Short-term Pasteurization of Breast Milk to Prevent Postnatal Cytomegalovirus Transmission in Very Preterm Infants.

BACKGROUND: Postnatally acquired cytomegalovirus (pCMV) infection through breast milk (BM) may cause severe illness and even death, yet BM is advantageous for preterm infants. Therefore, effective methods to prevent CMV transmission are needed. METHODS: To assess the effectiveness of short-term pasteurization (62°C for 5 seconds) in preventing CMV transmission via BM in preterm infants. Design: Prospective interventional bicentric cohort study with infant enrollment between 6/2010 and 1/2012. A cohort from the Tuebingen neonatal intensive care unit (NICU) from 1995-1998 served as historical controls. Differences in CMV transmission were compared with reference to the cumulative time at risk for CMV transmission. Setting: Two German level-3 NICUs. Eighty-seven preterm infants of 69 CMV immunoglobulin G-positive mothers with birth weight <1500 g or gestational age <32 weeks and 83 historical controls were included. Intervention: BM samples were short-term pasteurized from postnatal day 4 to discharge. Primary endpoint: CMV status at discharge, evaluated by polymerase chain reaction and short-term microculture from urine. RESULTS: Two of 87 (2.3%) study infants had a pCMV transmission. This compared to 17 of 83 (20.5%) controls. Total time under risk for infection was 9.6 years vs 10.0 years in controls, yielding an incidence of 0.21/year (95% confidence interval [CI], 0.03 to 0.75/year) vs 1.70/year (95% CI, 0.99 to 2.72/year), respectively. The risk ratio controls vs study infants was 8.3 (95% CI, 2.4 to 52.4) according to Cox proportional hazard model (P = .0003). CONCLUSIONS: Short-term pasteurization significantly reduces the incidence of pCMV infection through BM in the NICU. CLINICAL TRIALS REGISTRATION: NCT01178905.

Observational study on the influence of averaging time on oximetry results in infants and children.

AIM: Oximetry values are influenced by the averaging time (AT) used. We aimed to evaluate the effect of different ATs on number, duration, mean single event and total integral of desaturations in preterm infants and children to convert between parameters obtained with different ATs. METHODS: In a prospective observational study, 49 children underwent sleep laboratory-based polysomnography and 15 preterm infants were studied in the intensive care unit. Their raw red-to-infrared-saturation-data were reprocessed using seven different ATs (3-16 seconds). Desaturation thresholds were <80% (infants) and <90% (children), conversion formulas and their median percentage errors were calculated. RESULTS: We found a linear relationship between the logarithms of the ATs and those of the desaturation parameters, leading to a conversion formula with different exponents. Based on this relationship, the number of desaturations decreased from AT = 3s to AT = 16s by factor 0.28 (children) and 0.18 (infants); total oxygen saturation integral decreased by factor 0.72 (children) and 0.48 (infants). The desaturation duration increased by factor 1.89 (children) and 3.34 (infants). CONCLUSION: The number and total integral decreased, but the duration and mean single event integral increased with increasing AT. These changes were stronger in infants. Conversion formulas may facilitate comparisons between studies using different averaging times.

Karl-Peter Hadeler: His legacy in mathematical biology.

Karl-Peter Hadeler is a first-generation pioneer in mathematical biology. His work inspired the contributions to this special issue. In this preface we give a brief biographical sketch of K.P. Hadelers scientific life and highlight his impact to the field.

Quantitative measurement of melanoma spread in sentinel lymph nodes and survival.

BACKGROUND: Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival. METHODS AND FINDINGS: We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3-123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61-2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02-2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories. CONCLUSIONS: Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.

Three-dimensional assessment of facial development in children with unilateral cleft lip with and without alveolar cleft.

Children with cleft lip or cleft lip and alveolus represent a minor group in the cleft population. The aim of this study was to analyze the faces of these children. In a prospective, cross-sectional study, 344 healthy children and 30 children with cleft lip or cleft lip and alveolus were scanned three-dimensionally at the age of 0 to 6 years. Twenty-one standard anthropometric landmarks were identified, and the images were superimposed. Growth curves for normal facial development were calculated. The facial morphology of cleft children was compared with that of unaffected children.Facial morphology and growth in the transverse direction of the examined patients appeared broadened in all levels. Especially the nasal landmarks indicated a widening of the nose. The landmarks ac l, sbal l, sbal r, c l, sn l, and ls l differed significantly from unaffected children. In the sagittal and vertical dimensions, there was no significant difference compared with unaffected children.Our study demonstrates that surgical and orthodontic treatment can restore the vertical and sagittal dimensions of the face in children with cleft lip with and without alveolar clefts; however, the transverse dimension-especially the nose-remains too broad.

