Fate of patients with extracorporeal lung assist as a bridge to lung transplantation versus patients without--a single-center experience.

OBJECTIVES: Mechanical lung assist (MLA; extracorporeal membrane oxygenation (ECMO) or extracorporeal lung assist (ECLA)) is increasingly used as a temporary bridge to lung transplantation (LTx). This study was designed to evaluate the impact of preoperative MLA on the operative outcome, including longer-term survival, in comparison to patients undergoing LTx without preoperative MLA. METHODS: A total of 143 patients underwent LTx at our institution from 2002 to 2011. Forty-three percent (n=62) of patients presented with idiopathic pulmonary fibrosis and 71% (n=102) presented with severely elevated pulmonary artery pressure. RESULTS: Thirteen patients (9.1%) required pre-LTx MLA support (age 44 ±13 years, double LTx 73.3%, female gender 53%) whereas 130 patients did not (age 52 ±11 years, double LTx 41.5%, female gender 36.9%). In one patient, MLA was successfully weaned and the patient underwent subsequent LTx. All patients in the MLA group were intraoperatively supported with continuous ECMO. One patient had to be supported with MLA after LTx for a period of 8 days. The short-term and mid-term postoperative survival of the MLA patient group was not significantly different from the non-MLA group (LogRank p=0.28). The 30-day, 90-day and 1-year survivals were 95%, 90% and 71%, respectively, in the patients without MLA compared to 85%, 77% and 68% in the MLA group. CONCLUSIONS: MLA has no impact on long-term survival rate in LTx patients, but has an influence in postoperative survival. MLA support is a valuable tool to bridge unstable patients to LTx.

Characterization of the ovarian cycle in the two-toed sloths (Choloepus didactylus): an innovative, reliable, and noninvasive method using fecal hormone analyses.

Little is known about reproductive physiology in the two-toed sloth (Choloepus didactylus). Therefore, the aim of this study was to obtain detailed information about the ovarian cycle. Measurements of reliable gonadal steroids in the feces of this species were undertaken. For this purpose, fecal samples were collected one to three times per week from nonpregnant captive females (n = 2) over a 16-month period. Before assay analysis, the fecal samples were extracted with methanol. Radioimmunoassays and enzyme immunoassays for fecal progesterone, estradiol-17ß, pregnanediol-glucuronide (PdG), and estrone sulfate were tested for their ability to detect the ovarian activity. Using the lowest and highest progesterone values, the ovarian cycle length was comparatively analyzed. The ovarian cycle (n = 26) averaged between 31.4 ± 9.1 days (lowest progesterone) and 32.5 ± 7.5 days (highest progesterone) throughout the whole year. The length of the follicular phase, as indicated by low progesterone levels, was 18.1 ± 4.4 days (range 12-25 days), and the length of the luteal phase, as characterized by elevated progesterone levels, was 13.2 ± 1.8 days (range 11-16 days). In contrast, estradiol-17ß and estrone sulfate were not suitable to detect the cycle due to irregular collection intervals. Fecal progesterone and PdG, as well as estradiol-17ß and estrone sulfate, significantly correlated (r = 0.621, P < 0.01 and r = 0.606, P < 0.01). PdG concentrations (dilution factor (DF) 1:40) were considerably higher than progesterone concentrations (DF 1:10), PdG amounted in the range of 1326.7 ± 320.2 ng/g wet feces (animal S1) and 1373.8 ± 468.3 ng/g wet feces (animal S2) compared with progesterone concentrations in the range of 98.0 ± 17.0 ng/g (S1) and 105.9 ± 30.0 ng/g (S2). The estrone sulfate levels (DF 1:2) were similar to estradiol-17ß (DF 1:22). The mean fecal estradiol-17ß concentrations were 6.7 ± 0.9 ng/g for animal S1 and 7.5 ± 1.6 ng/g for animal S2. In conclusion, the ovarian activity of the two-toed sloth was studied using the noninvasive method by means of the fecal steroid monitoring. Progesterone was the most reliable fecal steroid hormone to determine the duration of the ovarian cycle independent of the weekly defecation rate. The course of progesterone concentrations resulted in a cycle length of 4-5 weeks length in the two-toed sloth. Thus, the reproductive activity of the two-toed sloth does not show any seasonality like the three-toed sloth.

