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Biomedical subjects

R A Schmidt

Publications and source records attributed to R A Schmidt.

At least 19 recordsLinked to original sources

A flow cytometric study of non-small cell lung cancer classified as T1N0.

Surgical resection currently offers the best chance for cure of non-small cell lung cancer but its efficacy is limited by subsequent tumor recurrence. Even the most favorable cancers (T1N0 tumors) recur 20% to 30% of the time within 5 years and there is currently no way to anticipate precisely which tumors will recur. To test whether DNA flow cytometric study might be useful in this regard, the authors performed a retrospective case-control study of 102 tumors (51 recurrent cases and 51 controls) from a prospective registry of patients with completely resected, meticulously staged T1N0 non-small cell carcinomas. Unbiased relative hazard ratios of recurrence were estimated for ploidy and proliferative rate, as well as for tumor histologic type and clinical variables. Ploidy abnormalities were slightly more common among cases (67%) than controls (57%) but this difference was not statistically significant. Estimation of proliferative rates was possible for 85 tumors but there was no significant difference between cases and controls and proliferative rates were not prognostic of recurrence. In multivariate analyses, the observed predictive value for each of the flow cytometric parameters was modest at best and smaller than that seen for tumor histologic type. These results suggest that flow cytometric analysis has limited value in guiding management of patients with early stage non-small cell carcinoma.

Carcinoma, Non-Small-Cell Lung

Tissue invasion by Pneumocystis carinii: a possible cause of cavitary pneumonia and pneumothorax.

Pulmonary cavitation and pneumothorax may complicate severe cases of Pneumocystis carinii pneumonia. Both complications likely result from tissue necrosis, although how such injury occurs is unknown. To investigate mechanisms of tissue destruction in P carinii pneumonia, histochemical, immunocytochemical, and electron microscopic studies were conducted in pulmonary wedge resections or autopsy specimens from patients with the acquired immunodeficiency syndrome (n = 7) or leukemia (n = 2). Tissue invasion, defined as Pneumocystis organisms in the interstitial compartment, was present in eight of nine cases. Organisms were found in alveolar septa (eight cases), pleura (six cases), and vessel walls (two cases). All cases with tissue invasion exhibited regional necrosis as well as extensive invasion of apparently viable parenchyma. Pulmonary cavitation occurred in seven of eight cases with tissue invasion, and six of these patients developed pneumothoraces. Despite extensive tissue invasion and necrosis there was little host inflammatory or stromal response. Ultrastructurally, both the tissue-invasive and intra-alveolar organisms were predominantly of the trophozoite form; they were present in much greater numbers than suggested by routine silver stains (which detect only cysts). Immunocytochemical techniques, which detect both trophozoite and cyst forms, were much more sensitive than silver stains. These results indicate that extensive tissue invasion by P carinii can occur in severe P carinii pneumonia. We hypothesize that such invasion is an important step in the development of pulmonary necrosis, cavitation, and pneumothorax.

Adolescent

Intrathecal administration of substance P in the rat: the effect on bladder and urethral sphincteric activity.

At the lumbosacral spinal cord level in the rat, substance P-positive neurons are present in dense concentration in the dorsal horn and the sacral parasympathetic nucleus. We undertook the present study to investigate the effect of intrathecal substance P (10 micrograms at the L6-S1 level) on urinary bladder and urethral sphincteric activity and to compare these effects with those of intravenous and intra-arterial administration. Three different bladder pressure responses were triggered by intrathecal substance P: (A) an immediate, strong bladder contraction (n = 5); (B) augmentation of the micturition reflex, as indicated by strong detrusor contractions in response to intravesical saline perfusion (n = 4); and (C) a slow, gradual increase to a high, steady peak (n = 8). The sphincteric electromyographic (EMG) activity was consistently increased. When substance P was given intravenously (n = 10) and intra-arterially (n = 3), the form, duration, and maximal amplitude of bladder contractions (owing to a direct smooth-muscle action) were comparable with those of Group A. The effects in intrathecal Groups B and C suggest that substance P provides a tonic influence on motor horn cells and on the preganglionic neurons in the sacral parasympathetic nucleus at the lumbosacral spinal cord level, where neuronal circuits controlling bladder and sphincteric activity are located.

Animals

Response of bladder, urethral and intracavernous pressure to ventral lumbosacral root stimulation in Sprague-Dawley and Wistar rats.

