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Biomedical subjects

W H Hoffman

Publications and source records attributed to W H Hoffman.

At least 37 records · Page 2Linked to original sources
PubMed1993

Role of synaptic excitation in the generation of bursting-induced epileptiform potentials in the endopiriform nucleus and piriform cortex.

1. The mechanism of generation of epileptiform excitatory postsynaptic potentials (e-EPSPs) induced by bursting activity in vitro was examined in slices of piriform cortex. 2. Previous study revealed that e-EPSPs in piriform cortex are generated in the subjacent endopiriform nucleus, perhaps with a contribution from the claustrum and deep part of layer III of piriform cortex. A puzzling feature of these e-EPSPs was their abrupt origin at long latency with little sign of preceding abnormal activity. 3. Systematic mapping revealed that within spatially restricted regions of the endopiriform nucleus there is an irregular buildup in extracellularly recorded multiunit activity and intracellularly recorded depolarization that precedes the onset of e-EPSPs. Analysis of latency revealed that these "slow-onset" e-EPSPs precede the more widely distributed "abrupt-onset" e-EPSPs, suggesting that they occur at sites of initiation. 4. The hypothesis was tested that the buildup associated with slow-onset e-EPSPs is dependent on synaptically mediated excitation. According to this hypothesis, all-or-none e-EPSPs originate when mutually excitatory (positive feedback) interactions within a population of cells in the endopiriform nucleus become self-regenerative. 5. Predictions from the regenerative positive feedback hypothesis that were successfully verified include the presence of excitatory synaptic connections between cells in the endopiriform nucleus; the consistent prediction of a subsequent e-EPSP from the occurrence of the accelerating buildup in population activity; the occurrence of inhibitory postsynaptic potentials (IPSPs) together with EPSPs during the buildup period; and the blockage of the buildup and e-EPSP by a low concentration of a specific excitatory amino acid antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). 6. Blockage of e-EPSPs by a concentration of DNQX that was much less than that required to block monosynaptic EPSPs in the endopiriform nucleus indicates that synaptic reverberation is mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) type excitatory amino acid receptors. 7. D-2-amino-5-phosphonovaleric acid (D-APV) reduced the duration and amplitude of e-EPSPs but did not block their occurrence, indicating that N-methyl-D-aspartate (NMDA) receptors have a boosting effect on e-EPSPs but are not required for their generation. This is in contrast to the induction of e-EPSPs by bursting activity for which NMDA receptor activation is required. 8. Outside the region of initiation e-EPSPs propagated through the endopiriform nucleus at a velocity of 0.1 m/s.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

The natural history of autonomous gonadal function, adrenarche, and central puberty in gonadotropin-independent precocious puberty.

Gonadotropin-independent precocity (GIP) is a syndrome marked by precocious pubertal development in the absence of pubertal levels of gonadotropins. To investigate the discrete patterns of central nervous system, gonadal, adrenal, and skeletal maturation in this syndrome, we conducted longitudinal studies spanning up to 10 yr in two such affected individuals. A cross-sectional analysis of adrenal androgen secretion was performed in nine additional patients to assess further the time course of adrenarche in GIP. Serial evaluations revealed progression of secondary sexual characteristics, statural growth, and skeletal maturation, all consistent with ongoing exposure to pubertal gonadal steroid levels. On the other hand, adrenarche (n = 11) and spontaneous and GnRH-stimulated gonadotropin secretion (n = 2) progressed in chronological age-appropriate manners despite long term pubertal levels of gonadal sex steroid secretion. After the development of central puberty, as documented by the appearance of pulsatile gonadotropin secretion, we sought to determine whether the potential for gonadal autonomy persisted. Despite complete pituitary desensitization induced by administration of a GnRH agonist, both patients studied demonstrated an ongoing capacity to secrete pubertal levels of gonadal steroids. Our study suggests that the timing of adrenarche and central puberty in these subjects with GIP was apparently unaltered by prolonged exposure to gonadal steroids. Subsequent to the development of central puberty, pulsatile gonadotropin secretion may override and, thus, mask the underlying defect(s) in adolescents and adults with histories of GIP.

Adrenal Glands↗
PubMed1992

Correlates of brain edema in uncontrolled IDDM.

