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Biomedical subjects

C W Nohr

Publications and source records attributed to C W Nohr.

14 recordsLinked to original sources

Late outcome of isolated gastric bypass.

OBJECTIVE: To complete a long-term (>5 years) follow-up of patients undergoing isolated gastric bypass for severe obesity. SUMMARY BACKGROUND DATA: Previous experience as well as randomized trials suggested that the ideal operation for obesity should rely on manipulation of satiety rather than the production of malabsorption. Such an operation should incorporate a small gastric pouch of less than 30 mL placed in a dependent position on the lesser curvature of the stomach, not dependent on staples, and separated from the remaining stomach with a retrocolic, retrogastric Roux-en-Y gastrojejunostomy without external support. METHODS: The authors established an obesity clinic where patients were seen six times during the first year and semiannually thereafter. Emphasis was placed on defining success in terms of approximation to normal body-mass index. RESULTS: Of 274 patients, 243 (89%) were followed up for 5.5 +/- 1.5 years. Before surgery, the patients were obese (n = 13), morbidly obese (n = 134), or super-obese (n = 96). The obese and morbidly obese group achieved an excellent result, and the super-obese a good result. Individual results showed considerable variation from the mean. CONCLUSIONS: This study of isolated gastric bypass with a 5.5-year follow-up rate of 88.6% revealed a success rate of 93% in obese or morbidly obese patients and 57% in super-obese patients. Isolated gastric bypass compares favorably with biliopancreatic diversion in terms of weight loss, maximum weight loss, weight regain, current body-mass index, and percentage of patients with a body-mass index less than 35 kg/m2.

Body Mass Index↗

The delayed hypersensitivity response and host resistance in surgical patients. 20 years later.

OBJECTIVE: A 20-year follow-up was conducted on research into the implications of a lack of a delayed-type hypersensitivity (DTH) skin test response among surgical patients. SUMMARY BACKGROUND DATA: The authors' original report showed that a failed DTH response was associated with increased hospital mortality, but the role of specific and nonspecific host defense elements, comorbid factors, nutritional supplementation, and the mechanism for anergy in this adverse outcome was unknown. METHODS: A data base of 4292 patients was analyzed and reported on individual studies designed to answer some of the above questions. RESULTS: Prospective studies showed a strong association between the DTH response and mortality: reactive patients, 2.9% (75/2576); anergic patients, 20.9% (239/1142, chi square = 265, p < 0.0000001). Antibody response to protein antigens was reduced in anergic patients. Antibody response to polysaccharide antigens was normal in all patients. The hallmark of anergy is a lack of T cells in the skin, as measured by mRNA signal (CD3) for T cells. The nonspecific component of host defense, as measured by circulating and exudate polymorphonuclear cell function, showed no statistically significant difference between elective reactive and elective anergic patients. Notwithstanding some mild malnutrition in anergic patients, parental nutrition failed to correct the DTH response or many of the cellular immune functions measured. CONCLUSIONS: Over the last 5 years, because of a reduction in overall patient mortality, the contribution of a reduced DTH response to septic related mortality has lost statistical significance in elective surgical patients. A reduced DTH response maintains its strong association to sepsis-related mortality in intensive care/trauma patients, and this is the group on which future research efforts should be concentrated.

Aged↗

The effect of the immunomodulator RU 41,740 (biostim) on the specific and nonspecific immunosuppression induced by thermal injury or protein deprivation.

We studied the effect of RU 41,740 (biostim), a primary macrophage stimulator, in the following two immunosuppressive conditions in rats: (1) a 30% full-thickness burn that leads to significant decreases in cell-mediated (delayed-type hypersensitivity [DTH]), humoral (anti-tetanus toxoid antibody production), and nonspecific immunity (Staphylococcus aureus 502a skin abscess) and (2) protein malnutrition using a 2% protein diet for eight weeks. Biostim administered by gastric intubation at dosages of 10 and 50 mg/kg of body weight for five days following thermal trauma did not prevent the DTH suppression induced by the thermal injury, but resulted in a significant dose-related increase in the amount of anti-tetanus toxoid antibody produced. In the malnourished rats given biostim at dosages of 10 and 50 mg/kg of body weight for seven days, there was a significant dose-related increase in the DTH response in the presence of continued protein depletion in these animals, with a modest but significant reduction in the S aureus 502a skin abscess at three days. Antibody production was not affected with this model. Biostim partially overcomes the suppression in humoral immunity following thermal injury, but not cell-mediated or nonspecific immunity. On the other hand, biostim augments both the cell-mediated and nonspecific immune suppression induced by prolonged protein deprivation but does not affect humoral immunity.

