Effects of stones and other physical factors on the induction of rodent bladder cancer.
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Animals↗
Biomedical subjects
S M Cohen
Publications and source records attributed to S M Cohen.
Long-lasting desensitization of bladder afferents following intravesical resiniferatoxin and capsaicin in the rat.
The present study was conducted to determine whether long-lasting desensitization of bladder afferents could be achieved using a single local application of the capsaicin (CAP)-like irritant resiniferatoxin (RTX), and to compare the effects of RTX and CAP on behavioral and histological endpoints. While rats were anesthetized, vehicle (VEH), RTX (10-100 nmol) or CAP (10-100 mumol) was instilled in the bladder (intravesical, i.ves.) via a cannula surgically implanted into the bladder dome. Beginning 1 week after treatment, once per week for 4 weeks, rats were tested behaviorally for desensitization to i.ves. RTX (10 nmol) using the abdominal lick test. Rats pretreated with low doses of RTX and CAP were partially desensitized at week 1; desensitization diminished over weeks 2-3. In contrast, rats pretreated with high doses of RTX or CAP were more completely desensitized at week 1, and desensitization did not diminish by week 4. Separate groups of rats tested 8 weeks after treatment showed substantial recovery. Rats pretreated with RTX but tested only with VEH for the first 3 weeks showed desensitization at week 4 approximately equivalent to that of RTX-treated rats tested with RTX every week. Sensitivity of corneal afferents to RTX (1.0 microgram/ml) at week 4 was not different between VEH- and RTX- or CAP-treated rats. Gross and histological examination of bladder tissue indicated that both RTX and CAP produced inflammation, which diminished in a dose- and time-dependent manner (1-8 weeks post-treatment).(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Intravesical↗
Role of cell proliferation in regenerative and neoplastic disease.
DNA replication does not have 100% fidelity. Consequently, a chemical can increase the risk of cancer either by directly damaging DNA (genotoxic) or by increasing the number of cell replications, or both. Increased cell proliferation can be produced by increasing cell births (by direct mitogenesis or regeneration following toxicity), or decreasing cell deaths (by inhibiting apoptosis or differentiation). Cell proliferation can affect the dose-response curve for genotoxic carcinogens and is the basis for carcinogenicity by nongenotoxic agents. Bladder carcinogens will be used to illustrate these mechanisms, and their implications with respect to human risk assessment will be presented.
2-Acetylaminofluorene↗
Trans- and cis-acting requirements for blastodermal expression of the head gap gene buttonhead.
The Drosophila gene buttonhead (btd) encodes a zinc-finger protein related to the human transcription factor Sp1. btd is expressed in the syncytial blastoderm embryo in a stripe covering the anlagen of the antennal, intercalary and mandibular head segments. btd has been characterized as a head gap gene, since these segments are deleted in btd mutant embryos. We report here that the cis-acting elements required for btd head stripe expression are contained in a 1 kb DNA fragment, located about 3 kb upstream of the promoter. The four maternal coordinate systems are necessary for correct btd head stripe expression, likely by acting through the 1 kb cis-acting control region. Expression of the btd head stripe depends on the anterior morphogen encoded by the gene bicoid (bcd). bcd-dependent activation also involves the activity of the morphogens of the posterior and dorsoventral systems, hunchback and dorsal, respectively, which act together to control the spatial limits of the expression domain. Finally, the terminal system takes part in the regulation of btd head stripe expression by enhancing activation at low levels of activity and repression at high levels of activity.
Animals↗
Laser energy and dye fluorescence transmission through blood in vitro.
PURPOSE: Because of the potential usefulness of evaluating and treating choroidal neovascularization obscured by blood, we designed this study to quantify the transmission of dye fluorescence and laser energy through blood. METHODS: Blood preparations anticoagulated with ethylenediaminetetraacetic acid with hematocrits of 0% (plasma), 46%, and 99% were placed in open cuvettes with path lengths of 100, 200, or 500 microns and were exposed for one minute to either 100% oxygen or 100% carbon dioxide. Each cuvette was then sealed. Photographs of the cuvettes of blood in front of a flask of fluorescein or indocyanine green solution were decoded and used to calculate the percent transmission of fluorescence through blood. Cuvettes of blood were also placed in the path of argon, krypton, and diode lasers for energy transmission measurements. RESULTS: Plasma transmission of fluorescein and indocyanine green fluorescence and argon, krypton, and diode laser energy was 89% to 100% for all samples tested. Transmission of fluorescein fluorescence and argon laser energy through 99% hematocrit samples were both less than 5%. Transmission of indocyanine green fluorescence through 100-, 200-, and 500-microns-thick cuvettes filled with 99% hematocrit blood was 57%, 34%, and 4%. Transmission of krypton laser energy was 50%, 25%, and 6%; and transmission of diode laser energy was 60%, 35%, and 12% through 99% hematocrit blood. Intermediate transmission values were obtained for 46% hematocrit samples. CONCLUSIONS: Krypton and, to a slightly greater degree, diode laser energy penetrate a thin film of blood. Indocyanine green fluorescence also penetrates a thin film of blood. If a layer of blood appears thinner than 500 microns, then indocyanine green angiography may be useful in imaging underlying pathologic features. If a lesion can be imaged with indocyanine green, then it can probably be treated with a krypton or diode laser.
