Identification of an extensive ζ-α globin gene deletion in a Chinese individual

We describe a novel alpha-thalassaemia-1 deletion that removes the entire zeta-alpha globin gene cluster. A Chinese couple were referred for counselling after two consecutive pregnancies ended with fetal hydrops. Gene mapping was used to demonstrate that the mother is heterozygous for the South-east Asia alpha-thalassaemia-1 deletion (zeta zeta zeta alpha alpha/zeta zeta--SEA), while the father carries an alpha-thalassaemia-1 deletion of more than 100 kilobases (zeta zeta alpha alpha/----). This newly discovered deletion extends for unknown distances 3' and 5' of the zeta-alpha globin gene cluster and has been designated (--HW).     

TNF alpha and Fas mediate tissue damage and functional outcome after traumatic brain injury in mice.

Tumor necrosis factor-alpha (TNFalpha) and Fas are induced after traumatic brain injury (TBI); however, their functional roles are incompletely understood. Using controlled cortical impact (CCI) and mice deficient in TNFalpha, Fas, or both (TNFalpha/Fas-/-), we hypothesized that TNFalpha and Fas receptor mediate secondary TBI in a redundant manner. Compared with wild type (WT), TNFalpha/Fas-/- mice had improved motor performance from 1 to 4 days (P<0.05), improved spatial memory acquisition at 8 to 14 days (P<0.05), and decreased brain lesion size at 2 and 6 weeks after CCI (P<0.05). Protection in TNFalpha/Fas-/- mice from histopathological and motor deficits was reversed by reconstitution with recombinant TNFalpha before CCI, and TNFalpha-/- mice administered anti-Fas ligand antibodies had improved spatial memory acquisition versus similarly treated WT mice (P<0.05). Tumor necrosis factor-alpha/Fas-/- mice had decreased the numbers of cortical cells with plasmalemma damage at 6 h (P<0.05 versus WT), and reduced matrix metalloproteinase-9 activity in injured brain at 48 and 72 h after CCI. In immature mice subjected to CCI, genetic inhibition of TNFalpha and Fas conferred beneficial effects on histopathology and spatial memory acquisition in adulthood (both P<0.05 versus WT), suggesting that the beneficial effects of TNFalpha/Fas inhibition may be permanent. The data suggest that redundant signaling pathways initiated by TNFalpha and Fas play pivotal roles in the pathogenesis of TBI, and that biochemical mechanisms downstream of TNFalpha/Fas may be novel therapeutic targets to limit neurological sequelae in children and adults with severe TBI.     

Use of long catheters for multipatient anesthetic monitoring at high respiratory frequencies

Anesthetic gases from several patients can be monitored simultaneously with a centrally located mass spectrometer. Such monitoring requires catheters from patient to spectrometer that are several meters long. Scamman (J Clin Monit 1988;4:227–229) found that when the respiratory frequency is high, as with infants, the CO₂ signal from the patient is unacceptably distorted during passage down the catheter. This is due to Taylor dispersion of the input signal. An outline of the theory of Taylor dispersion is given. The equations describe the interaction between the velocity distribution (which, in laminar flow, is parabolic) and the radial diffusion of CO₂. This interaction keeps a tracer signal together in a pulse, as it moves down the tube with themean velocity, spreading somewhat as it proceeds. How much does an initially sharp signal become blurred? The spread of such a signal when it reaches the detector, measured in time, can be expressed in various ways. Measurement is complicated, however, by the fact that the gas pressure may fall by as much as a factor of 10 along the line. The resultant expansion and acceleration of the gas cannot be ignored. A full treatment of this complication is given elsewhere, but the following simple equation is described: {ie237-1} Typically, the spread time is up to a quarter of a second for catheters of 50 m, such as used by Scamman. This is comparable with the period of CO₂ rise and fall for infants and explains the serious distortion in wave form that Scamman found. Some distortion can be eliminated by reducing R to 0.1 or less, but the extent of this improvement is small. Ideally, for fast-breathing patients, the catheter length should be reduced to 20 m or less, if possible.     

示差导数光谱法测定感冒通片中双氯灭痛和扑尔敏的含量

本文利用示差导数光谱法对感冒通片中双氯灭痛和扑尔敏进行定量测定。本法用同一样品液,在同一测定条件下完成,具有操作简便、快速、灵敏度高和重现性好等特点,双氯灭痛和扑尔敏的平均回收率分别为99.5%和97.3%,变异系数分别为0.42%和0.63%.     

Hepatic pseudotumor in long-standing biliary atresia patients undergoing liver transplantation.

A pseudotumor, giant regenerative nodule, or macroregenerative nodule is an unusual benign hepatic lesion in biliary atresia (BA) patients. This tumor may mimic malignant transformation and may preclude liver transplantation (LT). The clinical and imaging surveillance of patients after the Kasai procedure is therefore an important aspect of management of BA patients. Our objective is to report our experience and describe the incidence, imaging, and pathologic features of pseudotumors in BA patients awaiting LT. From August 1990 to December 2006, 133 LTs for BA were performed. Five (3.8%; 4 female, 1 male) patients were diagnosed with pseudotumor. The patients' records were reviewed. The diagnostic imaging modalities used were abdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI). Histologic confirmation of the lesions was obtained in all cases. All underwent the Kasai operation in early infancy. Six of 7 lesions in 4 of 5 patients were demonstrated by pretransplant imaging. Two of 7 tumors were detected by US. Five of 7 lesions were detected by CT, and 5 of 7 lesions were demonstrated by MRI. In 1 patient, the lesion was not seen in the US, CT, or MRI but was found during surgery and confirmed by histology. An additional tumor was found incidentally during histologic examination in a patient previously diagnosed to have 2 tumors by CT and MRI. In another patient diagnosed to have 2 tumors on imaging, pathology revealed only a single tumor. In conclusion, although unusual, pseudotumor should be included in the differential diagnosis of liver masses in BA children.     

Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.

We tested the hypothesis that astrocytic matrix metalloproteinase-9 (MMP-9) mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP-9 co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model where blood was injected into striatum, MMP-9 was colocalized with astrocytes surrounding the hemorrhagic lesion. Because MMP-9 is present in blood as well as brain, we compared four groups of wild type (WT) and MMP-9 knockout (KO) mice: WT blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and KO blood into WT brain. Gel zymography showed that MMP-9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. However, edema was ameliorated when MMP-9 was absent in either blood or brain or both. To further assess the mechanisms involved in astrocytic induction of MMP-9, we next examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly upregulated MMP-9 in conditioned media within 1 to 24 h. Hemoglobin-induced MMP-9 was reduced by the free radical scavenger U83836E. Taken together, these data suggest that although there are large amounts of MMP-9 in blood, hemoglobin-induced oxidative stress can trigger MMP-9 in astrocytes and these parenchymal sources of matrix degradation may also be an important factor in the pathogenesis of hemorrhagic brain edema.     

Nutritional Status Outcomes for Children: Ethnic, Cultural, and Environmental Contexts

The objective of this literature review was to explore the relationship between nutritional status outcomes among ethnically diverse children and cultural and environmental contexts. Articles from the literature on anthropometric/body composition measures, diet, and physiologic outcomes among ethnically diverse children were identified through on-line literature searches and references from articles reviewed. These studies were critically reviewed and selected if they reported findings resulting from use of accepted methodologies. Explanations consistent with evaluation of results from the studies and reports were developed by synthesis of the findings. Children from underserved, ethnically diverse population groups were at increased risk for obesity, increased serum lipid levels, and dietary consumption patterns that do not meet the Dietary Guidelines for Americans. More than 80% of all US children consume more than the recommended amount of total fat and saturated fat. These factors, which were noted during childhood, may track into adolescence, placing these children at increased risk for the early onset of chronic diseases such as non-insulin-dependent diabetes mellitus, cardiovascular disease, hypertension, and some forms of cancer. Although federally funded food assistance programs are changing rapidly, currently they provide foods that, when eaten as recommended, exceed the Dietary Guidelines for these children. Future interventions to improve the health and nutritional status of our nation's children, especially those from underserved, ethnically diverse groups, should be culturally appropriate and implemented at the levels of individuals, families, and communities. J Am Diet Assoc. 1996; 96:891-900,903.     

Effect of Food on the Pharmacokinetics of a New Hydroxypropyl-β-Cyclodextrin Formulation of Itraconazole

Study Objective . To compare the pharmacokinetics of a single 100-mg oral dose of itraconazole administered as 10 ml of a 10-mg/ml itraconazole solution in hydroxypropyl-β-cyclodextrin under fasting versus postprandial conditions. Design . Open-label, two-way, randomized, crossover study. Setting . Janssen Research Foundation, Belgium. Patients . Twelve healthy volunteers. Interventions . Blood samples were obtained for pharmacokinetic analyses immediately before dosing and at regular intervals up to 96 hours after each dose. Blood and urine samples were obtained for hematologic, biochemical, and urinary safety analyses at baseline and at the end of the study. Measurements and Main Results . The mean peak plasma concentrations of both itraconazole and its active metabolite hydroxy-itraconazole were significantly higher under fasting conditions than under postprandial conditions. The mean times to peak concentration for both the parent compound and its metabolite were significantly shorter under fasting than under nonfasting conditions. The mean areas under the curve (AUC_0–∞ and AUC_{0–24 hrs}) were also significantly higher under fasting than under postprandial conditions. Conclusions . Our findings suggest that the higher bioavailability of this new formulation of itraconazole may be of benefit in seriously ill patients who are not able to ingest adequate quantities of food. The fact that the solution was also well tolerated and was not associated with clinically significant changes in any laboratory value further underscores the potential utility of this dosing form.     

Structure and culture of schools of public health to support academic public health practice.

Schools of public health have been cautioned about producing graduates and research that were disconnected from public interest. Although institutions may implement a variety of strategies to rectify the situation, institutional structural and cultural barriers impede progress. Public health practice coordinators in accredited schools of public health were surveyed to describe the presence of structural and cultural barriers to academic public health practice using the Stevens model. Administrative leadership and faculty reward systems are described as critical to advance academic public health practice.     

Boerhaave's syndrome complicating acute myocardial infarction. Case report

A case of spontaneous rupture of the oesophagus (Boerhaave's syndrome) following acute myocardial infarction is presented. Conservative management with chest drainage and parenteral, later jejunostomy, feeding was successful. Progress was monitored with methylene blue swallow. A review of the literature revealed only two previous cases of this type.