Oral progestin induces rapid, reversible suppression of ovarian activity in the cat

The influence of oral progestin (altrenogest; ALT) on cat ovarian activity was studied using non-invasive fecal steroid monitoring. Queens were assigned to various ALT dosages: (1) 0 mg/kg (control; n = 5 cats); (2) 0.044 mg/kg (LOW; n = 5); (3) 0.088 mg/kg (MID; n = 6); or (4) 0.352 mg/kg (HIGH; n = 6). Fecal estrogen and progestagen concentrations were quantified using enzyme immunoassays for 60 days before, 38 days during and 60 days after ALT treatment. Initiation of follicular activity was suppressed in all cats during progestin treatment, whereas controls continued to cycle normally. Females (n = 6) with elevated fecal estrogens at treatment onset completed a normal follicular phase before returning to baseline and remained suppressed until treatment withdrawal. All cats receiving oral progestin re-initiated follicular activity after treatment, although MID cats experienced the most synchronized return (within 10-16 days). Mean baseline fecal estrogens and progestagens were higher (P < 0.05) after treatment in HIGH, but not in LOW or MID cats compared to pre-treatment values. The results demonstrate that: (1) oral progestin rapidly suppresses initiation of follicular activity in the cat, but does not influence a follicular phase that exists before treatment initiation; and (2) queens return to normal follicular activity after progestin withdrawal. This study provides foundational information for research aimed at using progestin priming to improve ovarian response in felids scheduled for ovulation induction and assisted breeding.     

Characterization of the estrous cycle and assessment of reproductive status in Matschie's tree kangaroo (Dendrolagus matschiei) with fecal progestin profiles

The population of Matschie’s tree kangaroos (Dendrolagus matschiei) held in North American zoos has declined to critically low numbers, and information on the reproductive biology of tree kangaroos is limited. The objectives of this study were to (1) characterize the temporal features of the estrous cycle through the measurement of fecal progesterone metabolite (i.e., progestin) concentrations and (2) determine the reproductive status of female tree kangaroos in the captive population of North America through the identification of estrous cyclicity. Fecal pellets and observations of estrous behaviors were collected from 16 captive female tree kangaroos. Fecal pellets were sampled and extracted with methanol, and progestin concentrations were quantified using a radioimmunoassay (RIA) for progesterone and its metabolites. A progestin profile was obtained for each female by plotting fecal progestin concentrations for every third day over a 120-day period. Profiles for 12 of 16 females showed evidence of estrous cyclicity (P < 0.01). The mean length of the estrous cycle was estimated at 58.9 ± 2.4 days (n = 11). Progestin concentrations were low during the first 15-20 days of the luteal phase and remained elevated above baseline only during the last 30.2 ± 3.2 days of the luteal phase, which averaged 46.6 ± 2.5 days in duration. The progestin profile observed in the estrous cycle of Matschie’s tree kangaroos in this study is very similar to that seen in the non-pregnant cycle of several other species in the family Macropodidae.     

Fecal endocrine profiles and ejaculate traits in black-footed cats (Felis nigripes) and sand cats (Felis margarita)

Information regarding the reproductive biology of black-footed cats (BFC) and sand cats (SC) is extremely limited. Our objectives were to: (1) validate fecal hormone analysis (estrogens, E; progestagens, P; androgens, T) for noninvasive monitoring of gonadal activity; (2) characterize estrous cyclicity, ovulatory mechanisms, gestation, and seasonality; and (3) evaluate male reproductive activity via fecal androgen metabolites and ejaculate traits. In both species, the estrous cycle averaged 11-12 days. In BFC (n = 8), estrus lasted 2.2 ± 0.2 days with peak concentrations of E (2962.8 ± 166.3 ng/g feces) increasing 2.7-fold above basal concentrations. In SC (n = 6), peak concentrations of E (1669.9 ± 83.5 ng/g feces) during estrus (2.9 ± 0.2 days) were 4.0-fold higher than basal concentrations. Nonpregnant luteal phases occurred in 26.5% (26 of 98) of BFC estrous cycles, but were not observed in SC (0 of 109 cycles). In both species, P concentrations during pregnancy were elevated (32.3 ± 3.0 μg/g feces BFC; 8.5 ± 0.7 μg/g feces SC) ∼10-fold above basal concentrations. Fecal T concentrations in males averaged 3.1 ± 0.1 μg/g feces in BFC and 2.3 ± 0.0 μg/g feces in SC. Following electroejaculation, 200 to 250 μl of semen was collected containing 29.9 (BFC) to 36.5 (SC) × 10⁶ spermatozoa with 40.4 (SC) to 46.8 (BFC)% normal morphology. All females exhibited estrous cycles during the study and spermatozoa were recovered from all males on every collection attempt, suggesting poor reproductive success in these species may not be due to physiological infertility.     