Towards patient-specific finite-element simulation of MitralClip procedure.

MitralClip is a novel minimally invasive procedure to treat mitral valve (MV) regurgitation. It consists in clipping the mitral leaflets together to close the regurgitant hole. A careful preoperative planning is necessary to select respondent patients and to determine the clipping sites. Although preliminary indications criteria are established, they lack prediction power with respect to complications and effectiveness of the therapy in specific patients. We propose an integrated framework for personalized simulation of MV function and apply it to simulate MitralClip procedure. A patient-specific dynamic model of the MV apparatus is computed automatically from 4D TEE images. A biomechanical model of the MV, constrained by the observed motion of the mitral annulus and papillary muscles, is employed to simulate valve closure and MitralClip intervention. The proposed integrated framework enables, for the first time, to quantitatively evaluate an MV finite-element model in-vivo, on eleven patients, and to predict the outcome of MitralClip intervention in one of these patients. The simulations are compared to ground truth and to postoperative images, resulting in promising accuracy (average point-to-mesh distance: 1.47 +/- 0.24 mm). Our framework may constitute a tool for MV therapy planning and patient management.

[Pericardial effusion. Differential diagnostics, surveillance and treatment]. / Perikarderguss. Differenzierte Diagnostik, Überwachung und Therapie.

Cardiac tamponade can be a life-threatening condition due to the high variability of clinical symptoms and the associated risk of rapid hemodynamic deterioration. Therefore, accurate diagnosis followed by immediate intervention is necessary. Common clinical features of cardiac tamponade are pulsus paradoxus, tachycardia, elevated jugular venous pressure and hypotension; however, although these can be indicative of cardiac tamponade they are non-specific. Instant confirmation of the clinical diagnosis of cardiac tamponade can be pursued with echocardiography which also enables a clear estimation of the current hemodynamic situation. Thus in contemporary clinical practice echocardiography plays a key role in the management of cardiac tamponade and must be consulted with regards to final treatment decisions. Common practice includes pericardial puncture under echocardiographic and/or X-ray guidance but only in cases of significantly sized pericardial effusions. Whenever there is a limited sized but hemodynamically significant effusion, inferior pericardiotomy should be the preferred treatment strategy. In cases of cardiac tamponade following chest trauma a full median sternotomy can be a suitable approach for surgical treatment.

Coronary artery disease: a new manifestation in Dubowitz syndrome.

We report here a case of coronary artery disease in a patient with Dubowitz syndrome. A 19-year-old man suffered from recurrent angina after an anterior wall myocardial infarction. Coronary angiogram demonstrated severe stenoses of the left main and obtuse marginal vessels, as well as occlusion of the left anterior descending artery. The patient was successfully treated with coronary artery bypass graft surgery.

Cytokine gene expression in monocytes of patients undergoing cardiopulmonary bypass surgery evaluated by real-time PCR.

Cardiopulmonary bypass (CPB) surgery induces systemic release of proinflammatory cytokines causing unspecific inflammatory reactions. This study deals with the development of a sensitive technique for detecting changes at the mRNA level in monocytes of patients undergoing CPB surgery, by using real-time PCR. Blood samples from patients undergoing elective coronary artery bypass grafting were obtained at six different time points. RNA was extracted from isolated monocytes and cDNA was synthesized by reverse transcriptase. CPB surgery induced gene expression of IL-1beta, IL-6, IL-8, and TNF-alpha, followed by a decrease below the preoperative expression values 6 h post CPB. High significant increases in gene expression for IL-8 at the end of surgery (p = 0.001) were detected. Real-time PCR is a powerful tool for getting simultaneously numerous sensitive, accurate, and reliable results from small amounts of biological material. This method avoids time-consuming and hazardous post-PCR manipulations and decreases the potential risk of PCR contamination.

Multiple arterial thromboembolisms in a patient with the 20210 A prothrombin gene mutation.

