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BACKGROUND: The aim of this article is to make physicians of all specialties aware of the possible variations of clinical course in human cowpox infection. This has been a matter of current interest since the detection of a first cluster of infections among owners of white pet rats in the Krefeld area in the spring of 2008. Two further cases arose in the Krefeld area in November 2008, and there have since been multiple further reports from various regions in Germany and the neighboring countries. METHOD: The authors report on the first six documented cases of infection with cowpox virus among young persons owning pet rats, with both typical and atypical clinical courses. RESULTS: The clinical, molecular biological, and serological findings confirmed cowpox virus infection in all six cases. The DNA sequence of the cowpox virus hemagglutinin gene was identical in all patients. The infections had arisen after direct contact with pet rats. CONCLUSIONS: Molecular genetic analysis of the cases described here suggests that the observed occurrence of cowpox virus infection among human beings and pet rats in multiple geographical areas represents a unitary epidemiological event that has not yet come under control. Further cases can be expected. [ABSTRACT FROM AUTHOR]

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The compounds referred to as bis (tryptophan)s (BTs) have shown activity as antimicrobials. The hypothesis that the activity of these novel amphiphiles results from insertion in bilayer membranes and transport of cations is supported by planar bilayer voltage-clamp studies reported herein. In addition, fluorescence studies of propidium iodide penetration of vital bacteria confirmed enhanced permeability. It was also found that BTs having either meta-phenylene or n-dodecylene linkers function as effective adjuvants to enhance the properties of FDA-approved antimicrobials against organisms such as S. aureus . In one example, a BT-mediated synergistic effect enhanced the potency of norfloxacin against S. aureus by 128-fold. In order to determine if related compounds in which tryptophan was replaced by other common amino acids (H 2 N-Aaa-linker-Aaa-NH 2 ) we active, a family of analogs have been prepared, characterized, and tested as controls for both antimicrobial activity and as adjuvants for other antimicrobials against both Gram-negative and Gram-positive bacteria. The most active of the compounds surveyed remain the bis(tryptophan) derivatives.

Juvenile xanthogranuloma (JXG) is a disorder of disputed origin thought to be related to the dermal/interstitial macrophage. A 5-year-old female presented with an aggressive systemic JXG that developed 5 months after the diagnosis of T-cell acute lymphoblastic leukemia (T-ALL). Examination of the T-cell receptor gamma (TCR-γ) rearrangement in T-ALL blasts, JXG infiltrated lymph node biopsies and micro-dissected JXG histiocytes revealed an identical bi-allelic TCR-γ rearrangement in all samples, thus providing evidence for a clonal relationship between T-ALL and JXG in this case., (Copyright © 2011 Wiley-Liss, Inc.)

The pharmacologic modulation of the platelet-activating factor antagonist WEB 2086BS on the release of metabolites of the arachidonic acid and the cytokine TNF alpha was investigated in an ex vivo xenograft model of hyperacute rejection. Pig kidneys were perfused for 60 min in a perfusion system with oxygenated heparinized human or autologous porcine blood, respectively. During autologous perfusion, no alterations in the mediator response could be detected, whereas xenogeneic perfusion induced progressive release of mediators. Treatment by the platelet-activating factor antagonist WEB 2086BS resulted in a significantly reduced liberation of the cytokine TNF alpha and of prostanoids. The histological findings verified that a hyperacute rejection in the xenogeneic perfused organs had occurred, which was mitigated by the treatment with WEB 2086BS. This observation confirms that inflammatory mediators play a decisive role in hyperacute xenogeneic rejection. The results suggest that suppression or manipulation of mediator-specific tissue receptors by receptor-antagonists could be an additional therapeutic mode to control hyperacute rejection in xenogeneic transplantation.

