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Biomedical subjects

L Emerson

Publications and source records attributed to L Emerson.

At least 19 recordsLinked to original sources

Malignant islet cell tumor with sarcomatous differentiation.

Malignant mesenchymal neoplasms of the pancreas are rare and malignant islet cell tumors with sarcomatous dedifferentiation are rarer still. We present a case of malignant islet cell tumor with sarcomatous differentiation, which to our knowledge is only the second reported case showing such a combination of morphologic features. Clinically, the neoplasm was not hormonally active and immunohistochemical staining was negative for gastrin, glucagon, insulin and somatostatin. The sarcomatous component strongly reacted with an antibody directed against vimentin, and a minority of cells stained strongly with antisera directed against desmin and smooth muscle actin. The spindle cell component was nonreactive with antibodies directed against Factor VIII. The myogenous direction of differentiation in the present tumor is similar to that seen in the prior case report of malignant islet cell tumor with rhabdomyosarcomatous differentiation.

Actins↗

Neutralization of cardiac toxins oleandrin, oleandrigenin, bufalin, and cinobufotalin by digibind: monitoring the effect by measuring free digitoxin concentrations.

Oleandrin plant poisoning is common in children and the plant extract is used in Chinese medicines. The toxicity is due to oleandrin and the deglycosylated metabolite oleandrigenin. Bufalin and cinobufotalin (toad cardiac toxins) are also widely used in Chinese medicines like Chan SU, and Lu-Shen -WU. Severe toxicity from bufalin after consumption of toad soup has been reported. Taking advantage of structural similarities of these toxins with digitoxin, we demonstrated that these compounds can be rapidly detected in blood by the fluorescence polarization immunoassay for digitoxin. The cross reactivities of these compounds with digoxin assay were much lower. For example, when a drug free serum was supplemented with 10 microg/ml of oleandrin, we observed 127.7 ng/ml of digitoxin equivalent but only 2.4 ng/ml of digoxin equivalent concentration. Digibind neutralized all cardiac toxins studied as evidenced by significant fall of free concentrations. When aliquots of serum pool containing 50.0 microg/ml of oleandrin were supplemented with 0, 10.0, 25.0, 50.0, 100, and 200 microg/ml of digibind, the mean free concentrations were 30.6, 23.3, 16.0, 10.7, 7.8 and 5.5 microg/ml respectively. Similarly, with 50.0 microg/ml of oleandrigenin (total concentration: 36.2 ng/ml), the free concentration was 14.5 ng/ml digitoxin equivalent in the absence of digibind and 5.4 ng/ml in the presence of 200 microg/ml of digibind. In another specimen containing 500 ng/ml bufalin (total concentration: 156.9 ng/ml), the free concentration was 8.6 ng/ml in the absence of digibind and none detected in the presence of 100.0 microg/ml digibind. Because such neutralization may also occur in vivo, digibind may be useful in treating patients exposed to these toxins.

Bufanolides↗

Relative efficacy of various exogenous glycosaminoglycans in providing a bladder surface permeability barrier.

PURPOSE: To investigate the relative efficacy of heparin (H), pentosanpolysulfate (PPS) and hyaluronic acid (HA) in preventing the absorption of 14C labeled urea in protamine pretreated bladders compared with saline pretreated control bladders. MATERIALS AND METHODS: Control Group - Rabbit bladders were pretreated with phosphate buffered saline (PBS) followed by instillation of 14C-urea. Radioactivity was determined in blood, bladder and fluid drained from the bladder. Protamine Group - Bladders were pretreated with of PBS followed by protamine sulfate. The bladders were then treated with 14C-urea and radioactivity determined as above. GAG Groups - Bladders were pretreated with saline and protamine as described above followed by instillation of: Group 3A - HA, Group 3B - H and Group 3C - PPS. The bladders were then treated with 14C-urea and radioactivity determined as described above. RESULTS: Protamine treated bladders demonstrated significantly more radioligand uptake in bladder tissue compared with control bladders. There was no significant difference in radioligand uptake in bladders treated with PPS and H compared with control. While not significantly different, there was considerably more radioligand concentration in the blood of rabbits with bladders treated with protamine and protamine-HA compared with those of control rabbits and those treated with protamine-PPS and protamine-H. CONCLUSIONS: Exogenous GAG's are effective in providing an epithelial permeability barrier in protamine pretreated bladders. There is a difference in the relative efficacy of the various GAG's in producing this effect.

