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N Rosenblum

Publications and source records attributed to N Rosenblum.

18 recordsLinked to original sources

Phase I trial of multiple cycles of high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell support as front-line therapy.

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with either filgrastim alone or in combination with cyclophosphamide and paclitaxel. Patients then received three or four cycles of high-dose carboplatin (area under the concentration-time curve [AUC] 16), paclitaxel (250 mg/m(2)), and topotecan (10-15 mg/m(2)), with the latter two agents administered as 24-hour infusions and supported with PBSC and filgrastim. Cycles were repeated every 28 days. RESULTS: Twenty patients were enrolled onto the trial and were assessable for toxicity and clinical outcome. Dose-limiting toxicities were stomatitis and prolonged hematopoietic recovery. The maximum-tolerated dose of topotecan was 12.5 mg/m(2) when given with high-dose carboplatin and paclitaxel for three cycles. Four cycles were able to be given with a dose of topotecan of 10 mg/m(2). The pharmacokinetics of each compound were not affected by the other agents. Eleven (85%) of 13 patients with assessable disease responded. CONCLUSION: Multiple cycles of high-dose carboplatin, paclitaxel, and topotecan can be safely administered with filgrastim and PBSC support. The recommended doses for phase II study are carboplatin AUC 16, paclitaxel 250 mg/m(2), and topotecan 10 mg/m(2). Trials are currently being conducted with this regimen as front-line treatment in patients with advanced ovarian cancer and extensive small-cell carcinoma. This approach remains experimental and should be used only in the context of a clinical trial.

Adult↗

Comparison of two different doses of preoperative recombinant erythropoietin in men undergoing radical retropubic prostatectomy.

OBJECTIVES: To determine whether the response to recombinant erythropoietin is dose dependent in men undergoing radical prostatectomy and to elucidate the relative cost-effectiveness of two dosing regimens. METHODS: A prospective, open-label study comparing the effectiveness, cost, and safety of two different doses of recombinant erythropoietin was performed in men undergoing radical retropubic prostatectomy. The first 100 men received 600 IU/kg (high dose) of epoetin alfa. A second group of 100 men received 300 IU/kg (low dose). All men received two doses of erythropoietin on preoperative days 14 and 7, provided their baseline hematocrit levels were less than 48%. Hematocrit levels were measured at baseline (more than 14 days before surgery), at the time of anesthesia induction, in the recovery room postoperatively, on the first postoperative day, and on the morning of discharge. RESULTS: The mean increase in hematocrit from baseline to induction for the high and low-dose groups was 4.50 and 4.69, respectively (P = 0.7225). Six men (6%) in the high-dose group and seven (7%) in the low-dose group required allogenic blood transfusions. The mean cost of high and low-dose epoetin alfa was $1218 and $656, respectively. The cost per percentage point increase in hematocrit in the low-dose group was significantly less than in the high-dose group. No thromboembolic events occurred in the high or low-dose group. CONCLUSIONS: In men undergoing radical retropubic prostatectomy, the administration of epoetin alfa on preoperative days 14 and 7 was a safe and effective treatment strategy for reducing the risk of allogenic blood transfusions. The 300 IU/kg dosing regimen was significantly more cost effective than the 600 IU/kg dosing regimen.

Cost-Benefit Analysis↗

Radical retropubic prostatectomy. Preoperative management.

The morbidity of radical prostatectomy is minimized by identifying men who are at significant cardiovascular risk and excluding them from the procedure. Preoperative management designed to minimize surgical and medical complications and exposure to allogenic blood products increases the benefit-to-risk ratio of radical prostatectomy over other treatment options for localized prostate cancer.

Anesthesia↗

Post-urethral suspension obstruction.

Urethral obstruction is a consequence of surgery to treat stress incontinence in women. Although its incidence is relatively low, it still presents a challenging problem for the urologist. Recent work has focused on clarifying the etiology and incidence of this condition, as well as providing new definitions on bladder-outlet obstruction in women. In addition, effective, less invasive ways of treating this condition have been described.

Female↗

The role of preoperative epoetin alfa in men undergoing radical retropubic prostatectomy.

