Solution Ca/P ratio affects calcium phosphate crystal phases

Summary Previous studies on brushite formation and dissolution concluded that brushite was stable only in acidic solutions with pH<6.5. Francis in 1965 predicted that, at pH range 3.5–6.5, brushite would be the preferred phase at low solution Ca/P ratio and hydroxyapatite at high Ca/P ratio. This work presents room-temperature experimental evidence that solution Ca/P ratio affects calcium phosphate crystal phases and that brushite can be the preferred phase in certain supersaturated aqueous solutions containing Ca⁺⁺ and Pi, with or without Mg⁺⁺, even at pH 7.0. Solution mixtures were prepared containing initial [CaCl₂]=0.1−10.0 mM, [Na₂HPO₄]=0.1−100.0 mM, [MgCl₂]=0 or 3 mM. By addition of NaCl, the ionic strengths in terms of osmolarity were also varied from 100 to 800 mosM. Precipitates were isolated from solutions on the 7th, 14th and 21st days and identified by x-ray diffraction. Results indicated that in the presence of 3 mM Mg⁺⁺ and relatively high initial apparent activity products (Ca⁺⁺)(Pi), brushite, whitlockite and hydroxyapatite were obtained as transformation products of initially formed amorphous calcium phosphate when solution Ca/P ratios had low, medium and high values, respectively. In the absence of Mg⁺⁺, whitlockite was not found. However, with or without Mg⁺⁺, when (Ca⁺⁺)(Pi) was relatively low, only brushite was formed by direct crystallization. We concluded that although solutions were mixed at 23°C, pH 7.0, the results were useful in explaining the in vivo calcium phosphate crystal phases observed in renal and dental calculi.     

Radiation following percutaneous balloon aortic valvuloplasty to prevent restenosis (RADAR pilot trial).

OBJECTIVES: We wished to determine the feasibility and early safety of external beam radiation therapy (EBRT) used following balloon aortic valvuloplasty (BAV) to prevent restenosis. BACKGROUND: BAV for calcific aortic stenosis (AS) has been largely abandoned because of high restenosis rates, i.e., > 80% at 1 year. Radiation therapy is useful in preventing restenosis following vascular interventions and treating other benign noncardiovascular disorders. Methods: We conducted a 20-patient, pilot study evaluating EBRT to prevent restenosis following BAV in elderly patients with calcific AS. Total doses ranging from 12-18 Gy were delivered in fractions over a 3-5 day post-op period to the aortic valve. Echocardiography was performed pre and 2 days post-op, 1, 6, and 12 months following BAV. RESULTS: One-year follow-up is completed (age 89 +/- 4). There were no complications related to EBRT. Eight patients died prior to 1 year; 5 of 10 (50%) in the low-dose (12 Gy) group and 3 of 10 (30%) in the high-dose (15-18 Gy) group. None of these 8 patients had restenosis, i.e., > 50% loss of the initial AVA gain, and only three deaths were cardiac in origin. One patient underwent aortic valve replacement and none repeated BAV. By 1 year, 3 of the initial 10 (30%) in the low-dose group and 1 of 9 (11%) in the high-dose group demonstrated restenosis (21% overall). CONCLUSIONS: EBRT following BAV in elderly patients with AS is feasible, free of early complications, and holds promise in reducing the 1 year restenosis rate in a dose-dependent fashion.     

Comparison of cartilage histopathology assessment systems on human knee joints at all stages of osteoarthritis development

ObjectiveTo compare the MANKIN and OARSI cartilage histopathology assessment systems using human articular cartilage from a large number of donors across the adult age spectrum representing all levels of cartilage degradation.DesignHuman knees (n = 125 from 65 donors; age range 23–92) were obtained from tissue banks. All cartilage surfaces were macroscopically graded. Osteochondral slabs representing the entire central regions of both femoral condyles, tibial plateaus, and the patella were processed for histology and Safranin O – Fast Green staining. Slides representing normal, aged, and osteoarthritis (OA) tissue were scanned and electronic images were scored online by five observers. Statistical analysis was performed for inter- and intra-observer variability, reproducibility and reliability.ResultsThe inter-observer variability among five observers for the MANKIN system showed a similar good Intra-class correlation coefficient (ICC > 0.81) as for the OARSI system (ICC > 0.78). Repeat scoring by three of the five readers showed very good agreement (ICC > 0.94). Both systems showed a high reproducibility among four of the five readers as indicated by the Spearman’s rho value. For the MANKIN system, the surface represented by lesion depth was the parameter where all readers showed an excellent agreement. Other parameters such as cellularity, Safranin O staining intensity and tidemark had greater inter-reader disagreement.ConclusionBoth scoring systems were reliable but appeared too complex and time consuming for assessment of lesion severity, the major parameter determined in standardized scoring systems. To rapidly and reproducibly assess severity of cartilage degradation, we propose to develop a simplified system for lesion volume.     

