Post market surveillance registry (PIONEER) of the Yukon Choice PC-Elite Coronary Stent System for percutaneous coronary intervention in Indian acute coronary syndrome population.

AIM: The aim of this study was to assess the safety and efficacy profile of a newer generation biodegradable DES, the Yukon Choice PC Elite with a temperature controlling mechanism, in patients with acute coronary syndrome (ACS). METHODS: This prospective multi-center study (PIONEER Registry) was conducted in an Indian ACS population, therefore providing data in real world clinical practice. Patients with ACS underwent DES implantation in de novo native-vessel coronary lesions with the Yukon Choice PC Elite biodegradable polymer DES and were followed up for a year. RESULTS: A total 999 patients were evaluated. The majority of patients were male (79.2%). A total of 6.7% of the patients had a history of prior myocardial infarction (MI) and 2.7% of patients had a history of previous coronary artery bypass graft. The clinical presentations of the patients included: unstable angina pectoris (UA) (46.4%), ST-segment elevation MI (STEMI) (38.1%), and Non-ST-segment elevation MI (NSTEMI) (15.4%). Implantation of the device was successful in 99.9% of cases. The median stent length and stent size were 21.0 mm (Range: 8.0-40.0 mm) and 2.8 mm (Range 2.0-4.0 mm), respectively. Through to one-year clinical follow-up after percutaneous coronary intervention, all-cause death occurred in 4 of 999 patients (Crude Percentage: 0.4%). Cardiac death, MI, TLR, and stent thrombosis were occurred in 1 (0.1%), 8 (0.8%), 12 (1.2%) and 1 (0.1%) patients, respectively. CONCLUSION: The results of this post marketing surveillance registry suggest favorable safety and efficacy outcomes associated with the Yukon Choice PC Elite biodegradable DES in a real world Indian ACS population.

Knowledge, attitude and practices relating to zoonotic diseases among livestock farmers in Punjab, India.

Zoonotic diseases cause significant health and economic impact in developing countries such as India. Many zoonotic diseases are prevalent in the livestock and as an occupational zoonosis in the livestock farmers in India. Lack of knowledge on the disease transmission, prevention and control measures is a potential high risk for the occurrence of zoonotic diseases in the livestock and its keepers in India. We conducted this study to understand knowledge, attitude and practices of livestock farmers regarding zoonoses. Five villages from each of the 22 districts of the state were conveniently selected (n = 110). Farmers available at village community sites were enrolled in the study and requested to complete a custom designed questionnaire (n = 558). In addition, livestock farmers attending basic livestock husbandry training were also surveyed (n = 301). Data from questionnaires was used to create three index variables: (a) knowledge score; (b) attitude score and (c) practice score. Association between demographic and other explanatory variables with knowledge score was evaluated using linear regression analyses. Similarly, the association between knowledge and attitude score with practice score was evaluated. Of the 859 participants, 685 (80%) livestock farmers had heard the term 'zoonoses' but only 345 (40%), 264 (31%) and 214 (25%) farmers were aware of the zoonotic nature of tuberculosis, Japanese encephalitis and taeniosis, respectively. For practices, 23% farmers reported consumption of raw milk and only 10% and 8% livestock farmers ever got their animals tested for brucellosis and tuberculosis, respectively. The low level of education and being a cattle farmer were negatively associated with the farmer's knowledge on zoonotic diseases. The attitude score was positively associated with the practice score of the participants. The results indicate need for educating the livestock farmers particularly those with a low level of education to reduce the health and economic impact of zoonotic diseases in India.

Exploring animal rabies endemicity to inform control programmes in Punjab, India.

