A comparison of in-house and shared RapidPlan models for prostate radiation therapy planning.

Knowledge-based planning (KBP) can increase plan quality, consistency and efficiency. In this study, we assess the success of a using a publicly available KBP model compared with developing an in-house model for prostate cancer radiotherapy using a single, commercially available treatment planning system based on the ability of the model to achieve the centre's planning goals. Two radiation oncology centres each created a prostate cancer KBP model using the Eclipse RapidPlan software. These two models and a third publicly-available, shared model were tested at three centres in a retrospective planning study. The publicly-available model achieved lower rectum doses than the other two models. However, the planning-target-volume (PTV) doses did not meet the local planning goals and the model could not be adjusted to correct this. As a result, the plans most likely to satisfy local planning goals and requirements were created using an in-house model. For centres without an existing in-house model, a model created by another centre with similar planning goals was found to be preferred. Variations in local planning practices including contouring, treatment technique and planning goals can influence the relative performance of KBP. The value of publicly available KBP models could be enhanced through standardisation of planning goals and contouring guidelines, providing information related to the planning goals used to create the model and increased flexibility to allow local adaptation of the KBP model.

Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases.

Color and scent: how single genes influence pollinator attraction.

A major function of angiosperm flowers is the recruitment of animal pollinators that serve to transfer pollen among conspecific plants. Distinct sets of floral characteristics, called pollination syndromes, are correlated with visitation by specific groups of pollinators. Switches among pollination syndromes have occurred in many plant families. Such switches must have involved coordinated changes in multiple traits and multiple genes. Two well-studied floral traits affecting pollinator attraction are petal color and scent production. We review current knowledge about the biosynthetic pathways for floral color and scent production and their interaction at the genetic and biochemical levels. A key question in the field concerns the genes that underlie natural variation in color and scent and how such genes affect pollinator preference, reproductive isolation, and ultimately speciation.

Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programmes. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1-infected drug users receiving antiretroviral therapy (ART) for at least six months in Hanoi, Vietnam. The mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA <1000 copies/mL). Correlates of viral suppression include self-reported > or = 95% adherence (P < 0.01) and current use of trimethoprim/sulphamethoxazole (P < 0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (P = 0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlight the need for adherence promotion, risk reduction programmes, and population-based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited.

Analysis of the relation between stent implantation pressure and expansion. Optimal Stent Implantation (OSTI) Investigators.

Palmaz-Schatz stents were implanted in 79 lesions in 76 patients, and serially expanded at 12, 15, and 18 atm of pressure using noncompliant balloons. By core lab analysis, intravascular ultrasound demonstrated marked stent expansion as pressure was raised, which was not apparent by angiography.

Regression of nifedipine-induced gingival hyperplasia following switch to a same class calcium channel blocker, isradipine.

Patients with nifedipine-induced gingival hyperplasia (GH) often require continued calcium channel blocker therapy. Switches to diltiazem and verapamil have been described; however, these drugs are of a different chemical class and present therapeutic limitations in some patients. The purpose of this study was to evaluate the effect on nifedipine-induced GH of a switch to a dihydropyridine derivative with a low incidence of GH. Fourteen patients with nifedipine-induced GH were given a medical exam and a periodontal exam. The following parameters were assessed: probing depth (PD), gingival margin (GM), gingival thickness (GT), plaque index (PI), and gingival index (GI). Intraoral photographs, study models, and a gingival biopsy for histological examination were taken. Following baseline measures, patients were randomized to continued treatment with nifedipine or an equivalent dose of isradipine in a single-blind fashion. Biweekly periodontal parameters were taken for 8 weeks. At the end of 8 weeks, some patients elected to receive 4 weeks of open label isradipine therapy, with biweekly examination continuing through the open label phase. The isradipine treatment arm showed a mean decrease in PD of 0.59 mm at week 8 (P < 0.05). No other measured parameter (GM, GT, PI, GI) was significantly changed, compared either to baseline or to the alternate treatment arm. Clinically, 60% of patients treated with isradipine exhibited a decrease in hyperplasia, while 66% of patients treated with nifedipine demonstrated an increase in hyperplasia, a significant difference (P < 0.05). When combined with open label data, patients switching therapy to isradipine exhibited an increase in GM (increase in recession) of 0.74 mm from baseline to week 12 (P < 0.05). No patients treated with isradipine exhibited an increase in gingival overgrowth. All patients exhibited adequate control of hypertension. We conclude that in hypertensive patients with nifedipine-induced GH, switching hypertensive therapy to isradipine may result in a regression of GH. When coupled with aggressive oral hygiene treatment, this drug may provide a reasonable option for patients requiring dihydropyridine treatment.