Pattern of faecal 20-oxopregnane and oestrogen concentrations during pregnancy in wild plains zebra mares

Regulative endocrine mechanisms influence the reproductive behaviour and success of mammals, but they have been studied predominantly in domestic and captive animals. The study aims at describing the pattern of faecal 20-oxopregnane and oestrogen concentrations during pregnancy in wild plains zebra Equus quagga chapmani. Data were collected during wet and dry seasons 2007-2009. Enzyme Immunoassays were used to determine 20-oxopregnane and oestrogen concentrations in faecal samples (n = 74) collected from individual mares (n = 32) whose dates of foaling were known through long-term monitoring. Hormonal profiles were described with a General Additive Model (GAM: Hormone ∼ Days to Foaling). Faecal 20-oxopregnanes have a complex cycle during pregnancy (GAM, n = 70, R² = 0.616, p < 0.001). From −250 days to foaling, faecal 20-oxopregnane concentrations were above the baseline levels found in non-pregnant mares, peaking in the last 50 days. Faecal oestrogen levels showed a clear peak in mid-pregnancy (GAM, n = 62, R² = 0.539, p < 0.001). The sex of the foetus and season had no detectable effect on hormone concentrations during pregnancy. High levels (>200 ng/g DW) of faecal 20-oxopregnanes associated with high (>160 ng/g DW) faecal oestrogen levels indicate mid-pregnancy in c.90% of cases (16/17). High faecal 20-oxopregnanes (>200 ng/g DW) and low faecal oestrogen levels (<160 ng/g DW) indicate late pregnancy, again in c.90% of cases. Two faecal samples would allow the stage of pregnancy to be determined with confidence.     

Carbohydrate counting with an automated bolus calculator helps to improve glycaemic control in children with type 1 diabetes using multiple daily injection therapy: An 18-month observational study

Aims

This study aimed to investigate the effect of carbohydrate counting (carbC), with or without an automated bolus calculator (ABC), in children with type 1 diabetes treated with multiple daily insulin injections.

Methods

We evaluated 85 children, aged 9–16 years, with type 1 diabetes, divided into four groups: controls (n = 23), experienced carbC (n = 19), experienced carbC + ABC (n = 18) and non-experienced carbC + ABC (n = 25). Glycated haemoglobin (HbA1c), insulin use, and glycaemic variability – evaluated as high blood glucose index (HBGI) and low blood glucose index (LBGI) – were assessed at baseline and after 6 and 18 months.

Results

At baseline, age, disease duration, BMI, HbA1c, insulin use, and HBGI (but not LBGI; p = 0.020) were similar for all groups. After 6 months, HbA1c improved from baseline, although not significantly – patients using ABC (according to manufacturer's recommendations) HbA1c 7.14 ± 0.41% at 6 months vs. 7.35 ± 0.53% at baseline, (p = 0.136) or without carbC experience HbA1c 7.61 ± 0.62% vs. 7.95 ± 0.99% (p = 0.063). Patients using ABC had a better HBGI (p = 0.001) and a slightly worse LBGI (p = 0.010) than those not using ABC. ABC settings were then personalised. At 18 months, further improvements in HbA1c were seen in children using the ABC, especially in the non-experienced carbC group (−0.42% from baseline; p = 0.018).

