Advantage of 3D volumetric dosemeter in delivery quality assurance of dynamic arc therapy: comparison of pencil beam and Monte Carlo calculations.

OBJECTIVE: To evaluate the accuracy of pencil beam calculation (PBC) and Monte Carlo calculation (MCC) for dynamic arc therapy (DAT) in a cylindrically shaped homogenous phantom, by comparing the two plans with an ion chamber, a film and a three-dimensional (3D) volumetric dosemeter. METHODS: For this study, an in-house phantom was constructed, and the PBC and MCC plans for DAT were performed using iPlan® RT (BrainLAB®, Heimstetten, Germany). The A16 micro ion chamber (Standard Imaging, Middleton, WI), Gafchromic® EBT2 film (International Specialty Products, Wayne, NJ) and ArcCHECK™ (Sun Nuclear, Melbourne, FL) were used for measurements. For comparison with each plan, two-dimensional (2D) and 3D gamma analyses were performed using 3%/3 mm and 2%/2 mm criteria. RESULTS: The difference between the PBC and MCC plans using 2D and 3D gamma analyses was found to be 7.85% and 28.8%, respectively. The ion chamber and 2D dose distribution measurements did not exhibit this difference revealed by the comparison between the PBC and MCC plans. However, the 3D assessment showed a significant difference between the PBC and MCC (62.7% for PBC vs 93.4% for MCC, p = 0.034). CONCLUSION: Evaluation using a 3D volumetric dosemeter can be clinically useful for delivery quality assurance (QA), and the MCC should be used to achieve the most reliable dose calculation for DAT. ADVANCES IN KNOWLEDGE: (1) The DAT plan calculated using the PBC has a limitation in the calculation methods, and a 3D volumetric dosemeter was found to be an adequate tool for delivery QA of DAT. (2) The MCC was superior to PBC in terms of the accuracy in dose calculation for DAT even in the homogenous condition.

Coexistence of primary sclerosing cholangitis in a patient with myasthenia gravis.

Myasthenia gravis (MG) is an immune-mediated disease that compromises the postsynaptic membrane of the neuromuscular junction. Primary sclerosing cholangitis (PSC) is considered an immune-mediated cholestatic liver disease. Both MG and PSC include an autoimmune pathogenesis, so there is some evidence that patients with MG or PSC have a higher risk of developing autoantibodies and other immune disorders than normal controls, but the coexistence of these two disorders has never been documented. We report a 40-year-old woman who presented with MG when she was 20 years old and developed PSC 20 years after a thymectomy. Liver biochemistry revealed cholestasis. Magnetic resonance imaging showed multifocal strictures and beads involving the intrahepatic bile ducts. A liver biopsy confirmed sclerosing cholangitis. Serological analysis demonstrated positive autoantibodies (Anti-nuclear antibodies, anti-smooth muscle antibodies). Repetitive stimulation had a decremental response, and antibodies to acetylcholine receptors were detectable. To our knowledge, this is the first case of PSC in a patient with MG. The main characteristics of both MG and PSC combination are discussed.

Hamartoma fibrolipomatoso de nervo mediano: relato de caso / Fibrolipomatous hamartoma of the median nerve: case report

Fibrolipomatous hamartoma is a rare benign neoplasm that in some cases is associated with macrodactylia. We describe a 31-year-old man who had a tissue enlargement in the wrist, second and third fingers of the left hand since infancy. At 23-years-old he began with continuous, progressive and high intensity pain that occurred more frequently at night, localized in the left hand. It was associated with paraesthesias and hypostesias predominantly at the fingers described above. Investigation with X-ray, ultrasonography, electrodiagnosis, magnetic resonance image of the left wrist and hand showed carpal tunnel syndrome with macrodactylia by fibrolipomatous hamartoma of the median nerve. The patient did not a have good response to clinical therapy, so he was submitted to a surgical decompression of the left carpal tunnel, and after three months of follow up is asymptomatic.

