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Biomedical subjects

G Efron

Publications and source records attributed to G Efron.

At least 37 records · Page 2Linked to original sources
PubMed1984

High arginine levels in intravenous hyperalimentation abrogate post-traumatic immune suppression.

Trauma victims often suffer immune system failure. Oral arginine has strong immune-enhancing properties. The metabolic, hormonal, and immune effects of increasing concentrations of arginine as part of post-trauma intravenous hyperalimentation (IVH) were studied. Groups of 11-14 rats, 275-350 g, underwent jugular vein catheterization and bilateral closed femoral fractures under anesthesia. IVH was started immediately postinjury at a rate of 0.8-1 ml/100 g body wt/hr and continued for 5 days. Twenty percent dextrose and three different amino acid mixtures were given as follows: (A) FreII (1.55 g ARG/1); (B) FreIII (4.05 g ARG/1); (C) modified FreIII (7.9 g ARG/1). All rats lost weight over the 5-day postinjury period; however, rats in groups B and C lost significantly less weight than rats in group A (-3.4 +/- 0.8% of initial body weight and -3.6 +/- 0.9% vs -6.1 +/- 1.2%, P less than 0.05). Rats in group A had negative cumulative nitrogen balance, while those in groups B and C were in highly positive balance. No significant difference in body weight change or nitrogen balance was noted between groups B and C. Trauma-induced thymic involution as assessed by thymic weight and lymphocyte content was greatest in group A, which received the lowest amount of arginine, and was linearly abrogated by increasing the amount of arginine administered (A less than B less than C). Thymocyte immune responsiveness increased with the amount of arginine given as assessed by mitogenesis in response to Con A (stimulation index: A--151.3 +/- 28.8 vs B--243.6 +/- 29.2, P less than 0.01 vs C--321.8 +/- 22.3, P less than 0.001 vs A and P less than 0.02 vs B) and PHA (A--65.0 +/- 14.3 vs B--67.7 +/- 15.3, NS, vs C--117 +/- 14.0, P less than 0.005 vs A and B).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1984

Inhibition of host immunity by fluid and mononuclear cells from healing wounds.

Severe trauma impairs host immunity, which in turn renders the host susceptible to infection often terminating in death. This impairment occurs 7 to 14 days after injury, a time when wound healing is at its maximum. We examined the interactions of wound healing to host immunity by studying the in vitro and in vivo immune effects of wound components (i.e., wound fluid [WF] and wound mononuclear cells [WMNC]). Lewis male rats (RT-1(1] weighing 300 to 350 gm underwent 7 cm dorsal skin incisions and subcutaneous placement of polyvinyl alcohol sponges. At 7 and 10 days after wounding, sponges were removed and WF was separated from the cellular elements. The cell suspension was purified to contain 80% to 90% WMNC. Ten percent WF from 7- and 10-day-old wounds inhibits normal thymic lymphocyte blastogenesis to concanavalin A and phytohemagglutinin. Addition of 5 X 10(4) WMNC leads to similar inhibition. WF and WMNC from 10-day-old wounds also inhibit in vitro allogeneic responses tested in one way MLR of Lewis splenocytes with inactivated ACI (RT-1a) spleen cells by 75% to 96% and 85% to 98%, respectively. The inhibitory action of WF is heat resistant (56 degrees C for 30 minutes) and noncytotoxic. In vivo allogeneic responses, tested by grafting ACI skin onto Lewis recipients, were inhibited by intraperitoneal administration of 10-day-old WF (p less than 0.01). We conclude that WF contains factor(s) that inhibit in vitro and in vivo immune responses. WMNC exhibits the same action, suggesting that they may be the source of the WF inhibitory factor(s). These findings may explain host immunosuppression after severe trauma.

Animals↗
PubMed1983

Fluid and mononuclear cells from healing wounds inhibit thymocyte immune responsiveness.