Absorption↗

Rapid detection of bladder cancer: a comparative study of point of care tests.

PURPOSE: We assessed sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the bladder tumor antigen (Bard BTA), fibrinogen/fibrin degradation products (AuraTek FDP), urinary cytology and hemoglobin dipstick tests in the urine of patients presenting to a urology clinic. MATERIALS AND METHODS: A total of 130 patients (60 with bladder cancer) provided a urine sample, which was divided into appropriate aliquots for each of the tests cited above. The endoscopist, pathologist, cytologist and the person performing the BTA/FDP/hemoglobin dipstick were blinded as to the results of the other tests, and the tests were read independently by a second blinded evaluator. RESULTS: Comparative results demonstrate a clear superiority of FDP in sensitivity (81%) and overall accuracy in bladder cancer detection (p = 0.0001) while cytology and BTA were marginally better than FDP in specificity. CONCLUSIONS: The anticipated lack of specificity of the hemoglobin dipstick was confirmed as well as the inadequacy of urinary cytology, particularly in the well differentiated tumors. Our findings with BTA were disappointing. The superiority of the FDP, first demonstrated here, was particularly striking in its ability to detect even well differentiated tumors. The simplicity and significantly better overall performance of FDP make it a reliable test for detection of transitional cell carcinoma of the bladder and a potential alternative to urinary cytology with important implications for clinical practice and health economics.

Aged↗

Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis.

OBJECTIVES: On the assumption that interstitial cystitis (IC) is the result of a defective mucous lining of the bladder epithelium, a study was carried out to investigate the activity of hyaluronic acid (HA) in the treatment of IC. HA is an important glycosaminoglycan (GAG) present in all connective tissues, including the GAG layer of the vesical mucosa. It exhibits a variety of pharmacologic properties that enhance its appeal for the therapy of IC. METHODS: A total of 25 patients, with the characteristic picture of IC and refractory to other medical treatments, participated in a trial of HA. Patients received 40 mg of HA intravesically on a weekly basis for 4 weeks, then monthly. Response to therapy was evaluated by symptom score, voiding diaries, and visual analog scales. RESULTS: An initial positive (complete+partial) response of 56% at week 4 increased to 71% by week 12. This response was maintained until week 20; beyond week 24 there appears to be a moderate decrease in the effectiveness of the medication. There was no significant toxicity attributable to the presence of HA in the bladder. CONCLUSIONS: The response of refractory IC patients to the intravesical administration of HA was gratifying. In the past, many therapies for IC that were initially considered promising failed the test of a controlled study. Further studies will establish the effectiveness of this particular preparation of HA in the treatment of IC.

Administration, Intravesical↗

Intralesional administration of biological response modifiers in the treatment of localized cancer of the prostate: a feasibility study.

