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Biomedical subjects

B Hall

Publications and source records attributed to B Hall.

At least 37 records · Page 2Linked to original sources

Pregnancy outcome after treatment for acute lymphoblastic leukemia during childhood or adolescence.

To evaluate gonadal function and pregnancy outcome after treatment for acute lymphoblastic leukemia during childhood or adolescence, 44 former patients who were less than 20 years of age at diagnosis, 5 or more years from diagnosis, and 18 or more years of age were contacted. Thirty-nine (88%) provided information regarding pregnancy outcome. Gonadal function as estimated by the ability to conceive or sire a pregnancy, was not impaired despite treatment with substantial cumulative doses of methotrexate, 6-mercaptopurine, vincristine, and 1-asparaginase. Twelve patients reported a total of 27 pregnancies. There were four spontaneous abortions, one stillborn, and 22 liveborn infants. The birthweights were 1928 to 4536 g (median, 3430 g). Two infants had congenital anomalies. The childrens' ages ranged from 1 month to 10 years, 2 months (median, 6 years, 1 month). None has been diagnosed with any type of childhood cancer. The results of this study suggest that pregnancy outcome is not affected adversely by treatment received during childhood or adolescence for acute lymphoblastic leukemia.

Abortion, Spontaneous

Regulation of hepatic glycine catabolism by glucagon.

Glucagon stimulates 14CO2 production from [1-14C] glycine by isolated rat hepatocytes. Maximal stimulation (70%) of decarboxylation of glycine by hepatocytes was achieved when the concentration of glucagon in the medium reached 10 nM; half-maximal stimulation occurred at a concentration of about 2 nM. A lag period of 10 min was observed before the stimulation could be measured. Inclusion of beta-hydroxybutyrate (10 mM) or acetoacetate (10 mM) did not affect the magnitude of stimulation suggesting that the effects of glucagon were independent of mitochondrial redox state. Glucagon did not affect either the concentration or specific activity of intracellular glycine, thus excluding the possibilities that altered concentration or specific activity of intracellular glycine contributes to the observed stimulation. The stimulation of decarboxylation of glycine by glucagon was further studied by monitoring 14CO2 production from [1-14C]glycine by mitochondria isolated from rats previously injected with glucagon. Glycine decarboxylation was significantly stimulated in the mitochondria isolated from the glucagon-injected rats. We suggest that glucagon is a major regulator of hepatic glycine metabolism through the glycine cleavage enzyme system and may be responsible for the increased hepatic glycine removal observed in animals fed high-protein diets.

3-Hydroxybutyric Acid

Expanded phenotype and ethnicity in Setleis syndrome.

Setleis syndrome, an autosomal recessive disorder characterized by "coarse" face, temporal cutis aplasia, double upper eyelashes, absent lower eyelashes, chronic conjunctivitis, and prominent thick lips, was reported previously in 8 Puerto Rican children. We report on 3 unrelated children (one mentally retarded) with Setleis syndrome who are not of Puerto Rican descent. Two of our patients had imperforate anus, which has not previously been reported. The evolution of the phenotype over time is illustrated.

Abnormalities, Multiple

New haemocompatible polymers assessed by thrombelastography.

Mimicry of the nonthrombogenic surface of the erythrocyte has been advocated as the starting point for the development of nonthrombogenic biomaterials. Phosphorylcholine forms 88% of the outer surface of the erythrocyte, and so materials containing it should be nonthrombogenic. We have evaluated the thrombogenicity of such materials and compared them with Dacron and PTFE. Three materials containing phosphorylcholine were used: a naturally occurring phospholipid (dipalmitoylphosphatidylcholine, DPPC), a polymerized phospholipid (diacetylenic phosphatidylcholine, DAPC) and a polyester polyurethane (Polyester G). The thrombogenic potential of these materials was assessed by material thrombelastography (MTEG). This technique uses human whole blood at 37 degrees C, without an air interface, and records the elasticity of the blood clot produced. Since each material is evaluated with a control surface, extraneous differences due to factors other than the test material are eliminated. Analysis, and examples of the MTEG traces are shown and discussed. The phosphorylcholine containing materials were found to have a reduced amount of clotting factor activation, but only DPPC was better than Dacron and PTFE. MTEG demonstrated the known thrombogenicity of Dacron towards platelets. A striking reduction in platelet activation was shown for the three phosphorylcholine containing materials. These three materials show only 25% of the platelet activation of PTFE. These materials warrant further investigation as potentially very useful biomaterials.

Biocompatible Materials

Biomembranes as models for polymer surfaces. V. Thrombelastographic studies of polymeric lipids and polyesters.

Our approach to the design of haemocompatible biomaterials is based upon the concept that coating a polymer or metal surface with phosphatidylcholine polar groups (corresponding to the major phospholipid of the human erythrocyte outer cell membrane) will improve their haemocompatibility. We have examined the effect on blood coagulation of a number of substrates: those normally used in prosthetic devices such as polyethylene terephthalate (Dacron), expanded polytetrafluoroethylene, silicone and new polymers which contain the phosphatidylcholine head group (phosphorylcholine). The effect on coagulation of blood exposed to these substrates was determined by the technique of material thrombelastography, a relatively new method for the in vitro screening of biomaterial thrombogenicity. The results obtained with Dacron, polytetrafluoroethylene and silicone are compared with those obtained with a phospholipid-dipalmitoyl-phosphatidylcholine, a polymerized phospholipid-diacetylenicphosphatidylcholine, and a range of recently synthesized polyesters, each of which contains the phosphorylcholine polar head group.

