Effects of Increasing Gestation,Cortisol and Maternal Undernutrition on Hypothalamic Neuropeptide Y Expression in the Sheep Fetus

We have characterized the localization and the ontogenetic changes in Neuropeptide tyrosine (NPY) before birth and investigated the regulation of NPY expression by cortisol and undernutrition in the fetal sheep hypothalamus during late gestation. Using immunohistochemistry, we have identified NPY-containing neurons in the infundibular nucleus and the internal layer of the median eminence in fetal hypothalami collected between 110 and 147 days gestation. NPY projections were also present in the paraventricular nucleus (PVN) of fetal hypothalami at all ages between 110 days gestation and term. There was a significant increase in the amount of immunoreactive NPY/g hypothalamus between 87 and 113 days and 131–140 days gestation and a further significant increase after 141 days gestation. The total hypothalamic content of immunoreactive NPY increased significantly between 87 and 113 days and 141–145 days gestation. The levels of NPY mRNA: 18S rRNA in the mediobasal region of the fetal hypothalamus were significantly higher at 145–146 days gestation than at any earlier gestational age between 116 and 141 days gestation. Cortisol (2.5–3.0 mg/24 h) was infused intrafetally between 109 and 116 days gestation. The ratio of NPY mRNA: 18s rRNA in the mediobasal region of the fetal hypothalamus was significantly higher in the cortisol-infused group when compared with the saline-infused control group at 116 days gestation. Maternal, and hence fetal undernutrition, was induced between 110 and 146 days gestation. At 145–146 days gestation the ratio of NPY mRNA: 18S rRNA in the mediobasal region of the fetal hypothalamus was significantly higher in the undernutrition group when compared with control animals. We have therefore demonstrated that NPY is present in the hypothalamus of the sheep fetus before birth and that hypothalamic NPY content and NPY mRNA increase before delivery. We have also found that glucocorticoids and undernutrition stimulate increases in NPY mRNA levels in the hypothalamus before birth.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 1: 6-Methyl Derivatives

A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.     

Magnetic resonance imaging reveals no ventriculomegaly in polydrug abusers

Previous studies of cerebral structure in substance abusers yielded controversial results, largely due to issues of subject selection and/or limitations of experimental techniques. The purpose of the present study was to assess whether the ventricle-to-brain ratio (VBR), determined volumetrically by magnetic resonance imaging (MRI), differed in polysubstance abusers (n = 10), as compared with age-matched controls (n = 10). Subjects were male volunteers 21–39 years of age. The values of VBR in the polydrug abuse group were not larger than those in control group, nor was there any tendency toward relative ventriculomegaly in the substance abusers. Therefore, the present findings provide no evidence that polysubstance abuse produces abnormalities of gross brain structure in relatively young and physically healthy men.     

Excision of a Clival and Upper Cervical Pheochromocytoma by an Extended Maxillotomy Approach: A Case Report

By use of an extended maxillotomy approach, greater surgical access is provided to the midline skull base in comparison with lateral approaches. We describe this technique used to debulk a tumor extending from the sphenoid sinus across the craniocervical junction to the second cervical vertebrae.     

Pulmonary aspiration complicating intraoperative small-bowel decompression: a case report and literature review

When conservative management of intestinal obstruction fails, the surgeon has two operative choices for decompression: the open procedure with enterotomies and suction and the closed procedure consisting of retrograde stripping and nasogastric suction. A previously undocumented complication of the latter procedure — pulmonary aspiration — is reported in a 20-year-old man with small-bowel obstruction. Practical modifications to the technique of small-bowel decompression are suggested. They include feeding the nasogastric tube into the distal duodenum, using a wider bore tube, inserting an esophageal balloon before extubation, using a nasogastric tube with suction throughout extubation and, immediately postoperatively, making a more conscious effort to remove all gastric contents before extubation, and milking the contents distally through the ileocecal valve.     

Detection of haematoporphyrin derivative and haematoporphyrin excited states in cell environments

The photosensitiser currently used in the photodynamic therapy of cancer is haematoporphyrin derivative. Pulsed laser studies of this material and also of the "parent" molecule haematoporphyrin in polyoma-transformed fibroblast cells have now been studied. We report, for the first time, the observation of the triplet absorption of these sensitisers in cells. The corresponding triplet-triplet spectra are red shifted compared to aqueous buffer, lambda(max) 420 nm shifts to 460 nm. We also report our failure to observe singlet oxygen from the cells even though the triplet state can be seen to interact with the oxygen and even though singlet oxygen can be readily detected with the same sensitisers bound to serum albumin.     