The tissue distribution of cellular adhesion molecules (CAMs) was studied in specimens from 10 normal human kidneys and in 52 biopsies from kidney allografts with cell-mediated rejection. In addition to the vascular presence of ICAM-1, a common finding in normal kidneys, expression of ICAM-1 on tubular cells was observed in 22 graft biopsies. Compared with normal kidneys, where VCAM-1 was present on Bowman's capsules and few proximal tubular cells, a markedly enhanced expression of VCAM-1 in numerous tubuli (including distal tubular segments) was observed in 51 graft biopsies. In 41 graft specimens VCAM-1 appeared also in variable numbers of peritubular capillaries. Infiltrating leukocytes carrying VCAM-1 were observed in 7 grafts. ELAM-1 could not be found in normal kidneys but was restricted to some peritubular capillaries in 29 grafts. Comparable results were obtained with cultured renal tubular cells when stimulated by TNF-alpha. That the induced appearance of adhesion molecules was in fact related to actual cellular synthesis was demonstrated by Northern blot analysis. Thus, little ICAM-1 specific mRNA of 3.4-kb length could be detected in unstimulated cultured renal tubular cells, but hybridization was markedly increased after stimulation with TNF-alpha. A substantial amount of VCAM-1 specific mRNA of 3.2-kb length was present already in unstimulated renal tubular cells. Likewise, synthesis of VCAM-1 mRNA was enhanced by stimulation with TNF-alpha. TNF-stimulated endothelial cells also showed weak synthesis of VCAM-1 mRNA. The results provide further evidence that constitutive and inducible expression of cell adhesion molecules contributes to the process of allograft rejection.

Radiofrequency catheter ablation has been shown to be an effective form of treatment of accessory pathways in patients with WPW-syndrome and other supraventricular tachycardias. However, the biophysical parameters so far used in vivo neither correlated with the size of the myocardial lesion nor did they provide any information about contact of the electrode with the myocardial wall. In this study, 104 radiofrequency energy applications were performed on excised pig myocardium in circulating heparinized pig blood, and in blood alone, and root mean square (rms) voltage, current and phase angle were measured using a specially developed device. The calculated effective power and output power differed by only 2-7% measured at the point of maximum current during coagulation. A progressive drop in current following a rise in impedance led to a phase shift of more than 80 degrees with a decrease in effective power to 17% of the output power. Hence, apparent output power was mainly ineffective power. The time-dependent variations of phase angle, impedance and current were found to be useful for distinguishing between the coagulated media. These results show that physical parameters measured during radio-frequency catheter ablation may help to monitor electrode position in the clinical situation and reduce the number of ineffective energy applications.

A 35-year-old woman underwent heart transplantation in 1986 because of dilated cardiomyopathy that developed after mitral valve replacements in 1971, 1975, and 1982. Additionally, a carcinoma of the left breast was diagnosed in 1984, leading to mastectomy, and in 1985 a local recurrent tumor had to be resected. In 1988 her gallbladder was removed after repeated episodes of biliary colic. Despite her eventful history, the patient is in good physical condition with normal heart performance and no signs of progression of the breast cancer under triple-drug immunosuppression.

After cardiac transplantation, bacterial mediastinitis is a rare but dangerous early complication. Of the 113 patients who underwent heart or heart-lung transplantation at our hospital from August 1981 to April 1989, 8 developed purulent mediastinitis. Treatment involved surgical débridment, local irrigation, drainage, and high-dose systemic antibiotics. No patient died of an acute mediastinal infection. In 2 cases, however, chronic mediastinitis led to the formation of a huge mycotic aneurysm of the ascending aorta. Eleven days after surgical intervention for rupture, 1 patient died of aneurysmal rerupture; the 2nd patient remains well 16 months after prosthetic replacement of the ascending aorta and reconstruction of the necrotic proximal portion of the left coronary artery with a saphenous vein patch.

