Sleep and breathing in amyotrophic lateral sclerosis.
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Biomedical subjects
Publications and source records attributed to K A Ferguson.
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STUDY OBJECTIVE: To evaluate the interaction between craniofacial structure and obesity in male patients with obstructive sleep apnea (OSA). DESIGN: Retrospective analysis of a cohort of OSA patients. The relationships between neck circumference (NC), body mass index, apnea severity, and craniofacial and upper airway soft-tissue measurements from upright lateral cephalometry were examined. Patients were divided into groups; small to normal NC (group A), intermediate NC (group B), or large NC (group C). SETTING: A university teaching hospital and tertiary sleep referral center. PATIENTS: A consecutive series of patients with OSA who underwent polysomnography and lateral cephalometry. MEASUREMENTS AND RESULTS: Group A patients were less obese and had more craniofacial abnormalities such as a smaller mandible and maxilla and a more retrognathic mandible. Group B patients had both upper airway soft-tissue and craniofacial abnormalities. Group C patients were more obese with larger tongues and soft palates, and an inferiorly placed hyoid. Group C patients also had fewer craniofacial abnormalities than group A or B patients. There was no difference in airway size among the three groups. CONCLUSIONS: We conclude that there is a spectrum of upper airway soft-tissue and craniofacial abnormalities among OSA patients: obese patients with increased upper airway soft-tissue structures, nonobese patients with abnormal craniofacial structure, and an intermediate group of patients with abnormalities in both craniofacial structure and upper airway soft-tissue structures.
OBJECTIVE: To determine the safety of providing outpatient abortion services for women with complicated advanced pregnancies. METHODS: During a 10-year period, 124 abortions were performed after 14 menstrual weeks' gestation at an outpatient abortion facility for indications of fetal anomaly, diagnosed genetic disorder, or fetal death. Gestational lengths ranged from 15-34 menstrual weeks. Fetal diagnoses included a variety of chromosomal abnormalities, malformations, and death. Techniques for performing the late abortions included a serial multiple laminaria method of cervical dilation. Abortions performed after 20 menstrual weeks were effected by instillation of intra-amniotic hyperosmolar urea or induction of fetal death by injection of digoxin and/or hyperosmolar urea into the fetus, followed by artificial rupture of membranes, induction of labor, and assisted expulsion or instrumental extraction of the fetus. At less than 20 weeks, dilation and evacuation following serial multiple laminaria treatment of the cervix was the method of choice. RESULTS: The median gestational age was 23 menstrual weeks. The median procedure time for all cases was 12 minutes and median blood loss was 125 mL. Procedure time increased with length of gestation (P = .00). Blood loss was only slightly increased by gestation length (P = .154) and not by procedure time (P = .299). Complication rates were not significantly related to gestation length (P = .895). There was one major complication in this series. There were no uterine perforations and one cervical laceration. CONCLUSION: Outpatient abortion may be performed safely in most cases of fetal disorder, including death, through 34 menstrual weeks under proper conditions.
Neonatal anthropometry, including timed skinfold measurements, was performed on 55 products of selected pregnancies. These skinfold measurements were compared with published standards of measurements obtained by similar techniques. Values outside the 3rd percentile to 97th percentile range were overlaid on the birth weight/menstrual age relationship of these subjects. Seven of 10 subjects with the lowest midtriceps skinfolds weighed more than 2500 g at birth (2 more than 3500 g) and 2 of 4 with the largest midtriceps skinfold had birth weights less than 4000 g. This comparison emphasizes the imprecision of birth weight as a measure of quality of fetal growth. Since skinfold thickness measurement is cumbersome for clinical use, other neonatal measures that may be more readily available to the clinician were examined for correlation with skinfolds. Simple birth weight/crown-heel length ratio was found to have the closest relationship of the parameters examined. Although estimated fetal weight was found to be the ultrasonography-derived parameter best correlated with skinfold thickness, ultrasonography discriminated poorly between babies with normal and low skinfolds. Low skinfold thickness predicted thermal vulnerability in the nursery better than did birth weight.
