Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression

Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coagulation in infected vessels. Whereas uninfected endothelial cell cultures showed essentially undetectable TF mRNA and activity, both TF mRNA and activity were present after R rickettsii infection. TF mRNA levels were transient, peaking at 4 hours after the initiation of infection, whereas the peak of TF activity occurred at 8 hours. Induction of the TF response requires the intracellular presence of R rickettsii organisms, because uninfected rickettsia were ineffective and the response was blocked by inhibiting rickettsial entry using cytochalasin B. TF induction was not mediated by endothelial cell release of soluble factor, because no response was induced using culture medium conditioned by R rickettsii-infected cells. Furthermore, preadsorption of suspensions of R rickettsii with polymyxin B to remove contaminating lipopolysaccharide did not eliminate the TF response. Induction of TF in vital endothelial cells during R rickettsii infection could be the trigger for vascular thrombus formation of RMSF.     

MR gated subtraction angiography: evaluation of lower extremities

We report the first clinical experience with a new method for projective imaging of blood vessels (angiography) using magnetic resonance. Vascular contrast is produced noninvasively by the phase response of moving protons. Diastolic and systolic gated images produce, respectively, flow signal and flow void; the difference image is a map of the pulsatile flow: an arteriogram. Preliminary studies are presented of the lower extremities of one healthy volunteer and four patients (one each with occlusive disease, soft-tissue tumor, arteriovenous malformation, and venous femoral-popliteal graft). Patient data are compared with accompanying conventional arteriograms, and the new method is discussed.     

Indications for breast imaging in women under age 35 years

To determine appropriate indications for breast imaging in young women, the authors correlated patient histories with mammographic and/or sonographic findings and biopsy or follow-up results for 625 patients aged 13-34 years. The only important indications were a palpable mass and suspicion of an abscess. Of the 335 studies performed for evaluation of a palpable mass, 184 (55%) were normal, 28 (8%) were compatible with benign disease, and 123 (37%) were suggestive of malignancy. Biopsies were performed in 73 patients; the findings were benign in 67 cases, and carcinoma was found in six. Imaging studies were considered helpful in four of the 15 cases of suspected abscess, in that the studies established the presence and extent of an abscess. Studies in 275 women were performed for a variety of other indications. The findings were normal in 239 (87%) studies, benign in 21 (8%), and suggestive of malignancy in 15 (5%); there were no known carcinomas in any of the patients. Women with the "low-yield" indications identified in this study should be followed up clinically rather than referred for imaging studies.     

Irradiation induces release of von Willebrand protein from endothelial cells in culture

Human umbilical vein endothelial cells in tissue culture were irradiated with doses between 0 and 40 Gy, and the released von Willebrand (vW) protein and that which remained associated with the cells was quantitated. Doses of 20 Gy and higher produced a statistically significant increase in amount of vW protein secreted. This release was present whether the cells were labeled continuously throughout the experiment or just prelabeled before irradiation. An increase in fibronectin secretion was not observed. The release response to radiation was slow, reaching significance close to 24 hours after irradiation. The release of vW protein was not due to cell lysis, because the secreted vW protein contained very little of the large 260- kilodalton vW precursor subunit present in cell lysates and the cells appeared intact by immunofluorescence staining.     

Metformin improves performance in high‐intensity exercise,but not anaerobic capacity in healthy male subjects

The aim of this study was to determine the ergogenic effects of metformin in high‐intensity exercise, as well as its effects on anaerobic capacity, in healthy and physically active men. Ten subjects (mean (± standard deviation) maximal oxygen uptake (_2max) 38.6 ± 4.5 mL/kg per min) performed the following tests in a cycle ergometer: (i) an incremental test; (ii) six submaximal constant workload tests at 40%–90% (_2max); and (iii) two supramaximal tests (110% (_2max). Metformin (500 mg) or placebo was ingested 60 min before the supramaximal test. There were no significant differences between the placebo and metformin groups in terms of maximum accumulated oxygen deficit (2.8 ± 0.6 vs 3.0 ± 0.8 L, respectively; P = 0.08), lactate concentrations (7.8 ± 2.6 vs 7.5 ± 3.0 mmol/L, respectively; P = 0.75) or O₂ consumed in either the last 30 s of exercise (40.4 ± 4.4 vs 39.9 ± 4.0 mL/kg per min, respectively; P = 0.35) or the first 110 s of exercise (29.0 ± 2.5 vs 29.5 ± 3.0 mL/kg per min, respectively; P = 0.42). Time to exhaustion was significantly higher after metformin than placebo ingestion (191 ± 33 vs 167 ± 32 s, respectively; P = 0.001). The fast component of recovery was higher in the metformin than placebo group (12.71 vs 12.18 mL/kg per min, respectively; P = 0.025). Metformin improved performance and anaerobic alactic contribution during high‐intensity exercise, but had no effect on overall anaerobic capacity in healthy subjects.     