Previous studies estimate that one-third of the annual global burden of rabies (~20,000 cases) occurs in India. Elimination of canine rabies is essential to reduce this burden. Surveillance of animal cases can assess both the risk to humans and the efficacy of control strategies. The objective of this study was to describe the spatial and temporal occurrence of reported confirmed cases of rabies in animals in Punjab, India, from 2004 to 2014. We analysed passive surveillance data on 556 samples submitted from 2004 to 2014 to GADVASU, Ludhiana, Punjab, India. Regression and time series analyses were conducted to understand seasonal and long-term variation of cases and identify cross-correlation of monthly cases between species. Spatio-temporal analyses assessed spatial autocorrelation of date of reporting, mean geographic centres of disease occurrence and clustering of cases using Kulldorff's space-time permutation statistic. The annual number of submissions and proportion of confirmed cases were consistent throughout 2004-2014. Most submissions (320; 57.6%) were confirmed rabies cases, including dogs (40.6%), buffalo (29.7%) and cattle (23.1%). Regression analysis of monthly cases in dogs showed seasonal variation with significant increases in cases in March and August. Monthly case numbers in buffalo decreased over time. Long-term temporal trend was not detected in dog and cattle cases. Time-series models identified significant cross-correlation between dog and buffalo cases, suggesting that buffalo cases were spillover events from dogs. Significant spatio-temporal variation or clusters of cases were not detected. These results indicate that rabies cases in animals-and therefore, the potential for exposure to humans-were temporally and spatially stable during 2004-2014 in Punjab, India. The endemic nature of rabies transmission in this region demands a coordinated, sustained control programme. This study provides baseline information for assessing the efficacy of rabies control measures and developing seasonally targeted dog vaccination and rabies awareness strategies.

Single Versus Multi-visit Endodontic Treatment of Teeth with Apical Periodontitis: An in vivo Study with 1-year Evaluation.

BACKGROUND: Apical periodontitis (AP) is one of the most prevalent diseases of the teeth. Treatment of AP is based on the removal of the cause, i.e., bacteria from the root canals. Achievement of adequate bacterial eradication in one appointment treatment remains a controversy. AIM: This prospective study was conducted with the objective to compare the periapical healing of teeth with AP treated in (a) single visit versus (b) two visits, either with or without Vitapex as an intracanal medicament. SUBJECTS AND METHODS: Patients were selected randomly from the Department of Conservative Dentistry and Endodontics. Forty-three patients (81 teeth) met the inclusion criteria, i.e., AP (both symptomatic and asymptomatic) visible radiographically size ≥2 mm × 2 mm, not suffering from any immune-compromising disease, age between 16 and 65 years and tooth not accessed previously. Patients were randomly divided into three groups, i.e., single-visit group (Group 1), multi-visit group without any intracanal medicament (Group 2), and multi-visit group with Vitapex as interim intracanal medicament (Group 3). Comparison was done radiographically using periapical index (PAI). The primary outcome measure was the change in periapical radiolucency after 1 year assessed by PAI scores. The Mann-Whitney U-test was used to evaluate differences between groups at baseline (immediate postoperative) and at the 12-month follow-up evaluation. Change in PAI score for each group from baseline to 12-month follow-up evaluation was tested with the Wilcoxon signed rank test. The secondary outcome measures, proportion of teeth in each group that could be considered improved (decreased PAI score) or healed (PAI <2), were assessed with the Chi-square test. RESULTS: No statistically significant difference in periapical healing was found between three groups. CONCLUSION: After 1-year evaluation, no difference in periapical healing was found between single-visit treatment and multi-visit treatment groups with the given sample size.

Long-term results of cemented, posterior cruciate ligament-retaining total knee arthroplasty in osteoarthritis.

Two hundred fifty-four total knee arthroplasties (TKAs) in 223 patients (82 men and 141 women) with osteoarthritis were reviewed. Average patient age at surgery was 68 years (range: 37-90 years). No patient was lost to follow-up. Average follow-up was 16.8 years (range: 15.2-23.2 years). Preoperatively, 175 (69%) knees had a varus deformity. The posterior cruciate ligament (PCL) was retained in all 254 knees, and all prostheses were cemented. Clinically, 91% of knees were rated as excellent; however, functionally, only 23% of knees were rated as excellent. There were 13 (5%) complications. Revision was performed in 10 (4%) knees. Survivorship analysis showed average implant survival for all revisions was 96.3% (range: 91.9%-98.3%) at 15 years and 82% (range: 60%-92.6%) at 23 years. Long-term results of cemented, PCL-retaining TKA for osteoarthritis are excellent in terms of improved clinical function and pain relief.

Unexpected anthropophagic behaviour in Anopheles quadriannulatus.

