The sites of close and involved margins were histologically reviewed. RESULTS: Involved and close margins occurred in 14 and 55 per cent of cases, respectively. The number of involved vs clear or close margins was equivalent in tumour stage one (90 vs 82 per cent), node-negative (100 vs 84 per cent) and perineural or lymphovascular invasion (20 vs 21 per cent) cases. Close or involved margins were similarly likely to be posterior (59 per cent) as anterior (41 per cent, p = 0.22), lateral (57 per cent) as medial (43 per cent, p = 0.34), and mucosal (59 per cent) as deep (41 per cent, p = 0.22). Local recurrence occurred in 28 per cent of cases at a median of 12 months, and was more likely in cases with involved (50 per cent) than clear or close margins (25 per cent, p = 0.10). Disease-free survival was worse in involved margins cases (p = 0.002). CONCLUSION: Involved margins are common in early tongue tumours, and are associated with increased local recurrence and worse survival. Close or involved margins occur in all directions and all tumour types. A wider margin may be justified.

Suramin protects the murine motor nerves from the toxic effects of presynaptic Ca(2+) channel inhibitors.

The purpose of this study is to investigate whether suramin is capable of preventing the neurotoxic effects of Ca(2+) channel inhibitors at the presynaptic sites. Mouse diaphragm and triangularis sterni preparations were used for this study in order to measure the muscle tension and nerve terminal Ca(2+) current, respectively. Both omega-conotoxin MVIIC and omega-agatoxin IVA markedly inhibit the nerve-evoked muscle contractions as well as the nerve terminal Ca(2+) current respectively. Pretreatment with suramin (0.3 mM) significantly reduced the inhibitory effect of nerve-evoked muscle contractions and Ca(2+) current induced by either omega-conotoxin MVIIC or omega-agatoxin IVA but not that induced by the non-selective Ca(2+) channel blocker, Cd(2+). Neither suramin nor Ca(2+)-channel toxins significantly affect Na(+)- and K(+) currents of the nerve terminals. These findings indicate that suramin selectively interferes the action of presynaptic Ca(2+) channel neurotoxins and thus reduces their depressant effects on the muscle contractions. The implication of these findings is that suramin and its derivatives may potentially become useful agents in management of intoxication of Ca(2+) channel neurotoxins.

'Best clinical practice': assessment of processes of care and of outcomes in the US Military Health Services System.

The National Quality Management Program of the Military Health Services System of the United States has undertaken a series of projects whose objective is the active, on-going monitoring and improvement of the effectiveness and efficiency of the care provided to a broad population that encompasses troops on active duty, retirees and dependents. The analytic activities consist of (1) identification by clinical panels of conditions and procedures of interest; (2) collection of data from electronic repositories and from charts to characterize the patients, how they are managed, the clinical outcomes they experience, the resource costs their care entails, and, from questionnaires, their functional status and level of satisfaction, and (3) generation of 'report cards' that inform organizational units down to the level of the hospital of the characteristics of their patients, their practices, and the risk-adjusted outcomes they achieve. The patterns of care employed by the hospitals that obtain the best risk-adjusted outcomes and resource utilization ('best clinical practice') are identified and made known. In addition, (4) a systematic process of developing outcomes-based practice guidelines has been devised. It intent is to serve as a decision-support tool for clinicians. Initial estimates have been obtained of the probable consequences of the application of this tool to operative interventions in childbirth. Use of the tool would result in a higher occurrence of elective Caesarean sections, a reduced rate of emergency Caesarean sections and much lower use of forceps, with an overall improvement in outcomes and lower resource costs. This program is currently in the early phases of implementation. The two principal requirements for the immediate future are (1) education of the clinical and administrative communities in the use of the data and the decision-support tools and (2) evaluation of the consequences of the use of the data by the clinical and administrative communities.

Multiple types of Ca2+ channels in mouse motor nerve terminals.

We measured neurotransmitter release and motor nerve terminal currents in mouse phrenic nerve-diaphragm and triangularis sterni preparations, to evaluate the role of Ca2+-channel subtypes in regulating transmitter release. Saturated concentrations of either omega-agatoxin IVA [omega-Aga-IVA (0.3 microM), a blocker of P-type Ca2+ channels] or omega-conotoxin MVIIC [omega-CTx-MVIIC (2 microM), a P- and Q-type Ca2+-channel blocker], inhibited nerve-evoked muscle contractions and the amplitude of endplate potentials respectively. In contrast, combined treatment with nifedipine (50 microM, a blocker of L-type Ca2+ channels) plus omega-conotoxin GVIA [omega-CTx-GVIA (2 microM), a blocker of N-type Ca2+ channels] did not elicit inhibitory effects on nerve-evoked muscle contractions, endplate potentials or nerve terminal waveforms. Because of the non-linear relationship between endplate potentials and Ca2+ signals, a small decrease in presynaptic Ca2+ entry can significantly reduce the amplitude of the endplate potential. Thus, we applied 3,4-diaminopyridine (3,4-DAP, a K+-channel blocker) or high Ca2+ (10 mM) to accelerate and amplify the endplate potentials and Ca2+ currents. The endplate potentials amplified by 3,4-DAP or by high Ca2+ correspondingly proved to be quite resistant to both omega-Aga-IVA and omgea-CTx-MVIIC; omega-Aga-IVA exerted only a partial inhibitory effect on endplate potentials, and the omega-Aga-IVA-resistant component was further inhibited by omega-CTx-MVIIC. The component that was resistant to the two toxins could be completely blocked by the non-selective Ca2+ channel blocker Cd2+ (300 microM). A combination of the two toxins had no significant effects on either spontaneous transmitter release or postsynaptic resting membrane potentials of the diaphragm preparation and the Na+ and K+ waveforms of the triangularis sterni preparations. This finding suggests a preferential inhibitory effect at a presynaptic site. Measuring the Ca2+ currents in the triangularis sterni also revealed partial inhibition by omega-CTx-MVIIC with further incomplete inhibition by omega-Aga-IVA. Cd2+ (300 microM) abolished the toxin-resistant component of the Ca2+ current. In contrast, a combination of nifedipine (50 microM) with omega-CTx-GVIA (2 microM) was without inhibitory effect. We conclude that multiple types of Ca2+ channels, i.e. omega-Aga-IVA-sensitive, omega-CTx-MVIIC-sensitive and toxin-resistant Ca2+ channels, coexist in mouse motor nerve terminals.

