Therapy with gentamicin-PMMA beads, gentamicin-collagen sponge, and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats.

INTRODUCTION: In spite of new surgical techniques and recently developed antibiotics, there is no satisfactory solution for the treatment of chronic posttraumatic osteomyelitis. The introduction of local antibiotic treatment with gentamicin-PMMA beads according to Klemm has provided new stimuli for the treatment of chronic osteomyelitis. With the development of collagen as an absorbable carrier substance, the disadvantages of the rigid carrier system became evident. Due to the varying surgical techniques and different forms of adjuvant therapy, it is difficult to assess therapeutic methods and compare different studies. Therefore, it seemed appropriate to study the effect of local treatment with different antibiotic carriers in the setting of an animal study. MATERIALS AND METHODS: The proven rat model for Staphylococcus aureus-induced osteomyelitis was used to compare the results of monotherapy with cefazolin, gentamicin-PMMA beads, or gentamicin-containing collagen sponge with the combination of local and systemic antibiotic treatment. RESULTS: Single-agent therapy with parenterally administered cefazolin reduced the CFU from 3.7 x 10(6) to 2.9 x 10(4) g(-1) of tibial bone. The effect on osteomyelitis was more pronounced with the local application of antibiotics. The best results were achieved with the gentamicin-containing collagen sponge which reduced the bacterial colony count to 1.4 x 10(2) CFU/g compared with 9.8 x 10(2) CFU/g achieved with gentamicin-PMMA beads. The effect was most marked using a 4-week combination therapy with local application of the gentamicin-containing collagen sponge and systemic administration of cefazolin. In 9 of 11 animals, no bacteria could be detected in the bone. CONCLUSION: Each of the treatment modalities resulted in a significant therapeutic effect. Due to its ability to quickly release large amounts of gentamicin, the flexible gentamicin-containing collagen sponge proved to be superior to the rigid PMMA system. Although the gentamicin-containing collagen sponge provided high antibiotic concentration at the site of implantation, an additive effect was attained when combined with systemic antibiotic treatment.

Synergy of HBO2 and a local antibiotic carrier for experimental osteomyelitis due to Staphylococcus aureus in rats.

A standard rat model of Staphylococcus aureus-induced osteomyelitis was used to compare the effect of HBO2, a local antibiotic carrier (gentamicin-containing collagen sponge) and the combination of HBO2 with a local antibiotic carrier. For the induction of osteomyelitis, a defined Staphylococcus aureus suspension was inoculated into the medullary cavity. Arachidonic acid was used as sclerosing agent. With that procedure an infection rate of more than 95 percent was attained. Prior to the treatment interval surgical debridement of the soft-tissue infection was performed. In the control group the extent of infection was 4.9 x 10(6) CFU x g(-1) of tibial bone three weeks following implantation of organisms. Subsequent to debridement of the soft tissue infection, the bone infection decreased slightly with a value of 3.7 x 10(6) CFU x g(-1) of tibial bone at the end of the experiment. HBO2 as single-agent therapeutic reduced the infection to 1.7 x 10(5) CFU x g(-1) of tibial bone. Due to its high local antibiotic level, the gentamicin-collagen sponge achieved a reduction in organisms to 1.4 x 10(2) CFU x g(-1) of tibial bone. The effect was most marked using a 4-wk combination therapy with local application of the gentamicin-containing sponge and additional treatment with HBO2. In 9 of 11 animals, bacteria were no longer detectable in the processed bone substance. Each of the treatment modalities resulted in a significant therapeutic effect. No complete healing of the infection was achieved with the flexible collagen sponge characterized by pronounced and rapid release of gentamicin. In combination with hyperbaric oxygen an additive effect was attained and thus a significant improvement of treatment.

Therapy with hyperbaric oxygen and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats.