Conclusions

CarbC helped to improve glycaemic control in children with type 1 diabetes using multiple daily injections. ABC use led to greater improvements in HbA1c, HBGI and LBGI compared with patients using only carbC, regardless of experience with carbC.     

Effectiveness of exercise with or without thermal therapy for community-dwelling elderly Japanese women with non-specific knee pain: A randomized controlled trial

Knee pain is a common health problem in the elderly population, for which non-invasive treatments are recommended as a first line treatment in the management of knee pain. A randomized controlled trial was conducted to determine the effects of exercise with or without thermal therapy in community-dwelling elderly women with chronic knee pain. Women over 75 years of age with knee pain (n = 150) were randomly assigned into four groups; exercise (Ex) and heat/steam generating sheet (HSGS) (n = 38), Ex (n = 37), HSGS (n = 38), or health education (HE) (n = 37). The Ex group attended a 60-min comprehensive training program twice a week for 3-months. The HSGS group placed two sheets on the knee for five hours per day. Functional fitness, visual analog scale (VAS), and Japanese knee osteoarthritis measure (JKOM) were assessed at baseline and post-intervention. The results showed VAS improvements in the Ex + HSGS and HSGS groups. Total JKOM score, muscle strength, and functional mobility significantly improved in the Ex + HSGS group compared with the HE group. The odds ratio (OR) for VAS and functional mobility improvement was more than eight times as great in the Ex + HSGS group (OR = 8.60, 95% confidence interval (CI) = 2.82–32.73) compared with the education group. Ex or HSGS alone were insufficient in enhancing functional fitness or improving pain and quality of life. The combined effects of both Ex and heat therapy seems to have an added benefit of decreasing pain, improving physical function and increasing quality of life. Trial Registration Number: JMA-IIA00110.     

The effects of multidimensional exercise on functional decline, urinary incontinence, and fear of falling in community-dwelling elderly women with multiple symptoms of geriatric syndrome: A randomized controlled and 6-month follow-up trial

This study assessed the effects of multidimensional exercises on functional decline, urinary incontinence, and fear of falling in community-dwelling Japanese elderly women with multiple symptoms of geriatric syndrome (MSGS). Sixty-one participants were randomly assigned either to an intervention (n = 31) or to a control group (n = 30). For 3-month period, the intervention group received multidimensional exercise, twice a week, aiming to increase the muscle strength, walking ability, and pelvic floor muscle (PFM). Outcome variables were measured at baseline, and after intervention and follow-up. The functional decline of the intervention group decreased from 50.0% at baseline to 16.7% after intervention and follow-up (Q = 16.67, p < 0.001). For urinary incontinence, the intervention group decreased from 66.7% at baseline to 23.3% after intervention and 40.0% at follow-up (Q = 13.56, p = 0.001), whereas the control group showed no improvement. Intervention group showed greater and significant decrease in the score of MSGS compared to control group (F = 12.66, p = 0.001). Within the subjects that showed improvement to normal status of MSGS, a significantly higher proportion demonstrated increased maximum walking speed at follow-up (Q = 6.50, p = 0.039). These results suggest that multidimensional exercise is an effective strategy for reducing geriatric syndromes in elderly population. An increase in walking ability may contribute to the improvement of MSGS.     

Soins palliatifs chez les patients en insuffisance cardiaque terminale

Purpose

Heart failure is a common disease and its progression to end-stage heart failure is responsible of high mortality. The aim of this retrospective study was to assess the access to integrated palliative care to the usual management, 6 months prior to their death, and especially during the last hospitalization.

Patients and methods

A retrospective study was performed in patients who died of heart failure in 2009 in two hospitals. The analysis was performed on 20 cases of each institution. The records of consecutive patients were included in an anti-chronological order from 31st December 2009.

Results

For their last hospitalization, 37 patients (93%) were hospitalized in emergency. Within 3 days prior to death, the most frequent symptoms were dyspnea (n = 33, 82%), and pain (n = 30, 75%). Therapeutic most frequently used were oxygen (n = 31, 77%) and analgesics (n = 30, 75%). No patient was seen by a psychologist. The decision to limit treatment for comfort care was reported for 24 patients (60%) and the median of the average time between the decision and death was 2 days (Q1–Q3, 1–5 days).

