Computer simulation of neuronal toxicity in the spinal cord

Abstract

The use of computers to model biological systems is a relatively new research tool. For examplel it is possible to write mathematical systems to model neuronal activity involved in memory and learning and to model blood flow in any organ such as the brain. There is also an interest in designing computer-controlled machines to simulate human activities such as hand movements and vision. One of the most important uses of computer modeling is as a research tool to test hypotheses and aid in formulating new hypotheses. This enables the investigator to apply preliminary tests on several experimental strategies and select for animal experimentation the ones that are most likely to produce unambiguous and interpretable results. In the following articlel we describe a computer model of neuron toxicity in the mammalian spinal cord. [Neural Res 1997; 19: 340–348]     

Changes in the levels of indoleamine phytochemicals during véraison and ripening of wine grapes

Abstract: Melatonin and serotonin have previously been described in mature wine grapes and finished wines, but the metabolism of these signalling molecules in the development of wine grapes has not previously been investigated. We harvested wine grapes at different stages of development from lag phase through véraison from eight different commercial vineyards representing a diversity of growing conditions, management practices, merlot varietals and localized ecosystems to determine whether different patterns in melatonin and serotonin can be found in wine grapes during seed development and berry maturation. Melatonin was detected in 45% of the fully developed purple, postvéraison grapes but only found in 23% of prelag phase samples. However, the actual concentration of melatonin was highest in wine grapes harvested at the early stage of véraison when the seed is developing. Serotonin was not detected in any of the prelag phase grapes but was consistently detected in 30–35% of grapes harvested during the véraison transition at consistent levels of about 8–10 μg/g. Interestingly, the nitrogen storage compound γ‐aminobutyric acid was also found at about 115 μg/g in 77% of early stage green grapes and declined in both prevalence and concentration with ripening. Together, these data are indicative of a potential role for these molecules in the development and maturation of wine grapes.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Cutaneous Blood Flow and Peripheral Resistance in Type II Diabetes as Compared to Intermittent Claudication Patients

Insulin deficient, type I diabetic patients have reduced skin blood flow reserve. It is not known whether these skin perfusion abnormalities also exist in non-insulin dependent (type II) diabetic patients. An additional open question is whether the reduced skin blood flow is due to increased resistance of the cutaneous microvasculature or to decreased peripheral perfusion pressure due to increased atherosclerosis in the diabetic population. We measured skin blood flow by laser Doppler flowmetry in patients with type II non-insulin treated diabetes. Limb systolic blood pressure was measured distally using a sensitive sonar Doppler device at the finger and toe. The ratio of pressure to flow was computed as an index of peripheral blood flow resistance. To assess the effect of cutaneous blood flow resistance, we elicited maximal vasodilation by increasing local skin temperature directly at the site of the laser Doppler probe. We compared blood flow and pressure in diabetic patients with the values in non-diabetic control patients. As a further control population, we also assessed these same parameters in non-diabetic patients with peripheral vascular disease, which may be expected to decrease large arterial blood flow pressure without directly affecting the microvasculature. There were 68 type II diabetic patients, 18 non-diabetic control subjects, and 25 non-diabetic patients with intermittent claudication. We measured skin blood flow at the dorsal surfaces of the finger and toe, sites with primarily nutritive capillary perfusion, and at the plantar surfaces of the finger and toe, where arteriovenous shunt perfusion predominates. Heat stimulated flow was markedly lower for the diabetic patients at the finger dorsal surface (16.5 ± 1.4 ml/min/100 g vs 29.8 ± 4.4 ml/min/100 g in the non-diabetic group (p < 0.05). The resistance index was 13.2 ± 1.9 in the diabetic patients and 6.8 ± 1.7 in the controls (p < 0.05). At the toe dorsum, basal temperature flow was significantly lower in the diabetic group (0.6 ± 0.1 ml/min/100 g) than in the non diabetic group (1.1 ± 0.2 ml/min/100 gm) with resistance index almost twice as high (379 ± 32) in the diabetic group versus non-diabetic controls (208 ± 36) [p < 0.01 for both comparisons]. With the local application of heat, there was a much larger increase in flow in the non-diabetic subjects than in the diabetic group. The resistance index dropped much more with heat stimulation for the non-diabetic patients (10.8 ± 3.3) than for the diabetic patients (50.6 ± 10.4) [p < 0.01] There was a lesser rise in flow at the toe pulp surface with heat in the diabetic patients (31.3 ± 3.0 ml/min/199 gm) than in the control subjects (45.4 ± 5.9 ml/min/100 gm; p < 0.05) with a higher resistance index (13 ± 4) than in the non-diabetic subjects (4 ± 1) [p < 0.05]. The claudication patients had substantially greater flow at the toe dorsal surface at basal temperature (2.2 ± 0.4 ml/min/100 gm) with significantly lower resistance index (126 ± 24) than the non-diabetic controls (p < 0.05). At 44°C, toe dorsum flow was significantly higher (17.8 ± 3.7 ml/min/100 gm) than in the diabetic patients with lower resistance index (17.0 ± 6.6) [p < 0.05]. Toe pulp flow at basal temperature was significantly higher (10.1 ± 2.0 ml/min/100 gm) than in either the diabetic (3.8 ± 0.6) or non-diabetic control groups (3.5 ± 1.4) [p < 0.05]. Skin blood flow is impaired in diabetes. The reduction is due to increased resistance in the capillary bed rather than to reduced perfusion pressure. The increased resistance was found only in the diabetic patients, not in the non-diabetic patients with peripheral vascular disease. To the contrary, there appeared to be a compensatory decrease in skin flow resistance in the patients with peripheral vascular disease. Thus, there is a small vessel disease which impairs cutaneous perfusion in diabetes, but there is no such effect on skin blood flow in non-diabetic patients with large vessel disease.     

