A patient with insidious onset of exertional dyspnoea.

The case history is presented of a 42 year old woman with pulmonary artery occlusion due to tuberculous vasculitis that masqueraded as chronic pulmonary artery embolism and led to severe life threatening haemoptysis necessitating emergency pneumonectomy. It is concluded that obliterative tuberculous endarteritis of the pulmonary arteries should be considered in the differential diagnosis of any acquired obstruction of pulmonary arteries.

Chronic paracoccidioidomycosis in a female patient in Austria.

Presented here is a case of chronic paracoccidioidomycosis that occurred in a Cuban female living in Austria and was first misdiagnosed as tuberculosis. The clinical picture was one of progressive pulmonary insufficiency with fever, weight loss and productive cough. Since antituberculous therapy was started but did not achieve a long-term clinical response, an intensive diagnostic work-up was performed. Paracoccidioides brasiliensis was then diagnosed by histopathology, serology, microbiology and molecular identification. Antifungal therapy was commenced immediately with amphotericin B (1 mg/kg/day) for 10 days, followed by voriconazole (200 mg/day po) for at least 3 months, and the lesions disappeared almost completely. This report presents the first published case of imported paracoccidioidomycosis in a female patient in Austria.

A double-hand transplant can be worth the effort!

BACKGROUND: Composite-tissue transplantation offers a new therapeutic option for patients with loss of a hand. Little is known, however, about the long-term outcome after such a transplant with regard to graft function and immunosuppression and its side effects. We here report on our experience with a double-hand transplant performed more than 18 months ago. METHODS: Both distal forearms and hands of an age-, gender-, and size-matched cadaveric donor were transplanted to a 47-year-old policeman 6 years after loss of both hands. He received antithymocyte globulin as induction therapy and tacrolimus, mycophenolate mofetil, and prednisone as maintenance immunosuppression. Ganciclovir and co-trimoxazole were given prophylactically for cytomegalovirus and Pneumocystis carinii infection. A special rehabilitation program based mainly on cognitive therapy was designed and continued for 1 year. RESULTS: Apart from a small area of skin that became necrotic early and some arteriovenous fistulas in the left forearm, which required ligation 6 months after transplantation, there were no surgical complications. One acute rejection episode occurred on day 55 and resolved completely after high-dose steroids and topical tacrolimus. Despite ganciclovir prophylaxis, virus replication was observed. The patient became negative for cytomegalovirus only after additional treatment with foscarnet (Foscavir) and cidofovir. At the end of 18 months, graft function with regard to motility is overall 60% of normal and enables the patient to pursue activities he could not with his myoelectric prostheses. CONCLUSIONS: Excellent long-term results can be achieved with double-hand transplantation. Prerequisites are an appropriate surgical technique, careful immunosuppression, and an extensive rehabilitation program.

Prenatal diagnosis of de novo mosaic deletion 13q associated with multiple abnormalities.

A case of prenatal diagnosis of de novo mosaic deletion of the long arm of chromosome 13 (del(13)(q13.3)) is presented. Routine scanning in a 27-year-old primigravida at 25 weeks' gestation showed fetal bilateral hydronephrosis. Detailed anomaly scanning in our tertiary referral center further demonstrated posterior meningoencephalocele, sloping forehead, microcephaly, syndactyly and hypoplastic thumbs. Both genetic amniocentesis and cordocentesis revealed a mosaic karyotype, 46,XY/46,XY,del(13)(q13.3). Sonographic findings were confirmed by postmortem autopsy and additional abnormalities such as agenesis of corpus callosum, hypoplastic cerebellum and macroglossia were diagnosed. Detailed sonography in this case thus revealed multiple malformations that prompted fetal karyotyping at 25 weeks' gestation.

High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia.

Childhood acute lymphoblastic leukaemia (ALL) is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potential mechanism in the trafficking of leukaemia cells is the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells, and its ligand stromal cell-derived factor-1 (SDF-1), produced by stromal cells in bone marrow and extramedullary organs. Functionality of CXCR4 was demonstrated by a high correlation between cell surface density of CXCR4 and transendothelial migration of leukaemia blasts towards a gradient of SDF-1 (r = 0.73, P = 0.001). Inhibition of SDF-1-induced migration by an anti-CXCR4 monoclonal antibody (78.33 +/- 23.86% inhibition) evidenced the specificity of CXCR4 to SDF-1. In order to evaluate clinical significance of CXCR4 expression, lymphoblasts from the bone marrow of 73 patients with and without extramedullary organ infiltration were compared. Multiparameter flow cytometry revealed that lymphoblasts from patients with high extramedullary organ infiltration, defined as ultrasonographically measured enlargement of liver or spleen, expressed the CXCR4 receptor at higher fluorescence intensity (median 66.12 +/- 66.17) than patients without extramedullary organ infiltration (median 17.56 +/- 19.29; P < 0.001). Consequently, high expression of CXCR4 was strongly predictive for extramedullary organ involvement, independently of the peripheral lymphoblast count. Highest CXCR4 expression was seen in mature B ALL (median 102.74 +/- 92.13; P < 0.003), a disease characterized by a high incidence of extramedullary bulky disease. As high expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood ALL, we suggest that CXCR4 and its ligand play an essential role in extramedullary invasion.

