Intraoperative reduction of vasopressors using processed electroencephalographic monitoring in patients undergoing elective cardiac surgery: a randomized clinical trial.

Intraoperative vasopressor and fluid application are common strategies against hypotension. Use of processed electroencephalographic monitoring (pEEG) may reduce vasopressor application, a known risk factor for organ dysfunction, in elective cardiac surgery patients. Randomized single-centre clinical trial at Jena University Hospital. Adult patients operated on cardiopulmonary bypass or off-pump coronary artery bypass grafting were randomised to receive anesthesia with visible or blinded pEEG using Narcotrend™. In blinded-Narcotrend (NT) depth of anesthesia was extrapolated from clinical signs, hemodynamic response and anesthetic concentration, supplemented by target indices between 37 and 64 in the visible-NT group. Intraoperative norepinephrine requirement (primary endpoint), fluid balance, extubation time, delirium occurrence and adverse events were evaluated. Patients of the intent-to-treat population (visible-NT: n = 123, blinded-NT: n = 122) had similar patient and procedural characteristics. Adjusted for type of surgery intraoperative Norepinephrine application was significantly reduced in visible-NT (n = 120, robust mean of cumulative dose 4.71 µg/kg bodyweight) compared to blinded-NT patients (n = 119, 6.14 µg/kg bodyweight) (adjusted robust mean difference 1.71 (95% CI 0.33-3.10) µg/kg bodyweight). Although reduction in patients operated on cardiopulmonary bypass was higher the interaction was not significant in post-hoc subgroup analysis. Intraoperative fluid balance was similar among both groups and strata. Extubation time was non-significantly lower in visible than in blinded-NT group. Overall postoperative delirium risk was 16.4% without differences among the groups. Adverse events-sudden movement/coughing, perspiration or hypertension-occurred more often with visible-NT, while one blinded-NT patient experienced intraoperative awareness. Titration of depth of anesthesia in elective cardiac surgery patients using pEEG allows to reduce application of norepinephrine.

[Fatigue after head and neck cancer-results of a survey using the Multidimensional Fatigue Inventory (MFI-20)]. / Fatigue nach Kopf-Hals-Tumorleiden ­ Ergebnisse einer Befragung mit dem Multidimensional Fatigue Inventory (MFI-20).

BACKGROUND: Fatigue resulting from cancer and its treatment can lead to a reduction in quality of life. The frequency and intensity of fatigue syndrome after cancer therapy in the ENT field are largely unknown. Therefore, during follow-up consultations, the authors conducted a random survey with the help of the Multidimensional Fatigue Inventory (MFI 20). METHODS: During aftercare consultations, 66 patients were interviewed (average age 63 years, 21 women). All patients had received radiotherapy an average of 2 years previously (range 1-4 years). All respondents were in full remission at the time of the survey. According to recommendations, evaluation of the MFI-20 was carried out in 5 subgroups: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. For comparison with standard values, respondents were grouped by age into under and over 60 years and were also evaluated by gender. RESULTS: Regardless of gender, our patients reported clearly elevated scores in all subgroups. Particularly participants aged under 60 years reported very high scores. The clarity of the results surprised the authors. CONCLUSION: Fatigue represents a very profound and prolonged impairment for the patients of our study. Since fatigue can still be present a long time after completion of treatment, patients should be asked about it specifically using a standardized inventory during follow-up. In order to cope with fatigue syndrome, specific therapeutic recommendations aimed at activation, such as regular physical activity, nutritional advice, and complementary measures, can be made.

Variants in the genes DCTN2, DNAH10, LRIG3, and MYO1A are associated with intermediate Charcot-Marie-Tooth disease in a Norwegian family.

INTRODUCTION: Charcot-Marie-Tooth disease (CMT) is a heterogeneous inherited neuropathy. The number of known CMT genes is rapidly increasing mainly due to next-generation sequencing technology, at present more than 70 CMT-associated genes are known. We investigated whether variants in the DCTN2 could cause CMT. MATERIAL AND METHODS: Fifty-nine Norwegian CMT families from the general population with unknown genotype were tested by targeted next-generation sequencing (NGS) for variants in DCTN2 along with 32 CMT genes and 19 other genes causing other inherited neuropathies or neuronopathies, due to phenotypic overlap. In the family with the DCTN2 variant, exome sequencing was then carried out on all available eight family members to rule out the presence of more potential variants. RESULTS: Targeted NGS identified in one family a variant of DCTN2, c.337C>T, segregating with the phenotype in five affected members, while it was not present in the three unaffected members. The DCTN2 variant c.337C>T; p.(His113Tyr) was neither found in in-house controls nor in SNP databases. Exome sequencing revealed a singular heterozygous shared haplotype containing four genes, DCTN2, DNAH10, LRIG3, and MYO1A, with novel sequence variants. The haplotype was shared by all the affected members, while the unaffected members did not have it. CONCLUSIONS: This is the first time a haplotype on chromosome 12 containing sequence variants in the genes DCTN2, DNAH10, LRIG3, and MYO1A has been linked to an inherited neuropathy in humans.

