Prognostic significance of micropapillary pattern in pure mucinous carcinoma of the breast

Breast carcinoma with micropapillary architecture is associated with aggressive behavior. Similar micropapillary pattern in pure mucinous carcinoma has been noticed and has been shown to convey poor prognosis. In this study 17 cases of pure mucinous carcinoma of the breast seen during a 10-year period have been reviewed, with special reference to micropapillary pattern. Diffuse micropapillary pattern was seen in 6 of 17 cases of mucinous carcinoma of the breast and demonstrated reverse polarity immunostaining pattern with "Epithelial Membrane Antigen." In all cases, the tumor cells showed grade I morphology, and no lymph node metastases were noticed. All the tumors except 1 expressed strong estrogen and progesterone receptor expression, however, all the cases were negative for Her-2/neu expression. In this present study, mucinous carcinomas with micropapillary pattern showed a low nuclear grade, higher incidence of hormone receptor positivity, and lower incidence of Her-2/neu similar to mucinous carcinomas without micropapillary pattern, thus explaining their indolent behavior.     

Incidence of and risk factors for genital human papillomavirus infection in women drug users

A total of 230 women drug users were prospectively studied. At 6-month intervals, interviews, HIV testing, and cervicovaginal lavage sampling for human papillomavirus (HPV) were performed. HPV was detected and typed using a MY09/MY11 polymerase chain reaction system. 230 women without high-risk HPV (types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58. 59, 68, 73 and 82), with or without non-high risk HPV types at baseline, were included in analyses. Incidence rates of and factors associated with HPV infections of all types and high-risk types (types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) were analyzed. Baseline median age was 40 years (range 24-65); 62% of women were Hispanic, 20% black, and 16% white; 54 (24%) were HIV seropositive; 172 (75%) were without detectable HPV; 58 (25%) had only low-risk or untypeable HPV. The incidence rates for any and for high-risk type HPV infection were 9.5/100 and 4.8/100 person-years, respectively. HIV-positive women had a significantly increased hazard rate for any HPV (HRadj: 3.4; 95% CI: 1.4 to 8.0) and for high-risk HPV (HRadj 3.0; 95% CI: 1.4 to 6.6), adjusted for race, sexual behaviors, condom use, and history of other sexually transmitted infections. HIV infection was independently associated with a substantial and significantly increased risk for any and for high-risk genital HPV infection and was the most important risk factor found.     

Clinical experience with low profile fixed wire balloon catheter system for percutaneous transluminal coronary angioplasty

Clinical records of the first 45 consecutive patients (66 lesions) in whom the Probe TM a balloon on the wire, was used for percutaneous transluminal coronary angioplasty have been reviewed. The aim of this analysis was to establish the efficacy and safety of this device. Majority of the lesions taken up were considered severe and difficult to cross. The probe was the 1st catheter used in 51 lesions (77%) and in 15 lesions (23%) it was used after other balloon catheters. In 88% (58/66) of lesions treated the Probe reduced the stenosis to less than 50% of the luminal diameter. Of the 45 patients treated 39 (87%) had a successful result. Of the 19 patients with multiple lesions 74% (14/19) had complete revascularisation and in 16% (3/29) had the most significant vessel dilated. Two patients (3%) required urgent coronary artery bypass surgery for acute occlusions. There was no hospital death. Of 50 probe devices used 5 (10%) malfunctioned: the balloon ruptured (at 5 Bars pressure) in 2 instances, balloon twisted causing "Volvulous" in 1 and balloon failed to deflate in 2 cases. The probe has significant advantages over other balloon systems for treating severe coronary lesions because of its low profile. It is however a delicate catheter system and prone to malfunction if not handled with care. Our results show that it is an excellent system for opening difficult and tight coronary lesions.     