Conclusion

Patients with terminal heart failure have many symptoms often requiring multidisciplinary care. This type of study relating practices shows that there is still a lot to do to integrate palliative care in the usual management of patients with heart failure.     

Submicroscopic infections among children with adequate clinical and parasitological response (ACPR)

The aim of the study was to re-assess the treatment outcomes of Gabonese children, treated with sulfadoxine-pyrimethamine (SP) and artesunate-mefloquine (AM) and categorized by microscopy as adequate clinical and parasitological response (ACPR), using polymerase chain reaction (PCR). Dried blood spots were collected at day 0 and day 28 and stevor gene amplification was performed to detect Plasmodium falciparum infections. Plasmodial DNA was found in 27.5% (n = 19/69) of the isolates collected at day 28; this proportion was 34.3% (n = 12/35) in the SP group and 20.6% (n = 7/34) in the AM group. This study underlines the need of an accurate and more appropriate technique such as PCR to evaluate antimalarial drug efficacy during clinical trials.     

Neuropeptide Y reduces acetylcholine release and vagal bradycardia via a Y2 receptor-mediated, protein kinase C-dependent pathway

The co-transmitter neuropeptide Y (NPY), released during prolonged cardiac sympathetic nerve stimulation, can attenuate vagal-induced bradycardia. We tested the hypothesis that NPY reduces acetylcholine release, at similar concentrations to which it attenuates vagal bradycardia, via pre-synaptic Y2 receptors modulating a pathway that is dependent on protein kinase A (PKA) or protein kinase C (PKC). The Y2 receptor was immunofluorescently colocalized with choline acetyl-transferase containing neurons at the guinea pig sinoatrial node. The effect of NPY in the presence of various enzyme inhibitors was then tested on the heart rate response to vagal nerve stimulation in isolated guinea pig sinoatrial node/right vagal nerve preparations and also on ³H-acetylcholine release from right atria during field stimulation. NPY reduced the heart rate response to vagal stimulation at 1, 3 and 5 Hz (significant at 100 nM and reaching a plateau at 250 nM NPY, p < 0.05, n = 6) but not to the stable analogue of acetylcholine, carbamylcholine (30, 60 or 90 nM, n = 6) which produced similar degrees of bradycardia. The reduced vagal response was abolished by the Y2 receptor antagonist BIIE 0246 (1 μM, n = 4). NPY also significantly attenuated the release of ³H-acetylcholine during field stimulation (250 nM, n = 6). The effect of NPY (250 nM) on vagal bradycardia was abolished by the PKC inhibitors calphostin C (0.1 μM, n = 5) and chelerythrine chloride (25 μM, n = 6) but not the PKA inhibitor H89 (0.5 μM, n = 6). Conversely, the PKC activator Phorbol-12-myristate-13-acetate (0.5 μM, n = 7) mimicked the effect of NPY and significantly reduced ³H-acetylcholine release during field stimulation. These results show that NPY attenuates vagal bradycardia via a pre-synaptic decrease in acetylcholine release that appears to be mediated by a Y2 receptor pathway involving modulation of PKC.     

Complications of transseptal catheterization for different cardiac procedures

Background

Cardiac tamponade is the main complication of transseptal catheterization that is necessary for a variety of cardiac interventions and electrophysiology procedures.

Methods

A retrospective assessment of all consecutive procedures that required transseptal puncture by the same experienced operator (with already > 100 previous trans-septal procedures) during the period 2000–2012 was performed. We recorded any puncture-related complications of pericardial effusion and cardiac tamponade (acute or delayed).

