[Perioperative antibiotic prophylaxis]. / Perioperative Antibiotikaprophylaxe.

In times of growing bacterial resistance against antimicrobiotic drugs the broad prescription of antibiotics in human medicine must be carefully considered. The perioperative antibiotic treatment is in the center of that conflict. On the one hand an efficient pathogen reduction for the preemptive treatment of infectious complications is desired but on the other hand it is suspected that this promotes the selection of multiresistant pathogens which could lead to an increase of more complicated nosocomial infections. The aim of this article is a critical appraisal of this subject on the basis of the 2012 guidelines of the German working group of Hygiene in Hospital and Practice (AWMF) and the 2010 recommendations of the Paul-Ehrlich-Gesellschaft.

Immunostimulants and Toll-like receptor ligands obtained by screening combinatorial lipopeptide collections.

Synthetic lipopeptides carrying the head group of bacterial lipoproteins are specific ligands of Toll-like receptors (TLR). The three fatty acids containing lipopeptides with the tripalmitoyl-S-glyceryl-cysteinyl N-terminus (Pam(3)Cys) are agonists of TLR2. The structurally related lipopeptides with a head group lacking the fatty acyl residue at the amino-terminus (Pam(2)Cys) stimulate TLR2 and 6. To investigate the influence of the peptide chain of lipohexapeptides with a free N-terminus with regard to their ability to enhance B-cell proliferation, a randomized S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-pentapeptide amide collection Pam(2)CysXXXXX and 5 x 19 subcollections (Pam(2)CysOXXXX, Pam(2)CysXOXXX, Pam(2)CysXXOXX, Pam(2)CysXXXOX, Pam(2)CysXXXXO, O: all protein amino acids except Cys) were prepared by parallel solid-phase synthesis. The collection represents synthetic lipopeptide analogues of the numerous bacterial lipoproteins and of mycoplasma lipoprotein. Each of the 95 subcollections is characterized by one defined and four degenerated amino acid positions thus comprising 19(4) individual lipopeptides with free N-terminal amino groups. High-performance liquid chromatography electrospray mass spectrometry (HPLC-ESI-MS) was applied for the analytical characterization of the lipohexapeptide amide subcollections and for the individual lipohexapeptide amides. The subcollections were tested for polyclonal activation of murine spleen cells, deconvolution led to highly active single S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-pentapeptide amides.

Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats.

Glomerular filtration rate (GFR) was determined in 53 cats using an inulin single-injection method. Thirty healthy young adult cats were used to establish normal values. The procedure was also used in 23 cats that were either older than 10 years or had borderline serum creatinine levels. The total clearance was calculated from the decay of the serum inulin concentration after injection of 3000 mg/m(2)body surface area using a two-compartment model. Concomitant inulin and iohexol clearance in nine cats showed excellent correlation between the two methods. Calculated normal values for GFR in 30 healthy cats were 35.9-58.5 (median 46.0) ml/min/m(2)or 2.07-3.69 (median 2.72) ml/min/kg. A few cats with normal creatinine or blood urea nitrogen levels were detected as having reduced GFR and therefore being in a state of early renal dysfunction. The study indicates that single-injection inulin clearance is a valuable tool for routine GFR measurement in cats. An "inulin excretion test" using only one blood sample 3h after the administration of 3000 mg/m(2)body surface area could prove an attractive alternative for the assessment of renal function in daily practice.

Generation of 8-epi-prostaglandin F(2alpha) in isolated rat kidney glomeruli by a radical-independent mechanism.

