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Biomedical subjects

J A French

Publications and source records attributed to J A French.

At least 19 recordsLinked to original sources
PubMed2001

Interactions among paternal behavior, steroid hormones, and parental experience in male marmosets (Callithrix kuhlii).

Male black tufted-ear marmosets (Callithrix kuhlii) contribute to the rearing of their offspring. Here we evaluated predictions of hypotheses suggesting that (1) T and E2 influence infant-care behavior in male marmosets, (2) levels of T and E2 are modulated by paternal experience, and (3) paternal behavior and levels of T and E2 in male marmosets covary with stress. We observed the behavior of marmosets in their family groups following the birth of infants and evaluated urinary concentrations of T, E2, and the stress hormone cortisol (CORT) among fathers before and after the birth of young. Urinary levels of T, E2, and CORT were lower among males who carried infants at high rates than males who carried at low rates, and T and CORT levels were negatively correlated with carrying rates across all males. Males had significantly lower T levels while carrying the second compared to the first litter and slightly lower rates of infant-carrying, possibly due to assistance provided by offspring of the first litter. There were increases in CORT levels of fathers after the birth of the first litter, but decreases in CORT after the birth of the second. Our results suggest a relationship in C. kuhlii between paternal behavior, hormones, and paternal experience. Rates of infant-carrying appear to be linked to hormone levels, and hormone levels in turn are affected by experience caring for young. Our data also suggest that T, E2, and CORT have synergistic influences on infant-carrying behavior or alternatively that associations between T and E2 and rates of infant-carrying are influenced by stress or other glucocorticoid-related variables. Finally, we propose a hypothesis suggesting that experience-related changes in hormones reinforce the commitment of males to successful breeding partnerships.

Animals↗
PubMed2000

Management of epilepsy in adolescents and adults.

Epilepsy is the most common serious neurological disorder affecting an estimated 50 million people worldwide. Particular focus should be placed on a safe diagnosis, seizure and syndrome classification, and choice of pharmacological and surgical options for a range of patient populations with different health-care requirements. Eight new antiepileptic drugs were licensed in the 1990s with more to come. These new drugs along with earlier resective surgery have led to a better outcome for many more people with this condition.

Abnormalities, Drug-Induced↗
PubMed2000

Pre- and postpartum sex steroids in female marmosets (Callithrix kuhlii): is there a link with infant survivorship and maternal behavior?

Recent studies in primates have suggested that pre- and peripartum sex steroid hormones may be important determinants of maternal behavior and motivation, since higher levels of prepartum estrogen are associated with maternal competency and infant survivorship. To test the cross-species generality of this finding, we monitored excreted profiles of estradiol (E(2)), progesterone metabolites (pregnanediol glucuronide; PdG), and E(2):PdG ratios throughout pregnancy in black tufted-ear marmosets (Callithrix kuhlii). Additionally, we wanted to determine the extent to which variability in maternal carrying effort was related to hormonal factors and relative levels of maternal experience. For six females, hormonal profiles were determined by enzyme immunoassay for two pregnancies, one in which infants survived at least 2 weeks postpartum and one in which infants did not survive. Our within-subjects analyses revealed significant differences in mean prepartum E(2) levels for females in the different infant survival conditions. In contrast to previous findings, however, females exhibited significantly higher prepartum E(2) levels when their infants did not survive a minimum of 2 weeks postpartum, relative to when their infants did survive. Maternal carrying effort was also negatively and significantly correlated with prepartum E(2) levels. Unlike previous reports in callitrichid primates, then, our data suggest that high concentrations of prepartum E(2) in callitrichid primates are not necessarily associated with competent maternal behavior and may instead be associated with poor infant survivorship and inadequate maternal care. Further, our results appear to be convergent with research focusing on human mothers and may represent a common underlying mechanism linking prepartum estrogen and postpartum affect and behavior in some primates.

Animals↗
PubMed2000

Antiepileptic drug interactions.