Intravital lectin perfusion analysis of vascular permeability in human micro- and macro- blood vessels.

We previously applied intravital lectin perfusion in mouse models to elucidate mechanisms underlying vascular permeability. The present work transfers this technique to human models, analysing vascular permeability in macro- and microvessels. Human vascular endothelial surface carbohydrate biochemistry differs significantly from its murine counterpart, lacking alpha-galactosyl epitopes and expressing the L-fucose moiety in the glycocalyx; the poly-N-lactosamine glycan backbone is common to all mammals. We examined extensively lectin binding specificities in sections and in vivo, and then applied the poly-N-lactosamine-specific lectin LEA and the L-fucose-specific lectin UEA-I in human intravital perfusions. Transendothelial transport differed in macrovessels and microvessels. In microvessels of adult human fat tissue, rectal wall and rectal carcinomas, slow transendothelial transport by vesicles was followed by significant retention at the subendothelial basement membrane; paracellular passage was not observed. Passage time exceeded 1 h. Thus we found barrier mechanisms resembling those we described previously in murine tissues. In both adult and fetal macrovessels, the vena saphena magna and the umbilical vein, respectively, rapid passage across the endothelial lining was observed, the tracer localising completely in the subendothelial tissues within 15 min; vesicular transport was more rapid than in microvessels, and retention at the subendothelial basement membrane briefer.

Connexin 26 in human fetal development of the inner ear.

Specialized for intercellular communication, gap junctions have been theorized to provide a means (the epithelial and connective tissue gap junction systems) by which fluid and ions might be transported for maintenance of high levels of endolymphatic K+ [Kikuchi et al., 1994. Acta Otolaryngol. 114, 520-528] in the inner ear. A primary constituent of these gap junctions is connexin 26 (Cx26), a protein encoded by the gene GJB2 and found in both epithelial and connective tissue cells. It has been shown that a mutation in Cx26 accounts for 50% of patients with autosomal recessive nonsyndromic hearing loss. In the present study, we document the emergence and distribution features of Cx26 through various stages (weeks 11-31) of gestation in human, fetal cochleae. Comparative patterns of Cx26 distribution are also presented in the mature rat. The cochleae were fixed in 4% paraformaldehyde within 2 h post mortem. Immunohistochemical studies were performed using a rabbit polyclonal antibody raised against synthetic peptide and corresponding with amino acids 108-122. Specimens were mounted into paraffin sections. Results show that Cx26-like immunoreactivity is evident at a prenatal age of 11 weeks and maintains a high intensity of reactivity through 31 weeks of gestation. The appearance of this reactivity seemed to modulate in parallel with the onset of development and histological maturation as well as provide functional maintenance. In the human fetal cochlea, Cx26-like immunoreactivity distribution resembled adult patterns by fetal week 20. At the completion of morphological development by week 31, reactivity appeared to achieve an adult profile of distribution. Descriptions and discussion of Cx26 distribution patterns are presented in detail.

A new biliodigestive anastomosis technique to prevent reflux and stasis.

BACKGROUND: The Roux-en-Y procedure for biliodigestive drainage is most widely accepted, but 10% to 15% of patients postoperatively suffer from a blind-loop syndrome or cholangitis due to motility disorders. A new biliodigestive technique is evaluated in a rat model to prevent these complications. METHODS: This experimental study in Wistar rats compares the Roux-en-Y technique with a new biliodigestive anastomosis creating a jejunal loop with luminal occlusion. Clinical parameters, small bowel motility, bacteriologic growth, and liver histopathology were evaluated in native and postoperative animals within a study period of 180 days. RESULTS: Both operative procedures were well tolerated. After 6 months intense fibrosis of the liver and high-grade purulent cholangitis were observed in animals in the Roux-en-Y group. In these animals enterobacter and enterococci overgrowth was found. Myoelectric small bowel recordings revealed significant impairment of slow-wave frequency, aboral velocity, and action potentials (percentage of phase III) in Roux-en-Y animals. CONCLUSIONS: Motility disorders after conventional Roux-en-Y biliodigestive anastomosis are pivotal for histomorphological damage and infectious findings and can be prevented by using the new technique to create a jejunal loop with luminal occlusion.

