[Sarcomatoid renal cell carcinoma. A rare and aggressive variation of primary renal cell carcinoma]. / Das sarkomatoide Nierenzellkarzinom. Eine seltene und aggressive Variante des primären Nierenzellkarzinoms.

Every year, renal cell carcinoma (RCC) is responsible for the highest proportion of cancer-associated deaths in relation to all other malignant urological diseases. Initially called carcinosarcoma, the sarcomatoid differentiation confers higher aggressiveness on any of the different subtypes of RCC, with a frequency of ca. 1%. The presence of a sarcomatoid component makes the disease locally aggressive, which typically presents an advanced grade that is associated with fast progression and fatal outcome in a vast proportion of cases, with median survival lower than 1 year. This is important for predicting the outcome for patients undergoing nephrectomy due to RCC, since chemotherapy in a certain group of patients with progressive disease can be a reasonable alternative to the failure of immunotherapy in sarcomatoid renal carcinoma. We report our experience with sarcomatoid RCC in four patients with extensive tumor progression in comparison to the literature.

Retrograde jejunogastric intussusception due to suture concretion.

We describe a patient who presented with acute small bowel obstruction five years after Roux-en-Y reconstruction. Computed tomography and operative exploration showed a retrograde intussusception at the gastrojejunostomy due to an intraluminal suture concretion. We describe the preoperative imaging, endoscopic and intraoperative findings, and review the literature.

Matrix metalloproteinase inhibitor prevents acute lung injury after cardiopulmonary bypass.

BACKGROUND: Acute lung injury (ALI) after cardiopulmonary bypass (CPB) results from sequential priming and activation of neutrophils. Activated neutrophils release neutral serine, elastase, and matrix metalloproteinases (MMPs) and oxygen radical species, which damage alveolar-capillary basement membranes and the extracellular matrix, resulting in an ALI clinically defined as adult respiratory distress syndrome (ARDS). We hypothesized that treatment with a potent MMP and elastase inhibitor, a chemically modified tetracycline (CMT-3), would prevent ALI in our sequential insult model of ALI after CPB. METHODS AND RESULTS: Anesthetized Yorkshire pigs were randomized to 1 of 5 groups: control (n=3); CPB (n=5), femoral-femoral hypothermic bypass for 1 hour; LPS (n=7), sham bypass followed by infusion of low-dose Escherichia coli lipopolysaccharide (LPS; 1 microgram/kg); CPB+LPS (n=6), both insults; and CPB+LPS+CMT-3 (n=5), both insults plus intravenous CMT-3 dosed to obtain a 25-micromol/L blood concentration. CPB+LPS caused severe lung injury, as demonstrated by a significant fall in PaO(2) and an increase in intrapulmonary shunt compared with all groups (P<0.05). These changes were associated with significant pulmonary infiltration of neutrophils and an increase in elastase and MMP-9 activity. CONCLUSIONS: All pathological changes typical of ALI after CPB were prevented by CMT-3. Prevention of lung dysfunction followed an attenuation of both elastase and MMP-2 activity. This study suggests that strategies to combat ARDS should target terminal neutrophil effectors.

Free radicals and other reactive oxygen metabolites in inflammatory bowel disease: cause, consequence or epiphenomenon?

Oxygen-derived free radicals and other reactive oxygen metabolites have emerged as a common pathway of tissue injury in a wide variety of otherwise disparate disease processes. This has given rise to the hope that efforts directed towards the pharmacologic control of free radical-mediated tissue injury (Reilly, P.M., Schiller, H. J. and Bulkley, G. B. (1991) Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am. J. Surg. 161: 488-503) may have particular application to patients suffering from Crohn's disease and/or ulcerative colitis. However, because tissue injury by any mechanism, even direct mechanical trauma, can elicit an inflammatory response which entails the secondary generation of toxic oxidants by neutrophils and tissue macrophages, it is important that the evidence for this association be examined critically, so as to discriminate the possibility of an etiologic role for these toxic compounds from their presence as a reflection of injury caused primarily by other agents. Similarly, in considering the therapeutic potential of free radical ablation for the treatment of patients with IBD it is important to distinguish between interventions that might specifically block the fundamental injury mechanism from those which would act in a more nonspecific, anti-inflammatory role.

