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Biomedical subjects

W Zimmerli

Publications and source records attributed to W Zimmerli.

At least 127 records · Page 7Linked to original sources

Humoral immune response to pneumococcal antigen 23-F in an asplenic patient with recurrent fulminant pneumococcaemia.

Host defence mechanisms were analysed in a patient with three episodes of fulminant pneumococcaemia and one episode of bacteraemic epiglottitis with Haemophilus influenzae type b. The first episode took place 11 years after splenectomy for blunt abdominal trauma. Investigations revealed several host defence mechanisms to be impaired. In addition to the patient's asplenia, an inherited C2-deficiency was noted. Assessment of IgG subclasses repeatedly revealed markedly low IgG4 concentrations. These were not due to an increased turnover of IgG4, as could be shown following infusion of intravenous IgG. In addition, IgG2 concentrations were low in the patient who lacked G2M(23). Opsonic mediating antibodies against type 23-F pneumococci were in the range of those of non-immune volunteers 6 months after vaccination with a 23-valent pneumococcal vaccine. These antibodies did not increase after a septic episode with 23-F capsular-type pneumococci. Neutrophil function was apparently normal.

Adolescent↗

Pretreatment with ibuprofen augments circulating tumor necrosis factor-alpha, interleukin-6, and elastase during acute endotoxinemia.

Plasma levels of tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) were monitored after intravenous administration of Escherichia coli endotoxin with or without ibuprofen pretreatment to healthy volunteers. Intravenous endotoxin (n = 7) resulted in elevated plasma TNF alpha concentrations with maximal levels at 90 min (369 +/- 44 pg/ml, P less than .001 vs. saline controls, n = 7). The rise in TNF-alpha was followed by a rise in plasma IL-6 (27 +/- 12.8 ng/ml), peaking 30-90 min thereafter. Pretreatment with ibuprofen (n = 6) caused a significant augmentation and temporal shift in cytokine elaboration with maximal TNF alpha levels (627 +/- 136 pg/ml) at 120 min and IL-6 peaks (113 +/- 66 ng/ml) at 180 min. In ibuprofen-treated volunteers, the additional increase in TNF alpha was paralleled by increased levels of circulating elastase. In vitro experiments suggest a causal relationship between these events. Thus, the cyclooxygenase inhibitor ibuprofen blunts the clinical response to endotoxin but augments circulating cytokine levels and leukocyte degranulation.

Adult↗

Killing of nongrowing and adherent Escherichia coli determines drug efficacy in device-related infections.

Antimicrobial therapy of device-related infections often fails, despite the in vitro susceptibility of the infecting strain. Therefore, alternative laboratory-based in vitro tests are required to predict the outcome. Fleroxacin, ciprofloxacin, aztreonam, and co-trimoxazole were tested against Escherichia coli ATCC 25922 in vitro and in the tissue-cage animal model. The importance of early treatment was evaluated by starting the drugs either 30 min before or 4, 12, and 24 h after bacterial challenge. Results were compared with the in vitro drug efficacy against nongrowing and adherent Escherichia coli ATCC 25922. The alternative in vitro tests correlated highly with the outcome in the tissue-cage animal model. In the prophylaxis group (drug given 30 min before bacterial challenge), co-trimoxazole was less efficacious than the other three drugs (P less than 0.001). In delayed treatment, ciprofloxacin showed the highest cure rate. It was also more potent than the other drugs against nongrowing and adherent E. coli ATCC 25922. The efficacies of aztreonan, fleroxacin, and ciprofloxacin dropped significantly (P less than 0.01) when the time interval between bacterial challenge and the start of treatment was delayed to greater than 4 h. These data emphasize (i) the need for proper timing of prophylaxis in patients undergoing implant surgery, and (ii) the possibility of successful treatment of established device-related infections with drugs which kill not only growing but also nongrowing and adherent bacteria.

Animals↗

[Preventive use of antibiotics for internal medicine diseases].