Improved procedural results of coronary angioplasty with intravascular ultrasound-guided balloon sizing: the CLOUT Pilot Trial. Clinical Outcomes With Ultrasound Trial (CLOUT) Investigators.

BACKGROUND: Indiscriminate use of balloons larger than the angiographic reference segment lumen results in high rates of ischemic complications after percutaneous transluminal coronary angioplasty (PTCA). We hypothesized that angiographically unsuspected atheromatous remodeling with vessel expansion (the Glagov phenomenon) at and adjacent to PTCA target lesions would safely accommodate oversized balloons in selected patients undergoing PTCA with intravascular ultrasound (IVUS) guidance. METHODS AND RESULTS: After angiographically guided PTCA of 104 lesions in 102 patients, IVUS was performed, and if atheromatous remodeling was present, PTCA was repeated with larger balloons sized halfway between the lumen and external elastic membrane. Plaque occupied a mean of 51+/-15% of the angiographically "normal" reference segments. Further balloon upsizing by 0.25 to 1.25 mm was therefore performed in 76 lesions (73%), increasing the nominal balloon-to-artery ratio from 1.12+/-0.15 after standard PTCA to 1.30+/-0.17 after IVUS-guided PTCA (P<.0001). As a result, the angiographic minimal luminal diameter further increased from 1.95+/-0.49 to 2.21+/-0.47 mm, the % diameter stenosis fell from 28+/-15% to 18+/-14%, and the IVUS lumen area rose from 3.16+/-1.04 to 4.52+/-1.14 mm2 (all P<.0001). The incidence of angiographic dissection was not increased after IVUS-guided balloon upsizing (37% versus 40%, P=.67), and major complications occurred in only 2 patients (1.9%). CONCLUSIONS: The demonstration by IVUS of atheromatous remodeling permits the safe use of balloons traditionally considered oversized, resulting in significantly improved luminal dimensions without increased rates of dissection or ischemic complications.

Using sociological concepts in the study of Indian medical systems: medical system, role & profession.

Now-a-days there is renewed interest all over the world in the medical systems other than modern medicine, identified as 'alternative' or 'conplementary' medicine. Research on these medical systems of India, as well as of other Asian societies continues to thrive. In this study, efforts has been made to place these systems in a frame work using the tolls of sociology. The research undertaken encompassed more than this, private clinics and the government hospitals of these systems in Hyderabad and miscellaneous, clinics, such as bone setters also.

Coronary artery plaque morphology in stable angina and subsets of unstable angina: an in vivo intracoronary ultrasound study.