Prediction model for the incidence and prevalence of type 1 diabetes in childhood and adolescence: evidence for a cohort-dependent increase within the next two decades in Germany.

OBJECTIVE: To provide data on type 1 diabetes (T1D) epidemiology in childhood over a period of 20 years and to predict prevalence and cohort-age-specific incidence rates (IRs) for the next two decades in Germany. METHODS: The Baden-Wuerttemberg Diabetes Incidence Registry (DIARY) includes children and adolescents below 15 years of age with new onset of T1D (period 1987-2006, n = 5108 cases). RESULTS: The mean age- and sex-standardized IR was 15.3/100 000/year (95% CI 14.8-15.7) and the average increase in the IR was 4.4% per year (95% CI 3.9-4.9). Within the next 20 years (2007-2026), the risk for developing diabetes will increase like the square of a linear function with calendar year for all age ranges. There is a strong correlation between the predicted IRs of the cohorts and the observed IRs (n = 300; root mean square error = 0.56; r(2) = 0.71) and a negative correlation between mean age at onset and T1D IR (p = 0.02). On 31 December 2006, the prevalence of T1D was 0.126% (95% CI 0.121-0.132). The predicted prevalence (end of 2026) is estimated to be 0.265% (95% CI 0.25-0.28; predicted cases: n = 2950; 95% CI 2900-3000). CONCLUSIONS: In comparison to observations made in the past, the risk of disease rises even faster than expected: The younger the child, the quicker the increase of the cohort-age-specific IR and the higher the risk for T1D during lifetime.

Measles in the European past: outbreak of severe measles in an isolated German village, 1861.

OBJECTIVES: We examined measles mortality in the European past in an outbreak in an isolated German village, Hagelloch, in 1861. METHODS: Pfeilsticker's contemporary thesis was used to describe the measles case fatality ratio (CFR) and complications. Data on onset of prodromes and rash was used to determine index cases and secondary cases of measles within the household. The church register provided information on survival in 1862. RESULTS: The epidemic affected nearly all children under 14 years of age. The overall CFR was 6.4%(12/187), and 10%(7/70) for children under five years of age; 44% of children were secondary cases (82/187). Secondary cases had higher CFR than index cases (RR = 3.03 (95% CI: 0.91-10.07). Boys had higher CFR than girls (RR = 4.46 (1.03-19.22)). Boys infected by a girl had higher CFR than boys infected by other boys (RR = 6.30 (1.18-85.64)). Children who survived measles virus infection in 1861, did not have higher mortality in the following year compared with those who had not had measles in 1861 (RR = 0.24 (0.07-0.82)). CONCLUSIONS: Severe measles in the European past had determinants similar to those observed more recently in low-income countries. BRIEF SUMMARY: The measles case fatality was 6% in rural Germany in 1861. Mortality was highest for boys infected in the household by a girl. There was no excess mortality after the acute phase of measles infection.

Safely Inserting Neonatal Chest Drains.

BACKGROUND: Inserting a chest drain for a left-sided neonatal pneumothorax carries a risk of penetrating the pericardium. We identified reference ranges for the chest wall thickness (CWT) and distance between the pericardium and parietal pleura to improve safety of chest tube insertion. METHOD: We prospectively measured the CWT using ultrasound in 20 neonates (body weight [BW] 640-2,700 g, age <10 days) at the usual site of puncture in the 4th and 5th intercostal space (ICS). Furthermore, we measured the minimal distance between the parietal pleura and the cardiac silhouette in 131 neonatal chest X-rays (birth weight, 420-4,930 g [divided into 11 weight groups]; age <10 days). Both data sets were transformed into weight-dependent percentiles (Ps). We considered the difference between the sum of P 2.5 for the CWT plus P 2.5 for pleura-heart distance minus P 97.5 for the CWT as a safe corridor for placing the tip of the needle. RESULTS: At both ICSs, curves for the above metrics did not cross, indicating a narrow but safe corridor for each BW with at least 97.5% probability. This safety corridor was 4.6-5.2 mm wide for the 4th and 2.8-3.4 mm for the 5th ICS. CONCLUSION: These data offer a reference for left-sided chest drain insertion for BW <2,700 g, which may help to improve safety of the procedure.

