Morphologic and biochemical changes in articular cartilages of immature beagle dogs dosed with difloxacin.

Quinolones are efficacious antibacterial compounds, but they have been associated with arthralgia in human patients; experimentally, they have caused lesions in articular cartilages of immature animals. The earliest morphologic and biochemical changes induced in articular-epiphyseal cartilage complexes by difloxacin, a fluoroquinolone, were investigated in 27 3-month-old Beagle dogs that were dosed orally with the drug at 300 mg/kg body weight per day. Paraffin-embedded sections of humeral and femoral heads that were stained with either hematoxylin and eosin or toluidine blue and fast green were evaluated histologically, and lesions were scored according to established criteria. Although morphologic changes were not observed in cartilages of the control dogs or of the treated dogs in the 24-hr group, the severity of lesions, as represented by mean scores for lesions, increased during the 36-48 hr after dosing. The initial morphologic change, observed in cartilages from the treated dogs of the 36- and the 48-hr groups, was necrosis of chondrocytes that was rapidly followed by disruption of extracellular matrix and formation of fissures. Although glycosaminoglycan was aggregated along the margins of fissures, its concentration was not reduced in cartilages of any group of treated dogs. Collagen, however, was depleted from the cartilages of the dogs that were euthanized 36 or 48 hr after the first dose of difloxacin. Because degenerative changes were observed ultrastructurally in chondrocytes by 24 hr in a previous study, it was concluded that collagen was lost from affected cartilages as an early sequel to the degeneration of chondrocytes.     

Ciprofloxacin treatment failure in a patient with resistant Streptococcus pneumoniae infection following prior ciprofloxacin therapy

Reported here is the case of a patient with underlying chronic obstructive pulmonary disease (COPD) in whom ciprofloxacin treatment of a lower respiratory tract infection failed subsequent to ciprofloxacin treatment of an exacerbation of COPD several weeks earlier. During the second course of ciprofloxacin therapy, the patients condition continued to deteriorate, and she was admitted to the intensive care unit. Bilateral pneumonia was diagnosed. Streptococcus pneumoniae, serotype 11A, resistant to ciprofloxacin was isolated from the sputum. Sequencing revealed a S79F mutation in parC and there was evidence of an efflux pump. The patient improved rapidly after administration of azithromycin and ampicillin/sulbactam. This report of treatment failure due to ciprofloxacin-resistant Streptococcus pneumoniae shows that fluoroquinolones should be avoided when treating patients who have recently received this class of antibiotics.     

Contrast rectification and distributed encoding By ON-OFF amacrine cells in the retina.

The encoding of luminance contrast by ON-OFF amacrine cells was investigated by intracellular recording in the retina of the tiger salamander (Ambystoma tigrinum). Contrast flashes of positive and negative polarity were applied at the center of the receptive field while the entire retina was light adapted to a background field of 20 cd/m(2). Many amacrine cells showed remarkably high contrast gain: Up to 20-35% of the maximum response was evoked by a contrast step of only 1%. In the larger signal domain, C50, the contrast required to evoke a response 50% of the maximum, was often remarkably low: 24 of 25 cells had a C50 value of < or =10% for at least one contrast polarity. Across cells and contrast polarity, the dynamic ranges varied from extremely narrow to broad, thereby blanketing the range of reflectances associated with objects in natural environments. Although some cells resembled "contrast rectifiers," by showing similar responses to contrasts of opposite polarity, many did not. Thus for contrast gain and C50, individual cells could show a strong preference for either negative or positive contrast. In the time domain, the preference was strong and unidirectional: for equal contrast steps, the latency of the response to negative contrast was 20-45 ms shorter than that for positive contrast. The present results, when compared with those for bipolar cells, suggest that, on average, amacrine cells add some amplification, particularly for negative contrast, to the high contrast gain already established by bipolar cells. In the time domain, our data reveal a striking transformation from bipolar to amacrine cells in favor of negative contrast. These and further observations have implications for the input and output of amacrine cell circuits. The present finding of substantial differences between cells reveals a potential substrate for distributed encoding of luminance contrast within the ON-OFF amacrine cell population.     