A technique for visual confirmation of intrathoracic placement of tube thoracostomy using a fiberoptic laryngoscope in a cadaver.

PURPOSE: Safe intrathoracic placement of chest tubes is a continual challenge. Current techniques for determining the intrathoracic location of the thoracostomy site include blunt dissection and digital exploration, with subsequent tube placement. Using current techniques, complication rates for this procedure approach 30%. We present a novel technique using available endotracheal intubation technology for determining intrathoracic placement of tube thoracostomy. METHODS: One cadaver was used for placement of tube thoracostomy. Both sides of the thorax were prepared in the standard fashion for tube thoracostomy placement, and tube thoracostomy was performed on each hemithorax at interspaces 3 through 7. The right side of the thorax was used for standard thoracostomy placement, and the left side was used for fiberoptic visualization of thoracostomy placement using a video laryngoscope. Thoracic wall thickness was measured at all thoracostomy sites. Proper placement and any injuries were documented for each site. RESULTS: Chest wall thickness ranged from 2.4 to 3.8 cm on the right and 2.8 to 4.0 cm on the left. With use of fiberoptic thoracostomy, no injuries were generated. During the standard thoracostomy placement in the sixth intercostal space, a pulmonary laceration was caused using blunt dissection. CONCLUSIONS: Use of a fiberoptic laryngoscope offers a novel technique for direct visualization the thoracic space during tube thoracostomy. Further studies are needed to determine the safety of this technique in patients.

Light-harvesting in Acaryochloris marina--spectroscopic characterization of a chlorophyll d-dominated photosynthetic antenna system.

Oxygenic photosynthesis of the prokaryote Acaryochloris marina involves chlorophyll d (Chl d) as the major pigment [Miyashita et al. (1996) Nature 383, 402]. Four spectral forms of Chl d (peak wavelengths: 694, 714, 726 and 740 nm) are resolvable by low-temperature absorption spectroscopy on intact cells. Based on fluorescence spectra (at 290 K and 77 K) and on analysis of fluorescence induction curves we conclude: (1) excitation energy is efficiently transferred between the various spectral forms of Chl d and the PS II reaction center; (2) Chl d serves as a light-harvesting pigment for both, Photosystem II (PS II) and PS I; (3) excitation energy transfer between PS II units occurs.

Human botulism studied with single-fiber electromyography.

In two cases of mild human botulism, conventional electromyography (EMG) was normal. In one case, the investigation with reptitive nerve stimulation showed slightly abnormal results, but in the other case the findings were within normal limits. Single-fiber EMG showed abnormal neuromuscular function and at later investigations as well, when the patient no longer showed any muscular fatigability. The jitter was frequency dependent and decreased with higher innervation frequency. The single-fiber EMG findings normalized after three months. The results are in agreement with the known disturbance of acetylcholine release.

Co-transplantation of donor-derived hepatocytes induces long-term tolerance to cardiac allografts in a rat model.

