The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children

Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18 degrees C with occasional periods of circulatory arrest and represents marked physiologic extremes of temperature and perfusion. The safety of these techniques is largely dependent on the reduction of metabolism, particularly cerebral metabolism. We studied the effect of hypothermia on cerebral metabolism during cardiac surgery and quantified the changes. Cerebral metabolism was measured before, during, and after hypothermic cardiopulmonary bypass in 46 pediatric patients, aged 1 day to 14 years. Patients were grouped on the basis of the different bypass techniques commonly used in children: group A--moderate hypothermic bypass at 28 degrees C; group B--deep hypothermic bypass at 18 degrees to 20 degrees C with maintenance of continuous flow; and group C--deep hypothermic circulatory arrest at 18 degrees C. Cerebral metabolism significantly decreased under hypothermic conditions in all groups compared with control levels at normothermia, the data demonstrating an exponential relationship between temperature and cerebral metabolism and an average temperature coefficient of 3.65. There was no significant difference in the rate of metabolism reduction (temperature coefficient) in patients cooled to 28 degrees and 18 degrees C. From these data we were able to derive an equation that numerically expresses a hypothermic metabolic index, which quantitates duration of brain protection provided by reduction of cerebral metabolism owing to hypothermic bypass over any temperature range. Based on this index, patients cooled to 28 degrees C have a predicted ischemic tolerance of 11 to 19 minutes. The predicted duration that the brain can tolerate ischemia ("safe" period of deep hypothermic circulatory arrest) in patients cooled to 18 degrees C, based on our metabolic index, is 39 to 65 minutes, similar to the safe period of deep hypothermic circulatory arrest known to be tolerated clinically. In groups A and B (no circulatory arrest), cerebral metabolism returned to control in the rewarming phase of bypass and after bypass. In group C (circulatory arrest), cerebral metabolism and oxygen extraction remained significantly reduced during rewarming and after bypass, suggesting disordered cerebral metabolism and oxygen utilization after deep hypothermic circulatory arrest. The results of this study suggest that cerebral metabolism is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children. Deep hypothermic circulatory arrest changes cerebral metabolism and blood flow after the arrest period despite adequate hypothermic suppression of metabolism.     

Hemin enhances the in vitro growth of primitive erythroid progenitor cells

Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells.     

Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver

Dichloroacetic acid (DCA) is a chlorination byproduct found in finished drinking water. When administered in drinking water this chemical has been shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over the animal's lifetime. In this study, we investigated whether mutant frequencies were increased in mouse liver using treatment protocols that yielded significant tumor induction. DCA was administered continuously at either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice harboring the bacterial lacI gene. Groups of five or six animals were killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of treatment, there was no significant difference in mutant frequency between the treated and control animals at either dose level. At 60 weeks, mice treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60 weeks had a 2.3-fold increase in mutant frequency over the concurrent controls (P = 0.002). The mutation spectrum recovered from mice treated with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%) and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T transitions comprised 53.19% of the recovered mutants among control animals. Although only 19.15% of mutations among the controls were at T:A sites, 32.79% of the mutations from DCA-treated animals were at T:A sites. This is consistent with the previous observation that the proportion of mutations at T:A sites in codon 61 of the H-ras gene was increased in DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates DCA-associated mutagenicity in the mouse liver under conditions in which DCA produces hepatic tumors.      

Endoscopic stapled diverticulotomy: a real advance in the treatment of hypopharyngeal diverticulum

Between November 1993 and May 1996, 51 patients with a hypopharyngeal diverticulum were treated by endoscopic stapled diverticulotomy. Normal swallowing was resumed within 36 h of surgery in 73%, and in 93% by 72 h. Two patients required nasogastric feeding for 5–7 days. There were no operative deaths or serious operative morbidity, and there have been no recorded cases of clinical recurrence of pouches to date (maximum follow-up 562 days: 46 cases over 12 months). The low morbidity, short hospital stay and early return to normal feeding, combined with a relative absence of complications or pouch recurrence, make endoscopic stapled diverticulotomy the treatment of choice for the majority of patients.     

Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids

Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP ( n = 20) and standard Aptamil ( n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group ( n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg⁻¹) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil ( p < 0:01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.     

Field and model investigations of external gamma dose rates along the Cumbrian coast, NW England.

