Rapidly progressive glomerulonephritis (GN) is one of the harrowingchallenges in nephrology. The condition is histologically characterizedby extracapillary proliferation with crescent formation. Mostcrescentic glomerulonephritides occur in systemic autoimmunediseases and require prompt immunosuppressive treatment. Occasionally,patients with crescentic GN may be diagnosed with an additionallife-threatening disease, namely malignant neoplasms. Immunosuppressivedrugs may promote such malignancies. However, some patientsare initially diagnosed with both diseases, suggesting a moreintimate relationship between crescentic glomerulonephritisand malignancies. We recently encountered a 68-year-old man, referred to us fromthe urology department because of an increasing serum creatinine.He had initially presented with intermittent haematuria a monthearlier. Cystoscopy revealed an exophytic bladder tumour thatwas resected. Histological examination (Figure 1)  相似文献   
8.
Evaluation of Seldinger Technique Emergency Cricothyroidotomy versus Standard Surgical Cricothyroidotomy in 200 Cadavers     
Schaumann  Nikolaus M.D; Lorenz  Veit M.D; Schellongowski  Peter M.D; Staudinger  Thomas M.D&#x;; Locker  Gottfried J. M.D&#x;; Burgmann  Heinz M.D&#x;; Pikula  Branko M.D&#x;; Hofbauer  Roland ; Schuster  Ernst Ph.D&#x;; Frass  Michael M.D&#x; 《Anesthesiology》2005,102(1):7-11
Background: Percutaneous cricothyroidotomy is a lifesaving procedure for airway obstruction in trauma victims who need airway establishment and cannot be intubated or in whom intubation has failed.

Methods: The purpose of this study was to examine whether there is a training effect using Seldinger technique emergency cricothyroidotomy (group 1; Arndt Emergency Cricothyroidotomy Catheter Set; Cook Critical Care, Bloomington, IN) versus standard surgical cricothyroidotomy (group 2). Twenty emergency physicians performed five cricothyroidotomies with each method in a total of 200 human cadavers, comparing efficacy and safety (speed, success rate, and injuries).

Results: Seven attempts in group 1 and six in group 2 had to be aborted. Time intervals from the start of the procedure to location of the cricothyroid membrane were not significantly different between the groups. However, time to tracheal puncture (P < 0.01) and time to first ventilation (P < 0.001) were significantly longer in group 2. No time effect could be observed in both groups. The airway was accurately placed into the trachea through the cricothyroid membrane in 88.2% (82 of 93) of the cadavers in group 1 and in 84.0% (79 of 94) in group 2 (not significant). No injuries were observed in group 1, whereas there were six punctures of the thyroid vessels in group 2 (P < 0.05).  相似文献   

9.
In vivo effects of hypothermia on the microcirculation during extracorporeal circulation.     
Markus Kamler  Jan Goedeke  Nikolaus Pizanis  Vitaliy Milekhin  Fritz-Ulrich Schade  Heinz Jakob 《European journal of cardio-thoracic surgery》2005,28(2):259-265
OBJECTIVE: Induced hypothermia has been shown to be protective during cardiac surgery, but also in traumatic, ischemic, burn, and neurological injury. In previous in vivo animal experiments, we documented increased leukocyte/endothelial (L/E) cell interaction following normothermic extracorporeal blood circulation (ECC). This study was carried out to investigate whether reduced core temperature during ECC affects the damage to the microcirculation as evidenced by leukocyte adherence and edema formation. METHODS: Intravital fluorescence microscopy was used on the dorsal skinfold chamber preparation in Syrian golden hamsters. ECC was introduced via a micro-rollerpump (1 ml/min) and a 60 cm silicon tube (1mm inner diameter) shunted between the carotid artery and the jugular vein after application of 300IE Heparin/kg per body weight. Experiments were performed in chronically instrumented, awake animals (age 10-14 weeks, weight 65-75 g). Animals of the experimental group were cooled to 18 degrees C body temperature while ECC, followed by a rewarming period (n=7), controls experienced ECC under normothermia (37 degrees C, n=7). RESULTS: 30 min ECC at 18 degrees C resulted in a decrease of rolling and adherent leucocytes (stickers) in postcapillary venules after 1, 4 and 8h compared with the control group (119+/-46 vs. 274+/-113 n/mm2, P<0.05, mean+/-SD; n=7 in each group). Functional capillary density was significantly reduced during hypothermia (80+/-16 vs. 148+/-16 cm/cm2, P<0.05), but restored after rewarming. In contrast, edema formation was markedly increased during hypothermia. CONCLUSIONS: Hypothermia during ECC significantly reduced L/E cell interaction in the early post-ECC period. Hypothermia markedly reduced microvascular perfusion, but was completely restored upon rewarming. Despite a reduced number of adherent leukocytes, no protection of endothelial barrier function was seen as a consequence of induced hypothermia.  相似文献   
10.
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1.
2.

Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Patients and Methods

We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.

Results

Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.

Conclusions

FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.  相似文献   
3.
Apoptosis is an essential ubiquitous process that controls the duration of the life span of cells, thus playing a crucial role in morphogenetic, histogenetic, and phylogenetic developmental processes. Apaf1 (apoptosis protease activating factor 1) is one of the central mediators of the intrinsic apoptotic pathway and a part of the apoptosome, which activates procaspase-3 and promotes cell death. Gene knockout of Apaf1 in mice leads to late embryonic lethality with malformations such as the persistence of interdigital webs and hyperplasia of brain and retina. Therefore, Apaf1 is generally believed to play a crucial role in developmental apoptosis and have a widespread expression. However, its pattern of expression in early development remains unknown. To specify whether Apaf1 indeed plays this key role, we investigated the pattern of gene expression for Apaf1 in mouse embryos on day 7, 9, and 12 of development. Our results show, that gene expression for Apaf1 first occurs within the embryo between day 7 and 9 of development, becoming more widespread toward day 12 and then includes structures, such as yolk sac, mesenchyme, cartilage, heart anlage, otic vesicle, peridermis, and anlagen of the spinal ganglia and vertebral bodies. Our results also show that gene expression for Apaf1 is not ubiquitous in early mouse development. This finding indicates that cell death processes are independent of or less dependent on Apaf1 during this time. Of interest, an active gene expression for Apaf1 is also present in organ anlagen such as heart or intestine, in which no obvious phenotype is seen after Apaf1 deletion. This finding suggests a possible role for Apaf1 in such anlagen as a putative alternative compensatory pathway, which could be switched on in the case of defects in the mediators that are normally involved in such organs.  相似文献   
4.
Ohne ZusammenfassungAus dem Luftfahrtmedizinischen Forschungsinstitut des Reichsluftfahrtministeriums. Leiter: Prof.H. Strughold.Warum ich zuletzt am liebsten mit der Natur verkehre, ist, weil sie immer recht hat und der Irrtum bloss auf meiner Seite sein kann.Goethe  相似文献   
5.
Background: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated.

Methods: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg [middle dot] kg-1 [middle dot] h-1) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat.

Results: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1).  相似文献   

6.
OBJECTIVE: As more patients are diagnosed with prostate cancer at an early stage, it is becoming increasingly important to refine the technique of surgical excision. For this purpose we have generated objective data comparing three different surgical approaches used by three experienced surgeons. METHODS: We prospectively compared three contemporary personal series of 50 consecutive radical prostatectomy (RP) patients. The health-related quality of life was evaluated preoperatively and in months 1, 3, 6, 12 and 24. RESULTS: Considering in turn the patients undergoing retropubic, perineal and laparoscopic RP, the median procedure time was 2 h and 27 min, 1 h and 50 min and 4 h, with a transfusion rate of 2, 0 and 8%, respectively. In the perineal group there were more wound infections. Median catheter drainage was 7, 10 and 7 days and zero, 13 and one patients needed reinsertion of a catheter. Early continence varied considerably, with 57.4, 11.4 and 6.3% of patients pad-free after 1 month, but there were no differences in social continence (zero or one pad) with 97.8, 97.8 and 91.9% after 2 years. The Litwin score for incontinence (preoperative minus postoperative) was -24, -41 and -63% after 1 month and -13, +3 and -29% after 2 years. Twenty-nine, five and 15 patients had a preoperative five-item version of International Index of Erectile Function (IIEF-5) score of > or = 17 points and a nerve-sparing procedure. After 2 years, 48.1, 0 and 0% had an IIEF-5 score of > or = 17 points without the use of phosphodiesterase type 5 (PDE-5) inhibitors, but when including patients using inhibitors there were no significant differences. CONCLUSIONS: A comparison of morbidity, short-term convalescence and long-term side-effects of different surgical techniques is strongly biased by both the preoperative status of patients and the skill of the surgeons. Overall, we found some differences in the short-term results (e.g. early continence) and comparable long-term results.  相似文献   
7.
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