Remote assessment of the Penn computerised neurocognitive battery in individuals with 22q11.2 deletion syndrome.

BACKGROUND: Neurocognitive functioning is an integral phenotype of 22q11.2 deletion syndrome relating to severity of psychopathology and outcomes. A neurocognitive battery that could be administered remotely to assess multiple cognitive domains would be especially beneficial to research on rare genetic variants, where in-person assessment can be unavailable or burdensome. The current study compares in-person and remote assessments of the Penn computerised neurocognitive battery (CNB). METHODS: Participants (mean age = 17.82, SD = 6.94 years; 48% female) completed the CNB either in-person at a laboratory (n = 222) or remotely (n = 162). RESULTS: Results show that accuracy of CNB performance was equivalent across the two testing locations, while slight differences in speed were detected in 3 of the 11 tasks. CONCLUSIONS: These findings suggest that the CNB can be used in remote settings to assess multiple neurocognitive domains.

Influence of gestational diabetes mellitus on neonatal weight outcome in twin pregnancies.

AIMS: To evaluate the influence of gestational diabetes mellitus on neonatal birthweight, macrosomia and weight discrepancy in twin neonates. METHODS: An observational retrospective study was performed. One hundred and six women with gestational diabetes and twin pregnancy and 166 twin controls who delivered viable fetuses > 24 weeks were included. Impact of maternal pre-pregnancy BMI, smoking habit, method of conception, chorionicity, gestational age at delivery, mode of delivery and hypertensive complications were also analysed. The effect of maternal hyperglycaemia and metabolic control in gestational diabetes pregnancies was assessed. RESULTS: Gestational hypertension and pre-eclampsia were significantly higher in the group with gestational diabetes (21.5% vs. 6.3%, P = 0.007 and 6.2% vs. 0%, P = 0.025). There were no differences in the incidence of macrosomia (5.7% vs. 7.2%, P = 0.803), large for gestational age (10.3% vs. 13.2%, P = 0.570), small for gestational age (10.3% vs. 12.0%, P = 0.701), severely small for gestational age (6.6% vs. 7.8%, P = 0.814) or weight discrepancy (20.6% vs. 15.2%, P = 0.320) in the group with gestational diabetes compared with twin pregnancies without diabetes. There were no differences when comparing insulin-requiring gestational diabetes pregnancies and twins without diabetes for any of the neonatal weight outcomes. There was no relationship between third trimester HbA1c and neonatal birthweight or infant birthweight ratio. CONCLUSION: Gestational diabetes did not increase the risk of macrosomia or weight discrepancy of twin newborns. Furthermore, glycaemic control did not influence the rate of any of the weight outcomes in our study population. In twin pregnancies, gestational diabetes was associated with a higher risk of gestational hypertension and pre-eclampsia.

What is the relative contribution of blood glucose levels at different time points of the day to HbA1c in Type 1 diabetes?

AIMS: To evaluate the relative contribution of blood glucose levels at different time points of the day to HbA(1c) in Type 1 diabetes. METHODS: Consecutive home blood glucose records (n = 146) from 71 Type 1 diabetic patients who were on an intensive diabetes therapy programme were examined. Each home blood glucose record included six daily blood glucose profiles over 2 months. The relationship between glycaemic values at each time point and HbA(1c) measured at the end of each record period was analysed. RESULTS: Significant linear correlations were found between HbA(1c) and glycaemia at each time point of the day (ranged from 0.413 to 0.593), the strongest being with predinner glycaemia (r = 0.593; P = 0.000). Total daily glycaemia, mean preprandial and mean postprandial glycaemia were also significant and linearly correlated with HbA(1c) (r = 0.701; r = 0.686; r = 0.620, respectively; P < 0.0001). Multiple linear regression analysis showed that predinner, prebreakfast and post-breakfast glycaemia correlated significantly and independently with HbA(1c). The model accounted for 47.8% of the variance in HbA(1c). CONCLUSIONS: Our study shows that among individual time points, prebreakfast and predinner are those with more influence on HbA(1c) in Type 1 diabetes and, to a lesser extent, post breakfast. It also confirms that preprandial glycaemia better predicts overall glycaemic control in Type 1 diabetes than postprandial glycaemia.