OBJECTIVES: The primary aims of this pilot study were to establish the feasibility of intraprostatic administration of biological response modifiers (BRMs) and to investigate the toxicity and side effects of recombinant interferon (IFN)-alpha-2b injected into prostate glands harboring cancer. A secondary goal was to perform a preliminary assessment of the antitumor effect of this treatment. METHODS: Nine patients with histologically documented carcinoma of the prostate participated in the study. IFN was administered weekly for 5 weeks, under transrectal ultrasound visualization, with a modified gun that permitted the controlled injection of small volumes initially into the area of the tumor and later into the whole gland. Total doses of IFN ranged between 15 and 100 MU. RESULTS: The procedure resulted in minor local discomfort, comparable to a prostatic biopsy. Side effects from the drug were those anticipated from most BRMs (chills, fever, malaise, headache, fatigue), and in every case they were minor and self-limiting to several hours. Local adverse events were limited to gross hematuria (2 patients [22%]) and hematospermia (1 patient [11%]) and resolved spontaneously within 2 weeks. Antitumor activity, a secondary goal of the study, was noted in 3 (33%) patients with limited follow-up (mean 22.5 months). CONCLUSIONS: The results of this pilot study indicate that the intraprostatic administration of IFN-alpha-2b can be readily accomplished by the method described here and is associated with minor, self-limited toxicity. With the regimen and doses used, IFN demonstrated modest antineoplastic activity. Modifications of the schedule, routes, and amounts administered may result in enhanced therapeutic value.

Aged↗

Treatment of refractory interstitial cystitis.

Interstitial cystitis is the most therapeutically frustrating condition of the urinary tract. The vast array of treatments available clearly indicates that none is particularly effective. As the majority of patients fail to experience a significant and prolonged response to standard treatments, new options are frequently being developed. These include the oral administration of cimetidine, the intravesical use of hyaluronic acid and BCG, and total cystectomy with the formation of a continent urinary diversion. Unfortunately, the acceptance of many new treatments is based on incomplete evaluation, and this has resulted in a confusing array of disparate alternatives. Effective and durable treatment will not be available until the nature of the disease is better understood and the mechanisms of action of current therapies are elucidated.

Adjuvants, Immunologic↗

Interaction of valproic acid with nonsteroidal antiinflammatory drugs mefenamic acid and fenoprofen in normal and uremic sera: lack of interaction in uremic sera due to the presence of endogenous factors.

Valproic acid is an anticonvulsant that is strongly bound to serum albumin. The nonsteroidal antiinflammatory drugs mefenamic acid and fenoprofen are also strongly bound to albumin. We observed significant displacement of valproic acid from protein binding by mefenamic acid and fenoprofen at both therapeutic and slightly above therapeutic concentrations. The concentration of free valproic acid was higher in the uremic serum, as expected, but we observed no further displacement of valproic acid in the presence of mefenamic acid and fenoprofen. Known uremic compounds, hippuric acid and indoxyl sulfate, did not inhibit the interactions between valproic acid and mefenamic acid or fenoprofen. Treatment of uremic serum with activated charcoal at pH 3.0 removes endogenous interfering factors and corrects the binding defect of uremic serum for valproic acid. We observed significant displacement of valproic acid from protein binding by both mefenamic acid and fenoprofen in uremic serum after charcoal treatment. We conclude that endogenous factors are present in uremic sera that block interaction of valproic acid with mefenamic acid and fenoprofen.

Anti-Inflammatory Agents, Non-Steroidal↗

Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis.

PURPOSE: Based on the assumption that interstitial cystitis results from a defective mucous lining of the bladder epithelium, we investigated the activity of hyaluronic acid in the treatment of this disease. Hyaluronic acid is an important glycosaminoglycan present in all connective tissues, including the glycosaminoglycan layer of the vesical mucosa. It exhibits a variety of pharmacological properties that enhance its appeal for the therapy of interstitial cystitis. MATERIALS AND METHODS: A total of 25 patients with characteristic findings of interstitial cystitis refractory to other medical treatments participated in a trial of intravesical hyaluronic acid at a dose of 40 mg. weekly for 4 weeks and then monthly. Response to therapy was evaluated by symptom score, voiding diaries and visual analog scales. RESULTS: An initial 56% positive (complete plus partial) response rate at week 4 increased to 71% by week 12 and response was maintained until week 20. Beyond week 24 there was a moderate decrease in the effectiveness of the medication. There was no significant toxicity attributable to hyaluronic acid in the bladder. CONCLUSIONS: The response of patients with refractory interstitial cystitis to the intravesical administration of hyaluronic acid was gratifying. In the past many therapies for interstitial cystitis which were initially considered promising failed the test of a controlled study. Such a study to determine the activity of hyaluronic acid in patients with interstitial cystitis is currently under way.