Should results of ultrasound Doppler studies be reported in units of frequency or velocity?

There is a current tendency to report the results of ultrasound Doppler studies in units of velocity instead of Doppler frequency. This is probably motivated by the intuitive feeling that blood flow studies should naturally be reported in cm/s and the notion that "velocity" is a normalizing factor for Doppler ultrasound studies. In order to determine velocity, the Doppler angle theta or angle formed by the ultrasound beam and flow velocity vector, must be known. It is not possible, using currently available systems, to obtain an accurate estimate of this angle. The physics related to the Doppler equation are reviewed in this paper along with examples to illustrate the origin and magnitude of errors that could arise when reporting in units of velocity. Guidelines are provided for thinking about and reporting results of Doppler studies in units of velocity. An understanding of the Doppler equation and its use in clinical studies are promoted in this paper to enhance the diagnostic usefulness of Doppler ultrasound studies and to reduce serious errors which could lead to faulty information dictating patient management.     

Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding

Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4–5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p < 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), andp,p-dichlorodiphenyldichloroethylene (p,p-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, andp,p-DDE concentrations were corrected by total serum lipids, results from fasting and nonfasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.     

The wheat variety used in the diet of laying hens influences colonization with the intestinal spirochaete Brachyspira intermedia.

This study investigated whether feeding different wheat varieties to laying hens could influence colonization with the intestinal spirochaete Brachyspira intermedia. Fifty ISA-Brown laying hens were divided into two groups. One group were fed a laying-hen diet formulated with wheat variety Westonia, and one were fed the diet incorporating variety Stilleto. Each group was divided into 15 hens experimentally infected with B. intermedia and 10 uninfected controls. The 30 infected hens were housed in individual cages in one room, and the controls were similarly housed in another room. Following administration of cultures of B. intermedia strain HB60 by crop-tube over 3 days, cloacal swabs were taken for spirochaete culture every 3 to 4 days. The water content of caecal faeces, and egg production and body weight were measured weekly. The hens were killed after 4 weeks, the caeca cultured for spirochaetes and the viscosity of the ileal contents measured. A total of 48/120 (40%) of the excreta samples from infected hens fed Westonia contained B. intermedia, compared with 21/120 (17.5%) for Stiletto (P = 0.0002). The ileal viscosity of hens fed Westonia also was higher (P = 0.048), but viscosity was not clearly related to the non-starch polysaccharide (NSP) content of the wheats. Westonia had a slightly higher total NSP content than Stiletto, but the ratio of soluble to insoluble NSP was lower. Infected hens developed wetter excreta, but neither infection nor diet altered egg production. In conclusion, the wheat variety can influence colonization with B. intermedia, apparently through diet-related alterations in the intestinal microenvironment.     

Use of a T cell-specific monoclonal antibody, T10B9, in a novel allogeneic stem cell transplantation protocol for hematologic malignancy high-risk patients.

To reduce the toxicity of traditional conditioning regimens for allogeneic stem cell transplantation (allo-SCT), we used single-agent chemotherapy conditioning with either busulfan (total cumulative dose, 16 mg/kg) or melphalan (200 to 240 mg/m 2 ), followed by the anti-T cell-specific monoclonal antibody T10B9 (MEDI-500) daily for 3 days. T cell-replete SCT was performed from HLA-identical sibling donors. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of 7 additional days of T10B9 and delayed onset of cyclosporine (ie, on day +4 or +5). Twenty-six high-risk hematologic malignancy patients were entered onto this study. All 24 patients who survived longer than 8 days engrafted, although 1 patient experienced late graft failure. Deaths occurred in 21 of 26 patients because of infection (n = 7), progression/recurrence of primary disease (n = 6), aGVHD (n = 4), regimen-related toxicity (n = 1), and other causes (n = 3). Five of these patients are enjoying disease-free survival with a median survival of 1193 days after allo-SCT. The conditioning regimen induced modulation of surface expression of CD3 (but not CD4 or CD8) and was associated with decreasing tumor necrosis factor-alpha (but not interleukin-6) serum levels. In conclusion, single-agent chemotherapy conditioning with T10B9 produced durable engraftment and long-term survival in some patients who would not have qualified for a traditional allo-SCT.