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Biomedical subjects

R A Malt

Publications and source records attributed to R A Malt.

At least 109 records · Page 6Linked to original sources

Colostomy closure promotes cell proliferation and dimethylhydrazine-induced carcinogenesis in rat distal colon.

The influence of adaptive cell proliferation on colonic carcinogenesis was studied in male Fischer rats with a defunctioning transverse colostomy that was closed 4 wk later. Control observations were made in other rats after colonic transection, repeated at 4 wk, after laparotomy alone, or after permanent colostomy. Tumors were induced by 1,2-dimethylhydrazine (total dose, 300 mg/kg) over 11 wk, starting 2 days after the second operation. After creation of the colostomy, amounts of protein, RNA, and DNA in the distal colon halved in 4 wk (p less than 0.001), but returned to normal 7 days after restoration of colonic continuity. This reactive hyperplasia promoted the development of distal colonic carcinomas, as compared with rats having repeated transection of the bowel (incidence 32% vs. 6%; p less than 0.03). Although the amounts of protein and nucleic acid in the proximal colon were unchanged by transverse colostomy, values increased by 18%-59% 4 wk after colostomy closure (p = 0.05-0.002); nonetheless, the yield of tumors in this segment was unaltered. Suture-line cancers were commoner after repeat transection than after colostomy closure (76% vs. 39%; p less than 0.01). These data confirm the promotional effect of increased cell proliferation on intestinal carcinogenesis.

Animals↗

A prognostic model for clinical stage I melanoma of the lower extremity. Location on foot as independent risk factor for recurrent disease.

Thirteen variables were studied to determine their usefulness in predicting recurrent disease in 158 patients with stage I melanoma of the lower extremity. A Cox proportional hazards analysis demonstrated that three variables were independent risk factors for recurrent disease in these patients: (1) thickness, in millimeters, of the primary tumor (P = 0.000009), (2) primary tumor location on the foot (P = 0.0003), and (3) the number of mitoses/mm2 (P = 0.0244). Life-table analyses of patient subgroups defined by different combinations of these three variables demonstrated that thick (greater than or equal to 3.0 mm) melanomas of the foot were associated with recurrent disease much more frequently than tumors of similar thickness located on the thigh or calf. These data provide guidelines that can be used to evaluate results of surgical and/or adjuvant therapy studies for patients with melanoma of the lower extremity.

Foot Diseases↗

Pseudotumor at the confluence of the hepatic ducts as a pitfall of percutaneous transhepatic cholangiography.

Four patients with jaundice who had misleading diagnoses as a result of percutaneous transhepatic cholangiography are reported upon. Three of these patients actually had calculous disease and the fourth had pancreatic disease. The levels of obstruction were also roentgenographically inaccurate in three of the four patients. The primary cause of the error appears to be poor mixing of the contrast material with viscid stagnant bile, resulting in blurred definition and failure of the contrast material to traverse the common bile duct.

Aged↗

Synthesis and conservation of ribosomal proteins during compensatory renal hypertrophy.

The rate of synthesis of ribosomal proteins was investigated as an index of the rate of production of ribosomes in mouse kidney during the first few days after contralateral nephrectomy. Compensatory renal hypertrophy was not associated with a major increase in the synthetic rate of ribosomal proteins and rRNA. Instead, the ratio of the rate of ribosomal-protein synthesis to that of total protein synthesis remained nearly constant. The conformation of glutaraldehyde-fixed ribosomes and ribosomal subunits was unchanged. During the early stages of compensatory renal hypertrophy the accretion of rRNA is due largely to conservation of ribosomes that would otherwise have been degraded.

Animals↗

Nerve growth factor: acceleration of the rate of wound healing in mice.

Earlier studies have shown that removal of the submandibular glands of mice retards the rate of contraction of experimentally induced wounds and that communal licking of wounds accelerates contraction in intact animals [Hutson, J. M., Niall, M., Evans, D. & Fowler, R. (1979) Nature (London) 279, 793-795]. In the light of the observation that nerve growth factor (NGF) is secreted in high concentrations in mouse saliva, we have studied the effect of topically applied high molecular weight nerve growth factor (HMW-NGF) upon the rate of wound contraction in sialoadenectomized animals. Results show that HMW-NGF significantly accelerates the rate of wound contraction and that this phenomenon is probably dependent upon the enzymic activity of the protein. Neither diisopropyl fluorophosphate-inactivated NGF nor 2.5S NGF [isolated according to Bocchini, V. & Angeletti, P. U. (1969) Proc. Natl. Acad. Sci. USA 64, 787-794] displays this biological activity. Thus, it may be that one of the physiological roles of NGF in saliva is to promote wound healing by the licking process.

Animals↗

Differences in healing of skin wounds caused by burn and freeze injuries.

Circular, full-thickness dermal burn- and freeze-produced wounds were produced in rats to compare the difference in healing between the two types of thermal injuries. Contraction did not occur in wounds (n = 30) caused by freezing, while burn wounds (n = 30) contracted to less than one-third of original size by 21 days after injury. If the centers of the freeze-produced wounds (n = 12) were excised, contraction would then occur and proceed at the same rate as an open wound. Histologically, the degree of initial tissue destruction by the two types of injuries was similar. The burn wound contained only half the amount of collagen found in the freeze-produced wound. There was a greater and more rapid replacement of collagen in the burn wounds. With both injuries, the highest concentration of collagen was found on the fifteenth day and returned to normal by the twenty-eighth day. The burn wound contained three times the amount of collagen in normal skin, while the freeze-produced wound contained only 1 3/4 times the amount in normal skin. Contraction does not seem to occur in the healing of the freeze-injured skin because the slow removal and replacement of the residual matrix prevents contraction.

