Transoral laser microsurgery versus radiotherapy for T2 glottic squamous cell carcinoma: a systematic review of local control outcomes.

BACKGROUND: Systematic reviews comparing treatment of early glottic cancer with transoral surgery or radiotherapy demonstrate similar oncological outcomes. Most studies of 'early-stage' laryngeal cancer include Tis, T1a, T1b and T2 cases. The data are dominated by patients with T1 and Tis tumours, although extrapolating these results and applying them for T2 cases may be inappropriate. No previous systematic reviews have focused on T2 cancers as a separate group. OBJECTIVE OF REVIEW: This review compares local control outcomes for T2 glottic squamous cell carcinoma, treated with transoral microsurgery or external beam radiotherapy. TYPE OF REVIEW: This is a systematic review of case series and comparison studies, focusing on oncological outcomes. SEARCH STRATEGY: Independent searches of MEDLINE, EMBASE and the Cochrane Database were conducted by two authors, using the search terms: laryngeal/glottic/vocal cord combined with carcinoma/cancer/tumour and laser/microsurgery or radiotherapy. Studies of adult patients treated for primary T2N0 glottic squamous cell carcinoma (SCC) with laser surgery or curative radiotherapy were included. EVALUATION METHOD: Full text of studies satisfying the inclusion criteria were reviewed with extraction of local control and survival data and laryngeal preservation rates. The primary endpoint is local control at 5 years. RESULTS: Initial searches identified 3252 studies. Following full-text review of 183 papers, 59 studies met the inclusion criteria, all level IV evidence. A total of 48 studies specified 5-year local control for 1156 patients treated with transoral laser surgery and 3191 patients treated with radiotherapy. Weighted averages of local control at 5 years demonstrated similar results: 75.81% for radiotherapy versus 77.26% for transoral laser surgery. CONCLUSIONS: The results of this review indicate no difference in 5-year local control between radiotherapy and transoral surgery for T2 glottic SCC. The data demonstrated higher rates of local failure for T2b compared with T2a cases, although outcomes were similar between laser excision and radiotherapy for each substage. Further research focusing upon functional outcomes for T2 glottic tumours is imperative to guide decision-making, ideally with subgroup analysis of T2a and T2b cases.

Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.

The early growth response 2 gene (EGR2) is part of a multigene family encoding Cys2His2 type zinc-finger proteins and may play a role in the regulation of cellular proliferation. Egr2, (also known as Krox20) is the mouse orthologue of human EGR2 and was first identified as an immediate-early response gene, encoding a protein that binds DNA in a sequence-specific manner and acts as a transcription factor. Stable expression of Egr2 is specifically associated with the onset of myelination in the peripheral nervous system (PNS). Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage. We hypothesized that Egr2 may be a transcription factor affecting late myelin genes and that human myelinopathies of the PNS may result from mutations in EGR2. In support of this hypothesis, we have identified one recessive and two dominant missense mutations in EGR2 (within regions encoding conserved functional domains) in patients with congenital hypomyelinating neuropathy (CHN) and a family with Charcot-Marie-Tooth type 1 (CMT1).

Condom use problems during anal sex among men who have sex with men (MSM): findings from the Safe in the City study.

Our research aims were to: (1) assess the prevalence of two condom use problems: breakage or slippage and partial use (delayed application or early removal) among men who have sex with men (MSM) seeking services in urban US STD clinics; and (2) examine the association between these condom use problems and participant, partner and partnership characteristics. Analysis was restricted to HIV-negative MSM who reported having anal sex at least once in the preceding 3 months and who completed both the baseline and 3 month follow-up assessments. Two models were fitted using the generalized estimating equations (GEE) approach. A total of 263 MSM (median age=32 years) reported 990 partnerships. Partnerships with no condom use 422 (42.6%) were excluded. Thus, 207 MSM and 568 partnerships were included. Among condom users, 100% use was reported within 454 partnerships (79.9%) and <100% within 114 (20.1%), and 21(3.7%) reported both condom use problems, 25 (4.4%) reported only breakage, 67 (11.8%) reported only partial use, and 455 (80.1%) reported no errors. The breakage or slippage and partial use rates per condom used were 3.4% and 11.2%, respectively. A significantly higher rate of breakage or slippage occurred among non-main partnerships. Characteristics associated with increased odds for condom breakage or slippage were: lower education level (OR=2.78; CI: 1.1-7.5), non-main partner status (OR=4.1; CI: 1.5-11.7), and drunk or high during sex (OR=2.0; CI: 1.1-3.8), and for partial use: lower education level (OR=2.6; CI: 1.0-6.6), perceived partner sexually transmitted infections (STI) risk (OR=2.4; CI: 1.3-4.2), and inconsistent condom use (OR=3.7; CI: 2.0-6.6). A high percentage of MSM partnerships reported no condom use and among condom users, a sizable proportion did not use them consistently or correctly. MSM may benefit from interventions designed to increase proficiency for condom use with a particular focus on the behaviors of inconsistent and partial condom use.