Blood glucose, plasma sodium, bicarbonate (HCO3-), vasopressin, and hematocrit were monitored before and during treatment in patients with uncontrolled insulin-dependent diabetes mellitus (IDDM). These parameters were correlated with simultaneous serial cranial computed tomography readings of brain edema. Six of seven patients had positive computed tomography readings for brain edema on admission. Initial brain edema correlated directly with blood glucose (r = 0.79, P = 0.033) and inversely with HCO3- (r = -0.76, P = 0.047). At 6 h, brain edema still correlated with acidosis (HCO3-; r = -0.79, P = 0.033) but no longer with blood glucose. At that time, however, brain edema correlated with the rate of change in blood glucose (r = 0.915, P = 0.005). Results of interactive stepwise regression analysis suggest that the change in the calculated effective plasma osmolality plays a predominant role in the progression of brain edema during therapy (r = 0.995, P less than 0.001). Thus, although hyperglycemia and acidosis probably predispose to diabetic brain edema, osmotic factors may be major predictors of its evolution. No relationships were detected between brain edema and initiation of insulin therapy, plasma vasopressin, or changes in hematocrit. The factors responsible for initial brain edema and its progression, statistically identified in this study, require reassessment of common theories that attribute brain edema exclusively to therapy.

Adolescent↗
PubMed1991

Bursting-induced epileptiform EPSPs in slices of piriform cortex are generated by deep cells.

Previous study revealed that bursting activity generated by a variety of means in slices of piriform cortex induces persistent epileptiform EPSPs in superficial pyramidal cells by an NMDA-dependent process. The present study was undertaken to test the hypothesis that the observed epileptiform EPSPs in superficial pyramidal cells are driven by deep cells. This hypothesis was suggested by recent findings from in vitro studies of the properties of deep cells and in vivo studies indicating that the deep part of the piriform cortex or neighboring deep structures are involved in the generation of seizure activity in animal models of epilepsy. Results from simultaneous cell-pair recordings, examination of subdivided slices, and local application of excitatory and inhibitory agents provided strong evidence in support of this hypothesis. It was concluded that the endopiriform nucleus, a collection of cells immediately deep to the piriform cortex, plays a central role in generation, but that cells in the deep part of layer III and the claustrum may also contribute. Furthermore, it was found that generation of prolonged ictal-like activity only occurs in slices of piriform cortex in which the endopiriform nucleus is present. Implications of these findings for epileptogenesis are discussed.

Animals↗
PubMed1990

Autoantigenic determinants on human thyroglobulin. II. Determinants recognized by autoantibodies from patients with chronic autoimmune thyroiditis compared to autoantibodies from healthy subjects.

Using a panel of 20 well-characterized mouse monoclonal antibodies (mAbs) to native human thyroglobulin (Tg), the fine specificities of autoantibody responses in human autoimmune thyroiditis patients were compared to naturally occurring autoantibodies from healthy individuals. The antigenic determinants recognized by the human autoantibodies were assessed using competitive binding assays in which murine mAbs were inhibited by human autoantibodies. All determinants of human Tg recognized by the mouse were also responded to by the human subjects. Autoantibodies from adult and juvenile patients with chronic lymphocytic thyroiditis recognized principally 10 of 19 determinants defined by the panel of murine mAbs. The mAbs which define these 10 determinants do not react with Tg from seven other mammalian species; therefore, autoantibody responses in individuals with thyroiditis are directed primarily to species specific determinants of human Tg. These same determinants on human Tg were the principal ones recognized by the mouse following immunization. Particular patterns of fine specificities were not inherited from parents by probands or their siblings, even if identical twins. Naturally occurring Tg autoantibodies from healthy subjects recognized mainly thyroxine-containing cross-reactive determinants.

Adolescent↗
PubMed1990

Osmoregulation of vasopressin in diabetic ketoacidosis.

Osmoregulation of arginine vasopressin (AVP) is altered in diabetic ketoacidosis (DKA). With hyperglycemia, the AVP-plasma sodium (PNa) curve is displaced to the left, whereas the AVP-osmolality (Posm) curve is displaced to the right. The shift in the Na curve is explained by either resetting of the Na set point or by glucose acting as a nonpermeable solute, substituting for Na. Conversely, putative unmeasured solutes that, like urea, fail to affect AVP have been postulated to account for the right shift in the AVP-Posm curve. Therefore the respective roles of Posm = sigma [Xi] and plasma tonicity (Pton = sigma [sigmaiXi]), i.e., the sum of concentrations of all solutes [Xi] corrected (Pton) or not (Posm) for their relative cell permeability (sigma i), were studied in DKA. Indeed, Posm = sigma [Xi] exceeds Pton = sigma [sigma iXi] in DKA, since sigma i less than 1 for glucose. Potential determinants of AVP release (Posm, Pton, and PNa) were monitored in 7 patients with DKA. Conventional correlation analysis and two-dimensional (2D) graphs reproduced the paradox of an opposite shift in PNa and Posm set points for AVP release. However, by using the concept of tonicity instead of osmolality, 3D plots instead of 2D graphs, and multiple regressions instead of correlations, the AVP-PNa and AVP-Pton curves did not appear displaced. The concept of tonicity resolved the paradox of both osmolality and Na thresholds reset in opposite directions. Indeed, in states where a solute like glucose (with sigma less than 1) contributes substantially to plasma osmolality, Posm measured in vitro by the osmometer greatly exceeds Pton perceived in vivo by the osmoreceptor.