Hyperbaric oxygen (HBO2) is used as adjunctive therapy for chronic osteomyelitis, yet its efficacy remains controversial. A recently developed rat model for osteomyelitis due to Staphylococcus aureus was used to compare the results of treatment with HBO2, cefazolin, a combination of both, or no treatment. For the induction of tibial osteomyelitis, S. aureus was inoculated into the medullary cavity. Arachidonic acid was used as the sclerosing agent. With that procedure, an infection rate of 96% was attained. For long-term antibiotic treatment, a port system was developed and implanted. Hyperbaric treatment alone reduced the colony-forming units (CFU) from 2.9 x 10(6) to 6.2 x 10(5) x g(-1) of tibial bone. The effect on the infection was more pronounced with antibiotic therapy alone, 10.5 x 10(4) CFU per g of tibial bone were measured. However, changes were most marked using a 4-wk combination therapy consisting of HBO2 and an antibiotic agent. The colony count was 2.7 x 10(3) CFU. Each of the treatment modalities resulted in a significant therapeutic effect. The results not only demonstrated the effectiveness of HBO2 in the treatment of osteomyelitis, but revealed a potential additive effect with the combination of HBO2 and an antibiotic.

Satietin: Fos mapping of putative brain sites of action.

A purified extract of a blood-borne satiety factor, called satietin, was injected into the cerebral ventricles of rats that were either fed ad libitum or were food deprived. The animals were killed 2 h after injection and their brains subsequently sectioned and stained for Fos-like immunoreactivity (Fos-IR) to determine the putative sites of action for satietin in the brain. Fos-IR was induced in only a few locations, the most prominent sites being the bed nucleus of the stria terminalis, the central nucleus of the amygdala, and the parvocellular division of the paraventricular nucleus of the hypothalamus. Each of these areas has previously been implicated in the control of feeding behavior. Sites in the hindbrain that are associated with nausea were devoid of satietin-induced Fos-IR. Finally, these sites of action of satietin show some differences from sites that are prominently activated by other classes of anorectic agents.

Blood profile and balance study of rats given the putative anorectic agent satietin.

Satietin (SAT), a glycoprotein found in the plasma of a variety of animals, is a putative satiety agent. In experiments 1 and 2 rats received chronic third ventricle cannulas. At the start of the dark phase, in experiment 1, one group was infused with artificial cerebrospinal fluid (aCSF) and fed ad libitum (CON); a second group was infused with 100 micrograms/rat of human SAT and fed ad libitum in individual computerized pellet feeding modules; a third group was infused with aCSF and pair fed (PF) to the SAT-treated rats. The animals were killed 19.5 h later and blood was collected. Food and water intake and body weight were significantly, and comparably, reduced in the SAT-treated and PF group compared with the CON group. Plasma was assayed for a variety of nutrients, metabolites, enzymes, hormones, ions, and osmolality. Differential white cell counts were made. None of the above parameters differed significantly between the SAT and PF groups. Meal pattern analyses showed SAT treatment did not at any time alter meal size but significantly increased meal duration and intermeal interval during the first 6 h of the dark phase. In experiment 2 rats were placed in metabolic cages and infused with SAT or aCSF. Food and water intakes of the SAT group were suppressed for 1 day, whereas their body weights were significantly attenuated for 3 days. Urine volume and feces elimination were similar in the two groups over the 6-day measurement period. The normalcy of the data from experiment 1 is in accord with the possibility that SAT may act as a physiological satiety agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of components derived from HPLC purification of human satietin on ingestion, body weight, and taste aversion in the rat.