Heart rate variability - a potential early marker of sub-acute post-stroke infections.

OBJECTIVE: Infection is the most relevant complication after acute ischemic stroke. Activity of the autonomic nervous system seems to control post-stroke immunodepression. We investigated heart rate variability (HRV) indices that reflect autonomic readjustments as predictors of post-stroke infection. MATERIALS AND METHODS: Forty-three patients with acute ischemic stroke were enrolled in a prospective study. The predictability of sub-acute infections (day 4 ± 1 after admission) was investigated in 34 patients without acute infection by means of HRV indices obtained in the acute period (48 h after admission). RESULTS: Sub-acute infection could be predicted in patients without clinical or paraclinical (white blood cell count and C-reactive protein) signs of infection in the acute period at (i) day: increased HFnorm, reduced LFnorm and LF/HF; (ii) night: reduced LF and VLF (P < 0.05). CONCLUSIONS: HRV indices are candidates for early markers of developing post-stroke infections, preceding routine blood samples. Thus, HRV-based early diagnosis of post-stroke infection should be investigated in more detail as it may have implications as a novel tool for timely and appropriate treatment. A corresponding continuous HRV-based risk assessment using the ECG provided by the routine stroke monitoring system would be possible without any additional burden for patients and staff.

Genetic epidemiology of Charcot-Marie-Tooth in the general population.

BACKGROUND AND PURPOSE: the frequency of different Charcot-Marie-Tooth (CMT) genotypes has been estimated in clinic populations, but prevalence data from the general population are lacking. METHODS: our population-based genetic epidemiological survey included persons with CMT residing in eastern Akershus County, Norway. The participants were interviewed and examined by one geneticist/neurologist and classified clinically, neurophysiologically and genetically. RESULTS: two hundred and forty-five persons from 116 families had CMT. This corresponds to 1 per 1214 persons (95% CI 1062-1366) have CMT in the general population. CMT1 (motor conduction velocity (MCV) <38 m/s), CMT2 (MCV >38 m/s) and CMT intermediate (MCV 25-45 m/s) were found in 48.2%, 49.4% and 2.4% of the families. A total of 27.2% of the families and 28.6% of the affected had a mutation in the investigated CMT genes. The prevalence of the peripheral myelin protein 22 (PMP22) duplication and point mutation in the connexin32 (Cx32), myelin protein zero (MPZ) and mitofusin2 (MFN2) genes was found in 13.6%, 6.2%, 1.2%, 6.2% of the families, and in 19.6%, 4.8%, 1.1%, 3.2% of the affected, respectively. None of the families had point mutations in the early growth response 2 (EGR2), PMP22 or small integral membrane protein of lysosome/late endosome (SIMPLE) genes. CONCLUSIONS: CMT is the most common inherited neuropathy. At present, 43 CMT genes are known, and an examination of all known genes would probably only identify mutations in approximately 50% of those with CMT. Thus, it is probable that at least 30-50 CMT genes are yet to be identified.

Seroprevalence of influenza A and B in German infants and adolescents.

The objective of this study was to provide seroepidemiological information on influenza A and B antibodies in children and adolescents. Viral immunoglobulin G antibodies were determined retrospectively using enzyme-linked immunosorbent assays in a group of 1,111 children and adolescents. Sera (809) from healthy adult blood donors served as controls. In children, the prevalence of antibodies against influenza A was 82.0% and against influenza B 9.6%, whereas in adults the prevalence of antibodies against influenza A was calculated as 99.4% and against influenza B 56.7%. After decline of maternal antibodies during the first year of life, there was an increase of prevalence of influenza A antibodies up to 100% by the age of 12 years. In contrast, only 1-2% of children up to 9 years had influenza B antibodies increasing to 25% by the age of 18 years and to 70% among adults aged 30 years. Children aged 0-6 years had significantly lower concentrations and >12-15-year-old adolescents had significantly higher concentrations of antibodies against influenza A than adults. For all age groups of children and adolescents, significantly lower antibody concentrations against influenza B were measured in comparison to the blood donor control group. In conclusion, the annual influenza vaccination in children and adolescents may improve considerably the protection against influenza virus infection occurring during epidemics.