Creating a model to predict time intervals from induction of labor to induction of anesthesia and delivery to coordinate workload.

BACKGROUND: Induction of labor continues to become more common. We analyzed induction of labor and timing of obstetric and anesthesia work to create a model to predict the induction-anesthesia interval and the induction-delivery interval in order to co-ordinate workload to occur when staff are most available. METHODS: Patients who underwent induction of labor at a single medical center were identified and multivariable linear regression was used to model anesthesia and delivery times. Data were collected on date of birth, race/ethnicity, body mass index, gestational age, gravidity, parity, indication for labor induction, number of prior deliveries, time of induction, induction agent, cervical dilation, effacement, and fetal station on admission, date and time of anesthesia administration, date and time of delivery, and delivery type. RESULTS: A total of 1746 women met inclusion criteria. Associations which significantly influenced time from induction of labor to anesthesia and delivery included maternal age (anesthesia P <0.001, delivery P =0.002), body mass index (both P <0.001), prior vaginal delivery (both P <0.001), gestational age (anesthesia P <0.001, delivery P <0.018), simplified Bishop score (both P <0.001), and first induction agent (both P <0.001). Induction of labor of nulliparous women at 02:00 h and parous women at 04:00 or 05:00 h had the highest estimated probability of the mother having her first anesthesia encounter and delivering during optimally staffed hours when our institution's specialty personnel are most available. CONCLUSIONS: Time to obstetric and anesthesia tasks can be estimated to optimize induction of labor start times, and shift anesthesia and delivery workload to hours when staff are most available.

Momentary reductions of attention permit greater processing of irrelevant stimuli.

Momentary reductions of attention can have extremely adverse outcomes, but it remains unclear whether increased distraction from irrelevant stimuli contributes to such outcomes. To investigate this hypothesis, we examined trial-by-trial relationships between brain activity and response time in twenty healthy adults while they performed a cross-modal selective attention task. In each trial, participants identified a relevant visual letter while ignoring an irrelevant auditory letter, which was mapped either to the same response as the visual letter (congruent trials) or to a different response (incongruent trials). As predicted, reductions of attention (i.e., increases of response time) were associated not only with decreased activity in sensory regions that processed the relevant visual stimuli, suggesting a failure to enhance the processing of those stimuli, but also with increased activity in sensory regions that processed the irrelevant auditory stimuli, suggesting a failure to suppress the processing of those stimuli. Reductions of attention were also linked to larger increases of activity in incongruent than in congruent trials in anterior cingulate regions that detect response conflict, suggesting that failing to suppress the sensory processing of the irrelevant auditory stimuli during attentional reductions allowed those stimuli to more readily activate conflicting responses in incongruent trials. These findings indicate that heightened levels of distraction during momentary reductions of attention likely stem, at least in part, from increased processing of irrelevant stimuli.

Condom use in the year following a sexually transmitted disease clinic visit.