It has been shown previously that fluid obtained from 7-day-old wounds noncytotoxically inhibits normal thymic lymphocyte blastogenesis and that mononuclear cells (MNC) from the same wounds lack mitogenic responsiveness. The present series of experiments studies whether wound MNC are the source of the wound inhibitory factor(s) and the effect of adult thymectomy (ATDX) on their generation. Adult male Sprague-Dawley rats (300-350 g), intact or ATDX (performed at 8-10 weeks of age), underwent dorsal wounding (7 cm) and subcutaneous implantation of sterile Ivalon sponges. Seven days later sponges were harvested, wound fluid was obtained, and the cell pellet was purified to 90% MNC. Normal rat thymocyte blastogenesis (stimulation index) to Con A and PHA evaluated in a microculture system (10 separate experiments) was 169.9 +/- 10.0 and 30.1 +/- 3.7. Addition of 10% wound fluid markedly inhibited thymocyte mitogenesis--6.3 +/- 1.0 and 2.7 +/- 0.6, respectively (P less than 0.001). Heat-inactivated wound fluid (56 degrees C, 30 min) had similar inhibitory activity--3.4 +/- 0.9 and 2.7 +/- 0.6 (P less than 0.001). Normal thymic blastogenesis could also be inhibited by the addition of 5 X 10(4) wound MNC to the microculture system--4.4 +/- 1.1 and 1.9 +/- 0.3 (P less than 0.001). Wound fluid from ATDX rats had much less inhibitory activity (77.1 +/- 22.4 and 7.2 +/- 2.1, P less than 0.01) vs control wound fluid. In addition wound MNC from ADTX animals were also less immune suppressive (30.7 +/- 4.9 and 13.5 +/- 3.7, P less than 0.001) than control MNC. Forty-eight-hour supernatants of wound MNC from intact rats, added in 25% concentration to normal thymocyte cultures, demonstrated inhibition similar to that of the wound fluid from the same animals: 4.4 +/- 0.7 and 3.9 +/- 0.6, while ATDX MNC supernatants had minimal inhibitory activity (110.1 +/- 18.2 and 25.7 +/- 6.5, P less than 0.005). No cytotoxicity could be demonstrated in any of these experiments by trypan blue exclusion. It is concluded that 7-day-old wound fluid noncytotoxically inhibits thymocyte blastogenesis; this effect is also demonstrated by wound MNC and their supernatants, suggesting immune "suppressor" lymphocytes are present in wounds; ATDX, which abrogates suppressor cell induction, leads to marked diminution of wound inhibitory activity. The data suggest that important immune events occur at the wound site; their relation to normal wound healing remains to be elucidated.

Animals↗
PubMed1983

Cyclosporine A impairs wound healing in rats.

Cellular immune responses may play an important role in the early inflammatory and cellular phases of wound healing. Cyclosporine A (CSA), a new immunosuppressive agent, impairs cellular immunity and T-cell-dependent humoral immunity. Therefore, the effect of CSA-induced immunosuppression in a rat wound-healing model was studied. Sprague-Dawley rats underwent a standardized skin incision and subcutaneous implantation of sterile polyvinyl alcohol sponges. CSA was dissolved in olive oil and given by gavage to one group of animals at a total dose of 125 mg/kg/10 days. The control group received an equivalent volume of olive oil. Ten-day-old wounds were weaker in CSA-treated animals, both in the fresh state (282 +/- 19 g vs 380 +/- 27 g, P less than 0.01), and after formalin fixation (1111 +/- 74 g vs 1419 +/- 57 g, P less than 0.01). In addition, CSA-treated rats accumulated significantly less hydroxyproline in the wound sponge granuloma, an index of reparative collagen deposition. The impairment in wound healing occurred without differences in body weight gain or organ weights. There was a profound immunosuppression in the animals receiving CSA as determined by thymic lymphocyte blastogenesis in response to Con A and PHA. These findings suggest that immunosuppression in otherwise healthy animals impairs wound healing.

Adrenal Glands↗
PubMed1983

Cutaneous malignant melanoma: current views on pathogenesis, diagnosis, and surgical management.

Reliable cancer statistics reveal an unexplained increase in the incidence and rate of death from melanoma. Increased exposure to ultraviolet light does not seem to be a factor. Hormones may affect the incidence but do not influence survival. The recognition of the biologic evolution of different types of melanomas and the prognostic value of microstaging has had a major impact on the surgical management of cutaneous melanomas. Currently adequate excision is the only available curative treatment for melanoma and is most effective if performed on an early lesion. The extent of the excision should depend on the level of invasion and the bulk and location of the lesion. When clinically involved, dissection of the regional lymph nodes should be performed. The value of prophylactic node dissection of clinically uninvolved regional lymph nodes is unknown. Because of the low probability of regional lymph node involvement in thin lesions (less than 0.75 mm), prophylactic node dissection is not warranted. In contrast, there is a much higher incidence of spread to the regional lymph nodes reported in melanomas found to be thicker than 0.75 mm by microstaging. Prophylactic node dissection is probably worthwhile for these patients. Improved prospective randomized studies are needed to evaluate and determine the effectiveness of the various treatments that are being recommended.

Humans↗
PubMed1981

Metabolic and immune effects of arginine in postinjury hyperalimentation.

Nitrogen balance and thymic immune function studies were carried out in rats subjected to anesthesia, jugular vein catheterization, and bilateral femoral fractures, who were then given for 5 days: A) D5W; B) D20 FreAmine II (total arginine 1.55 gm/L); or C) D20 FreAmine III (4.05 gm of arginine/L). Administration of hypercaloric amino acid mixtures had strong positive effects on nitrogen retention and thymic function when compared to isotonic dextrose infusion. The administration of solution C had the most positive effect on nitrogen balance and on thymic immune function. The data suggest that increased arginine administration may prove beneficial to injured patients.

Amino Acids↗
PubMed1981

Arginine stimulates lymphocyte immune response in healthy human beings.

