NMDA receptor antagonists enhance 5-HT2 receptor-mediated behavior, head-twitch response, in PCPA-treated mice

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic 5-HT2 receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompetitive (MK-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsynaptic 5-HT2 receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin 5-HT2 receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the postsynaptic 5-HT2 receptors.     

Intraoperative laparoscopic complications

PURPOSE: The aim of this study was to assess various intraoperative and postoperative complications associated with laparoscopic colorectal surgery. Specifically, the impact of surgical experience and procedure type on complications was analyzed. METHODS: All patients who underwent laparoscopic surgery were analyzed by age, sex, surgical indications, procedure performed, procedure length, intraoperative and postoperative complications, incidence and causes for conversion, duration of postoperative ileus, and length of hospital stay. Patients were classified for type of procedure and chronologically into four consecutive groups. Procedures were also categorized into four different groups: GI, total abdominal colectomies; GII, segmental resections; GIII, diverting procedures; GIV, others (abdominoperineal resection, Hartmann's creation or closure, anterior resection, and rectopexy). RESULTS: Between August 1991 and October 1995, 167 patients of a mean age of 49.6 (15–88) years underwent laparoscopic colorectal procedures. All procedures were electively performed. Common indications for surgery included inflammatory disease in 70 (42 percent), neoplasia in 56 (33 percent), functional bowel disorders in 30 (18 percent), and other forms of colorectal disorders in 11 (7 percent) patients. The most significant variable affecting intraoperative laparoscopic complication rate was surgical experience measured as the time interval during which surgery was performed (P=0.02). Total complication rate decreased from 29 percent during the first period to 11 percent by the second period (P<0.04) and 7 percent during the third period (P<0.005). Thus, the learning curve appeared to have required more than 50 cases to achieve. Moreover, even after performance of 94 (1991–1993) procedures in GI and GIV, these procedures were associated with higher complication rates than were those procedures in GII and GIII (P=0.04). CONCLUSION: Surgical experience and case selection are the most critical variables by which the surgeon can decrease the intraoperative laparoscopic complication rate.     

Prospective comparison of open<Emphasis Type="Italic">vs</Emphasis>. laparoscopic colon surgery for carcinoma

Laparoscopy for colonic diseases began in 1990 and has established a role in benign disease. Early observations and experiences demonstrated feasibility of laparoscopic surgery for a variety of colonic disease processes, but the applicability to colonic carcinoma was unclear. METHODS: In 1990, we began a comparative study of open (OCR)vs.laparoscopic (LCR) approach to colon cancer. The study progressed 65 months, with 224 patients in OCR group and 191 patients in LCR group. Parameters studied are stage, location, length of specimen, number of lymph nodes resected, margins, postoperative course, wound complications, recurrence rates, and immediate and long-term survival. OCR were standardized by one group, and LCR were standardized by a second group. All patients undergoing LCR were given freedom to choose either OCR or LCR, and informed consent was obtained. RESULTS: Equal or greater lymph node retrieval, resections, and distal margins were evident with LCR. Benefits with LCR were shown with shorter hospitalization (5.7vs.9.7 days), less blood loss, less wound problems (1vs.14), and quicker return of bowel function. Survival, recurrence, and death rates were essentially the same. There were no trocar implants in the LCR group. CONCLUSION: After five years, this study shows that laparoscopy does no harm to the patient, offers comparable oncologic resections, and seems to be patient-friendly, with less pain, quicker return of bowel functions, shortened hospitalization, and quicker return to full activity.     

Recent developments in indocyanine green angiography

For the past year, indocyanine green angiography has been applied to evaluation of choroidal neovascularization, pigment epithelial detachment, retinal vascular disorders, and choroidal diseases and tumors. These applications have expanded the potential use of this technique. The relative safety of indocyanine green angiography has contributed to its continued wide-spread application.     

Common Sheath Reimplantation Yields Excellent Results in the Treatment of Vesicoureteral Reflux in Duplicated Collecting Systems

Purpose

We evaluated our 10-year experience with the surgical treatment of vesicoureteral reflux in uncomplicated duplicated collecting systems.

Materials and Methods

Between 1984 and 1994, 54 refluxing renal units (8 bilateral) in 37 female and 9 male patients required surgery. Patient age ranged from 7 months to 17 years (average 4.9 at surgery). Postoperative followup (average 14.2 months) included voiding cystourethrography and renal sonography or excretory urography.

Results

Common sheath ureteral reimplantation via an intravesical approach was performed in 48 of the 54 refluxing renal units. Of the remaining 6 renal units detrussorrhaphy was performed in 4, and ureteroureterostomy combined with ureteral reimplantation and partial lower pole nephrectomy were done in 1 each. Two treated renal units had persistent postoperative vesicoureteral reflux, which resolved after subureteral polytetrafluoroethylene (Teflon) injection. No renal unit had postoperative hydronephrosis. Contralateral reflux was identified in 1 patient who underwent unilateral reimplantation. Our overall success rate was 96 percent for the surgical correction of vesicoureteral reflux in uncomplicated duplicated collecting systems. Common sheath reimplantation had a 98 percent success rate.