PURPOSE: The safety and effects on hematocrit of recombinant human erythropoietin (epoetin alfa) were evaluated in men undergoing radical retropubic prostatectomy. MATERIALS AND METHODS: Between February 1, 1997 and November 2, 1998, 305 men with clinically localized adenocarcinoma of the prostate underwent radical retropubic prostatectomy performed by a single surgeon (H. L.). Of these men 283 with a baseline hematocrit of less than 48% received 600 IU/kg. epoetin alfa 14 days (-14) and 7 days (-7) before radical retropubic prostatectomy. Hematocrit was measured at baseline on day -14, on day -7, just before anesthesia induction on day 0, immediately postoperatively and on the day of discharge home. The number of allogeneic units transfused, and all intraoperative and postoperative complications were recorded. RESULTS: Mean hematocrit at baseline on day -14 and at induction on day 0 was 42.9% and 45.8%, respectively (p = 0.0001). The frequency of hematocrit decreasing, showing no change or increasing 0.1 to 1.9, 2.0 to 3.9 or greater than 4.0 hematocrit points was 16.5%, 0.5%, 23%, 22% and 38%, respectively. Of the men 17% had no increase in hematocrit. A weak correlation existed between baseline hematocrit and the erythropoietic response to epoetin alfa (r2 = 0.06). Mean change in hematocrit after treatment with epoetin alfa in the quartile baseline hematocrit groups 34.2 to 41.4, 41.5 to 43.2, 43.3 to 44.9 and 45.0 to 48.0 hematocrit points was 3.71, 2.45, 3.86 and 1.02 hematocrit points, respectively. Of the surgical candidates 22 (9.1%) achieved an induction hematocrit of greater than 51%. Of the 283 men receiving epoetin alfa 21 (7.4%) also received an allogeneic transfusion. The transfusion rate did not correlate with induction hematocrit. The only adverse cardiovascular event was an uncomplicated postoperative pulmonary embolus. CONCLUSIONS: Our prospective study demonstrates that epoetin alfa given preoperatively in 2 doses of 600 IU/kg. is safe for significantly increasing hematocrit in men before radical retropubic prostatectomy. It is intuitive that the significant increase in hematocrit decreases the requirement for allogeneic blood transfusion.

Adenocarcinoma↗

Phase I trial of multiple cycles of high-dose chemotherapy supported by autologous peripheral-blood stem cells.

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin and paclitaxel with hematopoietic peripheral-blood stem cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with cyclophosphamide, etoposide, and granulocyte-macrophage colony-stimulating factor (GM-CSF). After one cycle of conventional-dose carboplatin and cyclophosphamide with GM-CSF, patients received multiple cycles of high-dose carboplatin (area under the concentration-time curve [AUC], 12 to 20) and paclitaxel (250 mg/m(2)) with PBSC and GM-CSF repeated every 28 days. RESULTS: Twenty-four of 28 patients were assessable for toxicity and clinical outcome. Dose-limiting toxicities were dehydration, diarrhea, and electrolyte imbalances. The maximum-tolerated dose of carboplatin was AUC 16 (equivalent to a median of 1,189 mg/m(2)). The relationship of target AUC to measured AUC was linear (r(2) =. 29; P =.0011). The overall response rate was 96%, with a complete clinical response rate of 67%. The median time to progression from the first PBSC reinfusion was 49.5 weeks (range, 8 to 156+ weeks). CONCLUSION: Multiple cycles of high-dose carboplatin (AUC 16) and paclitaxel (250 mg/m(2)) can be safely administered with GM-CSF and PBSC support. Although this regimen is safe, feasible, and active, the use of multiple cycles of high-dose chemotherapy as front-line treatment remains experimental and should only be used in the context of a clinical trial.

Adult↗

Microscopic benign and invasive malignant neoplasms and a cancer-prone phenotype in prophylactic oophorectomies.

