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In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics.

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Nosocomial infections are a major problem in intensive care patients. Thirty-nine patients, requiring intensive care for 5 days or more (mean 15.8 days) were prospectively investigated, to determine the relation between colonisation and nosocomial infection. Thrice weekly, cultures from the oropharynx, respiratory and digestive tract were obtained. Colonization with aerobic gram-negative microorganisms of the oropharynx, respiratory and digestive tract significantly increased during the stay in the Intensive Care Unit. In 29 patients (74%) 78 nosocomial infections were diagnosed. The most frequent nosocomial infections were pneumonia (26 patients, 66.6%), catheter-related bacteraemia (11 patients, 28.2%), and wound infections (7 patients, 17.9%). In 59 instances (75.6%), colonization with the same potential pathogenic microorganism preceded the nosocomial infection. The overall mortality was 25.6% (10 patients), bacteraemia with aerobic gram-negative microorganisms being the cause of death in 7 patients.

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Gastric emptying was studied in 18 symptomatic and 16 asymptomatic patients after Billroth II (BII) resection (without vagotomy) and the possible relationships between emptying and postprandial symptoms in these patients were assessed. The BII patients were compared with 20 nonoperated patients who had duodenal ulcer disease and 16 healthy subjects. Gastric emptying of two test meals (a semisolid porridge meal and a solid pancake meal) was measured with a radionuclide technique. The major difference between the BII patients and control subjects and duodenal ulcer patients was an increased rate of emptying of the semisolid meal in the first 5 minutes after meal consumption. The percentage of the meal remaining in the stomach at 5 minutes after completion was significantly less in the symptomatic (45.3% +/- 4.3%) than in the asymptomatic BII patients (79.4% +/- 2.6%). A positive correlation was demonstrated between the initial emptying rate of semisolids and the intensity of postprandial nausea (p less than 0.01), vomiting (p less than 0.05), and vasomotor symptoms (p less than 0.001). The duration of the lag phase for solid and semisolid meals was shorter in BII patients than in healthy subjects but was as short in nonoperated duodenal ulcer patients. The duration of the lag phase for solid food in the BII patients correlated positively with the score for postprandial epigastric pain (p less than 0.001). The rate of emptying of the solid meal was lower in symptomatic BII patients (28.1% +/- 3.6% per hour) than in asymptomatic patients (47.8% +/- 7.2% per hour) and correlated with the severity of postprandial fullness and nausea. The emptying of the solid meal was inversely related to the initial emptying rate of the semisolid meal (p less than 0.05). Therefore, the results of this study support the assumption that many of the postprandial symptoms occurring after BII resection reflect alterations in gastric emptying. Some of the emptying abnormalities present after BII resection may be related to duodenal ulcer disease rather than to the surgical procedure.

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Electrical stimulation of osteogenesis was studied in rabbit femora in: (A) a transcortical electric field with a cortex-depolarizing or hyperpolarizing orientation derived from an intramedullary electrode and a ring-shaped counter electrode encircling the femoral shaft; and (B) an electric field derived from an electrode located in the medullary canal and the counter electrode in the abdominal wall. Electrodes were made of platinum. A direct current of 20 microA was applied during six weeks. Contralateral femora with dummy electrodes served as controls. Results were analyzed by optical densitometry of roentgenograms and histomorphometry of histologic slides. Under the conditions of these experiments bone growth was not stimulated by applying a cortex-depolarizing electric field. Significant stimulation of bone growth was only observed at an intramedullary cathode, when the anode was placed at a distance.

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Ceramic hydroxyapatite and tricalcium orthophosphate were radioactively labeled with their strontium-85 analogs. Porous blocks of these materials (dimensions 2.5 X 1.25 X 0.5 cm) were implanted into surgically created defects in dog femora. The fate of the implants was studied by roentgenography, radioactivity measurements, histology, and microradiography. The radioactivity over the implant site was followed for 22 weeks. Implants were retrieved after 20-25 and 50-55 weeks. Hydroxyapatite implants were not affected by biodegradation processes, while tricalcium orthophosphate implants were subject to extensive bioresorption (25%-30% in 22 weeks). Resorption debris from tricalcium orthophosphate implants was found in mononuclear phagocytes and multinuclear osteoclastlike cells. The supposition is that tricalcium orthophosphate is transformed into hydroxyapatite in a physiologic environment. Labeling of ceramic calcium phosphate implants with strontium-85 analogs offers an adequate technique to quantitate bioresorption in vivo.

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Cisapride is a newly developed substance that stimulates gastrointestinal motility, possibly enhancing acetylcholine release in the gut wall. The aim of our study was to investigate the effect of cisapride on oesophageal motor function in man. In a blind fashion and in random order six healthy volunteers received cisapride (0.5 mg/h intravenously, preceded by a three day oral loading at 10 mg tid) and matching placebo. Oesophageal contractions and lower oesophageal sphincter pressure were constantly recorded during a complete cycle of the interdigestive migrating motor complex and during two and half hours after a mixed test meal. Cisapride did not disturb the interdigestive migrating motor complex. In the fasting state the lower oesophageal sphincter pressure showed considerable interdigestive migrating motor complex phase-related variations, whereas amplitude and duration of the oesophageal contractions did not. In the dosis used cisapride was found to increase lower oesophageal sphincter pressure in the interdigestive and in the late postprandial state, but to have no effect in the early postprandial period. Amplitude and duration of oesophageal contractions were not affected by cisapride.