Evidence to Practice for Mental Health Task-Sharing: Understanding Readiness for Change among Accredited Social Health Activists in Sehore District,Madhya Pradesh,India

Involvement of community health workers (CHWs) within task-sharing to bridge the mental health treatment gap has been proven to be efficacious in randomized controlled trials. The impact of mental health programs based on task-sharing paradigm greatly depends on the performance of CHWs which, in-turn, is influenced by their readiness for change. However, there is dearth of literature assessing the role of readiness for change as an important predicator of CHW performance. The aim of this study is to examine the applicability of the readiness for change model and investigate its cultural and contextual nuances among Accredited Social Health Activists (ASHAs), a cadre of CHWs in India, to understand their engagement in mental health task-sharing. We conducted in-depth, semi-structured interviews with a purposive sample of n?=?12 key informants including ASHAs and other healthcare professionals in Sehore district, India. The interview guide consisted of open-ended questions based on the readiness for change factors including ASHAs’ attitudes towards their role in mental health care, perception of capability to implement mental health task-sharing, of support from the public health system, etc. Framework analysis with a combined inductive-deductive approach was employed to code the data and generate themes. Participants endorsed three readiness for change themes relevant to task-sharing among ASHAs including change valence or value ascribed to task-sharing, change-efficacy or the perceived ability to implement task-sharing, and job valence or value ascribed to their regular job role. In addition, they provided insights into the culturally and contextually salient aspects of these factors. Themes of personal empowerment, gaining respect and trust from community, professional duty, relationship with supervisors, and lack of resources availability were majorly highlighted. This is the first study to qualitatively investigate the applicability of the readiness for change model and its culture- and context-specific nuances among a cadre of non-specialist health workers in India. Our findings posit that implementation science models should strongly consider the culture and context within which they are being applied to enhance fit and relevance. Further, our results should be taken into consideration to adapt and validate measurement tools and build readiness for change in this population.

     

Ligament shortening compared to vaginal colpopexy at the time of hysterectomy for pelvic organ prolapse

Introduction and Hypothesis

The performance of a colpopexy at the time of hysterectomy for pelvic organ prolapse is a potential indicator of surgical quality. However, vaginal colpopexy has not been directly compared with the classic technique of ligament shortening and reattachment. We sought to test the null hypothesis that there is no difference in prolapse recurrence between the techniques.

Methods

We performed a retrospective chart review of 330 vaginal hysterectomies performed for prolapse, comparing symptomatic and/or anatomic recurrence rates between patients having a vaginal colpopexy (uterosacral ligament suspension or sacrospinous ligament suspension) and those having ligament shortening and reattachment. Clinically relevant variables significantly associated with recurrence in a univariate analysis were used to create a multivariable logistic regression model to predict recurrence.

Results

With a mean follow-up of 20 months, there was no significant difference between symptomatic and/or anatomic recurrence rates: 19.4 % of patients (41 of 211) having colpopexy vs. 11.8 % of patients (14 of 119) having ligament shortening (p?=?0.07). Baseline prolapse stage was higher in patients having colpopexy (median 3, IQR 2?–?5) than in those having ligament shortening (median 2, IQR 1?–?3; p?≤?0.0001). In the multivariable logistic regression analysis, the procedure performed was not associated with recurrence (OR 1.57, 95 % CI 0.79?–?3.12). A baseline prolapse of 4 cm or greater was associated with recurrence (OR 2.63, 95 % CI 1.32?–?5.22), as was the time since hysterectomy (OR 1.02 per month, 95 % CI 1.01?–?1.04).

Conclusions

When compared with vaginal colpopexy, selective use of the ligament shortening technique at the time of vaginal hysterectomy was associated with similar rates of prolapse recurrence. Preoperative prolapse size was the factor most strongly associated with recurrence.

     

Possible involvement of free radicals in the differential neurobehavioral responses to stress in male and female rats

The effect of restraint stress (RS) on neurobehavioral and brain oxidative stress parameters, and their modulation by antioxidants were evaluated in male and cycling female rats. Exposure to RS suppressed both open arm entries and open arm time in the elevated plus maze and these changes were more marked in males than in females. Assay of brain homogenates revealed that the behavioral suppression was associated with similar differential increases in malondialdehye (MDA) and decreases in glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels in males and females. Pretreatment with alpha-tocopherol (25 and 50 mg/kg) and N-acetylcysteine (100 and 200 mg/kg), attenuated the stress induced alteration of behavioral and oxidative stress markers in a consistent manner in both male and female rats. These findings suggest that males may be more susceptible than females to stress induced neurobehavioral changes and free radicals may exert a regulatory influence in such gender dependent responses to stress.     

