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Biomedical subjects

L Jacobson

Publications and source records attributed to L Jacobson.

At least 73 records · Page 4Linked to original sources
PubMed1998

The role of dual energy x-ray absorptiometry in aiding the diagnosis of pediatric osteogenesis imperfecta.

The role of dual energy x-ray absorptiometry (DEXA) in the evaluation of the pediatric patient with multiple fractures has not been well established. We retrospectively examined the medical records of 45 patients who had presented to our institution with multiple fractures of unknown cause, who were not known to have osteogenesis imperfecta, and who had obtained DEXA as part of their evaluation. Of these, 26 patients had sufficient clinical data for inclusion in this study. Patients underwent DEXA of the anteroposterior spine and whole body. A z score was calculated to normalize the DEXA values for age. The diagnosis of osteogenesis imperfecta was correlated with the outcome of each DEXA scan to assess the validity of DEXA as a diagnostic tool. The DEXA of the anteroposterior spine had the highest sensitivity at 91.7%, while DEXA of the whole body had the highest specificity at 100.0%. Decreased bone mineral density may be associated with osteogenesis imperfecta, and DEXA is helpful in detecting low bone mineral density that may be missed on plain radiographs of children with milder forms of osteogenesis imperfecta.

Absorptiometry, Photon↗
PubMed1997

Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.

Adrenal Cortex↗
PubMed1997

Large cups in normal-sized optic discs: a variant of optic nerve hypoplasia in children with periventricular leukomalacia.

OBJECTIVE: To evaluate optic disc morphologic features in children with periventricular leukomalacia (PVL). PATIENTS AND METHODS: Seventeen children with PVL (patient group) were compared with 17 sex- and age-matched, full-term healthy control children (control group). Clinical ophthalmological examination and digital image analysis of fundus photographs were performed in all children. In children with PVL, cerebral imaging was performed. RESULTS: Children with PVL had larger optic disc cupping (P<.02) than did control children. A large proportion of the children with PVL had strabismus, nystagmus, and restricted visual fields. CONCLUSION: Our study indicates that optic nerve hypoplasia in children with PVL is often associated with a normal-sized optic disc with a large cup. This unusual form of optic nerve hypoplasia most likely results from transsynaptic degeneration of optic axons caused by the primary bilateral lesion in the optic radiation.

Adolescent↗
PubMed1997

Identification of phospholipase A2 and neurotoxic activities in the venom of the New Guinean small-eyed snake (Micropechis ikaheka).

The Papua New Guinean small-eyed snake (Micropechis ikaheka) is recognised as a cause of life-threatening envenoming in certain parts of New Guinea. The clinical features suggest the presence of toxins acting at the neuromuscular junction and on muscle. We have used the mouse phrenic nerve hemidiaphragm preparation, a phospholipase A2 assay, and 125I-neurotoxin-binding radioimmunoassays to look for toxic activities in the crude venom and in preliminary high-performance liquid chromatography (HPLC) fractions. Micropechis ikaheka venom at 1 and 3 micrograms/ml completely abolished nerve-evoked muscle twitch within 70 min at 37 degrees C. There was also a sustained contracture of the muscle and some reduction in twitch tension evoked by direct stimulation; these were explained by the presence of phospholipase A2 activity. The venom inhibited the binding of 125I-alpha-bungaro-toxin to detergent-extracted human muscle acetylcholine receptor (AChR), and inhibited acetylcholine receptor function in a muscle cell line. It also inhibited binding of 125I-omega-conotoxin GVIA to detergent-extracted human frontal cortex voltage-gated calcium channels, but this appeared to be dependent on the phospholipase A2 activity. Identification of the main neurotoxic fractions following HPLC are shown.

Animals↗
PubMed1997

Utrophin abundance is reduced at neuromuscular junctions of patients with both inherited and acquired acetylcholine receptor deficiencies.

Congenital myasthenic syndromes are a heterogeneous group of conditions in which muscle weakness resulting from impaired neuromuscular transmission is often present from infancy. One form of congenital myasthenic syndrome is due to a reduction of the number of acetylcholine receptors (AChRs) at the neuromuscular junction. We describe four new cases of AChR deficiency, characterized by a reduction in both miniature endplate potential amplitude and AChR abundance accompanied by elongation of the neuromuscular junction and some decrease in postsynaptic folding. A number of cytoplasmic proteins are normally associated with the postsynaptic membrane and may contribute to the clustering of AChRs at the neuromuscular junction. We therefore investigated the expression of several of these proteins in these AChR-deficiency patients. In each patient, immunolabelling of the neuromuscular junction for rapsyn, dystrophin, beta-dystroglycan and a form of beta-spectrin was strong but that for utrophin was markedly reduced or absent. This suggested that a defect in utrophin expression might underlie the congenital AChR deficiency. However, a reduction in utrophin labelling was also seen in three patients with adult acquired autoimmune myasthenia gravis in whom AChR loss results directly from the extracellular binding of autoantibodies. We conclude that the loss of AChRs in AChR deficiency does not result from the absence of rapsyn or beta-dystroglycan and that reduction of utrophin is probably secondary to the loss of AChRs. The possible role of AChRs and/or utrophin in determining the extent of postsynaptic folding is discussed.

Action Potentials↗
PubMed1997

Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library.

The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies.

Adult↗
PubMed1997

Prescription opiate abuse in chronic pain patients: clinical criteria, incidence, and predictors.