Prevention of infection by the interniste is less explored than perioperative prophylaxis. Basically, prophylaxis in internal medicine may be considered in the following situations: in case of chronic recurrent infections, in case of persisting infections, after contact with a dangerous microorganism, after contact with a potentially infectious vector, during bacteremia or in case of an anatomical defect. For some of these situations (malaria, tuberculosis, rheumatic fever) clear guidelines exist which, however, are rather based on the consensus of experts than on scientific data. For other diseases (e.g. chronic recurrent urinary tract infections) clinical studies are the basis for a rational proceeding. For a third group of situations (e.g. Lyme disease, chronic bronchitis, leak of cerebrospinal fluid, implant) neither guidance nor sufficient clinical data exist. In these cases the proceeding is individual. The basis for the decision is given by clinical observations, single studies, theoretical considerations or cost-benefit analyses.

Anti-Bacterial Agents↗

[Infection of vascular prosthesis].

Infections of vascular grafts are rare, but often life-threatening. Clinical signs and symptoms must be actively sought for, since the association with past vascular surgery is not always evident. Clinical history reveals fever, delayed wound healing, ischemia, or possibly gastrointestinal bleeding. Signs are wound infection, fever, septic emboli, or a new vascular murmur. Laboratory findings are non-specific. In most cases, diagnosis can be made by scintigraphy techniques. Treatment with antibiotics alone is seldom successful, and may be complicated by progressive infection (suture insufficiency). Mortality and morbidity of vascular graft infection are high, so that prophylaxis and early diagnosis are of paramount importance.

Anti-Bacterial Agents↗

The role of formylpeptide receptors, C5a receptors, and cytosolic-free calcium in neutrophil priming.

Polymorphonuclear leukocytes (PMNL) exposed to chemoattractants or cytokines change their functional capacity. The effect of endotoxin-activated serum as a priming agent on human PMNL was tested. Pretreatment of PMNL with endotoxin-activated serum increased their oxidative burst in response to formylpeptide (FMLP) (P less than .02) and C5a (P less than .05). Priming for membrane depolarization was observed in PMNL preincubated with either endotoxin-activated serum, low concentrations of purified C5a, or endotoxin but not with decomplemented plasma. Primed PMNL had an increased number of FMLP but not C5a receptors as compared with control PMNL. The "resting" cytosolic free calcium was increased in primed PMNL (P less than .02). Intracellular calcium buffering abolished the priming effect of endotoxin-activated serum. Thus, endotoxin-activated serum can prime cellular responsiveness for membrane depolarization and superoxide production in response to FMLP and to C5a. Priming may be due to an increased resting cytosolic-free calcium.

Calcium↗

Correlation between in vivo and in vitro efficacy of antimicrobial agents against foreign body infections.

Implant-associated infections are often resistant to antibiotic therapy. Routine sensitivity tests fail to predict therapeutic success. Therefore experimental in vitro tests were sought that would better correlate with drug efficacy in device-related infections. The activity of six different antibiotics against methicillin-resistant Staphylococcus epidermidis was investigated. In vivo studies were performed with the guinea pig tissue-cage animal model; in vitro studies with minimum inhibiting and bactericidal concentrations, time-kill studies of growing and stationary-phase microorganisms, the killing of glass-adherent S. epidermidis. Drug efficacy on stationary and adherent microorganisms, but not minimum inhibiting concentrations, predicted the outcome of device-related infections. Rifampin cured 12 of 12 infections and was also the most efficient drug in any experimental in vitro test. Similarly, the failure of ciprofloxacin to eradicate foreign body infections correlated with its low efficacy on stationary-phase and adherent S. epidermidis.

Animals↗

Prospective endoscopic study of stress erosions and ulcers in critically ill neurosurgical patients: current incidence and effect of acid-reducing prophylaxis.

We studied prospectively 40 critically ill neurosurgical patients who required prolonged mechanical ventilation to determine the current incidence of stress-related gastroduodenal erosions and ulcers, and to assess endoscopically the efficacy of acid-reducing prophylactic treatment. Nineteen patients were randomized to receive ranitidine plus antacids if necessary to maintain gastric pH at greater than or equal to 4. The remaining 21 patients were given no drug prophylaxis. Gastric pH was significantly (p less than .001) higher in the treated group: 78% of pH readings were at greater than or equal to 4 as compared to 32% in the control group. However, after five study days, incidence and severity of stress lesions were similar in the two groups: nine patients in each group had more than five erosions, one treated patient had a gastric ulcer, and one control patient had duodenal ulcerations. No patient experienced clinically relevant upper GI bleeding. The lack of severe stress bleeding and the low ulcer rate contrast with results from earlier reports on similar patient populations. Furthermore, drug prophylaxis had no detectable benefit, as assessed endoscopically. These findings suggest that routine stress lesion prophylaxis may not be necessary in critically ill patients with comparable risk factors.

