Rapid rise in plasma glucagon induced by acute cold exposure in man and rat

The effect of acute cold exposure on the concentration of glucagon in the blood was investigated in man and in intact and adrenalectomized rats.In man fasted overnight acute cold exposure, which caused a twofold increase in O₂-consumption resulted in a rapid rise in plasma glucagon. The levels of insulin and blood glucose remained unaltered, while the concentration of serum free fatty acids and -hydroxybutyrate increased.In fasted intact rats acute cold exposure lead to similar effects. A close parallelism between the rise in plasma glucagon and the concentration of hepatic cycloAMP was observed. Adrenalectomy did not impair the cold induced rise in plasma glucagon and hepatic cycloAMP.It is concluded that acute cold exposure caused a rapid rise in the concentration of plasma glucagon leading to an increase in the concentration of hepatic cycloAMP, thus enhancing the rate of hepatic gluconeogenesis and ketogenesis. As these alterations were similar in the absence of glucocorticoids and medulla-derived catecholamines, it is suggested that glucagon may play a role in the metabolic adaptation to acute cold exposure.     

Effect of dynamization on gap healing of diaphyseal fractures under external fixation

We asked whether dynamization of externally fixed diaphyseal fractures could improve bone healing in comparison to rigid fixation of fractures having similar remaining gap sizes. To answer this question we evaluated metatarsal osteotomies in 12 sheep. The osteotomy with a 0.6-mm gap was stabilized with a specially designed high bending and torsional stiffness external ring fixator. Osteotomies in six sheep were stabilized rigidly (axial movement < 0.06 mm) or dynamically (axial movement 0.15-0.34 mm). The cyclical axial interfragmentary movement was caused by the load-bearing of the operated limb. With increasing healing time, the initially allowed movement was decreased by callus formation around the osteotomy. The reduction in interfragmentary movement was measured and monitored by a linear variable displacement transducer at the external fixator and a telemetry system. After 9 weeks the sheep were sacrificed and the healed bones were investigated biomechanically and histomorphologically. Compared to the rigidly fixed osteotomies, the dynamized osteotomies showed significantly (P < 0.05) greater (+41%) callus formation and 45% greater tensile strength of the newly formed bone in the cortical osteotomy gap. Histological analysis indicated that the effect of dynamization occurred mainly after the 5th week. RELEVANCE: From these results we conclude that dynamic fixation of diaphyseal gaps is advantageous in comparison to stable external fixation.     

Prevalence of hypovitaminosis a in children of peripheral districts of Campinas São Paulo, Brazil

The prevalence of hypovitaminosis A among children of the peripheral districts of the city of Campinas, S o Paulo, Brazil, was estimated by determining serum retinol levels by High Performance Liquid Chromatography (HPLC) in a sample of 131 children aged between three and ten years, between April 1991 and February 1992. A prevalence of 17.6% and retinol concentrations in the range of 0.35 to 0.70 micromol/L were found (CI=11.1-24.1; 95%), indicating the existence of public health risk Ophthalmological examinations, however, failed to detect any cases of xerophthalmy. Additional characterization of the sample was obtained from 341 children. The per capita income of the average household was surprisingly high for low-income areas. According to FAO-WHO standards, food consumption was adequate only for protein (133.96%). Adequacy levels were low for energy (87.76%) and particularly for vitamin A (66.13%) and iron (42.14%). Height for-age and weight-for-height anthropometric indices revealed that many children were located below -1 standard deviation.     

Effects of specimen length on the monosegmental motion behavior of the lumbar spine

STUDY DESIGN: An in vitro biomechanical analysis of the segmental motion behavior of the same segments in polysegmental (five segments), bisegmental, and monosegmental specimens using sheep lumbosacral spines. OBJECTIVES: To investigate the effect of specimen length on monosegmental motion behavior. These data may be helpful in planning in vitro tests and in comparing results of studies using specimens of different lengths. SUMMARY OF BACKGROUND DATA: The length of spinal specimens used for in vitro stability tests varies greatly, depending on the purpose of the study. Some investigators prefer testing specimens with one adjacent segment on either end of the region of interest. Others favor specimens as short as possible. METHODS: In a first step, seven sheep spine specimens, L3-S1 (note that sheep spines normally have seven lumbar vertebrae), each were tested without preload in a spine-loading apparatus. Alternating sequences of pure lateral bending, flexion/extension, and axial rotation moments (+/-3.75 Nm) were applied continuously. The motion in each single segment was measured simultaneously. Then, these polysegmental specimens were cut into two bisegmental specimens, L3-L5 and L6-S1, and tested in the same way. Finally, another vertebra was removed to obtain two monosegmental specimens, L3-L4 and L7-S1, and to test them as described. RESULTS: In general, the range of motion at L3-L4 and L7-S1 was smaller when tested in polysegmental than in monosegmental specimens. In polysegmental specimens (five segments), the range of motion at L3-L4 and L7-S1 was approximately 80% (range, 70.6-92.5%) and in bisegmental specimens approximately 95% (range, 66.7-100%) of their range of motion measured in monosegmental specimens. Neutral zone and coupled motions showed the inverse behavior. Significant differences were found. However, they were not consistent with either the loading direction or with the specimen length. CONCLUSIONS: For comparison of results, the specimen length should be kept constant within one experiment. Segmental motion behavior of specimens with different lengths should be compared only qualitatively.     

