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Biomedical subjects

A D Smith

Publications and source records attributed to A D Smith.

At least 181 records · Page 10Linked to original sources
PubMed1996

The substantia nigra as a site of synaptic integration of functionally diverse information arising from the ventral pallidum and the globus pallidus in the rat.

Voluntary behaviour in mammals requires the integration of information from different parts of the cerebral cortex, notably the limbic, associative and sensorimotor areas, in a neural network that eventually controls the muscles. One region of the brain that has been proposed to subserve such a function are the basal ganglia which receive inputs from all cortical areas. Although information from different cortical areas passes through the basal ganglia as a series of separate parallel pathways there are several sites where integration of the diverse information could occur. In this study we the identify a neural network at the synaptic level that may underlie a powerful mechanism for the integration, within the basal ganglia, of the diverse types of information arising from the cortex. By double anterograde tracing and immunocytochemistry at both the light and electron microscopic levels, we show that individual neurons in the substantia nigra pars reticulata and dopaminergic neurons in the pars compacta each receive multiple GABAergic synaptic inputs both from neurons in the ventral pallidum (which receive input from limbic areas via the nucleus accumbens) and from neurons in the globus pallidus (which receive input from associative and sensorimotor cortices via the neostriatum). Thus, information subserving functions such as emotion, motivation, cognition and movement converges onto basal ganglia output neurons, leading eventually to the muscles, and also on to the dopaminergic neurons which themselves subserve an integrative role by modulating the flow of information from the cortex through the basal ganglia at the level of the neostriatum and nucleus accumbens.

Animals↗
PubMed1996

Mediators of long-term memory performance across the life span.

An individual-differences approach was used to examine the component processes that predict episodic long-term memory performance. A total of 301 participants ages 20-90 received a 7-hr cognitive battery across 3 days. Key constructs hypothesized to affect long-term memory function were assessed, including multiple measures of working memory and perceptual speed. Latent-construct, structural equation modeling was used to examine the relationship of these measures and age to different types of long-term memory tasks. Speed was a key construct for all 3 types of memory tasks, mediating substantial age-related variance; working memory was a fundamental construct for free and cued recall but not spatial memory. The data suggest that both speed and working memory are fundamental to explaining age-related changes in cognitive aging but that the relative contributions of these constructs vary as a function of the type of memory task.

Adult↗
PubMed1996

New technique in managing ureteropelvic junction obstruction: percutaneous endoscopic pyeloplasty.

Endopyelotomy is currently advocated for management of the obstructed ureteropelvic junction (UPJ). Healing of the stented UPJ occurs by secondary intention. Regardless of the method employed, success rates approach 85%. In order to increase the rate of success, we have devised a method of performing endopyelotomy in conjunction with endoscopic suturing of the incised UPJ. Two methods were developed to allow for the placement of a single absorbable monofilament suture. In the first method, endopyelotomy is carried out in the standard antegrade manner, and endoscopic suturing is performed with the use of a second retroperitoneal access sheath at the UPJ. In the second method, endoscopic placement of the suture is carried out through the standard renal access sheath, with suturing performed via the nephroscope. We have performed endoscopic pyeloplasty in eight patients. With a mean follow-up of 12 months, the procedure was successful in seven of these patients. Endoscopic suturing of the UPJ is technically demanding, but once sufficient expertise is gained, it may be utilized for immediate tissue coaptation, possibly decreasing urinary extravasation and, it is hoped, maximizing the caliber of the UPJ.

Adult↗
PubMed1996

Use of structural imaging to study the progression of Alzheimer's disease.

Computed tomographic scans in the temporal lobe orientation are a valuable way of studying the medial temporal lobe. In patients with histopathologically-confirmed Alzheimer's disease the size of the medial temporal lobe is almost half that in age-matched controls and the rate of atrophy shown by yearly scans (15% per year) is 10-fold greater. Such a rapid rate of atrophy probably follows a catastrophic event in the brain indicating that Alzheimer's disease is distinct from accelerated normal ageing. The degree of medial temporal lobe atrophy is related to the density of neurofibrillary tangles in the hippocampus; it is a useful guide to diagnosis and has potential as a screening tool in populations. It is proposed that measurement of the rate of atrophy in asymptomatic individuals may be a predictor of Alzheimer's disease and could be used to monitor the effectiveness of therapies designed to retard the rate of neurodegeneration.