The putative satiety agent human satietin (h-SAT) once thought to be homogenous has been separated by high-performance liquid chromatography (HPLC) into components designated peak A (P-A, 53%/w) and Peak B (P-B, 47%/w); P-B contains a putative satiety agent. In Experiment 1, male Sprague-Dawley rats were divided into six (n = 9-11) groups (Grps) and ICV infused: Grp 1, artificial cerebrospinal fluid (a-CSF), 10 microliters/rat; Grp 2, albumin (ALB), 53 micrograms/rat; Grp 3, semipurified (sp) h-SAT (parent compound), 100 micrograms/rat; Grp 4, P-A, 53 micrograms/rat; Grp 5, P-B, 47 micrograms/rat; and Grp 6, P-A+B, 53+47 micrograms/rat, respectively. Compared to Grp 1, food intake, the first day postinfusion, was suppressed in Grp 3 (p < 0.01) and equally attenuated (p < 0.06) in Grps 5 and 6. Body weight remained suppressed (p < 0.05) in Grps 3, 5, and 6 for 3 days and in Grps 3 and 6 (p < 0.05) for an additional 3 days; Grps 2 and 4 did not differ from Grp 1. These data show P-B suppresses food intake comparably to P-A+B and causes a prolonged weight loss. In Experiment 2, sph-SAT and a recombination of P-A and P-B was tested for aversiveness using the two-bottle test. Both sph-SAT and P-A+B significantly suppressed food intake, but only sph-SAT was found to be aversive. These data show that most likely during HPLC processing of sph-SAT an aversive component was lost.

HPLC-purified human satietin does not produce conditioned taste aversion in rats.

Human satietin is thought to be an endogenous glycoprotein that can suppress food intake and body weight. However, it was also found to be aversive when rats infused intracerebroventricularly (ICV) with human satietin were subjected to a two-bottle taste aversion test. More recently, the human satietin previously thought homogenous was separated by HPLC into two Peaks, denoted as A and B. In the present study, male Sprague-Dawley rats were fitted with chronic third ventricle cannulas and presented with fluid for 1 h/day, while food was given ad lib. After training, the rats were ICV infused with either artificial cerebrospinal fluid, Peak A or Peak B of human satietin. Peak B significantly reduced short-term and 24-h food intake, whereas their fluid intake was nonsignificantly attenuated. Peak A had no affect on either food or fluid intake on the day it was administered. When the rats were given the two-bottle taste aversion test neither compound was found to be aversive. These data suggest that Peak B may contain satietin(s) which could be a candidate for an endogenous satiety agent.

Interaction of cholecystokinin-8 and pancreatic glucagon in control of food intake in dogs.

Feeding responses to continuous intravenous administration of graded doses of the COOH-terminal octapeptide of cholecystokinin (CCK-8) and pancreatic glucagon, alone and in combination, were determined in dogs fasted 4 h. Low doses of glucagon (50, 500, 5,000, 6,000 pmol.kg-1.h-1) had no effect on food intake, whereas higher doses (12 and 24 nmol.kg-1.h-1) depressed intake by 50-60%. Of the CCK-8 doses administered (50 and 400 pmol.kg-1.h-1), food intake was depressed only at the higher dose (53%). This effect was blocked by glucagon (50-5,000 pmol.kg-1.h-1). Simultaneous administration of 50 or 500 pmol.kg-1.h-1 of glucagon and 50 pmol.kg-1.h-1 of CCK-8, doses currently thought to produce plasma peptide levels similar to those occurring postprandially in dogs, had no effect on food intake. These results suggest that plasma levels of CCK and glucagon after a meal are not sufficient alone or in combination to produce satiety.

The effects of semi- and HPLC-purified human satietin and alpha-1-glycoprotein on ingestion and body weight.

Satietin is thought to be an endogenous glycoprotein that can suppress food intake (FI) and body weight (b.wt.). In Experiment 1, rats were ICV infused with either a-CSF or with 50 micrograms/rat of human satietin. FI was suppressed (p less than 0.05) for 2 days after infusion, whereas b.wt. was attenuated (p less than 0.05) for 14 days. In Experiment 2, the previously thought homogenous human satietin was further purified by HPLC and this yielded two peaks (A and B). Rats were ICV infused with either a-CSF or 50 micrograms/rat of Peak A, Peak B or the semipurified parent human satietin (sph-SAT) from which the peaks were derived. All three treatments suppressed (p less than 0.05) FI on day 1 after infusion and on day 2 in the groups that received Peak A and sph-SAT. Body weight was attenuated (p less than 0.01) in all the experimental groups on day 1 and for 2 and 10 days, respectively, in the Peak A and sph-SAT-treated groups. Immunostaining revealed Peak A contained both albumin and alpha-1-glycoprotein (A1G), whereas Peak B contained neither. In the last experiment rats were ICV infused with either a-CSF or 50 micrograms/rat of A1G or A1G that was put through the sph-SAT extraction procedure. FI was suppressed (p less than 0.01) and b.wt. attenuated in both experimental groups only on the first day postinfusion. These data suggest that some, but possibly not all, of the previously found biological activity attributed to sph-SAT might be due to contaminants of the preparation.

