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Biomedical subjects

P J Snyder

Publications and source records attributed to P J Snyder.

At least 19 recordsLinked to original sources

Isolated straight sinus thrombosis: clinical and neuroradiologic correlates.

A rare case of straight sinus thrombosis in a 36-year-old female with sudden onset of status migrainosus is presented. This condition was demonstrated by a linear density in the midline on a noncontrast computed tomography scan, as a filling defect at the location of straight sinus on magnetic resonance imaging, and by the inability to visualize blood flow in the straight sinus on magnetic resonance venography, with a similar demonstration on a 4-vessel digital subtraction angiography.

Adult

Absence of the adhesio interthalamica as a marker of early developmental neuropathology in schizophrenia: an MRI and postmortem histologic study.

Several recent studies have reported an association between midline cerebral malformations (e.g., corpus callosum, cavum septum pellucidum) and schizophrenia. The authors investigated whether absence of the adhesio interthalamica (AI), a midline structure that develops in concert with prominent features of the ventricular system soon after the bridge from the late embryonic stages to early fetal life, might constitute a marker of early developmental neuropathologic changes in schizophrenia. Eighty-two patients (54 men, 28 women) with a diagnosis of first-episode schizophrenia (FES) were recruited from consecutive admissions to a psychiatric inpatient service. Fifty-two healthy control subjects (30 men, 22 women) were recruited and matched to the patient sample on distributions of sex and age. Magnetic resonance imaging studies were performed, and the presence versus absence of the AI was determined for each subject. The length and volume of the third ventricle were measured for each subject. The AI was found to be absent more often among patients with FES compared with control subjects, and patients without an observable AI also had larger third-ventricle volumes. These differences in presence or absence of the AI observed in vivo (but not in a comparable postmortem sample of histologically fixed and prepared brain slices), which are likely related to third-ventricle enlargement, may represent yet another early developmental marker of cerebral malformation among patients with FES.

Adult

Transverse myelitis. Comparison with spinal cord presentations of multiple sclerosis.

We delineated the clinical and laboratory features that help distinguish acute myelopathic MS (MMS) from acute transverse myelitis (ATM), specifically testing the hypothesis that the symmetry of motor and sensory impairments at presentation can reliably distinguish between ATM and MMS. We reviewed 20 consecutive patients with ATM and 16 patients with MMS. Clinical criteria were used to assign patients to the ATM group. Patients assigned to the MMS group had onset of MS symptoms referable to the spinal cord and eventually fulfilled Poser's criteria for MS. The relative contribution of the symmetry of both motor and sensory symptoms for the accurate identification of ATM versus MMS was evaluated using a discriminant function analysis. Fifteen of 16 MMS patients and all 20 ATM patients presented with symptoms of motor dysfunction. Additionally, all patients in both groups presented with sensory complaints. MMS patients had asymmetric motor or sensory symptoms in all but one patient, whereas ATM patients exhibited symmetric weakness uniformly and symmetric sensory loss in all but one patient (statistically significant). None of the MS patients met criteria for ATM at presentation. None of the ATM patients developed MS over an average follow-up period of 4.5 years. In conclusion, MMS was easily distinguished from ATM in this study.

Acute Disease

A potential mechanism of slowed pubertal maturation after chronic administration of sodium valproic acid.

Sodium valproic acid (VPA) occasionally delays pubertal maturation in children and gonadal and skeletal growth in juvenile, seizure-prone, inbred DBA/2J mice. Fourteen-day-old mice received either VPA or control solution, and the medial preoptic area (mPOA) of the hypothalamus was studied after 4, 7, 10, 14, or 18 days by immunocytochemically processing for gonadotropin-releasing hormone (GnRH). Significant differences were found for the proportion of bipolar to unipolar neurons in the mPOA. VPA may slow pubertal maturation by altering neurochemical systems that normally play an important role in timing maturation of the GnRH pulse generator.

Animals

Cerebral hemispheric control of speech during the intracarotid sodium amytal procedure: An acoustic exploration.

