[Bacterial degradation of fibrin glue in vitro].
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Biomedical subjects
Publications and source records attributed to F Moesgaard.
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Total colectomy with ileorectal anastomosis (IRA) in familial adenomatous polyposis (FAP) leaves patients at risk for rectal cancer. To assess this risk, the rectal cancer incidence in 297 patients with FAP undergoing IRA since 1951 was determined in the population-based registers of Denmark, Finland and Sweden. At the same time, detailed data on 50 patients with FAP and invasive rectal cancer were obtained from 11 international polyposis registries. The cumulative incidence of rectal cancer was 13.1 per cent at 25 years. The 5-year survival rate of patients with FAP developing rectal cancer was 71 per cent. Combining both studies, the risk of dying from rectal cancer after IRA was 2.0 per cent at 15 years of follow-up. These results justify IRA as primary treatment for most patients; restorative proctocolectomy is preferred for some subgroups. The high all-cause mortality rate observed in this relatively young population necessitates lifelong surveillance of patients with FAP.
The duration of postoperative impairment in cell-mediated immunity was assessed by repeated skin testing with seven delayed type common antigens in 15 patients undergoing major elective abdominal surgery compared to a similar testing regimen in 10 healthy volunteers. All were skin tested four times, with 72-hour intervals, and in the surgical patients the first test was applied 2 days before surgery, followed by tests on postoperative days 1, 4 and 7. The tests were read after 48 h. Postoperatively, the skin test area decreased on day 3 (p less than 0.01) and recurred to preoperative levels on day 9. In contrast, the skin test area in the volunteers increased from test to test (p less than 0.001) during the study, confirming a previous finding of a vaccination effect. These results suggest that the postoperative immunosuppression is maintained for about 6-9 days.
The effect of the histamine-2 receptor antagonist ranitidine (100 mg intravenously every 12 hours for 72 hours) on postoperative serum antibody responses to preoperative immunization with six limit of flocculation tetanus toxoid and six limit of flocculation diphtheria toxoid was assessed in a double-blind, placebo-controlled randomized study in 26 patients undergoing major abdominal surgery. The preoperative antitetanus antibody level was less than 0.1 IU/ml in all patients, and they were inoculated with both antigens 48 hours before surgery. Serum samples for analysis of antitetanus toxoid and antidiphtheria toxoid were drawn before skin incision and on postoperative days 1, 3, 5, 7, 10, 14, 21, and 28. Ranitidine significantly increased the postoperative antibody response to tetanus toxoid, (p less than 0.01) and insignificantly increased that to diphtheria toxoid vaccination (p less than 0.2) compared with placebo.
Fifteen patients who developed a persistent perineal sinus after excision of the rectum and eight patients with a perineal fistula appearing after treatment of perineal abscesses were treated with instillation of fibrin adhesive to close the sinus or fistula. In 12 patients, the sinus tracts or fistulas were completely and permanently closed (52 percent). In five patients (22 percent), the fistulas healed after two or three attempts, while, in six patients (26 percent), the method failed to provide lasting closure. The method seems to be a valuable alternative in the treatment of a persistent, long and narrow perineal sinus or fistula.
Multiple myeloma (MM) is characterized by an increased susceptibility to infections and to other malignancies. Selected related immune functions were studied. Spontaneous and interleukin-2-stimulated natural killer (NK) cell activities were normal in 19 patients with MM compared with 62 controls. In contrast, interferon-stimulated NK cells had a significantly lower increase in activity in MM than in controls. The normal improvement in lytic NK cell activity after addition of indomethacin to the mononuclear cell cultures (to inhibit prostaglandin-mediated suppression) was not observed in cultures from MM patients. As reported for other lymphoproliferative disorders, the levels of soluble interleukin-2 receptors in serum were significantly higher in MM (600 U/ml median value) compared with controls (317 U/ml median value), P less than 0.0001, and the concentration of interleukin-2 receptors was significantly correlated with the concentration of monoclonal immunoglobulin in serum. Blood monocyte chemotactic responsiveness was significantly lower in MM patients with both zymosan-activated serum and f-Met-Leu-Phe as cytotaxins, suggesting reduced ability to accumulate at inflammatory foci. In contrast, release of reactive oxygen radicals, believed to be associated with the killing ability of monocytes, was normal after in vitro stimulation.
