Long gamma-ray bursts and core-collapse supernovae have different environments.

When massive stars exhaust their fuel, they collapse and often produce the extraordinarily bright explosions known as core-collapse supernovae. On occasion, this stellar collapse also powers an even more brilliant relativistic explosion known as a long-duration gamma-ray burst. One would then expect that these long gamma-ray bursts and core-collapse supernovae should be found in similar galactic environments. Here we show that this expectation is wrong. We find that the gamma-ray bursts are far more concentrated in the very brightest regions of their host galaxies than are the core-collapse supernovae. Furthermore, the host galaxies of the long gamma-ray bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae. Together these results suggest that long-duration gamma-ray bursts are associated with the most extremely massive stars and may be restricted to galaxies of limited chemical evolution. Our results directly imply that long gamma-ray bursts are relatively rare in galaxies such as our own Milky Way.

Effect of embryonic tissue immunization on chemically induced gastrointestinal tumors in rats. I. Can embryonic antigens act as rejection antigens?

Inbred WF rats were inoculated with crude suspensions prepared from liver and gut tissue of 12- to 15-day fetuses of the same strain. Rats previously unsensitized to syngeneic embryonic tissue were inoculated with fetal material sc three times during exposure to 1, 2-dimethylhydrazine dihydrochloride (DMH), a gastrointestinal (GI) carcinogen in rodents. Properly timed immunization inhibited the development, growth, and metastasis of primary GI tumors. This effects was observed in both sexes; however, it was more prounced in male rats. Nine WF rats with DMH-induced carcinoma of the GI tract were inoculated sc with syngeneic fetal tissue. Of 9 rats, 7 rejected the embryonal tissue implants, which thus demonstrated the presence of a concomitant immune response to embryonic antigen(s). Two rats in which fetal tissue grew out to palpable nodules had multiple GI tumors with metastasis and extra-GI tumors, i.e., a massive tumor load. Ten other rats with DMH-induced GI tumors were treated with unblocking serum. The unblocking serum was inoculated to counteract serum-blocking factors in vivo. These rats were inoculated intradermally with syngeneic fetal tissue. In all 10 rats, inflammation and necrosis were noted at the inoculation site after 24-72 hours, which thus demonstrated a delayed hypersensitivity reaction to embryonic antigens. Our experiments suggest that embryonic antigens common to fetal and tumor cells can induce immunity in an autochthonous host and can act as rejection antigens.

Immunologic surveillance against chemically induced primary colon carcinoma in rats.

A 1,2-dimethylhydrazine dihydrochloride-induced rat gastrointestinal tract tumor model was used to study the phenomenon of immunologic surveillance. In two different sets of experiments, a properly timed administration of antithymocyte globulin resulted in earlier tumor appearance, increased numbers of tumors, and increased multiplicity of gastrointestinal tumors. Results obtained from histologic examination of the gastrointestinal tract at different times after the last dose of 1,2-dimethylhydrazine dihydrochloride suggested that a normally functioning immune system effectively suppressed the growth of some nascent tumors. However, the immunosuppression of the host with antithymocyte globulin allowed the development of foci of microtumors into grossly visible neoplasms. Our experiments supported the concept that immunologic surveillance against neoplasia depends on the thymus cell system, although other possible mechanisms were not excluded.

Effect of unblocking therapy and levamisole on primary gastrointestinal tumors in rats: immunologic and histologic correlation.

The effect of multimodal immunotherapy was studied in WF rats bearing primary gastrointestinal (GI) tumors induced by 1,2-dimethylhydrazine dihydrochloride. The alterations induced in antitumor immune responses of the treated rats were studied in vitro and were correlated with tumor status in vivo. Multimodal immunotherapy consisted of unblocking serum, unblocked lymphoid cells, and levamisole. Such immunologic intervention resulted in significant inhibition of tumor growth, inhibition of metastases, and prolonged survival of the host. Serum blocking activity could be completely counteracted in 6 rats, all of which showed complete tumor regression. Of 20 rats, 8 showed inadequate counteraction of serum blocking activity and transient appearance of cytotoxic antibodies. All 8 rats showed marked tumor inhibition and prolonged survival. Six remaining rats succumbed from either GI or extra-GI tumors, although they survived significantly longer than untreated rats; these 6 rats had only transient counteraction of their serum blocking activity. All 20 tumors in 14 rats of the therapy group showed histologic evidence of tumor rejection. Our studies suggested that a complete counteraction of blocking activity in conjunction with methods capable of improving the specific and nonspecific immune competence of the host may be important to achieve optimal antitumor effects.