Matching of donors and recipients in cases of B cell chronic lymphocytic leukemia (CLL) is complicated by the fact that the cancer clone dominates the blood. A case of CLL was characterized for its antigenic phenotype using monoclonal antibodies. Iron beads were coated with the appropriate antibody and used to remove the cancer clone. A mixed lymphocyte culture (MLC) utilizing the purified cells as well as unpurified cells and sheep cell rosetted purified cells was performed with the donor. Using coated beads, the T cell population rose from 8% to 95% in one treatment versus 8% to 42% with sheep cells. MLC data were statistically better with bead-treated cells, and the results demonstrated the importance of this technique for transplantation matching.
Development of monoclonal antibodies to lymphoid cells has allowed for simple methods for the classification of leukemias. Using the monoclonal antibodies, B1, B4, T1, T11, Ia, CALLA, My7, My9, and a polyclonal TdT reagent, we report a number of unusual phenotypes analyzed by flow cytometry. Two cases of mixed linkage leukemia are reported, one marked with anti-CALLA and My9, the other marked with T11 and Ia. Three rare cases of pediatric CLL are reported. Both were of B cell origin with chromosome transformation. These studies demonstrate the clinical importance of monoclonal antibodies in leukemia classification. The results also show that the so-called rare leukemias may not be as rare as previously thought.
This study has defined a method for preparation and monolayer culture of cells from chorion laeve. Cell number and cell protein content are stable over 7 d in culture. The cells will divide in response to epidermal growth factor in the presence of a supplemented, enriched medium and a collagen matrix, but they lose steroidogenic activity over time in culture. This culture system can be used as the starting point for the development of a chemically defined hormone-supplemented, serum-free culture system for studies of chorion cell differentiation and fetal membrane cell interactions.
The ciliate, Tetrahymena, was provided a supplement of the fatty acid [1-14 C]18:2 delta 6.9. After a period of growth the cells were claimed, the lipids extracted, the polar lipids recovered and the mild alkali-labile fatty acid methyl esters generated. The fatty acids were resolved by high pressure liquid chromatography (HPLC), the 18:3 delta 6.9,12(gamma-linolenic acid) was recovered and its identity verified by high pressure liquid chromatography (HPLC), gas liquid chromatography (GLC), hydrogenation and oxidation. Fifty-three percent of the cell-associated label was found in gamma-linolenic acid; thus, a delta 12 fatty acid desaturase converts the 6,9 octadecadienoic acid to the 6,9,12 derivative. No carboxyl or methyl terminus restriction appears on delta 9 monoenoic or dienoic fatty acid desaturation in this cell as is found in higher plants and animals.
The desaturation of oleoyl-CoA by a microsomal preparation from Tetrahymena has been studied. Desaturation of oleoyl-CoA required oxygen and NADH, and was inhibited by cyanide. HPLC analysis of fatty acid phenacyl esters, prepared from TLC-purified phospholipid, confirmed that radioactivity appeared in oleate, linoleate and gamma-linolenate. Both the time course of desaturation and the apparent desaturation of 1-palmitoyl-2-[14C]oleoylphosphatidylcholine suggested that phospholipid-bound oleate could be a substrate for desaturation. In the crude microsomal preparation, acylation of oleoyl-CoA to give oleoyl phospholipid was rapid. Therefore, preincubation in the absence of NADH was employed to create [14C]oleoyl phospholipids, and kinetic studies were carried out upon subsequent addition of NADH. When data were plotted in a double reciprocal form, a linear function was observed.
Tetrahymena microsomes contain cytochrome b5 and an NADH-dependent cytochrome b5 reductase, but these proteins are present at only one-tenth the levels observed in rat liver microsomes. We show that both proteins can be partially purified by techniques developed for the rat liver proteins. We can show that cyanide inhibits the rate of exhaustion of NADH, and therefore reoxidation of cytochrome b5 by microsomes, and that stearoyl CoA enhances the rate of reoxidation of the cytochrome. Also, we find that a fragment of rat liver NADH-cytochrome b5 reductase can restore NADH-dependent cytochrome b5 reduction to Tetrahymena microsomes which have been treated with N-ethylmaleimide to eliminate endogenous reductase activity. These results indicate that there is considerable resemblance between the rat and Tetrahymena systems, and that desaturation of stearoyl and oleoyl groups may occur in Tetrahymena via pathways similar to those known in liver.
