The influence of androgens on hibernation phenology of free-living male arctic ground squirrels.

Free-living ground squirrel species are sexually dimorphic in hibernation phenology. The underlying causes of these differences are not yet known. Androgens, testosterone (T) in particular, inhibit hibernation. To determine the influence of endogenous androgens on annual timing of hibernation we first measured circulating levels of T and dehydroepiandrosterone (DHEA), an adrenal androgen implicated in non-mating season aggression in other species, in free-living male arctic ground squirrels (Urocitellus parryii, AGS). We also manipulated endogenous androgen levels by surgical castration, and consequently compared body temperature records from intact (n=24) and castrated (n=9) males to elucidate the influence of endogenous androgens on annual body temperature cycles. The highest T levels (0.53±0.10ng/mL) were in reproductively mature male AGS in spring; whereas, both immature males in spring and all males in late summer had T levels an order of magnitude lower (0.07±0.01 and 0.06±0.00ng/mL, respectively). DHEA levels were higher in males during the late summer compared to reproductively mature males in spring (120.6±18.9 and 35.9±2.3pg/mL, respectively). Eliminating gonadal androgens via castration resulted in males delaying euthermy by extending heterothermy significantly in spring (Apr 22 ±2.9) than reproductive males (Mar 28 ±3.9) but did not change the timing of hibernation onset (castrate: Oct 12 ±1.0 vs. intact: Oct 3 ±3.1). We conclude that while androgens play a significant role in spring hibernation phenology of males, their role in fall hibernation onset is unclear.

Efficient design of multituned transmission line NMR probes: the electrical engineering approach.

Transmission line-based multi-channel solid state NMR probes have many advantages regarding the cost of construction, number of RF-channels, and achievable RF-power levels. Nevertheless, these probes are only rarely employed in solid state-NMR-labs, mainly owing to the difficult experimental determination of the necessary RF-parameters. Here, the efficient design of multi-channel solid state MAS-NMR probes employing transmission line theory and modern techniques of electrical engineering is presented. As technical realization a five-channel ((1)H, (31)P, (13)C, (2)H and (15)N) probe for operation at 7 Tesla is described. This very cost efficient design goal is a multi port single coil transmission line probe based on the design developed by Schaefer and McKay. The electrical performance of the probe is determined by measuring of Scattering matrix parameters (S-parameters) in particular input/output ports. These parameters are compared to the calculated parameters of the design employing the S-matrix formalism. It is shown that the S-matrix formalism provides an excellent tool for examination of transmission line probes and thus the tool for a rational design of these probes. On the other hand, the resulting design provides excellent electrical performance. From a point of view of Nuclear Magnetic Resonance (NMR), calibration spectra of particular ports (channels) are of great importance. The estimation of the π/2 pulses length for all five NMR channels is presented.

Folic acid, riboflavin, thiamine, and vitamin B-6 status of a group of first-time blood donors.

Reference intervals for long-term status measures of folate, riboflavin, thiamine, and vitamin B-6 were determined in a select group of adults. Reference subjects had no adverse medical history and did not use tobacco, alcohol, or nutritional supplements, and their diets met > or =70% of the Australian recommended dietary intake for nutrients. Red blood cell concentrations of thiamine and folate were measured by microbiological methods. Vitamin B-6 and riboflavin status were measured on the basis of the erythrocyte aspartate transaminase activity coefficient and erythrocyte glutathione reductase activity coefficient, respectively. A survey of first-time blood donors, which was conducted in Australia in 1995, revealed a significant prevalence of low red blood cell thiamine concentrations (13%) when compared with the calculated normal reference intervals. However, the most important finding in the survey was that the group of healthy, nonanemic adults (first-time blood donors) was found to have a median red blood cell folate concentration 24% below the median concentration of the carefully selected (nonsupplemented) reference group. Plasma total homocysteine concentrations indicated folate deficiency in the reference group. Therefore, the 2.5th percentile cutoff for reference group red blood cell folate concentrations may have underestimated the prevalence of folate deficiency in the survey group. These data, coupled with the lack of Australian food-composition data for folate in particular, reinforce the need for monitoring nutritional status by both dietary and biochemical means. We recommend consideration of mandatory fortification of the Australian food supply with folic acid.

Reductive metabolism and hypoxia-selective toxicity of nitracrine.

