The neurochemistry of phenylketonuria

The mechanisms by which deficiency of hepatic phenylalanine hydroxylase causes central nervous system disease are reviewed. The neurological disease appears to be secondary to increased concentrations of phenylalanine and a decrease in the concentrations of other large neutral amino acids, especially methionine and tyrosine, within the central nervous system. This causes a deficiency of the neurotransmitter dopamine, reduced protein synthesis and demyelination. Similar mechanisms appear to be operating when blood phenylalanine concentrations are in the range expected for early continuously treated phenylketonuria. Conclusion The severe brain disease found in phenylketonuria is caused by a raised blood phenylalanine content which increases the brain free phenylalanine and decreases the concentration of other large neutral amino acids. Brain protein synthesis is decreased, myelin turnover is increased and there are abnormalities in amine neurotransmitter systems.     

Pain after barium enema: effect of CO2 and air on double-contrast study

One hundred fifty-one consecutive patients scheduled for double-contrast barium enema studies were assigned randomly to insufflation with either air or carbon dioxide (CO2) in a double-blind, prospective trial. Within 24 hours after the enema study, the patients were contacted by telephone by an interviewer, who completed a standard questionnaire. Radiographs from the enema studies were assessed for quality by two radiologists. Pain experienced after the procedure was graded from 0 (none) to 4 (severe). Clinically relevant (grades 2-4) pain was experienced by 30% of patients after insufflation with room air, compared with 11% of patients in whom CO2 was used for insufflation (P = .005). The mean pain score for CO2 was 0.4, and for room air, 1.2 (P less than .005). Although five patients experienced grade 4 pain after insufflation with air, no patient reported severe pain after CO2 insufflation. Post-evacuation films confirmed there was significantly less residual gas in the CO2 group. The quality of radiographs was equal in the two groups. CO2 has advantages for use in the double-contrast barium enema examination.     

Lifestyle risk factors for cancer: the relationship with psychosocial work environment

BACKGROUND: Psychosocial work characteristics (job demands, control, support, job strain and iso-strain [high job strain combined with social isolation at work]) may be linked to cancer risk, by affecting cancer-related lifestyles like smoking, high alcohol consumption, low intake of fruits and vegetables and lack of physical activity. METHODS: Cross-sectional data obtained from 3309 respondents participating in an ongoing prospective cohort study in the Netherlands on psychosocial factors and cancer risk were used to study the association between psychosocial job characteristics and lifestyle. Information on job characteristics and risk factor prevalence was collected from 20-65-year-old men and women, through self-administered questionnaires. Multiple logistic and linear regression analyses were undertaken by gender, with adjustment for age and education. RESULTS: No differences in the prevalence of lifestyle risk factors for cancer were found amongst the psychosocial work characteristics studied. Moreover, little evidence was found for a relation between job (or iso-) strain and cancer-related lifestyles in multivariate analyses. CONCLUSIONS: The present study found no support for the hypothesis that job strain or iso-strain are associated with a cancer-related lifestyle. Further research on the role of other psychosocial factors-like personality or social support outside work-in mediating associations between job characteristics and lifestyle, is warranted.     

肠缺血再灌流时肠内给予葡萄糖能增加肠粘膜血流量

目的探讨肠缺血再灌流损伤时肠内营养与肠粘膜血流改变的关系.方法SD大鼠分为三组,先制作空肠袋,然后将激光多谱勒探头和肠粘膜张力计放置在空肠袋两端,分别向袋内注射丙氨酸、葡萄糖及甘露醇.用动脉夹阻断肠系膜上动脉血流60分后,再恢复灌流60分.分别测定肠粘膜血流量和局部PCO2张力(PrCO2).结果缺血再灌流过程中,与甘露醇组比较,葡萄糖组粘膜血流量显著增加,PrCO2降低.结论缺血再灌流过程中,肠内给予葡萄糖能增加肠粘膜血流量,对缺血再灌流损伤的肠道提供保护作用.     

Biosynthesis and secretion of factor VII, protein C, protein S, and the Protein C inhibitor from a human hepatoma cell line

Using specific radioimmunoassays, 8 day cultures of Hep G2 cells were shown to contain in their supernatants 16, 74, and 828 ng/mL and in their cell lysates, 8, 55, and 48 ng/2 X 10(8) cells of factor VII, protein C, and protein S, respectively. These proteins and the protein C inhibitor were functionally active, and each of these activities was neutralized by their respective polyclonal antibodies. Although vitamin K had a modest effect, warfarin decreased the activity of secreted factor VII, protein C, and protein S by 50% to 90%. Protein C and protein S antigens were reduced three- to fourfold by warfarin. The protein C inhibitor antigen and activity were unaffected by vitamin K or warfarin treatment. Intrinsic labeling and immunoprecipitation indicated that factor VII, protein S, and the protein C inhibitor were secreted as 52,000, 77,000, and 58,000 molecular weight (mol wt) proteins, respectively. Protein C was secreted as a single-chain protein of about 65,000 mol wt, indicating that all of the vitamin K- dependent proteins are translated and secreted as single-chain molecules. Each of the four proteins studied represented their plasma protein counterparts structurally, functionally, and immunochemically. Thus, all of the known soluble components of the protein C pathway are produced by liver parenchymal cells.     

