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Biomedical subjects

W Zimmerli

Publications and source records attributed to W Zimmerli.

At least 163 records · Page 9Linked to original sources

Experimental hematogenous infection of subcutaneously implanted foreign bodies.

Implanted foreign bodies are highly susceptible to pyogenic infection. Whereas infection up to 3 months after surgery is probably due to perioperative bacterial contamination, little is known about the pathogenesis of late prosthetic infections. We employed an animal model to determine whether subcutaneously implanted foreign bodies were susceptible to experimental bacteremia. Tissue cages were implanted into guinea pigs, which were infected at the earliest 4 weeks later by intracardiac injection of Staphylococcus aureus Wood 46. The injection of 2 X 10(6) cfu did not result in any infection. Inoculation of 5 X 10(7) cfu resulted in a bacteremia of 10(2)-10(3) cfu/ml after 5 min and led to 11/26 selective tissue cage infections with no microbiological evidence of infection elsewhere. Higher inocula caused systemic infections with foci in different organs. Rifampin (7.5 mg/kg b.i.d.) was administered for 48 h, starting at different times after infection to establish the best timing for efficacious short-term therapy. When treatment was begun 1 h before or 3 h after inoculation, complete protection was observed, whereas 1/12 and 3/15 tissue cages remained infected when the first dose was not given until 24 h and 48 h, respectively, after inoculation. These experiments illustrate that implanted prostheses are highly susceptible even to bacteremias with low density of microorganisms. Prophylaxis can prevent such infections, whereas delayed short-term treatment may fail.

Animals↗

[Hematogenous infection of prostheses in man and in an animal model].

A case is reported which suggests a hematogenous route of infection in orthopedic prostheses. Furthermore, in a foreign body animal model the hypothesis was tested that implanted prostheses may be endangered during episodes of bacteremia. These experiments confirm the clinical impression that foreign bodies can be selectively infected during experimental bacteremia with Staphylococcus aureus.

Aged↗

[Infection in intensive care medicine: predisposition, pathogenesis and diagnosis].

Intensive care unit patients are a group with an increased risk for the development of septicemia. The combination of illness (trauma, burn, surgery, metabolic coma etc.) and iatrogenic factors (foreign bodies, ventilation, drugs etc.) make them more susceptible to severe infections. Rapid diagnosis of septicemia is important, since the prognosis is dependent on rapid treatment. Sedation and ventilation may mask the primary symptoms of septicemia, and in these cases the condition is not diagnosed until signs of complications (shock, disseminated intravascular coagulation, multiple organ failure) appear. Aside from clinical observation and laboratory results, hemodynamic symptoms may be indicative of septicemia. In the presence of septic signs, blood, tracheal secretion, urine etc. must be cultivated without delay, before starting empirical treatment. Surveillance cultures may make for more appropriate initial treatment, though they pose the problem of differentiation between colonization and infection.

Bacterial Infections↗

[Urinary tract infection in the diabetic patient].

Diabetic patients are said to be prone to infections. Several studies of different host defense mechanisms report defects in individual granulocyte functions and cell mediated immunity, especially in patients with poorly controlled diabetes. Diabetic females have an increased risk of developing urinary tract infections. This high susceptibility is probably due to local risk factors such as diabetic cystopathy and vaginitis, the latter being frequently associated with glucosuria. Urinary tract infections in diabetic individuals often have a complicated course which may be explained by the aforementioned compromised host defense mechanisms. Diabetics have an increased risk not only of lower, but also of upper urinary tract infections. Urinary tract infections such as emphysematous cystitis and pyelonephritis, as well as papillary necrosis as a complication of pyelonephritis, are not uncommon in diabetic patients. Rapid recognition and management of such complicated urinary tract infections is important.

Diabetes Complications↗

Comparative superoxide-generating system of granulocytes from blood and peritoneal exudates.

Blood polymorphonuclear leukocytes (PMN), upon interaction with specific chemotactic stimuli, leave the blood stream and migrate to tissues. At such a location, and upon contact with invading microorganisms, they generate superoxide (O2-) as a part of the respiratory burst of phagocytosis. We have compared the O2(-)-generating system of guinea pig peritoneal exudate PMN with that of peripheral blood PMN from the same species or of human origin. The rate of O2- production by casein-induced guinea pig exudate cells in response to a particulate stimulus (opsonized zymosan) was significantly decreased when compared with peripheral blood PMN. Furthermore, the activation time of the O2(-)-generating system was shorter in exudate than in peripheral blood PMN. Important differences in sensitivity to a metabolic inhibitor were found: (i) N-ethylmaleimide increased the activation time of the O2(-)-generating system only in guinea pig exudate cells and not in blood cells; (ii) when N-ethylmaleimide was added after complete activation of the PMN, the O2- production rate was inhibited in guinea pig as well as human blood PMN, but not in guinea pig exudate PMN. We conclude that exudation markedly alters one of the most important antibacterial mechanisms of PMN, the superoxide-generating system.

Animals↗

Pathogenesis of foreign body infection. Evidence for a local granulocyte defect.