Alzheimer Disease↗
PubMed1996

Fever following intracavitary bacillus Calmette-Guerin therapy for upper tract transitional cell carcinoma.

PURPOSE: We attempted to identify the source of fever during intracavitary upper tract instillation of bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: Of 34 patients who had previously undergone percutaneous resection of upper tract transitional cell carcinoma 18 received weekly intracavitary BCG through the nephrostomy tubes for 6 consecutive weeks. After treatment 6 all patients underwent nephroscopy and biopsy, and all cases were retrospectively reviewed. Parameters analyzed were BCG related symptoms, maximum temperature during treatment, maximum renal pelvic pressure during treatment, culture results, chest x-ray findings, pretreatment serum creatinine concentration, serum liver enzyme values, untoward events and treatments performed for BCG related complications. RESULTS: No obvious pattern in appearance of fever occurred. During 88 treatment episodes evaluated there were 14 temperature elevations to more than 100F in 7 patients (39%). Positive urine cultures were associated with fever in only 4 cases and none was positive for Mycobacterium. There was no correlation between greater renal pelvic pressures and fever. All chest radiographs and serum creatinine levels were unchanged, and liver enzymes were normal in all but 1 patient. Two patients had prolonged fever with elevations to greater than 104F following treatment: 1 died in a motor vehicle accident and 1 died after the third BCG infusion led to overwhelming sepsis. No source of fever was identified in either patient. CONCLUSIONS: Patients with low grade fever coincident with upper tract BCG may be treated conservatively simply by withholding the infusion. Fever greater than 103F should be considered an emergency condition with high potential for mortality. Immediate and aggressive attempts at identifying a source along with institution of antituberculous therapy are priorities.

Adjuvants, Immunologic↗
PubMed1996

Synaptic connections between spiny neurons of the direct and indirect pathways in the neostriatum of the rat: evidence from dopamine receptor and neuropeptide immunostaining.

UNLABELLED: The flow of cortical information through the basal ganglia occurs through the so-called 'direct pathway' and 'indirect pathways'. The object of the present work was to attempt to determine whether spiny neurons in the neostriatum that give rise to the direct pathway (i.e. the striatonigral/entopeduncular pathway) and those giving rise to the indirect pathways (i.e. striatopallidal pathway) are synaptically interconnected. The approach was to carry out double immunocytochemistry at the electron microscopic level using antibodies against peptides or dopamine receptor subtypes that are selectively associated with the neurons that give rise to the direct (substance P or D1 receptors) and indirect pathways (enkephalin or D2 receptors). Sections of perfuse-fixed rat neostriatum were immunostained to reveal both substance P immunoreactivity and D2 receptor immunoreactivity or enkephalin and D1 receptor immunoreactivity, respectively. Double peroxidase methods were employed using different chromogens that were distinguishable at both the light and electron microscopic levels. In the electron microscope substance P-immunoreactive terminals were seen in synaptic contact with dendritic structures that displayed immunoreactivity for D2 receptor. Similarly, enkephalin-immunoreactive terminals were seen in synaptic contact with D1-immunoreactive dendritic structures. Thus, axon collaterals of neurons giving rise to the direct pathway form synaptic contacts with neurons that give rise to the indirect pathway and axon collaterals of neurons giving rise to the indirect pathway form synaptic contact with neurons that give rise to the direct pathway. These results indicate that the two pathways of information flow through the basal ganglia are synaptically linked at the level of the neostriatum. KEYWORDS: spiny neurons, direct pathway,indirect pathways, rat neostriatum

Animals↗
PubMed1996

Chimeric rhinoviruses as tools for vaccine development and characterization of protein epitopes.