This article reviews the potential interactions of antiepileptic drugs (AEDs) and the pharmacokinetic and pharmacodynamic principles involved. It describes the absorptive and distributive properties of AEDs and the effects on protein binding, hepatic metabolism, and elimination resulting from co-administration of AEDs with food or other drugs. Drug behavior is a function of absorption, metabolism, distribution, and elimination. Administration of either multiple AEDs or a combination of AEDs plus drugs for other conditions can modify any of these physiologic processes, possibly resulting in complex interactions. These may include alterations in the bio-availability and absorption of a drug and changes in half-life and serum level through induction or inhibition of hepatic metabolism. In most cases, increases or decreases in serum concentrations will signal a drug interaction. In other cases, clinically significant drug interactions remain undetected owing to apparently stable serum concentrations. Co-administration of drugs may affect the rate of clearance of one or both drugs. The effect on clearance varies, owing to genetic factors, patient characteristics (age and presence of co-morbidities), and individual responses. AEDs that induce hepatic metabolism can also influence the metabolism of concomitantly administered non-epilepsy medications and can interfere with oral contraceptives, as well as vitamins D and K. Patients with renal insufficiency or advanced age may experience incomplete renal excretion and should receive reduced dosages of drug. Understanding the pharmacokinetics and pharmacodynamic properties of AEDs and the route of metabolism of all competing drugs is important for optimal management of patients with epilepsy and for prevention of avoidable drug interactions.

Anticonvulsants↗
PubMed1999

Hemispheric asymmetries in arousal affect outcome of the intracarotid amobarbital test.

OBJECTIVE: To evaluate changes in arousal and their impact on memory performance during the intracarotid amobarbital test (IAT). METHODS: Along with memory measures, level of arousal was evaluated through clinical ratings and nonverbal self-ratings in epilepsy patients undergoing IAT before anterior temporal lobectomy. RESULTS: Irrespective of seizure focus, left-sided amobarbital injection resulted in decreased objective and subjective arousal more often than right-side injection. Impaired objective arousal was greater when the left hemisphere was injected second, because of the presumed additive effects of systemic amobarbital residual from the first injection. Decreased objective arousal was related to poorer performance on memory testing following left-hemisphere injection. CONCLUSIONS: The IAT, as practiced in most centers, is biased, so patients with right temporal lobe seizure focus are more likely to "pass" the test, whereas patients with left seizure focus are more likely to "fail" the test. The significant impact of changes in arousal on memory testing needs to be considered when using IAT results to select patients for temporal lobectomy.

Adult↗
PubMed1999

Ventricular asystole during vagus nerve stimulation for epilepsy in humans.

Electrical stimulation of the vagus nerve, a recently available option for patients with refractory epilepsy, has demonstrated safety and efficacy. We report four patients with refractory epilepsy who experienced ventricular asystole intraoperatively during initial testing for implantation of the vagus nerve stimulator. Acute intraoperative vagus nerve stimulation may create ventricular asystole in humans. Extracorporeal cervical vagus nerve stimulation testing with continuous EKG monitoring intraoperatively before generator implantation is warranted.

Adult↗
PubMed1999

Androgen threshold to activate copulation differs in male rats prenatally exposed to alcohol, stress, or both factors.

Few male rats prenatally exposed to a combination of alcohol and stress copulate spontaneously. This study determined adult sensitivity to testosterone (T) in males prenatally exposed to alcohol, to stress, or to both factors. Sexually naive males were tested with receptive females following castration and implantation of 20-, 30-, or 45-mm Silastic T-filled capsules. Serum T levels provided by these implants were measured. The behavior shown by males exposed only to prenatal alcohol did not differ from untreated control animals at any T dosage. Prenatal stress alone diminished the copulatory potential below control levels only when the intermediate T dosage was provided. Few males exposed to both alcohol and stress copulated under the lowest or the intermediate dose of adult T replacement, but most ejaculated normally when the largest capsule was implanted. The threshold to the sexual behavior-activating-properties of adult T exposure was moderately raised by prenatal stress but was severely affected when prenatal stress was combined with alcohol. We conclude that a diminished sensitivity to androgen in adulthood underlies some copulatory deficits resulting from treatments that alter fetal T levels. Such deficits may be concealed when behavior is evaluated in gonadally intact animals.

Androgens↗
PubMed1999

Functional MRI and the Wada test provide complementary information for predicting post-operative seizure control.

Prediction of post-surgical seizure relief and potential cognitive deficits secondary to anterior temporal lobectomy (ATL) are important to pre-surgical planning. Although the intracarotid amobarbital test (IAT) is predictive of post-ATL seizure outcome, development of non-invasive and more precise means for determining post-ATL seizure relief are needed. We previously reported on a technique utilizing functional MRI (fMRI) to evaluate the relative functional adequacy of mesial temporal lobe structures in preparation for ATL. In the present study, we report follow-up outcome data on eight temporal lobe epilepsy (TLE) patients 1-year post-ATL who were evaluated pre-surgically using IAT and fMRI. Functional memory lateralization using fMRI predicted post-ATL seizure outcome as effectively as the IAT. In general, asymmetry of functional mTL activation favouring the non-epileptic hemisphere was associated with seizure-free status at 1-year follow-up. Moreover, when combined, fMRI and IAT provided complementary data that resulted in improved prediction of post-operative seizure control compared with either procedure alone.