Regulation of microvascular permeability by vascular endothelial growth factors.

Generation of new blood vessels from pre-existing vasculature (angiogenesis) is accompanied in almost all states by increased vascular permeability. This is true in physiological as well as pathological angiogenesis, but is more marked during disease states. Physiological angiogenesis occurs during tissue growth and repair in adult tissues, as well as during development. Pathological angiogenesis is seen in a wide variety of diseases, which include all the major causes of mortality in the west: heart disease, cancer, stroke, vascular disease and diabetes. Angiogenesis is regulated by vascular growth factors, particularly the vascular endothelial growth factor family of proteins (VEGF). These act on two specific receptors in the vascular system (VEGF-R1 and 2) to stimulate new vessel growth. VEGFs also directly stimulate increased vascular permeability to water and large-molecular-weight proteins. We have shown that VEGFs increase vascular permeability in mesenteric microvessels by stimulation of tyrosine auto-phosphorylation of VEGF-R2 on endothelial cells, and subsequent activation of phospholipase C (PLC). This in turn causes increased production of diacylglycerol (DAG) that results in influx of calcium across the plasma membrane through store-independent cation channels. We have proposed that this influx is through DAG-mediated TRP channels. It is not known how this results in increased vascular permeability in endothelial cells in vivo. It has been shown, however, that VEGF can stimulate formation of a variety of pathways through the endothelial cell, including transcellular gaps, vesiculovacuolar organelle formation, and fenestrations. A hypothesis is outlined that suggests that these all may be part of the same process.

Resection of Kommerell's diverticulum and left subclavian artery transfer for recurrent symptoms after vascular ring division.

OBJECTIVES: A Kommerell's diverticulum in patients with a right aortic arch may become aneurysmal and be an independent cause of tracheoesophageal compression, even after ligation and division of a left ligamentum. We review the indications for and results of Kommerell's diverticulum resection and left subclavian artery transfer in children with a right aortic arch who previously underwent vascular ring (ligamentum) division. METHODS: From 1998 through 2001, eight children have been referred with recurrent respiratory symptoms (n=8) and/or recurrent dysphagia (n=4) after vascular ring division. Each child had a right aortic arch with a left ligamentum and had undergone division of the ligamentum elsewhere. All had a Kommerell's diverticulum that was not addressed at the initial operation. All patients had a repeat left thoracotomy with resection of the diverticulum. Five patients had division and reimplantation of the left subclavian artery into the left carotid artery to relieve the sling-like effect of the retroesophageal left subclavian artery on the right aortic arch. One other patient had primary Kommerell's diverticulum resection and transfer of the left subclavian artery to the left carotid artery. RESULTS: The mean age at the initial operation was 1.7+/-0.9 years, and the mean age at reoperation was 8.0+/-3.7 years. In all patients postoperative bronchoscopy confirmed relief of the tracheal compression. There were no complications related to the subclavian artery transfer. Two patients developed postoperative chylothorax, one requiring thoracic duct ligation. The median hospital stay was 5 days. All patients had dramatic resolution of their preoperative symptoms. CONCLUSIONS: Kommerell's diverticulum is an important anatomic structure that can cause recurrent symptoms in patients with a right aortic arch after ligamentum division. In selected patients, reoperation with resection of the Kommerell's diverticulum and transfer of a retroesophageal left subclavian artery results in relief of symptoms. This technique has become our procedure of choice as a primary operation for children with a right aortic arch and a significant Kommerell's diverticulum.

Increased numbers of caveolae in retinal endothelium and pericytes in hypertensive diabetic rats.

