Hypoxia inducible factor-1 (HIF-1)-mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium.

Diarrhea is widespread in intestinal diseases involving ischemia and/or hypoxia. Since hypoxia alters stimulated Cl(-) and water flux, we investigated the influence of such a physiologically and pathophysiologically important signal on expression of the cystic fibrosis transmembrane conductance regulator (CFTR). Located on the apical membrane, this cAMP-activated Cl(-) channel determines salt and fluid transport across mucosal surfaces. Our studies revealed depression of CFTR mRNA, protein, and function in hypoxic epithelia. Chromatin immunoprecipitation identified a previously unappreciated binding site for the hypoxia inducible factor-1 (HIF-1), and promoter studies established its relevance by loss of repression following point mutation. Consequently, HIF-1 overexpressing cells exhibited significantly reduced transport capacity in colorimetric Cl(-) efflux studies, altered short circuit measurements, and changes in transepithelial fluid movement. Whole-body hypoxia in wild-type mice resulted in significantly reduced small intestinal fluid and HCO(3)(-) secretory responses to forskolin. Experiments performed in Cftr(-/-) and Nkcc1(-/-) mice underlined the role of altered CFTR expression for these functional changes, and work in conditional Hif1a mutant mice verified HIF-1-dependent CFTR regulation in vivo. In summary, our study clarifies CFTR regulation and introduces the concept of a HIF-1-orchestrated response designed to regulate ion and fluid movement across hypoxic intestinal epithelia.

[Migraine? Arnold Chiari Malformation? Or Just a Migraine?] / Migräne? Arnold-Chiari-Malformation? Oder doch einfach nur eine Migräne?

Migraine? Arnold Chiari Malformation? Or Just a Migraine? Abstract. In a young woman with a long-time headache in the sense of a migraine, a neurological reassessment including new findings of the existing MRI images of the skull resulted in the diagnosis of a Chiari malformation type 1. After successful operation of the MRI findings, the headache decreased significantly. However, since minor headaches of a different quality persist, a migraine plus malformation as an incidental finding are most likely.

[Retroperitoneal Fibrosis - on the Benefits of Trustworthiness in Everyday Practice]. / Retroperitoneale Fibrose ­ Fallbeispiel zur Glaubwürdigkeit von Patienten.

Retroperitoneal Fibrosis - on the Benefits of Trustworthiness in Everyday Practice Abstract. Despite negative radiology results, the described patient's back pain clearly had to be a somatic one - concluded by his primary care provider because of the patient's trustworthiness. The clinical presentation, histopathology of surgical excision and chemistry (IgG4) revealed the diagnosis of a retroperitoneal fibrosis. The symptoms as well as the fibrosis disappeared due to glucosteroid and rituximab therapy.

The Age-Related Performance Decline in Ironman 70.3.

Although the age-related decline in sport events has been well studied, little is known on such a decline in recreational triathletes for the Half Ironman distance. Indeed, the few existing studies concentrated on specific aspects such as top events, elite groups, some consecutive years, single locations, or age categories instead of analyzing all the data available. Therefore, the aim of the present study was to examine recreational triathletes' performance in three split disciplines (swimming, cycling, and running) as well as in overall race time by analyzing all data of Half Ironman finishers found on ironman.com (i.e., 690 races; years 2004 through 2018; 206,524 women (24.6%) and 633,576 men (75.4%), in total 840,100 athletes). The age-dependent decline in Half Ironman started earliest in swimming (from the very first age group on) with a smallest age group delta between 35-49 years in men and 40-54 years in women. The performance decline started at 26 and 28 years in men and women for running; at 34 years for men and 35 years for women in cycling; and at 32 years for men and 31 years for women with regard to overall race time. The results may be used by coaches and recreational athletes alike to plan a triathlon career.

[Odd Aspects of Hemochromatosis, a Widespread Disease]. / Hämochromatose ­ ungewohnte Aspekte einer Volkskrankheit.

Odd Aspects of Hemochromatosis, a Widespread Disease Abstract. This case series is written to investigate the odd aspects of hemochromatosis, a frequently encountered disease in our latitudes (and even a widespread disease in Ireland). One patient presented with bilateral digital artery occlusion and another one with bilateral rib fractures. Quite often, hemochromatosis comes with a surprise.

[How Does one Avoid Micturition? A Question That not Only Children ask]. / Wie vermeidet man die Miktion? Eine Frage, die sich nicht nur Kinder stellen.

We report the history of a 53-year-old kiosk woman who presented with acute urinary retention. The diagnosis of an underactive bladder could be established, which can emerge when the bladder is chronically overstretched, which, in her case, was due to long phases without micturition due to her obligation to care for the kiosk. Despite therapeutic approaches with myocholine and sacral neuromodulation the hypercapacity of the bladder remained. The therapy still consists of a suprapubic cystostomy.

[When the tissue tolerance fiber tears]. / Wenn der Gewebegeduldsfaden reisst .

We report a 65 year old patient who presented with both an aneurysm of the axillary artery and, some years later, with an acute aortic dissection type Stanford A. After surgical intervention of the dissection in the further workup, no specific etiology could be found. The most likely reason for the two aneurysms was the inadequately treated hypertension. Therefore, follow-up strategies aim to treat the risk factors which are known to promote aneurysm growth.

[Sitting just hurts!]. / Sitzen tut einfach weh!

We report on the history of a 53-year-old patient who went to his primary care physician due to pain while sitting. Clinical, gastroenterological and urological examination did not lead diagnostic. A radiography of the pelvis revealed a kinky sacrum and the MRT showed a tumor mass of about 9 cm in diameter. A plasmacytoma was histologically diagnosed in the biopsy.

[How is agonizing leg pain associated with an intrauterine device?]. / In welchem Zusammenhang stehen quälende Beinschmerzen und eine intrauterine Spirale?

We report on a typical clinical course of pelvic actinomycosis: initial uncharacteristic discomfort develops into a systemic illness associated with a pelvic mass, which progresses so fast that along with the systemic infection further symptoms can be reduced to its growth rate--tiredness, abdominal pain, micturition deficiency, and leg pain. Distinction between malignancy and pelvic actinomycosis could be made only intraoperative. After hysterectomy and with antibiotics the patient recovered quickly.

[My Back is Still Hurting!]. / Der Rücken tut aber noch immer weh!

We present the case of a 39-year-old man who reported to the primary care physician for low back pain. Pain persisted despite extensive assessment and therapy. During the course, bilateral femoral neck fractures occurred and due to multiple enrichments in scintigraphy chronic multifocal (sterile) osteomyelitis was suspected. In the further follow-up the appropriate diagnosis of osteomalacia was established in bone biopsy and adequate treatment with Vitamin D was initiated. During therapy, the patient was free of pain or discomfort.