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Biomedical subjects

M L Corman

Publications and source records attributed to M L Corman.

At least 19 recordsLinked to original sources
PubMed1995

Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives.

The erbB-2 oncogene encodes a transmembrane protein tyrosine kinase which plays a pivotal role in signal transduction and has been implicated when overexpressed in breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3 cells in culture. Chemistry efforts to modify selectively the quinoid moiety of GDM afforded derivatives with greater potency in vitro and in vivo. Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2 (FRE/erbB-2). Specifically, dosed intraperitoneally at 100 mg/kg, 17-(allylamino)-17-demethoxygeldanamycin and other 17-amino analogs were effective at reducing p185 phosphotyrosine in subcutaneous flank FRE/erbB-2 tumors. Modifications to the 17-19-positions of the quinone ring revealed a broad structure-activity relationship in vitro.

Animals↗
PubMed1995

erbB-2 oncogene inhibition by geldanamycin derivatives: synthesis, mechanism of action, and structure-activity relationships.

Overexpression of the erbB-2 oncogene has been linked to poor prognosis in breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3 cells in culture. Chemistry efforts to modify selectively the ansa ring of GDM afforded derivatives with greater potency in vitro and in vivo. Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2. Functional group modification in the ansa ring was performed stereoselectively and regiospecifically without the need for protection strategies. Essential functional groups that were required for anti-erbB-2 activity were the 7-carbamate and the 2,3-double bond. Modification of the functional groups at the other positions was permitted. Structure-activity relationships are described for 1-5-, 7-9-, 11-, 15-, and 22-substituted geldanamycins.

Animals↗
PubMed1991

Prospective, randomized trial of the biofragmentable anastomosis ring. The BAR Investigational Group.

A randomized trial was undertaken to compare the biofragmental anastomotic ring (BAR) with conventional intraperitoneal colorectal anastomotic techniques. Patients were randomized into one of two schemes: BAR versus sutured or BAR versus stapled anastomosis. There were 782 patients entered into the study and 283 patients (36%) had a sutured anastomosis, 104 patients (13%) had a stapled anastomosis, and 395 (51%) had the BAR. Comparison of the BAR with combined suture and stapled controls revealed no significant differences in wound complication, abscess rate, bleeding, anastomotic leaks, ileus, obstruction, or deaths. There were no differences in return of bowel function, return to normal diet, or hospital stay. Intraoperative difficulties occurred in 46 BAR patients (17%), and this was significantly higher (p less than 0.001) than for sutured (3%) but not for stapled anastomoses (11%). The occurrence of these problems did not adversely effect the outcome. The data suggest that the BAR is a safe, satisfactory alternative to sutured or stapled colorectal anastomoses.

Adolescent↗
PubMed1989

Comparison of the Valtrac biofragmentable anastomosis ring with conventional suture and stapled anastomosis in colon surgery. Results of a prospective, randomized clinical trial.

In a randomized, prospective study of 438 patients, the safety and efficacy of the Valtrac biofragmentable anastomotic ring (BAR) was compared with stapling and with conventional suture techniques. There was no significant difference in the morbidity, mortality, and clinical course of the patients. The BAR can effect reestablishment of intestinal continuity somewhat more rapidly, but its major advantage is its uniform applicability to all areas of the intestinal tract, except the low rectum.

Adolescent↗
PubMed1988

Long-term results of open and closed sphincterotomy for anal fissure.

Three hundred fifty patients who underwent open or closed lateral internal anal sphincterotomy for acute or chronic anal fissure between January 1981 and June 1985 were reviewed. Minimum follow-up was 14 months (mean, 37 months). No patient underwent an additional procedure at the time of sphincterotomy. Twenty-one failed to heal or developed a recurrence in the interval (6 percent). Five of these individuals were found subsequently to have Crohn's disease. Excluding these patients, the incidence of nonhealing was 4.6 percent. Eight patients (2.3 percent) developed postoperative infections requiring drainage, one half of which were associated with fistulas. Sixty patients (17 percent) complained of incontinence for flatus or feces. For two thirds, this was transient. There was no statistically significant difference in rate of healing or morbidity when comparing the open with the closed method.