What causes the death of patients with cutaneous squamous cell carcinoma? A prospective analysis in 1400 patients.

INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is a common tumor of elderly Caucasian patients. METHODS: Competing multivariable risk models to analyze different types of cSCC associated death (local infiltration [LI], locoregional [LR], and distant metastases [DM]) in terms of prognostic factors. RESULTS AND DISCUSSION: 1400 patients were analyzed. In the adjusted multivariable subdistribution hazard approach for tumor volume, the best model for death of cSCC overall revealed the presence of desmoplasia (HR 4.52; p < 0.001), bone invasion (HR 10.06; p < 0.01), and immunosuppression (HR 3.19; p = 0.003) as significant factors. Death due to LI indicated desmoplasia (HR 15.39; p < 0.01) and bone invasion (HR 16.9; p < 0.001) as significant factors. For death by LM, immunosuppression with a HR of 3.27; p = 0.004 was the only significant prognostic factors as well as in death by DM with a HR of 4.54; p = 0.02. CONCLUSIONS: The three types of death caused by cSCC can be distinguished based on risk factors with different weights. Patients with these factors should be monitored closely.

A thirteen-year analysis of Plasmodium falciparum populations reveals high conservation of the mutant pfcrt haplotype despite the withdrawal of chloroquine from national treatment guidelines in Gabon.

BACKGROUND: Chloroquine resistance (CR) decreased after the removal of chloroquine from national treatment guidelines in Malawi, Kenia and Tanzania. In this investigation the prevalence of the chloroquine resistance (CQR) conferring mutant pfcrt allele and its associated chromosomal haplotype were determined before and after the change in Gabonese national treatment guidelines from chloroquine (CQ) to artesunate plus amodiaquine (AQ) in 2003. METHODS: The prevalence of the wild type pfcrt allele was assessed in 144 isolates from the years 2005 - 07 by PCR fragment restriction digest and direct sequencing. For haplotype analysis of the chromosomal regions flanking the pfcrt locus, microsatellite analysis was done on a total of 145 isolates obtained in 1995/96 (43 isolates), 2002 (47 isolates) and 2005 - 07 (55 isolates). RESULTS: The prevalence of the mutant pfcrt allele decreased from 100% in the years 1995/96 and 2002 to 97% in 2005 - 07. Haplotype analysis showed that in 1995/96 79% of the isolates carried the same microsatellite alleles in a chromosomal fragment spanning 39 kb surrounding the pfcrt locus. In 2002 and 2005 - 07 the prevalence of this haplotype was 62% and 58%, respectively. Pfcrt haplotype analysis showed that all wild type alleles were CVMNK. CONCLUSION: Four years after the withdrawal of CQ from national treatment guidelines the prevalence of the mutant pfcrt allele remains at 97%. The data suggest that the combination of artesunate plus AQ may result in continued selection for the mutant pfcrt haplotype even after discontinuance of CQ usage.

Modelling the topography of absolute defects in patients exposed to the anti-epileptic drug vigabatrin and in normal subjects using automated static suprathreshold perimetry of the entire 80° visual field.