Little information is available regarding the in vivo composition of angina producing culprit atherosclerotic lesions in various anginal syndromes. In this study we used intracoronary ultrasound to determine the composition of culprit lesions in various subsets of anginal syndromes and correlated this composition with the patient's clinical presentation. One hundred and forty six patients referred for angioplasty or atherectomy were classified as having either chronic stable angina (angina which was clinically unchanged for > 2 months), crescendo angina (an accelerating pattern of frequent or prolonged anginal episodes), severe rest angina (abrupt onset of prolonged angina) or post-infarction angina (angina within 2 weeks of acute myocardial infarction). Intracoronary ultrasound imaging of the culprit lesion was performed before intervention. Lesions were classified as soft, mixed fibrous without calcium, mixed fibrous with calcium or calcified. Analysis of the ultrasound images revealed that the majority of culprit lesions were soft in severe rest (71%) and post-infarction angina (73%) whereas, the majority of culprit lesions were mixed fibrous or calcified in chronic stable (69%) and crescendo (53%) angina (X2 = 22.73, p = 0.007). In addition, the frequency of intralesional calcium in chronic stable or crescendo angina was significantly higher than that in severe rest or stable angina. We conclude that the composition of culprit lesions in various anginal subsets are different. The lesion morphology in crescendo angina frequently resembles that in chronic stable angina; while those in severe rest and post-infarction angina are frequently similar. These findings may have implications for medical or interventional treatment of patients with angina.

Sharing the toxic burden in New Jersey.

As toxic pollution spreads throughout New Jersey, the environment induces illness and the fear of illness in an ever-increasing population. The questions to ask physicians and residents of New Jersey are: Who will share the burden? What is the cost of this burden?

Correlation of intracoronary ultrasound plaque characteristics in atherosclerotic coronary artery disease patients with clinical variables.

It was examined whether intracoronary ultrasound-defined plaque morphology of symptom-producing, severely stenosed, atherosclerotic coronary artery lesions is related to patient-related clinical variables. Data regarding anginal pattern (stable vs unstable), age, sex, history of smoking, diabetes, hypertension, hypercholesterolemia and lesion location were recorded in 146 hemodynamically stable patients referred for clinically indicated balloon angioplasty or directional atherectomy. Intracoronary ultrasound images of the lesions were obtained before and after the intervention. Lesions were classified as soft (homogeneous echoes less dense than adventitia) or hard (bright echoes with or without acoustic shadowing). Eighty-three lesions (57%) were classified as soft and 63 (43%) as hard. Univariate analysis showed anginal pattern, age, vessel location and history of smoking to be significantly related to plaque morphology. Multivariate analysis revealed only anginal pattern, age and vessel location to be independent predictors of plaque morphology. The frequency of echogenic hard plaque was significantly higher in patients aged > 60 years (56 vs 30%; p = 0.001), those with stable angina (69 vs 35%; p = 0.002), and lesions located in the distal arterial segments (68 vs 31%; p < 0.001) than in younger ones, those with unstable angina, and lesions in proximal segments, respectively. Based on previous studies, echogenic hard plaques are likely to be predominantly fibrous or calcific, or both, whereas low-echogenicity soft plaques are likely to be fibrocellular, lipid rich or thrombotic, or a combination. This difference in plaque morphology is probably due to differences in the predominant mechanism of plaque formation (i.e., slow growth vs rupture/thrombosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis.

