Effects of genetic vs. environmental factors on cardiovascular autonomic function: a twin study.

AIMS: Cardiovascular autonomic function is often assessed in patients with diabetes by measuring heart rate variability and baroreflex sensitivity, the heritability of which is not fully understood. The present study was aimed to determine the effects of genetic and environmental factors on heart rate variability and baroreflex sensitivity in monozygotic and dizygotic adult healthy twin pairs. METHODS: A total of 101 (63 monozygotic, 38 dizygotic) adult twin pairs (n = 202; mean age 44.3 years) were investigated. Anthropometric variables and serum metabolic markers were measured, while environmental characteristics were evaluated by questionnaires. Linear and spectral indices of heart rate variability and baroreflex sensitivity were determined by non-invasive methods. All measurements were adjusted for age and gender (model 1) and for all significantly relevant covariates (model 2). Heritability A-C-E structural equation models were used for characterizing the proportion of additive genetic, shared and unshared environmental influences. RESULTS: Genetic influence of different cardiovascular autonomic indices was estimated between 10.3 and 39.4%, common environmental influence was found between 0.0 and 33.2%, while unshared environmental influence was observed between 60.6 and 81.4% in model 1 analysis. In multivariable-adjusted heritability estimates (model 2), the magnitude of the genetic effects decreased to 0.0%, common environmental influence was nearly unchanged (values between 4.4 and 14.5%), while unshared environmental influence slightly increased (values between 85.5 and 96.5%). CONCLUSIONS: Unshared environmental but not genetic factors have substantial influence on cardiovascular autonomic function, suggesting that appropriate treatment of all modifiable environmental factors is of importance in order to prevent or ameliorate cardiovascular autonomic neuropathy.

[Reduced availability of potential cornea donors: reasons and suggestions]. / Limitierte Verfügbarkeit von potenziellen Hornhaut-Spendern: Gründe und Verbesserungsvorschläge.

AIM: The purpose of the study was to analyse the number of potential cornea donors in relationship to the number of actual donors. Furthermore, the reasons for the discrepancy between the number of the potential and actual donors were analysed. METHODS: Over a period of 6 months data were collected from 6 hospitals and the institute for forensic medicine of the university hospital. The reasons why only a few actual donors from a big pool of potential donors remain for transplantation were investigated. RESULTS: Circumstances related to the medical staff were causal for refusal in 37 % of the cases. In 23 % the cause for refusal was related to the relatives (23 %). Furthermore, in 16 organisational problems caused a failure in cornea donation. 18 % were excluded due to contraindications. A total rate of 6 % actual donors was achieved. CONCLUSIONS: The final consent rate was only 6 % out of all potential donors. Organisational failure was only 16 % in contrast to 60 % refusal due to causes relating to medical staff and relatives. Therefore, further education of physicians and the public is needed.

Web-based collaborative training of clinical reasoning: a randomized trial.

BACKGROUND: Clinical reasoning skills are essential for medical practice. Problem-based collaborative learning via the internet might prove useful in imparting these skills. AIM: This randomized study assessed whether web-based learning (WBL) is superior to face-to-face problem-based learning (PBL) in the setting of a 6-week cardio-respiratory course. METHODS: During winter term 2007/08, all 148 fourth-year medical students enrolled in the 6-week course consented to be randomized in small groups to diagnose a patient complaining of dyspnoea either using a virtual collaborative online module or a traditional PBL session. Clinical reasoning skills were assessed by means of a key feature examination at the end of the course. RESULTS: No significant difference between the mean scores of both study groups was detected (p = 0.843). In virtual learning groups, costs for diagnostic tests were significantly correlated to the number of contributions to online group discussions (r = 0.881; p = 0.002). Evaluation data favored traditional PBL sessions over virtual collaborative learning. CONCLUSION: While virtual collaborative learning was as effective as traditional PBL regarding the acquisition of clinical reasoning skills, it was less well accepted than traditional PBL. Future research needs to determine the ideal format and time-point for computer-assisted learning in medical education.

Contrast-enhanced power Doppler harmonic imaging--influence on visualization of renal vasculature.

To compare contrast-enhanced power Doppler (PD) harmonic imaging (CHI) with contrast-enhanced power Doppler fundamental imaging (CPD) in the depiction of renal cortical vessels, 20 healthy volunteers were subjected to PD imaging and HI assessment of the kidney after bolus injection of Levovist(R) (SH U 508A). System settings were standardized and the pulse-repetition frequencies (PRF) systematically toggled from 750 to 500 and 250. Videotapes were independently reviewed by three readers with regard to the presence of artefacts, the degree of Doppler signal enhancement, demarcation of vessels and the extent of visualization. The assessments were graded separately for each PRF in accordance with a multistage scoring system. In comparison to contrast-enhanced PD, artefacts were significantly lower with CHI for all PRF (p = 0.0001). Vessels were better visualized (p = 0.002) and less blurred (p = 0.006) with CHI than with CPD. There was no significant difference in the extent of Doppler signal increase between CPD and the contrast-enhanced harmonic mode. Combination of the contrast-enhanced harmonic method and PD allows the PRF to be lowered and, by balancing the greater susceptibility of PD to interference from clutter, increases the likelihood of detection of flow in small vessels.