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate in primary ventricular fibrillation or life-threatening ventricular tachycardia

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate, a chemical analog of bretylium tosylate, were studied using programmed cardiac electrical stimulation in 14 survivors of out-of-hospital cardiac arrest unassociated with acute myocardial infarction. Before bethanidine sulfate was administered sustained ventricular tachyarrhythmias (VT) were inducible in 11 patients and reproducible nonsustained VT was induced in 3 patients. Bethanidine sulfate shortened sinus cycle length and absolute and relative ventricular refractory periods measured during sinus rhythm, but did not alter ventricular effective refractory period measured during ventricular pacing. Bethanidine sulfate prevented inducible VT in 8 patients (57%), increased the number of extrastimuli needed to induce VT in 2 patients, and was ineffective in 4 patients. In contrast, in only 1 of 26 trials with other conventional and investigational antiarrhythmic drugs in these patients was VT prevented. Orthostatic hypotension was a prominent side effect of bethanidine sulfate therapy, but could be reversed in most patients by concomitant administration of protriptyline. Five patients in whom bethanidine sulfate was effective in the laboratory have been treated chronically (400 to 600 mg 4 times daily), and all are alive at 3 to 40 months. In the remaining 9 patients, 8 were treated empirically because no drug was effective in the laboratory and 1 was treated with quinidine, which appeared to be protective during testing. Four of these 9 patients, including the patient treated with quinidine, died suddenly during follow-up. Thus, although bethanidine sulfate therapy is difficult to initiate because of orthostatic hypotensive side effects, it may be useful in treating patients at high risk of recurrent cardiac arrest.     

Cost comparison of predictive genetic testing versus conventional clinical screening for familial adenomatous polyposis

BACKGROUND: Mutations of the APC gene cause familial adenomatous polyposis (FAP), a hereditary colorectal cancer predisposition syndrome. AIMS: To conduct a cost comparison analysis of predictive genetic testing versus conventional clinical screening for individuals at risk of inheriting FAP, using the perspective of a third party payer. METHODS: All direct health care costs for both screening strategies were measured according to time and motion, and the expected costs evaluated using a decision analysis model. RESULTS: The baseline analysis predicted that screening a prototype FAP family would cost $4975/ pound3109 by molecular testing and $8031/ pound5019 by clinical screening strategy, when family members were monitored with the same frequency of clinical surveillance (every two to three years). Sensitivity analyses revealed that the genetic testing approach is cost saving for key variables including the kindred size, the age of screening onset, and the cost of mutation identification in a proband. However, if the APC mutation carriers were monitored at an increased (annual) frequency, the cost of the genetic screening strategy increased to $7483/ pound4677 and was especially sensitive to variability in age of onset of screening, family size, and cost of genetic testing of at risk relatives. CONCLUSIONS: In FAP kindreds, a predictive genetic testing strategy costs less than conventional clinical screening, provided that the frequency of surveillance is identical using either strategy. An additional significant benefit is the elimination of unnecessary colonic examinations for those family members found to be non-carriers.     

Arterial repair after stenting and the effects of GM6001, a matrix metalloproteinase inhibitor

OBJECTIVES: This study compared the extracellular matrix (ECM) and cellular responses after stenting to balloon angioplasty (BA) and to determine the late effects of matrix metalloproteinase (MMP) inhibition on arterial repair after stenting. BACKGROUND: Although stenting is the predominant form of coronary intervention, there is limited understanding of the early and late arterial response. METHODS: In a double-injury rabbit model, adjacent iliac arteries in 87 animals received BA (3.0 mm diameter) or stenting (3.0 mm NIR). Rabbits were treated for 1 week postprocedure with either GM6001 (100 mg/kg per day), an MMP inhibitor or placebo and sacrificed at 1 week or at 10 weeks' postprocedure. Arteries were analyzed for morphometry, collagen content, gelatinase activity, cell proliferation and DNA content.RESULTS: Stented arteries had significant increases in collagen content (2-fold) at 10 weeks compared to BA-treated arteries. At one week, overall gelatinase activity was increased >2-fold in stented arteries, with both 72 kD and 92 kD gelatinase activity. Stented arteries also had increases in both intimal DNA content (1.5-fold) and absolute cell proliferation (4-fold). Compared to placebo, GM6001 significantly inhibited intimal hyperplasia and intimal collagen content, and it increased lumen area in stented arteries without effects on proliferation rates. CONCLUSIONS: Stenting causes a more vigorous ECM and MMP response than BA, which involves all layers of the vessel wall. Inhibition by MMP blocks in-stent intimal hyperplasia and offers a novel approach to prevent in-stent restenosis.     

Effect of exercise on articular cartilage

This review primarily focuses on how the macromolecular composition and architecture of articular cartilage and its unique biomechanical properties play a pivotal role in the ability of articular cartilage to withstand mechanical loads several magnitudes higher than the weight of the individual. Current findings on short-term and long-term effects of exercise on human articular cartilage are reviewed, and the importance of appropriate exercises for individuals with normal and diseased or aberrated cartilage is discussed.     

Lymphoma. Presenting as an intramuscular small cell malignant tumor

The authors report two patients who presented with a mass in their thigh muscles. On the basis of the histologic appearance, a diagnosis of small cell malignancy was made. Further investigations including electron microscopy and immunoperoxidase techniques were necessary to accurately identify these tumors as lymphoma. Intramuscular lymphoma is rare, but it should be considered in the differential diagnosis, when the tumor consists of small cells. Special techniques are mandatory for a definitive diagnosis.