Results

A total of 393 procedures were retrieved: Group 1 [ablation of left-sided accessory pathways (n = 77), atrioventricular nodal reentry tachycardia-left septal access (AVNRT) (n = 12), and Inoue balloon mitral valvuloplasty (n = 27)], and Group 2 [atrial fibrillation (AF) ablation procedures: ostial pulmonary vein isolation (PVI) (including RF (n = 76) and cryo-balloon (n = 30)), circumferential PVI (n = 51), and combined procedures (n = 120)]. In total, 5 cases of tamponade were recorded, four of them were acute and one delayed (occurring 1 h after the procedure). All tamponade cases occurred only during or after AF ablation procedures (cryo-balloon ablation = 1, circumferential PVI = 2, and combined procedures = 2). In one case emergency atrial repair following median sternotomy was necessary, and in another a surgical drainage through a limited thoracotomy was performed. The other three cases were treated with pericardiocentesis and drainage for 12 h. No patient was on uninterrupted oral anticoagulation during the procedure.

Conclusions

AF ablation is associated with a higher incidence of tamponade compared to other procedures that require transseptal access. Such procedures should only be performed in hospitals with access to emergency surgical support.     

Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation

Atrial dilatation is an independent risk factor for thromboembolism in patients with and without atrial fibrillation (AF). In many patients, atrial dilatation goes along with depressed contractile function of the dilated atria. While some mechanisms causing atrial contractile dysfunction in fibrillating atria have been addressed previously, the cellular and molecular mechanisms of atrial contractile remodeling in dilated atria are unknown. This study characterized in vivo atrial contractile function in a goat model of atrial dilatation and compared it to a goat model of AF. Differences in the underlying mechanisms were elucidated by studying contractile function, electrophysiology and sarcoplasmic reticulum (SR) Ca²⁺ load in atrial muscle bundles and by analyzing expression and phosphorylation levels of key Ca²⁺-handling proteins, myofilaments and the expression and activity of their upstream regulators. In 7 chronically instrumented, awake goats atrial contractile dysfunction was monitored during 3 weeks of progressive atrial dilatation after AV-node ablation (AV block goats (AVB)). In open chest experiments atrial work index (AWI) and refractoriness were measured (10 goats with AVB, 5 goats with ten days of AF induced by repetitive atrial burst pacing (AF), 10 controls). Isometric force of contraction (FC), transmembrane action potentials (APs) and rapid cooling contractures (RCC, a measure of SR Ca²⁺ load) were studied in right atrial muscle bundles. Total and phosphorylated Ca²⁺-handling and myofilament protein levels were quantified by Western blot. In AVB goats, atrial size increased by 18% (from 26.6 ± 4.4 to 31.6 ± 5.5 mm, n = 7 p < 0.01) while atrial fractional shortening (AFS) decreased (from 18.4 ± 1.7 to 12.8 ± 4.0% at 400 ms, n = 7, p < 0.01). In open chest experiments, AWI was reduced in AVB and in AF goats compared to controls (at 400 ms: 8.4 ±0.9, n = 7, and 3.2 ± 1.8, n = 5, vs 18.9 ± 5.3 mm×mmHg, n = 7, respectively, p < 0.05 vs control). FC of isolated right atrial muscle bundles was reduced in AVB (n = 8) and in AF (n = 5) goats compared to controls (n = 9) (at 2 Hz: 2.3 ± 0.5 and 0.7 ± 0.2 vs 5.5 ± 1.0 mN/mm², respectively, p < 0.05). APs were shorter in AF, but unchanged in AVB goats. RCCs were reduced in AVB and AF versus control (AVB, 3.4 ± 0.5 and AF, 4.1 ± 1.4 vs 12.2 ± 3.2 mN/mm², p < 0.05). Protein levels of protein kinase A (PKA) phosphorylated phospholamban (PLB) were reduced in AVB (n = 8) and AF (n = 8) vs control (n = 7) by 37.9 ± 12.4% and 29.7 ± 10.1%, respectively (p < 0.01), whereas calmodulin-dependent protein kinase II (CaMKII) phosphorylated ryanodine channels (RyR2) were increased by 166 ± 55% in AVB (n = 8) and by 146 ± 56% in AF (n = 8) goats (p < 0.01). PKA-phosphorylated myosin-binding protein-C and troponin-I were reduced exclusively in AVB goat atria (by 75 ± 10% and 55 ± 15%, respectively, n = 8, p < 0.05). Atrial dilatation developing during slow ventricular rhythm after complete AV block as well as AF-induced remodeling are associated with atrial contractile dysfunction. Both AVB and AF goat atria show decreased SR Ca²⁺ load, likely caused by PLB dephosphorylation and RYR2 hyperphosphorylation. While shorter APs further compromise contractility in AF goat atria, reduced myofilament phosphorylation may impair contractility in AVB goat atria. Thus, atrial hypocontractility appears to have distinct molecular contributors in different types of atrial remodeling.     