[Vascularization of fibroadenomas: contrast harmonic imaging compared with contrast-enhanced power doppler]. / Vaskularisation von Fibroadenomen: Kontrast-Harmonic-Imaging in Vergleich mit kontrastverstärktem Power Doppler.

PURPOSE: To compare contrast material-enhanced harmonic power Doppler ultrasonography (CHI) with conventional contrast-enhanced power Doppler ultrasound (CPD) in depicting the vascularity of fibroadenomas. MATERIALS AND METHODS: Forty patients with fibroadenomas (aged 19-61 years) underwent conventional contrast-enhanced and harmonic power Doppler US. According to a standardized examination protocol, serial dynamic scans were obtained before and at 30, 90 and 150 seconds after injection of contrast agent. Video-taped scans were independently reviewed by three blinded readers with regard to parameter artifacts, degree of Doppler signal enhancement, demarcation of vessels and extent of vessel visualization. RESULTS: The number of intratumoral power Doppler signals depicted was similar with both techniques at 30-90 seconds after contrast administration; however, after 90 seconds, CPD depicted significantly more intratumoral signals than did CHI (p < 0.0001). CHI was superior to CPD with regard to "blooming" or motion-related artifacts (p < 0.0001). CONCLUSION: CHI balances the increased susceptibility of CPD to interference from clutter artifacts and thus allows the depiction of vessels that may have been obscured on CPD at similar system settings.

[Tissue harmonic imaging sonography. Is the image quality in routine abdominal ulstrasound improved?]. / Tissue Harmonic Imaging Sonographie. Wird die Bildqualität bei Routine-Ultraschalluntersuchungen im Abdomen verbessert?

PURPOSE: Evaluation and statistical analysis of the influence of THI with pulse-inversion technology on image quality in abdominal ultrasound in comparison to conventional sonography. MATERIAL AND METHODS: In 25 patients 398 ultrasound images of the abdomen were evaluated in a prospective, double blind study. 49% of the images were obtained with THI sonography, 51% with conventional sonography, respectively. Image parameter, anatomical region and image plane were kept constant by using a switchable ultrasound probe. Image contrast, delineation of organs, detection of vessels and artifacts in cystic structures were evaluated by four radiologists using a 3-grade scale. The interobserver variability was determined. RESULTS: The results of all groups showed statistically significant improvement compared to conventional sonography. High agreement of the evaluaters was achieved for image contrast and delineation of organs, less agreement in detection of vessels and artifacts in cystic structures, respectively. CONCLUSION: Image contrast and delineation of organs to neighboring structures as well as reduction of artifacts in cystic structures and vessels are statistically significantly improved with THI sonography using pulse-inversion technology in comparison to conventional sonography.

Increase of experimental hypertension following inhibition of prostaglandin biosynthesis.

To demonstrate the role of endogenous renal prostaglandins as modulators of the renin-angiotensin-system in renal hypertension, rats with acute and chronic renal hypertension were pretreated with different inhibitors of the prostaglandin biosynthesis (indomethacin, mefenamic acid, acetylsalicylic acid. Development and course of acute and chronic renal hypertension after treatment were highly significantly different from untreated animals concerning elevation, duration and intensity of renal hypertension. Moreover, indomethacin enhanced renal vasoconstrictor effect of angiotensin II in the dog; accordingly, inhibition of prostaglandin biosynthesis increases acute and chronic renal hypertension. It seems that prostaglandins play an important part in blood pressure regulation.

Interactions between brain angiotensin and prostaglandins in rats.

Experiments were performed to investigate the influence of prostaglandins (PG) on local angiotensin II (ANG II) generation in the brain and on the blood pressure (BP) effects of brain ANG II. In indomethacin pretreated Sprague-Dawley rats renin was injected into the lateral brain ventricle. At 15 min after renin injections cerebrospinal fluid (CSF) concentrations of ANG I and ANG II were markedly and equally increased in a dose-dependent manner in the indomethacin treated and in the untreated groups. At 60 min ANG I decreased in both groups, more marked in indomethacin pretreated animals. Intracerebroventricular (ICV) injections of PGI2 induced a marked local ANG II formation in CSF without effecting plasma renin concentration. ICV renin injections were followed by dose-dependent, long lasting (greater than 2 h) BP increases. Pretreatment with indomethacin increased the BP effects of ICV renin. ICV ANG II injections increased BP. ICV pretreatment with either PGI2 or PGE1 inhibited the central ANG II pressor responses. These studies indicate that PG attenuate whereas inhibition of their biosynthesis enhances the BP effects of endogenous brain ANG II in rats. It is suggested that PG may act as inhibitory modulators of the central actions of ANG II and they may participate in feedback mechanisms of the renin angiotensin system (RAS).

Hypotensive action of an intra-nasally applied angiotensin II-antagonist.