Multiple pulmonary nodules

A 48-year-old post-menopausal female was referred to us in view of her chest radiograph showing multiple pulmonary nodules (Figure 1). She complained of fever and arthralgia since one month. She had been diagnosed as allergic rhinitis with mild episodic asthma since childhood on the basis of symptomatology and was on inhaled steroids and bronchodilators for the same. There was no history of receiving oral corticosteroids or leukotreine antagonists for asthma. Clinical examination did not reveal any abnormality.     

Role of tissue harmonic imaging in focal hepatic lesions: comparison with conventional sonography

Background: The purpose of the present study was to compare iissue harmonic imaging (THI) and conventional sonography in focal hepatic lesions. Methods: Fifty patients with focal hepatic lesions were enrolled for study. Conventional grayscale and THI was performed in all the patients and two sets of images of the lesions were recorded (one each for THI and conventional) and assessed for fluid–solid differentiation, detail and overall image quality. These images were compared with conventional sonographic images and graded better, same or worse as per the case. Lesions were confirmed by fine‐needle aspiration cytology (FNAC)/surgery/other modalities such as computed tomography (CT) or magnetic resonance imaging (MRI). Results: Out of 50 patients with focal hepatic lesions, 21 patients had metastatic lesions (two single; 19 multiple) five patients had hepatocellular carcinoma (HCC), five patients had hydatid cysts, nine had simple hepatic cyst whereas five patients had liver abscess, three had focal fatty infiltration; and lymphoma and hemangioma were seen in one patient each. The first observer ranked THI better than standard sonography in 40 patients (80%) for fluid–solid differentiation, in 38 (76%) for detail and in 39 (78%) for overall image quality. The second observer ranked THI better than standard sonography in 39 patients (78%) for fluid–solid differentiation, in 40 (80%) for detail and in 42 (84%) for overall image quality. Tissue harmonic imaging provided additional information in eight patients (16%) and resulted in treatment alteration in three patients (6%). Conclusion: Tissue harmonic imaging was significantly better than conventional sonography for fluid–solid differentiation, detail and total image quality in focal hepatic lesions, especially in obese patients and patients with poor acoustic window.     

Natural history of secundum atrial septal defect revisited in the era of transcatheter closure

BACKGROUND: Several reports in the past have described the natural history of atrial septal defects, most dealing with a decrease in size or spontaneous closure of the defect. Some recent articles have also described an increase in size of the defect in a sizable number of cases which may be important in the current era of transcatheter closure. We analyzed the data of 52 consecutive cases diagnosed to have secundum atrial septal defect in the first year of life, seen over the last six years at our center. METHODS AND RESULTS: All infants with a defect size of > or =4 mm on echocardiography were included. The first and the last echocardiographic images with a minimum interval of 6 months were used for analysis. Cases were divided into three groups depending upon the defect diameter (small: 4-5 mm, moderate: 6-8 mm and large: > or =9 mm). The age ranged from one day to 12 months (mean 2.9 +/- 3.2 months). On a follow-up of 0.7 to 7.0 years (mean 2.9 +/- 1.4 years), the septal defect reduced in size in 24 (46%) cases with complete closure in 14 of these. The size remained same in 13 (25%) and enlarged in 15 (29%) cases. The likelihood of closure was highest in small defect group as compared to the large defect group (p < 0.05). Similarly, enlargement was more often seen in large defects. CONCLUSIONS: Small atrial septal defects of 4 mm to 5 mm are very likely to decrease in size or completely close on follow-up. Larger defects, on the other hand may remain large or enlarge further in a significant proportion of cases. A close observation is required for these cases if being considered for transcatheter closure.     

Total anomalous pulmonary venous connection: surgical experience in Indians

BACKGROUND: We report a retrospective analysis of the demographic. morphological and clinical profiles of patients along with results of operative repair for total anomalous pulmonary venous connection. METHODS AND RESULTS: In the last 15 years, 248 patients (168 boys, 80 girls) underwent repair for total anomalous pulmonary venous connection. Their ages ranged from I day to 24 years (median 8 months) and 145 of them were < or = 1 year of age. The patients' weight ranged from 2 to 52 kg (median 5 kg). About 70% of patients (n = 174) were less than the 50th percentile of predicted weight for age and sex. The anomalous connection was supracardiac in 134 (54%), cardiac in 80 (32.2%), infracardiac in 9 (3.6%) and mixed in 25 (10.1%) patients. Fifty (20.2%) patients had obstructed drainage and 76 patients (30.2%) had moderate or severe pulmonary arterial hypertension. Forty-five patients (18.1%) had to be operated upon on an emergency basis. All the patients were operated upon using moderately hypothermic cardiopulmonary bypass. In 114 patients, circulatory arrest was used. There were 45 (19.1%) in-hospital deaths. The major causes of early death were pulmonary arterial hypertensive crisis in 19 (7.7%) and low cardiac output syndrome in 17 (6.9%) patients. Age < or = 1 year (odds ratio 2.16; 95% confidence interval: 1.22-3.82, p=0.008), severe pulmonary arterial hypertension (odds ratio 5.86; 95% confidence interval: 2-17, p=0.001), and need for emergency surgery (odds ratio 3.65; 95% confidence interval: 1.59-8.38, p=0.002) were independent risk factors for early death. Follow-up ranged from 1 to 180 months (median 48 months). There were 4 lake deaths. Actuarial survival at 12 years was 92.6% +/- 2.8%. CONCLUSIONS: In Indian circumstances, mortality continues to be high in infants with total anomalous pulmonary venous connection. Severe pulmonary arterial hypertension appears to be the most important predictor of operative mortality. Severe malnutrition, delayed diagnosis and late referrals possibly contribute to the high mortality.