Search PubMed⌕ Search

Biomedical subjects

A D Smith

Publications and source records attributed to A D Smith.

At least 217 records · Page 12Linked to original sources

Complications of intracavitary bacillus Calmette-Guerin after percutaneous resection of upper tract transitional cell carcinoma.

Percutaneous resection and intracavitary instillation of bacillus Calmette-Guerin (BCG) is currently being used in treatment protocols in select patients in whom the standard nephroureterectomy for upper tract transitional cell carcinoma is undesirable. However, the complications of BCG in these patients are not well defined. Among 16 patients treated in this manner 4 (25%) had asymptomatic granulomatous involvement of the renal pelvis discovered during regular followup nephroscopy and biopsy: 2 had recurrent carcinoma at discovery, whereas the other 2 remain free of disease. The significance and therapeutic consequences of BCG granulomatosis are unknown. Continued followup is necessary to identify any complications of BCG therapy.

BCG Vaccine↗

Special considerations in the technique of laparoscopic ureterolithotomy.

Laparoscopic ureterolithotomy was performed in 2 men, accompanied in 1 by unroofing of a complex renal cyst. This new technique is indicated as an alternative to open lithotomy when more conventional minimally invasive measures have failed and in patients in whom laparoscopy is being performed for another indication. Modifications in technique are necessary depending on the location of the stone. Laparoscopic ureterolithotomy should not be performed unless a guide wire or catheter can be placed past the stone preoperatively. The technique is described in detail.

Aged↗

Laparoscopic excision of urachal cyst.

The treatment of choice for persistent urachal anomaly is radical surgical excision intended to prevent complications, notably malignancy in a retained remnant. We report a case of the radical laparoscopic excision of an infected urachal cyst. This effective alternative to an open technique has the advantages inherent in minimally invasive surgery.

Adolescent↗

Percutaneous approach to indeterminate caliceal filling defects.

Although the radiologic characteristics and endoscopic appearance of aberrant renal papillae have been described, a tissue diagnosis is the only way to exclude a low-grade urothelial malignancy. We report on three caliceal filling defects managed percutaneously in which biopsy findings confirmed aberrant papillae.

Adult↗

Endourologic management of retained surgical drains and nephrostomy tubes.

A retained surgical drain or nephrostomy tube is a troublesome predicament that often has necessitated open surgical extraction. To assess the efficacy of endoscopic techniques in the management of this problem, several types of drains and tubes were placed intraperitoneally in a female pig and left for 3 weeks. Flat drains could be removed by traction. Jackson-Pratt drains could be removed by clearing the lumen of amorphous material with a guidewire and releasing the external adhesions with a 9.5Fr rigid ureteroscope passed beside the tube. The retained re-entry nephrostomy tubes could be removed under fluoroscopic control by using stone-grasping forceps and electrocautery inside the tube to incise the tissue holding the Malecot flanges. This latter method also was successful in a patient who had received intracavitary BCG after percutaneous tumor resection. Endourologic techniques can reduce the number of open operations that need to be performed to remove retained drains and tubes.

Aged↗

Endourologic management of complications in renal allografts.

Because of the altered anatomy, the presence of immunosuppression, the possibility of graft rejection, and the serious implications of a problem involving a solitary kidney, the transplanted kidney presents unique challenges in the diagnosis and treatment of urologic complications. Historically, the mortality rate in these patients has been as high as 68%, and as many as 15% of the allografts have been lost. Today, endourologic procedures are used for prompt diagnosis, temporization, and even definitive management of many urologic complications, and many patients and allografts are being saved. The authors review present techniques and suggest others that may be available in the future.

Humans↗

Use of random systematic mutagenesis to generate viable human rhinovirus 14 chimeras displaying human immunodeficiency virus type 1 V3 loop sequences.

Random systematic mutagenesis was used to generate a library of human rhinovirus 14 chimeras that each display a segment from the V3 loop of human immunodeficiency virus type 1. The sequence XXIGPGRAXX, where X could be any of the 20 amino acids, was inserted at the neutralizing immunogenic site II of human rhinovirus 14 between VP2 residues 159 and 160. Twenty-five unique chimeric viruses were isolated, and the identity of their randomized residues was determined. A nonrandom amino acid distribution that may reflect structural requirements for viability was observed at the randomized positions. Fifteen of 25 chimeras were neutralized by one or more of a panel of four anti-human immunodeficiency virus type 1 V3 loop antibody preparations, indicating that antigenicity had been successfully transplanted. Libraries of chimeric viruses produced by using the techniques described may be a source of vaccines and other immunotherapeutic reagents. The random systematic mutagenesis methodology described should be generally useful for the rapid transplantation of foreign sequences into viral coat and other proteins to produce libraries containing members with the desired properties.