Adolescent↗
PubMed1990

Thyroid autoantibodies in black and in white children and adolescents with type 1 diabetes mellitus and their first degree relatives.

Genetic susceptibility is an important issue in understanding the mechanism of the autoimmune endocrinopathies and in assessing the risk of these conditions in pediatric patients. To this end, we evaluated autoantibodies to thyroid antigens, thyroglobulin (TgA) and microsomal antigen (TMA), in white and in American black juvenile patients with Type I diabetes mellitus (DM) to determine the predictive value of thyroid autoantibodies for the development of autoimmune thyroid disease. Sera from 159 patients (77 black and 82 white) with Type I DM were evaluated. A greater number of whites (41/82 or 50%) than blacks (12/72 or 16%) had thyroid autoantibodies (p less than 0.01). Fourteen patients (4 black and 10 white) exhibited hypothyroidism, and all had both TgA and TMA. Three patients (all black) had Graves' disease, one of whom had both TgA and TMA. Families of each racial group that had a diabetic child (proband) with thyroid autoantibodies (seropositive) or without thyroid autoantibodies (seronegative) were assessed for TgA and TMA as well as autoimmune thyroid disease. The prevalence of thyroid autoantibodies among siblings of seropositive probands was significantly greater than among the siblings of seronegative probands (p less than 0.01). The white sibling population showed a closer association of thyroid autoantibody prevalence with increasing age (p less than 0.05) than the blacks. Significantly more parents of probands than control parents exhibited thyroid autoantibodies (p less than 0.01). The general pattern of inheritance of either racial group showed that if one or both parents had thyroid autoantibodies, their progeny developed a significantly higher prevalence of thyroid autoantibodies than those of the seronegative parents. While there was no increase in overt thyroid disease among siblings of seropositive probands, a risk of developing autoimmune thyroid disease is probably imparted to these siblings by virtue of the thyroid autoantibodies.

Adolescent↗
PubMed1989

Relationship of plasma clonidine to growth hormone concentrations in children and adolescents.

The relationships of plasma clonidine to increases in growth hormone, blood pressure response and degree of sedation were studied in nine children with short stature after a 0.15 mg/m2 oral clonidine tolerance test. A direct correlation was found between the peak plasma clonidine concentration and the increase in plasma growth hormone (P = 0.055). The patients experienced varying degrees of blood pressure reduction and sedation that were unrelated to age. No correlation was found between the plasma clonidine concentration and degree of blood pressure reduction or degree of sedation. The half-life of oral clonidine ranged from 1.75 to 2.38 hours, which is significantly less than that for adults.

Adolescent↗
PubMed1989

Type I diabetes in an adolescent with common variable immunodeficiency.

A male adolescent with common variable immunodeficiency developed type I diabetes approximately 1 year after the initiation of immunoglobulin therapy. Immunologic evaluation revealed decreased numbers of T cells and an intrinsic B cell defect in immunoglobulin production. Lymphocytes from the patient failed to generate normal suppressor activity. There were no insulin or islet cell antibodies present in the patient's serum or in the commercial immunoglobulin preparations he received. The patient's HLA phenotype included HLA-DR3 and 4, placing him genetically at high risk for type I diabetes.

Adolescent↗
PubMed1989

X chromosome instability associated with familial Turner syndrome.

A family with two members (two generations) exhibiting Turner syndrome is described. Cytogenetic studies on these individuals showed the presence of multiple X chromosome changes. Evidence is presented to show that the maternally inherited X chromosome is the chromosome involved in the structural alterations observed. The effect of a tendency of the maternal X chromosome to break at specific sites on the development of the Turner phenotype and abnormal karyology is discussed.

Child, Preschool↗
PubMed1989

Frequency and variation of the posterior pituitary bright signal on MR images.