Blood↗
Endophthalmitis after pars plana vitrectomy. The Postvitrectomy Endophthalmitis Study Group.
PURPOSE: To describe the clinical course and incidence of culture-proven postvitrectomy endophthalmitis in 18 patients from five academic centers and three private practices. METHODS: Patients undergoing pars plana vitrectomy for recent trauma or endophthalmitis were excluded. The average age was 58 years (range, 21-85 year). Sixty-one percent of the patients (11/18) had diabetes mellitus. The indication for initial vitrectomy was vitreous hemorrhage (n = 10), macular epiretinal membrane (n = 3), recurrent retinal detachment with proliferative vitreoretinopathy (n = 2), retinal detachment with retinoschisis (n = 1), proliferative diabetic retinopathy with tractional retinal detachment (n = 1), and dislocated intraocular lens (n = 1). None of these eyes received prophylactic intraocular antibiotics during the vitrectomy. RESULTS: All eyes were treated with intraocular antibiotics after the diagnosis of postvitrectomy endophthalmitis was made. Final visual acuity ranged from 20/20 to no light perception and included five eyes with 20/50 or better visual acuity and 11 eyes with less than 5/200 visual acuity. Nine eyes had a final visual acuity of no light perception. Of the 16 eyes infected with a single organism, 71% (5/7) of eyes infected with coagulase-negative staphylococci retained 20/50 or better final visual acuity compared with no eyes (0/9) infected with other organisms (P = 0.005). Two eyes infected with both coagulase-negative Staphylococcus and Streptococcus had a final visual acuity of 20/400. Three eyes with a total hypopyon later had enucleation or evisceration. Based on the data from four medical centers, the incidence of endophthalmitis after pars plana vitrectomy performed over the last 10 years was 9/12,216 (0.07%). CONCLUSION: Endophthalmitis after vitrectomy is rare. Postvitrectomy bacterial endophthalmitis caused by organisms other than coagulase-negative staphylococci has a poor visual prognosis.
Adult↗
The initial worcester experience with laparoscopic hysterectomy.
STUDY OBJECTIVE: To examine three community hospital's experience with the first 108 attempted laparoscopic hysterectomies. DESIGN: Retrospective analysis of hospital and office charts using a standardized data-collection sheet. SETTING: All procedures were performed at the Medical Center of Central Massachusetts, St. Vincent's Hospital, or the University of Massachusetts Medical School, Worcester, Massachusetts. PATIENTS: The first 108 patients to have a laparoscopic hysterectomy attempted. Ninety procedures were completed successfully. MEASUREMENTS AND MAIN RESULTS: Areas that were analyzed were indications for surgery, type of laparoscopic hysterectomy, surgeons' instrument preference, failure to complete the operation, complications, and relative cost. Surgical indications, patient demographics, and complication rates were comparable with those unpublished papers. However, our data showed no improvement in estimated blood loss or operating room time with increased operator experience. Review of pathology reports indicated no cases in which an unsuspected malignancy was encountered. CONCLUSIONS: Laparoscopic hysterectomy can be performed safely and successfully by generalists in obstetrics and gynecology. Additional study is required to know whether variables such as operating room time and expense will improve as this procedure is increasingly performed by generalists rather than specialists.
Adult↗
Effects of sodium ascorbate, sodium saccharin and ammonium chloride on the male rat urinary bladder.