A survey of the contribution to external dose from gamma rays originating from intertidal sediments in the vicinity of the British Nuclear Group Sellafield site showed that the major anthropogenic contributions were due to (137)Cs and (60)Co. At some sites, traces of other anthropogenic radionuclides were detected, namely (106)Ru, (125)Sb, and (154)Eu. The proportions of fine grained material (<63 microm) were used to improve model predictions of dose contribution due to external exposure to gamma rays, using the CUMBRIA77/DOSE77 model. Model dose predictions were compared to those directly measured in the field. Using the new proportions of fine grained material (1-17.5%) in conjunction with field gamma-ray spectra, model predictions were improved considerably for most sites. Exceptions were at Drigg Barn Scar and Whitehaven Coal Sands sites, which had their own unique characteristics. The highest (60)Co activity concentrations in this study were detected at Drigg Barn Scar. These relatively high activity concentrations of (60)Co were due to the presence of (60)Co in mussels and barnacles, hence upsetting the fine sediment relationships used in previous dose calculations. Whitehaven Coal Sands was unusual in that it contained higher levels of radionuclides than would be expected in sandy sediment. The mineralogy of these sediments was the controlling factor on (137)Cs binding, rather than the proportion of fine grained material. By adjusting the effective fine grained sediment proportions for calculations involving (60)Co and (137)Cs at Drigg Barn Scar and Whitehaven Coal Sands respectively, the CUMBRIA77/DOSE77 model predictions could be improved upon significantly for these sites. This work highlights the influence of particle size and sediment composition on external dose rate calculations, as well as the potential for external dose contributions from biota.     

9:30-9:45. Preliminary Evaluation of F-18 Fluorocholine (FCH) as a PET Tumor Imaging Agent

The purpose of this study was to develop and evaluate an F-18 labeled choline tumor imaging agent.FCH was synthesized through the intermediate F-18 fluorobromomethane that was used to alkylate dimethylethanolamine. The isolated FCH was evaluated in PC-3 human prostate cancer cells, PC-3 human prostate cancer xenograft studies, and human prostate and brain tumor patients.FCH was accumulated at a slightly lower rate than FDG in the cultures of PC-3 cells. Inhibition of choline transport and phosphorylation by hemicholinium-3 resulted in a 90% decrease in FCH uptake without altering FDG uptake. FCH had a similar biodistribution as C-14 choline in mice, with the liver and kidneys being the primary sites of uptake. Tumor uptake of FCH and FDG were comparable at 45-60 mins after injections. The tumor:blood ratio was higher for FCH (5.3 +/- 2.4) than for FDG (3.2 +/- 0.3). Brain uptake of FCH was 10% that of FDG. FCH-PET studies were compared to FDG-PET studies. In the prostate cancer patients, more lesions have been seen on the FCH studies than on the FDG studies, and the standardized uptake values (SUV) have been higher with the FCH. Decreases in FCH-PET SUV have been noted in patients treated by androgen deprivation. Patients with suspected recurrent brain tumors have had more clearly defined abnormal accumulation on the FCH-PET scans than on the FDG-PET scans. The FCH is not accumulated by normal cortex.FCH is a promising imaging agent for the evaluation of metastatic prostate cancer and recurrent brain tumor.     

Quality of Care for Acute Myocardial Infarction in Rural and Urban US Hospitals

CONTEXT: Acute myocardial infarction (AMI) is a common and important cause of admission to US rural hospitals, as transport of patients with AMI to urban settings can result in unacceptable delays in care. PURPOSE: To examine the quality of care for patients with AMI in rural hospitals with differing degrees of remoteness from urban centers. METHODS: This cohort study used data from the Cooperative Cardiovascular Project (CCP), including 4,085 acute care hospitals (408 remote small rural, 893 small rural, 619 large rural, and 2,165 urban) with 135,759 direct admissions of Medicare beneficiaries ages 65 and older for a confirmed AMI between February 1994 and July 1995. Outcomes included use of aspirin, reperfusion, heparin, and intravenous nitroglycerin during hospitalization; use of beta-blockers, aspirin, and angiotensin-converting enzyme (ACE) inhibitors at discharge; avoidance of calcium channel blockers at discharge; and 30-day mortality. FINDINGS: Substantial proportions of Medicare beneficiaries in both urban and rural hospitals did not receive the recommended treatments for AMI. Medicare patients in rural hospitals were less likely than urban hospitals' patients to receive aspirin, intravenous nitroglycerin, heparin, and either thrombolytics or percutaneous transluminal coronary angioplasty. Only ACE inhibitors at discharge was used more for patients in rural hospitals than urban hospitals. Medicare patients in rural hospitals had higher adjusted 30-day post-AMI death rates from all causes than those in urban hospitals (odds ratio for large rural 1.14 [1.10 to 1.18], small rural 1.24 [1.20 to 1.29], remote small rural 1.32 [1.23 to 1.41]). CONCLUSIONS: Efforts are needed to help hospital medical staffs in both rural and urban areas develop systems to ensure that patients receive recommended treatments for AMI.     

代谢综合症基线调查

目的：通过对豫宛市30岁以上人群代谢综合症（MS）发病率的词查、统计和分析，旨在唤起人们对此病的重视和预防。方法：利用年度体检之机采用三级分组法对30岁以上人群进行有关MS指标的检测和统计，依据亚洲及我国体重指数标准及2004年中华医学会糖尿病分会诊断代谢综合症标准。共计调查人数3987人（男1981人，女2006人）。结果：30岁以上MS患病率，青年有10％～13％，中老年后可渐增至20％～30％。结论：MS是中老年多见的代谢异常疾病。已严重威胁着人们的生命健康。