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A 5 to 12 year follow-up study of 132 patients with nonobstructive duodenal ulcer treated by HSV without a drainage procedure was done. The results of pre- and postoperative gastric emptying studies and pre- and postoperative acid secretion studies were related to recurrent ulceration and postoperative complaints. The almost 9 percent of instances of recurrent ulceration were found in the group of patients with preoperative PPAO values greater than 40 mmol/hr. In all 13 patients with preoperative PPAO values greater than 60 mmol/hr, HSV was considered a failure. It was concluded that at least the latter group should be excluded from HSV. In 4.3 percent of patients serious gastric stasis after HSV was cause for reoperation. In spite of meticulous denervation and peroperative open pH metry, inadequate vagotomy, defined as percent reduction of PIAO values after HSV less than 75 percent, was found in 33 out of 117 patients. In an experimental study, vascular occlusion alone also gives a positive Grassi test. From both facts the relative value of this test can be concluded. Symptoms after inadequate vagotomy were again clearly related to preoperative PPAO values.

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Blocks of porous ceramic hydroxyapatite (dimensions, 2.5 X 1.25 X 0.5 cm; sintering temperature, 1300 degrees; macroporosity, 56%; average pore size 0.18 mm2) were implanted into surgically created defects in dog femora. The implants were retrieved up to 3.5 years after implantation. The implants were 3.5 years after implantation. The implants were firmly attached to the bone. Histologic evaluation suggests that optimal contact between bone and implant should be provided to accelerate bone ingrowth. Bone growth in the pores reached a maximum level after 35 weeks, at which time about one-third of the pore space was filled with bone. When measuring the relative surface areas of bone and ceramic on histologic slides, no change in ceramic mass could be detected, indicating that hydroxyapatite ceramics are not affected by biodegradation processes. The implants effectively provided a scaffold for bone growth bridging a larger bone defect.

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Techniques for the measurement of gastric emptying using radionuclides are reviewed as a basis for a discussion of gastric emptying tests. A new technique for the noninvasive quantitative measurement of antral motility is described, whereby measurements of redistribution of gastric contents between fundus and antrum and actual gastric emptying are obtained simultaneously. These tests provide more relevant insight into the pathophysiology of gastric motility disturbances than that previously obtained by conventional gastric emptying studies.

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A theory for the mechanism of electrical bone stimulation proposes that passage of an electric current reduces the local PO2 and raises the pH near the cathode, thereby creating a favorable environment for osteogenesis. To study the effects of electric current passage on the PO2, PCO2 and pH in the vicinity of the electrodes in vivo, a wire electrode spiralled around the catheter of a clinical mass spectrometer was placed in dog muscle. Electrodes were made of stainless steel or platinum. With a cathode located in the tissue, a 20-microA direct constant current caused a drop in PO2 of 5-10 mmHg and a drop in PCO2 of 2-6 mmHg, both reaching plateaus again within five to 20 minutes. The time required to reach this new equilibrium was shorter for platinum than for stainless steel. When the electric current was turned off, PO2 and PCO2 reversed to their original values. Because of the high buffer capacity of tissue, it is highly unlikely that 20-microA current would induce a change in pH.

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Two kindreds with the multiple endocrine neoplasia type 2A syndrome were studied. Of one of these we examined 150 members, 20 of whom were treated with thyroidectomy for medullary carcinoma and nine with bilateral adrenalectomy for pheochromocytoma. Of the second kindred 50 members were examined, seven of whom were thyroidectomized and seven treated with bilateral adrenalectomy. Pheochromocytomas were invariably found on both sides, even in four cases in which the adrenals on one side appeared to be completely normal, not only at preoperative roentgenologic examination but also on inspection during the operation. The microscopic finding of micronodules and a cluster of abnormal medullary cells identical with those found in pheochromocytomas in one of the apparently normal adrenals represents a first stage in the development of diffuse medullary hyperplasia as well as nodular hyperplasia. This is in accordance with the fact that in the MEN type 2A syndrome pheochromocytomas are always multicentric and multiple in origin. On the basis of these findings we conclude that all patients with the MEN 2A syndrome who show symptoms and signs of active pheochromocytoma should be subjected to bilateral adrenalectomy, even when one or both of the adrenals appear to be normal at roentgenologic investigation.

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We evaluate whether highly selective vagotomy (HSV) might disturb functional integrity of the lower esophageal sphincter (LES). Special interest was directed to changes in position of the LES in relation to the diaphragm, LES pressure, and pH reflux pattern. The conditions of 20 patients were evaluated by manometric studies and by 12-hour overnight pH measurements before and 14 days after HSV; five of them were also studied one year after HSV. The results indicate: (1) There is a slight elongation of the LES in the early postoperative phase, which seems to disappear after one year. (2) The position of the diaphragm as measured manometrically by the pressure inversion point descends in relation to the LES 14 days after HSV, and it does not seem to return to its original position after one year. (3) There is no significant change in LES pressure after HSV. (4) There is no increase in reflux after HSV.

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The results of a prospective study of 60 patients with nonobstructive duodenal ulcer treated by highly selective vagotomy show that the gastric acid secretion postoperatively is effectively reduced. Judgment of completeness of highly selective vagotomy is only possible by means of an intragastric pH-metry during operation. The Hollander test answers it insufficiently. In a number of patients, highly selective vagotomy caused a fast initial phase of gastric emptying of porradge. The impression is that the contractional activity of the antrum has the same pattern before and after highly selective vagotomy.

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