BACKGROUND: The occurrence of approximately 5% of common epithelial malignant tumors of the ovary can be traced to inheritance of risk. One prophylactic strategy to decrease the probability of development of disease in individuals within families where this mendelian-dominant pattern of occurrence is apparent is to remove the ovaries of individuals at risk for ovarian cancer. The procedure, when done for this purpose, is recommended soon after completion of childbearing. PURPOSE: Our goal was to compare the histologic features of the ovaries of women at increased risk for ovarian cancer to those at no known increased risk for the disease. METHODS: Ovaries removed for prophylaxis from 20 women considered to be at increased risk for developing ovarian cancer were examined histologically. During the course of this work, it seemed apparent that these ovaries contained numerous atypical features compared with the expected appearance of normal ovaries. Hence, we expanded the study to include a control group whose ovaries were removed for reasons unrelated to cancer. The study, therefore, was not blinded. The increased risk in the cancer-prone individuals was determined by family history, specifically the presence of at least one first-degree relative and one second-degree relative with ovarian and/or breast cancer and positive linkage or mutational analysis of BRCA1 in some. The difference in mean ages of patients in the control and high-risk groups was not statistically significant. The difference among both groups with respect to the number of atypical features as well as the intensity of those features was ascertained by computing probabilities using Fisher's exact test (two-sided) for rows x columns contingency tables. RESULTS: Two unanticipated microscopic or near-microscopic malignant neoplasms and other benign and borderline tumors were discovered in the ovaries of the high-risk individuals. Of substantial interest was the finding that among the ovaries of high-risk women, 85% presented two or more and 75% presented three or more of the following histologic features: surface epithelial pseudostratification; surface papillomatosis; deep cortical invaginations of the surface epithelium, frequently with multiple papillary projections within small cystic spaces (microscopic papillary cystadenomas); epithelial inclusion cysts, frequently with epithelial hyperplasia and papillary formations; cortical stromal hyperplasia and hyperthecosis; increased follicular activity; corpus luteum hyperplasia; or hilar cell hyperplasia. Two or more or three or more such changes were observed in a lesser percentage (30% or 10%, respectively) of ovaries obtained from the control individuals, with a statistically significant difference (P = .001 or P = .00007, respectively), particularly considering that a detailed determination of a family history of cancer in the control group was not possible. CONCLUSIONS: The frequency of these changes in the high-risk ovaries compared with control ovaries suggests a characteristic histologic preneoplastic phenotype defined by an increased frequency and intensity of the above-described histologic features in the high-risk ovaries. Limited access to numerous small (stage I) ovarian cancers or cancer-prone ovaries by any one pathologist may explain the failure to identify the phenotype in the past. IMPLICATIONS: We suggest that the ovaries removed from ovarian cancer-prone individuals as a preventative measure should be thoroughly examined histologically to identify or rule out microscopic or near-microscopic invasive neoplasms.

Adult↗

Immunohistochemical localization of Lyn (p56) protein in the adult rat brain.

Expression of a sarcoma proto-oncogene, c-lyn, was mapped in the adult rat brain using immunohistochemistry. Lyn protein was prevalent in restricted cell populations of the olfactory bulb and the basal forebrain which included nuclei of accumbens, fundal striatum, bed stria, ventral pallidum and central amygdala as well as deep entorhinal and pyriform cortices. Tightly packed Lyn-positive cells formed discrete multiple stripes crossing perpendicular to the rostral limb of the anterior commissure, and intense masses surrounding the caudal limb. In the thalamus, the habenula, anterodorsal nucleus and medial geniculate body, together with the paraventricular hypothalamic nuclei, had prominent reactive neuronal somata and dendrites in the neuropil. The lateral septal nucleus also had intense Lyn-positive neurons with overlapping dendritic fields. In addition, scattered neurons were evenly distributed throughout the striatum. The red, interpeduncular, auditory and trigeminal tract nuclei were intensely reactive. The cerebellar molecular layer was uniformly labeled except for a few isolated fiber bundles in the lowest part of this layer. The granule cells adjacent to the Purkinje cell layer appeared in reactive patches. In the spinal cord, the posteromarginal nucleus had intense labeling. The significance of this highly localized distribution pattern of Lyn protein may be related to connections forming functional compartments serving signal transduction within specific central nervous system circuitry.

Animals↗

Improved treatment planning for the Syed-Neblett template using endorectal-coil magnetic resonance and intraoperative (laparotomy/laparoscopy) guidance: a new integrated technique for hysterectomized women with vaginal tumors.