Implanted foreign bodies are highly susceptible to pyogenic infections and represent a major problem in modern medicine. In an effort to understand the pathogenesis of these infections, we studied the phagocytic function in the vicinity of a foreign body by using a recently developed guinea pig model of Teflon tissue cages subcutaneously implanted (Zimmerli, W., F.A. Waldvogel, P. Vaudaux, and U.E. Nydegger, 1982, J. Infect. Dis., 146:487-497). Polymorphonuclear leukocytes (PMN) purified from tissue cage fluid had poor bactericidal activity against a catalase-positive microorganism. When compared with blood or exudate PMN, they exhibited a significant reduction in their ability to generate superoxide in response to a particulate or a soluble stimulus (72 and 57%, respectively, P less than 0.001). Not only their total contents in myeloperoxidase, beta-glucuronidase, lysozyme, and B12 binding protein were significantly reduced (by 62, 21, 47, and 63%, respectively, P less than 0.01), but also their capability for further secretion of residual B12 binding protein upon stimulation. Ingestion rates of endotoxin-coated opsonized oil particles were reduced by 25% (P less than 0.05). In an effort to reproduce these abnormalities in vitro, fresh peritoneal exudate PMN were incubated with Teflon fibers in the presence of plasma. Interaction of PMN with the fibers led to significant increases in hexose monophosphate shunt activity and exocytosis of secondary granules (P less than 0.01). PMN eluted after such interaction showed defective bactericidal activity, oxidative metabolism, and granular enzyme content similar to those observed in tissue cage PMN. The local injection of fresh blood PMN into tissue cages at the time of, or 3 h after, inoculation with 100 microorganisms (Staphylococcus aureus Wood 46) reduced the infection rate from 50 to 56 cages to 1 of 21 (P less than 0.001) and 3 of 8 cages (P less than 0.001), respectively. These results suggest that the in vivo as well as in vitro interaction of PMN with a nonphagocytosable foreign body induces a complex PMN defect, which may be partly responsible for the high susceptibility to infection of foreign bodies.

Animals↗

[Deleterious course in tumor patients with ectopic ACTH secretion and secondary Cushing's syndrome].

Ectopic ACTH secretion with secondary Cushing's syndrome was observed in two patients with metastatic islet cell carcinoma and oat cell carcinoma of the lung respectively. Both patients were young (27 and 31 years), male, and developed severe hypokalemia, metabolic alkalosis and hypertension. Besides excessively increased ACTH-secretion, increased free urinary cortisol, 17-hydroxy- and 17-ketosteroids were found. The dexamethasone suppression test was negative. Inhibitors of adrenal steroid synthesis (aminoglutethimide, trilostan, o,p'-DDD) did not significantly change cortisol secretion and hypokalemia, and clinical symptoms persisted. Radiotherapy (5000 cGy) resulted in a partial remission of short duration in one patient. Both patients, however, died of metabolic complications 2 and 8 months after the diagnosis of Cushing's syndrome.

ACTH Syndrome, Ectopic↗

In vitro efficacy of several antibiotics against intracellular S. aureus in chronic granulomatous disease.

We report the case of a one-year-old boy with chronic granulomatous disease (CGD), characterized by a defect in the polymorphonuclear leukocytes (PMN) which ingest, but do not kill catalase-positive bacteria such as S. aureus. This well-known observation led us to study the ability of clindamycin, rifampin, co-trimoxazole (TMP-SMX), methicillin and gentamicin to kill intracellular S. aureus in CGD and in normal PMN. Clindamycin killed S. aureus more effectively when these bacteria were intracellular than in the absence of PMN; rifampin was equally active on the same microorganisms in presence and absence of PMN, whereas TMP-SMX, methicillin and gentamicin were less effective in killing intracellular S. aureus. Similar results were obtained in CGD and in normal PMN. These results suggest that clindamycin and rifampin would be a reasonable choice in the treatment of staphylococcal infections in patients with CGD.

Anti-Bacterial Agents↗

Pathogenesis of foreign body infection: description and characteristics of an animal model.

An animal model involving the subcutaneous implantation of tissue cages into guinea pigs and subsequent infection with Staphylococcus aureus was used for study factors pertinent to foreign body infection. Whereas 10(8) colony-forming units (cfu) of S. aureus strain Wood 46 did not produce any abscesses in the absence of foreign material, 10(2) cfu was sufficient to infect 95% of the tissue cages despite the presence of polymorphonuclear leukocytes (PMNLs) in sterile tissue cage fluid. Opsonization of S. aureus by tissue cage fluid was adequate during the first hour of infection, but opsonic coating of the organisms decreased at 20 hr after the induction of infection. PMNLs from sterile tissue cage fluid showed decreased phagocytic and bactericidal activities when compared with PMNLs from either blood or peritoneal exudate obtained after short- or long-term stimulation (P less than 0.001).

Animals↗

[Surgery in the regional and district hospitals of German Switzerland].

The Regional Hospital is the hub in the surgical service for the broad population. According to its importance, it has furthermore an eminent role in instruction and postgraduate teaching. The requirements and profile for such competent medical chiefs are delineated. The broad surgical requirements, the executive duties in hospital administration, which are shared with the nursing and administration services, and the permanent personal education make it mandatory, that the position of the head surgeon be partitioned by two equally competent and polyvalent general surgeons. The ultimate responsibility for such adequate positioning rests with the political authority.

General Surgery↗