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Biomedical subjects

W Graninger

Publications and source records attributed to W Graninger.

At least 181 records · Page 10Linked to original sources

[Do effects of biological response modifiers in vitro correspond to clinical results?].

There has been renewed interest in drug-host defence interaction because of increasing numbers of immunocompromised individuals in whom even a marginal influence on host response may have a beneficial effect on clinical outcome. The immunomodulating activity of several antibiotics has been investigated in the past. Unfortunately most of these studies have focussed on in vitro effects. Many controversies arise from the use of non-standardized techniques. In vivo experiments performed in animals might be far from the clinical situation. The effect of antibiotics on pagocyte function has been studied most intensively. Immunostimulating and depressing activities of antibiotics have been described. The clinical relevance is still controversial, e.g., the intracellular uptake of an antibiotic does not necessarily mean better microbial killing. Synergistic activities have been found with some macrolides and newer cephalosporins, but until now clinical studies in humans are still missing. Not only patients with abnormal host defence mechanisms, but also patients with transient immunosuppression during operations or after burns, could benefit from antibiotics with additional immunomodulating activities. More studies in humans are required before optimal clinical applications can be recommended.

Adjuvants, Immunologic↗

Drug sensitivity of Plasmodium falciparum in Gabon. Activity correlations between various antimalarials.

The sensitivity of Plasmodium falciparum to chloroquine, mefloquine, quinine, halofantrine, and sulfadoxine/pyrimethamine has been investigated at Lambaréné, in the Gabonese rain forest, between April and September 1992. WHO standard micro in vitro tests were performed. Of 43 isolates tested for response to chloroquine all were resistant to the drug with mean EC 50 and EC 90 values of 1.86 and 4.18 mumol/l blood, respectively, indicating the highest degree of resistance ever reported from Central Africa. With sulfadoxine/pyrimethamine 19 out of 27 isolates showed 90% inhibition of schizont maturation at a pyrimethamine concentration of at least 75 nmol/l blood medium mixture, indicating 30% of resistance to sulfadoxine/pyrimethamine. In contrast all isolates tested were fully inhibited by mefloquine at 3.2 mumol/l blood (40 isolates), quinine at 5.12 mumol/l blood medium mixture (41 isolates) and halofantrine at 3 nmol/l blood medium mixture (40 isolates) indicating full sensitivity to these drugs. A significant positive correlation was found between responses to quinine and mefloquine. The response to halofantrine was positively correlated with the responses to quinine and mefloquine, in the case of chloroquine and halofantrine an inverse relationship was observed. Compared with previous data from Gabon, the findings suggest a substantial increase of chloroquine resistance, in contrast to reports from neighbouring countries, which show stabilising or even declining chloroquine resistance patterns.

Animals↗

Oropharyngeal decontamination with gentamicin for long-term ventilated patients on stress ulcer prophylaxis with sucralfate?

The incidence of nosocomial pneumonia in long-term ventilated patients has been reduced by stress ulcer prophylaxis with sucralfate. In a double-blind trial we studied whether gentamicin administered topically to the oropharynx (OPG) had additional clinical benefits in these patients. 67 critically ill adult patients fulfilled entry criteria for > or = 5 days on ventilation. The OPG group received 40 mg gentamicin, the control group received 5% dextrose topically administered to the oropharynx 4 times a day. During OPG, pharyngeal colonization rate (21 vs 44%) and tracheal secretion colonization rate (12 vs 41%) were significantly lower than during placebo (p < 0.05). Despite these differences nosocomial pneumonia rate (3 vs 12%), duration of mechanical ventilation [15.8 +/- 11.1 vs 19.9 +/- 37.5 days (means +/- SD)] and mortality (27 vs 41%) were not significantly affected by OPG. Moreover, 13 of 15 bacteria (87%) that occurred during OPG were resistant to gentamicin. Despite its reduction of bacterial colonization rates of pharyngeal and tracheal secretions, OPG did not seem to offer additional clinical benefits in long-term mechanically ventilated patients on stress ulcer prophylaxis with sucralfate.

Administration, Topical↗

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with rheumatoid arthritis and systemic lupus erythematosus.

Serum levels of the soluble form of the intercellular adhesion molecule-1 (sICAM-1) have been advocated as a parameter of clinical relevance in determining the activation of the immune system in inflammatory disease(s). We have determined sICAM-1 levels in 46 patients with rheumatoid arthritis (RA), in 53 patients with systemic lupus erythematosus (SLE), and in 82 healthy controls using a commercially available ELISA system. When compared to the healthy controls, sICAM-1 levels of the patients did not differ statistically significantly nor was there any difference between the patient groups. However, there was a strong correlation within the patient groups between sICAM-1 levels and conventional measures of disease activity. Thus, although sICAM-1 may be of theoretical interest with regard to immune activation, our results do not support the view of sICAM-1 providing additional information to the clinical rheumatologist when it is compared to more conventional measures such as acute-phase proteins or clinical activity scores.