Isoprostanes comprise a group of free radical-catalyzed products of arachidonic acid. However, there is recent evidence pointing towards an enzyme-dependent formation of isoprostanes. With the use of isolated rat glomeruli we addressed the mechanisms of isoprostane generation. Synthesis of prostanoids and isoprostanes, including 8-epi-PGF(2alpha), was studied under conditions favouring radical formation. Cultured glomeruli formed different prostanoids including 8-epi-PGF(2alpha). Upon LPS challenge cyclo-oxygenase (COX)-2 expression was enhanced, and this was paralleled by a 2 - 9-fold increase in prostanoid formation, including isoprostanes. Addition of COX-isoform unselective inhibitors (diclofenac, indomethacin) or a selective inhibitor (NS-398) suppressed the synthesis of prostanoids, 8-epi-PGF(2alpha) and total isoprostane fraction; however, inhibition of the latter was less pronounced. Antioxidants such as butylated hydroxytoluene (BHT), nordihydroguaiaretic acid (NDGA), or dimethylurea exhibited an only minimal inhibitory effect on 8-epi-PGF(2alpha) synthesis. Moreover, ROS-generating drugs (menadione, methylviologen) or NADPH-driven radical formation were unable to cause the generation of significant amounts of 8-epi-PGF(2alpha) by rat glomeruli. In contrast, the total isoprostane fraction could be increased by menadione addition. These data provide further evidence for a radical-independent, but COX-dependent formation of 8-epi-PGF(2alpha) in renal tissue. Regarding the other isoprostanes, both radicals and COX enzymes contribute to their formation. Based on our data we assume that elevated release of vasoactive 8-epi-PGF(2alpha) has to be expected under conditions when the prostanoid system in the kidney is stimulated, e.g. under inflammatory conditions. Regarding renal oxidative injuries, the usefulness of 8-epi-PGF(2alpha) as a representative marker molecule of oxidative stress has to be questioned.

Generation of the isoprostane 8-epi-prostaglandin F2alpha in vitro and in vivo via the cyclooxygenases.

F2-isoprostanes are isomers of the prostaglandin PGF2alpha. At least one compound of this group, 8-epi-PGF2alpha, exhibits biological activity, and therefore special interest is focused on the mechanism of isoprostane formation: enzyme catalyzed or radical mediated. We analyzed the formation of isoprostanes in vitro and in vivo. In both systems, purified cyclooxygenase isoenzymes and cell models specific for the cyclooxygenase isoenzymes, 8-epi-PGF2alpha formation could be totally suppressed by cyclooxygenase inhibitors. Indomethacin inhibited concentration-dependent 8-epi-PGF2alpha formation in platelets stimulated with calcium ionophore, arachidonic acid or thrombin. Nordihydroguaiaretic acid, an antioxidant, blocked isoprostane formation with a similar IC50 value as thromboxane B2 synthesis, pointing toward cyclooxygenase as the primary target of inhibition. Based on the turnover number, cyclooxygenase-2 formed higher levels of 8-epi-PGF2alpha than cyclooxygenase-1. Endogenous 8-epi-PGF2alpha production in rat mesangial cells correlated well with the mRNA and protein expression of cyclooxygenase-2 during interleukin-1 induction. However, in contrast to human platelets, which produced different forms of isoprostanes, rat mesangial cells appeared to form only 8-epi-PGF2alpha. Further, this indicates that mesangial cells may represent a cellular origin for renal 8-epi-PGF2alpha formation. Next, we analyzed the formation of isoprostanes in humans. A direct correlation was observed between indomethacin treatment and the decrease in 8-epi-PGF2alpha and isoprostane levels, but compared with other prostanoids the inhibition was less pronounced. In summary, based on the in vitro studies, a clear cyclooxygenase-dependent formation of isoprostanes, especially 8-epi-PGF2alpha, was observed. However, in vivo additional formation via cyclooxygenase enzyme-independent mechanisms is likely.

Familial glomerulopathy with giant fibrillar (fibronectin-positive) deposits: 15-year follow-up in a large kindred.

A 15-year clinical follow-up is reported for a familial glomerulopathy characterized on light microscopy by the glomerular deposition of giant fibrillary deposits (Virchows Arch A Pathol Anat Histol 388:313-326, 1980). On electron microscopy, the deposits consist of randomly oriented fibrils (12 to 16 nm in width and 120 to 170 nm in length). These deposits show positive immunoreactivity for fibronectin. One hundred fifty-seven of 197 family members within five generations were investigated. The disease is characterized by the occurrence of albuminuria in the third to fourth decades of life and slow progression to end-stage renal disease over a period of 15 to 20 years with the occurrence of generalized distal tubular acidosis (renal tubular acidosis type IV), hypertension, and the nephrotic syndrome. The frequent occurrence of otherwise unexplained microalbuminuria in young individuals of generations IV and V could be indicative of incipient glomerular disease. In one affected male individual and in his unaffected sister, renal cell carcinoma was diagnosed, raising the possibility that this familial glomerulopathy might be associated with an increased risk to develop renal cell cancer by direct or indirect (associated genetic predisposition) mechanisms. The disease relapsed in one renal transplant, raising the possibility of the presence of a transferable factor that could be part of the deposited fibrillar material or, alternatively, interfere with the glomerular handling of the deposited material.

[Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study]. / Pravastatin zur Behandlung der primären Hypercholesterinämie: Schweizer Multizenter-Studie.

Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects. Pravastatin is a new potent cholesterol-lowering agent, which selectively inhibits hepatic HMG-CoA-reductase. In a double-blind, placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory, the efficacy and safety of 6 months' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors. Compared to baseline and after 26 weeks' therapy, pravastatin significantly reduced total cholesterol (pravastatin vs placebo, -17% vs +7%, p < 0.0001) and LDL cholesterol (-26 vs +2%, p < 0.0001). The total/HDL cholesterol ratio ( = "atherogenic index") was comparable in the two groups at baseline (5.9 +/- 1.1 vs 6.3 +/- 0.9), and was distinctly lowered by pravastatin but not placebo (-20 vs 0%, p < 0.0001). In 11 patients in whom the reduction of serum total cholesterol after 13 weeks' treatment with 20 mg pravastatin was still below target (on average -9.1%), doubling of the dose produced a further decrease of 4.3%. Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo. Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects. There were 5 dropouts during the study, 2 patients in the pravastatin group and 3 in the placebo group. These findings document that pravastatin, administered in a single daily dose of 20 to 40 mg, effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated.

[Swiss simvastatin multicenter study: 1. Efficacy of 10 mg simvastatin daily in patients with primary hypercholesterolemia]. / Schweizerische Simvastatin-Multizenter-Studie: 1. Wirksamkeit von 10 mg Simvastatin pro Tag bei Patienten mit primärer Hypercholesterinämie.

In a Swiss multicenter study with determination of lipid and lipoprotein parameters in a central laboratory, the efficacy of simvastatin, MSD, was evaluated in patients with primary hypercholesterolemia. Lipid and lipoprotein values were determined in 109 patients before and after 6 weeks' therapy with 10 mg simvastatin per day. A significant decrease in total cholesterol, LDL-cholesterol and apo B, of 21.1, 25.8 and 24.1% respectively, was observed. No influence of simvastatin on apo A-II was found, but HDL-cholesterol and apo A-I were slightly increased (+6.1 and 4.4% respectively). The data show that HMG-CoA reductase inhibitors constitute a new class of effective drugs for the treatment of hypercholesterolemia.

Antihypertensive efficacy and well-being during monotherapy and combination therapy with ketanserin.

The effects of ketanserin on blood pressure and well-being were investigated in 188 patients, aged 41-82 years, with mild to moderate essential hypertension. At entry, 107 were untreated, 42 were taking the diuretic combination hydrochlorothiazide (50 mg/day) plus amiloride (5 mg/day) and another 39 were taking the beta-blocker atenolol (100 mg/day). A single-blind, 4-week placebo run-in period was followed by 12 weeks' oral ketanserin treatment at 20 or 40 mg twice a day. This regimen significantly reduced systolic and diastolic blood pressures in each group. Response rates were greater in patients aged over 60 years. Compared with placebo, sleep disturbances, daytime fatigue and overall weakness decreased during ketanserin treatment (P less than 0.05 for all), but the incidence of dry mouth and stuffy nose increased. In patients older than 60 years there was a greater reduction of complaints than in younger patients. Ketanserin proved effective and well tolerated, improving peripheral circulatory symptomatology, particularly in older patients and those with a good blood pressure response.

[Blood pressure lowering action and tolerance of ketanserin in mono- or combination therapy]. / Blutdrucksenkende Wirksamkeit und Verträglichkeit von Ketanserin in Mono- oder Kombinationstherapie.