Prevalence of the diabetic foot syndrome at the primary care level in Germany: a cross-sectional study.

AIMS: The diabetic foot syndrome (DFS) is an important complication of diabetes mellitus resulting in amputations, disability and reduced quality of life. DFS is preventable. The aim was to investigate the prevalence of the DFS at the primary care level in Germany. METHODS: This was a cross-sectional study of the prevalence of DFS, associated factors and glycaemic control at the primary care level in Germany. We examined an unselected sample of participants with known diabetes who were insured by Deutsche BKK, a large healthcare insurer. RESULTS: Three hundred and forty-one general practitioners examined 4778 participants with diabetes mellitus: 366 (7.7%) participants (mean age 49 +/- 16 years) had Type 1 and 4412 participants (mean age 66 +/- 10 years) had Type 2 diabetes. DFS was diagnosed in 138 patients, resulting in a prevalence of 3.6%[95% confidence interval (CI) 1.9, 6.0] in Type 1 and 2.8% (95% CI 2.3, 3.4) in Type 2 diabetes. DFS was independently associated with age, duration of diabetes, height, current smoking and insulin therapy. There was no significant effect of glycaemic control on the risk of DFS. The prevalence of other abnormal foot findings was: peripheral neuropathy 9.7%, peripheral arterial disease 14.8% (absent dorsalis pedis), 12.4% (absent tibialis posterior), acute diabetic foot ulcer 0.8%, amputations of lower extremities 1.5%, and amputations limited to toes 0.5%. CONCLUSIONS: The prevalence of the DFS at the primary care level in Germany is 2.9%. Almost 50% of patients with DFS had major or minor amputations. Common risk factors such as hyperkeratosis and poor glycaemic control can be modified. Effective therapeutic approaches in addition to methods for primary and secondary prevention of DFS should be used more widely.

Serum zinc levels during oral glucocorticoid therapy.

The course of serum zinc (S-Zn), plasma albumin (P-Alb), urinary zinc, serum alkaline phosphatase, and plasma alpha 2-macroglobulin levels was monitored in 14 adult hospitalized patients receiving oral glucocorticoid therapy, about 40-50 mg prednisone daily for various skin diseases. Within 3 days S-Zn decreased slightly from 12.6 +/- 2.3 mumol/liter (mean +/- SEM) to 11.1 +/- 2.5 mumol/liter. Then the level rose to about 14-15 mumol/liter and remained elevated, but within the normal range for the next 2 weeks. The P-Alb level showed parallel fluctuations although less pronounced. The S-Zn/P-Alb ratio increased from 0.024-0.029. No consistent patterns could be seen in the fluctuations occurring in the additional parameters studied. The possible role of ACTH on the S-Zn regulation is discussed.

Phenytoin increases 65zinc absorption in the rat.

A single oral dose of 65Zn was given to groups of rats, 6 or 7 in each, which were started on phenytoin. The drug was given in daily doses of 10, 50, and 100 mg for 10 days. The retention of 65Zn was followed by a whole body counter, and the net absorption of 65Zn was calculated. All phenytoin doses studied were found to increase zinc absorption significantly.

Serum alkaline phosphatase and serum zinc levels in the diagnosis and exclusion of zinc deficiency in man.

In the present study we monitored serum zinc (Zn) and serum alkaline phosphatase (AP) levels during Zn supplementation in (A) a young zinc depletion syndrome (ZDS) patient with severe Zn deficiency, (B) three acrodermatitis enteropathica (AEP) patients with mild Zn deficiency and (C) 7 elderly and 3 younger patients without Zn deficiency. In (A) serum Zn and serum AP values were low, but following parenteral Zn the parameters rose to normal levels (r = +0.79, p less than 0.001). In (B) serum Zn and serum AP levels decreased when oral Zn was stopped, but shortly returned to normal upon reinitiation of Zn. In (C) Zn therapy caused a rise in the serum Zn concentration whereas the serum AP activity decreased (r = -0.01, p greater than 0.1). The results suggest that serial determinations of serum Zn and serum AP during Zn supplementation may be a valid tool in the diagnosis of severe and mild Zn deficiency as well as in the exclusion of the diagnosis.