Adult↗

Treatment of Candida albicans fungaemia with fluconazole.

Sixty-five patients with Candida albicans fungaemia, admitted to intensive care units, were treated intravenously with fluconazole. All patients had at least one blood culture which was positive for C. albicans. The first group of 34 consecutive patients received fluconazole at a dose of 5 mg/kg bodyweight/day and the subsequent 31 patients received 10 mg/kg/day. Thirty patients in each group were evaluated. The clinical response rate was 60% in the 5 mg/kg once daily group and 83% in the group which received 10 mg/kg/day. Eradication of C. albicans from the blood was achieved in all but two patients in the 5 mg/kg group and in all patients in the 10 mg/kg group. As regards other sites of infection, eradication was achieved in only nine of 25 cases from the 5 mg/kg group and in 11 of 23 cases from the 10 mg/kg group. Death related to fungal infection occurred in eight patients receiving 5 mg/kg/day and in one patient receiving 10 mg/kg/day. Fluconazole was reasonably well tolerated. Raised concentrations of liver enzymes were observed in 14 patients. Other adverse effects were fatigue, nausea, gastric pain, sleepiness and epileptic seizure. In conclusion, fluconazole at a dose of 10 mg/kg/day would seem to be an effective and safe drug for the management of C. albicans fungaemia.

Adolescent↗

Parenteral administration of 8-methoxypsoralen in photopheresis.

BACKGROUND: Extracorporeal photochemotherapy (EP) is used for the treatment of cutaneous T-cell lymphoma (CTCL), progressive systemic sclerosis (PSS), pemphigus vulgaris, and rheumatoid arthritis. During this procedure, the oral administration of the photoactive drug 8-methoxypsoralen (8-MOP) results in an unpredictable range of serum levels and in side effects limiting its efficacy. OBJECTIVE: To circumvent this limitation, extracorporeally administrable 8-MOP (EX-8-MOP) was developed. It is administered directly to the leukocyte/plasma concentrate in the treatment bag of the EP apparatus before irradiation with UVA light. METHODS: Efficacy, tolerance, and side effects of EX-8-MOP were evaluated in 108 consecutive treatments of 16 patients who had previously been treated with oral 8-MOP (91 treatments). RESULTS: With EX-8-MOP constant drug levels for UV light exposure were obtained; for equivalent levels only a small fraction of the oral dose (1/250 to 1/500) was required with none of the side effects associated with oral 8-MOP. Effective and reproducible inhibition of lymphocyte proliferation and cell viability was attained. No difference in clinical efficacy could be observed. CONCLUSION: EX-8-MOP eliminates the need for premedication and drug level monitoring of 8-MOP and should improve the effectiveness of EP.

Administration, Oral↗

Polymyositis: MRI-appearance at 1.5 T and correlation to clinical findings.

The thigh regions of 10 patients suffering from polymyositis were examined by magnetic resonance imaging (MRI) at 1.5 T; follow-up examinations were performed in all patients. MRI findings were correlated with findings at physical examination and serological parameters. In four patients focal areas of hyperintensity on T2-weighted (T2W) spin echo (SE) images were found within muscles. They were not detectable on T1-weighted (T1W) images. In three of these cases enhancement within the musculature was seen following i.v. administration of Gd-DTPA on T1W images. In another five patients there was varied replacement of muscle by fatty tissue. In one patient the muscle appeared completely normal. On follow-up three patients showed definite changes in imaging findings; two correlated well with clinical and biochemical findings while the third exhibited massive deterioration clinically with mild improvement on imaging. Seven patients exhibited no change on MRI; four of these had shown a significant clinical change in the course of the disease, whilst three were clinically stable. In our small series MRI using SE technique (T1W and T2W) and contrast enhancement to date seems to be of limited value for the assessment of muscular changes during therapy. The i.v. use of Gd-DTPA did not add to MRI's diagnostic value in this series.

Adult↗

The efficacy of teicoplanin in the treatment of endocarditis caused by gram-positive bacteria.