Goldenhar's syndrome: congenital hearing deficit of conductive or sensorineural origin? Temporal bone histopathologic study.

BACKGROUND: Oculoauriculovertebral dysplasia (OAVD) (Goldenhar's syndrome) is a congenital syndrome with ipsilateral deformity of the ear and face, epibulbar lipodermoids, coloboma, and vertebral anomalies. Goldenhar's anomaly has often been associated with a degree of congenital hearing deficits, almost always of a conductive origin, but a sensorineural component is also suspected in some cases, evident through malformations of the inner ear. PATIENTS AND METHODS: Both temporal bones of a 10-day-old deceased patient with oculoauriculovertebral dysplasia were examined by light microscopy. RESULTS: The ear deformities included deformity of the auricle, atresia of the external auditory canal, and malformation of the tympanic cavity and ossicles. Abnormalities of the stria vascularis and the semicircular canals were also demonstrated. Further inner ear deformities were not identified in this case. CONCLUSION: These histopathologic findings appear to confirm the conductive component of the congenital hearing deficit, but a sensorineural component could not be omitted. The ear alterations favor early developmental field defects. The causes of this condition are controversial. Recent results in genetic research pertaining to the MSX class genes permit better understanding of the variety, variability, and different degrees of severity of the anomalies described here.

Immunohistochemical and morphological studies on the human fetal cochlea: a comparative view on methods.

The preservation of morphology and antigenicity can vary uncontrollably with human fetuses since these rely heavily on immediate fixation of the temporal bone following spontaneous abortion. Once good fixation is established, there is the question of the approach taken for morphologic and immunohistochemical studies. To achieve maximal preservation for the purpose of studying normal and pathologic fetal cochleae, commonly used preparation methods for analyzing the cochlea were reviewed and compared for both immunohistochemical and morphologic studies. Cochleae obtained after spontaneous abortion ranged from the 9th gestational week to birth. Four different methods were compared for morphologic study: the block surface method; a microslicing technique; paraffin; and celloidin sectioning. For immunohistochemical study, three methods were compared: pre-embedding; paraffin; and frozen sectioning. For morphologic preservation, the block surface method gave best overall results, showing good representation of the fetal cochlea for surface preparation, light, and electron microscopy. Celloidin sectioning was also found to show good light microscopic results for both the middle and inner ear. To achieve optimal results, preservation quality, fixation procedures, and antibody all contribute to the efficacy of a methods choice.

Tumor microcirculation evaluated by dynamic magnetic resonance imaging predicts therapy outcome for primary rectal carcinoma.

Contrast enhanced dynamic studies of malignant tumors performed by computed tomography or magnetic resonance imaging (MRI) are increasingly applied to characterize tumor microcirculation for the prediction of therapy outcome. The aim of our study was to correlate perfusion index (PI) values determined in primary rectal carcinoma before chemoradiation with therapy outcome. In 17 patients with clinically staged T3 primary rectal carcinoma, dynamic MRI was performed before the onset of therapy using an ultrafast T1-mapping sequence. On the basis of the acquired data sets, PI values were calculated on a pixel-by-pixel basis. To characterize the heterogeneity of tumor microcirculation, relative cumulative frequency histograms of PI values within the tumors were computed. Subsequent resection of the tumors allowed correlating PI with histopathological classification. In 12 of 17 patients, T-downstaging as a response to therapy was found, whereas in the remaining 5 patients no therapy response was observed after chemoradiation. A statistically significant difference between both groups was found for the mean PI (P < 0.001; 8.5+/-1.7 ml/min/100 g versus 11.4+/-0.7 ml/min/100 g). Analyzing the cumulative frequency histograms for both groups revealed an optimal discrimination for a P1 value of 12.6 ml/min/100 g. The fraction of pixels in the tumor with PI values larger than 12.6 ml/min/100 g was significantly different (P < 0.001) between therapy-responding (3+/-3.6%) and therapy-nonresponding tumors (21+/-4.3%). The results indicate either a reduced supply of nutrients as well as chemotherapeutic agents attributable to increased shunt flow or highly aggressive tumor cell clusters characterized by increased angiogenic activity. Noninvasive PI measurements by dynamic MRI in rectal carcinoma before therapy seem to be of predictive value for therapy outcome in patients scheduled for preoperative chemoradiation.

Cerebro-oculo-facio-skeletal syndrome as a human example for accelerated cochlear nerve degeneration.