Administration, Intravesical↗

Biofeedback: a noninvasive treatment for incontinence after radical prostatectomy.

OBJECTIVE: Will a program using biofeedback help patients with post radical prostatectomy incontinence to achieve continence by increasing their ability to contract pelvic floor muscles? STUDY DESIGN: Twenty-seven patients who had undergone incontinent radical prostatectomy were evaluated for urinary incontinence and treated at the Urology Biofeedback Laboratory at our institution. Patients were assessed by urodynamic studies including uroflow, postvoid residual measurement, and cystometrogram before biofeedback was initiated. The protocol provided for 10 weekly sessions of 15 minutes' duration with additional reinforcement sessions at 1, 3, 6, and 12 months. Subjective symptoms related to urgency, frequency, nocturia, and number of pad changes were reported by patients before treatment and at each visit. Digital evaluation of the pelvic floor muscle contraction was objectively graded from 0 to 3 (nil to strong) and was completed before and after treatment. These subjective and objective findings were used to determine success of treatment. RESULTS: Of the 27 patients completing the full treatment course, 13 (48%) had complete success, 7 (26%) had significant improvement but were not completely dry, and 7 (26%) had failure, for a total improvement rate of 74%. CONCLUSIONS: A biofeedback training program is an effective, minimally invasive, and well-accepted method that can be offered as a first-line option to patients who have undergone radical prostatectomy and want to improve the postsurgical problem of urinary incontinence. Patient motivation is an important factor in success. Nurses have an opportunity to use their expertise in this program to assist these patients to return to continence.

Aged↗

Cimetidine in the treatment of interstitial cystitis.

OBJECTIVES: To assess the effect of the H2-antagonist cimetidine in the treatment of patients with interstitial cystitis (IC) refractory to other conservative therapies. METHODS: A group of 9 patients previously treated conservatively for IC without success were entered in the study. They were thoroughly investigated and treated with cimetidine at the dose of 300 mg orally twice a day for 1 month. RESULTS: Six of the 9 patients (66%) experienced various degrees of symptomatic relief while on the drug. Of these, 4 (44%) have noted a complete and sustained response to the medication. CONCLUSIONS: The encouraging results observed in this pilot study together with the simplicity and tolerance of the treatment makes it an alternative when other options have been exhausted. Its use as a first-line monotherapy remains speculative.

Administration, Oral↗

The bladder mucus (glycosaminoglycan) layer in interstitial cystitis.

The thin mucus or glycosaminoglycan layer of the bladder may be implicated in the pathogenesis of interstitial cystitis. We developed a specific anti-mucus, antisera stabilization technique to study the ultrastructural morphological appearance of the layer, and have used this technique to compare the surface morphology of 10 control and 10 interstitial cystitis patients. The electron micrographs demonstrate the ultrastructural characteristics of the pathological changes seen in interstitial cystitis but they did not show any significant difference in the morphological appearance of the mucus or glycosaminoglycan layer between the 2 groups.

Adult↗

Endoscopic balloon dilation of the prostate: early experience.