O hamartoma fibrolipomatoso é neoplasia benigna rara que em alguns casos esta associada com macrodactilia. Descrevemos o caso de homem de 31 anos que apresentava desde o nascimento aumento de volume em região de punho, segundo e terceiro quirodáctilos da mão esquerda. Aos 23 anos iniciou dor contínua, de forte intensidade, predominante no período noturno e de evolução progressiva em mão esquerda. Associada à dor havia hipoestesia e parestesias de predomínio nos segundo e terceiro quirodáctilos esquerdos. A investigação complementar com radiografia, ultrassonografia, estudo eletrofisiológico e ressonância magnética de mão e punho esquerdos confirmaram a suspeita de síndrome do túnel do carpo secundária a macrodactilia com hamartoma fibrolipomatoso do nervo mediano. O paciente foi submetido à descompressão cirúrgica do túnel do carpo esquerdo devido a ausência de resposta ao tratamento clínico e evoluiu com melhora dos sintomas em avaliação após três meses do procedimento.

Estudo da condução nervosa motora na doença de McArdle: relato de caso / Motor nerve conduction study in McArdle disease: case report

McArdle disease (glycogenosis type V) is a metabolic myopathy with symptoms of exercise intolerance caused by deficiency of the enzyme myophosphorylase. In these patients, the motor nerve conduction studies after a short period of maximal voluntary muscle contraction or repetitive stimulation reveals characteristic findings of the disease. A 37-year-old man presented symptoms of exercise intolerance, muscular fatigue and cramps in the beginning of the physical activity with [quot ]second wind[quot ] phenomenon. The motor nerve conduction studies after a voluntary contraction of 30 and 90 seconds presented decrease in the amplitude of the compound muscle action potential in median, ulnar and deep peroneal nerves; and decrement after 200 stimulation at the 40 Hz in deep peroneal nerve. The electromyography presented myopathic pattern and during the ischemic exercise electric silence was not proven. The characteristic of electrophysiological studies are discussed with emphasis at the importance of the motor nerve conduction studies in the patients with suspicion of metabolic myopathy.

A doença de McArdle (glicogenose tipo V) é miopatia metabólica com sintomas de intolerância ao exercício, causados pela deficiência da enzima miofosforilase. Nesses pacientes, o estudo da condução nervosa motora após período de esforço muscular máximo ou ao estímulo repetitivo pode revelar achados característicos da doença. Descrevemos o caso de um homem de 37 anos com sintomas de intolerância aos exercícios, fadiga muscular e cãibras no início da atividade física com a presença do fenômeno de "second wind". O estudo da condução nervosa motora apresentava redução na amplitude do potencial de ação muscular composto após esforço de 30 e 90 segundos em nervos mediano, ulnar e fibular profundo e decremento após 200 estímulos a 40 Hz em nervo fibular profundo. A eletromiografia de agulha apresentava padrão miopático e durante o exercício isquêmico não se evidenciou silêncio elétrico. Discutimos as características eletrofisiológicas enfatizando a importância do estudo da condução nervosa motora e teste de estimulação repetitiva nos pacientes com suspeita de miopatia metabólica.

Potential of adenoviral p53 gene therapy and irradiation for the treatment of malignant gliomas.

We investigated the combined effects of p53 gene transfer and irradiation and its still unclear interaction mechanism in human gliomas. Four human glioma cell lines expressing mutant type p53 (U373 and A172) and wild-type p53 (D54MG and EFC-2) were transfected by adenoviral vectors bearing p53 gene at 50 multiplicity of infection. Two days after transfection, cells were irradiated (3, 6, and 9 Gy). The cytotoxicity was evaluated by clonogenic assay. The quantitative analysis of apoptosis and cell cycle analysis were performed using flow cytometry. Irradiation combined with adenoviral p53 transfection significantly increased cytotoxicity, which was additive in cell lines with wild-type p53 and more than additive in cell lines with mutant p53. The combination of two modalities increased the apoptotic population by 14% in A172 cells and 20% in D54 MG cells, which were the sum of apoptosis from each modality. Adenoviral p53 transfection increased the G1 phase fraction and concomitant decrease of radioresistant S phase fraction in A172 and D54MG cells. Our study demonstrated that p53 gene transfer combined with irradiation increased absolute cytotoxicity in human glioma cells used in this experiment. The interaction mechanism for increased cytotoxicity involved, in part, increased apoptosis and change of cell cycle profile.

Evaluation of bosentan, pinacidil and nitroprusside on human pulmonary arteries: comparison with rat pulmonary arteries.