PURPOSE: Long-term clinical studies have now shown that tight control of blood pressure in type 2 diabetes reduces the risk of diabetes-related death and common diabetic complications, including diabetic retinopathy. However, the mechanisms by which hypertension enhances diabetic microvascular disease, especially diabetic retinopathy, are poorly understood. We developed an experimental model of hypertension in diabetic rats and studied the early ultrastructural changes in retinal capillaries under these conditions. METHODS: Hypertension was induced in diabetic BioBreeding (BB) rats by unilateral nephrectomy, weekly subcutaneous mineralocorticoid and 0.9% oral saline. Serial blood pressures and ultrastructural features of retinal capillaries were recorded in four groups: normotensive Wistar rats, normotensive diabetic rats, hypertensive Wistar rats and hypertensive diabetic rats. RESULTS: A significant and sustained increase in systolic blood pressure occurred in both groups of nephrectomised rats. There was a significant increase in the number of caveolae (i) in both pericytes and endothelial cells in animals with hypertension and diabetes together compared with all other groups and (ii) in pericytes in animals with diabetes alone. The number of direct contacts between pericytes and endothelial cells was reduced in diabetic and hypertensive diabetic animals. Hypertension and diabetes had an interactive effect in producing retinal capillary basement membrane thickening. CONCLUSIONS: In the BB rat hypertension and diabetes have an interactive effect in increasing the number of caveolae in both endothelial cells and pericytes. We speculate that this may be a reflection of changes in calcium and nitric oxide metabolism in these animals.

Differential effects of vascular endothelial growth factor-C and placental growth factor-1 on the hydraulic conductivity of frog mesenteric capillaries.

Vascular endothelial growth factors (VEGFs) are known to increase vascular permeability. VEGF-A acts on two receptor tyrosine kinases, VEGF receptor-1 (VEGF-R1 or flt-1) and VEGF receptor-2 (VEGF-R2, flk-1 or KDR). VEGF-C acts only on VEGF-R2 on vascular endothelial cells, whereas placental growth factor-1 (PlGF-1) acts only on VEGF-R1. The effects of perfusion of these receptor-specific proteins on hydraulic conductivity (L(p)) was measured in frog mesenteric capillaries. The effect of PlGF on L(p) was not conclusive, and overall fluid flux did not increase during that time. VEGF-C acutely and transiently increased L(p) (4.5 +/- 0.9-fold), which was more obvious in a subset of vessels, in a similar manner to that reported for VEGF-A. In the subset of vessels in which VEGF-C significantly increased L(p) acutely, there was a sustained 12-fold increase in L(p) 20 min after perfusion, but this was not seen in those vessels which did not respond acutely to VEGF-C, or in vessels exposed to PlGF-1. L(p) was also increased 24 h after perfusion with VEGF-C, but not with PlGF-1. Western blot analysis showed that VEGF-R1 and VEGF-R2 are both present in frog tissue. These data show that the VEGFs that stimulate VEGF-R2 chronically increase L(p), but not those that stimulate VEGF-R1 only. This supports the hypothesis that chronic increases in microvascular permeability induced by VEGF are mediated via activation of VEGF-R2 rather than VEGF-R1.

[Nutritional management of radiation-induced enteritis: apropos of a case]. / Manejo nutricional en la enteritis rádica: a propósito de un caso.

We present a case of a 46-year-old woman who is hospitalized in March of 1997 for a picture of severe mixed malnutrition. We describe the clinical history since the diagnosis of an endometrium carcinoma in 1995, treated with radiation therapy, with the aim of determining the etiology of the severe malnutrition picture, as well as the different complications she presented in the course of her hospitalization that justify the decisions made in the choice of the nutritional support.

Supraarterial decompression myotomy for myocardial bridging in a child.