BACKGROUND: Cerebro-oculo-facio-skeletal (COFS) syndrome is a rare autosomal-recessive disorder that includes microcephaly, severe mental retardation, and multiple congenital anomalies. Otologic findings are usually limited to descriptions of the auricles. PATIENT AND METHODS: The authors report inner ear histopathologic findings of a deceased 13-year-old patient with COFS. A histologic study of the inner ear in COFS syndrome has not yet been described. This patient was documented as having a profound bilateral sensorineural hearing loss at the age of 2 years. RESULTS: Histologic evaluation revealed accelerated neural and neuronal degeneration at the cochlear and retrocochlear levels. Remaining myelinated nerve fibers, counted in the spiral lamina, had degenerated by up to 97% when compared with normal innervation densities. Afferent nerve fibers innervating inner hair cells were completely absent, whereas medial efferent fibers to outer hair cells were found. Vestibular nerve fibers were less affected. CONCLUSION: The authors report inner ear findings that differ from animal models of primary cochlear neural degeneration and that resemble the pattern of hereditary cochlear nerve degeneration reported in Friedreich's ataxia.

Vascular permeability and hyperpermeability in a murine adenocarcinoma after fractionated radiotherapy: an ultrastructural tracer study.

Large radiation doses cause postradiation vascular hyperpermeability by disrupting endothelia. The cumulative sequences of small doses (fractionated radiotherapy) standard in clinical practice cause it too, but not by endothelial disruption: the mechanisms are unknown. In this study, correlated fluorescent and ultrastructural localisation of a tracer revealed the architecture, fine structure and function of microvessels in mouse AT17 tumours, before and after 42 Gy fractionated radiation. Before irradiation, tumour vascular permeability lay in the normophysiological range defined by the gut and cerebral cortex. A double barrier regulated permeability: vesicular transport through the endothelial wall required approximately 2 h and then the basement membrane charge barrier trapped tracer for 2 h longer. Irradiation abolished the double barrier: tracer passed instantly through both endothelial wall and underlying basement membrane, forming diffusion haloes around microvessels within 2-5 min. Structurally, irradiated tumour microvessels were lined by a continuous and vital endothelium with closed interendothelial junctions; endothelial basement membranes were intact, though loosened. Irradiated endothelia exhibited extremely active membrane motility and intracellular vesicle trafficking. Radiation treatment raised vascular permeability by enhancing transendothelial transcytosis, and by altering the passive filter properties of the subendothelial basement membrane. This type of vascular hyperpermeability should be susceptible to pharmacological modulation.

[Results of doppler sonography in normally functioning transjugular portosystemic shunts]. / Dopplersonographische Ergebnisse in normal funktionierenden transjugulären portosystemischen Shunts.

PURPOSE: The objective of this study was to evaluate blood flow changes inside normally functioning transjugular intrahepatic portosystemic shunts (TIPS), using Colour Doppler ultrasound (CDUS) and pulsed Doppler ultrasound (PDUS). MATERIAL AND METHODS: In a prospective study 72 patients (mean age 54, range 36-78 years) underwent TIPS placement, portal angiography, CDUS and PDUS examinations. Along the TIPS Doppler measurements were taken at the portal in the central part and at the venous end of the TIPS. RESULTS: In well functioning TIPS the mean peak velocity (PV) on the portal side was 39 cm/s (range 22-72 cm/s), in the area of the incoming right portal end, branch 62 cm/s (range 40-109 cm/s) and at the site of the incoming hepatic vein 139 cm/s (range 88-220 cm/s). In the punctured portal and hepatic vein the mean PV was 25 cm/s (range 15-30 cm/s) and 18 cm/s (15-22 cm/s) respectively. CONCLUSION: A velocity gradient between the portal and the venous side of the TIPS is a normal finding, caused by the branches of the portal and hepatic vein, joining the TIPS from the side and is characteristic of a normally functioning TIPS.

Epstein-Barr virus-negative boys with non-Hodgkin lymphoma are mutated in the SH2D1A gene, as are patients with X-linked lymphoproliferative disease (XLP).

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency, which most often manifests itself after Epstein-Barr virus (EBV) infection. The main clinical phenotypes include fulminant or fatal infectious mononucleosis, dysgammaglobulinaemia and malignant lymphoma. We have recently cloned the SH2D1A gene, which has been shown to be mutated in approximately 70% of XLP patients. Now we report five novel SH2D1A mutations in patients from five unrelated XLP families. No mutations were found in another three XLP families. In three boys with early onset non-Hodgkin lymphoma (NHL) from two unrelated families a deletion of SH2D1A exon 1 and a splice site mutation were found, respectively. These patients did not show any laboratory or clinical signs of a previous EBV infection. A fourth EBV-uninfected and unrelated boy with a stop mutation in the SH2D1A gene shows only signs of dysgammaglobulinaemia. Development of dysgamma-globulinaemia and lymphoma without evidence of prior EBV infection in four of our patients suggests that EBV is unrelated to these phenotypes, in contrast to fulminant or fatal infectious mononucleosis. The role of SH2D1A as a putative tumour suppressor gene remains to be investigated.

