Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

Genome-wide association analysis for lethal brachycephalic-like facial dysmorphia in Labrador Retrievers.

A GWAS was performed for inborn X-linked facial dysmorphia with severe growth retardation in Labrador Retrievers. This lethal condition was mapped on the X chromosome at 17-21 Mb and supported by eight SNPs in complete LD. Dams of affected male puppies were heterozygous for the significantly associated SNPs and male affected puppies carried the associated alleles hemizygously. In the near vicinity to the associated region, RPS6KA3 was identified as a candidate gene causing facial dysmorphia in humans and mice known as Coffin-Lowry syndrome. Haplotype analysis showed significant association with the phenotypes of all 18 animals under study. This haplotype was validated through normal male progeny from a dam with the not-associated haplotype on both X chromosomes but male affected full-sibs with the associated haplotype.

Depletion of STAT5 blocks TEL-SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice.

The spleen tyrosine kinase (SYK) was identified as an oncogenic driver in a broad spectrum of hematologic malignancies. The in vivo comparison of three SYK containing oncogenes, SYK(wt), TEL-SYK and IL-2-inducible T-cell kinase (ITK)-SYK revealed a general myeloexpansion and the establishment of three different hematologic (pre)diseases. SYK(wt) enhanced the myeloid and T-cell compartment, without leukemia/lymphoma development. ITK-SYK caused lethal T-cell lymphomas and the cytoplasmic TEL-SYK fusion induced an acute panmyelosis with myelofibrosis-type acute myeloid leukemia (AML) with up to 50% immature megakaryoblasts infiltrating bone marrow, spleen and liver, additional MPN features (myelofibrosis and granulocyte expansion) and MDS stigmata with megakaryocytic and erythroid dysplasia. LKS cells were reduced and all subsets (LT/ST/MPP) showed reduced proliferation rates. SYK inhibitor treatment (R788) of diseased TEL-SYK mice reduced leukocytosis, spleen and liver infiltration, enhanced the hematocrit and prolonged survival time, but could not significantly reduce myelofibrosis. Stat5 was identified as a major downstream mediator of TEL-SYK in vitro as well as in vivo. Consequently, targeted deletion of Stat5 in vivo completely abrogated TEL-SYK-induced AML and myelofibrosis development, proving Stat5 as a major driver of SYK-induced transformation. Our experiments highlight the important role of SYK in AML and myelofibrosis and prove SYK and STAT5 inhibitors as potent treatment options for those diseases.

CXCR4-SERINE339 regulates cellular adhesion, retention and mobilization, and is a marker for poor prognosis in acute myeloid leukemia.

The CXCR4 receptor is a major regulator of hematopoietic cell migration. Overexpression of CXCR4 has been associated with poor prognosis in acute myelogenous leukemia (AML). We have previously shown that ligand-mediated phosphorylation of the Serine339 (CXCR4-S339) residue of the intracellular domain by PIM1 is implicated in surface re-expression of this receptor. Here, we report that phosphorylation of CXCR4-S339 in bone marrow (BM) biopsies correlated with poor prognosis in a cohort of AML patients. To functionally address the impact of CXCR4-S339 phosphorylation, we generated cell lines-expressing CXCR4 mutants that mimic constitutive phosphorylation (S339E) or abrogate phosphorylation (S339A). Whereas the expression of CXCR4 significantly increased, both CXCR4-S339E and the CXCR4-S339A mutants significantly reduced the BM homing and engraftment of Kasumi-1 AML cells in immunodeficient mice. In contrast, only expression of the CXCR4-S339E mutant increased the BM retention of the cells and resistance to cytarabine treatment, and impaired detachment capacity and AMD3100-induced mobilization of engrafted leukemic cells. These observations suggest that the poor prognosis in AML patients displaying CXCR4-S339 phosphorylation can be the consequence of an increased retention to the BM associated with an enhanced chemoresistance of leukemic cells. Therefore, CXCR4-S339 phosphorylation could serve as a novel prognostic marker in human AML.

[Patient oriented communication. Dealing with risks and errors]. / Patientenbezogene Kommunikation. Vom Umgang mit Risiken und Fehlern.

Informed consent builds the basis for a legal medical intervention. Sufficient documentation supports the physician's defence in litigation. In case of negligence, however, special skills for a patient oriented communication are essential.

A high-resolution comparative radiation hybrid map of equine chromosome 4q12-q22.