The strongly anthropophilic behaviour of Anopheles gambiae Giles sensu stricto (Diptera: Culicidae), the most important malaria vector in Africa, has been demonstrated by field and laboratory studies. Other members of the An. gambiae complex express varied degrees of anthropophily. Anopheles quadriannulatus (Theobald) species A and B are more zoophilic members of the complex and hence are considered to be of no medical importance. Olfactometer experiments with An. quadriannulatus species A have demonstrated attraction to both human and cow odour. To extend these olfactometer observations a choice experiment was conducted in an outdoor cage with a human and a calf as baits, using laboratory-reared mosquitoes. Anopheles gambiae s.s. (from Liberia) and two strains of An. quadriannulatus species A (SKUQUA from South Africa, SANGQUA from Zimbabwe), marked with different coloured fluorescent powders for identification purposes, were released simultaneously and given an equal opportunity to feed on either host. The experiment was repeated six times. Bloodmeals were identified using the precipitin technique. Anopheles gambiae s.s. showed highly anthropophagic behaviour, taking 88% of bloodmeals from the human host. In contrast, both strains of An. quadriannulatus fed with equal frequency on the human or the calf; the response to either host was not significantly different. These results confirm the olfactometer findings and demonstrate anthropophagic behaviour not previously recorded in this species. This finding has implications for prospective manipulation of host preference for genetic control purposes.

Long-term results of retention of the posterior cruciate ligament in total knee replacement in rheumatoid arthritis.

We analysed the long-term results with a mean follow-up of 10.2 years, of 66 total knee replacements in 42 patients with rheumatoid arthritis. In all cases the posterior cruciate ligament was retained. There were only three complications (4.5%). Revision surgery was necessary in five knees (7.6%), including one (1.5%) with infection. At the final follow-up, 75.8% of knees were rated excellent clinically. Only 15% had an excellent function score. The survival rate of the implant was 90.7% at 19 years. The clinical, radiological and survivorship analysis shows that the posterior-cruciate-retaining knee arthroplasty performs well in rheumatoid arthritis.

Long-term results of Kinematic Condylar knee replacement. An analysis of 404 knees.

We present the long-term results of the Kinematic Condylar Knee Arthroplasty followed in a prospective fashion. Between October 1982 and March 1988, 404 consecutive replacement arthroplasties were carried out on 335 patients. Of these, 354 knees had osteoarthritis, 45 rheumatoid arthritis and five other diagnoses. At the time of final follow-up 158 patients (188 knees) had died. No patient was lost to follow-up. The minimum follow-up for all living patients was ten years (10 to 17). The mean age at surgery was 68 years (30 to 92). There were seven complications (1.7%). Sixteen knees (3.9%) were revised, four because of infection. Survivorship was 99.4% (CI 97.9 to 99.8) at five years, 98.2% (CI 96.1 to 99.2) at ten years and 92.6% (CI 87.6 to 95.6) at 17 years.

Cemented hemiarthroplasties for elderly patients with intertrochanteric fractures.

The results of 55 consecutive hemiarthroplasties in 54 elderly patients with intertrochanteric fractures were reviewed. The mean age of the patients was 84.2 years (range, 73-99 years). Standard cemented hemiarthroplasty was used and the fractured posteromedial fragment was retained. Two patients were lost to followup and 12 patients died within 6 months of their fractures. The mean length of followup was 13.6 months (range, 6-24.6 months) for the remaining 40 patients (41 hips). Nineteen patients maintained the same walking category as before fracture and eight of these patients had no increase in the dependency on walking aids. The greatest deterioration of walking function occurred in the subgroup of six patients who had a history of confusion and frequent falls. The medical complications are comparable with those described in other series. There were few surgical complications. The authors of this study think that the use of standard cemented hemiarthroplasty is a reasonable alternative to a sliding screw device for the treatment of intertrochanteric fractures. Longer-term studies with larger numbers of patients are required to address the issues of late complications and whether the reconstructions are durable enough for the long-surviving patients.

Enumerative and binomial sampling plans for armored scale (Homoptera: Diaspididae) on kiwifruit leaves.

