Biomedical subjects

J J Higgins

Publications and source records attributed to J J Higgins.

53 records · Page 3Linked to original sources

PubMed1994

Pyridoxine-responsive hyper-beta-alaninemia associated with Cohen's syndrome.

We report intermittent seizures, lethargy, and Cohen's syndrome in a 4-year-old girl with hyper-beta-alaninemia and a partial deficiency of beta-alanyl-alpha-ketoglutarate transaminase (AKT). To examine the role of beta-alanine (beta ALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of beta ALA. At concentrations of 10 to 25 mM, beta ALA caused more than a 50% reduction in the growth of her cells compared with normal control skin fibroblasts. The addition of 0.1 mM of pyridoxine to the culture medium abolished these toxic effects and increased her skin fibroblast AKT enzyme activity more than twofold. During a 2-year period of clinical observation, there were no further episodes of seizures or somnolence in our patient while she received oral pyridoxine therapy.

4-Aminobutyrate Transaminase↗

PubMed1994

Leukocyte functions of young dairy calves fed milk replacers supplemented with vitamins A and E.

Holstein calves (n = 44) were fed milk replacers from d 3 to 45 with low or high concentrations of vitamin A (7000 or 87,000 IU/kg) and vitamin E (11.2 or 57 IU/kg) to examine the influence of vitamin concentrations on vitamin bioavailability and leukocyte functions. Concentrations of alpha-tocopherol in plasma reflected increased vitamin E but were unaffected by increased vitamin A. Plasma retinol concentrations were greatest with high supplementation of vitamins A and E at wk 3; however, at wk 6, plasma of calves fed high vitamin A and low vitamin E contained the most retinol. Increased supplementation of vitamin A improved fecal consistency compared with that for calves fed the low vitamin A diet at wk 3 and 4. At wk 3, calves that received increased supplementation of vitamins E and A had enhanced neutrophil bactericidal activity compared with that of calves with increased individual vitamins. Lymphocyte DNA synthesis and chemotactic index were unaffected by dietary treatments. Results indicate that increased vitamin A in milk replacer did not affect plasma vitamin E concentrations, benefited fecal scores regardless of vitamin E concentrations, but was only beneficial to bactericidal activity of neutrophils in conjunction with increased vitamin E.

Animal Feed↗

PubMed1993

Isolated horizontal supranuclear gaze palsy as a marker of severe systemic involvement in Gaucher's disease.

Type 3 neuronopathic Gaucher's disease (GD3) is phenotypically heterogeneous. In many GD3 patients, progressive myoclonus and dementia dominate the illness, with death secondary to progressive CNS disease. We have designated this group as GD3a. We studied 14 children with Gaucher's disease, isolated horizontal supranuclear gaze palsy, and aggressive systemic disease, and designated this group as GD3b. In comparison with 13 children with type 1 non-neuronopathic Gaucher's disease, the GD3b children presented earlier, and were shorter, underweight, and more prone to cardiopulmonary, hepatic, and skeletal complications. One-half of the children died in childhood or adolescence of systemic complications. Patients with at least one copy of the mutation that causes substitution of asparagine for serine at amino acid 370 of glucocerebrosidase did not develop neurologic signs. Patients homoallelic for the mutation causing substitution of leucine for proline at position 444 had severe systemic disease; neurologic signs were frequently, but not invariably, present. Early diagnosis and timely enzyme replacement therapy promise to improve the prognosis in GD3b.

Adolescent↗

PubMed1993

The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann-Pick disease type C.

Niemann-Pick disease type C (NP-C) is a neurovisceral lipidosis characterized by defective intracellular trafficking of cholesterol and lysosomal accumulation of unesterified cholesterol, believed to be an offending metabolite. We studied the effect of cholesterol-lowering agents on hepatic and plasma cholesterol levels in NP-C by randomly assigning 25 patients with NP-C to one of five treatment regimens containing different combinations of cholestyramine, lovastatin, nicotinic acid, or dimethyl sulfoxide (DMSO). Unesterified cholesterol content was measured in liver biopsies before and after 4 months' treatment. All drug regimens except DMSO alone reduced hepatic and plasma cholesterol levels. Toxicity was limited and did not prevent any patient from completing the study. The combination of cholestyramine, lovastatin, and nicotinic acid lowered cholesterol levels in liver and blood with minimal side effects. A controlled clinical study will be necessary to determine if this regimen influences the rate of neurologic progression.