Chimeric human rhinoviruses (HRVs) have the potential to serve as vaccines against a wide variety of diseases. Such vaccines can be developed optimally by generating libraries of chimeric HRVs displaying immunogens from dangerous pathogens or tumor cells in many different conformations. Extremely large numbers of conformationally defined presentations of foreign epitopes can be produced efficiently by flanking transplanted epitopes with linkers, or adapters, of small segments of randomized amino acids. In addition, the individual residues of the immunogenic sequences can be encoded in proportion to their prevalence in databases, generating composite immunogens that function as mimotopes. The diversity of sequences and conformations improves the likelihood of generating immunologically valuable vaccine candidates. Chimeric viruses thus generated can be propagated and purified to select for viruses whose growth and physical stability are like those of wild-type HRV. Viruses containing a foreign epitope in antigenically relevant conformations can then be captured by immunoselection with neutralizing antibodies directed against the foreign pathogen. Using this approach, we have been able to generate HRV chimeras that present V3 loop sequences of the human immunodeficiency virus type 1 (HIV-1) in immunologically relevant conformations. Antisera directed against such chimeras can neutralize multiple strains of HIV-1 in cell culture, suggesting that the HRV14:HIV-1 chimeras may be presenting their V3 loop sequences in manners that mimic those of multiple strains of HIV. Immunologically interesting chimeras can be examined using X-ray crystallography to yield detailed information about the structures of chimeras with immunogenic epitopes. This information may lead to a greater understanding of key functional and structural elements of immunogenicity. The chimeric HRV system allows one to present virtually any protein epitope or mimitope thereof, identify viruses with immunological characteristics that mimic those of the foreign pathogen, and examine the structures of these immunogenic sequences at the atomic level.

Epitopes↗
PubMed1996

The Glidewire technique for overcoming urethral obstruction.

PURPOSE: Using the hydrophilic Terumo Glidewire we developed a less traumatic, yet effective alternative method to filiforms and followers for cases of urethral obstruction. MATERIALS AND METHODS: The initial step and cornerstone of our method is the passage of the Glidewire per urethra in a manner similar to a filiform. After the appropriate intravesical location of the Glidewire is confirmed using a ureteral catheter, it is exchanged for a standard polytetrafluoroethylene (Teflon) coated guide wire. Urethral dilation and/or catheter placement is then performed. RESULTS: This technique was successful in 19 of 20 attempts, several of which followed unsuccessful passage of filliform catheters. Urethral obstruction due to strictures, bladder neck contractures and benign prostatic hyperplasia in our group was treated effectively. Furthermore, no complications occurred due to the technique. CONCLUSIONS: The Glidewire method is safe and effective for treating most cases of urethral obstruction. Therefore, we recommend this technique over standard filiforms and followers when flexible or rigid cystourethroscopy is not immediately available.

Drainage↗
PubMed1995

Laparoscopic enterolysis and placement of an intestinal sling before radiation therapy for the treatment of prostate cancer.

We present an interesting application of laparoscopy in a man who was otherwise not a candidate for radiotherapy because of an adherent loop of small bowel in the proposed treatment field. Laparoscopic enterolysis was performed and the involved segment was displaced out of the pelvis; a synthetic mesh was placed to serve as a sling to prevent caudal migration back into the pelvis. The patient had a rapid recovery and subsequently completed a full course of radiotherapy. The experienced laparoscopist may find this a good alternative to open surgery in patients with a fixed loop of small bowel who require radiation therapy for pelvic malignancies.

Adenocarcinoma↗
PubMed1995

Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy.

The modulatory actions of dopamine on the flow of cortical information through the basal ganglia are mediated mainly through two subtypes of receptors, the D1 and D2 receptors. In order to examine the precise cellular and subcellular location of these receptors, immunocytochemistry using subtype specific antibodies was performed on sections of rat basal ganglia at both the light and electron microscopic levels. Both peroxidase and pre-embedding immunogold methods were utilized. Immunoreactivity for both D1 and D2 receptors was most abundant in the neostriatum where it was mainly contained within spiny dendrites and in perikarya. Although some of the immunoreactive perikarya had characteristics of interneurons, most were identified as medium-sized spiny neurons. Immunoreactivity for D1 receptor but not D2 receptor was associated with the axons of the striatonigral pathway and axons and terminals in the substantia nigra pars reticulata and the entopeduncular nucleus. In contrast, D2 immunoreactivity but not D1 immunoreactivity was present in the dopaminergic neurons in the substantia nigra pars compacta and ventral pars reticulata. In the globus pallidus, little immunoreactivity for either D1 or D2 receptor was detected. At the subcellular level, D1 and D2 receptor immunoreactivity was found to be mainly associated with the internal surface of cell membranes. In dendrites and spines immunoreactivity was seen in contact with the membranes postsynaptic to terminals forming symmetrical synapses and less commonly, asymmetrical synapses. The morphological features and membrane specializations of the terminals forming symmetrical synapses are similar to those of dopaminergic terminals previously identified by immunocytochemistry for tyrosine hydroxylase. In addition to immunoreactivity associated with synapses, a high proportion of the immunoreactivity was also on membranes at non-synaptic sites. It is concluded that dopamine receptor immunoreactivity is mainly associated with spiny output neurons of the neostriatum and that there is a selective association of D1 receptors with the so-called direct pathway of information flow through the basal ganglia, i.e. the striatoentopeduncular and striatonigral pathways. Although there is an association of receptor immunoreactivity with afferent synaptic inputs a high proportion is located at extrasynaptic sites.