Bosentan (endothelin ETA/ETB antagonist), pinacidil (potassium channel opener) and nitroprusside (nitric oxide donor) were examined on isolated ring preparations of human intralobar pulmonary artery (3rd-5th generation, internal radius > or = 1 mm), rat main pulmonary artery (1st generation; internal radius > or = 1 mm) and rat intralobar pulmonary artery (3rd generation; internal radius 0.1-0.3 mm). The potency of endothelin-1 was the same in all three artery types. In human intralobar artery and rat main pulmonary artery, bosentan (3 and 10 microM) shifted the endothelin-1 concentration response curve to a higher concentration range (endothelin-1 concentration ratios, in human intralobar and rat main pulmonary artery, respectively: 3 microM bosentan, 4.5 and 8.1; 10 microM bosentan, 13.5 and 19.5), but caused no significant block of endothelin-1 in rat intralobar artery. The latter finding may be due to the reported presence of ETB receptors in rat intralobar arteries and the higher potency of bosentan on ETA than on ETB receptors. In contrast, the potencies of nitroprusside and pinacidil (relaxation of submaximal contractions to the thromboxane-mimetic, U46619) agreed on human and rat intralobar arteries but were 6 to 16-fold lower than on rat main pulmonary artery. We conclude that data obtained on pulmonary arteries from rats can be useful in predicting the effects of vasoactive drugs in human pulmonary arteries but selection of the most appropriate rat artery for study will depend on the drug group under investigation. For potassium channel openers and nitric oxide donors, good agreement between human and rat data will be found when using pulmonary arteries from the same anatomical location even though they differ markedly in size. In contrast, for endothelin antagonists, agreement is more likely to be found in arteries of comparable size, despite their different anatomical locations.

Isolated hypoglossal nerve palsy in Behçet's disease.

Isolated hypoglossal nerve paresis as a manifestation of Behcet's disease has not been reported. We describe a 42-year-old man with isolated unilateral hypoglossal nerve paresis, who had had a five-year history of recurrent orogenital aphthae and relapsing arthritic manifestations. It is suggested that the nerve disorder represents a form of mononeuritis that may occur in Behcet's disease.

Effects of endothelin receptor selective antagonists, BQ-123 and BQ-788, on IRL 1620 and endothelin-1 responses of airway and vascular preparations from rats.

IRL 1620 (Suc-[Glu9, Ala11,15]ET-1(8-21), a selective ETB receptor agonist) contracted rat trachea and bronchus. The maximum response to IRL 1620 was less than that to endothelin-1 (ET-1) and, compared with ET-1 responses, IRL 1620 responses reached equilibrium more quickly. IRL 1620 responses were antagonized by the selective ETB antagonist, BQ-788 (3 microM), but not by the selective ETA antagonist, BQ-123 (3 microM). ET-1 concentration-response curves were shifted only in the presence of both BQ-123 and BQ-788 (3 microM). In the presence of BQ-123, the time course of ET-1 responses changed from being slow and sustained (ETA, see below) to being more like that to IRL 1620 (ETB). IRL 1620 did not contract pulmonary artery preparations from rats but ET-1 produced slow and sustained contractile responses which were antagonized by BQ-123 but not by BQ-788. Thus, ET-1 contracts rat pulmonary artery and aorta predominantly via ETA receptors (responses blocked by BQ-123) and functional ETB receptors are unlikely to be present (no responses to IRL 1620). In contrast, ET-1 contracts rat trachea and bronchus via ETA and ETB receptors (tissues contracted to IRL 1620, ET-1 responses were blocked by a combination of BQ-123 and BQ-788 and ET-1 responses resembled ETB in character when ETA receptors were blocked.

Pinacidil-induced relaxation in pulmonary arteries isolated from pulmonary hypertensive and normotensive rats and pre-contracted with different spasmogens.