Amino Acid Sequence↗

Libraries of human rhinovirus-based HIV vaccines generated using random systematic mutagenesis.

Human rhinovirus (HRV), an immunogenic and relatively nonpathogenic virus, has been engineered to display HIV-1 immunogens with the intent of developing a vaccine against AIDS. HIV immunogens from the V3 loop have been placed into the neutralizing immunogenic (NIm) sites on the surface of HRV14 naturally recognized by the immune system. To increase the likelihood of recovering viable chimeras displaying the transplanted HIV-1 V3 loop sequences in conformations that mimic that of HIV, we have used random systematic mutagenesis to produce libraries of chimeric HRV14 in which the transplanted epitope from HIV-1 is flanked by one or more randomized amino acid residues. This allows the HIV epitope to be accommodated into the HRV coat proteins in many conformations, some of which should result in the production of viable, immunogenic hybrids. Using this approach, a library containing the sequence XXIGPGRAXX, where X could be any of the 20 amino acids, was generated. A nonrandom distribution of residues was found at the randomized positions, which may be a reflection of the structural requirements for viability. A subset of chimeras was identified that reacted with neutralizing anti-HIV-1 V3 loop antibody preparations, indicating that the antigenicity of the epitopes had been transplanted. Another chimeric virus library was designed to reflect the natural diversity of the V3 loop by incorporating amino acids at frequencies similar to those found among naturally occurring isolates of HIV-1. Powerful selection techniques utilizing anti-HIV-1 V3 loop neutralizing antibodies are being employed to isolate efficiently antigenic chimeras that could serve as potential vaccine candidates.

AIDS Vaccines↗

The diagnosis of Alzheimer's disease: a question of image?

The most common cause of dementia in the developed world is Alzheimer's disease. Histopathology is required to confirm diagnosis, but most evaluations of the accuracy of clinical criteria and neuroimaging in the diagnosis of dementia of the Alzheimer type are without such confirmation. The average specificity of clinical criteria alone is about 75%. This paper discusses the contribution of simple structural (x-ray computed tomography [CT]) and functional (Tc-99m-HMPAO single photon emission computed tomography [SPECT]) imaging to the diagnosis of Alzheimer's disease in 71 histopathologically confirmed cases (47 with Alzheimer's disease, 16 with other dementias, 8 controls) and 84 living controls. Medial temporal lobe atrophy assessed by temporal lobe-oriented CT gave 94% sensitivity and 93% specificity, while parietotemporal hypoperfusion on SPECT revealed 96% sensitivity and 89% specificity. The combination of both changes yielded a sensitivity of 90% and a specificity of 97%. These investigations clearly enhance diagnostic accuracy, can be readily applied in the clinical situation, and could be used in epidemiologic studies of Alzheimer's disease.

Alzheimer Disease↗

Monosynaptic innervation of trigeminal motor neurones involved in mastication by neurones of the parvicellular reticular formation.

In order to determine whether neurones in the parvicellular reticular formation are in direct synaptic contact with motor neurones innervating masticatory muscles, a combined retrograde and anterograde transport study was carried out in the rat at both light and electron microscopic levels. The animals received injections of the retrograde tracers wheat germ agglutinin conjugated to horseradish peroxidase or cholera toxin B conjugated to horseradish peroxidase into the masticatory muscles and of the anterograde tracer biocytin into the ipsilateral parvicellular reticular formation. The trigeminal motor nucleus was then examined for both anterograde and retrograde labelling in the light and electron microscopes. Retrogradely labelled motor neurones were identified in the trigeminal motor nucleus. They were large and their locations within the nucleus depended on the muscle injected. In addition, terminals anterogradely labelled with the biocytin that was injected in the parvicellular reticular formation were identified throughout the motor nucleus. At the electron microscopic level, the retrogradely labelled cells were found to receive input both from distinct types of unlabelled terminals and from terminals that were anterogradely labelled from the parvicellular reticular formation. The labelled terminals comprised one of the four classes of afferent terminals, being 1-2 microns in diameter and densely packed with spherical vesicles. They formed mostly asymmetrical but also symmetrical synapses with the labelled perikarya and dendrites. Anterogradely labelled terminals were also observed to form both symmetrical and asymmetrical synaptic contacts with unlabelled structures in the motor nucleus. It is concluded that neurones in the parvicellular reticular formation form direct synaptic contact with motor neurones of masticatory muscles. This pathway may represent the anatomical substrate by which the reticular formation exerts at least part of its influence on mastication. Since the parvicellular reticular formation receives input from the substantia nigra pars reticulata, it is possible that this pathway represents a system whereby the basal ganglia directly influence orofacial movement.