Centrilobular emphysema: CT-pathologic correlation

Over a 5-year period, 25 patients who had undergone chest computed tomography (CT) died and were autopsied. Their lungs were fixed in the inflated state and were assessed for the presence and severity of centrilobular emphysema (CLE). Three radiologists independently evaluated the CT scans for nonperipheral low-attenuation areas, peripheral low-attenuation areas, pulmonary vascular pruning, pulmonary vascular distortion, and pulmonary density gradient. The CT criterion that best correlated with the presence and severity of CLE was the nonperipheral low-attenuation area. With this CT criterion, lung destruction was correctly identified in 13 of 15 cases. The absence of this criterion resulted in correct identification of eight of ten normal lungs. These preliminary data suggest that CLE can be reliably identified and quantified with current CT scanners.     

L-3,4-dihydroxyphenylalanine (levodopa) lowers central nervous system S-adenosylmethionine concentrations in humans.

To determine whether levodopa reduces the levels of S-adenosylmethionine in the human central nervous system, cerebrospinal fluid (CSF) concentrations of S-adenosylmethionine, methionine, 3-methoxytyrosine, levodopa and 5-methyltetrahydrofolate were measured in six children with dopamine deficiency before and after treatment. In four, the lack of dopamine was secondary to a reduction in concentration of levodopa and these were treated with levodopa together with a peripheral dopa-decarboxylase inhibitor. In the other two, levodopa in the central nervous system naturally accumulated due to a congenital deficiency of aromatic-L-amino acid decarboxylase and these were treated with pyridoxine (which in this condition lowers central levodopa concentrations). Raising levodopa concentrations in the central nervous system caused a fall in CSF S-adenosyl-methionine concentration and a rise in CSF 3-methoxytyrosine concentration. No change was observed in CSF methionine concentration and in all patients CSF 5-methyltetrahydrofolate concentration was normal. With one exclusion there was a linear relationship between CSF S-adenosylmethionine and 3-methoxytyrosine concentrations. This is the first demonstration of such effects in humans and the implications upon levodopa therapy are discussed.     

Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients

Serial pulmonary imaging has proved to be effective in the evaluation of patients undergoing total joint arthroplasty. A clinical dilemma arises in asymptomatic patients whose postoperative pulmonary images differ from the preoperative images. The authors prospectively evaluated 403 patients with serial imaging to determine the significance of changed postoperative images in asymptomatic patients undergoing total hip or knee arthroplasty. Twenty-two (5.5%) patients had significant changes on postoperative images. Seventeen were asymptomatic; all but one underwent pulmonary angiography. Documented pulmonary emboli were demonstrated in 100% of patients whose postoperative images changed to indicate a high probability of pulmonary embolism, 71% whose images changed to a moderate probability, and 0% whose images changed to indeterminate probability. Overall, pulmonary emboli occurred in 76% of all asymptomatic patients with significantly change postoperative images. Asymptomatic pulmonary embolism is a significant occurrence after total hip or knee repair, and a changed lung scan with appropriate clinical evaluation is an accurate indicator of pulmonary emboli in asymptomatic postarthroplasty patients.     

Effect of repeated sampling and prestimulation on saliva buffer capacity and flow rate values in children

Abstract— Great variations reported in the frequency distribution of buffer capacity values may partly be due to methodological differences in saliva sampling. In this study we wanted to see to what extent these variations are due to repetition and prestimulation. 9-yr-old schoolchildren ( n : 41, 23 girls and 18 boys), who had never had saliva samples taken before, participated in the present study. The repetition tests were carried out between 9 and 11 a.m. on three subsequent days. The effect of prestimulation was tested 4 days later with the same subjects. The buffer capacity of the samples was determined electrometrically immediately after sampling using the commercial Dentobuff-test. The intraindividual analysis revealed a significant increase in flow rate but not in buffer capacity along with repetition of the sampling. The analysis further showed that the buffer capacity of children accustomed to saliva sampling increased significantly through prestimulation of 1 min. The use of prestimulation resulted in substantial changes also in the frequency distribution of the buffer capacity values. Our results emphasize the importance of proper sampling conditions in saliva collection when screening children for high caries risk.