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.

Monochorial diamniotic dizygotic twins in a German Shepherd Dog: A case report.

CASE REPORT: A 6.5-year-old clinically healthy German Shepherd Dog with regular oestrous cycles of 6 months was presented for pregnancy diagnosis on day 38 after ovulation (p.ov.). Ultrasonography revealed three individual placental sites in progressed resorption and two vital adequately developed foetuses sharing a joint placenta. On days 41 and 48 p.ov., sonographic signs indicated normal development of both foetuses, but on day 52 p.ov., both foetuses were found to be dead. A caesarean section was performed the same day. Examination of the removed uterus confirmed the diagnosis of a "twin" pregnancy with two foetuses sharing the same placental site but separate amniotic membranes. One foetus showed generalized oedema (anasarca). Bacterial culture of swabs taken from inside the placental cavity was negative. At histological examination of the uterus, no signs of inflammation were found. Serum relaxin concentrations (day 38, 41, 48 and 52. p.ov.) were consistent with those of bitches with normal pregnancies. Cytogenetic analysis of the two foetuses revealed dizygotic twins, one male and one female according to SRY-PCR. By genotyping 17 high-polymorphic canine microsatellites, it could be demonstrated that the two foetuses developed from two different oocytes.

Allelic heterogeneity of FGF5 mutations causes the long-hair phenotype in dogs.

Hitherto, the only known mutant gene leading to the long-hair phenotype in mammals is the fibroblast growth factor 5 (FGF5). In many dog breeds, the previously discovered FGF5:p.Cys95Phe mutation appeared completely concordant with the long-hair phenotype, but for some breeds, the long-hair phenotype could not be resolved. First, we studied the role of the FGF5:p.Cys95Phe and FGF5:g.145_150dupACCAGC mutations in 268 dogs descending from 27 breeds and seven wolves. As these mutations did not explain all the long-hair phenotypes, all exons and their neighbouring regions of FGF5 were re-sequenced. We detected three novel mutations in the coding sequence and one novel non-coding splice-site mutation in FGF5 associated with the long-hair phenotype. The FGF5:p.Ala193Val polymorphism was perfectly consistent with long hair in Akitas and probably in Siberian huskies, too. Dogs of the long-hair breed Samoyed were either homozygous or compound heterozygous for the FGF5:p.Ala193Val or the FGF5:p.Cys95Phe polymorphisms respectively. The two newly detected polymorphisms FGF5:c.559_560dupGG and FGF5:g.8193T>A and the known mutation FGF5:p.Cys95Phe explained the long-hair phenotype of all Afghan hounds analysed. An FGF5:c.556_571del16 mutation was found in one longhaired Eurasier. All long-hair-associated mutations follow a recessive mode of inheritance, and allelic heterogeneity was a common finding in breeds other than Akita.

Fine mapping of a quantitative trait locus for osteochondrosis on horse chromosome 2.

In this study, we refine a quantitative trait locus for equine osteochondrosis (OC) on horse chromosome (ECA) 2 to a genome-wide significant interval at 20.08-30.94 Mb. The marker set contained 27 newly developed microsatellites equidistantly distributed over ECA2 and 44 nucleotide polymorphisms, located in 16 positional candidate genes for OC. Genotyping was performed in 211 Hanoverian horses from 14 paternal half-sib groups. A NCDN-associated SNP and haplotype were significantly associated with OC in fetlock and/or hock joints. This study is a further step towards the identification of genes responsible for OC in horses.

Refinement of a quantitative trait locus on equine chromosome 5 responsible for fetlock osteochondrosis in Hanoverian warmblood horses.

In this report, we provide 29 new informative microsatellites distributed over a region of 21 Mb on horse chromosome (ECA) 5 and refine a quantitative trait locus (QTL) for fetlock osteochondrosis dissecans (OCD) to a genome-wide significant interval between 78.03 and 90.23 Mb on ECA5. Genotyping was performed in 211 Hanoverian warmblood horses from 14 paternal half-sib groups. Within this OCD-QTL, collagen type XXIV alpha 1 was identified as a potential functional candidate gene for equine osteochondrosis. This report is a further step towards unravelling the genes that cause equine osteochondrosis.

Suspected X-linked facial dysmorphia and growth retardation in related Labrador retriever puppies.

Seven male Labrador retriever puppies from four different litters were identified with a brachycephalic-like face and skull, associated with low birth weight, severe growth retardation, and reduced abilities to crawl and suckle, which were not compatible with survival. Excessive doming of the cranium, brachygnathia superior and inferior, and an abnormally opened fontanelle were found in all affected puppies by computed tomography and at post-mortem examination. Pedigree analysis supported an X-linked recessive mode of inheritance.

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.

Remote memory in Parkinson's disease and senile dementia.