The spatial dispersion of armored scale insects; greedy scale, Hemiberlesia rapax (Comstock); and latania scale, Hemiberlesia lataniae (Signoret), was investigated on kiwifruit, Actinidia deliciosa (A. Chevalier) C. F. Liang et A. R. Ferguson, leaves in New Zealand. A universal description for dispersion was determined using Taylor's power law, which encompassed a wide range of different orchards, blocks, block sizes, sampling times, scale control practices, regions and seasons. Scale density significantly altered dispersion, especially at the high densities found on unsprayed kiwifruit. Most commercially managed kiwifruit blocks had low densities of <0.5 scale per leaf and had a slightly aggregated scale dispersion. Wilson and Room's binomial model, which incorporates a clumping pattern as a function of density, gave a significant relationship between the proportion of infested leaves and scale density. The optimal leaf sample sizes were estimated for predetermined levels of sampling reliability. Where population estimates require a high degree of precision and enumerative sampling methods are used, 2,500 leaves should be sampled when scale densities are near the current spray threshold of 4% infested leaves and 500 leaves at 20% infested leaves. For management-decision sampling, where a lower level of precision was acceptable, enumerative sampling would require that 400 leaves be sampled at 4%; or 85 leaves at 20% infested leaves. With binomial sampling to achieve an equivalent level of precision an increased sample size of 6-11% is required.

Agonist-induced GTPgamma35S binding mediated by human 5-HT(2C) receptors expressed in human embryonic kidney 293 cells.

The 5-HT(2C) receptor as heterologously expressed in various mammalian cells mediates inositol 1,4,5-triphosphate (IP(3)) signal by activating G(q/11) subtypes of G proteins, but minimally promotes agonist-induced GTPgamma35S binding in membranes due to slow GTP turnover rates of the G proteins. Here we discovered robust (over 200%) agonist-induced GTPgamma35S binding mediated by the human receptor expressed in human embryonic kidney (HEK) 293 cells, and investigated its pharmacology. Agonists concentration-dependently increased GTPgamma35S binding in isolated membranes, which was competitively blocked by antagonists. Intrinsic efficacies of agonists from GTPgamma35S binding were comparable to those from IP(3) measurement. Pertussis toxin treatment largely blocked serotonin-induced GTPgamma35S binding, serotonin high affinity sites by 70% without altering the total binding sites, and reduced IP(3) release by 40%. GTPgamma35S-bound Galpha subunits from serotonin-activated membranes were mainly Galpha(i), judging from immobilization studies with various Galpha-specific antibodies. Inhibition of forskolin-stimulated cAMP formation, however, was not observed. Apparently, the 5-HT(2C) receptor-mediated GTPgamma35S binding is a unique phenotype observed in HEK293 cells, reflecting its coupling to pertussis toxin-sensitive G(i) subtypes, which contribute to the IP(3) signal, along with pertussis toxin-insensitive G(q/11) subtypes.

Efficient functional coupling of the human D3 dopamine receptor to G(o) subtype of G proteins in SH-SY5Y cells.

1 The D3 dopamine receptor presumably activates Gi/Go subtypes of G-proteins, like the structurally analogous D2 receptor, but its signalling targets have not been clearly established due to weak functional signals from cloned receptors as heterologously expressed in mostly non-neuronal cell lines. 2 In this study, recombinant human D3 receptors expressed in a human neuroblastoma cell line, SH-SY5Y, produced much greater signals than those expressed in a human embryonic kidney cell line, HEK293. Quinpirole, a prototypic agonist, markedly inhibited forskolin-stimulated cyclic AMP production and Ca2+-channel (N-type) currents in SH-SY5Y cells, and enhanced GTPgamma35S binding in isolated membranes, nearly ten times greater than that observed in HEK293 cell membranes. 3 GTPgamma35S-bound Galpha subunits from quinpirole-activated and solubilized membranes were monitored upon immobilization with various Galpha-specific antibodies. Galphao subunits (not Galphai) were highly labelled with GTPgamma35S in SH-SY5Y, but not in HEK293 cell membranes, despite their abundance in the both cell types, as shown with reverse transcription-polymerase chain reaction and Western blots. N-type Ca2+ channels and adenylyl cyclase V (D3-specific effector), on the other hand, exist only in SH-SY5Y cells. 4 More efficient coupling of the D3 receptor to Go subtypes in SH-SY5Y than HEK293 cells may be attributed, at least in part, to the two D3 neuronal effectors only present in SH-SY5Y cells (N-type Ca2+-channels and adenylyl cyclase V). The abundance of Go subtypes in the both cell lines seems to indicate their availability not a limiting factor.