In this study, we present a comprehensive 5000-rad radiation hybrid map of a 40-cM region on equine chromosome 4 (ECA4) that contains quantitative trait loci for equine osteochondrosis. We mapped 29 gene-associated sequence tagged site markers using primers designed from equine expressed sequence tags or BAC clones in the ECA4q12-q22 region. Three blocks of conserved synteny, showing two chromosomal breakpoints, were identified in the segment of ECA4q12-q22. Markers from other segments of HSA7q mapped to ECA13p and ECA4p, and a region of HSA7p was homologous to ECA13p. Therefore, we have improved the resolution of the human-equine comparative map, which allows the identification of candidate genes underlying traits of interest.

[Malpractice considerations and the legal social reality]. / Haftungsrechtlicher Anspruch und sozialrechtliche Realität.

According to German civil law the physician's services rendered to the patient must be in accordance with the medical state of art, which must regularly be adapted to successfully evaluated innovations. In the German statutory health insurance most of the services are financed under budgets. Budgets do not satisfactorily reflect the growing needs of an innovative medical system. Hence, the legislative organs have to take action in order to carry out a reform of the statutory health system that enables free enterprise, competition and the patient's free choice of services.

Remote memory in patients with acute brain injuries.

Remote memory was investigated in an unselected sample of 26 patients with either unilateral tumours in the temporal lobes or traumatic brain injuries. Six patients underwent excisions within the left temporal lobe, and nine patients were operated on within the right temporal lobe. In both groups, patients with excisions including and sparing the hippocampal formation were studied. Their performance was compared to that of 11 patients with moderate to severe head trauma and to a normative sample of 214 healthy controls. Remote memory was assessed using a famous events test with items of extremely low salience that had been proven to be of low difficulty for those old enough at the time of the event's actuality. The results show severely disturbed retrograde memory functions in the left temporal tumour group. These patients achieved similar scores to patients with severe traumatic brain injury. Right hemispheric patients showed a pattern of results comparable to that of healthy controls. The strongest effects were in the free recall part of the test. In most of the patients, no graded memory loss was observable. No consistent association to recent memory function could be identified. Since most of the remote memory test items used denoted famous names which were cued by rich semantic information, the type of deficit seen may be best understood in terms of a specific dysfunction of the semantic stores containing information about famous proper names.

[Prerequisites in prescribing practice: physician decision processes]. / Voraussetzungen der Verordnung: Entscheidungsabläufe beim Arzt.

Selecting a drug for proper treatment of the patient is still primarily the physicians choice. The selection is usually not influenced beforehand but subject to control in a case of malpractice. It must be taken into consideration, however, that about half of the practising doctors in Germany are working in their own practice. The vast majority of these are participating in the statutory health insurance system. Their therapeutic measures have to be in accordance with the social code, it's by-laws, regulations and guidelines. Drugs may only be prescribed if a curable decrease has been determined and the range of potential prescriptions has been scrutinised. Two "negative lists" have to be observed. In addition to this, the prescription must be effective, sufficient and may not exceed the necessities. If there are therapeutic alternatives the drugs efficacy must be taken into evaluation. Since the beginning of 1993 the doctor's choice is also influenced by the overall budgeting of drug expenses and the fear of personal liability for a budget excess.

[Results of cryptorchism therapy. A study of 232 patients]. / Katamnestische Untersuchungen an andrologischen Patienten zur Beurteilung der Therapie des Hodenhochstands.

232 patients had been treated for cryptorchidism. The disorder was unilateral in 126, bilateral in 106 patients. Therapy was performed either with human chorionic gonadotropin in 102 cases (hCG total dose of 18.000 I.U.) or surgery in 129 cases. Testicular descent was achieved in 51.5% by hormonal therapy and in 51.9% by surgery. Unilateral cases were subject to successful treatment in 53.2%, bilateral cases in 50%. The influence of initial finding (inguinal vs. abdominal retention) and age of the patients on results were analysed. Inguinal retention (n = 240) was successfully treated in 50.8%, abdominal retention (n = 94) in 54.3%. Testicular descent after therapy was found in 52.9% for patients 2-9 years of age (n = 119), in 50% for patients 10-13 yrs. of age (n = 88) and in 48% for patients older than 13 (n = 25). Regular findings after therapy was noted in 51.7% of all 232 patients. Method of therapy, initial finding and patients age, however, could not be shown to influence results significantly.