Vasorelaxant responses to the potassium channel opening drug, pinacidil, were obtained on preparations of pulmonary artery and aorta taken from rats with pulmonary hypertension (induced by chronic hypoxia or monocrotaline) and pre-contracted either submaximally with endothelin-1 (ET-1), PGF2 alpha, U46619 (thromboxane-mimetic) or noradrenaline (NA), or with 80 mM K+. In pulmonary artery, but not aorta, from pulmonary hypertensive rats the maximum relaxant response to pinacidil was increased, when compared with data in control rats, irrespective of the spasmogen used to precontract the tissues. The increase in maximum was associated with relaxation to below the tissue resting baseline and probably reflected the presence of inherent contractile tone in arteries from pulmonary hypertensive rats. In addition the potency (-log EC50) of pinacidil was increased in pulmonary arteries from pulmonary hypertensive rats but this was seen only in preparations contracted with ET-1 (30-fold increase) or NA (seven-fold increase) and not in those contracted with PGF2 alpha, U46619 or K+. As a result, in ET-1 contracted preparations from pulmonary hypertensive rats pinacidil was 29-fold more potent on pulmonary artery than on aorta. To explain the increase in potency it is speculated that during the development of pulmonary hypertension the mechanism whereby ET-1 and NA contract pulmonary arteries may change from one in which Ca2+ influx plays only a minor role to one in which Ca2+ influx predominates, although no direct evidence to support this speculation has yet been obtained.

Risk factors for acute myocardial infarction in a southern Chinese population.

Although the mortality rate from coronary artery disease in Hong Kong is only one-fourth of that of northern Europe and the United States, the disease has been and remains the second major cause of death (after all cancers combined). Beginning in 1987, we have conducted a case-control study of acute myocardial infarction in four Hong Kong hospitals. This study, one of the biggest case-control studies conducted in the Chinese population of both men and women, confirms the importance of several risk factors--cigarette smoking, history of hypertension, history of diabetes, body fatness, and lack of physical activity--previously described in data collected in western populations. In addition, more adverse childhood experience was also found to be an important risk factor of acute myocardial infarction. Further research in appropriate intervention measures in education in the prevention and cessation of smoking, the control of blood pressure, diabetes, and overweight, and adequate exercise could significantly help reduce the risk of acute myocardial infarction in the Hong Kong Chinese population.

Lipids, lipoproteins and other coronary risk factors in Chinese male survivors of myocardial infarction.

OBJECTIVE: To assess the importance of an abnormal lipid profile as a risk factor in relation to non-biochemical risk factors, and to define the risk levels for lipid, lipoprotein and apolipoprotein in a Chinese population. PATIENTS AND METHODS: Serum lipids, lipoproteins, apolipoproteins and other cardiovascular risk factors were studied in 89 Chinese men 3 months after acute myocardial infarction and 56 controls. RESULTS: Cases had higher mean total cholesterol (TC), LDL- and VLDL-cholesterol, triglycerides and apolipoprotein B (Apo B), and lower mean HDL-cholesterol and apolipoprotein AI (Apo AI). Mean BMI was also higher, as was the prevalence of smokers and subjects with a history of hypertension. In univariate analysis, the odds ratios for TG > or = 1.6 mmol/l, LDL-cholesterol > or = 4.1 mmol/l, VLDL-cholesterol > or = 0.73 mmol/l, Apo B > or = 104 mg/dl were of the same order of magnitude as being a current smoker, having a BMI > or = 24.3 kg/m2, and a history of hypertension. High HDL-cholesterol (> or = 1.39 mmol/l) and Apo AI (> or = 139 mg/dl) were protective factors. The odds ratios for successively higher quartile values of cholesterol were not statistically significant. Multiple logistic regression identified smoking habit, history of hypertension, obesity, high Apo B and low Apo AI concentrations as independent risk factors for myocardial infarction. CONCLUSIONS: In a Chinese population, low serum Apo AI and high Apo B are risk factors for myocardial infarction of a comparable magnitude to smoking, hypertension and obesity.

Pentoxifylline in the treatment of acute ischaemic stroke--a reappraisal in Chinese stroke patients.

A double-blind, randomized and placebo-controlled trial was conducted on 110 Chinese patients with ischaemic stroke who were stratified into 2 subtypes (cortical and lacunar infarcts) according to their clinical and CT findings. Treatment was started within 36-48 hours after the stroke onset. Pentoxifylline was administered intravenously in a dose of 600 mg daily for 5 days, together with oral aspirin 150 mg daily. Neurological deficits were scored on admission and at one week. Demographic data were comparable between the treatment and placebo groups. For cortical infarcts, there were significantly more patients in the placebo group who deteriorated and died than in the treatment group (p < 0.02). As for the lacunar infarcts, there was no difference between groups in the numbers of patients who improved or deteriorated. Our study shows that the positive effect of pentoxifylline can be demonstrated only in patients with cortical infarction. Early deterioration and mortality were significantly decreased in these patients. The clinical course of lacunar infarction was not affected by pentoxifylline. It is not clear whether aspirin may potentiate the antiplatelet function of pentoxifylline and contribute to its temporary clinical efficacy in this way.