Conclusions

Although a duplicated collecting system increases the risk for surgical treatment, the presence of a duplication anomaly does not adversely affect surgical outcome. Modifications of procedures commonly performed in the surgical treatment of single system reflux to accommodate common sheath reimplantation have excellent surgical results with minimal morbidity.     

Combined finasteride and flutamide therapy in men with advanced prostate cancer

Objectives

To evaluate the efficacy of combined finasteride and flutamide therapy in men with advanced prostate cancer by determining (1 ) the short-term tolerability of finasteride monotherapy and its effect on serum prostate-specific antigen (PSA) and hormone (testosterone, dihydrotestosterone) levels, and (2) the effects of the addition of flutamide on tolerability and on serum PSA and hormone levels.

Methods

Thirteen hormone-naive men with advanced prostate cancer (4 with Stage D2, 1 with Stage D1, 1 with Stage DO, 7 with rising PSA levels after radical prostatectomy [n = 2]or definitive radiation therapy [n = 5]) were initially treated with 5 mg finasteride daily. Flutamide (250 mg three times a day) was added after serum PSA levels stabilized.

Results

Finasteride alone (median 5 weeks) had no significant effect on serum PSA levels (P>0.05). Combined finasteride and flutamide resulted in a mean 91% reduction in serum PSA levels, with 85% of men achieving a nadir serum PSA level of less than 4.0 ng/mL and 46% achieving undetectable levels (0.2 ng/mL or less). Finasteride alone had no significant effect on serum testosterone levels (P>0.05) but did result in a mean 74% reduction in serum dihydrotestosterone levels. Combined finasteride and flutamide resulted in a mean 56% increase in serum testosterone levels but had no additional effect on serum dihydrotestosterone levels (P>0.05). Side effects occurred in 85% (gynecomastia or breast tenderness in 62% [8 of 13]and diarrhea in 23% [3 of 13]) of men on combined therapy. Potency was preserved in 66%. Combined finasteride and flutamide therapy was withdrawn from 15% (2 of 13) because of flutamide-induced diarrhea and from 23% (3 of 13) because of disease progression. All remaining patients (8 of 13) have serum PSA levels below 4.0 ng/mL and 4 of these 8 have undetectable levels. These men have received combined finasteride and flutamide for a median 11 months (range 6 to 19).

Conclusions

Finasteride monotherapy is inadequate therapy for advanced prostate cancer, but combined finasteride and flutamide may be a reasonable alternative for men with advanced prostate cancer who refuse conventional hormone therapy.     

Equity and extramarital sexuality

Equity theory has recently been found to be a useful framework for under-standing the effects of imbalances in intimate contractual relationships such as marriage. Equitable couples seem to be happier, more satisfied with their relationship, and more confident that it will last than are their more mismatched, i.e., inequitable, counterparts. Furthermore, inequitable couples predictably act to set things right in their marriage. They either restore actual equity to the relationship or psychologically set their relationship in balance. If neither works, they may leave the field. Extramarital sex may be viewed as an equity restoration mechanism in that (1) it may be used by the deprived partner to achieve actual equity, (2) it may indicate a partner's readiness to leave the relationship because he feels he can do better, or (3) it may represent a desire to achieve equity in an alternative relationship(s) when inequity pervades the primary one. The hypothesis that the inequitable/underbenefited group should be more likely than the equitable group or the inequitable/overbenefited group to have engaged in extramarital sex was tested using data from a large-scale Psychology Todayquestionnaire. The results indicated that men and women in inequitable/under-benefited relationships had more extramarital affairs and began their extramarital activities earlier than did men and women in equitable and inequitable/over-benefited relationships. Alternative explanations of this finding, sex-role demands and length of the relationship, are explored and discarded as untenable. Research supported in part by National Institute of Mental Health Grant MH 26681.     

Postsurgical, chronic, nonprogressive, cutaneous ulcers: a possible variant of pyoderma gangrenosum associated with diabetes mellitus

Two patients developed persistent ulcers on the trunk after cutaneous surgery. Both had "chemical" diabetes mellitus. Bacteriologic and histopathologic studies of the ulcers were not revealing of cause. The characteristics of the ulcers are described, and are contrasted with typical lesions of pyoderma gangrenosum and Meleney's postoperative progressive synergistic bacterial gangrene. We believe these patients had variant lesions of pyoderma gangrenosum.     

The application of population pharmacokinetic analysis to large scale clinical efficacy trials

Summary Results have been presented that demonstrate the ability to conduct population pharmacokinetic analysis as a component of clinical efficacy and safety trials. This method of analysis offers the potential to determine the pharmacokinetics of a drug in the actual patients receiving medication and to evaluate relationships between pharmacokinetics and drug action. However, active involvement in the protocol design, and data collection process are required to ensure the quality of the resultant data set.     

A unique case of three autografts for acute myelogenous leukaemia with subsequent long term survival in second remission

We report here a patient with acute mycloid leukaemia who relapsed 20 months after undergoing a double autograft procedure in first remission. He was reinduced and subsequently underwent a third autologous bone marrow transplantation in second remission using bone marrow harvested in second remission and a Busulphan and Cyclophosphamide conditioning regimen. Although the engraftment was very slow, he has remained in second remission for 34+ months. This case demonstrates that durable disease-free survival can be attained by a second preparative therapy, even in second remission, for patients relapsed after autologous bone marrow transplantation.