Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-ß1 in patients with grade 3 chronic degenerative joint disease of the knee.

OBJECTIVE: The aim of this study was to preliminarily evaluate the efficacy and outcomes of injectable genetically engineered chondrocytes virally transduced with TGF-ß1 (GEC-TGF-ß1) compared to placebo. DESIGN: A multi-center, double-blinded, placebo-controlled, randomized study of adults with knee osteoarthritis. A total of 102 patients were 2:1 randomized to GEC-TGF-ß1 or placebo. Primary outcomes assessed were (1) function of the knee joint, scored using the International Knee Documentation Committee (IKDC); and (2) pain, measured by Visual Analog Scale (VAS). Secondary endpoints assessed were pain and analgesic use, quality of life (QOL), and adverse events (AEs) including need for total knee arthroplasty after treatment. RESULTS: IKDC showed significant improvement in the GEC-TGF-ß1 group over the placebo at week 12 (least mean square difference (LSMD): 10.3; P = 0.0342), week 52 (LSMD: 13.6; P = 0.0082), and overall (LSMD: 8.6; P = 0.0453). VAS Analysis showed a significant improvement in GEC-TGF-ß1 group compared to placebo at weeks 12 (LSMD: -13.8; P = 0.0162), 52 (LSMD: -13.1; P = 0.0332), and overall (LSMD: -10.1; P = 0.0350). Reduction in pain severity at week 12 and 52, frequency at 24 h and week 52, and the percentage of patients in the GEC-TGF-ß1 group receiving analgesics at week 4 (27 vs 40%) and 12 (27 vs 37%) was observed. CONCLUSIONS: GEC-TGF-ß1 patients had more positive responses on the IKDC, VAS, and were less likely to require analgesics. TRIAL NUMBER: ClinicalTrials.gov (NCT01221441) - "Study of TG-C in Patients with Grade 3 Degenerative Joint Disease of the Knee".

Prospective analysis of splinting the first carpometacarpal joint: an objective, subjective, and radiographic assessment.

Predisposing factors contributing to the development of first carpometacarpal (CMC) osteoarthritis include an inherent laxity or incongruency of this joint, a shallow trapezium saddle, and heavy stresses placed on the joint with pinching and grasping. Splinting is a common mode of conservative treatment for CMC osteoarthritis. This study assessed the objective and subjective responses of patients with CMC osteoarthritis who wore short and long opponens splints, as well as radiographic changes associated with wearing of the splints. The study evaluated 26 hands. Each patient was assigned at random to wear the long or the short splint first. Patients wore the splints for one week. They then documented function in their splints (on 22 activities of daily living) and rated splint satisfaction and pain levels on visual analog scales. One week after application of the first splint, the second splint was applied and worn for one week, and all measures were repeated. On the final visit, tip pinches were evaluated and x-rays were taken to assess subluxation. One-way repeated-measure analysis and paired comparison were used to analyze the pinch, pain, radiographic, and splint-rating measures. Descriptive statistics were used to assess activity-of-daily-living function and splint preference. Both splints appear to reduce subluxation at the first CMC joint in patients with grades 1 and 2 osteoarthritis. The majority of the patients picked the short splint when asked at the end of the study which splint they preferred. The splints do not appear to increase pinch strength or affect pain levels associated with the performance of pinch strength measurements. This study supports anecdotal evidence that patients with CMC osteoarthritis get pain relief with splinting.

Management of hypercholesterolemia: practice patterns for primary care providers and cardiologists.

This retrospective study, conducted as part of a private practice quality assurance process for patients with coronary artery disease (CAD), compares practice patterns in the LIFEHELP lipid clinic and non-lipid clinic settings at the Heart Institute of St. Petersburg. Quality assurance parameters included documentation of low-density lipoprotein (LDL) cholesterol, initiation of lipid-lowering therapy, and achievement of the Second National Cholesterol Education Program (NCEP II) goal for CAD patients of LDL cholesterol < or =100 mg/dL. A total of 934 patient charts with ICD-9 codes of 410-414 for ischemic heart disease were randomly selected and reviewed by a utilization review nurse. A higher level of documentation and treatment of elevated LDL cholesterol to NCEP II goal in CAD patients was found for those followed in the lipid clinic. Among non-lipid clinic physicians, cardiologists documented and treated elevated LDL cholesterol more frequently than primary care physicians. Women and the elderly subgroups received improved care in the lipid clinic setting. Screening activities and risk-factor management by cardiologists within a lipid clinic, therefore, demonstrated an improved standard of care that came closer to achieving national guidelines in the secondary prevention of CAD.

Effect of rate-dependent left bundle branch block on global and regional left ventricular function.