Abscess↗
PubMed1988

Rectal prolapse. Surgical techniques.

The varied operative procedures available for the treatment of rectal prolapse can be confusing. Most of the maneuvers are relatively esoteric and can be performed successfully only by the few surgeons who have developed the specialized techniques. It is recommended, therefore, that the surgeon who is less experienced with rectal prolapse adopt one of the standard operations. A rectopexy or suspension procedure without resection can be performed safely with good results, low morbidity, and a low mortality rate. Anterior resection with or without sacral fixation, an operation familiar to most surgeons, also offers an excellent cure rate. The Thiersch-type approach should probably be reserved for those patients who cannot tolerate laparotomy. The material chosen should be one of the commercially available synthetic products; wire should not be used. The Silastic-impregnated Dacron prosthesis for this operation has some potential benefit, especially for the incontinent patient. Results of further studies are awaited.

Anal Canal↗
PubMed1986

Are we really operating on diverticulitis?

The results of elective surgery for diverticulitis in 100 consecutive patients were reviewed. Follow-up was possible in 82 individuals. Seventy-seven (94 percent) were improved. There was no inflammatory change apparent on histologic examination of the resected specimens in 24 percent of patients. These individuals were less likely to have favorable results. There are a number of preoperative factors which may predict the likelihood of a successful surgical outcome.

Adult↗
PubMed1985

Anal incontinence following obstetrical injury.

Insufficient attention has been given to the anatomical anomaly as a predisposing factor for obstetrical injury. The operative approach and results in 28 patients indicate that excellent function can be achieved by recognition of the deformity and by the appropriate repair.

Adult↗
PubMed1985

Rectal prolapse in children.

Rectal prolapse in children is an uncommon clinical entity in western countries. Treatment is generally supportive with surgery reserved for the intractable case. If operative intervention is advised, it should consist of one of several limited procedures that can be safely performed with low morbidity: anal encirclement, presacral packing, sclerosing injection, or linear rectal cauterization.

Child, Preschool↗
PubMed1982

Mortality, morbidity, and patterns of recurrence after abdominoperineal resection for cancer of the rectum.

Records of 230 patients who underwent abdominoperineal resection between 1963 and 1976 were reviewed. The median age of the patients was 62 years. The mortality rate was 1.7 per cent, and the morbidity rate was 61 per cent. One hundred eighty patients were followed for five to 13 years to identify patterns of recurrence. Ten-year survival for Dukes' A, B, and C lesions was 83 per cent, 57 per cent, and 31 per cent, respectively. Seventy-eight patients (43 per cent) had recurrent cancer; 10 per cent had local lesions, and 33 per cent had distant lesions. Dukes' B lesions had a greater latency for local recurrence than Dukes' C lesions. Dukes' A lesions with distant recurrence had a greater latency than Dukes' B or C lesions. Once recurrence was established, the survival rate was not significantly different, regardless of Dukes' stage or local or distant site. Radiation therapy for established local recurrence or chemotherapy for established distant recurrence did not seem to alter survival rates.

Adult↗
PubMed1982

Electrocoagulation of rectal cancer.

Electrocoagulation is an effective treatment modality for localized cancer of the distal rectum. Proper selection remains the key to successful treatment. Of potentially curable patients with cancer of the rectum followed up for a median of five years, 69 per cent had no evidence of cancer at the end of the study period. Gross tumor morphology defined two distinct groups with regard to outcome after electrocoagulation. Ninety-two per cent of patients with polypoid/exophytic tumors as compared to 33 per cent of patients with ulcerative lesions had successful treatment. Based on these results, the authors believe that lesions that are exophytic represent early cancers with a low incidence of nodal spread and, as such, can be treated by electrocoagulation with confidence. As a palliative measure, the the authors found electrocoagulation to yield equivocal results.

Adenocarcinoma↗