Fertilization and early embrology: Monozygotic twinning in the human is associated with the zona pellucida architecture

Six cases of identical twin pregnancies which occurred in 2163cycles of in-vitro fertilization during a 3 year period arereported. Monozygosity was confirmed when the number of fetusesexceeded the number of embryos replaced (n = 4) or when twoconcepti were observed in a single amniotic sac (n = 2). Eachof the reported pregnancies resulted from replacement of embryoseither with naturally thin zonae pellucida or embryos whosezonae had been breached during micromanipulation for assistedfertilization (subzonal sperminsertion) or assisted hatching.That such cases exclusively gave rise to monozygosity suggestsa link between the physical state of the zona pellucida, hatching,and generation of identical twins.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.     

Uptake and biotransformation of sevof lurane in humans: A comparative study of sevof lurane with halothane, enflurane, and isoflurane

Study Objective: To compare the volatile anesthetic sevoflurane with halothane, enfurane, and isof urane on the uptake and biotransformation in humans.

Design: Prospective pharmacokinetic study of sevofurane administration in human subjects.

Setting: Inpatient surgery clinic at a university medical center.

Patients: Thirty-two Japanese patients, free of systemic diseases, undergoing minor elective surgery with endotracheal general anesthesia.

Interventions: The patients were assigned randomly to one of four groups: halothane, enflurane, isofurane, or sevofurane. One of the four volatile anesthetics being investigated [equivalent to 1.1 minimum alveolar concentration (MAC): halothane, 0.85%; enfurane, 1.85%; isofurane, 1.27%; and sevofurane, 1.88%; in inspired concentrations throughout the first hour of anesthesia] was administered for 60 minutes.

Measurements and Main Results: In all patients, serum and urinary fluoride concentrations were measured. The concentrations of all gases were measured separately with a mass spectrometer. The cumulative uptake of each anesthetic agent during a certain period was calculated as an integration of the uptake rate per minute. The results for one-hour inhalation of sevofurane (1.1 MAC) showed an uptake (corrected for body surface area and MAC) of 490 ml/m²/MAC and estimated degradation rate of 3.3%. For purposes of comparison, similar studies of halothane (uptake, 653 ml/m²/MAC; degradation rate 15.7%), enfurane (1150 ml/m²/MAC; 1.3%), and isofurane (439 ml/m²/MAC; 0.6%) were also conducted. Sevofurane had a peak serum inorganic fluoride concentration of 19.3 μmol/L, and no abnormality in hepatic or renal functions was observed in any of the subjects during the two weeks postoperatively.

Conclusions: Accurate determinations of uptake and degradation rate for sevoflurane and three other volatile anesthetics in Japanese patients were obtained. These findings have established that, despite its relatively large MAC *1.71%), sevoflurane has a small uptake due to its low solubility. However, the degradation rade was shown to be as high as 3.3%, resulting in a higher serum fluoride concentration than seen after administration of isoflurane, halothane, and (possibly) enflurane.     

Why do long-distance runners not have more bone? A vital biomechanical explanation and an estrogen effect

Inanimate structures cannot detect and repair their fatigue damage or microdamage, so to minimize it they need more structural material and strength. Living bone handles this matter differently. Bone modeling drifts adapt bone architecture and strength to the loads on bones in ways that tend to keep strains from exceeding a “modeling threshold” range. Strains (or equivalent features) above that threshold switch mechanically controlled modeling ON. Where strains stay below that threshold, this modeling goes OFF. Repeatedly loading-deloading a bone causes microdamage in it, and basic multicellular unit (BMU)-based bone remodeling normally repairs it. Where strains stay below an operational “microdamage threshold,” remodeling can repair whatever microdamage happens for as long as it happens. Strains above that threshold can cause too much microdamage to repair completely and lead to fatigue fractures of trabeculae or whole bones. The modeling threshold normally lies comforably below the microdamage threshold. Since modeling normally adjusts bone architecture to keep strains from exceeding the modeling threshold, this keeps strains below the microdamage threshold, too, and voluntary activities do not cause more microdamage than remodeling can repair. Therefore, long-distance runners do not need more bone mass and strength than nonrunners of comparable age, sex, and body size.     