Consistent condom use can prevent sexually transmitted infections (STIs), but few studies have measured how the prevalence of consistent use changes over time. We measured the prevalence and correlates of consistent condom use over the course of a year. We did a secondary analysis of data from an HIV prevention trial in three sexually transmitted disease clinics. We assessed condom use during four three-month intervals for subjects and across their partnerships using unconditional logistic regression. Condom use was also assessed for subjects during all three-month intervals combined. The 2125 subjects reported on 5364 three-month intervals including 7249 partnership intervals. Condoms were always used by 24.1% of subjects and 33.2% of partnerships during a three-month interval. Over the year, 82% used condoms at least once but only 5.1% always used condoms. Always use of condom was more likely for subjects who had sex only once (66.5%) compared with >30 times (6.4%); one-time partnerships (64.1%) compared with main partnerships (22.2%); and in new partnerships (44.0%) compared with partnerships that were not new (24.5%). Although consistent condom use may prevent STIs, condoms were rarely used consistently during the year of follow-up.

Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination.

Hereditary demyelinating peripheral neuropathies consist of a heterogeneous group of genetic disorders that includes hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinical and pathologic variation and overlap between these disorders. We have identified five novel mutations in the myelin protein zero (MPZ) gene, encoding the major structural protein (P0) of peripheral nerve myelin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, but rather represent a spectrum of related "myelinopathies" due to an underlying defect in myelination. Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative).

Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice.

It has been suggested that increased collagenase-3 (MMP-13) activity plays a pivotal role in the pathogenesis of osteoarthritis (OA). We have used tetracycline-regulated transcription in conjunction with a cartilage-specific promoter to target a constitutively active human MMP-13 to the hyaline cartilages and joints of transgenic mice. Postnatal expression of this transgene resulted in pathological changes in articular cartilage of the mouse joints similar to those observed in human OA. These included characteristic erosion of the articular cartilage associated with loss of proteoglycan and excessive cleavage of type II collagen by collagenase, as well as synovial hyperplasia. These results demonstrate that excessive MMP-13 activity can result in articular cartilage degradation and joint pathology of the kind observed in OA, suggesting that excessive activity of this proteinase can lead to this disease.

Unilateral cochlear implantation in children with a potentially useable contralateral ear.

Increasingly, children are considered for a unilateral CI, even if the contralateral ear falls outside current audiological guidelines, especially if they are not considered to be reaching their educational potential. The primary aim was to investigate the benefit of unilateral CI in children currently outside UK [National Institute for Health and Care Excellence Technology Appraisal Guidance. 2009. Cochlear implants for children and adults with severe to profound deafness. NICE technology appraisal guidance [TAG166]. Available January 29, 2016 from http://www.nice.org.uk/ta166 ] audiological guidelines in the contralateral ear. The secondary aim was to measure compliance. A retrospective case review with standard demographic data was performed. Forty-seven children were identified as having received a unilateral CI with the contralateral ear falling outside of current UK audiological criteria. These children were allocated to two groups; with hearing between 50 and 70 dB, and 70 and 90 dB at 2 and 4 kHz in the contralateral ear, respectively. Categories of auditory performance (CAP) were assessed. Pre- and post-operative CAP scores demonstrated a statistically significant improvement in auditory perception. We would suggest that assessing candidacy in individual ears and subsequent unilateral CI, has given these children a benefit they may not otherwise have acquired if they only had bilateral hearing aid.

RAS is required for epidermal growth factor-stimulated arachidonic acid release in rat-1 fibroblasts.

Previous studies have provided suggestive evidence for an interaction between ras activation and signalling pathways involved in agonist-stimulated arachidonic acid release in a variety of cell systems. In order to clarify this interaction, we have measured epidermal growth factor (EGF)-stimulated arachidonic acid release in rat-1 fibroblasts transfected with the N-17 dominant negative mutation of ras. Cells transfected with the N-17 ras mutant, display a markedly attenuated arachidonic acid-release response to EGF, compared to sham-transfected and non-transfected cells. In contrast, the response to phorbol myristate acetate (PMA) was not attenuated in the N-17-mutant expressing cells. No differences were detected between sham-transfected and N-17 mutant expressing cells in levels of immunodetectable EGF receptor, cytosolic phospholipase A2 or mitogen-activated protein (MAP) kinase. Attenuation of EGF-stimulated arachidonic acid release in the N-17 mutant expressing cells, was accompanied by a marked diminution in EGF-stimulated tyrosine phosphorylation of MAP kinase. We conclude that the signalling pathway involved in epidermal growth factor-stimulated arachidonic acid release is similar to the signalling pathway for mitogenic responses to epidermal growth factor and requires ras activation, likely followed by a downstream cascade of kinases eventuating in MAP kinase activation.