A new electrode system for determination of visceral oxygen tension is presented. The system consists of a transcutaneous oxygen electrode (E5242 Radiometer A/S. Copenhagen), which is screwed into a suction ring and fixed to the organ by applying a vacuum. The electrode membrane is then in contact with the organ surface via a fluid layer with a thickness of a few micrometres, without interference from atmospheric air and without mechanical disturbance of the membrane. The electrode system was tested on the gastric and colonic wall in six pigs. As reference, a silicone tonometer was placed subserously beneath the vacuum-fixed electrode. The silicone tonometer was connected to a second transcutaneous oxygen electrode. The tissue oxygen tension was changed by subjecting the animals to various inspiratory concentrations of oxygen and to hypovolaemia. The oxygen tension measured by the vacuum-fixed electrode (PO2vac) was compared with the oxygen tension measured by the tonometer (PO2tono). A good correlation was demonstrated between PO2vac and PO2tono, the correlation coefficient being 0.8619, confirming that the suction-fixed oxygen electrode measures tissue oxygen. The lowest possible vacuum to hold the electrode unit in place was between 4.0 and 6.7 kPa. Provided the measuring time did not exceed 3 min. vacuum had only slight influence on the measured oxygen values. The mean change in PO2vac induced by varying the vacuum from 7 to 26 kPa, and 26 to 7 kPa, was only +0.23 kPa (-1.2 to +1.9) and +0.19 kPa (-0.3 to +1.3), respectively. The mean stabilization time, defined as the time from electrode application until achieving 95% of the equilibration value, was 66 sec (SEM, 3.4 sec) and 57 sec (SEM, 3.0 sec) on the gastric and colonic wall, respectively. The measured values of PO2vac varied significantly between different areas on the gastric wall (p less than 0.001). When several surface measurements were performed throughout the investigated area, the mean oxygen tension approached the oxygen tension measured by the tonometer. It is concluded that the vacuum-fixed electrode constitutes a reliable, easy and, noninvasive method for measurements of the oxygen tension in the gastric and colonic tissue.
This study included 236 patients treated with endoscopic biliary endoprostheses. Malignant strictures were responsible for the obstruction in 87% of the patients. The 1-week and 1-month mortality for patients with malignant strictures was 10% and 22%, respectively, whereas that of patients with benign conditions was 3% and 10%, respectively. The major complication encountered was the frequent hospital readmissions of patients owing to clogging of their endoprostheses. Late clogging had an overall occurrence of 33% and presented with recurrence of jaundice with or without fever or pain. Late signs of cholangitis occurred in 15% of the patients, whereas other late complications were rather infrequent. Although 10-french endoprostheses had a significantly longer patency period than 7-french--that is, 6 months versus 2 months (p = 0.01)--the proportion of patients in whom clogging occurred was nearly the same, 30% for 10-french and 32% for 7-french endoprostheses.
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In a 55-year-old woman, a 1 x 5 cm fistula developed in the ileoanal anastomosis after restorative proctocolectomy with J-pouch ileoanal reservoir and temporary ileostomy for intractable ulcerative colitis. The fistula extended between the pouch and the sacral bone. Lasting closure was achieved by intrafistular placement of a collagen sponge containing gentamicin and soaked in metronidazole solution and pouch drainage through a transanal Foley catheter.
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Human immunodeficiency virus (HIV) infection is characterized by a progressive impairment in immunocompetence leading to severe opportunistic infections and malignancies. In a double-blind, placebo-controlled study, the potential impact of immunomodulation by oral ranitidine, 600 mg daily, for 28 days was studied in 18 HIV-positive patients (CDC group II). All were without clinical signs of infections and were not treated with other known immunomodulating agents. Several immunological parameters related to HIV infection were studied and confirmed to be impaired early in HIV infection. Spontaneous and in vitro interleukin-2- and interferon-alpha-stimulated natural killer cell activity improved in the ranitidine-treated patients in contrast to a decrease in nontreated patients (#p less than 0.03, #p less than 0.01, #p less than 0.02 between groups, respectively). Furthermore, T-cell blastogenesis to phytohemagglutinin stimulation and soluble interleukin-2 receptors in serum increased in ranitidine-treated patients compared with nontreated patients (#p less than 0.01). However, ranitidine treatment did not change CD4+ cell counts. Although the significant improvement in immunocompetence shown in this study is small, the present result indicates the need for further trials with immunomodulation by ranitidine in HIV-infected individuals.
The influence of perioperative whole-blood transfusion and transfusion with erythrocyte suspension (SAG-M blood) on postoperative depression of cell-mediated immunity (CMI) was investigated in 67 patients who underwent elective resection for colorectal cancer. Cell-mediated immunity was assessed pre- and postoperatively by skin testing with seven common delayed-type hypersensitivity (DTH) antigens. The postoperative skin-test response decreased more in the patients who received whole blood (15 patients) than in those who received SAG-M blood (16 patients) (60% versus 42%, p less than 0.001) and in those who did not receive a blood transfusion (36 patients) (60% versus 40%, p less than 0.001). The enhanced postoperative immunosuppression in patients who received whole-blood transfusions persisted after matching according to age, sex, height, weight, hemoglobin and serum albumin levels, duration of surgery and diagnosis. Thus, perioperative transfusion with SAG-M blood does not enhance surgically induced immunosuppression as effectively as does transfusion with whole blood.