FTCH is a recently developed material which consists of a collagen fleece containing fibrinogen, thrombin, and aprotinin integrated into its surface. FTCH is highly effective in sealing of tissues and in establishing hemostasis. We evaluated FTCH in experimentally produced liver (n = 6) and splenic (n = 12) injuries in 18 adult mongrel dogs. The stability of the parenchymal seal of the splenic injuries was tested by splenic tissue pressure elevation after temporary ligation of the splenic vein. No breakthrough bleeding occurred up to a parenchymal pressure of 16.3 +/- 5 mm Hg. Complete hemostasis was easily achieved in all animals before closure. When the dogs were re-explored postoperatively at intervals of either 14 or 30 days, there was no gross evidence of recurrent bleeding. Histologic examinations demonstrated a partially regenerated capsule covering an unspecific fibrovascular granulation tissue and progressive resorption of FTCH without significant inflammatory response. We conclude the following: FTCH provides adequate hemostatic control of experimental liver and splenic injuries. FTCH has excellent tissue compatibility and can be applied easily and safely to hemorrhaging parenchymal wounds. It will not replace adequate surgical techniques, but could be useful as a quickly available and easily applicable hemostatic means in diffuse or acute bleeding of liver and spleen.

At least seven members of a family coming from southern Germany (Franconia) have manifested Emery-Dreifuss syndrome within four generations. This syndrome is characterized by slowly progressing atrophic pareses, generally in a humeroperoneal distribution, premature joint contracture, and cardiomyopathy with reduction of functional capacity. Up to now four members of this family have died from cardiac causes between the age of 39 and 46 years. Three family members have now been thoroughly examined; they showed typical muscular atrophies and contractures. The two older patients were diagnosed as having a cardiomyopathy with a complete atrioventricular block and ventricular tachycardia. Electromyographic and histological findings indicate a primary neurogenic process. Regular cardiological examinations combined with effective therapy (for example, implantation of a cardiac pacemaker and treatment with antiarrhythmic drugs) will be necessary in treating the serious arrhythmias. Progressive myocardial insufficiency required heart transplantation in one of our patients, which was successfully performed. Macroscopic and microscopic examination of the explanted heart showed a dilatative cardiomyopathy with hypertrophy and dilatation of both atria and ventricles, differences in the diameters of individual heart muscle cells, and a predominately focal interstitial fibrosis.

The first successful heart-transplantation carried out in the Department for Cardiovascular Surgery of the University of Munich, Klinikum Grosshadern is reported. The recipient, 32 years old at the time of operation, had sustained a large antero-lateral-septal myocardial infarction in June 1980; thereafter the left ventricular ejection fraction was severely impaired (e.f. = 19%). Yet, the operation was definitely planned some year later, after the patient had survived an embolus to the right lung, an acute left heart failure and a small ulcer of the stomach. The operation was performed on 8-19-1981. The donor was a 23 year old young man, who had met a fatal motorcycle accident 10 days ago. The man was pronounced dead in the afternoon of the preoperative day according to the criterions of the German Society for Surgery by means of a carotid angiogram. Donor and recipient were well matched in regard to blood group, HLA-A2-System and finally cross-match-test. Transplantation was carried out according to the technique of Lower and Shumway. Immediately p.o., immunosuppressive therapy was started using azathioprine, cortisone and antihuman thymocyte globulin. Two acute rejections were noted, the first from p.o. day 6 to 15, the second from p.o. day 22 to 34. The second acute rejection was complicated by a pneumatosis cystoides intestinii, which caused a change of the immunosuppressive therapy to Cyclosporin A. No further complications were registered in the following p.o. course, the patient is discharged since Christmas 1981.