A 10-year-old boy presented with a history of exertional chest pain. An electrocardiogram demonstrated an inferior apical myocardial infarction. Cardiac catheterization revealed myocardial bridging of the left anterior descending coronary artery with evidence of intramyocardial obstruction during systole. The patient underwent successful treatment with supraarterial decompression myotomy and remains symptom free at 1 year.

[Critical analysis of the evolution of commercial preparations for enteral nutrition during 1988-1996]. / Análisis crítico de la evolución de los preparados comerciales enterales en el período 1988-1996.

Enteral nutrition is a form of nutritional support that is continually growing and expanding, and within this area especially the enteral preparations or formulae. The object of the present is to analyze the evolution of the commercially available nutritionally complete enteral preparations between 1988 and 1997, illustrating the variations that have occurred both from the quantitative and form the qualitative points of view. A progressive increase is seen in the absolute number of available enteral formulae, with the increase in both polymeric formulae with dietary fiber, and that of formulae designed for specific diseases being significant (p < 0.05). The standard polymeric formulae and the oligomeric formulae decrease, but not in a significant manner. There is a special discussion or the characteristic and the usefulness of the polymeric formulae with dietary fiber ad the formulae designed especially for specific diseases. The clinical efficacy of most of these special formulae is controversial, with there not being sufficient objective clinical evidence at present that justifies their routine use.

Hepatobiliary dysfunction as the initial manifestation of disseminated cryptococcosis.

A case of hepatobiliary dysfunction as the initial manifestation of disseminated cryptococcosis is described. The patient was admitted with symptoms of hepatitis with cholestatic jaundice. Antibody tests for hepatitis B and C and human immunodeficiency virus were negative. The patient continued to deteriorate clinically. Eventually, the patient succumbed to hepatic failure. Autopsy disclosed systemic cryptococcosis that caused extensive necrosis of the liver. In review of the literature, only nine cases of cryptococcal infection presenting as hepatitis, cholangitis, and cholecystitis as initial manifestation were reported. Four of these patients had been subjected to exploratory laparotomy for clinical suspicion of acute abdomen. One patient developed cirrhosis as a result of cryptococcal hepatitis. Two patients succumbed to hepatic failure. Cryptococcosis is known to occur commonly in immunocompromised patients, yet only two reported cases presenting as hepatitis were associated with immunocompromised status.

Efficacy of octreotide in the regression of a metastatic carcinoid tumour despite negative imaging with In-111-pentetreotide (Octreoscan).

We present the case of a 52-year old patient diagnosed with carcinoid tumour of the rectum with liver metastases in which treatment with somatostatin analogues (octreotide) proved very effective in the disappearance of the symptomatology and dramatic efficacy in the regression of the tumour. Imaging by octreoscan was always negative. The role of octreotide in the treatment of carcinoid tumour and the usefulness of In-111-pentetreotide (octreoscan) in the localization and prediction of the response to treatment with octreotide is discussed. We conclude that the negative result of the scintigraphic image with octreoscan does not necessarily suppose the inefficacy of octreotide treatment. We believe that this may constitute an important issue since some patients may be denied octreotide treatment in the absence of a positive octreoscan result.

Decreased heart-period variability in patients with panic disorder: a study of Holter ECG records.

This study investigated cardiac autonomic function in patients with panic disorder and normal controls using Holter ECG records. A decrease in ultra-low frequency power (< 0.0033 Hz) is known to be associated with an increased risk for cardiovascular mortality in humans. Twenty-four-hour ECG was recorded in 29 patients with panic disorder and 23 normal controls using Holter records. Data for 20 h and also 20000 s of awake and 20000 s of sleep periods were analyzed using spectral analysis to quantify absolute and relative heart-period variability in ultra low (ULF: < 0.0033 Hz), very low (VLF: 0.0033-0.04 Hz), low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency bands. The patients with panic disorder had significantly lower total and absolute ULF power, which was more pronounced during sleep. The patients also had significantly lower relative ULF power and significantly higher relative LF power during sleep. There was a significant increase of relative LF power from awake to sleep period only in the patient group. The decrease in total and ULF power may increase the risk of mortality and sudden arrhythmic death in patients with panic disorder if they experience a cardiac event. The higher relative LF power during sleep also suggests a possible higher sympathetic drive in the patients during sleep.