Algisyl-LVR™ with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart

Background

Left ventricular (LV) wall stress reduction is a cornerstone in treating heart failure. Large animal models and computer simulations indicate that adding non-contractile material to the damaged LV wall can potentially reduce myofiber stress. We sought to quantify the effects of a novel implantable hydrogel (Algisyl-LVR™) treatment in combination with coronary artery bypass grafting (i.e. Algisyl-LVR™ + CABG) on both LV function and wall stress in heart failure patients.

Methods and results

Magnetic resonance images obtained before treatment (n = 3), and at 3 months (n = 3) and 6 months (n = 2) afterwards were used to reconstruct the LV geometry. Cardiac function was quantified using end-diastolic volume (EDV), end-systolic volume (ESV), regional wall thickness, sphericity index and regional myofiber stress computed using validated mathematical modeling. The LV became more ellipsoidal after treatment, and both EDV and ESV decreased substantially 3 months after treatment in all patients; EDV decreased from 264 ± 91 ml to 146 ± 86 ml and ESV decreased from 184 ± 85 ml to 86 ± 76 ml. Ejection fraction increased from 32 ± 8% to 47 ± 18% during that period. Volumetric-averaged wall thickness increased in all patients, from 1.06 ± 0.21 cm (baseline) to 1.3 ± 0.26 cm (3 months). These changes were accompanied by about a 35% decrease in myofiber stress at end-of-diastole and at end-of-systole. Post-treatment myofiber stress became more uniform in the LV.

Conclusions

These results support the novel concept that Algisyl-LVR™ + CABG treatment leads to decreased myofiber stress, restored LV geometry and improved function.     

Do Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD) progress differently?

Our study aimed to compare cognitive status and declines in AD with/without small vessel disease (SVD) and SIVD at baseline and 1-year follow-up. Patients with Alzheimer's disease without small vessel disease (AD(−)SVD) (n = 148), Alzheimer's disease with small vessel disease (AD(+)SVD) (n = 94) and SIVD (n = 60) were recruited from database of multiple centers in Korea. Basic demographics and detailed neuropsychological results were compared. AD, regardless of SVD, showed worse memory and better executive function than SIVD at baseline. Mini-Mental State Examination scores and visual memory function declined more in AD than those in SIVD whereas Barthel Activities of Daily Living (B-ADL) scores declined more in SIVD. AD showed different patterns of cognitive impairment compared with SIVD. After 1 year, AD showed more rapid cognitive decline in some domains. Further investigations with longer follow-up duration may be needed to confirm the cumulative effects of SVD in AD and different patterns of decline between AD and SIVD.     

Non-allele specific antibody responses to genetically distinct variant forms of Plasmodium vivax Duffy binding protein (PvDBP-II) in Iranians exposed to seasonal malaria transmission