Demonstration of effective antitumor immunity in an autochthonous host bearing primary colon tumors induced by 1,2-dimethylhydrazine dihydrochloride.

The role of host defense mechanisms in preventing the development of subclinical tumors into invasive tumors in an autochithonous host was studied in a model of rat colon carcinoma induced by 1,2-dimethylhydrazine dihydrochloride (DMH). Multiple gastrointestinal (GI) tumors were induced in inbred WF female rats exposed to DMH. In vitro and in vivo data suggested that the excision of the "first" GI tumor induced specific antitumor immune responses. After a complete excision of the first GI tumor, only 2 additional GI tumors were observed in 10 rats, whereas 13 and 12 additional GI tumors in 10 and 9 rats, respectively, were observed if the first GI tumor was left in situ or permitted to grow in an isolated segment of the colon. Furthermore, immunosuppression with antithymocyte globulin decreased the effectiveness of antitumor immunity induced by the immunizing first GI tumor. These experiments supported the view that an effective antitumor immunity is induced against successive tumors of an organ after a complete excision of a tumor originating in the same organ. The results of these experiments are discussed in relation to the observations of multiple primary neoplasms in humans.

Effects of diet on colon carcinogenesis and the immune system in rats treated with 1,2-dimethylhydrazine.

The effects of different types of diets on colon carcinogenesis by 1,2-dimethylhydrazine and on the immune system were studied in W/Fu rats. Six different types of diets were used in two sets of experiments. Rats in each group were fed the respective diets immediately upon weaning. 1,2-Dimethylhydrazine dihydrochloride was administered s.c. at a dosage of 15 mg/kg weekly in two divided doses. The rats were followed by sequential laparotomies for the development of gastrointestinal (GI) tumors until death. Tumors appeared earlier, and the total number of GI tumors, particularly those of the colon, was higher in rats fed diet enriched with fat from animal sources. In these rats the GI tumors metastasized more frequently, and their survival, after appearance of the first GI tumor, was significantly shortened. The diet low in animal fat and enriched with carbohydrate reduced the number of GI tumors and delayed their appearance. Semisynthetic elemental diet accelerated the appearance of colon tumors without increasing the total number of GI tumors over the life span of the animals. Serum cholesterol levels evaluated during carcinogenesis suggest a correlation between serum cholesterol levels and the increased frequency of colonic tumors. The alterations in serum immunoglobulin G levels, lymphocyte counts, and surface immunoglobulin-bearing lymphocytes evaluated at different times during carcinogenesis suggested a biphasic ("M type") immune response. Rats fed low residue diets and/or diets containing fat from animal sources had depressed serum immunoglobulin G levels. However, the pattern of immune response was similar in groups of rats fed different types of diets.

Ability of nonviable Staphylococcus aureus Cowan I to bind ionized calcium in vitro and ex vivo in an extracorporeal perfusion system.

During immunoadsorption of plasma immunoglobulin G (IgG) and/or its complexes, using nonviable Staphylococcus aureus Cowan I (SA) as an immunoadsorbent, we observed a consistent drop in plasma calcium during every immunoadsorption procedure. The percentage of decrease in plasma calcium was directly dependent on the amount of SA adsorbent present. Although SA can bind both IgG and calcium, the degree of binding of IgG was greater than that of calcium. Calcium could not be detected in the IgG fraction of the plasma SA, however, could bind an appreciable amount of ionized calcium. Extracorporeal perfusion of plasma over SA greatly decreased plasma calcium in a hypercalcemic patient, indicating the feasibility of this method in such patients. Questions concerning the significance of lowering calcium levels as a concomitant of other effects observed in cancer patients undergoing immunoadsorption therapy using SA evolve from the above and become a new focus for attention.

Specific immunoadsorption of IgG antibody in a patient with chronic lymphocytic leukemia and autoimmune hemolytic anemia. A new form of therapy for the acute critical stage.