Adolescent↗

PubMed1992

Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome).

We describe the clinical and laboratory studies of an 11-year-old girl with prominent orofacial dyskinesia, dystonia, and progressive dementia. Investigations revealed hypoprebetalipoproteinemia, acanthocytosis, atypical retinitis pigmentosa, and evidence of iron deposition in the pallidal nuclei. Electroneuromyography and skin and sural nerve biopsies were normal. The "eye-of-the-tiger" sign, used to describe the pallidal nuclei in Hallervorden-Spatz syndrome, was present on T2-weighted MRIs (GE Signa, 1.5 T). Phase-contrast microscopy of whole blood showed 80 to 90% acanthocytes whose morphology was confirmed by electron microscopy. High-resolution lipoprotein electrophoresis demonstrated an absence of the pre-beta fraction. This case differs phenotypically from the previous reports of Hallervorden-Spatz disease with acanthocytosis by the presence of prominent orofacial dyskinesia and abnormal serum lipoproteins.

Acanthocytes↗

PubMed1992

A clinical staging classification for type C Niemann-Pick disease.

Analysis of the temporal sequence of neurologic events, neurophysiologic abnormalities, and longevity in 36 Niemann-Pick type C patients revealed two clinical subgroups with five stages of severity within each group. Patients with a preschool onset (group I; n = 18) had a higher mortality than did patients with a school-age onset (group II; n = 18). An asymptomatic phase (stage 0) was defined by biochemical and histopathologic evidence of disease. The initial manifestations of stage 1 were a movement disorder (group I) and cognitive difficulties (group II) accompanied by impaired vertical saccadic eye movements and abnormal acoustic reflexes. Stage 2 was characterized by the sequential occurrence of vertical supranuclear gaze palsy (VSGP), cognitive difficulties, and dysarthria in group I and a movement disorder, VSGP, and dysarthria in group II. Pyramidal tract signs and abnormal brainstem auditory evoked responses defined stage 3 in both groups. Stage 4 culminated in a nonambulant, vegetative state.

Adolescent↗

PubMed1992

Evaluation of reproductive traits in Bos taurus and Bos indicus crossbred heifers: relationship of age at puberty to length of the postpartum interval to estrus.

Records of age at puberty (AAP) and duration of the postpartum interval to estrus (PPI) for heifers calving first at 2 yr of age were used to determine the relationship between the two reproductive traits. The study from which these records were obtained was designed in a 2 x 2 x 2 factorial arrangement of treatments. Angus x Hereford (AH; n = 148) and Brahman x Hereford (BH; n = 148) heifers were allotted within breed after weaning by weight into light (LW) and heavy (HW) weight blocks. Heifers were assigned by age to different levels of energy (low or high) in diets calculated to reach a target weight of 55% (LE) or 65% (HE) of their projected mature weight by the onset of the breeding period. Data were analyzed within breed and included only records for which both AAP and PPI were available. Pearson correlation coefficients for AAP to PPI were r = -.12 (P = .20) and r = .05 (P = .71) for AH and BH, respectively. Eliminating animals that experienced dystocia from the analyses yielded correlations of r = -.27 (P = .02) and r = .06 (P = .65) for Ah (n = 69) and BH (n = 51), respectively. When energy level, weight block, and energy level x weight block were included in the model for PPI, analyses of variance indicated that PPI among AH heifers was influenced most by the weight at which heifers began the trial after weaning (P = .01) but not by energy level (P = .23) or the interaction of energy level x weight block (P = .48).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Response of young dairy calves with lasalocid delivery varied in feed sources.