Animals↗
PubMed1995

Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer's disease.

The effect of the apolipoprotein E genotype on the development of late onset Alzheimer's disease is still debated. Neuropathological studies of Alzheimer's disease have found a great extent of amyloid deposition in cortex and blood vessel walls in association with the apolipoprotein E epsilon 4 genotype [Rebeck G. W. et al. (1993) Neuron 11, 575-580; Schmechel et al. (1993) Proc. natn. Acad. Sci. U.S.A. 90, 9649-9653]. In contrast, the relationship of apolipoprotein E genotype to neurofibrillary pathology in Alzheimer's disease has been less clear. In this study we present evidence on the influence of the apolipoprotein E genotype on Alzheimer's disease related pathology in a series of 76 autopsy cases that had pathology that fulfilled the CERAD criteria for Alzheimer's disease. We found that the presence of the apolipoprotein E epsilon 4 allele is correlated with increased amounts of both amyloid and neuritic pathology in the neocortex as determined using an image analysis system. Comparison of plaque and tangle densities with the allele doses of epsilon 2 and epsilon 4 revealed a striking parallelism, suggesting that the alleles exert their effects very early in the pathological process before deposition of plaques and tangles. Although the apolipoprotein E epsilon 2 allele had a protective effect against both amyloid deposition and neurofibrillary tangle formation, in the presence of the epsilon 4 allele this protective effect against neuritic pathology was less marked than against amyloid deposition. This differential effect on amyloid deposition and the accumulation of neuritic pathology suggests that different molecular mechanisms are involved in the effect of apolipoprotein E on amyloid deposition and on tau phosphorylation.

Aged↗
PubMed1995

Fibrous coagulum: a new cause of retained fragments following extracorporeal shock wave lithotripsy.

PURPOSE: A previously unrecognized cause of retained fragments following extracorporeal shock wave therapy is identified. MATERIALS AND METHODS: Nine patients referred for percutaneous stone extraction following failure of multiple shock wave lithotripsy treatments had retained fragments embedded in soft tissue. The stones were evaluated by chemical analysis and the tissue was evaluated histologically. RESULTS: All stones contained calcium and histopathology confirmed the presence of fibrous tissue. Radiographs were unable to predict the presence of the substance preoperatively. CONCLUSIONS: We identified fibrous coagulum as a cause of retained fragments following shock wave lithotripsy. The material is soft tissue and cannot be ablated by further shock wave lithotripsy. These findings confirm that repeated shock wave lithotripsy is contraindicated, since stone fragmentation and passage may be inhibited by fibrous coagulum.

Blood Coagulation↗
PubMed1995

Incidence of negative hematuria in patients with acute urinary lithiasis presenting to the emergency room with flank pain.

OBJECTIVES: To determine the incidence of negative hematuria in patients with acute urinary lithiasis presenting to the emergency room with flank pain. METHODS: We retrospectively reviewed all 140 patients who presented with flank pain to the Long Island Jewish Medical Center emergency department from January 1, 1992, through December 31, 1992, and underwent intravenous urogram (IVU). We then calculated the incidence of negative hematuria in patients with acute urinary lithiasis (AUL) diagnosed by IVU based on the complete urinalysis alone or in combination with the urine dipstick test for blood. RESULTS: We found a 14.5% incidence of negative hematuria in patients with AUL when looking at the urinalysis alone. To our knowledge, this has never been reported in the literature. We also found that by considering a negative combination (urinalysis plus urine dipstick test) as a new definition of negative hematuria, the incidence of negative hematuria in patients with AUL was only 5.5% (P < 0.031). CONCLUSIONS: This is the first report in the literature documenting the incidence of negative hematuria in patients with AUL to be 14.5%. With the addition of the combination of urinalysis and urine dipstick test for hematuria, the incidence is only 5.5% and, therefore, represents a low yield when evaluated by IVU.

Acute Disease↗