Twenty-six patients with endocarditis caused by Streptococcus viridans (n = 12), Enterococcus faecalis (n = 5), Streptococcus bovis (n = 2), Staphylococcus aureus (n = 3) and Staphylococcus epidermidis (n = 4) were treated with teicoplanin at a dose of 600 mg/day in patients with normal renal function (creatinine clearance 80-120 mL/min) and at a dose of 400 mg/day in patients with moderately impaired renal function (creatinine clearance < 75 mL/min). In nine patients valve replacements were performed. Twenty-one patients were cured by medical treatment with teicoplanin, five patients had a surgical intervention during treatment which was subsequently stopped. Overall, eighteen patients with native valve endocarditis were cured. Out of eight patients with prosthetic valve endocarditis six patients were cured. In one patient teicoplanin therapy was withdrawn because of clinical failure. One patient had a clinical relapse. All cultures taken from blood, endocardium and excised artificial valves were sterile after a minimum of seven days therapy. Side effects were seen in seven patients and included a moderate increase in liver enzymes and mild leucopenia. No renal toxicity was observed, trough serum levels of teicoplanin were not correlated with renal function, a slight accumulation of teicoplanin on day 28 being seen. Our study confirms that teicoplanin is effective as single agent therapy in the treatment of endocarditis due to Gram-positive bacteria.

Adult↗

Autoantibody to the nuclear antigen RA33: a marker for early rheumatoid arthritis.

Sera from 47 patients with early (< 3 months) arthritis of any type were investigated for anti-RA33, a new anti-nuclear autoantibody characteristic of RA, and the diagnoses determined within the following 8-14 months. In addition, seven patients with unclassified arthritis of > 4 months duration, who were all anti-RA33 positive, were followed for up to 2 years to establish their final rheumatologic diagnoses. Four of 47 early arthritis patients' sera were anti-RA33 positive at the initial evaluation; 14 of these 47 patients (30%) could be classified as RA (according to established criteria) at the final evaluation. All four anti-RA33 positive patients belonged to the RA group (27% of RA patients); of the 33 non-RA patients none had anti-RA33 (P = 0.005). Rheumatoid factor was found in four RA (none of whom had anti-RA33), but also in two non-RA patients (P = 0.05). Finally, the study involved seven additional patients with longer standing, initially unclassified, anti-RA33 positive arthritis: in all of them a diagnosis of RA could be established within 3 years of disease onset. These results suggest that anti-RA33 helps to discriminate early RA from other forms of early arthritis and, in the absence of an established diagnoses, it is predictive of RA. Its discriminative capacity appears to be better than and complementary to that of RF.

Adolescent↗

Early bacterial infections in lung transplant recipients.

Early bacterial pulmonary infections within 2 weeks after lung transplantation were studied in 29 patients undergoing surgery between December 1989 and May 1992. Suspected pulmonary infections occurred in 11 patients (38 percent). The most common bacterial organisms isolated were Klebsiella pneumoniae (45 percent; 5/11), Pseudomonas aeruginosa (36 percent; 4/11), Escherichia coli (27 percent; 3/11), Staphylococcus aureus (18 percent; 2/11), and Enterobacter cloacae (18 percent; 2/11). The mortality due to infection was 3 percent (1/29) in the early postoperative period. None of the following variables was found to be of prognostic significance: positive donor cultures, ischemic time of the graft, use of cardiopulmonary bypass, number of courses of methylprednisolone for acute rejection, duration of postoperative intubation, and type of surgical procedure. The presence of infection in the early postoperative period did not influence long-term survival. In the absence of prognostic parameters, prompt adjustment of antibiotic therapy to the results of antibiograms remains the most important therapeutic step in the management of infections in the early postoperative period after lung transplantation.

Adult↗

Curing of chloroquine-resistant malaria with clindamycin.

A randomized comparative trial for treating adult patients with Plasmodium falciparum malaria was performed in Lambarene, Gabon. Forty-two patients received chloroquine (25 mg/kg for 48 hr) and 38 patients received clindamycin (5 mg/kg twice a day, for five days). Chloroquine treatment cured 15 patients (36%). Twenty patients (48%) showed recrudescent malaria by day 28 of follow-up (RI resistance) and seven patients (17%) showed persistent parasitemia after chloroquine treatment (RII/III resistance). In contrast, clindamycin treatment cured 37 of 38 patients (97%) and only one (3%) showed a recrudescence by day 28 (P < 0.001). Although the parasite clearance time was significantly longer after clindamycin treatment (median five days, range 3-6) than after chloroquine treatment (median four days, range 2-8) (P < 0.01), no differences were seen in the duration of symptoms after chemotherapy. In both treatment groups, no severe side effects occurred. Clindamycin can be used as a safe alternative to achieve radical cure in semi-immune adult patients with chloroquine-resistant P. falciparum malaria in Central Africa.