In this study we investigated lateralized control of speech during the intracarotid amobarbital procedure. Vowel segments were extracted from recordings made during two separate amobarbital procedures and involving two patients. Subjects were right-handed, presented with focal left mesial temporal epileptogenic foci. Age of onset of seizure disorders was 1.5 years for one subject and 16 years for the other. Recorded pre- and postinjection speech samples were digitized. Analyses were conducted on formants 1 and 2 (F1, F2) measures to determine the extent of formant fluctuation in the time course of the IAP. Preliminary results showed, for these two cases, that the left hemisphere is involved in the control of both F1 and F2 and the right in the control of F2 only. The data reveal the potential of coupling the IAP procedure and the acoustical analysis of speech in the study of cerebral control of speech.

Adult

Cerebral anesthesia for localization of speech: the contribution of W. James Gardner.

In 1949, the neurologist Juhn Wada reported the first use of a new procedure for determining the localization of speech and language in neurological patients: examination of the effects on speech and language after injecting a barbiturate, sodium amytal, into the internal carotid artery of each hemisphere in succession. By the 1960's, Wada's Intracarotid Amobarbital Procedure, or IAP, had become the method of choice for identifying the speech-dominant side in one kind of neurological patient, persons with epilepsy who are candidates for surgical resection, and it remains so today. In 1941, however, an American neurosurgeon, W. James Gardner, reported his use of a different anesthetization procedure for speech localization in neurological patients. Instead of injecting sodium amytal through the blood supply, as in IAP, Gardner injected procaine hydrochloride directly into cortical tissue. In this paper, we provide a brief biography of Gardner. We then discuss his method of cortical anesthetization, the theoretical and empirical background guiding his use of this method and his choice of patients, and, finally, the fate of Gardner's method within the scientific community.

Amobarbital

Testosterone pharmacokinetics after application of an investigational transdermal system in hypogonadal men.

This open-label, randomized, placebo lead-in, three-treatment crossover study in 19 hypogonadal men (27-82 years of age) evaluated dose proportionality of serum testosterone concentrations with application of one or two investigational transdermal testosterone systems for application to the arm or torso. Testosterone in vivo kinetics profiles were determined using DeMonS, a recently developed numerical deconvolution method that estimates drug absorption at different time intervals and/or drug disposition model parameters. After application of the investigational transdermal systems, the mean serum testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations were elevated to normal levels. Treatment allowed approximation of the normal circadian pattern of endogenous testosterone secretion, and the increase in serum testosterone concentrations was proportional to the surface area of systems applied. The investigational transdermal system provided effective testosterone replacement therapy as judged by pharmacokinetic parameters.

Administration, Cutaneous

The intracarotid amobarbital procedure: an historical perspective.

The intracarotid sodium amobarbital procedure (IAP) is currently regarded as the best method of the determination of hemispheric specialization for speech, and it is universally relied on as a prognostic test for patients with medically refractory epilepsy who are candidates for neurosurgical intervention. Since its initial development, the IAP also has been adapted for assessing lateralized mesiotemporal contributions to memory functioning in this patient population, and it is now in wide use for both basic and applied research in behavioral neuroscience on language, memory, visuospatial functions, emotion, attention, and consciousness. Despite the IAP's wide range of applications, little has been said about its history and development. This essay recounts and discusses this history.

Amobarbital

Lexicon size and its relation to foot preference in the African grey parrot (Psittacus erithacus).

To study footedness in parrots, an international survey of parrot owners was conducted. Responses were obtained from 524 individuals, including 70 owners of African Grey parrots (all animals > or = 10 months old). All respondents were given a 10-item questionnaire and a standard method for testing foot preference in their pets, and they were asked to count the number of separate words in their pets' lexicons of human speech sounds. Right-footed African Greys (N = 36) had significantly larger lexicons than left-footed African Greys (N = 34; P = 0.01). This difference could not be accounted for by group differences in training efforts or socialization/housing with conspecifics. A non-significant trend in the same direction was found in a comparison sample of Amazon parrots, although these genera are less adept than African Greys at learning human speech sounds. Other investigators have provided convincing evidence of lateralization, in the avian brain, for the analysis and memory of differing types of stimuli. In addition, there appears to be preferential left hypserstriatal activation for long-term memory consolidation. Our results suggest a relationship between lateral asymmetry for motor preference and asymmetric CNS mediation of a 'higher cognitive' function (i.e. the categorization and long-term mnestic processing of human speech sound.