The effect of daily dietary supplements of 30 gm of arginine HCl for 7 days on peripheral blood lymphocyte (PBL) mitogenic reactivity in vitro was measured in 21 healthy human volunteers. Arginine significantly increased stimulation indices of PBL following concanavalin A (Con A) (57.9 +/- 11.4 versus 216.9 +/- 46.6, P less than 0.01) and phytohemagglutinin (PHA) (84.1 +/- 12.8 versus 307.0 +/- 59.4, P less than 0.001) stimulation in a microculture assay utilizing RPMI 1640 medium supplemented with 10% heat-inactivated autologous serum. Similar enhanced blastogenesis was observed using medium supplemented with 10% heat-inactivated pooled AB normal human serum. In six volunteers studied following 3 days of similar arginine supplementation, blastogenic responses of their peripheral blood lymphocytes were already significantly enhanced, although not as greatly as after 7 days. Arginine had no effect on total peripheral blood lymphocyte counts and on T- and B-cell ratios. The effects of supplemental dietary arginine could not be duplicated in vitro by increasing the arginine concentration in the culture medium. Furthermore, dietary arginine supplementation did not increase cell viability in culture. Minimal side effects were noted, such as nausea or diarrhea, which responded to lowering the dose ingested at one time. No deleterious effects were noted on liver function test results. We conclude that supplemental dietary arginine is a safe nutritional stimulator of lymphocyte immune reactivity in healthy human beings.

Administration, Oral↗
PubMed1978

Primary management of operable breast cancer by minimal surgery and radiotherapy.

109 cases of breast cancer were treated by tumorectomy and radiotherapy or radiotherapy alone. Almost 30% with small tumors (T1, T2) were considered inoperable for medical reasons and 70% refused mastectomy. Over the past five years the number of patients refusing mastectomy has definitely increased. 59 cases of surgically resectable cancers (T1, T2, T3, N0, N1) had a minimum followup of two years (average 4 years +/- 3 months). Absolute and determinate survivals NED were 65% and 86%. There were four local recurrences (8%). Secondary mastectomy could be performed on three. Microscopic involvement of the surgical margin by cancer did not alter the local control rate. The cosmetic results were good in 98%. Gross removal of the tumor followed by radiotherapy may be offered as an alternative to mastectomy in patients with operable breast cancer.

Adult↗
PubMed1977

Elective postoperative radiotherapy for locally advanced colorectal cancer. A preliminary report.

Preoperative radiotherapy in colorectal carcinoma invalidates surgical staging and delays performing the surgical resection. Postoperative radiotherapy does neither. From October 1972, to December 1975, 40 patients at high risk for local recurrence (B2 and C) received postoperative radiotherapy. Lesions that were located in the rectum, rectosigmoid and low sigmoid colon were given 4600 rads in four and a half weeks through an inverted T-shaped field which encompassed the pelvic and paraortic nodes. Patients with tumors located above mid-sigmoid were treated to the entire abdominal cavity by the moving strip technique. Of 19 patients with rectal and rectosigmoid lesions, 14 (74%) are alive without evidence of disease. Two had local recurrence in the treated area. Of 21 patients with lesions above the mid-sigmoid, four have failed locally, while 11 (52%) are alive without evidence of disease. One of these 40 patients died to radiation enteritis. Although the follow up period is short, the results suggest that a moderate dose of radiation may prevent local recurrence in patients with locally advanced colorectal cancer.

Adult↗
PubMed1977

Operative complications of abdominal vagotomy.

To assess the incidence of operative complications, mortality, and accuracy of vagotomy in transabdominal vagotomy, 733 cases were reviewed. Statistics are compared with those of other authors. A loose comparison of patients operated on by resident surgeons versus those operated on by attending surgeons is also made. Our preference for immediate microscopic examination of vagotomy specimens is stressed. One unusual complication is described.

Abdomen↗
PubMed1977

A simple method of posterior rectopexy for rectal procidentia.

A simple method of posterior rectopexy as a treatment for rectal procidentia involved a series of horizontal nonabsorbable purse string sutures placed between the posterior one-third of the circumference of the rectum and the sacrum. The procedure seems to be effective.

Adult↗
PubMed1975

Experimental production of elevated serum folate in dogs with intestinal blind loops. II. Nature of bacterially produced folate coenzymes in blind loop fluid.

Jejunal and ileal blind loops were constructed in separate groups of dogs and the folate coenzymes present in these loops were investigated. Although only those dogs with high blind loops had appreciably elevated folate levels active for Lactobacillus casei but not Streptococcus faecalis, every blind loop appeared to contain four folate compounds--5-formyltetrahydrofolic acid, 5-methyltetrahydrofolic acid, tetrahydrofolic acid and a compound tentatively identified as 5-formyltetrahydrofolic triglutamate. Why increased levels of 5-methyltetrahydrofolate alone are present in the serum of dogs with a high blind loop is discussed.

Animals↗