A population-based study on variations in the use of adjuvant systemic therapy on postmenopausal patients with early stage breast cancer.

PURPOSE: To assess adherence to treatment recommendations regarding adjuvant systemic therapy of postmenopausal patients with early stage breast cancer. METHODS: A population-based cohort of women from Eastern Thuringia/Germany with first diagnosis of breast cancer in 1995-2000 was studied. The use of adjuvant therapy was assessed separately for patients with positive and negative nodal status fitting polytomous logistic regression models. RESULTS: Among 396 women with positive lymph nodes and 832 with negative lymph nodes, 92.9% and 87.3% received an adjuvant systemic treatment, respectively. Age, comorbidity, hormone receptor status, histological grading, and additionally, in nodal positives, the number of involved lymph nodes, were associated with treatment patterns. Age had the strongest impact on treatment decision. Older women more often received hormone- or no adjuvant therapy. However, 26.3% of the women with lymph node involvement and positive hormone receptor status received no hormone therapy, whereas 35.7% of women with negative hormone receptor status received hormone therapy. CONCLUSION: The number of patients with adjuvant systemic therapy is high in women with positive and those with negative lymph nodes, reflecting adherence to the recommendations. Better outcome could be expected if hormone therapy was used adequately in receptor positives. Further follow-up is required to monitor the outcome and changes in adherence to treatment recommendations.

Influence of ovarian stimulation on the detection of human papillomavirus DNA in cervical scrapes obtained from patients undergoing assisted reproductive techniques.

OBJECTIVE: To determine whether gonadotropin stimulation influences the detection of human papillomavirus (HPV) DNA in cervical scrapes. DESIGN: Prospective, controlled study. SETTING: Tertiary care infertility clinic. PATIENT(S): Two hundred ninety-four patients enrolled in an IVF or IUI program. Two thousand two hundred sixty-two women from an ongoing screening study who were of similar age served as a control group. INTERVENTION(S): Cervical scrapes were obtained with a cytobrush before and after ovarian stimulation with gonadotropins. MAIN OUTCOME MEASURE(S): Human papillomavirus status was assessed with a general primer (GP) polymerase chain reaction (PCR) using the GP5+/GP6+ system. In GP-PCR-positive samples, high-risk HPV types were identified with a cocktail of digoxigenin-labeled oligonucleotides. Viral load was evaluated by semiquantitative analysis of the PCR products. RESULT(S): The prevalence of high-risk HPVs was 7.8% before stimulation and 6.8% after stimulation and, thus, was similar to the prevalence in controls (8.4%). Twenty-nine patients were positive for high-risk HPVs: 14 were positive before and after stimulation, 6 were negative before and positive after stimulation, and 9 were positive before and negative after stimulation. Positivity for high-risk HPVs and viral load did not correlate directly with serum estrogen levels. CONCLUSION(S): Ovarian stimulation has no significant effect on the prevalence of HPV DNA in cervical scrapes obtained from patients undergoing assisted reproductive techniques.

A study of human head vibrations using time-averaged holography.

Intact human cadaver heads were subjected to vibrations. The resonant frequencies over a range of 500 to 3000 Hz were determined. Vibration patterns at three frequencies were presented by means of time-averaged holography. The displacements were quantified and the highest amplitudes were found in the temporal region. Antinode centers were found superimposed on the squamatic suture. This method of holographic interferometry allows sensitive deformation measurements to be taken on intact human heads or skulls.

Holographic investigation of the impact response of human heads.

The impact response of intact human cadaver heads was studied by means of double-pulsed holography using a ruby laser, and the transient deformation process at the surface of the skull was recorded. Frequency and acceleration measurements following impact were obtained. On frontal impact, the shock wave reached the opposite pole after 0.2 to 0.3 msec, and maximum amplitudes were found in the temporal regions. On impact to the vault, the deformation wave reached the skull base after 0.15 to 0.175 msec. Centers of maximum amplitude were recorded in the parietal and temporal regions. Deviations in the interference lines occurred at some sutures, revealing discontinuities. High-frequency components of the shock wave were demonstrated. The authors believe that fracture mechanisms may be elucidated by further studies of impact responses.