Growth, age at weaning, fecal scores, and blood metabolites of young dairy calves were measured to determine the most effective method of lasalocid administration. Forty Holstein bull calves were blocked by date of birth and assigned randomly to one of four treatment groups: no lasalocid; lasalocid in starter; lasalocid in prestarter and starter; or lasalocid in milk, prestarter, and starter for a 12-wk period. Calves were fed milk twice daily until they consumed 227 g/d of prestarter, at which time the p.m. milk feeding was discontinued, and starter was offered for ad libitum intake as a mixture with the 227 g/d of prestarter. When total dry feed consumption reached 1.3% of birth weight, the calf was weaned. When the calf was 5 wk of age, the prestarter was discontinued. Daily gain tended to be greatest during the first 6 wk for the calves receiving lasalocid in milk, prestarter, and starter. These calves also were weaned with less variation in days to weaning. By wk 8 through 12, there were no differences in gain among the treatment groups.

Animal Feed↗

PubMed1992

Neutrophil and lymphocyte response to supplementation with vitamins C and E in young calves.

Calves, beginning at 3 d of age, were bottle-fed milk replacer unsupplemented, or supplemented with 10 g of vitamin C, or supplemented with 10 g of vitamin C plus 57 IU of vitamin E/kg of dry milk replacer (10 calves per treatment). Neutrophils from wk 2 and 4 blood samples were assayed for Staphylococcus aureus phagocytosis and neutrophil-mediated, antibody-dependent cellular cytotoxicity, and lymphocytes from those samples were assayed for concanavalin A-induced, phytohemagglutinin-induced, or pokeweed mitogen-induced proliferation. Ocular and nasal discharges of calves supplemented with vitamins C or C and E were less than those of controls for wk 1 to 8. Calves receiving supplementation with vitamin C and E tended to have higher mitogen-induced lymphocyte proliferative responses at wk 2. Neutrophil-mediated phagocytosis and antibody-dependent cellular cytotoxicity were lower at wk 2 and 4 for calves supplemented with vitamin C than for controls. Neutrophil function of calves supplemented with vitamins C and E together was near, or slightly higher than, that of unsupplemented calves for wk 2 and 4, suggesting that the addition of vitamin E negated the adverse effects that vitamin C alone had on neutrophil functions.

Animals↗

PubMed1991

Predictors of survival and characteristics of childhood stroke.

To determine predictors of outcome we reviewed 226 medical records of patients admitted to Children's National Medical Center with the diagnosis of cerebrovascular disease from 1978 to 1988. Ninety-five cases of stroke were identified by either neuroimaging techniques (87), autopsy (7), or clinical examination (1). Causal factors implicated in 89% of the patients included infectious (21%), vascular (18%), hematologic (15%), cardiac (13%) problems, minor trauma (8%) or miscellaneous (14%) causes. Patient outcome (n = 88) included residual impairment in 54%, complete resolution of their initial deficit in 23%, and death in 23%. Among patients with abnormal CT findings (n = 60), a logistic regression model revealed that patients with hemorrhage were at a significant risk (p = 0.0469) for death (odds ratio (OR) = 5.5, 95% confidence interval (CI) 1.2-24.5); those with an altered level of consciousness (stupor or coma) on presentation were also at risk (p = 0.0166; OR = 6.94, CI 1.7-28.5). The sensitivity and specificity of this model were 57% and 93%, respectively. No other clinical, laboratory, or demographic variable analyzed was predictive of outcome.

Cerebrovascular Disorders↗

PubMed1991

Evaluation of reproductive traits in Bos taurus and Bos indicus crossbred heifers: effects of postweaning energy manipulation.