Correlation of subepithelial haze and refractive regression 1 month after photorefractive keratectomy for myopia.

PURPOSE: To relate myopic regression after photorefractive keratectomy (PRK) to subepithelial haze at the first postoperative month. METHODS: One hundred nineteen eyes of 119 patients underwent excimer laser PRK for treatment of myopia up to -8.00 D. Eyes were examined at 1, 3, 6, 9, and 12 months after surgery. All eyes received fluorometholone 0.1% for the first 5 postoperative months in a tapered dose. Dexamethasone 0.1% qid for 1 month was prescribed to all eyes with a spherical equivalent refraction less than plano, followed by an augmented dose of fluorometholone 0.1%. Eyes with myopia greater than -0.75 D at 12 months, as well as those that had received dexamethasone at any postoperative interval--regardless of refractive outcome--were considered to be regressed. Eyes that regressed and those that did not regress were compared statistically (Chi-squared statistical criterion with Yate's correction) regarding haze grade. RESULTS: Forty-seven percent (56 of 119) of eyes regressed. In 89.28% (50 of 56) of eyes, subepithelial haze grade was 1 to 2, and in 10.71% (6 of 56), subepithelial haze was graded 0 to 0.5 at 1 month. Fifty-three percent of eyes (63 of 119) did not regress and in all, subepithelial haze was graded 0 to 0.5 at the first month. The correlation between regression and haze grade 1 or more at the first postoperative month was statistically significant (P<.001). CONCLUSION: Mild to marked subepithelial haze (grade 1 to 2) at the first postoperative month after PRK for myopia is strongly related to regression of initial refractive effect and increasing myopia.     

软腭等离子射频打孔消融治疗阻塞性睡眠呼吸暂停综合征

目的：探讨等离子低温射频软腭打孔消融对阻塞性睡眠呼吸暂停低通气综合征的临床疗效。方法：对65例经多导睡眠图监测确诊为阻塞性睡眠呼吸暂停低通气综合征的患者行软腭等离子低温射频打孔消融术，缩短软腭及悬雍垂。结果：术后随访3～6个月，患者均取得了满意效果。患者射频治疗前和治疗12周后多导睡眠参数比较显示：治疗后Ⅰ Ⅱ期睡眠时间明显缩短，Ⅲ Ⅳ期睡眠时间明显延长，睡眠效率及最低脉氧饱和度(LSpO2)均显著提高(P＜0．05)；呼吸暂停低通气指数减低及打鼾时间缩短与治疗前相比差异非常显著(P＜0．01)。患者射频治疗12周后软腭长度及悬雍垂长度的缩短及鼾声评级的降低均较治疗前有显著差异(P＜0．01)。Epworth嗜睡程度评分亦较治疗前明显降低(P＜0．01)。结论：等离子低温射频软腭打孔消融对于轻度OSAHS患者具有较好的近期疗效，且方便、安全、微创、康复快，无不良反应，有较好的发展前景，值得推广应用。     

Do men undergoing sterilizing cancer treatments have a fertile future?

This study was designed to assess the effect of cancer treatments on the natural and assisted reproductive potential of men. A cohort of men with cancer, in whom radiotherapy and/or chemotherapy was planned, were invited to participate. Twenty-two pre- and post-treatment semen samples were analysed. The reproductive potential of participants was assessed with respect to the current range of fertility treatment options available. Abnormal sperm concentrations were found in 27% of patients pre-treatment compared to 68% post-treatment following a mean latency of 20 months from treatment. Fifty-nine percent of patients experienced a clinically significant decrease in sperm, concentration following radiotherapy and/or chemotherapy; 23% developed azoospermia following treatment. Eighty-two percent of patients with testicular malignancy had oligo- or azoospermia post-treatment. Only one patient had a clinically significant reduction in the percentage of motile spermatozoa post-treatment. Cryopreservation of semen prior to treatment improved the fertility prospects of 55% of patients. Intracytoplasmic sperm injection (ICSI) enhanced the fertility prospects of a further 14%. In the absence of, or after depletion of, cryopreserved semen, ICSI could enhance the fertility prospects of 45% of patients. Fertilization has been achieved by ICSI using spermatozoa retrieved by testicular biopsy from an azoospermic testicular cancer survivor 8 years after chemotherapy. It was concluded that chemotherapy and/or radiotherapy may depress semen concentration to the extent of rendering a man infertile. The severity of the reduction in sperm concentration following treatment is unpredictable but likely to be most severe in those with testicular malignancy and those treated with radiotherapy or alkylating chemotherapy agents. Not all men are keen to undergo an appraisal of their post-treatment fertility potential, for reasons which are unclear. Improving awareness and education of patients concerning the effects of both cancer and cancer treatments on reproductive potential is essential. With the advent of ICSI, it is possible to offer a very reasonable chance of conception in all men with cancer who present for cryopreservation of semen prior to treatment in whom spermatozoa (even in very low concentrations) are present in the ejaculate.