Adolescent↗
PubMed1999

Depression in temporal lobe epilepsy before epilepsy surgery.

PURPOSE: This study examined the association of depression with laterality of epilepsy surgery in patients with temporal lobe epilepsy before standard lobectomy. METHODS: Forty-nine patients presented for EEG telemetry for localization of epilepsy and eventual temporal lobectomy. Patients underwent routine neuropsychiatric evaluation blinded for epileptic focus, including ratings on depression. Patients were grouped according to right (n = 25, M = 10/F = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance included side of surgery as grouping variable and sex, general depressive, cognitive depressive, and vegetative depressive symptoms as dependent variables. Chi2 analyses included categoric variables of sex, handedness, education, neuropathologic findings, and current affective disorders. t Tests were performed on variables of age, epilepsy duration, and cognitive function. RESULTS: Right and left temporal epilepsy groups did not differ with regard to sex, handedness, age, duration of epilepsy, education, cognitive function, and neuropathology. Patients with right temporal epilepsy rated higher on general, cognitive. and vegetative depression scores. Women scored higher on general, cognitive, and vegetative depression scores. Current affective disorders were more common in the right temporal epilepsy group. CONCLUSIONS: Depression ratings and diagnoses were more prominent in patients with right temporal lobe epilepsy and in women in particular. The strength of this laterality finding lies in the selection of patients, as all underwent epilepsy surgery. The finding on gender difference partly reflects the higher incidence of depression in women and needs further exploration. The laterality finding contrasts with recent findings in epilepsy, stroke, and trauma that associate depression with left hemispheric lesions. However, our results are consistent with findings in electrically hyperactive lesions such as gelastic and dacrystic epilepsy.

Adolescent↗
PubMed1999

Vigabatrin.

Vigabatrin (VGB) is a structural analogue of the inhibitory neurotransmitter gamma-amino butyric acid (GABA), which produces its antiepileptic effect by irreversibly inhibiting the degradative enzyme GABA-transaminase. This produces an increase in central nervous system (CNS) GABA levels. VGB is among the few antiepileptic drugs (AEDs) that was synthesized with a specific targeted mechanism in mind and was subsequently demonstrated to function by that mechanism. Tiagabine, a GABA reuptake blocker, is the only other "designer drug" among the currently available AEDs. Therefore, VGB is among the few AEDs for which the mechanism of action is well understood. Recently, safety issues have been raised with regard to the use of vigabatrin. This article reviews the mechanism of action, pharmacokinetics, safety, and efficacy of VGB.

4-Aminobutyrate Transaminase↗
PubMed1998

Medical causes of seizures.

Seizures are commonly encountered in patients who do not have epilepsy. Factors that may provoke such seizures include organ failure, electrolyte imbalance, medication and medication withdrawal, and hypersensitive encephalopathy. There is usually one underlying cause, which may be reversible in some patients. A full assessment should be done to rule out primary neurological disease. Treatment of seizures in medically ill patients is aimed at correction of the underlying cause with appropriate short-term anticonvulsant medication. Phenytoin is ineffective in the management of seizures secondary to alcohol withdrawal, and in those due to theophylline or isoniazid toxicity. Control of blood pressure is important in patients with renal failure and seizures. Non-convulsive status epilepticus should be considered in any patient with confusion or coma of unclear cause, and electroencephalography should be done at the earliest opportunity. Most ill patients with secondary seizures do not have epilepsy, and this should be explained to patients and their families. Only those patients with recurrent seizures and uncorrectable predisposing factors need long-term treatment with anticonvulsant medication.

Acute Kidney Injury↗
PubMed1998

Close proximity of the heterosexual partner reduces the physiological and behavioral consequences of novel-cage housing in black tufted-ear marmosets (Callithrix kuhli).