Seven subjects with rate-dependent left bundle branch block (RDLBBB) and 13 subjects with normal conduction (control group) underwent upright bicycle exercise radionuclide angiography to determine the effects of the development of RDLBBB on global and regional left ventricular function. Six of the seven subjects with RDLBBB had atypical chest pain syndromes; none had evidence of cardiac disease based on clinical examination and either normal cardiac catheterization or exercise thallium-201 scintigraphy. Radionuclide angiograms were recorded at rest and immediately before and after RDLBBB in the test group, and at rest and during intermediate and maximal exercise in the control group. The development of RDLBBB was associated with an abrupt decrease in left ventricular ejection fraction (LVEF) in six of seven patients (mean decrease 6 +/- 5%) and no overall increase in LVEF between rest and maximal exercise (65 +/- 9% and 65 +/- 12%, respectively). In contrast, LVEF in the control group was 62 +/- 8% at rest and increased to 72 +/- 8% at intermediate and 78 +/- 7% at maximal exercise. The onset of RDLBBB was associated with the development of asynchronous left ventricular contraction in each patient and hypokinesis in four of seven patients. All patients in the control group had normal wall motion at rest and exercise. These data indicate that the development of RDLBBB is associated with changes in global and regional ventricular function that may be confused with development of left ventricular ischemia during exercise.

Evaluation of a QRS scoring system for estimating myocardial infarct size. III. Correlation with quantitative anatomic findings for inferior infarcts.

This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.

Myocardial infarct extension: incidence and relationship to survival.

Myocardial infarct extension, defined as reelevation or reappearance of creatine phosphokinase-MB (CK-MB) 48 hours after the onset of symptoms, was evaluated prospectively in 56 consecutive patients with acute myocardial infarction. Myocardial infarct extension occurred in eight patients (14%). The sensitivity, specificity and predictive accuracy in the diagnosis of myocardial infarct extension were 63%, 85% and 42%, respectively, for recurrent chest pain requiring morphine; 50%, 65% and 19% for recurrent ST-segment elevation on routine 12-lead ECGs; and 88%, 63% and 28% for reelevation of total CK. Three of the eight episodes of extension were clinically silent. Four of eight patients (50%) with extension died, compared with one of 46 patients (2%) without extension (p = 0.0009). CK-MB persisted for 72 hours or longer in 16 patients and identified seven of eight patients who subsequently had infarct extension. We conclude that myocardial infarct extension is an infrequent complication of acute myocardial infarction and is associated with a very high mortality rate. Persistence of CK-MB for 72 hours or more identifies a subgroup of patients at high risk for subsequent infarct extension and death.

Aneurysm of a saphenous vein bypass graft associated with aneurysms of native coronary arteries.

Aneurysm formation in saphenous vein aortocoronary bypass grafts is an extremely rare complication of coronary artery bypass surgery. Aneurysms of native coronary arteries are found in a small percentage of patients at autopsy. Reported is a case with multiple coronary artery aneurysms in which a dissecting aneurysm of the saphenous vein bypass graft also developed following coronary artery bypass surgery. This is the first report of such association.

Congenital aneurysm of left atrial appendage.

Congenital aneurysm of the left atrial appendage is a rare anomaly, usually presenting in adult life. The case reported is that of a 55-year-old man who died of cerebral embolism originating from a thrombus in a congenital aneurysm of the left atrial appendage. The cardiac silhouette 11 years previously had suggested a cardiac tumour or a pericardial cyst. As judged frm 14 published cases, the major manifestations of these aneurysms are an abnormal cardiac silhouette in the x-ray, supraventricular tachycardia, and systemic embolism. Angiocardiography appears to be the method of choice in establishing the diagnosis. Resection of th aneurysm is the recommended form of treatment.

Failure to produce blood pressure changes following pharmacological or surgical depletion of brain serotonin in the spontaneously hypertensive rat.

Spontaneously hypertensive (SH) and normotensive (Wistar-Kyoto, WKY) rats were examined for blood pressure changes following depletion of CNS serotonin (5-HT) by 3 separate techniques: (1) p-chlorophenylalanine, (2) 5,7-dihydroxytryptamine, and (3) a lesion of the dorsal and median raphe nuclei. All of these procedures failed to alter blood pressure in either hypertensive or normotensive rats, despite marked reductions (75-85%) in forebrain 5-HT. Moreover, treatment of 10 day-old hypertensive rat pups with intracisternal injections of 5,7-DHT (10 microgram) failed to alter the development of hypertension despite a 75-80% decrease in spinal cord 5-HT. These findings, which show that 5-HT depletion does not alter blood pressure in the SH or the WKY rat, do not lend support to the idea that 5-HT is involved in the regulation of blood pressure or in the development and maintenance of hypertension in the SH rat.

Granulomatous hepatitis as a manifestation of quinidine hypersensitivity.

Histologic pictures have been conflicting in previous cases of quinidine-associated hepatitis. We report a case of reversible granulomatous hepatitis from quinidine hypersensitivity, with granuloma induction occurring within three days after readministration of quinidine. Fever, urticaria, and mild thrombocytopenia were associated clinical findings. Both light and electron microscopic study results are reported.

Meningeal carcinomatosis. Case report and review of the literature.

Untreated meningeal carcinomatosis is a uniformly fatal type of metastatic disease presenting with many protean signs and symptoms. We achieved significant palliation and long-term survival in our patient, using combined chemotherapy and radiotherapy; responses to both intrathecal methotrexate and experimental oral CCNU were observed.