The antihypertensive efficacy and tolerability of the 5HT2-receptor antagonist ketanserin was investigated in 188 patients aged 41 to 82 years with mild to moderate essential hypertension. Ketanserin was given as monotherapy (n = 107) as well as in combination with either the diuretic hydrochlorothiazide/amiloride (n = 42) or the betablocker atenolol (n = 39) for 12 weeks. Compared to placebo, ketanserin lowered systolic blood pressure by 11 +/- 16 (SD), 9 +/- 13 and 9 +/- 11 mm Hg (p less than 0.01 for all) and diastolic blood pressure by 9 +/- 10, 10 +/- 9 and 7 +/- 9 mm Hg (p less than 0.001 for all), in the three treatment groups; body weight, serum sodium, potassium, uric acid, cholesterol and triglycerides remained unchanged. The incidence of withdrawals due to unwanted effects was 4% on ketanserin monotherapy, and 12% and 10% on the diuretic/ketanserin and the betablocker/ketanserin combination respectively. Well-being during ketanserin therapy was improved in the older patients in particular; sleep disturbances, daytime fatigue and overall weakness decreased. Ketanserin was well tolerated in combination with the diuretic, whereas in combination with the betablocker the occurrence of dry mouth and stuffy nose was slightly higher. - Ketanserin proved to be an effective antihypertensive drug comparable to other blood pressure lowering agents. It can be combined advantageously with a potassium sparing diuretic or a betablocker. The greater efficacy and tolerability in patients greater than or equal to 60 years qualify ketanserin primarily as an antihypertensive agent for older patients.

MRI in Cockayne syndrome type I.

MRI findings are reported from two patients with Cockayne syndrome (CS) type I, aged 11 and 37 years. Changes were compatible with diffuse white matter hypomyelination. Basal ganglia calcification was present in both, marked cerebellar atrophy in the older patient. MRI may support the diagnosis of CS in the appropriate clinical context. The view that CS is a dysmyelinating disorder is further substantiated.

[Atrioventricular block in Lyme carditis]. / Atrio-ventrikuläre Blockierung bei Lyme-Karditis.

Lyme disease, due to infection with Borrelia burgdorferi transmitted by ticks, is most frequently manifested by arthritis and neurological complications. In approximately 8% of cases, however, carditis, usually reflected in AV block, is the leading symptom. The case histories of 2 males and 1 female aged 23 to 37 years with AV block caused by Borrelia burgdorferi are presented. Main symptoms were exertional dyspnea, palpitations, dizziness and syncope. One patient was treated with diclofenac and two with penicillin. The course was uniformally benign and cardiac abnormalities disappeared within 1-3 weeks.

[McArdle disease: differential diagnosis of the increase in creatine kinase induced by the exercise test]. / McArdle-Krankheit: eine Differentialdiagnose des belastungsbedingten Creatinkinaseanstiegs.

In a Turkish couple presenting atypical precordial pain, muscle pain and a massive increase of creatine kinase during and one day after bicycle ergometry, suspicion of McArdle's disease was confirmed by a pathologic ischemic forearm worktest, a pathologic serial stimulation test and by pathologic glycogen content with lack of myophosphorylase activity on histochemical examination of thigh muscle tissue. Characteristic signs of McArdle's disease such as muscle weakness, muscle pain and muscle swelling, especially after exertion, were detected only after specific questioning of the patients. McArdle's disease was also detected by phosphor nuclear resonance in the two male children. Frequent consanguinity in the small isolated mountain village where the family originated explains why all four members of two generations are affected by the autosomal recessive disease.

[Sarcoidosis of the kidney]. / Sarkoidose der Niere.

Of 123 patients with sarcoidosis observed from 1971 to 1986, 4 had histologically proven renal involvement. Hypercalcemia was present in all of these 4 patients, hypercreatinemia in 3 and urolithiasis in one. Histologically renal interstitial nephritis or fibrosis was found in all 4 cases, and 3 cases showed sarcoid-like renale granulomas. In addition, nephrocalcinosis or mesangioproliferative glomerulonephritis was present in one patient each. Corticosteroid therapy corrected hypercalcemia in 3 patients and improved renal function in the patient with glomerulonephritis and in the case with interstitial fibrosis. One patient died of granulomatous myocarditis, renal insufficiency having been unaffected by corticosteroids.