Sodium saccharin administered at high doses to male rats beginning after 5 weeks of age produces mild urothelial hyperplasia but does not result in a significant increase in incidence of bladder cancer unless it is administered after an initiating agent. However, if it is administered in a two-generation bioassay, a significant incidence of bladder tumors is produced. The hyperplastic and tumorigenic effects are inhibited by co-administration with high doses of NH4Cl. The present experiment was designed to evaluate the effects of another sodium salt, sodium ascorbate, administered through the neonatal time period. Sodium saccharin administered as 5% of the diet produced urothelial hyperplasia and increased labeling index, and this was inhibited by co-administration with 1.23% NH4Cl. Four doses of sodium ascorbate was evaluated. The lowest dose, 0.91%, was without effect on the urinary tract. A slight effect (not statistically significant) was observed at a dose of 2.73%, and a significant proliferative response was detected at 4.56 and 6.84%. Recent studies suggest that a calcium phosphate-containing amorphous precipitate forms in the urine of rats fed high doses of sodium saccharin, producing cytotoxicity of the urothelium and consequent regenerative hyperplasia. This precipitate was observed in the present experiment in the rats administered the high dose of sodium saccharin or the higher doses of sodium ascorbate. Formation of this precipitate and induction of urothelial proliferation were inhibited by co-administration of NH4Cl, but somewhat higher doses of ammonium chloride were required for doses of sodium ascorbate compared to sodium saccharin. These results demonstrate that sodium ascorbate administered through the neonatal time period of the male rat produces urothelial hyperplasia in the dose responsive manner, with a no-effect level of 0.91% of the diet. The formation of the calcium phosphate-containing amorphous precipitate and urothelial proliferation were inhibited by co-administration with NH4Cl.
Ammonium Chloride↗
Urinary and urothelial effects of sodium salts in male rats.
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Animals↗
Is early oral feeding safe after elective colorectal surgery? A prospective randomized trial.
INTRODUCTION: The routine use of a nasogastric tube after elective colorectal surgery is no longer mandatory. More recently, early feeding after laparoscopic colectomy has been shown to be safe and well tolerated. Therefore, the aim of our study was to prospectively assess the safety and tolerability of early oral feeding after elective "open" abdominal colorectal operations. MATERIALS AND METHODS: All patients who underwent elective laparotomy with either colon or small bowel resection between November 1992 and April 1994 were prospectively randomized to one of the following two groups: group 1: early oral feeding--all patients received a clear liquid diet on the first postoperative day followed by a regular diet as tolerated; group 2: regular feeding--all patients were treated in the "traditional" way, with feeding only after the resolution of their postoperative ileus. The nasogastric tube was removed from all patients in both groups immediately after surgery. The patients were monitored for vomiting, bowel movements, nasogastric tube reinsertion, time of regular diet consumption, complications, and length of hospitalization. The nasogastric tube was reinserted if two or more episodes of vomiting of more than 100 mL occurred in the absence of bowel movement. Ileus was considered resolved after a bowel movement in the absence of abdominal distention or vomiting. RESULTS: One hundred sixty-one consecutive patients were studied, 80 patients in group 1 (34 males and 46 females, mean age 51 years [range 16-82 years]), and 81 patients in group 2 (43 males and 38 females, mean age 56 years [range 20-90 years]). Sixty-three patients (79%) in the early feeding group tolerated the early feeding schedule and were advanced to regular diet within the next 24 to 48 hours. There were no significant differences between the early and regular feeding groups in the rate of vomiting (21% vs. 14%), nasogastric tube reinsertion (11% vs. 10%), length of ileus (3.8 +/- 0.1 days vs. 4.1 +/- 0.1 days), length of hospitalization (6.2 +/- 0.2 days vs. 6.8 +/- 0.2 days), or overall complications (7.5% vs. 6.1%), respectively, (p = NS for all). However, the patients in the early feeding group tolerated a regular diet significantly earlier than did the patients in the regular feeding group (2.6 +/- 0.1 days vs. 5 +/- 0.1 days; p < 0.001). CONCLUSION: Early oral feeding after elective colorectal surgery is safe and can be tolerated by the majority of patients. Thus, it may become a routine feature of postoperative management in these patients.
Adolescent↗
Teaching awareness of cognitive bias in medical decision making.
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Bias↗
Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing.
Growth and patterning of the Drosophila wing is controlled by organizing centers located at the anterior-posterior and dorsal-ventral compartment boundaries. Interaction between cells in adjacent compartments establish the organizer. We report here that Serrate and Notch mediate the interaction between dorsal and ventral cells to direct localized expression of Wingless at the D/V boundary. Serrate serves as a spatially localized ligand which directs Wg expression through activation of Notch. Ligand independent activation of Notch is sufficient to direct Wg expression, which in turn mediates the organizing activity of the D/V boundary.
Animals↗
Nubbin encodes a POU-domain protein required for proximal-distal patterning in the Drosophila wing.