OBJECTIVES: The purpose of this study was to test the hypothesis that endothelial dysfunction occurs in humans before the development of structural coronary atherosclerosis when risk factors for this disease are present. BACKGROUND: Animal studies have demonstrated that known risk factors for coronary atherosclerosis (hyperlipidemia, hypertension, diabetes) result in impaired endothelium-dependent vascular reactivity before the development of structural atherosclerosis. Previous studies in patients have been unable to distinguish early structural atherosclerotic disease from dysfunctional endothelium. METHODS: Twenty-six patients with angiographically normal coronary arteries were studied at cardiac catheterization. The epicardial arteries were imaged using high resolution intravascular ultrasound to detect early structural changes and to determine changes in lumen size during pharmacologic provocation. A selective intracoronary Doppler velocity catheter was subsequently used to determine coronary blood flow velocity changes in response to the same pharmacologic provocation. Group I (9 patients) had no risk factors for atherosclerosis. Group II (17 patients) had one or more risk factors present. RESULTS: Although both Groups I and II had a normal microvascular vasodilator response to adenosine or papaverine infusion (estimated coronary flow increase 396 +/- 200% vs. 326 +/- 161% [mean +/- SD], respectively, p = 0.103), only Group I patients had an intact response to acetylcholine infusion (378 +/- 203% vs. 75 +/- 93% in Group II, p = 0.001). Group II patients had an abnormal epicardial artery cross-sectional area vasoconstriction response to acetylcholine infusion (-16.6 +/- 12.4% [13 patients] vs. 1.3 +/- 11.5% in Group I, p = 0.0007). An additional four Group II patients had severe spasm during acetylcholine infusion. Epicardial vasodilator response to nitroglycerin infusion, however, was preserved in Group II (14.6 +/- 4.3% vs. 9.6 +/- 3.5% in Group I, p = 0.212). All Group I patients had normal vessels by intravascular ultrasound. Of the 17 patients in Group II, 7 had minimal disease on ultrasound (intimal thickening or small eccentric plaque) in the study vessel. These patients did not respond differently from the 10 Group II patients without demonstrable disease on ultrasound. CONCLUSIONS: Patients with risk factors for coronary artery disease, normal coronary angiograms and no measurable disease by intracoronary ultrasound exhibit selective endothelial dysfunction at both the epicardial and microvascular levels. These findings may have implications for the treatment of "preclinical" coronary atherosclerosis.

Mechanisms of angiographically successful directional coronary atherectomy: evaluation by intracoronary ultrasound and comparison with transluminal coronary angioplasty.

To assess the mechanisms of luminal improvement, 40 patients undergoing directional coronary atherectomy and a matched control group of 25 patients undergoing angioplasty were evaluated with intracoronary ultrasound imaging before and after intervention. Despite similar sized vessels, a similar angiographic severity of diameter stenosis (75 +/- 12% for the angioplasty group vs 69 +/- 15% for the atherectomy group, p = NS), and a similar plaque burden (percent plaque area) before intervention (84 +/- 5% in the angioplasty group vs 85 +/- 13% in the atherectomy group, p = NS), the residual plaque area after intervention was significantly smaller in the atherectomy group (54 +/- 14%) compared with the angioplasty group (65 +/- 13%, p = 0.002). Despite excellent angiographic results, significant residual plaque was noted after either successful intervention. Based on the absolute changes in lumen area, plaque area, and vessel area, improvement in the lumen area in the atherectomy group occurred as a result of plaque "compression" (48%), plaque removal (37%), and vessel expansion (15%). In the angioplasty group, plaque "compression" accounted for 94% of the improvement in lumen area, whereas vessel expansion contributed 6%. Thus "compression" of plaque remains the major mechanism of luminal improvement during atherectomy.

Construction of cDNA libraries from cultures of Armillaria mellea.

1. Conditions were established for growth of mycelial cultures of Armillaria mellea such that the production of its lysine-specific proteinase was maximized. Proteinase synthesis was confirmed by immunoprecipitation. 2. Mycelia grown under these same conditions were used as a source of RNA and this RNA was translatable in a wheat germ translation system to produce proteins with M(r) in the range < 10,000- > 90,000. 3. Double-stranded cDNA was prepared and was inserted into the EcoR1 site of lambda gt10 and lambda gt11 using an adaptor ligation strategy. Packaging of these materials yielded large cDNA libraries. The form lambda gt10 contained 2.9 x 10(6) pfu/ml with 70% recombinants whereas that from lambda gt11 contained 2.2 x 10(6) pfu/ml with 60% recombinants.

Intracoronary ultrasound imaging: correlation of plaque morphology with angiography, clinical syndrome and procedural results in patients undergoing coronary angioplasty.