Biocompatible Materials

Sequence and polyadenylation site determination of the murine immunoglobulin gamma 2a membrane 3' untranslated region.

We have determined the nucleotide sequence of the murine immunoglobulin gamma 2a membrane 3' untranslated region (1413 nucleotides) and approximately 679 nucleotides of downstream sequence. Two AATAAA hexanucleotide sequences are present in the 2092 nucleotide interval. The first one functions as the major polyA signal, directing cleavage and polyadenylation at a site 20 nucleotides downstream. Within 41 nucleotides downstream of the major membrane polyA signal are two sequences with 75% homology to the consensus sequence, (C/T)GTGTT(C/T)(C/T), identified by McLauchlan et al. [Nucl. Acids Res. 13, 1347-1365 (1985)]. An 80% homology match to the Berget consensus sequence, CA(C/T)TG, begins five nucleotides 3' of the major polyA site (used 20 times more than the second, downstream polyA site) [Berget Nature 309, 179-182 (1984)]. The second AATAAA, located 73 nucleotides 3' of the first, directs cleavage and polyadenylation 18 nucleotides downstream at a minor polyA site. One match with 75% homology to the McLauchlan consensus sequence begins 17 nucleotides 3' of the second (weaker) polyA site. No matches to the Berget consensus sequence are located near this second, weaker polyA site.

Animals

Renal serine production in vivo: effects of dietary manipulation of serine status.

Renal serine production in rats was quantitated by simultaneously measuring renal blood flow and the renal arteriovenous difference for this amino acid. The rate of synthesis was 0.24 +/- 0.02 mumol.min-1.100 g-1 in rats fed a diet containing 12% casein. This rate was not altered by the inclusion of an additional 1% serine in the diet for 7 days or by acute infusion of serine, although both protocols increased blood serine by 50%. When rats were fed a diet in which protein was entirely replaced by crystalline amino acids the rate of renal serine production was also 0.25 +/- 0.05 mumol.min-1.100g-1. Omission of serine or both serine and glycine from this diet did not alter the rate of renal serine synthesis. Renal serine production does not respond to the serine content of the diet.

Animals

Comparison of flow cytometric data obtained using fresh and paraffin-embedded lymphoid tissue.

Flow cytometric (FCM) DNA analysis was carried out on 24 lymph nodes: 13 from benign reactive hyperplasias and 11 from non-Hodgkin's lymphomas. FCM was performed on two types of samples: (1) fresh cell suspensions and (2) suspensions prepared from formalin-fixed, paraffin-embedded sections. FCM of fresh samples detected aneuploidy in 23 of the 24 cases while FCM of paraffin-embedded samples detected aneuploidy in only 6 of the 24 cases. Those six cases were lymphomas considered histologically as having a poor prognosis. Only one case, a lymphoma, was euploid with both methods. The coefficients of variance determined in each case for both methods were found to be within "normal ranges," but were greater in the paraffin-embedded specimens. The results suggest that FCM DNA analysis of formalin-fixed, paraffin-embedded sections does not have as great a resolution capacity as does analysis of fresh cell suspensions, since the former failed to detect cell populations that had a small degree of aneuploidy (close to the 2n population).

DNA

A framework for the analysis of psychiatric health facility utilization.

Existing research that examines the general problem of health facility use often lacks sound theoretical specification. This problem is partly a function of conceptual difficulties in explaining health seeking behaviour and an absence of appropriate data with which to calibrate modelling endeavours. These problems are addressed in this paper where a logit model of health seeking behaviour and health facility use derived from discrete choice theory is presented. The structure of the model is general but in this case it is developed in the context of mental health facility use. A data set from Auckland, New Zealand is utilized to apply the modelling ideas presented. Results show that discrete choice theory can be adapted to the problem of mental health facility usage under conditions where the health care system offers real choice at any given level of care. In this case real choice implies a well-developed array of alternative facilities to choose from.

Adolescent

Material thrombelastography: an assessment of phosphorylcholine compounds as models for biomaterials.

The use of phosphorylcholine (PC) containing compounds as possible biomaterials has been evaluated by material thrombelastography (MTEG). The detailed analysis of the MTEG technique is discussed. A remarkable reduction of thrombogenicity by compounds containing the PC group is demonstrated. The results observed with a polymerised PC-lipid indicate potential use of such substances as biomaterials with minimal thrombogenicity.

1,2-Dipalmitoylphosphatidylcholine

Proteinuria and renal function in diabetic patients fed a diet moderately restricted in protein.