Duffy binding protein (DBP) is a leading vaccine candidate of Plasmodium vivax. The binding domain of DBP (DBP-II) is polymorphic, that may be a major challenge for development of a broadly effective vaccine against vivax malaria. The present investigation was undertaken to explore whether the sequence diversity of DBP-II causes variation in naturally acquired anti-DBP-II antibodies. In this study, the five genetically distinct variants were expressed, and anti-DBP-II responses were measured in P. vivax-infected individuals (n = 202). Finally, by performing immune-depletion ELISA experiments, antibody responses to the conserved sites of all allelic forms were evaluated using the corresponding and non-corresponding patients’ sera (n = 20). In this study, natural P. vivax infection produces IgG against all five examined variant forms of PvDBP-II with no statistically difference. Sequence analysis in the 20 selected samples (for antibody depletion experiment) showed eight distinct haplotypes, DBPI (n = 1), DBPIII (n = 3), DBPIV (n = 1), DBPV (n = 1), DBPVI (n = 5), DBPIX (n = 6), DBPX (n = 1), and DBP XI (n = 2). The results showed the presence of the cross-reactive antibody responses to heterologous variants of PvDBP-II in Iranian individuals who were infected with distinct allelic forms of the PvDBP-II. Therefore, it is proposed that the majority of antibodies recognized sharing B-cell epitopes and this could overcome the PvDBP-II variation as a one of the biggest challenges of PvDBP-II-based vaccine development.     

Sclérites,aspects cliniques, étiologiques et thérapeutiques : à propos d’une série de 32 observations

Purpose

To report on the various clinical presentations, etiological diagnosis, prognosis and treatment of patients with scleritis evaluated at a tertiary care eye center.

Methods

Retrospective, monocentric study on a series of 32 patients in a tertiary center.

Results

The mean age of included patients with scleritis was 46.8 years (range, 22 to 77 years). Nineteen patients were women and 13 were men. Twenty-six patients (81%) had anterior scleritis (15 nodular, 8 diffuse and 3 necrotizing), six (19%) had posterior scleritis. Unilateral inflammation was present in 24 patients (75%). Twelve out of the 32 patients (37.5%) had an underlying systemic disease: granulomatosis with polyangiitis (n = 3), Behçet's disease (n = 2), unspecified inflammatory arthritis (n = 2), psoriatic arthritis (n = 1), ankylosing spondylitis (n = 1), sarcoidosis (n = 1), Cogan's syndrome (n = 1) and ulcerative colitis (n = 1). Six patients (18.8%) were suspected of having infectious disease with herpes virus: clinical context and positive treatment response with oral valacyclovir. Systemic agents and topical agents were required in 28 patients (87.5%). The first line therapy was mainly oral non-steroidal anti-inflammatory drugs in 15 patients (47%) and oral corticosteroids in 8 (25%). Immunosuppressive drugs were required in 6 patients. The mean follow-up was 16.3 months. Six patients (19%) had a decrease in visual acuity.

Conclusion

The number of systemic disease in our series is similar to the main series in the literature. Treatment with valaciclovir might be effective in patients with suspected herpes simplex scleritis.     

Up-regulation of A 2B adenosine receptor in A 2A adenosine receptor knockout mouse coronary artery

In this study, we looked into possible compensatory changes of other adenosine receptors (ARs) in A_2A genetic knockout mice (A2AKO) as well as the functional role of nitric oxide (NO) in A_2A AR-mediated vasodilation. Gene expression of ARs from coronary arteries of A_2A AR wild type mice (A2AWT) and A2AKO was studied using real-time PCR. Functional studies were carried out in isolated heart and isolated coronary artery preparations. A_2B AR was found to be 4.5 fold higher in A2AKO than in A2AWT, while A_2A AR expression was absent in A2AKO. There was no difference in A₁ and A₃ ARs between WT and KO animals. The concentration-relaxation curve for adenosine-5′-N-ethylcarboxamide (NECA, non-selective AR agonist) in isolated coronary arterial rings in A2AKO was shifted to the left when compared to A2AWT. The concentration-response curve for A_2B selective agonist (BAY 60-6583) was also shifted to the left in A2AKO hearts. L-NAME, a non-specific NO synthase inhibitor, did not affect baseline coronary flow (CF) until the concentration reached 10 µM in A2AWT (76.32 ± 11.35% from baseline, n = 5). In A2AKO, the CF decreased significantly by L-NAME only at a higher concentration (100 µM, 93.32 ± 5.8% from baseline, n = 5). L-NMA (1 µM, n = 4), another non-specific NO synthase inhibitor, also demonstrated similar results in decreasing CF (59.66 ± 3.23% from baseline in A2AWT, while 81.76 ± 8.91% in A2AKO). It was further demonstrated that the increase in CF by 100 µM NECA was significantly blunted with 10 µM L-NAME (377.08 ± 25.23% to 305.41 ± 30.73%, n = 9) in A2AWT but not in A2AKO (153.66 ± 22.7% to 143.88 ± 36.65%, n = 5). Similar results were also found using 50 nM of CGS-21680 instead of NECA in A2AWT (346 ± 22.85 to 277 ± 31.39, n = 6). No change in CF to CGS-21680 was noted in A_2AAKO. Our data demonstrate, for the first time, that coronary A_2B AR was up-regulated in mice deficient in A_2A AR. We also provide direct evidence supporting a role for NO in A_2A AR-mediated coronary vasodilation. The data further support the role for A_2A AR in the regulation of basal coronary tone through the release of NO.     