BACKGROUND: Liver allografts transplanted between MHC-disparate mice, rats, and swine are spontaneously accepted in most strain combinations without requirement for immunosuppression. The underlying mechanism has, however, remained elusive. Here, we demonstrate that co-transplantation of donor-derived hepatocytes protect Lewis (RT1.A1) cardiac allografts from acute and chronic rejection in DA (RT1.Aa) recipients indefinitely. METHODS: Livers of donor Lewis rats were harvested and the hepatocytes separated from hepatic leukocytes by collagenase digestion and gradient separation. DA recipient animals were transplanted Lewis cardiac allografts and simultaneously intraportally infused either Lewis-derived hepatocytes or hepatic leukocytes. Recipient animals were either not further treated or received a single dose of 15 mg/kg cyclosporine. RESULTS: Donor hepatocytes alone significantly protected syngeneic cardiac allografts from rejection, whereas hepatic leukocytes failed to influence graft survival. In combination with cyclosporine, recipient cardiac allografts were indefinitely protected from rejection. Graft-infiltrating cells in tolerant animals presented as clusters of CD4+ T cells and stained mostly positive for interleukin-4, whereas graft-infiltrating cells in rejected allografts were predominantly positive for interferon-gamma. Adoptive transfer of splenocytes derived from tolerant animals protected Lewis cardiac allografts from rejection in DA recipients without immunosuppression. In contrast, hepatic leukocytes protected only 50% of the allografts from rejection. CONCLUSION: We propose that donor hepatocytes induce permanent engraftment of syngeneic allografts by establishing a Th2 type alloresponse that is transferable to new graft recipients. The results of this study demonstrate that liver parenchymal cells significantly mediate spontaneously liver-induced tolerance.

Videomicroscopy provides accurate in vivo assessment of pulmonary microvascular reactivity in rabbits.

When defining the mechanism of hypoxic pulmonary vasoconstriction (HPV), investigators have employed ex vivo preparations because of the belief that accurate, quantitative assessment of pulmonary microvessels could not be obtained in vivo. We hypothesize that accurate, quantitative assessment of pulmonary microvascular reactivity can be performed using a simple, in vivo preparation. Our aim was to provide this quantitative assessment in a defined animal model, and to confirm that the chosen preparation could discriminate changes in microvascular reactivity as influenced by endogenous mediators. New Zealand rabbits were instrumented for in vivo microscopy and direct measurement of subpleural arterioles. Rabbits were first randomized to either control (n = 7) or endotoxin (n = 5), infusion of Escherichia coli lipopolysaccharide (200 Fg/kg). All rabbits were then exposed to a repeated protocol of normoxia (21% O2) for 20 min and then hypoxia (15% O2) for 10 min over 2 h. The changes in arteriole diameter were measured at the end of each interval. Normal pulmonary arterioles repeatedly constrict 15+/-3.5% during hypoxia. Altering endogenous vasoactive mediators, as with infusion of endotoxin, caused a loss of hypoxia-induced vasoconstriction. The results of our study validate this experimental preparation for the reliable quantification of pulmonary microvascular reactivity and investigation of hypoxic pulmonary vasoconstriction under both normal and pathologic conditions.

Invasive arterial BP monitoring in trauma and critical care: effect of variable transducer level, catheter access, and patient position.

OBJECTIVES: (1) To determine the validity of current recommendations for direct arterial BP measurement that suggest that the transducer (zeroed to atmosphere) be placed level with the catheter access regardless of subject positioning: and (2) to investigate the effect of transducer level, catheter access site, and subject positioning on direct arterial BP measurement. DESIGN: Prospective, controlled laboratory study. SETTING: Large animal laboratory. SUBJECTS: Five Yorkshire pigs. INTERVENTIONS: Anesthetized animals had 16F catheters placed at three access sites: aortic root, femoral artery, and distal hind limb. Animals were placed in supine, reverse Trendelenburg 35 degrees, and Trendelenburg 25 degrees positions with a transducer placed level to each access site while in every position. MEASUREMENTS AND MAIN RESULTS: For each transducer level, five systolic and diastolic pressures were measured and used to calculate five corresponding mean arterial pressures (MAPs) at each access site. When transducers were at the aortic root, MAP corresponding to aortic root pressure was obtained in all positions regardless of catheter access site. When transducers were moved to the level of catheter access, as current recommendations suggest, significant errors in aortic MAP occurred in the reverse Trendelenburg position. The same trend for error was noted in the Trendelenburg position but did not reach statistical significance. CONCLUSIONS: (1) Current recommendations that suggest placing the transducer at the level of catheter access regardless of patient position are invalid. Significant errors occur when subjects are in nonsupine positions. (2) Valid determination of direct arterial BP is dependent only on transducer placement at the level of the aortic root, and independent of catheter access site and patient position.