The most recently characterized genetic defect contributing to venous thrombophilia is the 20210 A prothrombin gene mutation. We describe a patient with this defect who had arterial thrombosis resulting in considerable mesenteric ischemia. Several environmental factors, which might otherwise be considered of low thrombotic risk, may also have contributed to her condition. The recognition of the potential for novel presentations of hypercoagulable states may contribute to a reduction in the morbidity associated with acute mesenteric ischemia.

Elevated cortical extracellular fluid glutamate in transgenic mice expressing human mutant (G93A) Cu/Zn superoxide dismutase.

Transgenic mice expressing a mutated (G93A) human Cu/Zn superoxide dismutase (SOD1) develop motor neuron pathology and clinical symptoms similar to those seen in patients with amyotrophic lateral sclerosis. Loss of motor neurons is most prominent in lumbar, followed by cervical cord and then brainstem. No significant cell death has been reported in motor cortex. The integrity of the cortical glutamate reuptake systems was evaluated using intracerebral microdialysis and western immunoblot assays for the glutamate transporters GLT-1, GLAST, and EAAC1. The basal extracellular fluid levels of aspartate, glutamate, glutamine, 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid were evaluated by HPLC. The extraction fraction of L-3H]glutamate, corrected with [14C]mannitol, was also evaluated. GLT-1, EAAC1, and GLAST protein levels were determined by semiquantitative chemiluminescence immunoblot of proteins from membrane-enriched fractions. The relative optical density of film was translated into relative protein level by comparison with a standard control mouse. The SOD1 mutant mice demonstrated a significant (p < 0.05) increase in basal levels of extracellular aspartate and glutamate. In addition, when the glutamate extraction fraction was challenged with exogenous unlabeled glutamate (500 microM) by reversed microdialysis, the glutamate extraction fraction in the mutant SOD1 mice was decreased significantly from control levels. The SOD1 mutant mice demonstrated no difference in the cortical protein levels of the glutamate transporter subtypes. This study demonstrates that in areas of no visible pathology and no loss of glutamate transporter proteins, SOD1 mutant mice have elevated extracellular fluid aspartate and glutamate levels and a decreased capacity to clear glutamate from the extracellular space.

Influence of 5-fluorouracil on colonic healing and expression of transforming growth factor-beta 1.

BACKGROUND: Administration of chemotherapeutic agents in the immediate postoperative period may have beneficial effects by decreasing local cancer recurrence rates, but this must be weighed against possible impairment of wound healing. Since local expression of transforming growth factor-beta1 (TGF-beta1) is normally upreglated following creation of experimental colonic anastomoses, this study examines the effects of 5-fluorouracil (5-FU) on colonic healing and on the local expression of TGF-beta1. MATERIALS AND METHODS: Forty-eight male Sprague-Dawley rats underwent transection of the descending colon with primary anastomosis and were then randomly assigned to receive either intraperitoneal 5-FU (20 mg/kg/day) or saline (SAL). On Postoperative Days (PODs) 3, 5, and 7, bursting pressure (BP, mm Hg) and bursting energy (BE, mm Hg xs) were determined in situ. Anastomotic and nonoperated segments of colon were harvested and analyzed using the semiquantitative reverse transcriptase-polymerase chain reaction to determine the relative expression of TGF-beta1 normalized to that of a constitutive gene. RESULTS: Progressive increases in BP and BE were observed in both the 5-FU and the SAL groups, across the time course examined. Overall, these measures were decreased in the 5-FU groups compared to SAL, significantly so on PODs 5 and 7; BP, 127.8 +/- 7.6 vs 161.1 +/- 7.2 and 139.9 +/- 10.9 vs 186.0 +/- 8.6; BE, 1093.6 +/- 190.0 vs 2207.9 +/- 308.2, and 1518.5 +/- 326.5 vs 3279.3 +/- 225.7, respectively. Anastomotic TGF-beta1 expression also increased progressively in both groups over the postoperative time course. Expression in the 5-FU group, however, was significantly decreased compared to that in the SAL group on POD 3; 0.42 +/- 0.05 vs 0.84 +/- 0.04. Interestingly, this preceded the reduction in BP and BE in the 5-FU group on PODs 5 and 7. TGF-beta1 expression in nonoperated colonic segments did not change during the time points studied or in response to 5-FU administration. CONCLUSIONS: Wound healing following a colonic anastomosis is associated with local increases in TGF-beta1 expression, which in turn is diminished by the administration of 5-FU. If this deleterious effect on wound healing could be counteracted, then chemotherapy administration in the immediate postoperative period may become safer.