Animals

Dystrophin expression in a Duchenne muscular dystrophy patient with a frame shift deletion.

The exon 45 deletion is a common dystrophin gene deletion. Although this is an out-of-frame deletion, which should not allow for protein synthesis, it has been observed in mildly affected patients. We describe a patient with an exon 45 deletion who produced protein, but still had a severe Duchenne muscular dystrophy phenotype. RT-PCR analysis and cDNA sequencing from the muscle biopsy sample revealed that the exon 45 deletion induced exon skipping of exon 44, which resulted in an in-frame deletion and the production of dystrophin. A conformational change in dystrophin induced by the deletion is proposed as being responsible for the severe phenotype in the patient. We feel that the variable clinical phenotype observed in patients with the exon 45 deletion is not due to exon splicing but may be the result of other environmental or genetic factors, or both.

Base Sequence

Long-term follow-up mortality study of petroleum refinery and chemical plant employees.

A previous report presented the 1948-1983 mortality patterns of the Shell Deer Park Manufacturing Complex employees who were employed for at least 3 months from 1948 through 1972. The present study updates the earlier investigation by extending the vital status follow-up through 1989 and by expanding the cohort to include employees hired after 1972. As in the previous study, the overall mortality and cancer mortality for both refinery and chemical employees were quite favorable compared to residents in the local population. Among refinery workers, cancers for which a suspicion of work-relatedness was raised in the previous study, i.e. leukemia and cancers of the central nervous system and biliary passage/liver, no supportive evidence was found in this update. For both refinery and chemical plant employees, the mortality rate due to cancers of all lymphopoietic tissue increased with increasing duration of employment; this finding was also noted by the original study. This was also evident for lymphoreticulosarcoma in refinery employees and for leukemia in chemical plant employees. However, elevations of cancers of all lymphatic and hematopoietic tissue are primarily confined to employees who started work at the complex before 1946. By contrast, deaths from cancer of all lymphatic and hematopoietic tissue for employees hired after 1945 were 22% lower than the comparison population. Seven deaths with mesothelioma mentioned on the death certificates were identified, with 3.2 deaths expected, resulting in a statistically nonsignificant SMR of 219.

Adult

A novel splice site mutation in a Becker muscular dystrophy patient.

A Becker muscular dystrophy patient was found to have a single base substitution at the 5' end of intron 54. This single base substitution disrupts the invariant GT dinucleotide within the 5' donor splice site and was shown to cause an out of frame deletion of exon 54 during mRNA processing. This is predicted to produce a truncated dystrophin protein which is more consistent with a DMD phenotype. However, small quantities of normal mRNA are also transcribed and these are sufficient to produce a reduced amount of normal molecular weight dystrophin and give rise to a milder BMD phenotype. This indicates that a single base substitution at an invariant dinucleotide of the splice site consensus sequence may still allow read through of the message and allow the production of some normal protein. This shows that there are a greater number of possible intronic mutations that can lead to a mild phenotype and it also underlines the importance of performing cDNA analysis when screening for small gene alterations in the BMD patient population.

Base Sequence

Neuropsychiatric side effects related to treatment with felbamate.

Seven patients with refractory seizure disorders and neuropsychiatric symptoms believed secondary to felbamate are presented. Five were on concomitant valproic acid (and other agents). Anergia, apathy, bradyphrenia, and increased irritability were prominent. One patient on felbamate monotherapy had a new-onset psychosis. Felbamate's NMDA receptor antagonism and GABA potentiation (perhaps enhanced by valproic acid use) are discussed as possible mechanisms of these side effects.

Adult