Reproductive traits were evaluated in Bos taurus and Bos indicus crossbred heifers that were fed different diets during the postweaning period. The study was designed in a 2 x 2 x 2 factorial arrangement of treatments. Angus x Hereford (AH; n = 148) and Brahman x Hereford (BH; n = 148) heifers were sorted after weaning by body weight into light (LW) and heavy (HW) weight blocks. Heifers in each weight block were assigned to diets calculated to reach a target weight of 55% (LE) or 65% (HE) of their projected mature weights by the start of the breeding season. Puberty was determined after a 160-d observation period and characterized by the following criteria: 1) behavioral estrus, 2) presence of a palpable corpus luteum (d 6 to 10; estrus = d 0), and 3) rise in serum progesterone above 1 ng/ml (d 6 to 10). A higher (P = .01) proportion of AH heifers than of BH heifers reached puberty by the breeding season (93% vs 67%). Interactions of breed x weight block and energy level x weight block also contributed to this difference. Weight at puberty was heavier (P = .001) among HE than among LE heifers and greater for heifers in HW than for those in LW blocks (P = .02). Differences in prebreeding weight, body condition, average daily gain, hip height, and pelvic area were influenced selectively by breed, energy level, or weight block. Pregnancy rates were higher (P = .01) among AH than among BH heifers. Incidence and severity of dystocia was influenced by the breed x energy level interaction (P = .01). Brahman x Hereford heifers had less (P = .01) dystocia than AH heifers, HE heifers had less (P less than .02) dystocia than LE heifers, and HE-AH heifers had less (P less than .01) dystocia than LE-AH contemporaries. Subsequent duration of the postpartum interval to estrus was shorter (P = .002) among AH than among BH females. Pregnancy rates at the end of the 2nd yr were higher (P = .02) among LW than among HW females and weights were heavier (P = .001) at weaning among calves weaned from BH dams.

Animal Feed↗

PubMed1989

Neurological complications of hemolytic-uremic syndrome.

Of 78 children identified with hemolytic-uremic syndrome at the Children's Hospital, Boston, from 1976 to 1986, 16 patients (20.5%) had neurological manifestations during their hospitalization. The most common manifestations were significant alterations in consciousness (coma, stupor) in 12 patients, and either generalized or partial seizures in ten patients. Others included hemiplegia (4 patients), decerebrate posturing (3), cortical blindness (2), hallucinations (1), and dystonic posturing (1). Cranial computed tomographic scans were abnormal in eight of 11 patients scanned. The abnormalities included diffuse cerebral edema (4 patients), large vessel infarctions (3), diffuse multiple small infarcts (4), and multiple hemorrhages (1). Five patients died as a result of their central nervous system complications, and six had neurological sequelae at discharge. Five patients recovered and at discharge had no evidence of neurological dysfunction.

Brain↗

PubMed1989

Effects of energy and lasalocid on productivity of first-calf heifers.

One hundred forty-three crossbred, fall-calving first-calf heifers were used to determine the effects of two levels of energy and two levels of lasalocid on cow-calf productivity. Diets fed for approximately 110 d prepartum were calculated to provide a daily intake of 15.3 (LE) or 18.0 (HE) Mcal ME; diets fed for approximately 130 d postpartum were calculated to provide a daily intake of 17.8 (LE) or 21.0 (HE) Mcal ME. Two supplements were fed with each energy level to provide a calculated 0 (C) or 200 mg.hd-1.d-1 lasalocid (L). Heifers fed HE gained .06 kg more (P = .08) per day prepartum than LE heifers. There was an interaction (P less than .05) between treatment and prepartum days on trial for heifer weight approximately 2 wk prepartum and body condition at calving. Energy had no effect on heifer weight at 2 wk prepartum or condition score at calving when estimated and compared at 90 d on trial. However, regression estimates for 130 d on trial showed that HE heifers would have been 19 kg heavier (P less than .001) and would have had .4 unit higher condition score (P less than .01) than LE heifers. Energy and lasalocid had no effect (P greater than .05) on hip height or pelvic area at calving or on calf birth weight, calving ease score or gestation length. Cows fed HE weighed 17 kg more (P less than .05) and had .5 unit higher (P less than .001) condition score than LE cows at approximately 130 d postpartum. Lasalocid had little effect on postpartum changes in weight or body condition. Lasalocid supplementation to the LE diet tended to increase milk production and calf weight, whereas supplementation to the HE diet did not. Feeding the LE diet decreased (P less than .05) cycling activity by 18 percentage points and decreased (P less than .01) overall pregnancy rate by 25 percentage points. Lasalocid had no influence on reproductive performance.

Animal Feed↗

PubMed1988

Effect of sequential implanting with zeranol on steer lifetime performance.