Total condylar knee arthroplasty. 16- to 21-year results.

This study presents long term results of arthroplasty with posterior cruciate retention using the Total Condylar Knee implant. From 1976 to 1982, 139 patients had 159 knee arthroplasties using Total Condylar Knee prostheses. Sixty-three patients (72 knees) were available for followup at a minimum of 16 years (range, 16-21 years). The average age of the patients at the time of surgery was 61 years. There were 21 men and 42 women. Patients with 68 knees had osteoarthrosis, three had rheumatoid arthritis and one had posttraumatic arthritis. There were five delayed complications. One patient (one knee) underwent revision surgery and two patients (two knees) declined revision surgery because they were considered to be high surgical risks, as determined by their internists. The average preoperative score was 40.3 points and improved to 88.4 points at followup. Eighty-seven percent of the patients had a score equal to or more than 85 points at last evaluation. Prosthesis survivorship at 20 years was 98.6% for patients who had revision surgery. No femoral components were revised for aseptic loosening. Retention of the posterior cruciate in Total Condylar Knee prosthesis produces results comparable with the results of the original Total Condylar Knee prosthesis with cruciate sacrifice.

Postoperative patellar tilt in total knee arthroplasty.

The postoperative tilt of the patella was investigated in 80 consecutive bilateral total knee arthroplasties in 40 patients. We found that the greater the preoperative lateral tilt, the more likely the patella would tilt postoperatively. The obliquity of resection of the patella has a significant effect on the postoperative lateral tilt. Making the patella remnant thicker on the medial side can decrease the postoperative lateral tilt. A limited lateral peripatellar soft tissue release had no discernible effect on the postoperative lateral tilt of the resurfaced patella.

Plasmodium falciparum: enhanced gametocyte formation in vitro in reticulocyte-rich blood.

Concentrates of late stage parasites of the gametocyte-forming clone HB-3 were mixed with blood rich in reticulocytes from anemic patients, or with normal control blood, and kept under culture conditions for 4 days. Significantly more gametocytes were always formed in the reticulocyte-rich blood than in the control. This was true whether the anemic blood supported a larger asexual parasitemia than the control, or a lower one, or the same and without regard to the cause of the anemia. Gametocytes as a percentage of asexual forms were up to 10 times higher in reticulocyte-rich blood than in normal blood.

5- to 18-year follow-up study of cemented total knee arthroplasty for patients 55 years old or younger.

Seventy-two cemented total knee arthroplasties were performed on 52 patients who were 55 years old or younger. Results on 68 knees in 50 patients with an average follow-up period of 9.92 years are reported. The average age of the patients was 50.7 years (range, 30-55) at the time of surgery. The diagnosis was osteoarthritis in 37 knees, rheumatoid arthritis in 29 knees, and ankylosing spondylitis in 2 knees. The average preoperative Knee Society knee score was 23 and the average follow-up knee score was 97. All knees were rated as good or excellent for knee score. The average latest function score was 75 (preoperative, 36). Both knees in one patient required revision for loose components. This review demonstrates that cemented total knee arthroplasty in younger patients with osteoarthritis and rheumatoid arthritis can attain results comparable to the excellent results obtained in the older age groups.

Pharmacological characterization of U-101387, a dopamine D4 receptor selective antagonist.