Video-rate nonlinear microscopy of neuronal membrane dynamics with genetically encoded probes

Biological membranes decorated with suitable contrast agents give rise to nonlinear optical signals such as two-photon fluorescence and harmonic up-conversion when illuminated with ultra-short, high-intensity pulses of infrared laser light. Microscopic images based on these nonlinear contrasts were acquired at video or higher frame rates by scanning a focused illuminating spot rapidly across neural tissues. The scan engine relied on an acousto-optic deflector (AOD) to produce a fast horizontal raster and on corrective prisms to offset the AOD-induced dispersion of the ultra-short excitation light pulses in space and time. Two membrane-bound derivatives of the green fluorescent protein (GFP) were tested as nonlinear contrast agents. Synapto-pHluorin, a pH-sensitive GFP variant fused to a synaptic vesicle membrane protein, provided a time-resolved fluorescent read-out of neurotransmitter release at genetically specified synaptic terminals in the intact brain. Arrays of dually lipidated GFP molecules at the plasma membrane generated intense two-photon fluorescence but no detectable second-harmonic power. Comparison with second-harmonic generation by membranes stained with a synthetic styryl dye suggested that the genetically encoded chromophore arrangement lacked the orientational anisotropy and/or dipole density required for efficient coherent scattering of the incident optical field.     

The regional registry of gastro-intestinal cancer North Baden (2.2 million inhabitants)

Summary The advantages of a population-based registry are discussed. It is shown that a registry for gastro-intestinal cancer in a district with expert medical care based upon histo-pathological diagnosis, has the principal advantage that it limits the sites of material collection to a few effective contributors, thus providing highly accurate data. The disadvantage of collecting data by two separate steps should be tolerated. The geographic situation and the organization of the regional registry for gastro-intestinal cancer in North Baden are described and the incidences for these cancers for the years 1971–1975 are given for the population of 2.2 million.Supported by the DFG (SFB 136)     

Analgesia after inguinal herniorrhaphy with laparoscopic inspection of the peritoneum in children. Caudal block versus ilioinguinal/iliohypogastric block

The authors prospectively evaluated the efficacy of caudal epidural block versus local infiltration combined with ilioinguinal/iliohypogastric block for analgesia after inguinal herniorrhaphy with laparoscopic inspection of the peritoneum. During standardized anesthetic care, 24 children were randomized to Group I (caudal epidural block with 1.2 mL/kg of 0.25% bupivacaine) or to Group II (local infiltration with an ilioinguinal/iliohypogastric block). Postoperative pain scores were significantly lower at all four evaluation points in Group I than in Group II. Patients in Group I had a significantly decreased requirement for supplemental intravenous fentanyl. Intra-operative requirements for isoflurane were decreased in Group I. The expired concentration of isoflurane was 0.4 +/- 0.1 (mean +/- SEM) in Group I and 1.5 +/- 0.3 in Group II. Time to extubation was 3.8 +/- 0.5 minutes in Group I and 8.2 +/- 1.1 minutes in Group II. The time from arrival in the postanesthesia care unit until discharge home was 113 +/- 3 minutes in Group I and 152 +/- 11 minutes in Group II. Caudal epidural block was more effective than local infiltration in controlling pain after herniorrhaphy with laparoscopy in children and resulted in earlier discharge home.     

Identification of a clinically relevant immunodominant region of collagen IV in Goodpasture disease

BACKGROUND: The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive glomerulonephritis, with or without lung hemorrhage, whereas autoantibodies specific for the other alpha chains of the heterotrimeric type IV collagen probably do not cause disease. In this study, we have investigated whether differences in fine specificity of autoimmune recognition of the alpha3(IV)NC1 correlate with clinical outcome. METHODS: For mapping of antibody binding to type IV collagen, chimeric collagen constructs were generated in which parts of the alpha3(IV)NC1 domain were replaced by the corresponding sequences of homologous nonreactive alpha1(IV). The different recombinant collagen chimeras allowed the analysis of antibody specificities in 77 sera from well-documented patients. RESULTS: One construct that harbors the aminoterminal third of the alpha3(IV)NC1 was recognized by all sera, indicating that it represents the dominant target of the B-cell response in Goodpasture disease. Seventy percent of the samples recognized other parts of the molecule as well. However, only reactivity to the N-terminus of the alpha3(IV)NC1 correlated with prognosis, that is, kidney survival after six months of follow-up. CONCLUSION: The results indicate the crucial importance of antibody recognition of this particular domain for the pathogenesis of Goodpasture disease, thereby opening new avenues for the development of better diagnostic and therapeutic procedures.