[Insulinoma. Results of surgical treatment]. / Insulinome. Ergebnisse der chirurgischen Therapie.

The insulinoma is the most common pancreas tumour with endocrine activity, with more than 2,000 cases being described in the literature worldwide. The first successful extirpation was performed by Graham in 1928. Clinical appearance is characterized by severe paroxysmal hypoglycaemia together with inadequately increased serum insulin levels. Surgery is indicated in such situations because of limited effectiveness of medicamentous therapy. Surgical approach and long-time results are discussed in this paper, with reference being made to 13 cases of the authors.

Interaction of CCK-8 and somatostatin-14 in control of food intake in dogs.

interactions of cholecystokinin COOH-terminal octapeptide (CCK-8) and somatostatin-14 (SS-14) on food intake in dogs were examined by administration of graded doses of these peptides alone and in combination. In animals fasted 19 h, SS-14 (2,000 or 20,000 pmol.kg-1.h-1) had no effect on food intake. In animals fasted 4 h, food intake was not affected by 40 or 400 pmol.kg-1.h-1 SS-14 but was significantly (P less than 0.05) increased by 20% after 4,000 pmol.kg-1.h-1 SS-14. Feeding responses to simultaneous infusions of CCK-8 (50 or 400 pmol.kg-1.h-1) and SS-14 (40, 400, or 4,000 pmol.kg-1.h-1) were determined in animals fasted 4 h. Given alone, the high dose of CCK-8 (400 pmol.kg-1.h-1) significantly (P less than 0.01) depressed food intake by 55%. This effect was blocked by all doses of SS-14. In the absence of CCK-8, SS-14 had no effect except at the highest dose (4,000 pmol.kg-1.h-1), which significantly (P less than 0.01) stimulated food intake by 57%. This effect was blocked by both doses of CCK-8. Simultaneous infusion of lower doses of SS-14 (40 and 400 pmol.kg-1.h-1) and CCK-8 (50 pmol.kg-1.h-1) had no effect on food intake. These results suggest that plasma levels of CCK and SS-14 after a meal are not sufficient alone or in combination to produce satiety.

[Gambee single modified all-layer suture]. / Die einreihige modifizierte Allschichtennaht nach Gambee.

Our modified all-layer suture technique allows surgery of colon and rectum with a low rate of anastomotic leaks (2%). In experimental animal research on pigs we compared the modified all-layer suture with the Gambee and the stapling technique. The circulation was examined by radioactive marked microspheres, by microangiograms and by special injection preparations.

Human satietin: rapid development of tolerance and its specificity to feeding behavior in rats.

Semipurified human satietin (SP hSAT) significantly (p less than 0.05) reduced food intake for each of five consecutive days when injected intraperitoneally (2 mg/kg/day). Tolerance developed rapidly during the second and third days of injection but food intake of those animals receiving the highest doses of Sp hSAT (1 and 2 mg/kg/day) remained significantly below (p less than 0.05) that of the saline-injected animals. Food intake of rats receiving doses of 0.5 and 0.25 mg/kg/day Sp hSAT was below that of the saline-treated group for the first two days of injection (p less than 0.05) but not thereafter. Water intake fell in all satietin-treated groups on the first day of injection, thereafter, it was similar to the saline-treated group. In a second study Sp hSAT (1, 0.5, 0.25 mg/kg/day) was continuously infused IP by Alzet pumps. All doses of Sp hSAT significantly reduced food intake below that of the saline-treated group for the entire 7 days of infusion (p less than 0.05); water was not affected except on the first day of infusion (p greater than 0.01). In a third study, injection of purified human satietin (p hSAT) (2 mg/kg, IP) in fasted rats (24 hr) had no effect on water consumption either during fast or 24 hr postfast (p greater than 0.05). In a fourth study p hSAT was continuously heated to 37 degrees C. Aliquots were taken each day and injected (IP) into 4 naive rats (total of 24 rats) for a total of 6 days of heating (120 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Pyrrolizidine alkaloid-induced liver disease in horses: an early diagnosis.