Adolescent↗

Salmonella infection in total hip replacement: tests to predict the outcome of antimicrobial therapy.

We report a hematogenous implant infection with Salmonella dublin in a renal transplant patient with total hip replacement. A 16-month treatment with cotrimoxazole failed, as evidenced by culture and electron microscopy, despite persisting low MIC after therapy. Data from a foreign body animal model and in vitro tests, which take into account the properties of adhering and stationary-phase bacteria, explain the failure of a long-term treatment with cotrimoxazole. The patient was subsequently cured by ciprofloxacin which was successful in these tests. No relapse was noted after a follow-up of 1 year.

Adult↗

[Urinary tract infections: which studies? Whom to treat?].

Urinary tract infections are a common problem seen in ambulatory practices. For this reason it is important to have a cost-effective management. Clinical history and findings may allow to make the diagnosis. The laboratory costs can be reduced, if in case of cystitis a rapid test for detection of leucocytes replaces the urine culture. Urine cultures can be restricted to patients with complicated urinary tract infections. Single-dose with cotrimoxazole or 3-day treatment with trimethoprim is adequate for acute cystitis. The new quinolones are useful for the outpatient treatment of benign cases of acute pyelonephritis. In case of urethritis and prostatitis, the same drugs have an appropriate antimicrobial spectrum and an ideal bioavailability in the infected tissues.

Ambulatory Care↗

[Follow-up of extensive burns in an HIV positive patient. Case report].

The case of a 33-year-old HIV-positive patient who suffered from second- and third-degree burn injuries involving 30% of the body surface is reported. She was treated by early tangential excision of the burnt skin and split-thickness mesh grafting. The burn wounds healed without complications within the usual time, with excellent cosmetic and functional results. In spite of the successful treatment, she suffered from fever and various infections for several months. With the appearance of these constitutional symptoms, we recognized the AIDS-related complex. Her general condition deteriorated continuously and 10 months after the accident she had to be admitted to a hospital again. The skin had nevertheless healed perfectly and in spite of not having compression treatment for the grafts or physiotherapy, she did not show any signs of hypertrophic scars. Some important conclusions drawn from this case are discussed. The fact that healing occurred without complications is in contrast to the results reported in the literature concerning impaired wound healing in AIDS patients with anorectal surgery. We therefore believe that the reluctant and perhaps even anxious attitude of the medical and nursing staff towards performing technical and expensive procedures in HIV-positive burn patients is not justified.

AIDS-Related Complex↗

Purified human plasma kallikrein does not stimulate but primes neutrophils for superoxide production.

In patients with septicemia and septic shock the contact phase of blood coagulation is activated. It has been suggested that polymorphonuclear leukocytes (PMN) are directly activated by purified plasma kallikrein. This has been recently questioned because granulocytic elastase release induced by recalcification of normal and prekallikrein-deficient plasma was similar. We studied the interaction of different preparations of purified human plasma kallikrein with PMN. Cytosolic calcium shifts were measured with the quin2 method, PMN aggregation was assayed in an aggregometer, and superoxide production was quantitated as superoxide dismutase inhibitable cytochrome c reduction in a continuous assay. No increase of cytosolic free calcium was found during at least 5 min after adding 10 micrograms/ml plasma kallikrein to PMN. Similarly, highly purified plasma kallikrein from two different sources did not induce PMN aggregation at all, nor did it stimulate superoxide production. However, sequential exposure of PMN to plasma kallikrein and formylpeptide increased the superoxide production compared to stimulation with formylpeptide alone. This phenomenon which is called priming was observed at plasma kallikrein concentrations greater than or equal to 7 micrograms/ml. The active site of the molecule was required for the priming, because plasma prekallikrein, active site-inactivated plasma kallikrein, and soybean trypsin inhibitor treated kallikrein did not prime PMN. This indicates that the contact activation system may play a role in host defence against bacterial infection.