Mammary tumor induction was examined in female Fischer rats fed a low-corn oil, a high-corn oil, a high-lard, a high-beef tallow, or a high-coconut oil diet since weaning. The diets were prepared by adding the experimental fat to a basal diet containing sufficient essential fatty acids for growth. These diets differed only in the concentration or type of dietary fat. The rats were given a single i.v. dose (50 mg/kg body weight) of N-nitrosomethylurea at 50 days of age. Mammary tumor incidences 28 weeks after N-nitrosomethylurea treatment in rats on low-corn oil, high-corn oil, high-lard, high-beef tallow, and high-coconut oil diets were 33, 85, 65, 50, and 43%, respectively. The data show that an increase in fat intake enhances mammary carcinogenesis, but the magnitude of the increase depends on the type of fat. Further analyses showed that the total oleic and linoleic acid intake in the five groups of rats correlated positively (r = 0.95) with mammary tumor incidence, whereas the composition of the mammary tissue neutral lipids and phospholipids did not. Our data suggest that the total oleate and linoleate intake in the high-fat diet is the major factor influencing the incidence of tumors by N-nitrosomethylurea.
The major lipids of Tetrahymena membranes have been purified by thin-layer and high pressure liquid chromatography and the phosphatidylethanolamine and aminoethylphosphonate lipids were examined in detail. 31P-NMR, X-ray diffraction and freeze-fracture electron microscopy were employed to describe the phase behavior of these lipids. The phosphatidylethanolamine was found to form a hexagonal phase above 10 degrees C. The aminoethylphosphonate formed a lamellar phase up to 20 degrees C, but converted to a hexagonal phase structure at 40 degrees C. Small amounts of phosphatidylcholine stabilized the lamellar phase for the aminoethylphosphonate. 31P-NMR spectra of the intact ciliary membranes were consistent with a phospholipid bilayer at 30 degrees C, suggesting that phosphatidylcholine in the membrane stabilized the lamellar form, even though most of the lipid of that membrane prefers a hexagonal phase in pure form at 30 degrees C. 31P-NMR spectra also showed a distinctive difference in the chemical shift tensor of the aminoethylphosphonolipid, when compared to that of phosphatidylethanolamine, due to the difference in chemical structure of the polar headgroups of the two lipids.
From a population of 515 subfertile couples and 119 women with amenorrhea, 38 patients were karyotyped because of specific signs and symptoms suggestive of chromosomal abnormality. The indications for karyotyping included primary amenorrhea, secondary amenorrhea with gonadal failure before 35 years of age, stature of less than 147.5 cm, azoospermia with eunuchoidism, and personal or family history of more than 2 spontaneous abortions or more than 2 severely abnormal children. In addition, 19 patients from the same subfertile population were selected randomly for karyotyping to serve as controls. Using banding techniques, chromosomal abnormalities were found in 18 of the 38 specifically selected individuals, whereas no abnormality was found among those randomly selected. Three of the 18 patients had chromosomal abnormalities not previously described; their karyotypes were 46,XY/48,XY,+8,+21; 46,X,inv dup(Xq)/q26 leads to q21); and 46,XY,t(9;20)(q22;q12).
Tetrahymena grown with foreign sterols such as ergosterol incorporate them into cellular membranes at the expense of the native compound, tetrahymanol. It is shown that cells grown with ergosterol have a lessened capacity to produce the polyunsaturated linoleic and gamma-linolenic acids from [14C]oleic acid. However, the same cells have normal capacities to introduce double bonds at C-6 into linoleate, alpha-linolenate, or cis-vaccenate. Thus, a presumed 12-desaturase is inhibited in the presence of ergosterol, while desaturation at C-6 is unaffected.