AIM: (i) To map the spatial distribution of absolute visual field loss (AL) in patients exposed to vigabatrin and to compare the findings with AL in normal individuals, and (ii) to describe the relationship between the major risk factors for absolute loss (gender, age, cumulative dose), and the severity of field loss, expressed as the number of locations with AL per eye. METHODS: Visual field plots were retrospectively reviewed from 428 individuals. Perimetry was done with the Tübingen Automated Perimeter (using a threshold-oriented, marginally supraliminal strategy, 80° eccentricity, 99 test locations). Three hundred and sixty-one individuals were ophthalmologically normal, and 67 were patients exposed to vigabatrin who had performed reliably during perimetry prior to neurosurgery for epilepsy. Two hundred and sixty-six of the 361 normals were included on the empirical basis that they manifested AL at no more than 19 stimulus locations per eye (the 74th percentile). The frequency per eye of AL at each of 99 stimulus locations was determined for the normals and patients. The effects of age, gender and cumulative dose of vigabatrin on the number of ALs per individual was assessed by an analysis of covariance. A stochastic model was developed to determine the 50% probability of AL at each location. RESULTS: Thirty-nine of the 67 vigabatrin patients exhibited at least 20 locations with AL. The number of ALs was independent of age (p = 0.7603). The frequency of AL was 14.8% in the peripheral field and 1.0% in the central field (odds ratio 16.7; 95% CI 15.0-18.6%; p < 0.0001). Those exposed to vigabatrin exhibited a frequency of 17.1% ALs, compared to 5.2% for the normal individuals (odds ratio 3.77, 95% CI 3.6-4.0%; p < 0.0001). According to the modelled data, males exhibited 20.9% (95% CI 1.3-44%; p = 0.0360) more absolute losses than did females. The number of absolute losses per person doubled with an increase in cumulative dose of vigabatrin of 936 g (95% CI 775-1181 g). CONCLUSIONS: According to this retrospective study, the spatial configuration of absolute defects attributable to vigabatrin indicates sparing of the temporal field up to approximately 60° eccentricity. Such a finding is likely to explain, at least in part, the initially asymptomatic nature of the defect. This study reconfirms a (cumulative) dose effect of vigabatrin on the extent of absolute field loss, with a greater risk for male gender.

Immune surveillance of the normal human CNS takes place in dependence of the locoregional blood-brain barrier configuration and is mainly performed by CD3(+)/CD8(+) lymphocytes.

Despite the blood-brain barrier (BBB) the human CNS is continuously screened by blood-derived immunological cells. In certain brain areas the local BBB configuration grants passage of large molecules, whereas others are better shielded. We investigated whether these regional BBB compositions are paralleled by differences in the degree of cellular immunosurveillance by investigating tissue from 23 normal human brains for several CD markers, FoxP3, granzyme B, and perforin. Our results provide evidence that immunosurveillance is associated with locoregional BBB configuration and is mainly performed by CD3(+)/CD8(+)/granzyme B(-)/perforin(-) lymphocytes.

Phylogenetic nomenclature and evolution of mannose-binding lectin (MBL2) haplotypes.

BACKGROUND: Polymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23 MBL2 haplotypes, associated with enhanced susceptibility to several diseases. RESULTS: In this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardize MBL2 studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results. CONCLUSION: Using extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.

Vitamin D levels of XP-patients under stringent sun-protection.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by an increased skin cancer risk due to defective repair of ultraviolet (UV)-radiation induced DNA damage. Therefore patients with XP are required to apply stringent sun-protection. Since the skin needs UV-B irradiation for de novo vitamin D synthesis, it has been postulated that sun-protection may lead to a clinically relevant reduction of vitamin D levels. To investigate whether reduced vitamin D levels in XP-patients are caused by the stringent sun-protection measures employed, in this study we examined 15 patients with XP. The 25-hydroxyvitamin (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) serum levels were measured. Additionally, patients received a questionnaire about their sun-protection-behaviour. Serum levels for 25-OHD were decreased in 10 of 15 (67%) patients, however there was no statistically significant association between decreased 25-OHD serum levels and duration of sun-protection (p = 0.84). Results for 1,25-(OH)2D levels showed a probability of < 0.16 and between 0.16 and 0.77 for sun-protection duration of < 20 and 20 to 40 years, respectively (p = 0.0058). There was no statistically significant association between the duration of sun-protection with drometrizole trisiloxane and the probability of reduced 25-OHD and 1,25-(OH)2D levels. In conclusion, this investigation indicates that vitamin D serum levels in patients with XP may be normal, increased or decreased but this is not causally linked to the stringent photoprotective measures carried out in our group of investigated XP-patients.

The safety profile of alkylphosphocholines in the model of the isolated perfused vertebrate retina.

