Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin: a prospective, randomised, multicentre study

This study compared patients with moderate-to-severe community-acquired pneumonia (CAP) requiring hospitalisation, who received initial therapy with either intravenous ceftriaxone plus intravenous azithromycin, followed by step-down to oral azithromycin (n = 135), with patients who received intravenous ceftriaxone combined with either intravenous clarithromycin or erythromycin, followed by step-down to either oral clarithromycin or erythromycin (n = 143). Clinical and bacteriological outcomes were evaluated at the end of therapy (EOT; day 12-16) or at the end of study (EOS; day 28-35). At baseline, mean APACHE II scores were 13.3 and 12.6, respectively, with >50% of patients classified as Fine Pneumonia Severity Index (PSI) category IV or V. Clinical success rates (cure or improvement) in the modified intent-to-treat (MITT) population at EOT were 84.3% in the ceftriaxone/azithromycin group and 82.7% in the ceftriaxone/clarithromycin or erythromycin group. At EOS, MITT success rates (cure only) were 81.7% and 75.0%, respectively. Equivalent success rates in the clinically evaluable population were 83% and 87%, respectively, at EOT, and 79% and 78%, respectively, at EOS. MITT bacteriological eradication rates were 73.2% and 67.4%, respectively, at EOT, and 68.3% vs. 60.9%, respectively, at EOS. Mean length of hospital stay (LOS) was 10.7 and 12.6 days, and the mean duration of therapy was 9.5 and 10.5 days, respectively. The incidence of infusion-related adverse events was 16.3% and 25.2% (p 0.04), respectively. An intravenous-to-oral regimen of ceftriaxone/azithromycin was at least equivalent in efficacy and safety to the comparator regimen and appeared to be a suitable treatment option for hospitalised patients with CAP.     

Influence of native and hypochlorite-modified low-density lipoprotein on gene expression in human proximal tubular epithelium

Inflammatory infiltrates can modify (lipo)proteins via hypochlorous acid/hypochlorite (HOCl/OCl(-)) an oxidant formed by the myeloperoxidase-H(2)O(2)-halide system. These oxidatively modified proteins emerge in tubuli in some proteinuric and interstitial diseases. Human proximal tubular cells (HK-2) were used to confirm the hypothesis of detrimental and differential impact of HOCl-modified low density lipoprotein (HOCl-LDL), an in vivo occurring lipoprotein modification exerting proatherogenic and proinflammatory capacity. HOCl-LDL showed dose-dependent antiproliferative effects in HK-2 cells. Small dedicated cDNA macroarrays were used to identify differentially regulated genes. A rapid increase in the expression of genes involved in reactive oxygen species metabolism and cell stress, eg, heme oxygenase-1, thioredoxin reductase, cytochrome b5 reductase, Gadd 153, amino acid transporter E16, and HSP70 was found after HOCl-LDL treatment of HK-2 cells. In parallel, genes involved in tissue remodeling and inflammation eg, CTGF, VCAM-1, IL-1beta, MMP7, and VEGF were up-regulated. Quantitative RT-PCR verified differential expression of a subset of these genes in microdissected tubulointerstitia from patients with acute tubular damage, progressive proteinuric renal disease, and membranous glomerulonephritis (with declining renal function), but not in stable patients with proteinuria caused by minimal change disease. The demonstration of selective up-regulation of a subgroup of genes if proteinuria is accompanied by the presence of HOCl-modified (lipo)proteins support the potential pathophysiological role of the myeloperoxidase-H(2)O(2)-halide system and HOCl-LDL in renal disease.     

Chemical,radiochemical, and radionuclide purity of eluates from different commercial fission99Mo/99mTc generators

Seven⁹⁹Mo/^99mTc generators (using fission⁹⁹Mo) obtained from seven different manufactures were studied in 1984 and 1985 to test the quality of the eluates. We present the findings concerning the elution efficiency, radionuclide purity,⁹⁹Mo breakthrough, radiochemical purity, pH, and aluminium content of the eluates. One generator was overloaded with⁹⁹Mo by about 40%, while one generator had^99mTc yields of only about 80%. The eluates generally (although with some exceptions) exhibited a high and satisfactory radionuclidic purity and good radiochemical purity. The low-level determination of⁹⁹Mo break-through using a commercially available dose calibrator with a⁹⁹Mo assay shiled indicated a misleadingly high⁹⁹Mo content. All of the eluates had pH values of between 5.0 and 5.5, and the aluminium content was always below the detection limit of 1 g per milliliter of eluate. The generators performed well and proved their capability of functioning as reliable sources of sodium pertechnetate Tc99m. In all cases, the pertechnetate produced met the requirements of the European Pharmacopeia.This report is based on work conducted within the scope of a research poject devised by the Ministry of the Interior of the Federal Republic of Germany (Hammermaier et al. 1985). The present report reflects the opinions of the authors and does not necessarily express the views of the Federal Ministry of the Interior     

„Breast implant illness“ – Fakt oder Fiktion?

Journal für Ästhetische Chirurgie - Brustvergrößerungen mit Implantaten gehören zu den häufigsten ästhetisch chirurgischen Eingriffen. Trotz jahrzehntelanger...     

Dual antibiotic loaded bone cement in patients at high infection risks in arthroplasty: Rationale of use for prophylaxis and scientific evidence

In view of the demographic changes and projected increase of arthroplasty procedures worldwide, the number of prosthetic joint infection cases will naturally grow. Therefore, in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance. In the absence of a "miracle weapon" priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks, the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen. Instead of a "one size fits all" philosophy, it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors. A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre. The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.     