Adolescent↗

[Therapy of infections in gynecology].

Infections of the female genitals are among the most common conditions seen by primary care physicians. Approximately 75% of all women experience at least one episode of vaginitis during their reproductive life. Bacterial flora of the female genital tract is complex and dynamic. Those organisms which may cause gynecological infections in the appropriate setting are often present at a different stage in the woman's life as normal flora. The treatment of gynecological infections is dependent on the symptoms of the patient, the pathogen, and the medical history with regard to recurrences of the same disease. Since identification of the pathogen is often difficult, empirical therapy is administered frequently, which requires detailed knowledge of the most common bacterial pathogens and the resistance pattern of these organisms. An accurate initial diagnosis is the best basis for appropriate therapy, especially in view of the fact that once empirical antibiotic therapy has been administered, signs and symptoms are modified and the site of infection is rendered much more obscure.

Anti-Bacterial Agents↗

[Mefloquine and sulfadoxine/pyrimethamine overdose in malaria tropica].

A 39 year-old man with malaria due to Plasmodium falciparum received 3500 mg mefloquine over 3 days, in addition to 3250 mg chloroquine and 175/3500 mg sulfadoxine/pyrimethamine. He developed severe neuropsychiatric symptoms and had to be hospitalized. Treatment with diazepam, haloperidol and thioridazine achieved relief of the severe symptoms after 4 days. The patient was still suffering from discrete neuropsychiatric symptoms 8 months after treatment.

Adult↗

[Radiosynovectomy with dysprosium-165 iron hydroxide].

Treatment of chronic rheumatoid synovitis (RS) is directed to control the inflammatory process causing pain and disability. Radiation synovectomy is suggested to be an alternative to surgical treatment, but its clinical use has been restricted because of significant leakage (> 10%) associated with the use of the standard radionuclide 90-Yttrium (used as 90-Yttrium silicate colloid) and because of its long physical half-life of 64 hours prolonging the patients' stay in the hospital. 165-Dysprosium possesses promising nuclear properties for the treatment of patients suffering from RS. The maximum soft tissue penetration of its beta-particles is 5.7 mm which is the range being necessary to penetrate the inflamed synovia. Using as carrier ferric hydroxide macroaggregates (DFH) 165-Dy is expected to minimize the cumulative radiation dose to non-target organs by its very low leakage. Animal studies were performed in 13 rats and 6 rabbits to obtain the rationale and safety data for its clinical evaluation. These studies revealed that 98.2 +/- 0.6% of the injected dose remained in the joint with a nontarget organ uptake of less than 0.1%. Clinical results were obtained from 8 patients with rheumatoid arthritis. 24 hours after injection scintigraphy was performed over the treated joint and the liver region revealing no detectable leakage of the injected activity from the joint. Blood pool activity was also assessed revealing a leakage of 0.02% of the dose injected in the knee 24 hours after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Extracorporeal photochemotherapy for the treatment of systemic lupus erythematosus. A pilot study.

OBJECTIVE: To investigate the effectiveness and feasibility of extracorporeal photochemotherapy (ECP) in the treatment of an autoimmune disease with known cutaneous photosensitivity. METHODS: Ten patients with systemic lupus erythematosus (SLE) were treated with ECP in an open clinical trial. The efficacy of treatment was analyzed by means of established disease activity scores. RESULTS: Eight patients completed the trial. In 7 of the 8, there was a significant response to the treatment, with no or minor side effects. The clinical activity score in the group of 8 patients decreased from a median of 7 (range 4-9) to a median of 1 (range 0-5) (P less than 0.05). Laboratory abnormalities did not change significantly, but were mild at the outset. CONCLUSION: ECP led to clinical improvement of SLE without side effects. The effectiveness of this method should be investigated further in controlled clinical trials.

Adult↗

Cardiac involvement in systemic sclerosis.

OBJECTIVE: To assess the incidence and extent of cardiac involvement in systemic sclerosis (SSc) patients with no apparent cardiac symptoms. METHODS: Surface electrocardiography, ambulatory electrocardiography, radionuclide ventriculography, myocardial scintigraphy, and echocardiography were performed in 18 patients. RESULTS: These studies demonstrated ventricular tachycardia in 1 patient, nonsustained ventricular tachycardia in 5, supraventricular tachycardia in 6, decreased left ventricular ejection fraction in 2, decreased right ventricular ejection fraction in 8, and stress-induced reversible myocardial perfusion abnormalities in 6. CONCLUSION: These observations demonstrate a high rate of cardiac abnormalities in SSc patients without cardiac symptoms.

Aged↗