The Syed template (Alpha-Omega Services, Bellflower, CA) represents an advance in interstitial gynecologic brachytherapy; however, its appeal is diminished by inaccuracies in target definition secondary to suboptimal imaging of gynecologic tumors and the risk of viscus perforation during a "blind" procedure. Magnetic resonance (MR) scanning with an endorectal coil and computed tomography were studied as a possible tool to improve target definition and maximize treatment planning with Syed templates. Abdominopelvic contents could be visualized directly through a laparotomy incision or indirectly with a laparoscopic video display to allow further target definition and minimize complications associated with blind procedures after hysterectomy. The synthesis of these techniques with Syed template applications was attempted to potentiate the utility of this brachytherapy system. Five patients with apical vaginal tumors which arose after previous hysterectomies (two endometrial cancer recurrences, one recurrent uterine sarcoma, two primary vaginal cancers) were referred for radiotherapy. In three cases, external beam pelvic radiotherapy (median dose, 45 Gy; range, 45-50.4 Gy) was delivered initially. In all cases, the Syed applicator was used for the brachytherapy component of the treatment. In two cases, high-resolution MR images (400 x 400 microns) of the vaginal apex were obtained after insertion of an endorectal surface coil. The images defined the relationships between the template, target volume, bladder, rectum, and intestine. The other three cases were planned with computerized tomography (CT). In all cases, intraoperative examination of the abdominopelvic contents was provided when laparotomy and/or laparoscopy was performed by the surgical team. The median brachytherapy dose prescribed to the isodose envelope covering the target volume was 40 Gy (range, 31-50 Gy). In all cases, the target volumes could be encompassed by the 60 cGy/hr isodose line. Tumor volume estimation was better with MR than CT. Procedure time was shorter with laparoscopy than with laparotomy. In two cases, bowel displacement was performed (one tissue expander, one omental sling) to prevent viscus perforation by interstitial needles. Four of five patients responded completely to the treatment. In three cases, local control was maintained at a median follow-up of 11 months. In conclusion, endorectal coil MRI may be advantageous to CT of the pelvis in that it allows preplanning to be achieved with greater precision and with less planning time. Major intraoperative complications (i.e., perforation of hollow viscus organs) can be avoided when the course of interstitial catheters is visualized from above by the surgical team.(ABSTRACT TRUNCATED AT 400 WORDS)

Brachytherapy↗

Perioperative morbidity of intracavitary gynecologic brachytherapy.

PURPOSE: To define the incidence and severity of perioperative morbidity and its subsequent management with standard tandem and ovoid insertions and to evaluate pretreatment and treatment factors associated with an increased risk of perioperative morbidity. METHODS AND MATERIALS: Ninety-five tandem and ovoid insertions were performed at the Fox Chase Cancer Center between 1985 and 1992 for cervical (n = 91) and endometrial (n = 4) cancer. Patients were placed on antibiotics in 19%, usually for a positive routine preoperative urine culture, but no patient was given prophylactic antibiotic therapy. Deep-vein thrombosis prophylaxis was practiced for 70% of implants and included subcutaneous heparin (40%), graduated compression elastic stockings (16%), and external pneumatic calf compression (14%). All patients were placed on prophylactic diphenoxylate hydrochloride, with doses ranging from three to eight tablets/day. RESULTS: Intraoperative complications were seen in 3% of implants and included two perforations and a vaginal laceration in two patients. Twenty-four percent of implants (16 patients) developed temperatures of > 100.5 (range 100.6 to 103), although only one patient required implant removal because of fever. Management of fever included antibiotics in 35% and acetaminophen only in 65%. Five implants (5%) were removed emergently secondary to presumed sepsis (n = 1), exacerbation of chronic obstructive pulmonary disease, hypotension, change in mental status (n = 3), and myocardial infarction/congestive heart failure (n = 1). No patient developed a deep-vein thrombosis, pulmonary embolism, gastrointestinal obstruction, or died of a postoperative complication. Univariate analysis of pretreatment and treatment factors revealed older age (p < 0.005) and spinal/epidural anesthesia (p < 0.02) to be associated with increased perioperative morbidity, and older age (p < 0.05) and higher ASA classification (p < 0.02) to be associated with severe complications requiring removal of implant. Multivariate analysis revealed only older age (p < 0.01) to be significantly related to perioperative morbidity. CONCLUSIONS: Fever of > 100.5 was seen in 24% of implants and can be managed successfully without removal of the implant in 96% of cases. Use of antibiotics preoperatively and intraoperatively did not reduce the risk of perioperative temperature elevation. Use of routine diphenoxylate hydrochloride prophylaxis was tolerated without ileus or gastrointestinal obstruction clinically. Although routine deep-vein thrombosis prophylaxis is reasonable, our data would support a low risk of deep-vein thrombosis for untreated patients. Severe perioperative morbidity necessitated premature implant removal in only 5% of cases and was related to older age in multivariate analysis.

