Microsurgical repair after excision of large cancers. Apropos of 14 cases]

The specialty which has benefited the most from the rapid development of reconstructive microsurgery over the last decade, has been plastic surgery. In particular, the authors refer to reconstructive microsurgery after malignant tumor resection. Resections which used to cause serious psychological problems or which required multiple reconstructive procedures, can now be performed as a single stage procedure with good oncological, functional and aesthetic results. This experience concerns the treatment of 14 primary or recurrent malignant tumors of the skin and soft tissues using microsurgical techniques. The free latissimus dorsi musculocutaneous flap was the flap most commonly used. The authors also used the groin flap, the scapular flap, the tensor fasciae latae flap, the dorsalis pedis flap and finally the jejunum combined with the second metatarsus to reconstruct the mandible and the floor of the mouth. Complications consisted of complete necrosis of a dorsalis pedis flap and two revisions were performed for venous thrombosis. With a minimum follow-up of 5 years, one patient has developed a local recurrence and another has developed regional lymph node metastases. The functional and aesthetic results were quite satisfactory. The authors believe that microsurgery is a very valuable technique to treat difficult reconstructive problems.     

Plasma atrial natriuretic peptide in essential hypertension after treatment with terazocin.

The aim of this study was to evaluate the medium term effects of the selective alpha1-adrenenergic- blocker terazocin on atrial natriuretic peptide (ANP) levels in patients with moderate essential hypertension. The drug was given orally for 30 days. The daily dose was 1 mg for the first 7 days, 2 mg for the next 7 days and 5 mg for the remaining period of this clinical trial. At the end of this clinical trial, plasma ANP levels increased by 16.40% despite the drop in blood pressure while left atrial and ventricular diameters remained unchanged. These findings indicate that the increase of ANP plasma levels is not the result of a mechanical load on the left cardiac chambers but the result of a pharmacological action. These observations also indicate that terazocin exerts part of its antihypertensive action by increasing ANP plasma levels.     

Assessment of vector microfilarial uptake as a comparatively non-invasive technique for monitoring onchocerciasis treatment campaigns in the Americas

Summary Since 1992, efforts have been made to combat onchocerciasis in Guatemala through mass distribution of ivermectin. The impact of the campaign is assessed by taking skin-snips from sentinel groups within selected communities. This method gives an estimate of the prevalence and intensity of infection, and thus the efficacy of the treatment. In some communities people are becoming reluctant to volunteer for skin-snipping, and so there is a need for an alternative technique that will give quantitative results. In most hyperendemic communities in Guatemala, biting blackflies are so ubiquitous that few people object to allowing 10 to 20 flies to engorge upon them. We examined data on the quantitative uptake of microfilariae by Simulium ochraceum before and after ivermectin distribution to see whether results similar to skin-snip data could be obtained. Counts of microfilariae ingested by S. ochraceum are compared to the numbers found in skin-snips from the same volunteers. In a group of 31 untreated infected persons, a skin-snip survey detected 64.5% positive, while feeding flies (vector microfilarial uptake, VmfU) detected 96.8%. Post-treatment, in a sample of 58 of whom 52 (89.7%) had a history of infection, both skin-snips and VmfU detected 54.2%. Vector blood meals contained more microfilariae than a mg of skin before treatment, but both recorded about equal numbers after treatment. When the data set was subdivided to compare samples taken at 2–3, 6–8 and 14–17 months post-treatment, the effect of ivermectin was still apparent at 6–8 months, but had virtually disappeared by 14 months post-treatment. A surprising observation was that the flies ingested fewer microfilariae from treated persons than was expected from the skin densities as estimated by skin-snip. This effect lasted for over 8 months, and could indicate that ivermectin has a greater effect on transmission than previously suspected. We conclude that VmfU could be used as an alternative to skin-snipping, and discuss the ethical implications.     

Comparison of Output Particle Size Distributions from Pressurized Aerosols Formulated as Solutions or Suspensions

The delivery of particles as small as possible (preferably <5 µm) to the respiratory tract should be the aim of those formulating metered dose inhalers (MDIs). This may be facilitated by the formulation of solution, rather than suspension-type, pressurized aerosol units. Two series of MDIs were compared; one contained suspended micronized disodium fluorescein (0.1%, w/v), while the other contained the same concentration of dissolved salicylic acid. Either oleic acid, L--phosphatidylcholine, or sorbitan trioleate was incorporated at 0.15% (w/v) as suspending agent (disodium fluorescein) or solubilizing agent (salicylic acid). The propellant blend was 70% (w/w) Freon 12 and 30% (w/w) Freon 11 in all cases. This exhibited a vapor pressure of 50.6 psig (444.7 kPa) at 21°C. The output particle size distribution of the aerosol reaching the cascade impactor showed a mass median aerodynamic diameter (MMAD) of approximately 4 and 2 µm for the suspension and solution formulations respectively, regardless of the surfactant used. Larger MMADs were observed for solution aerosols formulated with oleic acid (2.32 µm) compared to those containing L--phosphatidylcholine (1.93 µm) or sorbitan trioleate (2.07 µm). Possible reasons for these observations are discussed.     

Peripheral-type benzodiazepine receptor (PBR) gene amplification in MDA-MB-231 aggressive breast cancer cells

Recent studies using human breast cancer cell lines, animal models, and human tissue biopsies have suggested a close correlation between the expression of the peripheral-type benzodiazepine receptor (PBR) and the progression of breast cancer. This study investigates the genetic status of the PBR gene in two human breast cancer cell lines: MDA-MB-231 cells, which are an aggressive breast cancer cell line that contains high levels of PBR, and MCF-7 cells, which are a nonaggressive cell line that contains low levels of PBR. Both DNA (Southern) blot and fluorescence in situ hybridization analyses indicate that the PBR gene is amplified in MDA-MB-231 relative to MCF-7 cells. These data suggest that PBR gene amplification may be an important indicator of breast cancer progression.     