Coaxial balloon dilation catheters recently have been introduced for transurethral dilation of the prostate. We applied endoscopically a specially designed high pressure, large diameter balloon catheter to patients with benign prostatic hyperplasia or primary bladder neck hyperplasia who presented with symptomatic, cystoscopic and urodynamic evidence of obstruction. We report our preliminary experience with 42 patients: 28 with benign prostatic hyperplasia and 14 with bladder neck hyperplasia. Six months after dilation 46% of the patients demonstrated at least a 25% improvement in subjective (symptom score) and objective (corrected peak flow rate) parameters, while 6 (21%) experienced excellent (greater than 50%) symptomatic improvement despite unchanged corrected peak flow rates and 3 (11%) showed significant (greater than 50%) improvement in corrected flow rate alone. At 1, 3, 6 and 12 months the symptom scores decreased by 70, 67, 61 and 59% (median) from pre-treatment levels. Men with benign prostatic hyperplasia fared better than those with primary bladder neck hyperplasia (74 versus 58% decrease at 6 months). Objective evaluation by corrected peak flow rates demonstrated 25, 24, 28 and 2% median improvement at 1, 3, 6 and 12 months, respectively. Patients with primary bladder neck hyperplasia had substantially greater increases than those with benign prostatic hyperplasia (47 versus 27% at 6 months). Immediately after dilation the serum prostate specific antigen level increased by at least 1.5 ng. per ml. in 16 of 22 patients, indicating significant tissue trauma. Complications included mild bleeding and pain for the initial 24 hours and transient urinary retention in 2 patients. Our experience demonstrates the safety of an endoscopic approach to balloon dilation of the prostate that allows the urologist to maintain a central role in the assessment of a new approach to the treatment of obstructed voiding dysfunction.

Aged↗

The mechanisms of continence in the Indiana pouch: a video-urodynamic study.

The ileocecal reservoir (Indiana pouch) is a large volume, low pressure continent reservoir well suited for urinary diversion. The mechanism of continence is believed to be the result of several factors, including the natural ileocecal valve resistance, resistance produced by the plication of the ileal segment and normal peristalsis of the ileum. We report the results of a video-urodynamic study in patients with an Indiana pouch, aimed at establishing the factors that contribute to continence and their relative significance. Video-urodynamic studies clearly demonstrate that continence in this type of urinary reservoir is dependent upon a synergism of the aforementioned factors in combination with the low intraluminal pressure of the detubularized bowel. Video-urodynamic studies offer an objective demonstration of the reservoir dynamics and its continence mechanisms, and provide an insight into the possible etiology of incontinence. Such studies also offer an objective means for critical comparison of the different continent urinary reservoirs.

Contrast Media↗

Maturation and degeneration of the fat body in the Drosophila larva and pupa as revealed by morphometric analysis.

Using morphometric and cytochemical techniques we have described changes taking place in the fat body cells during three different stages of development. The cell number remains constant at about 2200 cells during larval life and then decreases gradually and continuously throughout metamorphosis and the first 3 days of the adult stage until no more cells can be observed. Cell size increases rapidly during the larval period and decreases steadily during metamorphosis and adult stage. The size of the nuclei increases during the larval instars and decreases during the pupal interval. The change in nuclear size is correlated with the amount of DNA present throughout development implying the nuclear DNA is synthesized during the larval period and degraded gradually during metamorphosis. The cell size changes are due in large part to accumulation or loss of reserve substances: lipid droplets, glycogen deposits and protein granules. During metamorphosis the amount of lipid decreases slightly whereas glycogen experiences two loss cycles. The protein granules in the form of lysosomes continue to increase in amount during the first day of metamorphosis because of a short period of massive autophagy. Then the lysosomes decrease in amount throughout the remainder of metamorphosis. The lysosomes stain positively for lipofuscin.

Adipose Tissue↗

Urodynamic studies in interstitial cystitis.

Urodynamics, although not diagnostic of IC, are useful in the differential diagnosis of painful voiding disorders and provide a convenient way to quantitate response to therapy. They may prove useful as prognostic indicators of response to treatment and are of value in those patients in whom surgery is considered. Our studies suggest that IC is a progressive disease if not treated and that early diagnosis may improve response to treatment. Although similar information can be gathered by other means, we find urodynamics reliable, reproducible, and quantifiable and a valuable tool in the diagnosis, treatment, and follow-up of patients with IC.

Cystitis↗