Biomedical subjects
Publications and source records attributed to R Wood.
Total parenteral nutrition was provided to ten patients during pregnancy. No obstetrical or fetal complications attributable to the nutrition therapy occurred. All infants were at or above the tenth percentile in weight for gestational age. Total parenteral nutrition appears to be safe for the mother and fetus when given after the first trimester; the safety of total parenteral nutrition in the first trimester requires further study.
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We have examined for the presence of subtle hormonal abnormalities in women with long-standing unexplained infertility. For a full cycle serum LH, FSH, progesterone and oestradiol levels were measured about three times a week, and serial ultrasound scans of the ovaries made until the time of apparent ovulation. The results on 45 cycles in 35 women with unexplained infertility and in three normal volunteers are presented. Normal ovulatory cycles were defined by a length of 26-32 d, and progressive follicular maturation followed by disappearance or abrupt reduction in size of a follicle within 48 h of the recorded LH peak, followed by progressive and sustained rise in serum progesterone levels to more than 25 nmol/l and a luteal phase length of greater than or equal to 13 d. Thirty spontaneous cycles (28 women) were clearly normal while 15 spontaneous cycles (12 women) were abnormal. Abnormalities included luteinization of an unruptured follicle (eight cycles), absence of follicular development (two cycles), poor follicular development (two cycles), persistence of a large ovarian cyst from the preceeding cycle (two cycles) and one aluteal cycle. Six of the abnormal cycles were characterized hormonally by inappropriate elevation of serum LH levels throughout. If this study had been based only on serial ultrasound scans, all results on abnormal cycles might have been misinterpreted. If it had been conducted only with (multiple) progesterone determinations and the level of greater than 25 nmol/l had been taken as indicative of ovulation nine clearly abnormal cycles would have been considered as normal. We conclude that the combination of the hormonal and ultrasound assessment of ovulation increases our confidence for confirmation of normality and reveals various ovulatory disorders which are possibly due to an endocrinological defect or defects.
Twenty four patients with severe brain injury who had disturbed behaviours preventing rehabilitation or care in ordinary settings were treated in a token economy. This long-term follow-up study indicates that post-traumatic behaviour disorders can be lastingly improved, and that lengthy rehabilitation can have surprisingly good effects.
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In a retrospective study, medical records of a randomly selected sample of all infants less than 13 months old with tracheostomy of at least 1 month's duration were reviewed with respect to medical, demographic, and perinatal variables. Standardized outcome measures were used to document physical, cognitive, linguistic, and emotional development in a cross-sectional follow-up of all tracheostomized infants who were without primary mental retardation or neurological and physical handicap. The total sample of tracheostomized infants tended to be white, male, and premature, with moderate to severe medical illness in the perinatal period. There was a high rate of mortality and morbidity, with the majority of survivors presenting with multiple physical and mental handicaps. Follow-up of survivors without other major handicapping conditions suggested that long-term infant tracheostomy may be associated with impaired physical and emotional development, even when cognitive and language development are within normal limits. Pediatricians should be aware of the complex nature of this handicapping condition in order to coordinate appropriate interdisciplinary management.
The microsomal stearoyl-CoA desaturase system was examined in both the Morris hepatoma 7288CTC, maintained in the host Buffalo strain rat, and the Morris hepatoma 7288C, maintained in tissue culture. In vitro examination shows the stearoyl-CoA desaturase system to be similar in the 2 tissues. Both show extremely low overall stearoyl-CoA desaturase activity, having 4% and 8% of normal liver values respectively. Examination of the electron transport system showed both tissues have decreased electron transport components cytochrome b5 and cytochrome b5 reductase. Particularly noticeable were the extremely low levels of cytochrome b5 (2% compared with normal liver). Microsomes from both tissues showed a decreased ability to reduce an artificial electron acceptor, cytochrome c. With the low levels of cytochrome b5 observed in these tissues, the low levels of overall desaturase activity may be caused by lack of terminal enzyme, lack of sufficient cytochrome b5, or both. Analysis of the stearoyl-CoA desaturase system in cultured hepatoma cells suggests that these cells are similar to the host-grown tumor in this respect and may be used as a model in further examinations of the stearoyl-CoA desaturase system.