Abscess↗

Immunological responses to chronic heat exposure and food restriction in rats.

Immunological variables were studied in rats chronically exposed to high environmental temperature (35 degrees C). Responses were compared with those of rats at 25 degrees C both fed ad libitum and pair fed to the decreased intake found in heat-exposed rats. Heat-exposed rats showed slower delayed-type hypersensitivity responses to keyhole limpet hemocyanin. They showed lower counts of peripheral blood total T cells (OX19+) as well as helper T cells (W3/25+) and smaller numbers of splenic T cells. The thymus was decreased in size. Increased levels of serum IgG antitetanus toxoid antibodies were found in heat-exposed rats. [3H]-thymidine incorporation into Concanavalin A (ConA)-stimulated splenic lymphocytes was decreased in pair-fed rats but not significantly altered in heat-exposed rats compared with controls. Heat exposure alters some aspects of both cellular and humoral immune function in a manner different from that induced by comparable food restriction without heat exposure.

Animals↗

Assessing operative site infection in surgical patients.

We evaluated the contribution of altered host defense to the risk of developing an operative site infection. In part 1 of this study, we measured the following variables in 404 preoperative patients: cutaneous delayed-type hypersensitivity, age, serum albumin level, contamination status at the time of surgery, and the duration of surgery. Patients were examined daily postoperatively for the presence of an operative site infection (culture-positive drainage or infected tissue; overall rate, 17.3%). The above variables, plus previously defined risk factors, were examined by logistic regression analysis using the development of an operative site infection as the dependent variable. An equation to calculate the probability of developing a postoperative wound infection was thus derived. In part 2 of the study, a separate, matched group of 404 preoperative patients was used to test the validity of this predictive equation. A good fit of the model was obtained, with 70.3 wound infections predicted and 67 obtained (chi 2 = 0.8; not significant, ie, no difference between expected and observed wound infections at all probability deciles). We conclude that there are three determinants of an operative site infection, host defense (delayed-type hypersensitivity), acute and chronic physiologic derangement (albumin and age) and bacterial contamination risk at surgery (contamination status and duration of surgery).

Adult↗

The effect of indomethacin on burn-induced immunosuppression.

Recent interest in the role of prostaglandin inhibitors as immunomodulators following major injury prompted us to study the effect of indomethacin on burn-induced immunosuppression in rats as measured by the delayed-type hypersensitivity (DTH) skin test response, ability to contain an intradermal bacterial challenge (10(8) Staphylococcus aureus 502A injected intradermally), and overall survival from spontaneous burn wound sepsis. Fifty male Sprague-Dawley rats sensitized to keyhole limpet hemocyanin (KLH) were subjected to a 30% full-thickness scald burn. Group 1 (n = 24) received indomethacin at 0.5 mg/kg intraperitoneally once daily with the first dose given immediately following the burn. Group 2 (n = 24) received vehicle only. Prostaglandin E2 measured by radioimmunoassay on day 17 was 2553 +/- 832 pcg/ml serum (+/- SEM) in the vehicle group and 1042 +/- 231 pcg/ml in the indomethacin group (P = 0.058, unpaired t test). Burn injury induced a decrease in the DTH response to KLH and an increase in the Staph lesion size (P less than 0.05) which was not corrected by indomethacin treatment. All animals developed spontaneous burn wound sepsis by day 14. Survival after 17 days in the indomethacin group was 100% compared to that of the vehicle group, 79%, P less than 0.05 (Fisher exact test). We conclude that despite unmeasurable corrections of the burn-induced suppression of the DTH response and local nonspecific bacterial defenses, low-dose indomethacin improves survival following burn sepsis.