Dopamine D2-like receptors play an important role in the pharmacotherapy of psychotic disorders. Molecular and cellular techniques have identified distinct gene products (D2-long, D2-short, D3 and D4) displaying the D2 receptor pharmacology. However, the contribution of each subtype in antipsychotic effects of or their physiological role remain unclear. Here we describe the pharmacological effects of a selective D4 antagonist, U-101387. U-101387 displayed moderately high affinity (Ki = 10 nM) and selectivity for the dopamine D4.2 receptor expressed in clonal cell lines. It lacked measurable affinity for not only other dopamine receptors but also noradrenalin, serotonin and histamine receptor families (Ki > 2000 nM). It fully and dose-dependently antagonized quinpirole-induced cAMP inhibition (without producing any effect by itself) in stably transfected cells. U-101387 also displayed excellent oral bioavailability, brain penetration and other pharmacokinetic characteristics. Unlike classical neuroleptics (e.g., haloperidol), U-101387 neither blocked acute behavioral effects of amphetamine or apomorphine nor did it alter spontaneous locomotion by itself. Additionally, U-101387 was without effect in behavioral and biochemical tests predictive of extrapyramidal and neuroendocrine side effects. Consistent with the lack of autoreceptor function of D4, acute administration of U-101387 failed to alter dopamine neuronal firing by itself or reverse the inhibition produced by dopamine agonists and to affect monoamine turnover in areas innervated by the mesencephalic or hypothalamic dopamine neurons. However, U-101387 potently induced c-fos mRNA expression in the infralimbic/ventral prelimbic cortex to a level similar to that produced by the atypical antipsychotic, clozapine. This is consistent with the predominantly cortical distribution of the D4 receptor. Taken together, these results demonstrate that the D4-selective antagonist, U-101387, produces effects that are distinct from those of the nonselective D2 antagonists as well as D3-preferring agents. U-101387 offers a unique tool to understand the role of dopamine D4 receptors in diseases involving central dopamine systems.

Growth of Chinese hamster ovary (CHO) cells expressing the 5-HT2 serotonin receptor in suspension culture: an efficient method for large-scale acquisition of membrane protein for drug evaluation.

Chinese hamster ovary (CHO) cells expressing the rat 5-HT2 serotonin receptor were grown and evaluated in suspension culture to provide an efficient method of producing membrane-bound receptors for drug discovery. Expression of the 5-HT2 receptor in cells grown in batch suspension culture fluctuated as a function of culture age. Both receptor expression and receptor G-protein coupling were the highest early (1.9 pmol/mg membrane protein) but declined rapidly as the culture increased in age. However, addition of fresh serum-containing medium to stationary-phase cells reversed the decline and, after 24 h of growth, resulted in maximal receptor density and G-protein coupling. This serum response was found to be reproducible and lead to the establishment of a semi-continuous batch culture system in which cells were maintained in a growth state that supported high levels of membrane-incorporated and G protein-coupled receptors. In this system, 50% of the culture volume could be removed at 24-h intervals for membrane preparation and the lost volume replenished with fresh medium, resulting in a continuous supply of high-quality membrane preparations.

Effect of erythrocyte membrane on extracellular development of the erythrocytic cycle of Plasmodium falciparum.

We have earlier reported conditions that support the axenic development in vitro of a complete asexual erythrocytic cycle of Plasmodium falciparum. Up to 30% of merozoites showed initial differentiation into trophic forms (rings) viable at 14 hr. However, only approximately 1% of the merozoites would develop further into trophozoites and early schizonts viable at 36 hr. In efforts to increase the number of late stage parasites, we have now found a significant favorable effect of the addition of erythrocyte ghosts. Doubling the quantity of erythrocyte membrane in the erythrocyte sonicate medium resulted in approximate doubling of the number of trophozoites and early schizonts. These results indicate that components of the erythrocyte membrane are essential for the complete development of the erythrocytic cycle.

D4 dopamine receptor-mediated signaling events determined in transfected Chinese hamster ovary cells.

A Chinese hamster ovary (CHO) cell line stably expressing a recombinant human D4 dopamine receptor made from a synthetic gene has been used to determine potential D4-mediated signaling events. We designed and synthesized a modified gene coding for a human D4 receptor with reduced G + C content but unaltered encoded amino acids. Stable expression of this gene was obtained in two cell lines, inducible expression in CHO lacI cells and constitutive expression in HEK293 cells. In CHO lacI cells induced to express D4 receptors but not in uninduced cells, dopamine and quinpirole inhibit forskolin-stimulated cAMP accumulation and potentiate ATP-stimulated [3H]arachidonic acid release through a mechanism that requires protein kinase C but is unaffected by membrane-soluble cAMP analogs. In addition, D4 receptor activation causes an increase in the rate of extracellular acidification measured by microphysiometry. This response is unaffected by protein kinase C down-regulation but is inhibited by removal of extracellular sodium and inhibitors of NaH-1 exchange, suggesting the involvement of a Na+/H+ exchanger. All responses are blocked by clozapine and are sensitive to pertussis toxin. D4 receptors, like other G(i)/G(o)-linked receptors, mediate multiple signaling events, and the pathways activated are similar to those used by D2 and D3 receptors expressed in similar cells.