The effect of oral zinc loading on the absorption of 65zinc in the rat.

Seven groups of 8 rats each were orally loaded with zinc, the daily dose varying from 1.8 to 58 mg, corresponding to about 3 to 100 times of their estimated daily intake of zinc. To record the absorption of zinc, the rats were given a single dose of 65Zn. The retention of the isotope was measured in a whole animal counter at regular intervals. The dose of 58 mg was obviously toxic, since half of the animals died within 5 days. The net absorption of zinc in the remaining experimental groups was found to vary from about 7% in the group receiving the smallest loading dose to 1.8% in the group receiving the highest dose. From the absorption values, as determined by extrapolation of semilog retention curves, the total amount of absorbed zinc was estimated. It was found to differ from about 170 micrograms to about 530 micrograms zinc daily, increasing three times as the loading dose was increased 16 times. This discrepancy suggests the existence of regulatory mechanisms of the absorption of zinc from the intestine.

Effects of tetracycline on the absorption of 65zinc in rats.

The effects of tetracycline on the absorption of orally ingested 65Zn was studied on rats by whole body counting assay. 65Zn was given as a single dose to groups of rats, five in each, which were started on tetracycline. Tetracycline was given in daily doses of 25 mg, 50 mg, 100 mg, and 200 mg for 10 days. From the 6th day of the study, 65Zn retention when plotted against time in a semilog plot, approximated linearity. The net absorption of 65Zn in the various groups was determined by extrapolating to zero time the linear curve segment of individual retention curves. Except for the lowest tetracycline dosage, tetracycline significantly impaired 65Zn absorption. The elimination rate of retained 65Zn from the 6th day was significantly higher in the group receiving 200 mg tetracycline as compared with the control group.

Biomechanical changes in long limb bones of HAN-Wistar rats during postnatal development.

From a total of 648 male and 638 female HAN-Wistar rats the bones of 12 males and 12 females were examined at seven week intervals from the 35th to the 1129th day after birth. Biomechanical properties of the femora, tibiae and humeri were defined in a bending test using a tension testing machine. Load deflection diagrams in bending were produced, and the values of maximum bending load, bending breaking load, maximum deflection and ultimate deflection were correlated to age, body weight and bone length. The mean values of weight, bone length and biomechanical data are significantly higher in male rats. In both sexes biomechanical properties show a clear dependence on age. Up to the age of 330 days the tibia is more flexible than the femur or humerus. Values of partial correlation coefficients demonstrate that weight exerts more influence on the biomechanical properties of bones than age or bone length. With increasing weight, the loading capacity of bones rises in both sexes.

The Castillo-Morales approach to orofacial pathology in Down syndrome.

Infants with Down syndrome often present with a familiar orofacial disorder which exists at birth or becomes more pronounced by the end of the first year. The primary pathology includes hypotonicity of the perioral muscles, lips, and masticatory muscles and a protruding tongue, later followed by active tongue protrusion. This results in problems with sucking, swallowing, drooling and dentition. Early intervention methods employing the combination of Castillo-Morales Manual Orofacial Therapy and his specially designed palatal plate, can improve orofacial function, facial appearance and prevent secondary conditions like pseudoprognathism, dental diseases, malocclusions, open mouth habit and pseudomacroglossia. This retrospective study examines the outcome of therapy, as prescribed by Castillo-Morales, in 39 children with Down syndrome. Normally, the average age to begin oral therapy is between six to eight months. The children were treated with the Castillo-Morales Manual Orofacial Therapy and his palatal plate for an average of 17.9 months. In this study, clinical evaluations at the beginning and the end of therapy focused only on open mouth posture and tongue protrusion. In addition, the direct stimulating effect of the palatal plate on tongue protrusion was evaluated. Significant positive results were observed in all three areas.

[Efforts of general practitioners in the treatment of heart arrest in a rural area. A prospective pilot study]. / Praktiserende laegers indsats i behandlingen af hjertestop i et landområde. Et prospektivt pilostudie.

During a two year period, general practitioners in a local area were called to all 112 alarms (the number dialled in Denmark in emergencies) in order to improve the prognosis of patients with cardiac arrest. In 55% of the calls, the practitioners arrived within five minutes, whereas the ambulance arrived within five minutes in only 16% of the cases (p < 0.01). Three of ten patients with cardiac arrest survived without cerebral damage. In 23% of the cases final treatment was completed by the local practitioner.