Six Sprague-Dawley and six Wistar rats were used for electrostimulation of the L5 to S2 ventral roots. Landmarks for identification of the roots were developed; bladder, urethral and intracavernous pressures were recorded; and tail and leg movements were checked. Urethral sphincter contraction was elicited by stimulation of the L5-L6 ventral roots, while bladder contraction and penile erection were mediated by the L6-S1 ventral roots. The best sphincteric response and intracavernous pressure rise were obtained by stimulation of the L6 ventral root, and the highest bladder pressures by stimulation of the S1 ventral root. Stimulation of the S1-S2 ventral roots provoked ipsilateral tail movement; of L6, tail movement, hindleg muscle twitch, and slight toe spread; and of L5, hindleg stretch and plantar flexion. No significant differences were found between the two strains of rats, although a higher bladder pressure was recorded during stimulation of the L6 ventral root in Sprague-Dawley rats, which might be explained by a small caudal shift of the sacral parasympathetic nucleus in the Wistar strain.

Animals

Selective sacral rhizotomy in the management of the reflex neuropathic bladder: a report on 17 patients with long-term followup.

During the last 6 years 24 patients with cervical or thoracic spinal cord injuries and a severe reflex neuropathic bladder underwent selective dorsal sacral rhizotomy with the aid of intraoperative neurostimulation and urodynamic monitoring. Preoperative and postoperative evaluation was available in 17 patients. Followup ranged from 2 months to 5 years (mean 32 months). Mean bladder capacity increased significantly after rhizotomy (from 148 +/- 28.1 to 377 +/- 52.9 ml., p less than 0.001), as did mean volume to first contraction (from 99 +/- 28.6 to 270 +/- 39.3 ml., p less than 0.001). No significant changes in bowel or erectile function were noted. Continence was improved in 94%, with 14 patients remaining completely dry and voiding with electrical stimulation or intermittent self-catheterization. The long-term results of selective sacral rhizotomy compare favorably to more aggressive alternatives, such as augmentation cystoplasty or urinary diversion.

Adult

Continence after radical cystoprostatectomy and total bladder replacement: a urodynamic analysis.

Urodynamic evaluation was performed in 10 patients after radical cystoprostatectomy and continent urethral diversion with detubularized ileum and in 13 patients continent after radical prostatectomy. In both groups surgical techniques were modified to optimize preservation of the periurethral tissue at the prostatic apex. For the ileal neobladder group 9 patients (90%) were completely continent and 1 (10%) noticed moderate nocturnal incontinence. The urethral sphincteric mechanism was well preserved in these patients, with no significant difference between the 2 groups in mean functional urethral length (3.8 +/- 0.6 versus 3.6 +/- 0.8 cm., p = 0.55) or maximal urethral closure pressure (87 +/- 34 versus 74 +/- 20 cm. water, p = 0.26). Tubularization of the bladder or neobladder above the level of the external sphincter was noted in both groups. Continence after radical cystoprostatectomy with continent urethral diversion and after radical prostatectomy is dependent upon an intact urethral sphincteric mechanism as well as a compliant, low pressure reservoir, either bladder or a bladder substitute. Urinary incontinence after total bladder replacement with detubularized ileum can be minimized by preserving as much of the distal urethral sphincter as possible. This can be done by careful dissection of the prostatic apex, performed under direct vision, with an understanding of the anatomy of the urethral sphincter and its innervation.

Aged

Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis.

To investigate the possibility of a neural deterioration of the bladder wall in interstitial cystitis, bladder tissue from 10 patients with interstitial cystitis was compared with that from 10 control subjects by means of immunohistochemistry. An enhanced innervation of the bladder in the submucosa and detrusor muscle was found to represent an increase of sympathetic but not cholinergic neurons. In interstitial cystitis the number of neurons positive for vasoactive intestinal polypeptide and neuropeptide Y was higher and carried a larger number of axonal varicosities, whereas the number of neurons positive for substance P and calcitonin-gene-related peptide was not significantly different in both groups. We conclude that interstitial cystitis is associated with increased sympathetic outflow into the bladder and altered metabolism of vasoactive intestinal polypeptide and neuropeptide Y. Since similar changes have been observed in other inflammatory diseases of a presumably autoimmune nature, such as rheumatoid arthritis, Crohn's disease and colitis ulcerosa, the pathophysiology of interstitial cystitis may share common pathways with the latter. Experience in these diseases may facilitate a better understanding of the pathophysiology of interstitial cystitis and suggest new therapeutic concepts.

Adrenergic Fibers

Site of deafferentation and electrode placement for bladder stimulation: clinical implications.