The patient had been treated ten years previously for acromegaly. At present he was in hypercalcaemic crisis owing to multiple hyperparathyroid adenomas. He had multiple small pancreatic glucagonomas and a malignant duodenal gastrinoma which led to recurrent episodes of duodenal and gastric ulcers with perforations and hemorrhages. The hypercalcaemia increased the hypergastrinaemia significantly and probably accelerated the ulcer diathesis. This patient illustrates well how severe and complicated the clinical situation can be in patients with MEN-1 and emphasizes the importance of being aware of the syndrome.
Familial adenomatous polyposis is a dominant hereditary disease which includes early development of up to several thousand colorectal adenomas and subsequent development of colorectal adenocarcinoma in all of the untreated cases. In addition, various extracolonic manifestations may be observed. These include epidermoid cysts, osteomas, desmoids and gastroduodenal polyps. Conventional proctosigmoidoscopy is employed as the primary diagnostic method as all of the patients have rectal adenomata. Thereafter colonoscopic examination is undertaken and gastroduodenoscopy is performed on account of the risk of development of duodenal adenomas. Treatment consists of prophylactic colectomy at about the age of 15 years. An ileorectal anastomosis is most frequently made but construction of an ileoanal reservoir may be considered in selected cases. Regular prophylactic control examinations of first degree relatives of affected family members should commence at the age of ten years. Recent demonstration of a specific gene for polyposis on chromosome 5 will, together with demonstration of retinal pigmentation permit early preclinical diagnosis in future. Establishment of the Polyposis Register has resulted in earlier tracing and treatment of the condition and an improved prognosis.
Multiple myeloma is characterized by an increased susceptibility to infections and to other malignancies. In a double-blind, placebo-controlled study the potential impact of immunomodulation by ranitidine was studied in 20 patients with multiple myeloma. Three patients were untreated, while 17 after previous cytotoxic therapy were in a stable phase of their disease. All were without clinical signs of infections and at that time had not been treated with other immunomodulating agents. The patients were randomized to oral ranitidine 300 mg twice a day for 21 days or placebo, and several immunological parameters related to multiple myeloma were studied. The blood monocyte chemotactic response was improved in patients treated with ranitidine, and superoxide anion production increased from 2.02 nmol/min to 3.86 nmol/min (median values), while it was unchanged in patients given placebo (2.19-2.25 nmol/min) (P less than 0.005 between groups). Among ranitidine-treated patients spontaneous NK cell activity was unchanged, while in vitro interleukin-2- and interferon-alpha-stimulated NK cell activity decreased (P less than 0.03, respectively). As production of oxygen radicals constitutes an important mechanism of monocyte killing activity against microorganisms and probably against malignant cells, it is suggested that ranitidine may be of beneficial impact in the treatment of multiple myeloma.
Ten patients undergoing abdominal operations had oxygen saturation (SpO2) and transcutaneous (PtcO2) and subcutaneous (PscO2) oxygen tensions monitored continuously during the second and third postoperative nights from 11 pm to 7 am. At the end of the second postoperative night an oxygen stimulation test (10 l/min by face mask) was carried out in eight of the 10. Median SpO2 was 91% (range 82-95) on the second, and 91% (86-95) on the third, postoperative nights, respectively. Six patients had intermittent episodes of desaturation to less than 80%, each of less than one minute's duration. PtcO2, but not PscO2, followed the episodic variations in SpO2. PscO2 was 58 mmHg (46-69) on the second postoperative night and 61 mmHg (48-71) on the third postoperative night. PscO2 correlated with SpO2 in all but one patient who had lower PscO2 than expected from the measured SpO2 and estimated PaO2. Oxygen treatment increased individual PscO2 by 14 mmHg (9-49), PtcO2 by 38 mmHg (10-104), and SpO2 to 99% (95-100), but stable PscO2 was not achieved within the 20 minute period of treatment. These results obtained during continuous measurements show pronounced intersubject differences in oxygen tensions near the surgical wound in the late postoperative period. The results suggest that pulmonary oxygenation is the most important determinant of mean subcutaneous oxygen tension after uncomplicated elective abdominal operations.
On the basis of the literature and the authors own investigations, the present article provides a brief schematic review of the fraction of the physiological immune response which has hitherto been investigated in connection with surgical trauma. Surgery, anaesthesia and blood transfusion induce temporarily acquired immune suppression and thus a potentially increased risk for postoperative infectious complications and recurrence after cancer surgery. The pathological physiological alterations in immune function which develop as a result of anaesthesia, surgery and perioperative blood transfusion are reviewed. The clinical sequelae of preoperative and postoperative immune suppression are increased morbidity and mortality rates. Future research in this field must, therefore, be focussed on detailed investigation of the mechanisms which lead to postoperative immune suppression and development of methods to prevent these.