Efficacy of imipenem/cilastatin in patients with severe bacterial infections.

In this study imipenem/cilastatin was used successfully to treat 21 patients with a variety of severe infections caused by Gram-positive and Gram-negative aerobic bacteria. Overall clinical cure was achieved in 18 of 21 patients. Fourteen of 16 infecting organisms were eradicated by imipenem. In spite of in-vitro susceptibility to imipenem before therapy two species of Pseudomonas (Pseudomonas aeruginosa and Ps. fluorescens) could not be eliminated in two patients. Resistance developed in the strain of Ps. aeruginosa during treatment of a patient with pneumonia for eight days. The pneumonia was considered to be clinically cured. The strain of Ps. fluorescens became resistant during therapy in a patient suffering from an acute exacerbation of severe chronic bronchitis in whom the antibiotic treatment had failed. Imipenem/cilastatin proved to be highly effective and well tolerated in this group of patients.

[Renal involvement in Legionnaires' disease]. / Renale Mitbeteiligung bei der Legionärskrankheit.

9 consecutive cases of Legionnaires' disease are presented, all of which involved either a pathological urinary sediment or acute renal insufficiency. Diabetic glomerular sclerosis and terminal septic shock in one patient accounted per se for the urinary findings and terminal oliguric renal failure. In the remaining 8 patients the renal abnormalities are interpreted as manifestations of Legionnaires' disease: these were acute renal insufficiency in 6, requiring dialysis treatment in 4, proteinuria in 7, hematuria in 5, leukocyturia in 5 and cylindruria in 3 patients. One patient died of pneumonia and one patient, without Legionella-related renal involvement, of septic shock. Renal histology of 5 patients showed acute interstitial nephritis in one and diffuse sclerosing interstitial nephritis in a second patient, whose biopsy was obtained after 3 months' hemodialysis treatment. In 3 patients renal biopsy findings were explained by preexisting renal pathology, i.e. diabetic nephropathy, chronic transplant rejection and shock kidney respectively. Renal failure requiring hemodialysis and urinary abnormalities were largely reversible.

[Malignant pericardial effusion--a sign of unfavorable prognosis?]. / Maligner Perikarderguss--ein prognostisch ungünstiges Zeichen?

Malignant pericardial effusion (MPE) resulting in cardiac tamponade is a rare complication in neoplastic disease. From January 1975 to December 1984 the authors observed 22 patients with cytologically verified malignant pericardial effusion. The most frequent primary tumors were non-small cell lung cancer (6), breast cancer (5), non-Hodgkin lymphoma (4) and mesothelioma (4). 50% of the patients presented with MPE as the initial manifestation of the tumor. In the other group of patients MPE appeared after an average of 11 months following the diagnosis of malignant disease. The most frequent symptoms and clinical findings were dyspnea (100%), jugular venous distention (91%), and tachycardia (82%). During the first 24 hours after pericardiocentesis a median volume of 675 ml of predominantly serosanguinous effusion was drained. Besides intrapericardial drug instillation, patients also received local radiotherapy and systemic chemotherapy. At the time when MPE was diagnosed 77% of the patients exhibited advanced malignant disease. Mean survival time was 140 days. Malignant pericardial effusion is therefore regarded as an unfavorable prognostic factor.

[Acute iodine poisoning associated with sialadenitis, allergic vasculitis and conjunctivitis following administration of iodine-containing contrast media]. / Akuter Jodismus mit Sialadenitis, allergischer Vaskulitis und Konjunktivitis nach Verabreichung jodhaltiger Kontrastmittel.

Sialadenitis ("iodide mumps") and allergic vasculitis are rare sequelae to administration of iodinated contrast media. The condition is characterized by rapid, painless, bilateral enlargement of salivary glands following administration of iodinated contrast media. An 81-year-old female patient with moderate renal failure is described in whom marked sialadenitis, allergic vasculitis with (in part) bloody blisters developed following excretory urography and digital subtraction angiography of the renal arteries. Additional but mild symptoms included fever and conjunctivitis. All lesions subsided completely within four weeks. A relation between blood iodine concentration and extent of the lesions could be demonstrated. The highest iodine level in serum determined was 70 600 micrograms/100 ml.