Based on the clinical experience of treating neurogenic bladders by the electrical stimulation of the ventral sacral roots, neuroanatomical and neurophysiologic studies were designed to study the mechanism of detrusor-sphincter dyssynergia during electrical stimulation of the sacral roots. An experimental model was developed to decrease the stimulation response of the pelvic floor and external urethral sphincter muscles while preserving bladder contraction. The significance of the site of deafferentation and electrode implantation was evaluated under functional and clinical aspects. Our results indicate that a combination of intradural deafferentation and extradural electrode implantation may offer maximal deafferentation efficiency with minimal surgical risk. Intradural deafferentation is facilitated by a consistent arrangement of sacral roots with the dorsal roots running laterally to the ventral roots at the site of their exit from the dura. Detrusor-sphincter dyssynergia can be reduced by selective division of ventral sacral rootlets innervating the striated musculature of the pelvic floor and the urethral sphincter.

Afferent Pathways

Bladder rehabilitation with dorsal rhizotomy and ventral neuroprosthesis.

Two patients with severe neuropathic bladders were successfully treated with selective dorsal rhizotomy in conjunction with a ventral root neuroprosthesis. Both patients achieved stabilization of their renal function, continence, resolution of vesicoureteral reflux, and relief from indwelling urethral catheters. This alternative form of management avoids the complications of other operative approaches.

Adult

The effect of magnetic resonance imagers on implanted neurostimulators.

This in-vitro study was designed to investigate the safety of various implanted neurostimulators in magnetic resonance (MR) imagers. The effects of the static and changing magnetic fields and the radio frequency (RF) electromagnetic field generated by 0.35 and 1.5 T MR imagers on the voltage output of four models of implantable passive neurostimulators and two models of implantable self-powered neurostimulators was studied. The neurostimulators were mounted on a support and placed in the imagers. An oscilloscope monitored the voltages at the outputs of the neurostimulators. For an Avery single-channel stimulator, located at the isocenter, the amplitude of the output pulses induced by the 0.35 T imager was 6V; from a 1.5 T imager, it was 12 V. These amplitudes can cause discomfort and possible harm to a patient if the typical therapeutic value is 1-5 V. The amplitude of the stimulator receiver's output decreased to relatively safe values beyond 40 cm from the isocenter. By contrast, there was no significant voltage output from the Medtronic SE-4 receiver. For two models of self-powered neurostimulators, the Medtronic Itrel and the Cordis MK II, the programmed stimulus parameters were not affected by the pulsed magnetic fields of the MR imagers. However, the RF fields at the isocenter heated the metal case of the stimulators. The rotational and linear forces produced by the fixed magnet on the Cordis MK II were judged to be too strong for a patient with this implant to be scanned. The study showed that patients with certain types of implanted neurostimulators can be scanned safely under certain conditions.

Electric Stimulation Therapy

Primary malignant ectomesenchymoma of the orbit.

Malignant ectomesenchymoma (MEM) is a rare soft tissue tumour believed to arise from a pluripotential migratory neural crest cell and composed of both a mesenchymal element (most often rhabdomyosarcoma) and a neuroectodermal element (often neuroblastoma). Reported sites of origin are the abdomen, perineum or scrotum, the extremities, the middle ear, nasopharynx, face, and neck. We report the first case of an orbital MEM, with a review of the 17 cases previously reported from other sites.

Child, Preschool

Perineal pudendal neurotomy versus selective neurotomy of the S2 somatic contribution to the pudendal nerve. Effects on sacral-root-stimulated bladder and urethral responses in the dog.

In 10 dogs that underwent bilateral electrode implantation on the S2 ventral root, 5 then underwent a bilateral total perineal neurotomy of the pudendal nerve (group A) at 3 months and 5 bilateral division of the S2 somatic contribution to the pudendal nerve (group B). The effects of these 2 types of neurotomy on the bladder and urethral responses to electrostimulation were compared after another 3 months. In group A, the proximal and mid-urethral responses decreased significantly [69.1% (p = 0.004) and 79.6% (p = 0.002), respectively]. A decrease in bladder response [26% (p = 0.089)], although not significant, was also found. In group B, the decrease in the proximal urethral response was significant [67.8% (p = 0.012)]; the mid-urethral response (56.8%) was not statistically significant (p = 0.134). The bladder response decreased by 73.6% (p = 0.034). Thus, although pudendal neurotomy can be effective in reducing the outlet resistance, the pudendal nerve may have an important role in the regulation of micturition in the dog. Preoperative testing of the effect of a pudendal neurotomy by temporary nerve blocks is warranted to avoid undesirable side effects such as a decrease in bladder excitability.

Animals

Computer-aided diagnosis: development of automated schemes for quantitative analysis of radiographic images.