Animals↗

Residue-based interpretation of toxicity and bioconcentration QSARs from aquatic bioassays: polar narcotic organics.

Bioconcentration and toxicity estimation for a group of substituted phenols often categorized as "polar narcotics" can be confounded by pH-dependent ionization. Two methods of correction for ionization were applied to toxicity data obtained by U.S. EPA-Duluth for fathead minnows exposed to 30 different phenols in 37 bioassays. Toxicity QSARs with corrected data were substantially different from those obtained with raw toxicity data. When ionization-corrected toxicity data were used in the critical body residue (CBR) estimation process previously successful with neutral narcotic organics, several categories of CBR, apparently related to different modes of toxic action, resulted. Published data on lethal CBR for substituted phenols were in general agreement, although such information is limited. Elimination half-life rate constants, estimated from nonlinear curve fitting to time-toxicity information, were relatively constant for the Duluth bioassay data, averaging 0.3 days. Half-life information for small aquatic organisms, both from toxicity- and bioconcentration-based tests in the literature, was in a similar range. Much of the relatively high variability encountered experimental data for substituted phenols may in large part be due to differences in metabolic degradation between chemicals and species.

Animals↗

Technique and follow-up of percutaneous management of caliceal diverticula.

Between June 1985 and July 1992 we treated 20 patients who had symptomatic caliceal diverticula (13 in upper calix, 6 in middle calix, and 1 in lower calix) in whom long-term (3 months to 3 years) evaluation of persistent symptoms, physical condition, and radiologic findings was possible. Of the 20 patients, 19 had had stones in the diverticulum preoperatively, and the other had a huge diverticulum but no stones. Eighteen patients (95%) with stones preoperatively had been rendered stone free, and the other patient demonstrated only small residual stones in the area of the obliterated diverticulum. Sixteen patients (80%) had obtained complete resolution of their diverticula, and the remaining 4 had at least a 50 percent diminution of the original size of the lesion. All patients had been rendered free of infection and symptoms. Percutaneous management of caliceal diverticula is the most effective approach to rendering patients with caliceal diverticula stone free and achieving diverticular ablation.

Adolescent↗

A monosynaptic pathway from an identified vasomotor centre in the medial prefrontal cortex to an autonomic area in the thoracic spinal cord.

Chemical microstimulation (1 mM L-glutamate or 25 mM KCl) of the medial prefrontal cortex of anaesthetized rats produced falls in systolic and diastolic blood pressure of similar magnitude, without a change in heart rate. Application of the lectin Phaseolus vulgaris leucoagglutinin by iontophoresis from an adjacent barrel of the same micropipette revealed a direct projection to the central autonomic area of the thoracic spinal cord from this vasomotor area, which is equivalent to the region called prelimbic cortex by Krettek and Price [J. comp. Neurol. (1977) 171, 157-192] or Cg3 by Paxinos and Watson [The Rat Brain in Stereotaxic Coordinates (1986)]. Labelled axons descended in the dorsal corticospinal tract in the cervical spinal cord, where they displayed a few varicosities. In the thoracic spinal cord, labelled fibres occurred bilaterally in the gray matter, predominantly in the central autonomic area, where they displayed many varicosities. Electron microscope studies revealed that the anterogradely labelled varicosities in the central autonomic area were vesicle-filled boutons that formed asymmetric synaptic contacts. The synaptic targets were small dendrites or dendritic protrusions that were characterized by a high incidence of multivesicular bodies and coated vesicles. We conclude that a monosynaptic pathway that originates from a physiologically-defined vasomotor area in the medial prefrontal cortex terminates on a characteristic type of neuron in the central autonomic area of the thoracic spinal cord.