The present studies assessed the extent to which heterosexual pairmates could buffer marmosets (Wied's black tufted-ear marmoset, Callithrix kuhli) against stress. Six male and six female marmosets from established groups were exposed to two experimental manipulations together with a control condition. Each condition lasted a total of 4 days. For the two experimental conditions, animals were removed from the family group and housed in a novel cage for 48 h in either the presence or the absence of the heterosexual pairmate. During the 48-h novel-cage housing period and for 48 h upon reunion of the subjects with the family group, concentrations of urinary cortisol were measured in the first void sample of the day and behavioral observations were conducted. When animals were housed alone in a novel cage they exhibited significant elevations in levels of urinary cortisol after 24 and 48 h of novel-cage exposure. In contrast, when marmosets were housed in the novel cage in the presence of the pairmate, levels of urinary cortisol did not change across the 4-day period. The presence of the social partner also reduced the behavioral manifestations of exposure to novelty. Upon reunion with the family group, animals that had been housed in the novel cage alone spent significantly more time in close proximity to the pairmate than animals that had been housed with the partner. A second experiment was conducted to determine the effect that separation from the pairmate, only (independent of any effects of novelty), had on levels of cortisol. Concentrations of urinary cortisol were measured in subjects housed in the familiar home cage, but in the absence of the pairmate, over a 48-h period and compared to concentrations of excreted cortisol immediately prior to separation. Separation from the pairmate did not elevate cortisol levels when the subject was housed in the home cage, suggesting that elevated cortisol levels in animals housed alone in the novel cage were in response to novelty exposure rather than to separation from the pairmate. Since the physical presence of the heterosexual partner reduced the physiological and behavioral effects of novel-cage housing, social attachments might function as homeostatic regulators of HPA function in marmosets.

Animals↗
PubMed1998

Medial temporal lobe epilepsy: videotape analysis of objective clinical seizure characteristics.

PURPOSE: The syndrome of temporal lobe epilepsy has been described in great detail. Here we focus specifically on the clinical manifestations of seizures originating in the hippocampus and surrounding mesial temporal structures. METHODS: Seizure origin was confirmed in 67 cases by depth EEG recording and surgical cure after mesial temporal resection. RESULTS: Among nonlateralized manifestations, we commonly found oral automatisms, pupillary dilatation, impaired consciousness, and generalized rigidity. Appendicular automatisms were often ipsilateral to the seizure focus, whereas dystonia and postictal hemiparesis were usually contralateral. Head deviation, when it occurred early in the seizure, was an ipsilateral finding, but was contralateral to the seizure focus when it occurred late. Clear ictal speech and quick recovery were found when seizures originated in the non-language-dominant hemisphere, but postictal aphasia and prolonged recovery time were characteristic of seizure origin in the language-dominant hemisphere. CONCLUSIONS: These signs help to define the mesial temporal lobe epilepsy (MTLE) syndrome and often provide information as to the side of seizure origin.

Automatism↗
PubMed1998

Counselling issues in familial hypertrophic cardiomyopathy.

To illustrate the variable clinical presentations and rates of progression in familial hypertrophic cardiomyopathy (FHC), phenotypes and genotypes were compared in three FHC families with different genetic defects. In the first family, the FHC abnormality was a protein truncating mutation (Gln969X) in the cardiac myosin binding protein C gene. The second family had a missense change (Asn755Lys) in the same gene. A missense mutation (Arg453Cys) in the cardiac beta myosin heavy chain gene was present in the third family. Penetrance associated with the Gln969X defect was 27% in the age range 0 to 40 years. This was considerably less than the 93% penetrance (0 to 40 years) observed in the two families with missense mutations. The variable penetrance in FHC, as well as the unpredictability of sudden cardiac death, complicates clinical diagnosis and management, including genetic counselling. Although a genetic disease with a predominantly adult onset, there are counselling issues in FHC which set it aside from other adult onset disorders.

Adolescent↗
PubMed1998

Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene.

DNA studies in familial hypertrophic cardiomyopathy (FHC) have shown that it is caused by mutations in genes coding for proteins which make up the muscle sarcomere. The majority of mutations in the FHC genes result from missense changes, although one of the most recent genes to be identified (cardiac myosin binding protein C gene, MYBPC3) has predominantly DNA mutations which produce truncated proteins. Both dominant negative and haploinsufficiency models have been proposed to explain the molecular changes in FHC. This study describes two Australian families with FHC caused by different mutations in MYBPC3. The first produces a de novo Asn755Lys change in a cardiac specific domain of MYBPC3. The second is a Gln969X nonsense mutation which results in a truncated protein. Neither mutation has previously been found in the MYBPC3 gene. The consequences of DNA changes on the function of cardiac myosin binding protein C are discussed in relation to current molecular models for this disorder.

Amino Acid Sequence↗
PubMed1998

Functional MRI lateralization of memory in temporal lobe epilepsy.

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.

Adolescent↗
PubMed1997

Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition.

The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.

Anemia, Sickle Cell↗