Method for creation of the aortotomy site for saphenous vein grafts.

Saphenous vein coronary artery bypass grafting requires a proximal anastomosis of the vein to the aorta. A variety of techniques have been described to create the aortotomy. We have developed a four-sided knife (Xcision Scalpel; patent pending, Research Medical, Inc, Midvale, UT) that facilitates the creation of a more uniform circular aortotomy. The purpose of this communication is to describe the knife and the technique for its use.

Inhaled nitric oxide, right ventricular efficiency, and pulmonary vascular mechanics: selective vasodilation of small pulmonary vessels during hypoxic pulmonary vasoconstriction.

OBJECTIVE: In the setting of acute pulmonary artery hypertension, techniques to reduce right ventricular energy requirements may ameliorate cardiac failure and reduce morbidity and mortality. Inhaled nitric oxide, a selective pulmonary vasodilator, may be effective in the treatment of pulmonary artery hypertension, but its effects on cardiopulmonary interactions are poorly understood. METHODS: We therefore developed a model of hypoxic pulmonary vasoconstriction that mimics the clinical syndrome of acute pulmonary hypertension. Inhaled nitric oxide was administered in concentrations of 20, 40, and 80 ppm. RESULTS: During hypoxic pulmonary vasoconstriction, the administration of nitric oxide resulted in a significant improvement in pulmonary vascular mechanics and a reduction in right ventricular afterload. These improvements were a result of selective vasodilation of small pulmonary vessels and more efficient blood flow through the pulmonary vascular bed (improved transpulmonary vascular efficiency). The right ventricular total power output diminished during the inhalation of nitric oxide, indicating a reduction in right ventricular energy requirements. The net result of nitric oxide administration was an increase in right ventricular efficiency. CONCLUSION: These data suggest that nitric oxide may be beneficial to the failing right ventricle by improving pulmonary vascular mechanics and right ventricular efficiency.

[Results of nutritional treatment of anorexia nervosa: our experience (1989-1995)]. / Resultado del tratamiento nutricional de la anorexia nervosa: nuestra experiencia (1989-1995).

With the alm of evaluating the nutritional treatment of anorexia nervosa (AN) in our center, evolutive data were collected, as well as anthropometric and biochemical parameters, of out out patient department (OPD) as well as of our hospital admissions (HA) which took place between 1989-91 (period A) and between 1992-95 (period B). 79 cases of HA were included (5 men, 31 women), with a duration of hospitalization of 36.96 +/- 22.02 days, with the reason for release most often (86.84%) being reaching the agreed upon weight, and 124 cases of OPD (12 men and 112 women), who were followed for 11.53 +/- 12.13 months achieving a final release rate of 14.14%. The nutritional status (NS) of the HA patients upon admission was most often sever caloric malnutrition (CM) (64.55%), and upon release this was moderate CM (60.75%), while in the OPD the moderate CM was most frequent at the initial visit and at the last visit registered. The anthropometric parameter which was most affected, was the triceps fold (TF), followed by the wight (W). The biochemical abnormalities were few, with hypercholesterolemia and ferropenia being notable. The nutritional treatment in the OPD required the addition of dietary supplements in 31% of the cases, and of psycho-medication in 43%. In the HA cases, only 6 patients reached the agreed upon wight with a free oral diet, and 35 patients required dietary supplements, 20 needed mixed therapy (enteral nutrition and supplements), and 17 cases required enteral nutrition through a naso-gastric tube. Significant multivariant models are presented which find independent associations for the probability of release (lower age upon diagnosis, male, lower income, absence of bulimia's, no need for dietary supplements), of amenorrhoea (worse NS, absence of vomiting), and for the HA time (more interventionist treatment, lower weight, lower age). The comparison between periods, shows an initial contact of the patients with AN with our OPD, with a better nutritional status y recent years, as well as a better nutritional result, a greater tendency towards the use of enteral nutrition, and a shorter time of HA.