Durée de traitement des tuberculoses extrapulmonaires : six mois ou plus ? Analyse de la base de données TB-INFO

Purpose

The recommended duration of pulmonary tuberculosis therapy is 6 months. For extrapulmonary tuberculosis, treatment duration depends on tuberculosis involvement and HIV status. The objective of this study was to describe the main characteristics of a cohort of extrapulmonary tuberculosis patients, to compare patients with a 6-month treatment to those with more than a 6-month treatment, and to analyze the compliance of medical centres with recommended duration of treatment.

Methods

A retrospective cohort study of 210 patients with extrapulmonary tuberculosis was carried from January 1999 to December 2006 in two hospitals in the north-east of Paris. These patients were treated with quadruple therapy during two months, followed by dual therapy during 4 months (n = 77) or more (n = 66). The characteristics of each group were compared by uni- and multivariate analysis. The primary endpoint was the rate of relapse or treatment failure at 24-month follow-up after treatment completion.

Results

No relapse was observed after 24 months of follow-up after the end of treatment in the two groups. In univariate analysis, patients with lymph node tuberculosis were more often treated for 6 months than at other sites of tuberculosis (respectively 61% versus 40.9%; P = 0.02); the decision of treatment duration was related to medical practices (79.2% treated 6 months in one hospital versus 20.7% in the other, P < 0.001); patients living in private residence were more often treated during 6 months than patients living in residence (24.2% versus 10.3%, P = 0.042). In multivariate analysis, only hospital (P = 0.046), sex (P = 0.007) and private residence were significantly different in each group.

Conclusion

A period of 6 months seems to be sufficient to treat extrapulmonary tuberculosis (except for neuromeningeal localization).     

Cardiac surgery in nonagenarians: pushing the boundary one further decade

With increasing age of the general population, the necessity for cardiac surgery in the collective of patients aged 90 and older has been increasing. To aid in the choice of adequate therapy we investigated our experience for the group of nonagenarians undergoing surgical interventions. From 6/2000 to 9/2007, 17 patients aged 90 and older underwent open-heart surgery at our institution. We performed a retrospective data analysis including baseline preoperative clinical status, intra- and postoperative results and the long-term survival in the further postoperative course. We performed cardiac surgical procedures in 17 patients (male/female ratio 6/11), including isolated aortic valve replacement (n = 7), aortic root replacement (n = 2), isolated coronary bypass surgery (n = 4), combined coronary and valve surgery (n = 5), re-operative valve replacement (n = 1) and root replacement with arch repair (n = 1). Emergency procedures were performed in 11.8% (2/17). Mean age was 91.9 ± 1.2 years, ranging 90.1-94.2. Mean follow-up was 3.2 ± 2.2 years. The 30-day mortality was 17.6% (3/17), overall mortality at 42.9 follow-up patient years was 58.8% (10/17). We conclude that cardiac surgery procedures can be performed with therapeutic benefit for selected nonagenarians safely and with acceptable operative risk. After analysis our clinical experience we believe age alone not to be a contraindication for surgical intervention, consideration of the physiologic status of the patient reflects on the postoperative outcome. Survival of the patients investigated that survived the initial 30-day postoperative period was similar to the estimated survival of the equally aged general population in Germany.