Tissue selectivity and spasmogen selectivity of relaxant drugs in airway and pulmonary vascular smooth muscle contracted by PGF2 alpha or endothelin.

1. The spasmolytic effects of smooth muscle relaxant drugs with different mechanisms of action have been examined on isolated preparations of guinea-pig trachea and rat pulmonary artery. The preparations were contracted with concentrations of prostaglandin F2 alpha (PGF2 alpha) or endothelin selected to give approximately 80% of the agonist maximum response on each tissue. These concentrations also caused similar levels of tone (% of tissue maximum contraction) on each tissue. 2. With endothelin as the spasmogen, the potassium channel opening drug, pinacidil, was more potent on trachea (-log IC50 5.49) than on pulmonary artery (4.39), i.e. was airway-vascular selective, whereas with PGF2 alpha as the spasmogen it was more potent on pulmonary artery (6.01) than on trachea (5.27), i.e. was vascular-airway selective. 3. With endothelin as the spasmogen, fenoterol was also airway-vascular selective (8.35 on trachea; little effect on pulmonary artery), nitroprusside was vascular-airway selective (7.50 on pulmonary artery; 5.99 on trachea) and forskolin was non-selective (6.69 on trachea; 6.70 on pulmonary artery). Thus, the airway-vascular selectivity of the relaxant drugs varied with the drug. 4. On pulmonary artery, pinacidil, nitroprusside and forskolin were all more potent against PGF2 alpha than against endothelin, i.e. 42, 4 and 7 fold respectively. On trachea, these drugs were equipotent against PGF2 alpha and endothelin. 5. The results suggest that, in pulmonary artery, but not in trachea, the relative contribution of protein kinase C activation and calcium influx to the maintenance of tonic contractions to endothelin and PGF2 alpha may be different. If protein kinase C activation should be the predominant mechanism for endothelin in pulmonary artery, then it may be more difficult to reverse this with relaxant drugs that lower intracellular calcium. 6. The study indicates that the airway-vascular selectivity of relaxant drugs can be spasmogen-dependent as well as dependent on the mechanism of action of the relaxant drug. Thus, relaxant drugs, whether of interest for their airway or vascular effects, should be tested against a full range of spasmogens of likely pathophysiological importance.

Increased relaxation by felodipine on pulmonary artery from rats with monocrotaline-induced pulmonary hypertension does not reflect functional impairment of the endothelium.

The effects of the calcium entry blocking drug, felodipine, were examined against the spasmogens, noradrenaline, 5-hydroxytryptamine (5-HT) and endothelin on pulmonary artery preparations taken from rats treated with saline or monocrotaline (endothelium present) and from untreated rats (endothelium removed). In saline-treated rats, the potencies (negative log EC50) of noradrenaline, 5-HT and endothelin were 7.97, 5.25 and 8.39 respectively, and felodipine (10 nM) reduced the maximum responses to noradrenaline (28% reduction) and 5-HT (47% reduction), without reducing their potency. In monocrotaline-treated rats, the potencies of noradrenaline, 5-HT and endothelin were 8.43, 6.42 and 8.44, and felodipine significantly reduced the potencies of noradrenaline (0.60 log units) and 5-HT (0.48 log units) in addition to reducing their maximum responses (60% and 69% reductions, respectively). Felodipine had no effect on endothelin in either group of rats. Removal of the endothelium caused a small increase in the potency of 5-HT, but had no influence on the other spasmogens or on the effects of felodipine. It is concluded that monocrotaline treatment of rats leads to increases in a) the potencies of noradrenaline and 5-HT on pulmonary artery, and b) the effectiveness of felodipine against these two spasmogens. Neither of these increases can be attributed to monocrotaline-induced endothelial cell damage.

Creutzfeldt-Jakob disease in Hong Kong. A case report.

This is a report of a Chinese male, aged 67, who had been ill for 6 months and who was admitted with left hemiparesis and dementia. The diagnosis of Creutzfeldt-Jakob disease (CJD) was confirmed by serial electroencephalographic (EEG), computed tomographic (CT) and neuropathological studies. This is the first formal report of CJD occurring in Hong Kong.