The addition of ergosterol to cultures of Tetrahymena pyriformis results in (a) the accumulation of the sterol by the cells; (b) the inhibition of the synthesis of the pentacyclic triterpenoid alcohol, tetrahymanol; (c) the replacement of tetrahymanol by ergosterol in the ciliate membranes. The dry weight and lipid content of sterol-supplemented ciliates did not differ from the controls. Examination of the lipid classes revealed no change in composition except for a higher content of ergosterol in supplemented cells than tetrahymanol in control cultures. The relative proportions of triglycerides, the major classes of polar lipids, 1-alkyl phospholipids and phosphonolipids, appeared unaltered. A complex array of fatty acids is found in this ciliate. Several acids not reported previously in this organism were isolated and identified, and the novel fatty acid 18:2 delta 6, 11, was found in substantial amounts. Ergosterol supplementation altered the proportions of the fatty acids, although not all lipid classes were affected to the same extent. The changes noted were of three general types: (a) a shortening of the fatty acyl chain length in the acids of the normal series; (b) a lowering in the degree of unsaturation; (c) a discrimination between two isomers of lionoleate, 18:2 delta 6, 11 and 18:2 delta 9, 12. The former is elevated in the presence of ergosterol while the latter is depressed. Each class of polar lipids has a distinctive fatty acid composition. Among the glycerophospholipids, cardiolipin and phosphatidylcholine were least affected, while the mixture of 1-alkyl-2-acyl-sn-glycero-3-(2-aminoethyl)-phosphonate and 1,2-diacyl-sn-glycero-3-(2-aminoethyl)-phosphonate was most markedly altered. Sphingolipid fatty acid composition was influenced by ergosterol supplementation. Two changes were noted: (a) a reduction in the length of the hydrocarbon chain; (b) an increase in the proportion of alpha-hydroxy acids. The impact of ergosterol on the fatty acid composition of the polar lipids may be on fatty acid biosynthesis, on incorporation of fatty acids, or on the turnover rates of the fatty acyl groups. Ergosterol is concentrated in the ciliary (limiting) membrane, as are the polar lipids most affected. This localization allows the speculation that the change in fatty acid composition may be related to the maintenance of optimal membrane properties upon the introduction of the sterol.
Alteration of the fatty acid composition of monolayer cultures of LM cells grown in chemically defined medium was achieved by supplementation with fatty acids complexed to bovine serum albumin. Phospholipids containing up to 40% linoleate were found in cells grown in medium containing 20 mu g of linoleate/ml. Incorporation of linoleate into phospholipids reached a plateau after 12-24 hr, and cells remained viable for at least 3-4 days. Although linoleic, linolenic, and arachidonic acids were incorporated into LM cells equally well, only the latter was elongated by these cells under these experimental conditions. Nonadecanoic acid was incorporated to a lesser extent than the polyunsaturated fatty acids. Phosphatidylcholine and phosphatidylethanolamine of LM cells had different fatty acid compositions; phosphatidylethanolamine contained more longer chain and unsaturated fatty acids. Cells were also grown in the absence of choline and presence of choline analogs such as N,N-dimethylethanolamine, N-methylethanolamine, 3-amino-1-propanol, and 1-2-amino-1-butanol. The analog phospholipids in these cells had fatty acid compositions which were intermediate between those of phosphatidylethanolamine and phosphatidylcholine of control cells grown in the presence of choline. Linoleate was found in both phosphatidylcholine and phosphatidylethanolamine of cells supplemented with linoleate. The sphingolipid fraction of these cells, however, did not contain significant amounts of linoleate. When linoleate was present in the phospholipids, compensatory decreases in the oleate and palmitoleate content of phospholipids were observed. Lowering of the growth temperature to 28 degrees produced an increase in unsaturate fatty acid content of the phospholipids. When linoleate was supplied to cells grown at 28 degrees, there was no further increase in the unsaturated fatty acid composition of the phospholipids. Using both fatty acid supplementation and lowered growth temperature, LM cell membranes can be produced which have phospholipids with vastly different fatty acid compositions.
Male Sprague-Dawley rats underwent resection of 50 cm of either proximal or distal small intestine or sham-operation. 6-7 weeks after operation mucosal calcium-binding activity was measured in segments of duodenum ileum and remaining 'midgut'. Similar measurements were obtained from weight and age-matched unoperated rats. There was no difference in calcium-binding activity between unoperated and sham-operated animals. After proximal resection the binding activity increased significantly in duodenum and midgut but did not change in ileum. After distal resection the binding activity decreased in duodenum but was unchanged in midgut and ileum. These studies show that mucosal calcium-binding activity undergoes changes but alteration of the binding activity in remaining gut varies with the location of the small bowel resection.