The nubbin gene is required for normal growth and patterning of the wing in Drosophila. We report here that nubbin encodes a member of the POU family of transcription factors. Regulatory mutants which selectively remove nubbin expression from wing imaginal discs lead to loss of wing structures. Although nubbin is expressed throughout the wing primordium, analysis of genetic mosaics suggests a localized requirement for nubbin activity in the wing hinge. These observations suggest the existence of a novel proximal-distal growth control center in the wing hinge, which is required in addition to the well characterized anterior-posterior and dorsal-ventral compartment boundary organizing centers.
Animals↗
Laparoscopic-assisted perineal rectosigmoidectomy for rectal prolapse.
One of the important surgical principles in perineal rectosigmoidectomy (Altemeier's procedure) for full-thickness rectal prolapse is to ensure the complete resection of the redundant rectosigmoid colon to avoid recurrence of the prolapse. We present a new technique of laparoscopic assistance during this procedure, which helps achieve maximal mobilization and resection of the prolapsed portion.
Anastomosis, Surgical↗
Evaluation of effects of chitosan in preventing hemorrhagic cystitis in rats induced by cyclophosphamide.
Hemorrhagic cystitis is a common problem following cyclophosphamide or radiation therapy. Chitosan has been shown to be an effective hemostatic agent and promoter of wound healing in animal experiments. We evaluated the safety and efficacy of intravesical chitosan in an animal model of cyclophosphamide cystitis. Hemorrhagic cystitis was induced in female F344 rats by intraperitoneal cyclophosphamide, 100 mg/kg. Chitosan solution (0.3 ml) was instilled intravesically on day 1 (Group 1), on days 1, 3, and 5 (Group 2), or 1 hour after the administration of cyclophosphamide (Group 3). The rats in group 4 were treated with chitosan diluent on day 1 after cyclophosphamide, and the rats in group 5 received intravesical chitosan without cyclophosphamide. Sequential examination revealed decreased mortality and lower incidences of severe bladder bleeding, necrosis and inflammation in Group 3. Treatment delayed until after the appearance of the cystitis, especially repeated treatments, appeared to make the cyclophosphamide-induced changes worse. Used within 1 hour of cyclophosphamide administration, before the cystitis develops, chitosan seemed to have the possibility to inhibit the appearance of hemorrhagic cystitis. In addition to the changes in the bladder, severe changes occurred in the kidneys secondary to cyclophosphamide.
Administration, Intravesical↗
Saccharin-induced bladder cancer in rats.
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Animals↗
Effect of sodium saccharin on the neonatal rat bladder.
In a two-generation bioassay, high doses of dietary sodium saccharin (NaSac) produce bladder carcinoma in rats, whereas acid saccharin (HSac) does not effect the urothelium. NaSac and HSac administered as 5% of the diet to F0 Sprague-Dawley (SD) and F344 rats, continued through to the weaned male rats for ten additional weeks. Control 3H-thymidine labeling index (LI) was high prior to and at birth (approximately 11%), declining rapidly by weaning (to < 0.2). Neither NaSac nor HSac increased proliferation through 7 days of age. NaSac increased the proliferation rate at later times, whereas HSac did not. The LI decreased to control levels in NaSac-fed rats switched to control diet after weaning and increased in control-fed rats switched to NaSac after birth or weaning. In a second experiment, 5% NaSac did not affect urothelial morphology of SD rats through 7 days. By 21 days post-birth, urothelial hyperplasia occurred in NaSac-fed rat. The LI in treated versus control was similar through gestation, with a slight difference by 7 days. LI was significantly different by 21 days post-birth, but was similar between males and females. These results provide additional evidence for the increased cell proliferative effects of NaSac during the neonatal period, but not during gestation.
Animals↗
Cell interaction between compartments establishes the proximal-distal axis of Drosophila legs.
The appendage primordia of Drosophila are subdivided into compartments by the localized expression of transcription factors. Interaction between cells in adjacent compartments establishes organizing centres responsible for generating spatial pattern and promoting cell proliferation in the developing appendages. Localized expression of hedgehog (hh) in the posterior compartment of the leg imaginal disc directs expression of wingless (wg) in ventral-anterior cells and decapentaplegic (dpp) in dorsal-anterior cells near the anterior-posterior compartment boundary; wg then acts to specify ventral cell fate and to organize the dorsal-ventral axis of the leg. Interaction between wg-expressing ventral cells and dorsal cells near the anterior-posterior compartment boundary promotes axis formation in the leg. Here we show that the combined action of wg-expressing cells in the ventral-anterior compartment and dpp-expressing cells in the dorsal-anterior compartment activates expression of Distal-less, a gene required for proximal-distal axis formation in the limbs. These results demonstrate that sequential interaction between anterior-posterior and dorsal-ventral compartments establishes the proximal-distal axis of the limbs.
Animals↗