Adult↗

A common region of deletion on chromosome 17q in both sporadic and familial epithelial ovarian tumors distal to BRCA1.

Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans approximately 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.

Base Sequence↗

Volumetric analysis of small bowel displacement from radiation portals with the use of a pelvic tissue expander.

PURPOSE: Many techniques and devices have been used in an attempt to minimize gastrointestinal morbidity of pelvic irradiation. The value of a temporary intrapelvic tissue expander to displace small bowel from pelvic radiotherapy fields was analyzed by comparing volumetric treatment parameters of patients with and without such a device. METHODS AND MATERIALS: Between 1983 and 1991, 77 patients with a diagnosis of endometrial (n = 35), colorectal (n = 41), or anal carcinoma (n = 1) received adjuvant postoperative radiotherapy after undergoing treatment planning simulation with the use of small bowel oral contrast medium. Fourteen of these patients underwent surgical placement of a temporary intrapelvic tissue expander prior to radiotherapy, and 63 patients did not. Small bowel volume within the treatment portals was measured for both initial pelvic and conedown fields for all cases, and compared between the two patient groups. RESULTS: The volume of small bowel within the initial pelvic fields receiving full dose irradiation was significantly less among patients with a tissue expander. For patients with a tissue expander, mean volume receiving full dose irradiation was 25 cm3 (median 0 cm3, range 0-297 cm3), whereas the corresponding volume was 239 cm3 (median 181 cm3, range 0-943 cm3) without a tissue expander (p < .0001). A similar reduction of irradiated small bowel volume was noted in the conedown fields with the use of a tissue expander (p = .07). Volumes receiving less than full dose irradiation were also less within the initial pelvic (p = .0001) and conedown (p = .002) fields with a tissue expander. Multivariate analysis of patient and treatment-related parameters showed the use of a tissue expander to be the only factor correlated with decreased small bowel volume within the treatment field (p = .003). Morbidity related to placement and removal of the tissue expander was acceptable. Acute radiation-related morbidity was significantly less in patients irradiated with a tissue expander in place (p < .001). CONCLUSIONS: Placement of an intrapelvic tissue expander was correlated with decreased small bowel volume within the radiotherapy treatment field. Diminished radiation-induced acute gastrointestinal morbidity was noted with use of a tissue expander.

Aged↗

Intraperitoneal cisplatin and etoposide in peritoneal mesothelioma: favorable outcome with a multimodality approach.

Ten patients with histologically documented peritoneal mesothelioma were treated with intraperitoneal cisplatin 200 mg/m2, sodium thiosulfate rescue and etoposide 65-290 mg/m2 every 4 weeks for a maximum of six cycles. All had epithelial or mixed epithelial-fibrous histology. Toxicity was tolerable, with 50% sustaining grade 3 or 4 granulocytopenia. There was one episode of neutropenic fever. Grade 2 peripheral neuropathy occurred in one patient, grade 1 in five patients. Complete remission occurred in one of five patients with measurable disease. Median survival for patients whose tumors were surgically debulked to < 2 cm residua prior to treatment was 22 months, while it was 5 months for those with measurable, surgically inaccessible disease (P = 0.0731 by Cox regression proportional hazard model). These data suggest that patients who present with resectable disease may benefit from an aggressive adjuvant approach. This possibility warrants prospective testing in a randomized clinical trial.

Adult↗

The justification for a surgical staging system in endometrial carcinoma.