Animals↗

Mallory-Weiss syndrome. Evolution of diagnostic and therapeutic patterns over two decades.

During a 19-year period ending December 1978, we treated 40 patients with upper gastrointestinal bleeding secondary to the Mallory-Weiss syndrome. Thirty patients had the triad of vomiting, hematemesis and alcoholism. The presence of lacerations within the gastric cardia was associated with the presence of hiatal hernia (p = 0.03). Endoscopic examinations demonstrated 32 of 38 additional upper gastrointestinal lesions associated with the syndrome that could have been mistaken as the actual source of hemorrhage. During the second decade, as compared with the first decade, widespread use of fiberoptic esophagogastroscopy led to the identification of the bleeding lacerations in 71% of the patients (versus 47% in the first decade) and in 80% (versus 0% in the first decade) of the patients who required an operation to control the bleeding. Although there was a 7.5% mortality rate in the two decades, the incidence of operative treatment tended to decrease (42-24%; p = 0.13). More impressive were the decreases in transfusions (14 units to 5 units per patient) and in delays before surgery (38 hours to 17 hours) (p equal to 0.05). Improved endoscopic diagnosis facilitates prompt and economic treatment.

Aged↗

Left intrahepatic cholangiojejunostomy for proximal obstruction of the biliary tract.

Good palliation from high neoplastic obstruction of the biliary system was achieved by direct anastomosis of the duct draining hepatic segment III to a Roux-en-Y loop of jejunum in six patients. Roentgenologically guided transcutaneous drainage of intrahepatic ducts may be desirable as a preliminary to surgical drainage in severely icteric patients. With improvements in methods of transcutaneous intubation, the selection of proper patients for surgical drainage will be a fine point of judgment.

Adult↗

Contrasting effects of subtotal enteric bypass, enterectomy, and colectomy on azoxymethane-induced intestinal carcinogenesis.

Compensatory hyperplasia after extensive loss of functioning small or large intestine might predispose to the development of neoplasia in the residual adapted bowel. To test this hypothesis, male Fischer rats were randomized to receive 85 to 90% jejunoileal resection or bypass, subtotal colectomy, or no operation (controls). One week later, the first of six weekly s.c. injections of azoxymethane (15 mg/kg/week) was given. At the 36th week postoperatively, mean body weight after enterectomy or colectomy it was 78 to 79% of control. Adaptation after all three operations was characterized by 22 to 84% increments in villous height and crypt depth in the residual functioning ileum (p = 0.05 to 0.001); the depth of colonic crypts was unchanged. Fewer rats developed intestinal tumors after enteric bypass (36%) than after any of the other treatments (80 to 91%) (p = 0.01 to 0.001); the depth of colonic crypts was unchanged. Fewer rats developed intestinal tumors after enteric bypass (36%) than after any of the other treatments (80 to 91%) (p = 0.01 to 0.001). Compared with controls, bypass reduced the number of colonic tumors by 77% (p less than 0.001). Although resection did not affect colonic tumor yield, it tripled the incidence of tumors in the duodenum and jejunum (p = 0.025). Colectomy promoted rectal carcinogenesis (p less than 0.05). Anastomotic tumors were commoner after intestinal resection. the lower frequency of tumors after jejunoileal bypass contrasts with enhanced carcinogenesis after enterectomy or colectomy. Profound reduction in body weight may prevent the promotional effect of adaptive hyperplasia.

Adaptation, Physiological↗

Obstructing phytobezoar of an intrahepatic bile duct.

Drainage of a choledochal cyst with a cystogastrostomy allowed food to reflux into the liver, where it obstructed a major right hepatic duct and produced recurrent cholangitis. Partial hepatectomy was necessary for relief. Drainage of choledochal cysts with a long Roux-en-Y loop seems advisable.

Adult↗

Noncoordinate regulation of cytoplasmic RNA in compensatory renal hypertrophy.

To examine the regulatory role of mRNA in compensatory renal hypertrophy, the accumulation and decay of [3H]orotic acid in poly(A)-containing mRNA in mouse kidney was analyzed after unilateral nephrectomy during the period of maximal rRNA accretion. The distribution of radioactivity between newly synthesized poly(A)-containing and poly(A)-lacing polysomal RNA was altered, but no differences in mRNA half-life were observed in growth compared with effects of sham nephrectomy. Radioactivity in polysomal polyadenylated RNA was diminished by approximately 25% during growth where mice were labeled after nephrectomy, but if mice were labeled 18 h before operation, no difference was noted. Thus, accumulation of newly synthesized poly(A)-containing mRNA relative to RNAs that lack poly(A) is changed early in the course of renal hypertrophy. This noncoordinate regulation may represent a control mechanism effective early in induced cell growth involving mRNAs that lack poly(A).

Animals↗