The present experiments were performed to examine the effect of variation in protein intake on renal function and morphology in the non-clipped kidneys of Goldblatt hypertensive rats. After renal artery clipping, rats were put on diets containing 5 (LP), 17.5 (NP), or 51% (HP) protein. After 4 to 5 weeks, all rats had developed hypertension. GFR was directly correlated with protein intake (1.47 +/- 0.15 in HP, 1.19 +/- 0.14 in NP, and 0.93 +/- 0.08 ml/min in LP), as was SNGFR (44.2 +/- 1.89, 39.1 +/- 2.23, and 27.9 +/- 0.86 nl/min in HP, NP, and LP rats). The response of SNGFR to changes in loop of Henle flow rate was attenuated in NP and HP rats: the maximum decrease was reduced (30.0 +/- 5.2% in NP, 22.1 +/- 4.2% in HP) and higher tubular flow rates were required to elicit responses (V1/2, the flow rate at which the response is half-maximum, was 28.9 +/- 2.6 nl/min in NP and 28.2 +/- 1.4 nl/min in HP). In LP rats, the maximum response was a decrease of 47.7 +/- 2.5%, and V1/2 was 18.1 +/- 1.2 nl/min, values similar to those found in normal control rats. The weights of the non-clipped kidneys were 0.96 +/- 0.04 g (LP), 1.06 +/- 0.05 g (NP), and 1.36 +/- 0.06 g (HP). In the LP rats there was no difference between the non-clipped and clipped kidneys. Light microscopic evaluation showed a high incidence of focal glomerulosclerosis in non-clipped kidneys of HP rats, but no glomerular lesions in the non-clipped kidneys of LP rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Though endomyocardial biopsy has remained the gold standard for diagnosing acute cardiac rejection (AR), this invasive method does not provide adequate means for close monitoring of the rejection process. In order to assess the usefulness of M-Mode- and two-dimensional (2D) echocardiography for the noninvasive diagnosis of AR in heart transplant recipients on cyclosporin, 45 patients (mean age 40.6 +/- 8.8 years, 19.9 +/- 14.4 months postoperatively) were evaluated prospectively. Mean observation time was 9.1 +/- 4.8 months. Echocardiographic examination techniques were strictly standardized; besides measurements of left (LV) and right ventricular (RV) diastolic wall thickness and of the isovolumic relaxation time, computerized frame-by-frame-analysis was applied to LV short axis cross sections for the determination of diastolic cavity cross-sectional area and extent and mean velocity of systolic and diastolic area change. To account for technical and biological variability, 95%-confidence limits were calculated for each parameter from two rejection-free examinations, allowing identification of significant changes during AR. In this study, 36 biopsy-proven AR occurred in 19 patients. Compared to control values, mean heart rate increased from 86.2 +/- 10.2 to 94.6 +/- 15.1 b/min (p less than 0.05), diastolic septal + posterior wall thickness from 21.2 +/- 4.1 to 24.9 +/- 6.2 mm (p less than 0.001) and RV free wall thickness from 6.3 +/- 1.1 to 8.9 +/- 1.8 mm (p less than 0.001). Isovolumic relaxation time decreased from 73.2 +/- 14.4 to 54.8 +/- 16.6 ms (p less than 0.001), diastolic cross-sectional area from 12.8 +/- 2.0 to 11.1 +/- 2.2 cm2 (p less than 0.05), relative area change from 65.8 +/- 9.8 to 49.1 +/- 14.4% (p less than 0.001) and systolic and diastolic area change velocities from 28.1 +/- 7.8 and 41.8 +/- 8.5 cm2/s to 18.9 +/- 5.6 and 28.6 +/- 9.2 cm2/s, respectively (p less than 0.001). Though significant changes occurred during AR, most measurements remained within the normal range. Thus, in individual patients, AR could only be suspected in comparison to the control measurements. None of the examined parameters allowed to establish the diagnosis of AR in all instances. However, when the measurements of all parameters were considered together, 35 of the 36 AR diagnosed by biopsy could also be identified by echocardiography, including all requiring intensified immunosuppressive therapy. Mild AR was not always detected, and the differential diagnosis between LV hypertrophy and AR required an endomyocardial biopsy in some instances.(ABSTRACT TRUNCATED AT 400 WORDS)