The neural mechanisms for minimizing cross-modal distraction.

The neural circuitry that increases attention to goal-relevant stimuli when we are in danger of becoming distracted is a matter of active debate. To address several long-standing controversies, we asked participants to identify a letter presented either visually or auditorily while we varied the amount of cross-modal distraction from an irrelevant letter in the opposite modality. Functional magnetic resonance imaging revealed three novel results. First, activity in sensory cortices that processed the relevant letter increased as the irrelevant letter became more distracting, consistent with a selective increase of attention to the relevant letter. In line with this view, an across-subjects correlation indicated that the larger the increase of activity in sensory cortices that processed the relevant letter, the less behavioral interference there was from the irrelevant letter. Second, regions of the dorsolateral prefrontal cortex (DLPFC) involved in orienting attention to the relevant letter also participated in increasing attention to the relevant letter when conflicting stimuli were present. Third, we observed a novel pattern of regional specialization within the cognitive division of the anterior cingulate cortex (ACC) for focusing attention on the relevant letter (dorsal ACC) versus detecting conflict from the irrelevant letter (rostral ACC). These findings indicate novel roles for sensory cortices, the DLPFC, and the ACC in increasing attention to goal-relevant stimulus representations when distracting stimuli conflict with behavioral objectives. Furthermore, they potentially resolve a long-standing controversy regarding the key contribution of the ACC to cognitive control.

Prevalence and correlates of drug use and dependence in the United States. Results from the National Comorbidity Survey.

OBJECTIVES: To analyze nationally representative data on the lifetime and 12-month prevalences of use of and dependence on illegal drugs (marijuana/hashish, cocaine/crack, heroin, hallucinogens), nonmedical prescription psychotropic drugs (sedatives, tranquilizers, stimulants, analgesics), and inhalants; and to examine data on the sociodemographic correlates of use and dependence. METHODS: The data come from the National Comorbidity Survey, a structured diagnostic interview administered to persons aged 15 to 54 years that generates reliable diagnoses according to the definitions and criteria of DSM-III-R. RESULTS: Of the respondents, 51.0% used one of the above drugs at some time in their lives, and 15.4% did so in the past 12 months. These estimates are similar to those obtained in the 1991 National Household Survey of Drug Abuse, where lifetime prevalence was 45.2% and 12-month prevalence was 16.7% among respondents in the age range 15 to 54 years. Of National Comorbidity Survey respondents, 7.5% (14.7% of lifetime users) were dependent at some time in their lives and 1.8% were dependent in the past 12 months. The prevalence estimate for lifetime dependence was reduced to 5.3% when calculated the percentage of respondents in the age range of 28 to 54 years who reported an onset of dependence as of 10 years earlier (ie, when they were 18 to 44 years old) was computed. This is similar to the Epidemiologic Catchment Area Study estimate of 5.1% among respondents in the age range 18 to 44 years, a comparison that matches the two studies on year of assessment, age of risk, and cohort. Males were significantly more likely to report both lifetime and 12-month use and dependence. Use and dependence were found to be more common in cohorts born after World War II than those born before the end of the war. The demographic predictors of lifetime use differed from the predictors of lifetime dependence among users, and these, in turn, differed from the predictors of recent dependence among people with a lifetime history of dependence. CONCLUSIONS: Drug use and dependence are highly prevalent in the general population. The fact that there are differences in the correlates of first use, dependence among users, and persistence of dependence means that future research aimed at pinpointing modifiable risk factors must be based on disaggregated analyses of separate stages of progression.

Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey.