BACKGROUND: Alkylphosphocholines (APCs) are synthetic phospholipid derivatives, and have been demonstrated to inhibit ocular cell proliferation in vitro and in vivo. Currently, they are applied clinically for their antitumoral and antiparasitic properties, but have not yet been implemented for clinical use in proliferative ophthalmic disorders. The purpose of this study was to assess the safety of APC in the ex vivo model of the isolated perfused vertebrate retina. METHODS: Bovine retina preparations were perfused with an oxygen pre-equilibrated standard solution. The electroretinogram (ERG) was recorded using Ag/AgCl-electrodes. After recording stable b-wave amplitudes, an APC was applied at the following concentrations to the nutrient solution: 0.25 microM, 2.5 microM and 25 microM. To investigate the effects of APC on photoreceptor function, a test series at the same concentrations was performed to evaluate the effects of APC on the a-wave amplitude. Aspartate at a concentration of 1 mM was added to the nutrient solution to obtain stable a-wave amplitudes. Thereafter, APC was applied at the same concentrations to the nutrient solution. The recovery of the ERG amplitudes was followed up for 75 minutes. RESULTS: No reduction of the a- and b-wave amplitude was found at the end of the exposure time with APC added in each test series. No differences were found between the ERG amplitudes before and after application of APC at the end of the washout. CONCLUSIONS: In the ex vivo model of the isolated perfused vertebrate retina, APC has proved to be a safe compound in the concentrations applied. Thus, APCs should further be considered as promising candidates for future clinical applications in ophthalmology.

Effect of proximal humeral fractures on the age-specific prevalence of rotator cuff tears.

BACKGROUND: This study examined the effect of proximal humeral fractures on the age- and shoulder-specific prevalence of rotator cuff tears (RCTs) as well as the association with fracture severity, patient age, and clinical outcome. METHODS: Sixty-three fractures were treated conservatively; in 114 cases, minimally invasive osteosynthesis, and in 125 cases, open reduction and plate fixation were performed without rotator cuff reconstruction. After 4.4 years, all 302 patients were clinically and sonographically examined. RESULTS: We examined 139 two-part, 95 three-part, and 68 four-part fractures according to Neer and 134 A, 86 B, and 82 C fractures according to the AO classification. There were 52 patients (17%) with a complete rotator tear (RCT) only at the injured shoulder and 11 patients (4%) with a complete RCT only at the contralateral shoulder (p < 0.0001). Independent of the patient's age at follow-up, the prevalence of an RCT in the fractured shoulder was 13% higher than the prevalence in the opposite shoulder. Four-part fractures showed a significant association with a complete RCT (p = 0.047).Of 74 patients with a satisfactory or poor Constant Score, 33 (44.6%) had RCTs. In the remaining 228 patients with a good to excellent result, only 26 (11.4%) had RCTs. We showed that 66% of the RCTs observed at the fractured shoulder were caused by trauma. There was no association between treatment modality and a complete RCT. CONCLUSION: RCTs may need special attention in initial diagnostics, management, and follow-up especially in severe proximal humeral fractures.

Craniometric changes in patients with acromegaly from a surgical perspective.

OBJECT: The objective of this study was to evaluate and analyze morphometric and volumetric changes of the skull due to acromegaly in areas relevant for neurosurgical practice, focusing on the surgical implications. METHODS: On preoperatively acquired CT scans, cephalometric and volumetric measurements were performed on 45 patients with acromegaly (Group A) and 45 control patients (Group B). The authors determined thickness of the cranial vault, inner and outer diameters of the skull, and the diameter of sphenoidal and maxillary sinus, as well as frontal and maxillary sinus volumetry. The morphometric and volumetric CT data of the patients with acromegaly were compared with the data of a control group and correlated with clinical parameters. RESULTS: Cranial vault thickness differed significantly (p < 0.0001) between the 2 groups. A correlation of the vault thickness with preoperative human growth hormone, insulin-like growth factor-I levels, and duration of clinical history in acromegaly could not be established. The outer anterior-posterior skull diameter of Group A (18.47 ± 0.94 cm) differed significantly (p = 0.0146) from Group B (17.98 ± 0.93 cm) and correlated significantly with preoperative human growth hormone (r = 0.3277; p = 0.0299) and insulin-like growth factor-­I serum levels (r = 0.3756; p = 0.0120). Measurements of the anterior-posterior diameter of the sphenoidal sinus differed significantly (p = 0.0074) between patients with acromegaly and controls. Volumetric analysis of the frontal sinus resulted in a statistically significant difference (p = 0.0382) between patients with acromegaly (14.89 ± 10.85 cm3) and controls (10.06 ± 6.93 cm3). CONCLUSIONS: Significant craniometric changes and volumetric remodelling of the paranasal sinus occur in acromegaly. The bone alterations are of surgical importance for using the transsphenoidal approach. Detailed preoperative diagnostic examination and planning as well as selection of appropriate instruments are mandatory for safe and successful pituitary adenoma removal in patients with acromegaly.