OBJECTIVES: Opiates are commonly used to treat patients with chronic nonmalignant pain. There is much controversy over the definition, incidence, and risk factors of prescription opiate abuse in chronic pain treatment. The present study, done at the Seattle VA Medical Center, was designed to create opiate abuse criteria, test inter-rater reliability of the criteria, apply the criteria to a group of chronic pain patients, and correlate the risk of opiate abuse with the results of alcohol and drug testing. DESIGN/OUTCOME MEASURES: A committee of experienced pain providers designed a five-point prescription opiate abuse checklist based on DSM-III-R parameters. The criteria were then applied to patients enrolled in the pain clinic. The reliability of the criteria were determined using two providers who were familiar with every patient in the clinic. Drug, alcohol, and psychosocial testing were correlated with the risk of opiate abuse. RESULTS: A total of 19% (76/403) of all pain clinic patients were using chronic opiates. Thirty-four percent (26/76) met one, and 27.6% (21/76) met three or more of the abuse criteria. The criteria had an inter-rater reliability of > 0.9. There were no differences between chronic opiate users (n = 76) and opiate abusers (n = 21) for a history of drug or alcohol abuse or on psychosocial testing. CONCLUSIONS: Prescription opiate abuse criteria for use in patients with chronic nonmalignant pain were designed. The criteria had good reliability and can be applied during normal clinic interactions. The percentage of chronic opiate users who become opiate abusers in pain treatment is within the range reported by others. Past opiate or alcohol abuse or psychosocial testing on clinic admission failed to predict who would become an opiate abuser. The criteria can be used to identify patients who will subsequently require more intensive treatment or intervention or can be used as an outcome to measure to test the effectiveness of treatment strategies.

Adult↗
PubMed1997

Protein malnutrition increases plasma adrenocorticotropin and anterior pituitary proopiomelanocortin messenger ribonucleic acid in the rat.

The mechanism by which protein malnutrition increases circulating glucocorticoids is unclear. To determine whether ACTH synthesis and secretion also increase in protein malnutrition, rats were sham adrenalectomized or adrenalectomized and replaced with varying amounts of corticosterone before dietary protein deprivation. Pair-fed rats served as controls for reduced voluntary food intake in protein-deprived rats. Dietary protein deficiency, but not pair-feeding, increased resting plasma corticosterone in sham-adrenalectomized rats. Restraint-induced ACTH secretion was not inhibited by the increased basal corticosterone levels in protein-deficient rats. When increases in corticosterone were eliminated by adrenalectomy or controlled by adrenalectomy with low level corticosterone replacement, increases in resting plasma ACTH and anterior pituitary POMC messenger RNA expression occurred with protein deprivation that could be statistically discriminated by regression analysis from changes due to caloric restriction (pair-feeding) and overt glucocorticoid feedback resistance. We conclude that protein malnutrition increases pituitary-adrenocortical activity at least in part by specifically increasing the drive for ACTH synthesis and secretion.

Adrenocorticotropic Hormone↗
PubMed1996

[A study of children with retinoblastoma. Diagnosis is often delayed].

Retinoblastoma is an uncommon but highly malignant ocular tumour of the early childhood. The delay in diagnosis following presentation at a health care facility was studied for 22 consecutive cases derived from the National Retinoblastoma Center in Sweden. Four of the children were regularly examined owing to a family history of retinoblastoma, but among the remaining 18 children the delay in diagnosis exceeded one month in five cases (including all children presenting with squint). However, there was no appreciable delay once appropriate fundus examination had been performed, thus stressing the need of early ophthalmological assessment in all cases of children manifesting signs consistent with retinoblastoma.

Child, Preschool↗
PubMed1996

Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis.

OBJECTIVE: The objective of this study was to determine the cause of purpura fulminans, disseminated intravascular coagulation, or thrombosis in seven children with varicella. All children were found to have a lupus anticoagulant and acquired protein S deficiency. Thrombosis in five children was associated with presumed or documented infection with streptococcus. STUDY DESIGN: Coagulation tests included determinations of the activated partial thromboplastin time, the prothrombin time, the dilute Russell viper venom time, the prothrombin F 1 + 2 fragment, the C4b-binding protein (C4b), total and free protein S antigen, and clotting activities of factors II, V, VII, and X and of protein C and protein S. Autoantibodies to phospholipids, cardiolipin, and protein S were determined in enzyme-linked immunosorbent assays. RESULTS: All children had a lupus anticoagulant and acquired protein S deficiency. Thrombosis in five children was associated with presumed or documented infection with streptococcus. All children transiently expressed free protein S deficiency, elevated levels of IgG, IgM, or both binding to protein S, the lupus anticoagulant, and increased concentration of the F 1+2 fragment. Four children also had antiphospholipid or anticardiolipin antibodies. In one child a purified IgG fraction cross-reacted with both protein S and a specific varicella antigen. CONCLUSIONS: A subset of children with varicella infection, some of whom are coinfected with streptococcus, are prone to development of a lupus anticoagulant and an autoantibody to protein S, which results in acquired free protein S deficiency. Such children are at risk of having life-threatening thrombotic events.

Antibodies, Antiphospholipid↗
PubMed1996

Visual impairment in preterm children with periventricular leukomalacia--visual, cognitive and neuropaediatric characteristics related to cerebral imaging.

Thirteen preterm children, aged 4 to 14 years, with visual impairment due to periventricular leukomalacia (PVL) were evaluated for visual function, intellectual level, cognitive profile and motor function. Their visual impairment was characterized by low acuity, crowding, visual field defects and ocular motility disturbances. Their cognitive profile was uneven, often with considerably higher scores on verbal than on visual-spatial tasks. Nine children had normal intelligence, three had mild mental retardation and one had severe mental retardation. In all the children, visual impairment was complicated by visual perceptual difficulties, accounting for their greater visual handicap than would be expected from their visual acuities and strabismus alone. Though CT or MRI revealed bilateral PVL in all the children, six had no motor impairment consistent with cerebral palsy, which is an unexpected finding.

Adolescent↗