Calcium↗

[HIV infection caused by kidney transplant: case report and review of 18 published cases].

Since 1985 organ donors are routinely tested for the presence of HIV-antibodies, but prior to that time several patients acquired HIV-infection from grafts. In May 1984 a 65-year-old woman on hemodialysis received a cadaver kidney graft from a young iv drug addict. The transplant functioned perfectly with cyclosporin A immunosuppression. Retrospectively, 22 days after surgery HIV antigen was detected. At this time only a faint band of anti-p24 antibodies was found in the Western blot. Two years after surgery splenomegaly was found in the apparently healthy patient. During the third year thrombocytes fell and she developed lymphadenopathy and constitutional symptoms. Up to this time the immunological parameters were in the range of 10 healthy renal transplant patients with cyclosporin A treatment. In the 4th year T-lymphocytes dropped to values below 200 and the patient developed Pneumocystis carinii pneumonia. A few months later a pulmonary node, which later proved to be a B-cell lymphoma, appeared. Slightly less than 5 years after transplantation the patient died from clinically diagnosed pulmonary embolism. The progression of the HIV-Infection in this patient and in one of 18 patients in published reports show that the incubation period is several years shorter in renal transplant patients than in those who acquire HIV from blood products.

AIDS Serodiagnosis↗

[Intravascular catheter: prevention and therapy of infection].

Intravascular devices are widely used. If certain precautions are taken, catheter-related infections, and especially bacteremia, are infrequent. Special attention should be paid to the correct access (peripheral versus V. subclavia or V. jugularis interna), immediate stabilization of the position, the choice of dry dressings (transparent plastic dressings should be avoided on newly inserted or arterial catheters, as well as on damp wounds), and regular changing of peripheral lines. In the febrile patient with vascular access the infective source should be sought. If the insertion site shows signs of inflammation, or if septicemia occurs, catheters must be removed. In patients with peripheral suppurative thrombophlebitis, surgical excision of the vein must be considered. In contrast, in septic thrombophlebitis of a central vein, removal of the catheter and antibiotic and anticoagulation therapy may be sufficient.

Anti-Bacterial Agents↗

Role of gastric colonization in nosocomial infections and endotoxemia: a prospective study in neurosurgical patients on mechanical ventilation.

The role of gastric microbial colonization in nosocomial infections and endotoxemia was investigated prospectively in 40 neurosurgical patients requiring mechanical ventilation for greater than 48 h. Each was studied up to 7 d. Swabs from the nose and oropharynx were cultured at admission, and aspirates from the stomach and trachea were cultured daily until enteral alimentation was started. Patients were evaluated every second day for endotoxemia and coagulation activation. Of 153 gastric aspirates, 66.7% contained microorganisms at a mean quantity of 10(7) cfu/ml. Nosocomial pneumonia occurred in 15 patients, septicemia in 5, and meningitis in 1. The stomach was the evident source of infection in only 1 patient with pneumonia. Of 140 plasma samples, 12 (8.6%) from 10 patients showed detectable endotoxin levels, but there was no association between endotoxemia or coagulation activation and the presence of microorganisms in the stomach. The stomach was not an important source for nosocomial infections or endotoxemia, even in patients with high gastric pH.

Adult↗

[Implantable catheter system for ambulatory parenteral antibiotic chemotherapy. A prospective study].

17 patients with infectious diseases needed a long-term parenteral antibiotic therapy. Therefore a subcutaneous catheter system (Port-a-Cath) was implanted for intravenous application of the antibiotic drugs. With a total dwelling-time of 952 patient/days no catheter super-infection was observed. Due to postoperative hematoma in an anticoagulated patient one catheter system was not functioning temporarily. One had to be removed on suspicion of a fungous colonization which could not be verified after bacterial examination. Quality of life for all patients was unaltered so that ambulant therapy was possible in almost 20%.

Adult↗