Functional assessment of Ca(2+)-current in the mouse motor nerve terminals.

The purpose of this study was to characterize voltage-gated Ca2+ channels on the mouse motor nerve terminals. Mouse diaphragm and triangularis sterni preparations were used for this study in order to assess the functional Ca2+ channels in the transmitter release. The results showed that omega-conotoxin MVIIC (CTx-MVIIC, 0.5-1 microM) but not omega-conotoxin GVIA (1 mM) markedly inhibits not only the nerve-evoked muscle contractions accompanied by a decrease in the amplitude of end plate potentials (epps) in the mouse phrenic-nerve diaphragm but also the Ca(2+)-waveforms in the nerve terminals of triangularis sterni. The inhibitory effects of CTx-MVIIC were considered to be specifically presynaptic rather than myogenic, since none of the electrical properties of muscle fibers including action potentials, resting membrane potentials and the miniature endplate potential, were affected. Moreover, Na(+)- and K(+)-waveforms of the nerve terminals were unaffected by CTx-MVIIC. At a saturating concentration of 3-5 mM, CTx-MVIIC exerted a maximal inhibitory effect by 38% of 3,4-diaminopyridine-prolonged epps area and inhibited only the slow component of Ca(2+)-current, respectively, and the remaining fast component could be inhibited by subsequent addition of cadmium chloride (Cd2+). All of these findings indicate that at least two components (a slow CTx-MVIIC sensitive component and a fast Cd2+ sensitive component) of the mouse motor nerve terminals would cooperate in the induction of the transmitter release from motor nerve endings.

[Causes of maternal death. A 10-year case analysis].

The causes of maternal deaths in our hospital from 1981 to 1989 were analysed. There were 12,819 live births and 6 maternal deaths during this period, a maternal mortality rate of 46.69/per 100,000. The main cause of maternal deaths was acute fatty liver of pregnancy (50%), and next cardiac disease, acute hemorrhagic necrotic pancreatitis and hemorrhage of subarachnoid space (each 16.67%). There was no death due to obstetric hemorrhage, pregnancy induced hypertension syndrome or ectopic pregnancy. It is suggested that needle biopsy of the liver should be done for pregnant women with jaundice of unknown cause. Pregnant women with cardiac disease should be under the care of both obstetrician and internist in collaboration and cesarean section is indicated when the woman's cardiac function remains at grade 3 or 4.

[Prognostic nutritional index in hepatobiliary surgery].

Malnutrition has long been recognized as a potential source of increased morbidity and mortality in patients with various disorders, including those undergoing hepatobiliary surgery. To elucidate the role of malnutrition in postoperative complications in hepatobiliary surgery, the nutritional status of 73 patients was evaluated with the Prognostic Nutritional Index (PNI) devised by Dr. Mullen. PNI was calculated based on the following parameters: albumin, transferrin, triceps skin folds and delayed cutaneous hypersensitivity (DH). DH was performed with four skin antigens: candida, trichophyton, streptokinase/streptodornase and PPD. Based on the results the patients were stratified into two groups, a low-risk group with PNI less than 40 and a high-risk group with PNI greater than or equal to 40. Complications occurred in 10 of 34 patients (29%) in the low-risk group and in 15 of 39 patients (38%) in the high-risk group. There were 2 deaths in the latter and none in the former group, the difference was not statistically significant. We conclude that PNI fails to predict postoperative complications in hepatobiliary surgery patients. Either the formula of PNI, which is derived from gastrointestinal surgery patients, is not applicable to patients undergoing hepatobiliary surgery, or factors other than nutrition are involved in the development of postoperative complications in hepatobiliary surgery.

The role of the subependymal plate in glial tumorigenesis.

We have studied the sequential morphological events of glial tumorigenesis in neonatal dogs, using high titer subgroup C Bratislava-77 Avian Sarcoma Virus, given as 0.01 ml by intraventricular inoculation. The cells of the subependymal plate are those which seem to form the gliomas; cytoplasmic alterations are evident within 24 h after inoculation and microfoci of gliomas, contiguous with the subependymal plate of the lateral ventricles, are visible within 7 days. Independent tumors are present by the 10th post-inoculation day. These studies support the hypothesis of Globus and Kuhlenbeck, which implicates the cells of the subependymal palte in glial tumorigenesis.