Fatty acids of Sterculia foetida were added to the medium used to maintain the Morris hepatoma 7288C in culture. The effect of this supplement on the lipid composition was examined. Overall, monoene levels were decreased with 18:1 levels reduced by 40%. Saturated fatty acid levels were increased, with stearate (18:0) levels 220% of control values. No effect occurred on the level of polyunsaturates (18:2, 20:4, 22:5, 22:6). These changes in fatty acid makeup were observed in both neutral and phospholipid fractions, and all lipid classes were affected. Triglycerides were most affected with a 66% decrease in 18:1. There appeared to be little specificity of effect in the phospholipids with 18:1 levels decreased 40-60% in all classes. All classes were therefore dependent on an endogenous supply of 18:1. Examination of the distribution of geometrical isomers of 18:1 reveals that in all lipid classes, except diphosphatidylglycerol (DPG), the ratio of delta 11 to delta 9 isomer decreased toward the isomeric distribution displayed by total medium lipids. In DPG, although 18:1 levels were lowered, the isomeric distribution increased. DPG, synthesized and found in the mitochondria, may use a separate pool of 18:1 during synthesis. Cyclopropene fatty acids (sterculic and malvalic) were incorporated into both neutral and phospholipid fractions with preferential incorporation into triglycerides. Cyclopropene fatty acids were not selectively incorporated into any phospholipid species. Sphingomyelin did not incorporate cyclopropene fatty acids, indicating that a different class of acyltransferase is used in the formation of this phospholipid class.
A system is described in which an intermittent motion powder filling capsule machine is modified to fill liquids into hard gelatin capsules suitable for pilot scale or small production batches. The system is shown to be suitable for filling materials covering a wide range of viscosities and to give excellent fill weight uniformity which is largely independent of operating conditions. The process is clean and trouble-free.
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Enriched subcellular fractions of nuclei, mitochondria, endoplasmic reticulum (ER), plasma membrane, and cytosol were prepared from liver and hepatoma 7288CTC taken from male inbred BUF rats. Purity was established by marker enzyme activities and distribution of DNA, RNA, sialic acids, total phospholipids, and cholesterol. The subcellular fractions of hepatoma differed from those of liver: 5'-Nucleotidase activity was elevated in ER and mitochondria, cytosol RNA was increased, and cholesterol was elevated in all hepatoma subcellular fractions. Neutral lipid classes of hepatoma subcellular fractions differed quantitatively from those of liver: Hepatoma nuclei and mitochondria contained elevated levels of free fatty acids (FFA) and triglycerides (TG). Generally, the fatty acid profiles of FFA, TG, and sterol esters from hepatoma subcellular fractions were more uniform and showed less organelle specificity than did liver. Hepatoma FFA and TG contained lower percentages of palmitate and higher percentages of stearate in all subcellular fractions than did liver. The sterol esters from most hepatoma subcellular fractions compared to those from liver were characterized by much higher levels of long-chain fatty acids of 20 carbon atoms or longer. The oleate-to-vaccenate ratio in FFA of liver subcellular fractions exhibited some specificity, but not that of hepatoma subcellular fractions. The oleate-to-vaccenate ratio in the acyl chains of liver and hepatoma TG did not reveal organelle specificity.
Phospholipids from homogenate, nuclei, mitochondria, endoplasmic reticulum (ER), plasma membrane (PM), and cytosol of liver and hepatoma 7288CTC (from inbred male BUF rats) were analyzed for their concentrations, fatty acid compositions of individual lipid classes, and levels of octadecenoate positional isomers. The phospholipid concentrations of hepatoma mitochondria and ER were less than 60% of liver values. Sphingomyelin concentrations were elevated dramatically in hepatoma nuclei, mitochondria, and PM. Hepatoma nuclei and mitochondria contained only 25% or less the concentrations of phosphatidylethanolamine (PE) as those of liver, whereas ER, PM, and cytosol fractions of hepatoma contained equal or greater concentration of PE than did the corresponding liver fractions. The fatty acid profiles of the individual lipid classes were somewhat characteristic of liver organelles but not of hepatoma. Lipid classes thought to be located preferentially on the outer bilayer of liver PM contained lower percentages of polyunsaturated fatty acids than did hepatoma PM. For hepatoma generally the lipid classes tended to exhibit a more uniform fatty acid profile among organelles, the polyunsaturated fatty acid percentages were decreased, and the octadecenoate percentages were increased. Octadecenoates isolated from individual lipid classes of organelles contained high levels of cis-vaccenate, in addition to oleate, and some class and organelle specificity was observed in liver. In contrast, hepatoma octadecenoates exhibited little class or organelle specificity, and much higher oleate concentrations were found in PM phosphatidylcholine, PM PE, and ER PE in hepatomas than in liver.