Progressive and severe autoimmune hemolytic anemia developed in a patient with chronic lymphocytic leukemia (CLL) despite treatment with chlorambucil, high doses of corticosteroids and attempts to transfuse packed red blood cells. Splenectomy was not performed because of severe coronary artery disease. Direct antiglobulin tests revealed a warm red blood cell autoantibody of IgG-type with anti-e specificity. The patient was treated by extracorporeal immunoadsorption of plasma IgG using a cell separator and protein A as the immunoadsorbent. The patient responded by an increase in the hemoglobin levels and platelet counts after two treatments. Specificity of the procedure was shown by a decrease in the serum IgG and by the demonstration of the same reactivity to ficin-treated reagent red blood cell panel of the eluate from the protein A. Antibody titers of the patient's red blood cell eluate decreased from 1:128 to 1:64 and eventually the anti-e specificity was lost. This is a report of a novel approach to treatment of the acute phase of an autoimmune hemolytic anemia.

Ankle-level amputation.

Ankle-level amputation for diseases involving the foot can be achieved by the Pirogoff amputation instead of the Syme amputation with very good results. This technique provides a strong end-bearing stump and has the advantage that the amputated leg is essentially the same length as the patient's normal leg. With the use of modern prostheses, the results of rehabilitation are very good. We have used the Pirogoff technique for ankle-level amputations in 12 patients during the past 4 years with good results.

Five-year survival of 100 women with carcinoma of the breast diagnosed by screening mammography and needle-localization biopsy.

Carcinoma of the breast was studied in 100 women who underwent needle localization and open breast biopsy for lesions found by screening mammography from January 1980 to May 1987. The average age of the patients found to have carcinoma was 59.2 years, and 16 percent of patients were younger than 50 years of age. Pathologic examination revealed 62 patients with infiltrating ductal carcinoma, 31 patients with ductal carcinoma in situ, and seven patients with infiltrating lobular carcinoma. In 34 patients the carcinoma was microscopic. Thirty-six patients had carcinomas less than or equal to 1 centimeter, and 30 patients had carcinomas greater than 1 centimeter. Eighty-four patients were treated with total mastectomy and axillary dissection. Seven patients were treated with wide excision, axillary dissection and radiation therapy. Nine patients underwent lesser treatments. Among the 91 patients undergoing axillary dissection, 82 were node negative, eight had one to three positive nodes, and one had four or more positive nodes. One hundred percent of patients with ductal carcinoma in situ who underwent axillary dissections (24 of 31) were node negative. Only two patients received adjuvant hormonal therapy, and one woman received adjuvant chemotherapy. All patients were under observation for at least five years or to the time of death (mean follow-up period, 5.8 years). Of the 100 patients with complete follow-up, 92 are alive and disease free. Four patients with carcinoma that metastasized have died. Three patients are alive with known recurrence. One patient died of other causes six months after carcinoma was diagnosed. Widespread use of screening mammography coupled with judicious use of needle-localization biopsy will lead to the early diagnosis of carcinoma of the breast. Such early diagnosis of carcinoma does lead to an excellent (95 percent) five-year survival rate.

Obturator hernia needs a laparotomy, not a diagnosis.

The obturator hernia is rare, accounting for only 0.05% of all hernias and 0.2% of all small-bowel obstructions requiring laparotomy at our institution. Typically, there is a delay in diagnosis and surgical intervention, despite the presence of a bowel obstruction. A laparotomy is needed, not a preoperative diagnosis.

The impact of nutrition on infection.

It seems that the early impressions of Graves have been borne out by a series of increasingly objective measurements, some in animals, such as those in the studies of Robertson and of Cannon and their collaborators, and some in patients, such as those of Wohl, Law, Copeland, Dudrick, Meakins, Mullen, and their associates. This is by no means a complete review of the literature, but sufficient data have been presented to indicate that poor nutrition is followed by a great increase not only in total complications but also in infectious complications. This is most clearly seen in the more exaggerated cases of malnutrition but is observed to some extent with deficits of intermediate severity. So far, the studies do not pinpoint susceptibility to particular organisms but appear to implicate the mechanisms of defense against microorganisms on a categorical basis. The reverse effect, that is the impairment of nutritional status resulting from both chronic and acute infection, is too well known to require emphasis.

The role of preoperative factor V Leiden screening in different geographic populations.