Remote memory for public events was investigated in 14 demented patients with Parkinson's disease (PD), 14 non-demented PD patients, and 14 controls. These groups were compared with 16 demented patients with dementia that was due to Alzheimer or was of vascular origin (SDAVT), and with a group of elderly controls. The two demented groups were of a different age but displayed a comparable degree of dementia. Remote memory was assessed using a 'famous events' questionnaire with items both of comparable salience and difficulty. Results showed severely impaired retrograde memory functions in the two demented groups for both recall and recognition with non-demented PD patients performing similar to the controls. Remote memory impairments extended 30-40 years without any temporal graded memory losses. Non-demented PD patients and controls showed an inferior free recall performance, especially for the remote past. The two PD groups benefited from recognition to the same extent as the controls, whereas the improvement for SDAVT patients was inferior when compared to their elderly controls. In contrast to SDAVT patients, anterograde memory was associated with remote memory for specific decades in demented PD patients. The results are interpreted with respect to an underlying retrieval deficit with a superimposed anterograde impairment common to both types of dementia and an additional loss of storage sites in SDAVT patients.

Nutritional deficiencies in German middle-class male alcohol consumers: relation to dietary intake and severity of liver disease.

OBJECTIVE: The purpose of the present study was to compare the nutrient intake and the nutritional status between German middle-class alcohol consumers and non-drinkers. DESIGN: Cross-sectional study using patients with different stages of alcoholic liver disease (ALD) and healthy volunteers. SETTING: Southern Germany. SUBJECTS: Seventy-six hospitalized German middle-class alcohol consumers with different stages of alcoholic liver disease (ALD) and 22 healthy control subjects. METHODS: Subjects and controls were nutritionally assessed and mineral and vitamin content was measured in blood and urine. RESULTS: When compared with controls, alcohol consumers had significantly higher intakes of total calories, but intake of non-alcoholic calories did not differ between groups (P<0.05). Among drinkers, there was a decrease in percentage of energy derived from protein and fat and a significant increase in carbohydrates (P<0.05). With the exception of vitamin E, micronutrient intake of alcoholics was equal to that of controls; however, blood vitamin (vitamin C, retinol, lycopene, alpha- and gamma-carotene) and trace element (selenium, zinc) concentrations of alcohol-drinking patients were lower than those of non-drinkers. CONCLUSION: From the results of this study it is concluded that in German middle-class male alcohol consumers the status of several micronutrients is disturbed, although dietary intake hardly differs from that in non-alcoholic controls.

[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.

[Withholding medical care as physical injury--refusal to treat from the viewpoint of the lawyer. Special aspects of therapy in children]. / Arztliches Unterlassen als Körperverletzung--Therapieverweigerung aus Sicht des Rechtsanwaltes. Spezielle Aspekte der Therapie bei Kindern.

Medical treatment as well as refusal of treatment may be a source for tortious liability. Omitting treatment is generally accepted if the patient refuses consent. Special problems arise however, if the patient is not capable of consenting to therapeutic procedures. Assessing the patient's capability to consent is then the primary obligation. In absence of a respective capability the parents' will has to be accepted as the basis of therapeutic decision, as long as the objective medical needs of the patient remain in consideration. Omitting medically necessary treatment may not be justified with the opposing will of the parents.

[Data protection in telemedicine--legal aspects]. / Datenschutz in der Telemedizin--rechtliche Aspekte.

Recent developments in telemedicine have resulted in an increased flow of personalized medicinal data and therefore caused new in calculable risks and dangers to the right of privacy. This article discusses the particular problems of this issue: The patient's consent must be based on sufficient information about the intended data processing and data flow. Transmitting data into countries outside the European Community should prevail sufficient data protection according to the EC-Guideline. Particular attention mus be paid to the regulations of the new German Multimedia Legislature.

[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.

[Legal adjustment in a European frame]. / Rechtsanpassung auf europäischer Ebene.

The legal and practical problems discussed concerning telemedicine within the western world seem quite similar: quality, litigation, professional law, data protection and financing are the main tasks that any health system within the EU is facing now. The working group T 6 of the European Health Telematics Association establishes a good basis for analyzing and developing a legal framework. However, in addition to the ongoing discussion about the necessary legal adjustments the engagement of Germany concerning these European aspects needs enforcement.

Medical confidentiality and data protection as influenced by modern technology.

Confidentiality has been considered to be a basic element of the doctor-patient relationship worldwide since the time of Hippocrates. On the verge of entering a society in which communication plays a leading role, confidentiality alone can no longer protect the patient's rights. Increasing diagnostic activity multiplies the amount of data available for processing in health systems. On the other hand, the use of electronic medical records allows practically unlimited amounts of data to be saved. The compilation of any personal data, however, requires a legal basis such as the consent of the individual concerned, which is generally given within the doctor-patient relationship. Compiled medical data can be assigned to four main sectors: therapy, financing, administration and research. This division into four sectors is based on the need to reconcile the conflicting needs of the patient's right to informational self-determination and third-party interests. Data can be processed for one or more of these purposes insofar as a legal basis therefore (law or consent) exists. Using the data for purposes outside the sector for which they were compiled interferes with the individual's right to informational self-determination. Thus most data compiled in the course of therapy may not be processed for research purposes, unless made anonymous, thereby losing the chance of retracing the source of the data. However, new informational techniques can procure secure anonymized and retraceable data flow. The legislature has to consider these technologies in order to enable the enormous opportunities presented by new methods of data processing to be fully exploited in research.

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.