Supercritical fluids in medical radioisotope processing and chemistry,Part II: Applications – real and demonstrated

In Part I of this review series, an overview was presented on what the basic properties of supercritical fluids are and how they can, and are being used in many of today's industries as solvents for extraction, chromatography and reaction. A good part of this overview detailed the kinds of equipment needed, and techniques on how to use them for optimal performance. Part II of this series will delve into specific applications of supercritical fluid technology as it relates to aspects of medical isotope processing. The reader will note that very few applications of this technology to Nuclear Medicine have been published. Many potential applications cited within the context of this review derive from preliminary studies carried out in the author's laboratory. These examples are presented to spark interest in future developments of this nature. Copyright © 2003 John Wiley & Sons, Ltd.     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

Resection of pulmonary metastases following chemotherapy for high stage testicular tumors

BACKGROUND: Our objective was to analyze retrospectively our experience with 19 patients who had metastatic germ cell testicular tumor and had undergone resection of pulmonary metastases following chemotherapy. We wished to determine the necessity of thoracic surgery on these patients. METHODS: Of 103 patients in need of postchemotherapeutic surgery for metastatic germ cell testicular tumors, 19 patients (mean age 31) underwent surgery for thoracic masses following cis-platin based chemotherapy. Resection of pulmonary metastases was performed on patients with normal tumor markers after chemotherapy, who did not achieve complete radiological remission. Histopathological findings, correlation with the pathology of abdominal surgery and probable prognostic factors for disease-free and overall survivals were evaluated. RESULTS: Disease-free and overall survival rates were 14/19 (73%) and 16/19 (84%), respectively, within a median follow-up time of 30 months (15-212 months). Patients with and without viable tumor cells in their thoracic histopathological specimen had 40% and 85% disease-free survival rates, respectively (P < 0.05). Eight patients had both abdominal and thoracic postchemotherapy surgery. Only two (25%) of these patients had the same histopathological features at both sites. CONCLUSIONS: All patients with residual thoracic masses must be considered candidates for surgery, because there are no predictive factors to determine the thoracic pathology without surgery. With the resection of the pulmonary metastases only, surgery can be performed without significant morbidity and is essential to select patients for further chemotherapy, to remove all visible masses and to provide histopathological confirmation. Patients with viable tumor cells in the thoracic surgical specimen have a poor prognosis.     

中药空气消毒液消毒作用的实验研究

作者通过大量的基础实验和临床现场实验研究,成功研制了中药空气消毒液。研究结果证明:本品具有抗细菌,抗甲型、乙型流感病毒及单纯疱疹病毒的作角。该药液对以金黄色葡萄球菌为代表的G~+菌,以大肠杆菌、绿脓杆菌为代表的G~-菌的最小抑菌浓度为5％,最小灭菌浓度为20％,最短灭菌时间为5min。毒理试验证明长期使用此药液无毒副作用。本品在常温下保存性能稳定;对日常用品无损伤现象。临床试验结果证明本品喷雾空气消毒作用与常规紫外线照射法、过氧乙酸喷雾法基本相同。效果满意。     

Intra-abdominal desmoplastic small cell tumor presenting as an acute abdomen after trauma

The intraperitoneal mass most commonly encountered after blunt abdominal truama is a hematoma. However, one must also consider unusual bulky tumors that can have imaging characteristics similar to those of hematoma. The most typical of these neoplasms is lymphoma, but a desmoplastic small cell tumor also may be observed. The presentation and imaging findings of a desmoplastic small tumor are described.     

The distribution of lead in human hemopoietic tissue and spongy bone after lead poisoning and Ca-EDTA chelation therapy

Two iliac crest needle biopsies were taken from a 43-year-old lead-poisoned woman during and after completion of a Ca-EDTA treatment. By atomic absorption spectroscopy the first and second biopsy were found to contain 56, respectively 41.6 g lead/g wet tissue. In both biopsies 36% of the lead was extractable in 0.1 N HCl. Electron microbeam X-ray analysis proved to have too low sensitivity for quantitation of the lead in these biopsies. Laser microbeam mass analysis (LAMMA), performed only on the second biopsy, revealed a high and fairly constant residual lead concentration in all bone marrow cell nuclei (approximately 55 g/g) and a low lead concentration in the cytoplasm of the same cells (4–12 (g/g). The extracellular bone matrix lead was greatly concentrated in the superficial 3–6 m osteoid zone of the bony trabeculae and totally absent from deeper parts of the mineralized matrix. The LAMMA results are in good agreement with those of subcellular fractionation experiments and atomic absorption spectroscopy, provided that the relative volume fraction of nucleus and cytoplasm is accounted for. The high residual osteoid lead after completed chelation therapy indicates that lead has a stronger affinity for the organic than the mineral components of bone matrix.