Abscess↗

Malnutrition and humoral immunity: long-term protein deprivation.

The effect of long-term protein deprivation and refeeding on delayed-type hypersensitivity (DTH) and humoral immune function was investigated in rats. Animals previously sensitized to keyhole limpet hemocyanin (KLH) were placed on a 2% protein diet ad lib for 8 weeks, after which some groups of animals were refed for up to 4 weeks. Control rats received normal rat chow. Recall skin testing with KLH, and immunization with tetanus toxoid (TT) were used to assess DTH and humoral immune responses. Weight, DTH, and antibody responses declined progressively with protein deprivation. Refeeding restored skin test responses and humoral immunity. There was a direct correlation between degree of malnutrition as reflected by weight and antibody responses as well as between DTH and antibody responses. The data demonstrate that chronic protein deprivation modulates both DTH skin testing and humoral immune responses and show that under conditions of altered immune function, there is a correlation between DTH responses and humoral immune function.

Animals↗

In vivo and in vitro humoral immunity in surgical patients: antibody response to pneumococcal polysaccharide.

We have previously shown that the antibody response to a T cell-dependent protein antigen, tetanus toxoid is reduced in patients having surgery. Because most bacterial antigens are not protein but polysaccharide, we studied in vivo and in vitro antibody responses to a relatively T cell-independent polysaccharide antigen, 23 valent pneumococcal polysaccharide (Pneumovax) (PPS). Subjects were classified by skin testing with five standard antigens as reactive patients (R, positive response to any antigen, N = 5), anergic patients (A, no response, N = 7) or laboratory controls (C, reactive personnel, N = 8). Blood lymphocytes taken before and after immunization with 0.5 ml PPS were cultured in vitro. Quantities of total and anti-PPS IgG, IgM, and IgA in culture supernatants and serum were measured by radioimmunoassay. There was no difference in in vivo anti-PPS production in the three groups (p greater than 0.05 for all comparisons, Wilcoxon rank-sum test). Positive response rates (greater than twofold increase) for all classes of immunoglobulin were also similar in the three groups (X2(2) = 0.36, 0.36, and 0.81 for IgG, IgM, and IgA, p greater than 0.05). In in vitro studies, peak quantities of IgA anti-PPS produced by A were significantly less than C (0.64 X divided by 0.41 versus 2.03 X divided by 0.6, p less than 0.05, Wilcoxon rank-sum test). Synthesis of all other classes of Ig anti-PPS and simultaneous measurement of total Ig (nanograms per culture) produced in vitro were not significantly different among all groups (p greater than 0.05, Wilcoxon rank-sum test). In C, R, and A, peak in vitro isotype-specific anti-PPS production correlated with the magnitude of the in vivo serum response (Spearman rank correlation = 0.53, 0.60, and 0.59 for IgG, IgM, and IgA, p less than 0.05). We conclude that these data show normal in vivo antibody responses to a relatively T cell-independent bacterial polysaccharide antigen in surgical patients and a good correlation of in vivo- to in vitro-specific antibody responses. The data imply that a T cell defect is responsible for reduced humoral immunity to protein antigens. Because most bacterial antigens are not protein but polysaccharides, active immunization of patients with bacterial vaccines may produce effective immunity.

Adult↗

Host-defence mechanisms in surgical patients: case report of reduced polymorphonuclear neutrophil and antibody functions associated with surgical sepsis.

The authors evaluated the host-defence capability of a 33-year-old woman with a history of poor wound healing, gastrointestinal fistulas and bacterial and fungal sepsis after abdominal operations. The following tests gave normal results: hemoglobin, blood neutrophil and monocyte counts, delayed hypersensitivity skin test, serum albumin, immunoglobulin and complement levels, blood T- and B-cell percentages, in-vitro immunoglobulin synthesis and body cell mass. The following tests gave abnormal results: lymphocyte count, leukocyte adherence, in-vivo and in-vitro polymorphonuclear neutrophil chemotaxis, neutrophil bacterial killing and antibody response to tetanus toxoid. Decreased polymorphonuclear neutrophil and humoral immune functions could account for the woman's history of repeated surgical sepsis. Evaluation of host-defence mechanisms can illuminate the cause of repeated episodes of sepsis.