Groups of rats were fed a fat-free diet supplemented with 0.5% safflower oil (control) or the control diet containing 0.5% of 5,8,11,14-eicosatetraynoic acid (TYA). Blood was collected weekly and plasma lipids analyzed. After 4 weeks, the animals were killed and the liver lipids were analyzed in detail. The acetylenic fatty acid perturbed plasma neutral lipid and phospholipid class concentrations and reduced growth rates. Liver triglyceride concentrations were reduced dramatically in the TYA fed animals, suggesting interference with complex lipid synthesis. Plasma and liver triglycerides were shifted to higher molecular weight species suggesting that TYA affected fatty acid metabolism. The phospholipids showed an accumulation of 18:2 and a fall in 20:4 percentages indicating an inhibition in the conversion of linoleate to arachidonate. All major lipid classes exhibited an increase in 18:1 levels. Analysis of the octadecenoate positional isomers indicated the proportion of oleate increased substantually in all lipid classes whereas vaccenate proportions had fallen dramatically. All of the data collectively suggest that TYA inhibits the elongation of unsaturated fatty acids. A group of rats bearing hepatoma 7288CTC were also fed the TYA diet. Host liver lipids were affected by TYA similar to normal TYA fed animals, but the effects on hepatoma lipids were marginal.
A large group of rats was transplanted with hepatoma 7288CTC and 4 animals were sacrificed at 3-day intervals for four weeks. Lipid class concentrations, fatty acid class compositions, and the distribution of cis octadecenoate positional isomers in the major lipid classes were determined for heart, liver and lung at each time period. The hearts of host animals decreased in dry weight as hepatoma growth progressed. At day 30, heart weights were less than two-thirds of initial weights. Lipid class concentrations changed in all three tissues: cholesterol and free fatty acids increased in liver; triglycerides and cholesterol decreased and then increased in heart; and cholesterol, triglycerides and PC decreased in lung as tumor growth progressed. Hexadecenoate percentages exhibited a progressive decrease in all the lipid classes of heart and liver. Although total octadecenoate percentages showed only minor changes, oleate concentrations generally increased and vaccenate levels decreased in heart and liver lipids as tumor growth progressed. Palmitoleate, precursor of vaccenate, exhibited decreased concentrations early that resulted in decreased vaccenate levels. Decreased palmitoleate concentrations suggest inhibition of the delta 9 desaturase system, but normal oleate concentrations complicate this interpretation. Most of the changes in the lipids were detectable 3-6 days after transplantation, indicating the hepatoma affects the lipid metabolism of the host animal early and well in advance of nutritional stresses.
Headache classification has evolved through clinical experience because there are no objective findings which define causation or headache type. The resulting groupings are inconsistently defined, and may not be optimal for the study or treatment of headache patients. To determine whether the same headache types would have resulted if today's sophisticated statistical methods had been applied to standard data collected on unselected patients, 21 symptoms collected from 726 patients with acute headaches were analyzed. Five "natural' groupings or syndromes of symptoms were found in the data. Three were similar to traditional groupings: tension, migraine and cluster. Approximately one fourth of the patients had both tension and migraine symptoms, which suggests that the division of headaches into "tension' vs "migraine' has a large overlap. An "OCULAR' and a "URI' syndrome were also detected. Contrary to expectations, vascular headaches were not usually unilateral and patients with cluster headache symptoms were not usually males. The discrepancy between these findings and current perceptions may have been caused by differences in the populations or from biased patient selection in previous studies.
Cluster analysis was used to separate 726 headache patients into clusters of patients with similar symptoms. This was done to answer two questions: what "naturally occurring' groups of patients can be found? And how do these groups correspond to traditional headache types? When only two clusters were required, the best two clusters were tension and migraine-like. However, eight clusters could also be distinguished, and the migraine group then became very small. The clusters were tested for clinical interpretability by having 12 physicians name and prescribe treatment for the clusters. The suggested treatment was similar to what patients had actually received in about 2/3 of the cases but was rather different for the remainder. Further, the outcomes associated with different treatments appeared to vary by cluster. This suggests that the current method for classifying and treating headaches may not be optimal.
The effect of increased lung conductivity on ECG potentials was studied in human subjects undergoing pulmonary lavage of a whole lung. In this procedure, the air in the lung is replaced by physiologic saline solution, which is a highly conductive fluid. The same situation was simulated theoretically with an eccentric spherical model of the heart and torso. Both the experimental results and theoretical simulations show a decrease in body-surface potentials as the lung conductivity increases. In particular, a large decrease was observed in the posterior vector and the scalar Z lead both experimentally and theoretically. The model simulation shows that the scalar Z lead is maximal at a conductivity value that is very close to the typical normal lung conductivity, so that low voltages are predicted for low lung conductivities as well.