OBJECTIVES: This study was designed to establish the relation between ultrasound-derived atheroma morphology and the clinical, procedural and angiographic features of patients presenting for coronary angioplasty. BACKGROUND: Intracoronary ultrasound imaging provides accurate dimensional information regarding arterial lumen and wall structures. Atheroma composition may also be assessed by ultrasound; however, only limited studies have been performed in patients. METHODS: In 65 patients a diagnostic ultrasound imaging catheter or a combination imaging-angioplasty balloon catheter was used during coronary angioplasty to image both the lesion and the vessel segment just proximal to it (reference segment). Ultrasound images were analyzed for lumen, total vessel and plaque areas and were classified into five morphologic subtypes (soft, fibrous, calcific, mixed plaque and concentric subintimal thickening). These data were compared with angiographic morphologic features, procedural results and clinical angina pattern (stable vs. unstable). RESULTS: Morphologic analysis of the ultrasound images obtained from the lesion correlated well with the clinical angina syndrome. Compared with patients with stable angina, patients with unstable angina had more soft lesions (74% vs. 41%), fewer calcified and mixed plaques (fibrotic, soft or calcific components in one or more combinations [25% vs. 59%]) and fewer intralesional calcium deposits (16% vs. 45%) (all p < 0.01). There was no correlation between ultrasound and angiographic lesion morphologic characteristics for either the reference segment or the lesion. Ultrasound demonstrated greater sensitivity than angiography for identifying unstable lesions (74% vs. 40%). Dimensional analysis demonstrated a large plaque burden in the reference segments (45 +/- 15% of total vessel area). Postangioplasty plaque burden was also high (62 +/- 9%). There was a significant, but only fair correlation between lumen area determined by angiography and ultrasound for both the reference segment (r = 0.70, p < 0.001) and the postangioplasty lesion (r = 0.63, p < 0.05). CONCLUSIONS: Morphologic plaque classification by ultrasound is closely correlated to clinical angina but has little relation to established angiographic morphologic characteristics. Intracoronary ultrasound imaging during angioplasty identifies a large residual plaque burden in both the reference segment and the lesion. In the future, determination of plaque composition by intracoronary ultrasound may be important in selecting or modifying interventional therapeutic options.

Environmental hazards and public health: lessons for the practice of medicine and for public policy.

The separation of occupational and environmental disease from the mainstream of medical practice has deep roots in the culture of the profession. Medical practice centered on individual patient care as nineteenth-century science yielded the therapeutic triumphs of the twentieth century. Social issues seemed remote to medical practitioners as the rewards of scientifically based therapies upstaged the unglamorous aspects of preventive medicine. Public health was left to politicians and bureaucrats. Victorian ambivalence toward the less successful members of society reinforced the isolation of medicine from public policy. As a consequence, physicians are largely ignored in contemporary debates about environmental hazards, to the detriment of both society and the profession.

Percutaneous intravascular ultrasound imaging: validation of a real-time synthetic aperture array catheter.

This study was designed to validate the dimensional accuracy and ability to characterize atherosclerotic vessel morphology of a new percutaneously passed ultrasound catheter. The 5.5F catheter used for this study has a synthetic aperture array transducer providing a radial field of view perpendicular to the catheter and can be passed over a standard 0.014-in guide wire. Initial in vitro studies were performed to assess accuracy of dimensional and morphologic information. In vitro images of fixed human vessels demonstrated good boundary definition, and dimensional measurements were closely correlated with histological samples (luminal area, r = .97; maximal lumen diameter, r = .95; maximal wall thickness, r = .83). Morphological subtypes were also closely correlated, with increasing severity of histological atherosclerosis characterized by predictable changes in the ultrasound images. Subsequently, the catheter was passed percutaneously in 28 patients to obtain images of coronary (n = 20) and pelvic (n = 12) vessels. Ultrasound images were compared with simultaneous digital angiograms. Correlation between ultrasonic and angiographic estimations of vessel diameters was good (r = .92). We conclude that intravascular ultrasound imaging will be useful for dimensional and morphological characterization of vascular disease, for the study of regression or progression of atherosclerosis, and, potentially, for guidance of therapeutic interventions such as atherectomy and angioplasty.