Three trials involving 513 exotic crossbred steers were conducted to determine the effect of zeranol implanting in the suckling and growing phases on subsequent feedlot performance and carcass characteristics. Treatments were 1) unimplanted control, 0000; 2) implanted twice in the finishing phase, 00II; 3) implanted in the growing phase and twice in the finishing phase, 0III; 4) implanted in the suckling phase and twice in the finishing phase, I0II; 5) implanted in the suckling and growing phases with a single implant in the finishing phase, III0; and 6) implanted in the suckling and growing phases and twice in the finishing phase, IIII. Implanting in the suckling period did not significantly affect preweaning gain. Implanting in the growing period produced a treatment x trial interaction (P less than .05), but zeranol increased gains by an average of 8.4% over the three trials. Growing period gain was not influenced by implanting during suckling. Implanting twice during the finishing period increased gain (P less than .05) over unimplanted and III0 steers. Finishing gain was not influenced by previous suckling and(or) growing implant treatment. Lifetime ADG of steers was increased (P less than .05) by all implant treatments compared with unimplanted controls. Zeranol tended (P = .14) to improve feed conversion in the finishing phase. All implant treatments increased hot carcass weight (P less than .05), and all but III0 reduced fat deposition, as indicated by lower quality grade (P less than .05). Other carcass characteristics were not significantly affected by treatment. These trials demonstrated that implanting in the suckling and(or) growing phases of production did not reduce performance in the finishing phase.

Animals↗

PubMed1984

A model for the synthesis of chemical compounds in red blood cells, with an application to diabetes.

The amount of a substance produced and stored in red blood cells is modelled as the solution to a first-order differential equation involving the stochastic rate of production of the substance within each cell, the lifespans of the cells, and the birth and death rates of the cells. Estimation of the parameters of the model is outlined for a special case, and the model is fitted to a set of real data taken from clinically diabetic dogs.

Animals↗

PubMed1978

Fibrinogen clearance from alveoli.

In experiments lasting 311 +/- 8 (SE) min, we studied the clearance of 125I-fibrinogen ([125I])RIF) from distal lung units of anesthetized, ventilated dogs. We instilled varying concentrations of isosmolar, citrated [125I]RIF ranging from 0.75 to 4 mg/ml into alveoli of individual dogs, and we monitored clearance by the use of external detectors and blood and lymph sampling. Approximately 9% [125I]RIF passed into proximal airways according to detector signal analysis. Excluding airway flow, whole lung clearance of [125I]RIF occurred by degradation to small molecules that rapidly became evenly distributed in body extracellular water. The degradation appeared to take place within the distal airway and not within the lung interstitium because 131I-fibrinogen, injected intravenously, was degraded less in passing from plasma to right duct lymph. The intra-alveolar kinetics of [125I]RIF had 1.5 reaction order with a specific rate of 1.27 X 10(-5) ml(3/2)-mg(-1/2)-min(-1). The data indicate that fibrinogen clearance from alveoli occurs by both transbronchial bulk flow and intraalveolar degradation.

Animals↗

PubMed1977

Albumin clearance from alveoli: tissue permeation vs. airway displacement.

In anesthetized, ventilated dogs, clearance of 2 +/- 0.2 ml alveolar-instilled 1% isosmolar [125I]albumin ([125I]RISA) was separated into bulk airway displacement and transalveolar tissue permeation by the use of collimated external detectors and by sampling of blood and lymph. The detectors were positioned perpendicular to the plane of bronchial drainage, and collimator resolution was characterized by a 50% decrease in count rate for a 5-mm lateral (transbronchial) instillate shift. Detector signals demonstrated no airway shift in 10 dogs studied, the signal decay equaling [125I]RISA absorption determined by lung homogenates. The mean rate constants of [125I]RISA lung clearance and epithelial permeation were 4.08 X 10(-4)-min-1 and 5.48 X 10(-4)-min-1, respectively. The diffusional permeability coefficient of alveolar epithelium for albumin was 4.06 X 10(-9) CM-S-1. Absorbed [125I]RISA was separated into blood and lymph components by collecting lymph from the right lymphatic duct (RLD) and thoracic duct. Mean blood/lymph removal ratio was 6.3/1, and correlated with plasma/RLD lymph steady-state albumin concentration ratios in individual animals. Over a mean observation period of 5.4 h, an average of 12.3% [125I]RISA was cleared from the instilled region. The data suggest that this amount was cleared by permeation; there was little evidence of airway clearance.

Animals↗