Underestimated health hazard: proposal for an ergonomic microscope workstation.

Working daily for a long time with a standard microscope causes back pain, fibromyalgia, or tension headache in up to 80% of microscopists. These complaints may be prevented by an ergonomic design of the microscope workstation, leading to a beneficial and significant reduction of electromyographical activity in the most strained muscle groups as shown by surface electromyographic recordings.

Idiopathic maxillary pain: prevalence of maxillary sinus hyperreactivity in relation to allergy, chronic mucosal inflammation, and eosinophilia.

OBJECTIVE: In patients with chronic orofacial pain, an underlying sinus hyperreactivity may contribute to the clinical symptoms of a diagnosis of atypical odontalgia, trigeminal neuralgia, or temporomandibular disorders. The purpose of this study was to assess the prevalence of histamine-related maxillary sinus hyperreactivity in patients manifesting signs and symptoms of idiopathic maxillary pain and to correlate the respective findings with the presence or absence of chronic maxillary sinusitis-related diagnoses such as allergy, chronic mucosal inflammation, and eosinophilia. STUDY DESIGN: Fifty patients who had been assigned a diagnosis of idiopathic maxillary pain underwent skin allergy tests, maxillary sinus histamine provocation tests, and maxillary sinus mucosa biopsy. Histamine challenge to a selected area was performed during transoral sinuscopy of the maxillary sinus; a positive test result was defined as the development of a significant local mucosa response such as reddening and swelling. RESULTS: Comparison of the data showed most patients (38%) to have an absence of chronic maxillary sinusitis-related diagnoses, whereas the most common multiple diagnosis was found to be chronic mucosal inflammation in combination with eosinophilia (22%). Regarding the prevalence rates of positive histamine provocation test outcomes, a significant difference was found between the diagnostic subgroup "absence of chronic maxillary sinusitis-related diagnoses" (36.9%) and the diagnostic subgroups "chronic mucosal inflammation" (20%; P< .05), "chronic mucosal inflammation in combination with eosinophilia" (18.2%; P< .05), and "chronic mucosal inflammation in combination with eosinophilia and allergy" (14.3%; P < .01). An analysis of the distribution of chronic maxillary sinusitis-related diagnoses revealed absence of chronic mucosal inflammation-related diagnoses to be significantly more frequently associated with positive histamine provocation test outcomes than with negative histamine provocation test outcomes (41.2% vs 19.7%; P< .01), whereas chronic maxillary sinusitis (41.0% vs 29.4%), eosinophilia (26.2% vs 17.6%), and allergy (13.1% vs 11.8%) were found to be more prevalent in patients with negative histamine provocation test outcomes. CONCLUSIONS: The findings of this study suggest patients with idiopathic maxillary pain to be associated with a low rate of sinus hyperreactivity, whereas a positive test outcome with histamine provocation may not be linked to the presence of chronic maxillary sinusitis-related diagnoses such as allergy, chronic mucosal inflammation, and eosinophilia. Further investigations using a larger sample size of patients with idiopathic maxillary pain and nonidiopathic maxillary pain are necessary to demonstrate the presence or absence of an idiopathic maxillary pain-specific prevalence of maxillary sinus hyperreactivity.

Topographic variations in anatomical structures of the anterior neck of children: an ultrasonographic study.

OBJECTIVE: Tracheostomies in children are frequently used for temporary airway support during surgical procedures. In pediatric patients with congenital craniofacial malformations, preoperative assessment of the delicate anatomy of the airway is necessary. The purpose of this study was to assess the ultrasonographic anatomy of the anterior neck with regard to the performance of tracheostomy. STUDY DESIGN: Ultrasonographic investigation was done in 50 pediatric patients (age range, 6 to 15 years) to analyze the relationships among the anatomical structures that are of practical interest with respect to tracheostomy. RESULTS: The data reveal that information concerning variations in anatomical structures lying in the immediate vicinity of the tracheostomy site was readily obtainable with the techniques used. CONCLUSIONS: In pediatric patients requiring tracheostomy for surgical treatment of severe congenital craniofacial malformations, preoperative ultrasonography may be used to diagnose individual anatomical variations at the tracheostomy site.