Sagittal T1-weighted series with 3-mm sections have routinely been used for all cranial MR studies at our institution. It was apparent from examining these studies that the rate of occurrence of a normal posterior pituitary bright signal was lower than has been previously reported, particularly in older patients. This prompted both a retrospective and a prospective review and analysis of the posterior lobe bright signal in three patient categories. The overall frequency of posterior pituitary bright signal and the influence of sex and age were evaluated in one category. An age-related statistically significant decline in the frequency of posterior pituitary bright signal was found, with a decline rate of approximately 1% per year. An evaluation of the occurrence of anatomic variation in the location of posterior lobe bright signal was made in a second group of 1500 patients. Abberrant location of the posterior lobe was found to be uncommon and was seen most frequently in patients with a sellar fossula. Temporal variation in the presence or absence and size of the posterior lobe bright signal was evaluated in a third group of 36 patients who had at least two MR examinations available for review. Follow-up MR study showed an obvious posterior lobe bright signal in 8% of these patients for whom no bright signal was apparent at the time of initial examination. Loss of the posterior lobe bright signal was apparent in another 25% of patients. A significant change in size of the bright signal was apparent in 19% of patients within this category. Our results indicate that variation in the bright signal of the posterior pituitary lobe should be expected as a normal physiological occurrence.

Adolescent↗
PubMed1989

Bursting induces persistent all-or-none EPSPs by an NMDA-dependent process in piriform cortex.

Burst responses to stimulation of excitatory fiber tracts in olfactory cortex slices after removal of extracellular Mg2+ or decreases in extracellular Cl-, resulted in long-lasting changes in response properties of neurons following a return to normal bathing medium. After bursting activity, the response of pyramidal cells to stimulation of afferent or associational fiber systems consisted of the normal graded depolarizing postsynaptic potential and a new, high-amplitude depolarizing potential that followed the graded potential at a variable latency. The new late potential had a waveform that resembled the initial graded response, but it occurred in an all-or-none fashion with a discrete threshold and persisted for many hours. Threshold for the late potential was similar for different cells in the same slice and was not affected by intracellular current injection, indicating that a synchronized interaction among a large number of cells is involved in its generation. Properties of the late potential indicate that it is an EPSP. NMDA receptor antagonists (APV and ketamine) had little effect on the late potential but prevented its development if present during bursting activity. The possible relevance of these findings to the study of the neuronal substrate for long-term memory and epilepsy is discussed.

2-Amino-5-phosphonovalerate↗
PubMed1988

Pharmacokinetics of propylthiouracil in children and adolescents with Graves' disease in the hyperthyroid and euthyroid states.

The pharmacokinetics of propylthiouracil (PTU) was studied in 7 patients having Graves' disease when they were hyperthyroid and then again when they were euthyroid. Two additional euthyroid patients were also studied. The t1/2, Ke, Ka, apparent Vd, AUC and clearance were calculated. Serum T3 and T4 were also measured. PTU had an immediate effect in reducing T3 levels. Although there were intraindividual variations, the mean PTU elimination half-time did not change from the hyperthyroid state (1.47 h) to the euthyroid state (1.53 h). The mean Ka when hyperthyroid (2.12 h-1) was significantly increased (p less than 0.005) compared to when euthyroid (1.00 h-1). The calculated kinetic information indicates that the disposition of PTU in children is similar to that reported in adults.

Adolescent↗
PubMed1988

Autonomic dysfunction and adrenocortical unresponsiveness to ACTH.

A child is reported with adrenocortical unresponsiveness to ACTH and autonomic dysfunction. The latter consisted of cold extremities, progressive loss of tear production, the development of achalasia of the esophagus, pupillary dysfunction, and an abnormal histamine skin test. These findings suggest progressive parasympathetic denervation as a cause for the adrenocortical abnormality.

17-Hydroxycorticosteroids↗
PubMed1987

Ectopic prolactin secretion from a gonadoblastoma.

A 6.5-year-old girl developed isosexual, pseudoprecocious puberty secondary to a gonadoblastoma. The tumor was found to produce and secrete both immunoassayable and bioassayable prolactin based on immunohistochemical techniques and the presence of a prolactin gradient between the tumor vein and peripheral vein. The source of the prolactin was a Sertoli-like cell. Neither growth hormone nor growth hormone-releasing hormone was detected within the tumor. This case confirms the ectopic production of prolactin by neoplastic tissue.

Child↗
PubMed1987

Empty sella associated with inappropriate TSH secretion.

A child diagnosed with long-standing primary hypothyroidism at age 10 and subsequent pseudotumor cerebri after initiation of thyroid therapy developed an empty sella and inappropriate thyrotropin secretion. No other evidence of thyroid hormone resistance was evident nor was there evidence of other endocrine dysfunction. This case confirms previous reports of a relationship between autoimmune thyroid disease, pseudotumor cerebri, empty sella and inappropriate anterior pituitary function.

Adolescent↗