Nine adult horses were fed alfalfa hay cubes containing approximately 10% Senecio vulgaris until all horses had consumed approximately the same amount of toxic components of S vulgaris, pyrrolizidine alkaloids (PA). The amount of PA consumed was determined by the amount that induced clinical signs of PA toxicosis in 3 horses. The 6 other horses were given similar amounts per kilogram of body weight. An initial decrease of feed intake was observed when horses' diets were changed from alfalfa cubes to alfalfa/Senecio cubes, and feed intake was decreased further over 89 to 98 days. From 50 to 159 days, body weight decreased in all horses. Liver disease was induced in all 9 horses after they ate an average of 233 +/- 9.2 mg of PA/kg of body weight. Eight horses died or were euthanatized. Treatment with branched chain amino acids had no effect on mortality, but appeared to reduce neurologic problems. Clinical signs of PA-induced liver disease included ataxia, head pressing, and decreased feed intake. Other clinical signs of toxicosis were observed individual horses, but did not develop in most horses. Megalocytic hepatopathy developed. Liver abnormalities proceeded as PA was consumed and were severe in 8 of 9 horses before clinical signs of toxicosis appeared. Sulfobromophthalein sodium clearance did not decrease until PA-induced liver disease was advanced. Bile acid (BA) concentrations increased to greater than or equal to 50 mumol/L, in the 8 horses that died. One horse had hepatopathy and increased BA concentration, but survived. In this horse, BA concentration peaked at 33 mumol/L and then decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Ingestion, body weight and activity of rats receiving repeated intracerebroventricular infusions of rat satietin.

Satietin is a putative satiety agent that is found in a variety of species including man and the rat. In the first experiment male Sprague-Dawley rats were fitted with chronic third ventricle cannulas and placed in activity wheels. After recovery, animals were intracerebroventricularly (ICV) infused with either sterile rat satietin (r-SAT) (100 micrograms/rat) dissolved in 10 microliters saline (n = 6) or sterile saline (n = 8). Infusions were repeated the next two days. Infusions of r-SAT had no effect on the rats' water intake or activity but did suppress (p less than 0.05) their food consumption when compared to the controls, but only after the first and second infusions. Thus tolerance to r-SAT quickly developed using this schedule of administration. Notably, body weight of the r-SAT infused rats remained attenuated (p less than 0.01) for four days following the first infusion. In the second experiment the rats were ICV infused every fourth day with either r-SAT (100 micrograms/rat) (n = 10) or saline (n = 8) for a total of three infusions. Food, but not water, intake was significantly suppressed after the first and second infusions and lowered nonsignificantly after the third. Body weight was significantly reduced after the first r-SAT infusion and remained statistically reduced for seven days after the third infusion; at a time when the rats' food intake was normal. These data suggest that in addition to a r-SAT suppression of feeding, other r-SAT induced changes (possibly metabolic) may help reduce the rats' body weight. The above dose of r-SAT had no affect on the animals' rectal temperature. The data of the above two experiments reveal that r-SAT infused ICV into rats can suppress the animals' food intake and lead to a prolonged attenuation of body weight.

[Computer-assisted analysis of intestinal sounds for assessing the motility of the gastrointestinal tract]. / Rechnerunterstützte Darmgeräuschanalyse zur Motilitätsbeurteilung des Gastrointestinaltraktes.

Intestinal noise analysis by means of a computerized analyser is a method by which various functional states of the gastro-intestinal tract can be diagnosed. Interference noise from respiration and cardiac action can be suppressed by filtering. Frequency patterns determined were in good correlation with the clinical picture and auscultation findings. It is, basically, possible to identify the original causative organ.