Patients harboring a specific mutation in the coagulation factor V gene have been identified as being at significantly increased risk for venous thrombosis. A simple genetic test that identifies carriers of this mutation (the factor V Leiden allele) is available and may have utility in various clinical settings, including preoperative risk assessment for thromboembolic complications. In this regard, it is generally agreed that prospective studies addressing the role of preoperative factor V Leiden mutational analysis are needed to clearly define the clinical prognostic/diagnostic significance of the presence of this mutation in surgical patients. This report questions the role that population dynamics (genetic and environmental backgrounds of individual populations) plays in the analysis of factor V genotypic data in relation to postsurgical thromboembolic complications. We have determined that the frequency of individuals carrying the factor V Leiden allele is 7.9 per cent for our South Central Pennsylvania population (395 wild type, 32 heterozygotes, 2 homozygotes) using a polymerase chain reaction-restriction fragment length polymorphism technique that specifically detects the factor V Leiden mutation. This baseline population information is useful from both a clinical and a basic science viewpoint. However, considering the various unknown genetic and environmental differences between geographically distinct populations, the significance of this result, in terms of clinical management of our surgical patients, is yet to be determined.

First place winner of the Conrad Jobst Award in the gold medal paper competition. Nitric oxide synthase inhibitors N-monomethylarginine and aminoguanidine prevent the progressive and severe hypotension associated with a rat model of pancreatitis.

The objective of this study was to determine whether the observed vascular collapse and other pathologic features of severe pancreatitis may be related to the induction of nitric oxide synthase (NOS). The rat model of pancreatitis reported by Schmidt et al. was employed. Rats in the experimental groups received pretreatment with known NOS inhibitors, N-Monomethylarginine (NMMA) or Aminoguanidine (AG). Controls included sham-operated rats without pancreatic insult and a diseased control group which received pretreatment with normal saline (NS). Arterial blood pressure was continuously recorded with a femoral arterial catheter connected to a transducer and monitor. Fluid resuscitation for hypotension followed a strict protocol with the administration of 5.0 cc NS for sustained decreases in systolic blood pressure (SBP) below 90 mm Hg at 5-minute intervals. Laboratory parameters and histopathology confirmed the induction of pancreatitis, with 6 to 15-fold increases in serum amylase levels and an average of approximately 20% decrease in serum ionized Ca++ levels. Immunohistochemical studies of the pancreas revealed that pancreatic insult resulted in the induction of NOS. Rats in the saline control group (n = 5) became hypotensive (SBP less than 90 mm Hg) between 3 and 4 hours post pancreatic insult and required an average of 110.0 cc (3-4 x blood volume) of NS fluid resuscitation. Rats which were not resuscitated (n = 5) did not survive.(ABSTRACT TRUNCATED AT 250 WORDS)

Ex-vivo removal of mammalian immunoglobulin G: method and immunological alterations.

We have described a clinically feasible method capable of rapidly and repeatedly removing mammalian IgG extracorporeally by adsorption onto heat-killed, formalin-stabilized Staphylococcus aureus Cowan-I. In dogs, 2-13 grams of IgG were removed in 60-70 minutes, lowering the serum concentration of IgG by 30-70 percent. Serum IgG levels returned to pre-run values within 48-72 hours and, in some cases, were higher than pre-run levels at 48-72 hours. Serum biochemical alterations were generally transient and relatively modest. Peripheral lymphocyte counts showed minimal changes but the percentage of erythrocyte rosette forming cells appeared to increase with successive runs. This method is safe and efficient, and can be repetitively performed at short intervals in dogs. This method may prove useful in diseases in which rapid removal of circulating IgG is desired.

3D CT reconstruction in the surgical management of hepatic injuries.

We employed 3D reconstruction of CT images for evaluation of hepatic injuries in a series of eight trauma patients. One had additional reconstruction of a renal injury. 3D imaging provided precise anatomical delineation of damaged areas, particularly in relation to major vessels. Moreover, the imaging agreed with operative findings in every case. The 3D reconstruction facilitated decisions regarding intraoperative, reoperative and non-operative management. The improved imaging provided by 3D reconstruction may allow hepatic CT scans to be interpreted with greater ease and accuracy than conventional CT. We believe this is the first report of its use in liver trauma. Current indications may include postoperative confirmation of the extent of hepatic injuries, assessment before reoperation, and contribution to decisions regarding non-operative management. A limitation at present is the time taken for image production, but we suggest that in the future 3D imaging might contribute to evaluation before emergency surgery in patients with abdominal injuries.