Animals↗

Monosynaptic projections from the rostral ventrolateral medulla oblongata to identified sympathetic preganglionic neurons.

The rostral ventrolateral medulla oblongata plays an important role in the control of arterial blood pressure and it has strong descending projections into the intermediolateral nucleus of the thoracic spinal cord, where the majority of sympathetic preganglionic neurons are located. The purpose of this study was to see whether these projections form synaptic contacts with sympathetic preganglionic neurons in the rat. Projections from both the lateral part of the rostral ventrolateral medulla (rostroventrolateral reticular nucleus) and from the more medial region (lateral paragigantocellular nucleus) were investigated separately in view of their different functional roles in sympatho-regulation and their different chemical composition. Using anterograde tract-tracing of descending medullary pathways with Phaseolus vulgaris leucoagglutinin and retrograde labelling of sympatho-adrenal preganglionic neurons with cholera B chain conjugated to horseradish peroxidase, the existence of monosynaptic connections was sought by electron microscopy. Synaptic inputs from both the lateral and medial aspects of the rostral ventrolateral medulla oblongata were found on identified sympathetic preganglionic neurons. Synaptic specializations were of both the symmetrical and asymmetrical type. The targets of boutons forming asymmetrical synaptic contacts differed according to their origin: boutons originating from neurons in the rostroventrolateral reticular nucleus were mainly in contact with dendrites of sympathetic preganglionic neurons, while those originating from the lateral paragigantocellular nucleus mainly innervated the cell bodies. Our observations provide anatomical support for the view that there are two distinct classes of sympatho-regulatory cells in the rostral ventrolateral medulla, each of which can directly influence the activity of sympathetic preganglionic neurons; they also emphasize the importance of detailed investigation of the subregions of the ventrolateral medulla with respect to their sympatho-regulatory functions.

Animals↗

Failed endopyelotomy: implications for future surgery on the ureteropelvic junction.

During the last 8 years we performed 212 endopyelotomies with an overall success rate of 86%. To determine if the failed endopyelotomies resulted in a more difficult subsequent open corrective procedure, we compared the procedures and outcomes of 15 failed endopyelotomies with 16 control patients undergoing pyeloplasty who had not undergone a previous endopyelotomy. The variables of duration of the surgical procedure, average estimated blood loss, average number of transfusions and average length of hospitalization were analyzed for both groups. No statistically significant differences were detected for any of these variables. We conclude that despite a previously failed endopyelotomy, a subsequent open operation on the ureteropelvic junction, although slightly more difficult, was not associated with an increased morbidity rate nor less successful than de novo pyeloplasty. Therefore, we continue to advocate endopyelotomy as the procedure of choice for obstruction of the ureteropelvic junction.

Adolescent↗

Endopyelotomy in the elderly.

Elderly patients with ureteropelvic junction obstruction present higher risks for operative repair than younger patients and may benefit from a less invasive approach. We review 18 patients older than 65 years who underwent endopyelotomy for a primary (8) or secondary (10) ureteropelvic junction obstruction. Average followup was 32 months (range 3 to 80). Average operating time, including cystoscopy and patient positioning, was 85 minutes. Average hospital stay was 6.3 days. No intraoperative complications were encountered. One failure occurred immediately postoperatively and the patient underwent corrective pyeloplasty. One patient has had intermittent pain but a negative Whitaker test with no evidence of obstruction. The success rate is 88%. Endopyelotomy can be considered a safe and satisfactory procedure for initial treatment of significant ureteropelvic junction obstruction in the elderly.

Aged↗

Results of 212 consecutive endopyelotomies: an 8-year followup.

Between 1983 and 1991 we performed 212 endopyelotomies on 110 cases of primary and 102 of secondary obstruction of the ureteropelvic junction. Of the 189 patients in the series 89% have been followed for a minimum of 6 months postoperatively, 63% for more than 3 years (3 to 8-year followup). Our overall success rate has been 86% with little difference being detected between the success that we have obtained with primary and secondary obstructions (85% versus 86%). Other variables, such as patient age, sex or side of obstruction, have little bearing on the outcome of the procedure. Endopyelotomy is passing the test of time as a safe and reliable means to correct ureteropelvic junction obstruction. Endopyelotomy should be the first choice for the correction of ureteropelvic junction obstruction in most patients.

Adolescent↗