Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia

Autosomal-dominant familial hypercholesterolemia (FH) is characterized by increased plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and a substantial risk to develop cardiovascular disease. Causative mutations in three major genes are known: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). We clinically characterized 336 patients suspected to have FH and screened them for disease causing mutations in LDLR, APOB, and PCSK9. We genotyped six single nucleotide polymorphisms (SNPs) to calculate a polygenic risk score for the patients and 1985 controls. The 117 patients had a causative variant in one of the analyzed genes. Most variants were found in the LDLR gene (84.9%) with 11 novel mutations. The mean polygenic risk score was significantly higher in FH mutation negative subjects than in FH mutation positive patients (P < .05) and healthy controls (P < .001), whereas the score of the two latter groups did not differ significantly. However, the score explained only about 3% of the baseline LDL-C variance. We verified the previously described clinical and genetic variability of FH for German hypercholesterolemic patients. Evaluation of a six-SNP polygenic score recently proposed for clinical use suggests that it is not a reliable tool to classify hypercholesterolemic patients.     

Adiponectin levels are high in children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency

Objective: It has been shown that adiponectin serves as an insulin-sensitizing adipokine. Serum concentrations of adiponectin are low in children with obesity, and increase with fat mass loss, indicating that adiponectin can serve as a biomarker. Since the prevalence of overweight and obesity is increased in children with congenital adrenal hyperplasia (CAH), our study aimed to evaluate serum levels of adiponectin in a cohort of CAH children and adolescents, and their associations with clinical parameters such as chronological age (CA), body mass index (BMI), Tanner stage (TS), medication and metabolic control.
Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI.
Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 μg/L) compared to the matched controls (6.7 μg/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage.
Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients.     

Quality control in ambulatory health care. Results of an area-wide study by the public medical service of the Baden-Württemberg health insurance

Discussions surrounding the quality of nursing care, fueled by recurring press reports, prompted the State Nursing Insurance Associations in Baden-Wuerttemberg to request the Health Insurance Medical Service to perform a quality control of outpatient nursing care services in the state. Based on a coordinated concept and for the first time in the Federal Republic of Germany, all authorized ambulatory institutions area-wide were subjected to a uniform assessment (total survey) during an official inquiry time period. The end results of these controls failed to verify the judgement often propagated by the press based on individual cases that high-quality nursing care can no longer be afforded under the present circumstances. On the average, 55% of the personnel provided to patients by outpatient nursing services were health care professionals. What is more, this professional staff rendered 75% of all nursing care services. The evaluation of the accompanied medical visits indicated that the vast majority attempted to take active nursing care into account. With regard to quality assurance, a great optimisation potential was indicated primarily in the area of nursing documentation. Only in about 35% of the nursing documents inspected was the nursing procedure always clearly evident. A future problem could arise from the fact that of all nursing professionals with leadership responsibilities, at the time of the survey only about 37% had completed the requisite professional training qualification programme of 460 training hours. If the time before the interim deadline (March 31, 2002) is not utilised, the institutions in question could face consequences that could threaten their very existence. It is evident that a large number of outpatient nursing care services in the state of Baden-Wuerttemberg do not have their economic foundation in the domain of the Nursing Care Insurance Law, which affects both patient structure and care intensity. As a consequence, there is no quality control or inspection whatsoever for the majority of nursing care services rendered by ambulatory nursing care services at present because they are not under the jurisdiction of the German Federal Social Legislation SGB XI.     

Difficult airway management in a patient with severe aortic stenosis, coronary artery disease, and heart failure

We report a patient with aortic stenosis, coronary artery disease, and heart failure in whom awake fiberoptic intubation was performed because the patient's mouth opening was insufficient as a result of disc prolapse of the mandibular joint. We planned to perform this procedure during conscious sedation, spontaneous respiration, and with stable hemodynamic parameters (no tachycardia, hypertension, or hypotension). After oral premedication with dikaliumclorazepate, the patient received clonidine. Fiberoptic intubation was performed while the patient breathed spontaneously. Throughout the procedure, no adverse events occurred. Clonidine is a valuable adjunct for conscious sedation and can be used safely for sympathicolysis, even in patients with aortic stenosis.     

A novel method for encapsulation of poorly water-soluble drugs: precipitation in polyelectrolyte multilayer shells

A novel method to include poorly water-soluble substances into the polyelectrolyte capsules of defined size, stability, composition and affinity properties is proposed. Encapsulation explores the polarity gradient across the capsule wall. Capsules creation makes use of electrostatic interaction and can involve many substances as layer constituents, such as synthetic polyelectrolytes, proteins, nucleic acids, lipids and multivalent dyes. Using capsules made of synthetic polyelectrolytes as a model system was demonstrated how to prepare, to measure and to use this gradient for low molecular weigh materials encapsulation.     

Interdisciplinary longitudinal curriculum "Medical psychology,psychotherapy and psychosomatics" (MPPP) at the University of Ulm

We report the clinical part of the longitudinal curriculum MPPP which was developed by the departments of Medical Psychology, Psychotherapy and Psychosomatic Medicine at the University of Ulm. The commitment and creativity of the participating students in their two undergraduate years inspired us to offer them an interest-guided curriculum for their six clinical semesters. Our paper reports the extensive results of two evaluations that we conducted during the clinical part of this new teaching-model. It became evident that we were successful in transferring continuous, intense and patient-centred psychosomatic and psychosocial contents. Yet the transfer of basic and methodological knowledge was not realised to the extent the students would have appreciated. The positive results of our project encouraged us to expand the concept of an interest-guided curriculum onto the whole academic education in psychotherapy and psychosomatic medicine at our university.     

Using orbital sonography to diagnose and monitor treatment of acute swelling of the eyelids in pediatric patients

OBJECTIVE. Clinical signs of acute erythematous swelling of the periorbital region may be related either to benign superficial inflammation or to the more severe and potentially life-threatening condition of orbital infection. CONCLUSION. We recommend orbital sonography in every child with periorbital swelling and erythema. In contrast to superficial infection in which edematous swelling of the eyelid can be documented without lesions of the orbital content, either a hyper- or a hypo-echoic mass displacing the medial rectus muscle laterally is highly suggestive of orbital infection. Introducing sonography into early diagnostic interventions in pediatric patients avoids delaying appropriate treatment and allows disease monitoring on a daily basis.     

Radiation-induced osteosarcoma of the chest wall

A case of radiation-induced sarcoma of the chest wall is reported. Twenty-seven years 11 months after orthovoltage radiotherapy of the right breast a 69-year-old woman developed a radiation-induced osteosarcoma of the right thoracic wall. Initial diagnosis has been T-cell lymphoma of the skin. The right breast was irradiated with tangential fields and a total dose of 40 Gy, 2 Gy/day, 5 days a week. Orthovoltage treatment was performed in two courses of 20 Gy, 3 months apart. The clinical appearance of the secondary sarcoma was a diffuse infiltrated area in the irradiated breast which seemed to be fixed to the chest wall. Magnetic resonance imaging (MRI) demonstrated a mass in the right anterior thoracic wall which destroyed the fourth to the sixth rib. The tumor infiltrated the thoracic wall, including subcutaneous tissue and pericardium, as well as extending into the subphrenic space. Biopsy of the lesion revealed a poorly differentiated osteosarcoma. The patient's general condition precluded surgical or chemotherapeutic intervention; she died due to a cerebral stroke 6 months later. This case fulfilled all criteria for radiation-induced sarcoma, as there was a prior history of radiotherapy, latency period of several years, development of sarcoma within the irradiated field, and histologic confirmation of sarcoma.