The frequency of chromosome anomalies in human preimplantation embryos after in-vitro fertilization

Previous studies have reported chromosome aberrations in humanpre-embryos after in-vitro fertilization (IVF). Although thereason for these abnormalities is not clear, there is evidencethat they can arise during gametogenesis, fertilization or cleavage.The present study has examined further the incidence of chromosomeabnormalities in human pre-embryos after IVF, using oocytesrecovered from normal volunteer women and from women undergoinginfertility treatment in an embryo-replacement programme. Chromosomepreparations were performed for 75 pre-embryos. Of these 35(47%) gave at least one metaphase in which analysis was possible.The overall incidence of abnormal pre-embryos was 40% (14/35).The absolute frequency of aberrations was 9% for trisomies,3% for polyploidies, 26% for structural anomalies and 3% forhypodiploidies. Five pre-embryos were found to be mosaics, threeof which had each one trisomic metaphase. In five of the pre-embryosmultiple anomalies were found. In 13 of the 14 abnormal pre-embryosthe aberrations were found in only one metaphase. The presentstudy demonstrates that trisomic mosaicism may not be a rareevent in human pre-embryos. Further evidence is provided thatmitotic non-disjunction is important for the production of aberrationsin human pre-embryos     

New insights into water transport and edema in the central nervous system from phenotype analysis of aquaporin-4 null mice

Aquaporin-4 (AQP4) is the major water channel in the CNS. Its expression at fluid-tissue barriers (blood-brain and brain-cerebrospinal fluid barriers) throughout the brain and spinal cord suggests a role in water transport under normal and pathological conditions. Phenotype studies of transgenic mice lacking AQP4 have provided evidence for a role of AQP4 in cerebral water balance and neural signal transduction. Primary cultures of astrocytes from AQP4-null mice have greatly reduced osmotic water permeability compared with wild-type astrocytes, indicating that AQP4 is the principal water channel in these cells. AQP4-null mice have reduced brain swelling and improved neurological outcome following water intoxication and focal cerebral ischemia, establishing a role of AQP4 in the development of cytotoxic (cellular) cerebral edema. In contrast, brain swelling and clinical outcome are worse in AQP4-null mice in models of vasogenic (fluid leak) edema caused by freeze-injury and brain tumor, probably due to impaired AQP4-dependent brain water clearance. AQP4-null mice also have markedly reduced acoustic brainstem response potentials and significantly increased seizure threshold in response to chemical convulsants, implicating AQP4 in modulation of neural signal transduction. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the CNS associated with altered brain water balance.     

Does feeding regime affect physiologic and thermal responses during exposure to 8, 20, and 27° C?

Summary When the loss of body heat is accelerated by exposure to low environmental temperatures, additional substrates must be oxidized to provide energy to sustain temperature homeostasis. Therefore, the present investigation examined the relation between feeding regime [pre-experimental carbohydrate feeding (FED) vs a fast (FAST)], during 120 min of exposure to 8, 20, and 27° C in well-nourished men. The following were examined: tissue insulation (I; °C · m² · W^–1), rectal temperature (T _re; °C), and oxygen consumption ( O₂; ml · kg^–1 · min^–1). O₂, T _re, and I revealed no significant differences between treatments (FED vs FAST) at any temperature. At 27° C, I was less (P < 0.05) than at 20 and 8° C, and decreased (P < 0.05) as exposure time increased. At 8° C, O₂was higher (P < 0.5) than at 20 or 27°C, and O₂increased as time increased (P < 0.05). T _re decreased (P < 0.05) as time increased for all conditions. Respiratory exchange ratio (R) differed (P < 0.05) between treatments (FED vs FAST), temperature (8 vs 20° C), and across time. Values for R suggests that carbohydrate accounted for 56% and 33% of caloric utilization during the FED vs FAST conditions, respectively. At 8 vs 20° C, R represented 54% vs 30% of cabohydrate utilization. Across time, R demonstrated that in both conditions (FED vs FAST) there was a decreased reliance on carbohydrate utilization for energy provision. From these data it appears that while substrate utilization differed between dietary treatment and across time this did not differentially affect O₂or T _re during protracted exposure to 8, 20, and 27° C. The higher R in the 8° C condition for both dietary treatments demonstrates that carbohydrate utilization is increased in shivering cold-exposed humans. However, the reduction in R across time suggests that fat oxidation is also involved in metabolic heat production and core temperature maintenance during shivering in the cold.     

Postnatal development of somatostatin-containing neurons in the visual cortex of normal and dark-reared rats

Summary The distribution of somatostatin (SRIF)-immunoreactive neurons in the visual cortical areas 17, 18 and 18a of Wistar rats from birth to adulthood was followed in both normal and dark-reared animals. The SRIF neurons show difference in distribution amongst the three cortical areas studied as early as the first postnatal week. Area 17 was distinguished by fewer SRIF cells in the upper layers (I–III), which results in a lower overall density. The SRIF neurons in all areas appeared to increase in numbers up to about 3 weeks and then decline dramatically to adult levels, which were 14–19% of the peak levels. Although this decline was still obvious, it moderated to 25–31% in dark-reared animals. The greatest effect was seen in area 18 where, at 60 days of age, there were twice as many SRIF cells in darkreared as in normal controls. It is suggested that, under conditions of dark rearing, the overall pattern of development of SRIF neurons, being uninfluenced by extrinsic factors, reveals the cells' genetic potential.