The 1-nitroacridine nitracrine [NC,1-nitro-9-(dimethylaminopropyl-amino)acridine] is a potent hypoxia-selective cytotoxic agent in culture, but lacks activity against hypoxic tumor cells in vivo at therapeutically accessible doses. To clarify reasons for this failure in vivo the metabolism of NC was investigated in stirred suspension cultures of Chinese hamster ovary cells, in EMT-6 spheroids, and in mice. One major low molecular weight metabolite (identical to that generated by NaBH4/Pd/C reduction) was observed in hypoxic (less than 10 ppm O2) single cell suspensions, while [G-3H-acridinyl]NC formed trichloroacetic acid- and acetonitrile-insoluble macromolecular adducts (MA) at a rate seven-fold higher than in aerobic (20% O2) cultures. Formation of these adducts correlated with cytotoxicity under air or nitrogen, and hence may provide a dosimeter for NC-induced damage. Autoradiographic investigation of the distribution of MA in spheroids equilibrated with 5% O2 showed that the label was restricted to the outer cell layers rather than being localized in the hypoxic central region. Thus metabolic activation is probably too rapid, even in well-oxygenated cells, to allow adequate distribution to hypoxic microenvironments in tumors. In mice, levels of MA were higher in liver, kidney, spleen and lung than in Lewis lung tumors, indicating that oxygen concentration does not exert a dominant influence on relative rates of metabolic activation in vivo. The development of nitroacridines with useful hypoxic selectivity in vivo will require identification of analogs for which reductive metabolism is more completely inhibited at oxygen concentrations found in normal tissues.

Tracheobronchoplastic procedure in the treatment of advanced carcinoma of the right upper lung.

Lung cancer of the right upper lobe not infrequently invades the right lower trachea. A tracheobronchoplastic procedure is described that makes it possible to reconstruct the tracheal defect after excision of the growth, while preserving the uninvolved lobes of the right lung.

Duodenal ulcer in South Indian children.

Twenty-nine children with duodenal ulcer received treatment during an 18 year period. Twenty-five were followed over a period that ranged from 3 to 18 years; 53.8 percent of the patients who received medical treatment either had recurrence or persistence of ulcer symptoms during adolescence or adulthood. Two patients with acute bleeding ulcers have remained well after vagotomy and drainage procedures. Pyloric stenosis was the most common indication for surgical intervention and in all such cases the patients underwent truncal vagotomy and drainage procedures and continue to live without any symptoms, except one in whom anastomotic ulcer due to incomplete vagotomy has developed.

Success of sentinel lymph node mapping after breast cancer ablation with focused microwave phased array thermotherapy.

BACKGROUND: Breast cancer tumor ablation as part of a multimodality approach in the treatment of breast cancer is the subject of recent interest. This study was conducted to determine if the ability to perform sentinel node biopsy was impaired after thermal-induced ablation of breast cancer. METHODS: We studied patients who had sentinel node biopsy after preoperative focused microwave phased array for breast cancer ablation. RESULTS: Twenty-one patients with T1-T2 breast cancer and clinically negative axilla underwent wide local excision and sentinel node biopsy guided by blue dye and sulfur colloid. Surgery was done an average of 17 days after microwave ablation. Fifteen of 22 patients (68%) had histologic evidence of tumor necrosis. Sentinel lymph node mapping was successful in 19 of 21 patients (91%). Axillary metastases were detected in 42% of cases. CONCLUSIONS: This study documents successful sentinel lymph node mapping for patients treated with antecedent local tumor ablation using focused microwave phased array ablation.

Experimental investigation of an adaptive feedback algorithm for hot spot reduction in radio-frequency phased-array hyperthermia.

A computer-controlled adaptive phased array radiofrequency hyperthermia system for improved therapeutic tumor heating is experimentally investigated. Adaptive array feedback techniques are used to modify the electric-field in hyperthermia experiments with a homogeneous saline phantom target. A hyperthermia phased-array antenna system has been modified to implement adaptive nulling and adaptive focusing algorithms. The hyperthermia system is a ring phased-array antenna applicator with four independently controlled RF transmitter channels operating at a CW frequency of 100 MHz. The hyperthermia phased array is made adaptive by software modifications which invoke a gradient-search feedback algorithm that controls the amplitude and phase of each transmitter channel. The gradient-search algorithm implements the method of steepest descent for adaptive nulling (power minimization) and the method of steepest ascent for adaptive focusing (power maximization). The feedback signals are measured by electric-field short-dipole probe antennas. The measured data indicate that with an adaptive hyperthermia array it may be possible to maximize the applied electric field at a tumor position in a complex scattering target body and simultaneously minimize or reduce the electric field at target positions where undesired high-temperature regions (hot spots) occur.

Typhoid ileal perforations: a retrospective study.

This report examines the characteristics of 124 patients with typhoid ileal perforation treated over a 17-year period ending in 1986. Three adverse prognostic determinants were identified: prolonged fever/perforation interval, prolonged perforation/operation interval and multiple perforations. Simple closure was performed in 74 patients with a mortality of 31.1%, and trimming of the ulcer with closure in 38 patients with a 7.9% mortality.

The role of expectation in treatment for psychotic patients.