Preliminary results obtained with computer-aided diagnosis (CAD) from various radiographic examinations are very encouraging. However, CAD is still at an early stage of its development. It will be necessary to increase further the understanding of image features of normal and abnormal patterns, to establish databases, and to devise specific approaches for particular types of pathology. Although the existing schemes are designed to be applied to digital radiographs, similar techniques can be applied in the future to cross-sectional images such as CT, MRI, and ultrasound. We believe that CAD will become clinically practical in the near future.

Angiography

Treatment of unstable bladder.

We present our experience with 2 spinal-injury patients tested for urinary incontinence via implanted sacral nerve electrodes. In each patient, spinal injury occurred at the T-12 level, with presentation of spontaneous detrusor activity. Associated weakness of the voluntary sphincter mechanism was evident urodynamically. Neurostimulation via wire electrode in the S3 foramen produced good sphincter closure. Voiding secondary to spontaneous detrusor triggering could thereby be suppressed, eliminating embarrassing incontinence without interfering with the patient's ability to empty the bladder at regular intervals. The therapeutic principles of neurostimulation applicable to patients with spastic bladders are underscored by these 2 cases.

Adult

Urodynamics simplified.

Urodynamic equipment has grown ever more sophisticated, and though necessary for research, tends to discourage the average clinician. However, a great deal of information can be gleaned from relatively simple recording techniques that are easily adapted to office practice. The most important urodynamic information is obtained by recording static and dynamic urethral behavior during bladder filling. This article addresses changes in urethral behavior induced by patient position, bladder filling, and catheter movement in relation to detrusor behavior. Expected changes in cases of neurogenic bladder, bladder outlet obstruction, incontinence, and urge-frequency syndromes are outlined. The clinician can perform flow-rate studies, voiding cystourethrogram, and cystoscopy at separate times and pool the information to provide a therapeutic outline.

Ambulatory Care

Panlobular emphysema in young intravenous Ritalin abusers.

We studied a distinctive group of young intravenous Ritalin abusers with profound obstructive lung disease. Clinically, they seemed to have severe emphysema, but the pathologic basis of their symptoms had not been investigated previously. Seven patients have died and been autopsied: in four, the lungs were fixed, inflated, dried, and examined in detail radiologically, grossly, microscopically, and by electron probe X-ray microanalysis. All seven patients had severe panlobular (panacinar) emphysema that tended to be more severe in the lower lung zones and that was associated with microscopic talc granulomas. Vascular involvement by talc granulomas was variable, but significant interstitial fibrosis was not present. Five patients were tested for alpha-1-antitrypsin deficiency and found to be normal, as were six similar living patients. These findings indicate that some intravenous drug abusers develop emphysema that clinically, radiologically, and pathologically resembles that caused by alpha-1-antitrypsin deficiency but which must have a different pathogenesis. Talc from the Ritalin tablets may be important, but the mechanism remains to be elucidated.

Adult

Molecular characterization of the Spirometra mansonoides genome: renaturation kinetics, methylation, and hybridization to human cDNA probes.

High molecular weight DNA from pleroceroid larvae of the tapeworm Spirometra mansonoides was purified from isolated nuclei by conventional techniques. The DNA so isolated has a melting temperature (Tm) of 87 degrees C and a guanine plus cytosine (G/C) content of 44%. 5-Methyl cytosine could not be detected in plerocercoid DNA by HPLC analysis of DNA hydrolysates, by radiolabeling 5'-termini of MspI digests with polynucleotide kinase, or by comparing restriction patterns generated by MspI and HpaII. Renaturation kinetics demonstrated that the genome of S. mansonoides contains repetitive as well as single copy sequences and has a genome size estimated at approx. 1.6 X 10(9) bp. Hybridization was carried out between plerocercoid DNA and cDNAs for human beta-actin, alpha-tubulin and growth hormone (hGH). Rationale for this analysis was based on known homologies among actin and tubulin genes in numerous species and on apparent similarities between hGH and a plerocercoid growth factor that may be reflected in similar DNA sequence. Scanning densitometry of dot blots demonstrated that the hGH probe annealed to the same extent at low stringency (1 M NaCl, 55 degrees C) to DNA from plerocercoids, rat liver and chicken erythrocytes; but this interaction was less than to DNA from human lymphocytes, calf thymus and mouse skin. Similar results were obtained when restriction endonuclease digests of these DNAs were analyzed by Southern transfer. Little or no hybridization of the growth hormone probe to plerocercoid DNA was evident at higher stringency (1 M NaCl, 65 degrees C). In contrast, human tubulin and actin probes showed extensive hybridization to pleroceroid restriction fragments under the high stringency conditions.

Actins