Effect of bowel preparation and a fiber-free liquid diet on expression of transforming growth factor and procollagen in colonic tissue preoperatively and postoperatively.

PURPOSE: Dehiscence of colonic anastomoses is prevalent and potentially fatal. In an attempt to reduce the likelihood of anastomotic dehiscence, the colon is cleansed before surgery and fiber-free diets are prescribed postoperatively. However, fiber-free diets induce colonic atrophy and impair healing. This study was designed to investigate the effect of bowel preparation and postoperative fiber-free diet on the local gene expression of transforming growth factor-beta 1 and procollagen type I. METHODS: Four Sprague-Dawley rats underwent bowel preparation with a fiber-free liquid diet and polyethylene glycol in a balanced electrolyte solution for two days (fiber-free preoperative diet group), whereas four rats received standard chow with fiber (preoperative diet with fiber group). On the third day tissue was obtained from the descending colon of each rat to assess the effect of bowel preparation. Forty additional rats had their bowels prepared and underwent transection of the descending colon and anastomosis. These rats were then randomly assigned to continue on the liquid diet (fiber-free postoperative diet group) or rat chow (postoperative diet with fiber group). On postoperative days 3, 5, 6, 7, and 14, colonic tissue was obtained from the anastomosis and analyzed with the use of semiquantitative reverse transcriptase-polymerase chain reaction to examine the relative expression of transforming growth factor-beta 1 and procollagen type I genes normalized to that of a constitutive gene. RESULTS: There was a decrease in the expression of the transforming growth factor-beta 1 and the procollagen type I genes in the fiber-free preoperative diet group compared with the preoperative diet with fiber group; however, this difference only reached statistical significance for procollagen type I. Postoperatively, significant increases in the expression of the transforming growth factor-beta 1 and procollagen type I genes over baseline levels were observed around postoperative day 7 in both groups, which temporally correlates with active phases of collagen deposition in the wounded colon. Expression of the procollagen type I gene, however, was significantly decreased at this time in the fiber-free postoperative diet group compared with the postoperative diet with fiber group. CONCLUSION: Although necessary to reduce septic complications, preoperative bowel preparation has a detrimental effect on the expression of transforming growth factor-beta 1 and procollagen type I. A postoperative fiber-free liquid diet also may be detrimental to the expression of these transcripts in the bowel. Alternative methods for delivery of colonic fuels are needed to create a better environment for colonic healing while eliminating bacteria and bulk.

Long-term remission of two feet-one hand syndrome.

Two feet-one hand syndrome is also defined as bilateral plantar tinea pedis with coexistent unilateral tinea manuum. Toenails and fingernails may also be affected and the dermatophyte Trichophyton rubrum is the usual cause. When there is nail involvement, especially of the toenails, treatment with an oral antifungal agent should be considered because topical therapy alone is usually not effective. However, relapses are common. With the advent of new, more effective antifungal drugs such as itraconazole, terbinafine, and fluconazole, it is hoped that this troublesome and recalcitrant disorder may be better controlled.

cDNA sequence and differential mRNA regulation of two forms of glial cell line-derived neurotrophic factor in Schwann cells and rat skeletal muscle.