Measurement of chemiluminescence in freshly drawn human blood

Summary The aim of the present study was to investigate chemiluminescence (CL) of stimulated peripheral phagocytic cells (PC, i.e. granulocytes and monocytes) in patients with malignant disease at various stages. As a first step the zymosan-induced and luminol-amplified CL was determined in diluted whole blood samples from healthy volunteers. A characteristic daytime dependence of the CL activity was observed in six volunteers which had to be taken into account for blood sampling. The detectable CL was demonstrated to depend on the number of erythrocytes in the assay, but correction for this is not necessary for clinical investigation. The specific CL activity (activity related to 10³ PC, was significantly but identically increased both in 1) patients with acute inflammatory disease and 2) in patients with carcinoma. The total CL activity (activity/µl whole blood), however, was significantly increased in patients with acute inflammation as compared to the tumour group. This greatly reflects the leucocytosis of patients with acute inflammation. In a small number of patients with benign and malignant disease the CL of PC was measured both pre- and postoperatively. Operations in benign disease and palliative operations in malignancy did not influence the CL activity. In contrast, CL activity returned to normal after clinical cure by radical tumour resection.     

Cell death and disposal in retinoblastoma: an electron microscopic study

Background: Tumor necrosis and cell death are common features of retinoblastoma. In non-malignant retinal cells after ischemia, as well as in many nonretinal tumors, cell death occurs in at least two ways. We investigated whether similar patterns of cell death could be demonstrated in retinoblastoma cells. Methods: Nine globes with retinoblastoma from eight patients were studied. Paraffin sections stained with HE or the Feulgen method were examined by light microscopy. Several samples from each tumor were selected for electron microscopic study. Results: Ultrastructurally, two main types of cell death were identified. Type I was characterized by progressive lysis of the cytoplasm and karyoplasm. Nuclear chromatin either dissolved or was transformed into compact clumps becoming extracellular dense bodies. Phagocytosis of cell remnants by neighboring tumor cells, or occasional macrophages, was common. Type II was characterized by progressive condensation and shrinkage of the cytoplasm and nucleus. Type II was subdivided in two forms distinguished mainly by characteristic patchy vs crescentic chromatin condensation. Small parts of condensed cytoplasm were engulfed by neighboring tumor cells. Compact cell remnants then underwent either phagocytosis by neighboring retinoblastoma cells or progressive intercellular disaggregation. Conclusion: Retinoblastoma cells may undergo at least two types of cell death. Type I fits the definition of necrosis, while both forms of type II exhibited several features consistent with apoptosis. The types of cell death observed in retinoblastoma exhibited similarities to patterns observed in ischemic retina, as well as in other malignant tumors. Type II cell death (apoptosis) may play a role in limiting tumor growth.Presented in part at the 1993 ARVO Meeting in Sarasota, Fla., USA     

Intraperitoneal Versus Interpleural Morphine or Bupivacaine for Pain after Laparoscopic Cholecystectomy

Background: Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. This study was designed (1) to examine a novel route of opioid administration, the intraperitoneal injection; (2) to compare this to interpleural application, and (3) to compare opioid with local anesthetic effects under both conditions.

Methods: At the end of laparoscopic cholecystectomy, 110 patients received the following injections in a double-blind, randomized manner: Group 1 (n = 18) was given intraperitoneal morphine (1 mg in 20 ml saline) and 20 ml intravenous saline. Group 2 (n = 17) received intraperitoneal saline and 1 mg intravenous morphine. Group 3 (n = 15) received 20 ml 0.25% intraperitoneal bupivacaine and intravenous saline. Group 4 (n = 20) received interpleural morphine (1.5 mg in 30 ml saline) and 30 ml intravenous saline. Group 5 (n = 20) received interpleural saline and 1.5 mg intravenous morphine. Group 6 (n = 20) received 30 ml 0.25% interpleural bupivacaine and intravenous saline. Postoperative pain was assessed using a visual analog scale, a numeric rating scale, and the McGill pain questionnaire. Pain localization, supplemental analgesic consumption, vital signs, and side effects were recorded for 24 h.

Results: Neither intraperitoneal nor interpleural morphine produced significant analgesia after laparoscopic cholecystectomy (P > 0.05, Kruskal-Wallis test), whereas interpleural bupivacaine was effective (P < 0.05, Kruskal-Wallis test, up to 6 h postoperatively) but not intraperitoneal bupivacaine (P > 0.05, Kruskal-Wallis test). Shoulder pain was not prevalent in the majority of patients during the first 6 h. By 24 h, about half of the patients complained of shoulder pain, which was rated "low" by about one-third of all patients. No significant side effects occurred.     

Traumatic complications of acupuncture. Therapists need to know human anatomy

OBJECTIVES: To review the traumatic injuries that have been associated with acupuncture and to discuss how these adverse effects may be reduced by increased awareness of normal anatomy and anatomical variations. METHODS: Literature search accompanied by postmortem anatomical studies. RESULTS: Traumatic lesions after acupuncture have been described in thoracic and abdominal viscera, in the peripheral and central nervous systems, and in blood vessels. Deaths have been recorded from pneumothorax and cardiac tamponade. The anatomical structure of the body at several acupuncture points is such that needles can reach vulnerable structures. CONCLUSION: While the frequency of adverse effects of acupuncture is unknown and they may be rare, knowledge of normal anatomy and anatomical variations is essential for safe practice and should be reviewed by regulatory bodies and those responsible for training courses.     

CARD In Situ Hybridization: Sights and Signals

During the last decade, several strategies have been developed to improve the detection sensitivity ofin situ hybridization (ISH) by amplification of either target nucleic acid sequences prior to ISH (e.g.,in situ PCR), or the detection signals after the hybridization procedures (signal amplification). Here we outline the principles of tyramide signal amplification using the catalyzed reporter deposition (CARD) technique, summarize applications as well as possible limitations of CARD ISH, and discuss some future directions ofin situ nucleic acid detection using this amplification strategy.