Scalable production of embryonic stem cell-derived cardiomyocytes.

Cardiomyocyte transplantation could offer a new approach to replace scarred, nonfunctional myocardium in a diseased heart. Clinical application of this approach would require the ability to generate large numbers of donor cells. The purpose of this study was to develop a scalable, robust, and reproducible process to derive purified cardiomyocytes from genetically engineered embryonic stem (ES) cells. ES cells transfected with a fusion gene consisting of the alpha-cardiac myosin heavy chain (MHC) promoter driving the aminoglycoside phosphotransferase (neomycin resistance) gene were used for cardiomyocyte enrichment. The transfected cells were aggregated into embyroid bodies (EBs), inoculated into stirred suspension cultures, and differentiated for 9 days before selection of cardiomyocytes by the addition of G418 with or without retinoic acid (RA). Throughout the culture period, EB and viable cell numbers were measured. In addition, flow cytometric analysis was performed to monitor sarcomeric myosin (a marker for cardiomyocytes) and Oct-4 (a marker for undifferentiated ES cells) expression. Enrichment of cardiomyocytes was achieved in cultures treated with either G418 and retinoic acid (RA) or with G418 alone. Eighteen days after differentiation, G418-selected flasks treated with RA contained approximately twice as many cells as the nontreated flasks, as well as undetectable levels of Oct-4 expression, suggesting that RA may promote cardiac differentiation and/or survival. Immunohistological and electron microscopic analysis showed that the harvested cardiomyocytes displayed many features characteristic of native cardiomyocytes. Our results demonstrate the feasibility of large-scale production of viable, ES cell-derived cardiomyocytes for tissue engineering and/or implantation, an approach that should be transferable to other ES cell derived lineages, as well as to adult stem cells with in vitro cardiomyogenic activity.

Immunoaffinity localization of the enzyme xanthine oxidase on the outside surface of the endothelial cell plasma membrane.

BACKGROUND: Reactive oxygen metabolites generated from endothelial xanthine oxidase (XO) trigger reperfusion injury in many organs. We evaluated the possibility that endothelial XO was localized on the endothelial cell surface, as well as within the cytoplasm. METHODS: Primary cultures of bovine (BAECs) and porcine (PAECs) aortic endothelial cells were grown in media documented to be free of XO. Polyclonal and monoclonal antibodies were developed against XO. These antibodies were used to evaluate BAEC and PAEC for cell surface XO through immunofluorescence staining, hybridoma cell surface labeling, and endothelial cell surface binding. RESULTS: These antibodies bound specifically to the surface of these cells when the membrane was shown to be intact and impermeable (and the cytoplasm inaccessible) to immunoglobulins Moreover, hybridoma cells expressing monoclonal antibody to XO bound specifically to the endothelial cell surface. Finally, intact endothelial cells bound specifically to the anti-XO polyclonal antibodies immobilized to the surface of a Petri dish. The integrity of these endothelial cell plasma membranes was demonstrated by the subsequent growth and replication of these cells in culture. CONCLUSIONS: These findings indicate that XO is present on the outside surface of the endothelial cell plasma membrane. This would not only explain the known in vivo efficacy of intravascularly administered large molecular weight antioxidants (such as superoxide dismutase) but could have important implications for inflammatory signaling.

Meconium staining of amniotic fluid at midtrimester amniocentesis.

Meconium-stained fluid was found in six of the first 234 amniocenteses performed at the University of Washington Prenatal Diagnosis Center. The taps were done between 16 and 20 weeks from the last menstrual period. Although in each case there was a factor that could have produced fetal distress, in no instance did intrauterine demise occur. All the pregnancies have terminated in the births of healthy children. Therefore, we believe that meconium staining of midtrimester amniotic fluid may in fact reflect a transient episode of fetal compromise but that the finding cannot be used to prognosticate either impending fetal death or the presence of congenital malformations in the newborn.