Adult↗

Malnutrition and humoral immunity: short-term acute nutritional deprivation.

The effects of short-term acute nutritional deprivation and refeeding on immune function was investigated in rats. Animals previously sensitized to keyhole-limpet hemocyanin were starved for 72 hours and refed for 7 days. Recall skin testing with keyhole-limpet hemocyanin and immunization with tetanus toxoid (TT) were used to assess delayed-type hypersensitivity (DTH) and humoral immune responses. DTH was maximally depressed late, after refeeding had begun. Anti-TT responses were depressed early during starvation. Neither DTH nor anti-TT responses had returned to normal after a period of refeeding sufficient to restore weight. The data indicate that short-term acute nutritional deprivation may contribute to acquired immunodeficiency in patients undergoing surgery.

Animals↗

In vivo and in vitro humoral immunity in surgical patients.

In vivo and in vitro humoral immunity was studied in surgical patients. Laboratory controls (LC), delayed type hypersensitivity (DTH) skin test reactive (HR), and anergic (HA) patients were immunized with tetanus toxoid. Maximum in vivo antibody levels occurred 14 days after immunization. Eighty-six, 47, and 17% of LC, HR, and HA subjects, respectively, showed a positive response (X2(2) = 21.1 with Yates, p less than 0.0005). Peak in vitro antibody production in unstimulated lymphocyte cultures occurred at day 6 after immunization. Antibody responses in vitro were reduced in all surgical patients, worst in HA, and correlated quantitatively with in vivo antibody responses at day 14 (Spearman rank correlation = 0.794, p less than 0.001). Total IgG production in vitro was not decreased; 595, 1080, and 1538 ng IgG/culture were produced by LC, HR, and HA, respectively. These data demonstrate decreased in vivo and in vitro humoral immunity in all surgical patients, worst in those with decreased DTH responses. There is a kinetic and quantitative correlation between in vivo and in vitro responses, the latter being a biologic reflection of the integrity and magnitude of the in vivo process. Finally, failure to produce specific antibody is not due to failure of total IgG synthesis.

Antibodies, Bacterial↗

Primary peritonitis in children.

Ten cases of primary peritonitis in children demonstrate that the usual presentation is one of rapid onset of lower abdominal pain in girls, clinically indistinguishable from acute appendicitis. Recovery after appendectomy is rapid. Fewer cases have positive peritoneal cultures or associated illnesses than in historical descriptions. Contemporary primary peritonitis follows a more benign course than in the past.

Adolescent↗

Long- or short-limb gastric bypass?

The aim of this study was to determine whether longer limb length improved results of gastric bypass in patients who were morbidly obese (body mass index <50 kg/m(2)) or superobese (body mass index >50 kg/m(2). A total of 242 patients were followed for a mean of 5.5 years. The standard operation was a Roux-en-Y gastric bypass with a 40 cm Roux limb and a 10 cm afferent limb. The long-limb operation had a 100 cm Roux limb and a 100 cm afferent limb. Morbidly obese patients did not benefit from a long-limb bypass. The final body mass index was 28.6 +/- 4.7 kg/m(2) in the short-limb group and 28.5 +/- 3.8 kg/m(2) in the long-limb group. The superobese patients did benefit from a long-limb bypass. Final body mass index was 35.8 +/- 6.7 kg/m(2) in the short-limb patients and 32.7 +/- 5.1 in the long-limb patients (P = 0.049). A subgroup of 20 patients, all of whom had a body mass index greater than 60 kg/m(2), benefited the most from long-limb bypass. No macronutritional side effects unique to the long-limb bypass were encountered.

Anastomosis, Roux-en-Y↗