APOE and LRPAP1 gene polymorphism and risk of Parkinson’s disease

Epidemiologic findings suggest that lipids and alteration in lipid metabolizing protein/gene may contribute to the development of neurodegenerative disorders. The aim of the current study was to determine the serum lipid levels and genetic variation in two lipid metabolizing genes, low-density lipoprotein receptor-related protein-associated protein (LRPAP1) and apolipoprotein E (APOE) gene in Parkinson’s disease (PD). Based on well-defined inclusion and exclusion criteria, this study included 70 patients with PD and 100 age-matched controls. LRPAP1 and APOE gene polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism, respectively. Fasting serum lipid levels were determined using an autoanalyser. The logistic regression analysis showed that high levels of serum cholesterol [odds ratio (OR) = 1.101, 95 % confidence interval (CI_95%) = 1.067–1.135], LRPAP1 I allelic variant alone (OR = 2.766, CI_95% = 1.137–6.752) and in combination with APOE ε4 allelic variant (OR = 4.187, CI_95% = 1.621–10.82) were significantly associated with increase in PD risk. Apart from that, the high levels of LDL cholesterol appears to have a protective role (OR = 0.931, CI_95% = 0.897–0.966) against PD. The LRPAP1 I allelic variant may be considered a candidate gene for PD, predominantly in patients having the APOE ε4 allelic variant.     

Inhibition of thalamic excitability by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol: a selective role for δ-GABAA receptors

The sedative and hypnotic agent 4,5,6,7‐tetrahydroisoxazolo[4,5‐c]pyridine‐3‐ol (THIP) is a GABA_A receptor (GABA_AR) agonist that preferentially activates δ‐subunit‐containing GABA_ARs (δ‐GABA_ARs). To clarify the role of δ‐GABA_ARs in mediating the sedative actions of THIP, we utilized mice lacking the α₁‐ or δ‐subunit in a combined electrophysiological and behavioural analysis. Whole‐cell patch‐clamp recordings were obtained from ventrobasal thalamic nucleus (VB) neurones at a holding potential of ?60 mV. Application of bicuculline to wild‐type (WT) VB neurones revealed a GABA_AR‐mediated tonic current of 92 ± 19 pA, which was greatly reduced (13 ± 5 pA) for VB neurones of δ^0/0 mice. Deletion of the δ‐ but not the α₁‐subunit dramatically reduced the THIP (1 μm )‐induced inward current in these neurones (WT, ?309 ± 23 pA; δ^0/0, ?18 ± 3 pA; α₁^0/0, ?377 ± 45 pA). Furthermore, THIP selectively decreased the excitability of WT and α₁^0/0 but not δ^0/0 VB neurones. THIP did not affect the properties of miniature inhibitory post‐synaptic currents in any of the genotypes. No differences in rotarod performance and locomotor activity were observed across the three genotypes. In WT mice, performance of these behaviours was impaired by THIP in a dose‐dependent manner. The effect of THIP on rotarod performance was blunted for δ^0/0 but not α₁^0/0 mice. We previously reported that deletion of the α₁‐subunit abolished synaptic GABA_A responses of VB neurones. Therefore, collectively, these findings suggest that extrasynaptic δ‐GABA_ARs vs. synaptic α₁‐subunit‐containing GABA_ARs of thalamocortical neurones represent an important molecular target underpinning the sedative actions of THIP.     

The St. Jude experience

This paper covers our experience with the use of the St. Jude prosthetic heart valve from November 1979 through August 1983 in 91 patients operated on for aortic and mitral valve replacement. Nonfatal complications included hemorrhagic sequela due to anticoagulation, with an annual rate of 1 percent (1.4 percent per 100 patient years), thromboembolism with an annual rate of 0.8 percent (0.87 percent per 100 patient years), sternal infection 1 percent, operative cardiovascular accident 1 percent, and pericardial tamponade 1 percent.Operative mortality was 1 percent, early mortality (within 30 days) was 3 percent, and late mortality was 3 percent, with a total overall mortality of 7 percent. Excluding two patients who died from noncardiac causes, the overall mortality was 5 percent. The mortality rate per year was 2 percent. The survival rate 3.8 years postoperatively was 89 percent for mitral valve replacement patients and 93 percent for aortic valve replacement patients, for an overall 38 year survival rate of 92 percent. All patients were anticoagulated with warfarin. There were no instances of valve failure, replacement, or serious hemolysis. Eighty-three percent were active or working with a New York heart functional class I.In our experience, the complication rate with the St. Jude valve is as low or lower than that for any other mechanical prosthetic cardiac valve available in the world today.