Acute visual loss during pregnancy after bromocriptine-induced ovulation. The elusive tumor.

The evaluation of patients complaining of amenorrhea with or without galactorrhea has been greatly enhanced by the availability of serum prolactin determinations and advances in diagnostic radiology. Likewise, the treatment of these patients with ergot derivative has resulted in the return of normal menses, and many pregnancies have been reported. The present report is of a patient with hyperprolactinemic amenorrhea-galactorrhea successfully treated with bromocriptine. A pregnancy followed resumption of menses, and a suprasellar cromophobeadenoma became manifest by producing blindness of the patient. The case is presented with recommendations for diagnosis and treatment.

Diphenhydramine in insomniac family practice patients: a double-blind study.

One hundred eleven mildly to moderately insomniac patients participated in a double-blind, placebo-controlled study to establish the efficacy of diphenhydramine as an over-the-counter (OTC) sleep aid. A two-week crossover design was employed in which all patients received both diphenhydramine and placebo for one week each. The daily diphenhydramine dose was 50 mg at bedtime. Results obtained indicate that diphenhydramine improved various sleep parameters, including sleep latency, to a significantly higher degree than did placebo. In addition, patients on diphenhydramine reported feeling more restful the following morning and patients preferred the diphenhydramine drug to placebo despite experiencing more side effects. This study thus supports the use of 50 mg diphenhydramine as an OTC sleep aid in the treatment of temporary mild to moderate insomnia.

Dominant myotonia congenita: pedigree with skipping of one generation.

The skipping of one generation in a family pedigree with dominant myotonia congenita is reported. It is suggested that non-penetrance in this condition occurs and should be considered in genetic counselling as a rare, but realistic possibility.

The reinnervated motor unit in man. A single fibre EMG multielectrode investigation.

Motor units in patients with motor neurone disease and polyneuropathy were studied with a new multielectrode technique allowing fibre mapping. In these disorders which are characterised by reinnervation the motor unit fibre distribution is changed from a normal scattered pattern to grouping often in clinically uninvolved muscles without definite EMG abnormalities. The changes found with this multielectrode technique in man are in accordance with those found in reinnervated motor units studied histochemically in the experimental animal.

The normal motor unit in man. A single fibre EMG multielectrode investigation.

The motor unit in the normal EDC and biceps brachii muscle was studied with a multielectrode technique permitting recording from 44 sites 300 mum apart. It was found that the muscle fibres in man are scattered with no evidence of grouping, similar to the findings in glycogen depletion experiments in animals.

A rapid specific radioimmunoassay for unconjugated estriol in plasma.

A rapid, non-chromatographic radioimmunossaay for unconjugated estriol in pregnancy plasma has been developed which utilizes a commonly available antiestrogen antisera. Estradiol-17beta and estrone demonstrate 135% relative cross-reactivity with our antiserum, as compared with 100% for estriol. Specificity is achieved by purification of estriol with solvent partitioning using benzene: petroleum ether (1:1). The results obtained using this method are similar to a radioimmunoassay utilizing a highly specific, but commercially unavailable, antiestriol antiserum. The method is precise, with coefficients of variation ranging from 3.0 to 8.2%.

Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites.

Highly toxic metabolites of oxygen are generated normally by aerobic metabolism in most cells, and this generation is often greatly increased in pathologic conditions. When this oxidant flux exceeds the capability of the multiple endogenous antioxidant mechanisms, tissue injury ensues. The pharmacologic modification of this injury process, with agents that scavenge these reactive oxygen metabolites, block their generation, or enhance the endogenous antioxidant capability, has shown great promise in animal models of common clinical conditions, and has already been successfully applied in controlled clinical trials. This approach represents an interruption of tissue injury at its most basic level.