Predictive factors for high mortality in hypernatremic patients.

Hypernatremia (serum sodium level of > 145 mEq/L) is associated with high mortality. This study reports an analysis of mortality in 116 patients with hypernatremia from two large university-affiliated teaching hospitals. The purpose was to identify factors predictive of high mortality in hypernatremic patients. Medical records were reviewed to obtain the following data: serum sodium (Na+) levels; systolic (S) and diastolic (D) blood pressure (BP) at the time of admission and throughout the hospital course; status of cognitive function; and type of fluid administered. The patients were divided into two groups: expired and survived. Seventy-seven of 116 patients (66%) expired, while 39 patients (34%) survived and were discharged from the hospital. The mean age and gender for patients who died (70.9 +/- 15.4 years, 90% men) were not different from those who survived (66.4 +/- 17.3 years, 87% men). For the serum Na+ levels recorded at three different times (early, peak, and late), mean late serum Na+ level during hospital course was significantly higher in patients who died than in those who survived (151.2 +/- 9.2 v 143.1 +/- 8.0 mEq/L, respectively; P < .001). Mean admission serum Na+ level (154.9 +/- 5.5 v 155.1 +/- 7.7 mEq/L, respectively) and mean peak serum Na+ level (157.5 +/- 6.5 v 156.8 +/- 9.4 mEq/L, respectively) were not different between the two groups. Both SBP and DBP at the time of admission (P < .05) and throughout the hospital course (P < .001) were significantly lower in the patients who died than in those who survived. The cognitive abnormalities consisting of confusion, obtundation, and speech abnormality were significantly (P < .05) higher in the expired patients than in those who survived. Normal (isotonic) saline was used significantly more frequently (P < .00001) in patients who expired than in those who survived. Thus, this study suggests that a persistently elevated serum Na+ level (possibly caused by prolonged infusion of normal saline) in association with protracted hypotension portends a dismal prognosis in hospitalized hypernatremic patients.

Diffuse histoplasmosis in a patient with sarcoidosis.

A case is presented of a woman with a long history of sarcoidosis who developed diffuse histoplasmosis. Although association between these two entities has been described before, there are only a few case reports of histoplasmosis among sarcoid patients. Diagnosis was finally established by bone marrow biopsy which saved the patient's life.

Contrast echocardiography: influence of ultrasonic machine settings, mixing conditions, and pressurization on pixel intensity and microsphere size of Albunex solutions in vitro.

To use Albunex as a blood-flow tracer, the stability and consistency of microspheres under mixing conditions must be known. This study examined the effects of mixing conditions and machine settings on the size and echogenicity of Albunex solutions in vitro. Acoustic power, log compression, time-gain compensation, and transducer frequency were varied as Albunex solutions were imaged after mixing with magnetic stirring and pressurized. Higher acoustic power and lower transducer frequency decreased mean pixel intensity of Albunex solution images over time. Intensity, size, and number of Albunex microspheres were not significantly different between stirring speeds. The echogenicity of the Albunex solutions decreased with pressurization, and the critical pressure necessary to reduce the intensity to half its initial value increased with the logarithm of concentration (r = 0.91; p < 0.001). The microsphere size decreased with pressurization and remained smaller after pressure release (3.66 +/- 2.13 versus 1.47 +/- 0.95 microns; p < 0.01). These data indicate that acoustic power and transducer frequency may affect the physical properties of Albunex microspheres, decreasing mean videointensity. Pressure sensitivity of Albunex caused the decrease of videointensity and microsphere size.