Intranasal administration of the specific angiotensin II-antagonist (1-NSuc-5-Val-8-Phg) A II was investigated in anaesthetized rats with different forms of experimentally elevated blood pressure. Renin- or angiotensin II-induced blood pressure increases were markedly reversed by the angiotensin II-antagonist applied intra-nasally. In rats with acute accelerated elevation of blood pressure the analogue induced also a significant decrease. No change could be observed in rats with chronic renal hypertension.

Clinical and ultrasound evaluation of donor site morbidity after tram-flap for breast reconstruction.

The TRAM-flap has become a well-established method for breast reconstruction. Even though the aesthetic result is superior to implant reconstruction, a main disadvantage is the potential risk to create weakness of the abdominal wall. For evaluation of abdominal wall function, an imaging method has to be used which is able to prove functional properties of the remaining muscle. This study was undertaken in order to verify if ultrasound imaging is a reasonable method to examine muscle movements after TRAM-flap procedures in addition to clinical examination. In 8 patients, a DIEP-flap, in 11 patients, a free TRAM-flap, and in 3 patients, a pedicled TRAM-flap were used for breast reconstruction. Patients were examined 10-72 months (mean, 32 months) after surgery. Ultrasound imaging of the abdominal wall was performed in longitudinal as well as cross sections (multifrequent, 13 Mhz; Siemens Elegra, Erlangen, Germany). The diameter of the remaining muscle was measured 2 cm below the rib bow, at the level of the umbilicus, and at the level of the skin scar. The operated side was compared to the nonoperated contralateral side. In order to evaluate the contractility of the remaining rectus muscle, patients were invited to perform sit-ups during ultrasound monitoring of muscle movement. Clinically the functional testing was performed by the method of Janda (Muskelfunktionsdiagnostik, 2nd ed. Berlin: Volk- und Gesundheit; 1986). The abdominal wall was inspected for bulging or hernia formation. Additionally, patients answered a six-scale self-designed questionnaire concerning the impairment of daily living and pain. Muscle contractility as well as muscle diameter were graded into four degrees from 0-3. The highest degree of 3 with normal muscle contractility and muscle diameter was found in 1 of 5 patients after DIEP-flap. Degree 2, with reduced muscle contractility and reduced muscle diameter, was found in 10 of 22 patients, especially after unilateral TRAM-flap. Degree 1, with no muscle contractility and remaining muscle, and degree 0, with scar tissue, were found in 11 patients. Impairment in daily-life activity was found in 10 patients, while 8 patients complained of pain. Muscle strength scored by the method of Janda (Muskelfunktionsdiagnostik, 2nd ed. Berlin: Volk- und Gesundheit; 1986) reached 4 and 5 in 19 patients after all kinds of flap harvesting; 3 patients reached Janda 2 and 3 after unilateral free TRAM or unilateral DIEP-flap. In one patient, a hernia was detected after unilateral DIEP-flap; 10 patients showed bulging of the abdominal wall. Functional testing of the abdominal wall by the method of Janda as well as CT-scans or MRI for evaluation of the remaining muscle is reported in the literature. As there is a need for cost reduction in medical treatment, we were looking for a more cost-effective evaluation method compared to CT-scan or MRI. Ultrasound imaging of the donor site after TRAM-flap harvesting in order to evaluate the remaining function of the rectus muscle is not yet reported in the literature. We consider ultrasound imaging to be superior to CT-scan or MRI in terms of functional evaluation and cost effectiveness.

[Hyperthyroidism caused by a TSH producing pituitary adenoma]. / Hyperthyreose durch ein TSH-produzierendes Hypophysenadenom.

Elevated levels of free triiodothyronine (fT3) of 8.8 ng/dl (normal range 2.0 to 4.2) and free thyroxin (fT4) of 3.5 pg/ml (0.8 to 1.7) were found in the course of an examination of a 53-year old patient due to a planned hysterectomy. As thyrotropin (TSH) also was elevated with 5.8 mU/l (0.4 to 4.5), these findings corresponded to an inappropriate secretion of TSH (IST). Additional examinations revealed a blunted rise of TSH secretion after i.v. injection of 200 micrograms thyrotropin releasing hormone (TRH) as well as lacking suppression of TSH secretion after oral doses of 75 micrograms T3 during one week. alpha-TSH levels with 3.7 micrograms/l were elevated in comparison to a matched normal sample just as the molar ratio alpha-TSH/TSH with 6.95 and sex hormone-binding globulin (SHBG) with 175 nmol/l and showed an absence of inhibition in the T3 suppression test. These results were suggestive of neoplastic inappropriate secretion of TSH (nIST) due to a TSH-secreting pituitary adenoma. In concordance, the magnetic resonance imaging (MRI) showed a 1 cm tumor in the sella. The adenoma could also be visualized by 111In-octreotide and 123I-epidepride scintigraphies of the pituitary gland. After transsphenoidal resection, histological examination of the tumor resulted in the finding of a TSH-secreting adenoma. Postoperative TSH levels were not detectable, indicating the complete removal of the adenoma. Levels of fT3 and fT4 were slightly below normal with 1.9 pg/ml and 0.7 ng/dl, respectively. A control scintigraphy with 111In-octreotide following an equivocal MRI showed no uptake in the pituitary.