Subsidence resulting from simulated postoperative neck movements: an in vitro investigation with a new cervical fusion cage

STUDY DESIGN: A biomechanical in vitro subsidence test of different cervical interbody fusion devices was performed using a new testing protocol that simulates physiologic conditions. OBJECTIVES: To investigate the effect of simulated postoperative neck movements on the subsidence of the new WING cervical interbody fusion cage in comparison with two other cages and bone cement. SUMMARY OF BACKGROUND DATA: Cervical interbody fusion cages sometimes cause complications because of subsidence into the adjacent vertebrae with collapse of the intervertebral space. Complications such as cage dislocation or nonunion with instability also have been reported. To prevent such complications, the new WING cervical interbody fusion cage (Medinorm AG, Quierschied, Germany) has been developed. Its area of contact with the adjacent vertebrae is supposed to be large enough to resist excessive subsidence and small enough to prevent stress protection of the tissue growing in the cage. METHODS: In this study, 24 human cervical spine specimens were tested after stabilization with either a WING, BAK/C, AcroMed I/F cage or bone cement. Then, in a new testing protocol, 700 pure-moment loading cycles (+/-2 Nm) were applied in randomized directions (lateral bending, flexion-extension, and axial rotation alone or in combination with each other) to simulate the patient's neck movements during the first few postoperative days. Measurements of the subsidence depth (total height loss) in combination with flexibility tests (+/-2.5 Nm) were performed before cyclic loading and after 50, 100, 200, 300, 500, and 700 loading cycles. RESULTS: Cyclic loading caused subsidence in all four device groups, most distinct with BAK/C-cages (1.63 mm after 700 loading cycles) followed by the new WING (0.90 mm) and the AcroMed (0.82 mm) cages. No statistically significant difference could be found among the three cage designs. However, all three cage types showed a significantly higher subsidence depth than bone cement (0.48 mm;P = 0.023 between each of the three cage-types and bone cement). A moderate correlation between bone mineral density and subsidence depth could be found only in the BAK/C group (r2 = 0.495). A large subsidence depth after 700 loading cycles was associated with a large flexibility increase in the WING (r2 = 0.786) and AcroMed groups (r2 = 0.21), but with a small flexibility increase in the BAK/C group (r2 = 0.58). CONCLUSIONS: Postoperative neck movements caused subsidence in all cervical interbody implant types. The new WING cage and the AcroMed cage seemed to have a better resistance against subsidence than the BAK/C cage. However, all three cage types had a significantly higher subsidence tendency than bone cement.     

Modulation of 5-fluorouracil with methotrexate and low-dose N-(phosphon-acetyl)-L-aspartate (PALA) is inactive in advanced pancreatic carcinoma

Purpose: To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in patients with advanced pancreatic adenocarcinoma.Patients and methods: The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m² i.v. 15-minute infusion followed by methotrexate 200 mg/m² i.v. 30-minute infusion on day 1 and 5-FU 600 mg/m² i.v. push on day 2. Folinic acid was given at 15 mg/m² p.o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles were repeated every two weeks.Results: Thirty patients with advanced chemotherapy-naive pancreatic cancer were included; 26 had measurable disease. Median age 56 years (27–72); median PS 1 (0–2). One PR (3.9%) was achieved; nine patients had stable disease. Median time to progression was 91 days. Median survival was 177 days and one year survival was 13.3% (4 of 30 patients). Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients.Conclusions: Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with advanced pancreatic adenocarcinoma.     

X-radiation induces 8-hydroxy-2'-deoxyguanosine formation in vivo in rat mammary gland DNA

Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8- Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic lesion that is widely regarded as a reliable index of oxidative DNA damage. The purpose of this study was to examine the effects of X- radiation on levels of 8-OHdG in the context of an experimental model for breast cancer in which chronic radiation exposure has been shown to be carcinogenic in Sprague-Dawley rats. A secondary objective of this study was to determine if the use of phenol during DNA isolation affected the concentration of 8-OHdG subsequently measured. Our results indicate that a profoundly carcinogenic dose of radiation induced a small but significant increase in 8-OHdG concentration in mammary gland DNA, and that the use of a phenol-based versus a salt-based method of DNA isolation had no significant impact on the levels of 8-OHdG detected in either control or irradiated tissue.      

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus leucovorin in the second-line treatment of metastatic breast cancer: Results of a phase II study

Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC).Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m², leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m², weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m² was administered additionally on days 1 and 22, q 50 days.Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting.Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.     

1-取代吡唑烷酮类抗惊构效关系的研究

1-正癸基吡唑烷-3-酮(Ⅱ结构式见表1)是欧洲专利报道的一种新型减肥剂。White等报道该化合物可通过血脑屏障,并对γ-氨基丁酸氨基转移酶(GABA-T)有强烈的抑制活性,但对谷氨酸脱羧酶的抑制作用较弱,因此可引起脑内γ-氨基丁酸(GABA)水平的升高,故我们相信应有抗惊活性。经我们合成后,发现Ⅱ确有良好的抗癲痫活性,抗小鼠最大电