Four patients, originally diagnosed as schizophrenic and treated as though they had no hope for recovery, were later reassessed and given more optimistic expectations. The ensuing positive treatment results underscore the danger of equating diagnosis with prognosis, the danger of inaccurate or premature diagnosis, and the danger of neglecting psychotherapy for such patients.

Dissection of an aneurysmal ascending aorta in association with coarctation of the aorta.

A previously fit 21-year-old man presented with severel central chest pain. Clinical, electrocardiographic, and echocardiographic examination confirmed a dissection of an aneurysmal ascending aorta in the presence of previously undiagnosed severe aortic coarctation. Initial aortic dissection had occurred five days before admission. The medical and staged surgical management of the case are presented. Surgical survival with such a combination of lesions does not appear to have been previously recorded.

Adaptive radiofrequency hyperthermia-phased array system for improved cancer therapy: phantom target measurements.

A computer-controlled adaptive radio-frequency hyperthermia system for improved therapeutic tumour heating is experimentally investigated. Adaptive array feedback techniques are used to modify the electric-field and temperature distribution in hyperthermia experiments with homogeneous and heterogeneous phantom targets. A commercial hyperthermia phased-array antenna system at the SUNY Health Science Center in Syracuse, New York, has been modified to implement adaptive nulling and adaptive focusing algorithms. The hyperthermia system is the BSD Medical Corporation Model BSD-2000 with Sigma-60 annular phased-array antenna applicator. The transmit phased array system is made adaptive by software modifications which invoke a gradient-search feedback algorithm. The gradient-search algorithm implements the method of steepest descent for adaptive nulling (power minimization) and the method of steepest ascent for adaptive focusing (power maximization). The feedback signals are provided by electric-field short-dipole probe antennas. With an adaptive hyperthermia array using real-time measured data, it may be possible to maximize the applied electric field at a tumour position in a complex scattering target body and simultaneously minimize or reduce the electric field at target positions where undesired high-temperature regions (hot spots) occur. The measured phantom-target data indicate that adaptive nulling can reduce the electric field at one or more target positions while simultaneously focusing the electric field at a deep-seated position within the target.

Flucloxacillin concentration in serum and wound exudate during open heart surgery.

Per-operative serum and wound fluid concentrations achieved by two flucloxacillin dosage regimens were measured in twelve patients undergoing open heart surgery. One 500 mg bolus dose given after the induction of anaesthesia in six patients resulted in adequate serum concentrations (means decreasing from 69 to 9 mg/l) during surgery, but low wound fluid concentrations (mean 4.6 mg/l, range less than 2-7.8 mg/l) at the time of closure. An additional 500 mg bolus dose given after bypass in six further patients gave more satisfactory wound concentrations (mean 16 mg/l, range 8.6-22.5 mg/l). Disc absorption is a useful technique for assaying antibiotics in wound fluid, but the results are difficult to interpret since they represent a sum of concentrations in a complex and changing mixture of interstitial tissue fluid, blood and cardioplegia solution.

Study of cardiothoracic wound infection at St. Thomas' Hospital.

Wound infection occurred after 14.3 per cent of 433 open heart operations. In 309, saphenous veins were harvested for coronary artery bypass grafting (CABG) and 8.7 per cent of sternal wounds and 12.9 per cent of leg wounds were infected. Only 1.6 per cent of the remaining 124 patients who had open heart operations without leg surgery suffered sternal wound infections. In the CABG group sternal infection was theatre-related and significantly associated with length of pre-operative stay, diabetes and re-operation. Similar organisms were isolated from both leg and sternal wounds which suggest that organisms were transferred from legs to sternum with the veins. No clinically relevant cross infection was demonstrated. Skin disinfection and surgical technique seem more important than antibiotic prophylaxis in the control of these infections.

The differential activation of phosphatidylinositol-3 kinase and mitogen-activated protein kinases by PDGF-AA and IGF-I might explain the synergistic effect of the two growth factors on the proliferation of AKR-2B fibroblasts.

AKR-2B mouse fibroblasts express similar numbers of alpha- or beta-type PDGF receptors on their surface. Previous studies showed that PDGF-AA alone was unable to stimulate cell proliferation. Simultaneous addition together with insulin-like growth factor I (IGF-I), itself also inactive, led to a significant proliferation of the cells. In an effort to explain this synergism of the two growth factors we describe here the effects of the isoforms PDGF-AA or -BB and insulin-like growth factor I on three distinct signaling pathways, i.e., polyphosphoinositol turnover and [Ca2+]i increase, phosphatidylinositol-3 kinase, and mitogen-activated protein kinases. Whereas PDGF-BB effectively stimulated all three events, PDGF-AA failed to stimulate the phosphatidylinositol-3 kinase activity, but stimulated the mitogen-activated protein kinase to a maximum extent. In contrast IGF-I had no effect on mitogen-activated kinase but strongly stimulated phosphatidylinositol-3 kinase activity.