Three hundred and one patients with endometrial carcinoma who were surgically staged and treated postoperatively with irradiation at the Fox Chase Cancer Center or the Hospital of the University of Pennsylvania were retrospectively substaged by the 1988 FIGO staging system. For pathological stage I endometrial carcinoma, FIGO substage (IA/IB vs. IC) in addition to depth by thirds (< or = 2/3 vs. > 2/3), grade (1 or 2 vs. 3), age (< or = 60 vs. > 60), and type of postoperative irradiation (vaginal alone vs. external +/- vaginal) were predictive for 5-year cause-specific survival in univariate analysis. For all pathological stages, excluding IIIB and IV endometrial carcinoma, FIGO stage (I or II vs. III) in addition to depth by thirds (< or = 2/3 vs. > 2/3), grade (1 or 2 vs. 3), age (< or = 60 vs. > 60), and type of postoperative irradiation (vaginal alone vs. external +/- vaginal) were predictive for 5-year cause-specific survival in univariate analysis. Clinical stage (I vs. II or III) was not a significant predictor of outcome in univariate analysis. Multivariate analysis of the above factors revealed FIGO stage in addition to grade, age and depth by thirds to be independent predictors of outcome. In conclusion, the FIGO surgical staging system better predicts outcome compared with the prior clinical staging system, although the FIGO substaging needs refinement. Grade, age, and depth by thirds are equally important prognostic factors in addition to FIGO stage and can add to the predictive value of the current FIGO staging system.

Endometrial Neoplasms↗

Pharmacologic study of etoposide and cisplatin by the intraperitoneal route.

Based on the previous demonstration of a high peritoneal-to-plasma ratio of drug exposure for intraperitoneal (IP) etoposide, the authors performed a clinical/pharmacokinetic trial of etoposide (600 mg/m2) in combination with cisplatin (100 mg/m2). The drugs were administered concurrently IP, and allowed to dwell for 4 hours, after which the peritoneum was drained. Six patients received 13 cycles of treatment. Grade 4 neutropenia occurred in three patients; toxicity was otherwise moderate. Plasma etoposide concentrations reached a peak at 4.2 +/- 2.5 hours and declined exponentially with a terminal half-life of 9.5 +/- 3.6 hours. Peritoneal etoposide concentrations declined monoexponentially with a half-life of 3.7 +/- 2.6 hour. The calculated peritoneal-to-plasma ratio of unbound etoposide was 35. The plasma and peritoneal half-lives of ultrafilterable cisplatin were 21.7 +/- 14.1 hours and 1.8 +/- 0.7 hours, respectively. The peritoneal/plasma area under curve AUC ratio was 18.3. These pharmacokinetic indices for both drugs are consistent with those obtained with the use of each drug as a single agent. Thus, the concomitant use of one does not alter the pharmacokinetic activity of the other. The high AUC ratios support the further clinical development of these drugs in combination in the intraperitoneal setting.

Adenocarcinoma↗

Rectovaginal fistula or perineal and anal sphincter disruption, or both, after vaginal delivery.

The management of 52 patients with rectovaginal fistula or perineal and anal sphincter disruption, or both, after vaginal delivery is presented. Adequate physical intestinal preparation and postoperative diet and intestinal care are stressed. Preservation of perineal integrity is suggested whenever possible. Closure in anatomic layers is the technique of choice and sphincterotomy is advised in all instances of anal sphincter anastomosis. The technique for repair of an extensive cloacalike lesion is described in detail, as are three unusual complications of operation. Satisfactory anatomic and functional results were obtained in 100 per cent.

Adult↗

Pyloric stenosis and eosinophilic gastroenteritis in infants.

Eosinophilic gastroenteritis is known to cause gastric outlet obstruction in adults, but has been reported only rarely in infants presenting with pyloric stenosis, a common form of gastric outlet obstruction in children. We describe two infants who presented with classic clinical and radiographic evidence of pyloric stenosis and who were found to have histologic evidence of eosinophilic gastroenteritis on gastric antral biopsies. Their presentation is compared with the clinical and laboratory findings of 47 other infants with pyloric stenosis.

Dietary Proteins↗