Protein restriction has been used in the treatment of renal disease and may also be beneficial in the management of diabetic nephropathy. We evaluated the effects of moderate protein restriction (0.6 g/kg ideal body weight per day) for a 3-mo period on renal function in seven diabetic patients. Moderate protein restriction led to a decrease of approximately 50% in the albumin excretion rate in patients with overt proteinuria or microalbuminuria. This decrease occurred in some patients without a decrease in glomerular filtration rate, renal plasma flow, or plasma albumin concentration and may reflect subtle changes in filtration properties or permeability of glomeruli. In this pilot study moderate protein restriction has marked effects on albumin excretion irrespective of the initial degree of renal impairment. It is therefore suitable for longer-term study of its effects on the progression of renal disease in both patients with overt and incipient diabetic nephropathy.

Adult

Gluconeogenesis in liver and kidney of common murre (Uria aalge).

Phosphoenolpyruvate carboxykinase (PEPCK) in murre liver occurs in both cytoplasmic and mitochondrial forms. During a 3-day fast, hepatic PEPCK increases from 9.1 U/g with 19% cytosolic to 12.2 U/g with 35% cytosolic. The increase in activity is due almost entirely to increased cytosolic activity. PEPCK in murre kidney was present only in the mitochondrial compartment. Gluconeogenesis in vitro was determined in both hepatocytes and kidney tubules isolated from 3-day-fasted murres. In hepatocytes, lactate was the best substrate, but both pyruvate and alanine were good gluconeogenic substrates. This observation is consistent with the existence of a cytosolic form of PEPCK. In the kidney, glycerol was the best substrate but was only slightly better than lactate. Alanine and pyruvate were not as effective as gluconeogenic precursors, presumably because of the lack of cytosolic PEPCK. We propose that the major site of gluconeogenesis from amino acids in the murre is the liver, since this is a much larger organ than the kidney and has a cytosolic form of PEPCK necessary for gluconeogenesis from oxidized substrates.

Amino Acids

Pregnancy outcome following treatment during childhood or adolescence for Hodgkin's disease.

To evaluate the outcome of pregnancies occurring after the completion of treatment for Hodgkin's disease in children or adolescents, questionnaires were sent to 93 former patients diagnosed after January 1, 1960, who were currently 18 or more years of age and 5 or more years from the date of diagnosis of Hodgkin's disease. Forty-eight pregnancies were reported by twenty-two of the former patients or their spouses. Fifteen female patients had thirty-three pregnancies, of which three were electively terminated, two aborted spontaneously, four were stillborn, and twenty-four resulted in the birth of full-term infants, one of whom was small for gestational age. The spouses of seven male patients reported 14 pregnancies, of which two aborted spontaneously, three are in gestation, and nine resulted in the birth of full-term infants. Congenital anomalies were diagnosed in 9% (3/33) of the liveborn offspring, a frequency similar to that reported for the general population. The reported anomalies included lacrimal duct blockage, hydrocele, and ventricular septal defect. None of these children has been diagnosed with any type of childhood cancer.

Adolescent

Verapamil in essential hypertension: a comparison with atenolol plus hydralazine.

The effects of graded doses of verapamil were compared with those of a combination of atenolol and hydralazine in a double-blind, randomised, crossover trial in 16 patients with essential hypertension. During the placebo phase, mean arterial pressure (M.A.P.) was 123 +/- 17 mmHg. Verapamil (dose range 160-480 mg/day) lowered M.A.P. to 109 +/- 7 mmHg (p less than 0.01 vs placebo). The combination of atenolol (50-100 mg/day) and hydralazine (50-200 mg/day) lowered M.A.P. to 100 +/- 11 mmHg (p less than 0.001 vs placebo, p less than 0.05 vs verapamil). Neither regimen produced any deleterious effects on electrocardiographic intervals, echocardiographic indices of left ventricular function or plasma lipids. Verapamil was well tolerated and provided satisfactory alternative therapy in these patients with mild-to-moderate essential hypertension.

Adult

Cardiovascular and behavioral responses of gray wolves to ketamine-xylazine immobilization and antagonism by yohimbine.

Adult wolves (Canis lupus) were immobilized with 6.6 mg/kg ketamine hydrochloride (KET) and 2.2 mg/kg xylazine hydrochloride (XYL) administered intramuscularly. Induction time was 4.6 +/- 0.3 min (mean +/- SE). Immobilization resulted in significant bradycardia and hypertension (P less than 0.05). Twenty min after induction, the wolves were given 0.05-0.60 mg/kg yohimbine hydrochloride (YOH). Yohimbine given intravenously produced dose-related increases in heart rate (HR) with doses greater than 0.15 mg/kg resulting in extreme tachycardia (greater than 300 bpm). All doses of YOH caused a temporary decrease in mean arterial blood pressure (MABP) with some individual animals manifesting profound hypotension (less than 30 torr) at doses greater than 0.15 mg/kg. Increasing the dose of YOH above 0.15 mg/kg did not significantly decrease either arousal or ambulation times. Administering YOH at 40 or 60 min after induction resulted in decreased arousal and ambulation times. Stimulation by weighing and taking repeated blood samples during anesthesia did not shorten arousal times. We recommend that wolves immobilized with XYL-KET be antagonized with doses of YOH less than 0.15 mg/kg.

Animals