Variable Disposition of Ciprofloxacin in Critically Ill Patients Undergoing Continuous Arteriovenous Hemodiafiltration

Continuous arteriovenous hemodiafiltration (CAVHD) is being used increasingly in critically ill patients with acute renal failure (ARF). We prospectively evaluated extracorporeal and total systemic clearances (Cl_CAVHD and Cl_s) of ciprofloxacin during CAVHD in four patients with severe ARF to assess the adequacy of drug dosing. Ciprofloxacin serum and ultrafiltrate concentrations were measured by high-performance liquid chromatography. The Cl_CAVHD accounted for approximately 5.9% (range 2.8–11.6%) of Cl_s of ciprofloxacin. However, large variability in serum concentrations was observed with the normally recommended dose of 400 mg/day, and doses of up to 800 mg/day were required to maintain concentrations suitable for treatment of serious infections. High daily doses of ciprofloxacin required in these patients are likely related to altered pharmacokinetics in serious illness as well as to the increased extracorporeal clearance during CAVHD. Clinical studies to define appropriate dosing recommendations for ciprofloxacin during CAVHD are necessary to guide clinicians in optimum drug use.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Relative effect of surgery and radiotherapy on the internal jugular vein following functional neck dissection

We examined the internal jugular veins in three groups of patients who had undergone (1) a functional neck dissection and radiotherapy, (2) a functional neck dissection alone, or (3) radiotherapy alone, using a noninvasive color Doppler ultrasound scan. The internal jugular veins were ultrasonically bilaterally normal in 18% of patients who had undergone a functional neck dissection and radiotherapy, in 88% of patients who had undergone a functional neck dissection alone, and in 57% of patients who had undergone radiotherapy alone. The combination of a functional neck dissection and radiotherapy significantly affected the internal jugular vein when compared with a functional neck dissection alone.     

Detection of Aspergillus fumigatus by polymerase chain reaction.

Aspergillus fumigatus is an opportunistic nosocomial pathogen causing an often fatal pneumonia, invasive aspergillosis (IA), in immunosuppressed patients. Oligonucleotide primers were used to amplify a 401-bp fragment spanning the 26S/intergenic spacer region of the rDNA complex of A. fumigatus by the polymerase chain reaction (PCR). The primers were highly sensitive and specific: as little as 1 pg of A. fumigatus genomic DNA could be detected, and the primers only amplified DNA from A. fumigatus and not any other fungal, bacterial, viral, or human DNA tested. Using the PCR, we were able to detect A. fumigatus DNA in lung homogenates from immunosuppressed mice experimentally infected with A. fumigatus but not from immunosuppressed uninfected controls. There was 93% correlation between the culture results and the PCR results. In a retrospective clinical study, the sensitivity of the PCR for the detection of A. fumigatus in clinical samples was confirmed by positive amplification in three of three culture-positive respiratory samples from confirmed cases of IA. Because isolation of Aspergillus spp. may reflect contamination and colonization without infection, the feasibility of using the PCR was evaluated by analyzing culture-negative samples from both immunosuppressed patients at high risk for IA and immunocompetent patients with other lung infections. Only 2 of 10 patients were culture negative and PCR positive in the high-risk group, and 2 of 7 patients were culture negative and PCR positive in the immunocompetent group. The results indicate that PCR detection might be a valuable adjunct to current laboratory methods to diagnose IA.     

Ability of bacteria associated with chronic inflammatory disease to stimulate E-selectin expression and promote neutrophil adhesion.

Porphyromonas gingivalis, Pseudomonas aeruginosa, and Helicobacter pylori have been shown to be associated with adult periodontal disease, chronic lung infections, and peptic ulcers, respectively. The ability of these bacteria to stimulate E-selectin expression and promote neutrophil adhesion, two components necessary for the recruitment of leukocytes in response to infection, was investigated. Little or no stimulation of E-selectin expression was observed with either P. gingivalis or H. pylori when whole cells, lipopolysaccharide (LPS), or cell wall preparations added to human umbilical cord vein endothelial cells were examined. P. aeruginosa was able to induce E-selectin to near-maximal levels; however, it required approximately 100 to 1,000 times more whole cells or LPS than that required by E. coli. Neutrophil-binding assays revealed that LPS and cell wall preparations obtained from these bacteria did not promote endothelial cell adhesiveness by E-selectin-independent mechanisms. In addition, P. gingivalis LPS blocked E-selectin expression by LPS obtained from other bacteria. We propose that lack of E-selectin stimulation and the inability to promote endothelial cell adhesiveness are two additional indications of low biologically reactive LPS. We suggest that this property of LPS may contribute to host tissue colonization. In addition, the ability of P. gingivalis to inhibit E-selectin expression may represent a new virulence factor for this organism.     

Microsurgical anatomy of VII and VIII cranial nerves and related arteries in the cerebellopontine angle

Summary The relationships of VII and VIII cranial nerves and related arteries are reviewed in 26 preparations by microdissection techniques. These vessels may be grouped in large (AICA, PICA), medium (LA, SA, CSA, RPI) and small calibre (vasa nervorum, radicullar and medullar branches). The importance of these structures in acoustic neuroma surgery, vestibular neurectomy and cross-compression syndromes is discussed. Vascular loops and elongated arteries are normal structures present at birth.This work was supported by a grant from the AJ Roemmers Foundation     

Differential pattern of DNA-aneuploidy in human malignancies

The differential pattern of DNA-aneuploidy, detected by flow cytometry (FCM) regarding its frequency, grade and multiclonality, was investigated and correlated to tumor type, malignancy grade, tumor stage and prognosis in a multi-institutional study at the University of Münster. High resolution measurements using admixed normal blood reference cells were undertaken in 2413 cases of 13 different malignant diseases and in 776 benign lesions or samples. The incidence of DNA-aneuploidy was highest in melanomas, carcinomas, testicular tumors, sarcomas (75%-95%) and myelomas (65%). Acute leukemias showed an intermediate DNA-aneuploidy rate of 40% with special subgroups represented by common ALL (44%), p less than 0.05) and myelomonocytic/monocytic AML (47%, p less than 0.01). The lowest DNA-aneuploidy-rate was found in basal cell skin carcinomas (19%) and congenital melanocytic nevi (9%). No case of DNA-aneuploidy was observed in the 776 benign lesions or samples.--DNA-indices giving the grade of DNA-aneuploidy with 1.0 for normal diploid G1/0 cells were found distributed predominantly between 1.0 and 2.0 in the solid tumors, except testicular tumors, clustering around a triploid maximum at 1.5. DNA-indices of myelomas and acute leukemias generally ranged below 1.25 with lower DNA-aneuploidy grades in AML than in ALL (p less than 0.01).--In melanomas the aneuploidy rate was higher (86%) in metastases than in the primary tumors (54%, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)