Total RNA from rat Schwann cells grown in culture and adult rat skeletal muscle was reverse transcribed, amplified for glial cell line-derived neurotrophic factor (GDNF) messenger RNA (mRNA) using the polymerase chain reaction (PCR), and the PCR products sequenced. Two forms of GDNF were detected in the PCR step, one of a predicted size (GDNF633) and a second smaller form missing a 78-base pair sequence (GDNF555). Sequence analysis demonstrated that GDNF633 is similar to the published sequence of GDNF differing only at three nucleotides. Southern and Northern blot analyses reveal that the two forms are probably derived from a single RNA species that is alternatively spliced. Interestingly, GDNF633 mRNA was found to be selectively upregulated in denervated rat skeletal muscle at 1-2 weeks following axotomy, providing evidence that the innervation status of the muscle may determine the expression profile of the two alternatively spliced forms. Given these findings, we suggest that GDNF may function as a target-derived trophic factor for neuronal populations innervating skeletal muscle, including sensory neurons and spinal cord motoneurons.

Experimental rationale for the therapeutic use of neurotrophins in amyotrophic lateral sclerosis.

Current therapeutic efforts to treat chronic and progressive neurodegenerative disease include, for the first time, attempts to regenerate affected nervous tissue using neurotrophic factors. The rationale for using trophic factors includes the understanding that they support neuronal survival and regrowth processes. The potential benefits of trophic factor therapy will be no more realized in the near future than in the treatment of amyotrophic lateral sclerosis (ALS). ALS is pathologically characterized by the selective degeneration of specific populations of cranial and spinal motoneurons. Evidence for the existence of factors that support motoneurons has come from studies demonstrating that motoneurons receive trophic influences from various tissues, both central and peripheral, within their local environment. Although the identity of these putative tissue-derived factors has remained enigmatic, recent studies have demonstrated that several previously characterized trophic factors exhibit trophic influences on motoneurons. Among these are several members of the neurotrophin family, most notably brain-derived neurotrophic factor. These neurotrophins meet most of the criteria to be considered motoneuron trophic factors: they are locally available to motoneurons in vivo; motoneurons express specific receptors for these factors; and exogenous application of these factors mimicks the effects of the uncharacterized endogenous agents. The clinical use of these factors for the treatment of ALS, therefore, appears to be scientifically justified.

Spinal cord motoneurons express p75NGFR and p145trkB mRNA in amyotrophic lateral sclerosis.

In the present study, in situ hybridization was used to examine the expression of nerve growth factor (NGF) receptor (p75NGFR), trk (p140trk) and trkB (p145trkB) mRNA in spinal cord sections from patients with amyotrophic lateral sclerosis (ALS). We report that the expression of p75NGFR and p145trkB mRNA is elevated in alpha motoneurons in ALS sections. However, p140trk mRNA was not expressed in either ALS or control sections.

Lennert's lymphoma presenting as prurigo nodularis.

Lennert's lymphoma is a peripheral T-cell lymphoma that only rarely involves the skin. We present the case of a forty-two-year-old man who experienced severe pruritus for ten months. He was repeatedly diagnosed as having neurodermatitis and prurigo nodularis before subtle hematologic clues suggested, and subsequent examination of bone and lymph node biopsy specimens confirmed, the diagnosis of Lennert's lymphoma. This report describes the case and presents a brief review of Lennert's lymphoma.

The reliability of a second biopsy for determining residual tumor.

BACKGROUND: Often after biopsy a skin cancer appears to resolve clinically and a repeat biopsy may be done on the area in question before proceeding with further treatment. OBJECTIVE: Our purpose was to assess the value of a subsequent biopsy in the treatment of skin cancers previously diagnosed by biopsy results. METHODS: The results of a subsequent biopsy were compared with the results of Mohs micrographic surgery in 291 patients with biopsy-established basal cell carcinoma and squamous cell carcinoma. Pre-Mohs surgery curettings were examined in 60 of these patients to evaluate whether these could have caused false-negative Mohs results. RESULTS: One hundred nineteen patients had a negative second biopsy, of which 75 (63%) had residual tumor at surgery. Eight of 60 patients in whom the curettings were examined had negative results from both biopsy and Mohs surgery; tumor in the curettings was shown in six of these eight patients (75%). CONCLUSION: This study suggests that 63% or more of subsequent biopsy specimens for skin cancer may yield false-negative results and casts doubt on the usefulness of a subsequent biopsy before surgery.