OBJECTIVE: To study patterns of co-occurrence of lifetime DSM-III-R alcohol disorders in a household sample. METHODS: Data came from the National Comorbidity Survey (NCS), a nationally representative household survey. Diagnoses were based on a modified version of the Composite International Diagnostic Interview. RESULTS: Respondents with lifetime NCS/DSM-III-R alcohol abuse or dependence had a high probability of carrying at least 1 other lifetime NCS/DSM-III-R diagnosis. Retrospective reports have suggested that most lifetime co-occurring alcohol disorders begin at a later age than at least 1 other NCS/DSM-III-R disorder. Earlier disorders are generally stronger predictors of alcohol dependence than alcohol abuse and stronger among women than men. Lifetime co-occurrence is positively, but weakly, associated with the persistence of alcohol abuse among men and of alcohol dependence among both men and women. CONCLUSIONS: Caution is needed in interpreting the results due to the fact that diagnoses were made by nonclinicians and results are based on retrospective reports of the age at onset. Within the context of these limitations, though, these results show that alcohol abuse and dependence are often associated with other lifetime DSM-III-R disorders and suggest that, at least in recent cohorts, the alcohol use disorders are usually temporally secondary. Prospective data and data based on clinically confirmed diagnoses are needed to verify these findings.

Comparison of single-strand conformation polymorphism and heteroduplex analysis for detection of mutations in Charcot-Marie-Tooth type 1 disease and related peripheral neuropathies.

To compare the sensitivity of the mutation detection techniques single-strand conformation polymorphism analysis (SSCP) and heteroduplex analysis (HA), we analyzed a cohort of 73 patients with a diagnosis of a demyelinating neuropathy, but without the CMT1A duplication, for mutations in the coding region of the myelin genes PMP22, MPZ and Cx32. In total, 21 samples showed 13 distinct altered migration patterns by one or both methods. Ten altered patterns were detected by both SSCP and HA, two were false negative by HA, and one was false negative by SSCP. Our results suggest that either technique can be useful for mutation detection, but a combination of factors appears to affect the sensitivity of both techniques.

Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype.

BACKGROUND: Mutations in the early growth response 2 (EGR2) gene have recently been found in patients with congenital hypomyelinating neuropathy and Charcot-Marie-Tooth type 1 (CMT1) disease. OBJECTIVE: To determine the frequency of EGR2 mutations in patients with a diagnosis of CMT1, Dejerine-Sottas syndrome (DSS), or unspecified peripheral neuropathies. METHODS: Fifty patients and 70 normal control subjects were screened. RESULTS: A de novo missense mutation (Arg359Trp) in the alpha-helix of the first zinc-finger domain of the EGR2 transcription factor was identified in a patient diagnosed with a clinical phenotype consistent with DSS. This patient had a motor median nerve conduction velocity of 8 m/s. A sural nerve biopsy showed a severe loss of myelinated and unmyelinated fibers, evidence for demyelination, numerous classic onion bulbs, and focally folded myelin sheaths. DSS is a severe, childhood-onset demyelinating peripheral neuropathy initially thought to be inherited as an autosomal recessive trait. However, several dominant heterozygous mutations in the peripheral myelin protein 22 (PMP22) gene and dominant mutations in the peripheral myelin protein zero (MPZ) gene, both in the heterozygous and homozygous state, have been reported in patients with DSS. CONCLUSIONS: Hereditary peripheral neuropathies represent a spectrum of disorders due to underlying defects in myelin structure or formation.

Optimal culture conditions for in vitro antigen-induced proliferation of rat lymph node cells.

Popliteal and inguinal lymph node cells (LNC) from rats immunized with ovalbumin (OA) in Freund's adjuvant, were cultured with OA for 4 days in a variety of serum-supplemented media. Incorporation of [3H]thymidine into [3H]DNA was assessed as an index of antigen-induced lymphoproliferation. Optimal conditions for proliferation were found to comprise culture in flat-bottomed vessels, in the presence of RPMI 1640 medium adjusted to rat osmolality (310 mosmoles/kg) containing 5% v/v fresh syngeneic rat serum plus 4 X 10(-4) M 2-mercaptoethanol.

Myopericarditis as an initial presentation of meningococcemia. Unusual manifestation of infection with serotype W135.

Acute meningococcemia is a dramatic clinical syndrome from infection with the gram-negative diplococcus, Neisseria meningitidis. Although pericarditis may complicate the course of meningococcemia, it is distinctly unusual as a presenting sign. A case of disseminated meningococcemia presenting as acute myopericarditis is reported. The serotype isolated, type W135, was a sporadic cause of N. meningitidis in the Boston area. Although the patient had meningitis, bacteremia, and myopericarditis, his course was uncomplicated with early institution of antibiotic therapy.