Effect of chronic exposure to a GSM-like signal (mobile phone) on survival of female Sprague-Dawley rats: modulatory effects by month of birth and possibly stage of the solar cycle.

During 1997-2008 two long-term (I and II) and two life-long (III and IV) experiments were performed analyzing the effect of chronic exposure to a low-intensity GSM-like signal (900 MHz pulsed with 217 Hz, 100 µW/cm² average power flux density, 38-80 mW/kg mean specific absorption rate for whole body) on health and survival of unrestrained female Sprague-Dawley rats kept under identical conditions. Radiofrequency (RF)-exposure was started at 52-70 days of age and continued for 24 (I), 17 (II) and up to 36 and 37 months, respectively (III/IV). In the first two experiments (1997-2000) 12 exposed and 12 sham-exposed animals each were observed until they were maximally 770 or 580 days old. In experiment I no adverse health effects of chronic RF-exposure were detectable, neither by macroscopic nor detailed microscopic pathological examinations. Also in experiment II no apparent macroscopic pathological changes due to treatment were apparent. Median survival time could not be estimated since in none of the groups more than 50% of the animals had died. In the course of two complete survival experiments (2002-2005; 2005-2008) 30 RF- and 30 sham-exposed animals each were followed up until their natural end or when they became moribund and had to be euthanized. A synoptical data analysis was performed. Survival data of all four groups could be fitted well by the Weibull distribution. According to this analysis median survival was significantly shortened under RF-exposure in both experiments by 9.06% (95% CI 2.7 to 15.0%) (p=0.0064); i.e by 72 days in experiment III and 77 days in experiment IV as compared to the corresponding sham-treated animals (III: 799 days; IV: 852 days). Both groups of animals of experiment III showed reduced median survival times by 6.25% (95% CI -0.3 to 12.4%) (p=0.0604) compared to the corresponding groups of experiment IV (53 days: sham-exposed animals, 48 days: RF-exposed animals) which may be due to the fact that animals of experiment III were born in October and animals of experiment IV in May indicating that the month of birth affects life span. From the results of the last two experiments it has to be concluded that chronic exposure to a low-intensity GSM-like signal may exert negative health effects and shorten survival if treatment is applied sufficiently long and the observational period covers the full life span of the animals concerned. The current data show that survival of rats kept under controlled laboratory conditions varies within certain limits depending on the month of birth. In view of our previous observations regarding an inhibitory or no effect of RF-exposure on DMBA-induced mammary cancer during the 1997-2000 period, an additional modulatory influence on a year-to-year basis should be considered which might be related to changing solar activity during the the 11-years' sunspot cycle. These potentially complex influences of the natural environment modulating the effects of anthropogenic RF-signals on health and survival require a systematic continuation of such experiments throughout solar cycle 24 which started in 2009.

Long-term results after non-plate head-preserving fixation of proximal humeral fractures.

A retrospective study was conducted to evaluate displaced proximal humeral fractures treated with a non-plate head-preserving fixation and to detect factors predicting functional outcome. After a median follow-up period of 79.7 months, 105 patients with nine A-fractures, 36 B-fractures and 60 C-fractures (nine two-part-fractures, 41 three-part fractures and 55 four-part fractures) were assessed. Functional outcome was measured based on the Constant and UCLA scores. Of all patients, 70-75% had excellent or good Constant and UCLA scores. In 74% a good or satisfactory quality of initial reduction fracture was achieved. About one-fifth (21%) of the fractures showed a secondary displacement. Twenty-seven percent of the patients had signs of humeral head necrosis and 22% had implant related problems. There were significant correlations between a high final score and young age, low AO fracture severity, good quality of fracture reduction and residual osseous deformity, absence of secondary fracture displacement, implant-related complications, shoulder arthrosis and humeral head necrosis at the time of follow-up. In conclusion, the non-plate head-preserving fixation of proximal humeral fractures is an alternative treatment for displaced proximal humeral fractures. Especially in severely displaced C-fractures in older patients, non-anatomical reduction leads to a high rate of secondary displacement, residual osseous deformity and only a fair shoulder function. For these cases alternative methods such as prosthetic replacement should be chosen.

Clinical and radiological evaluation of minimally displaced proximal humeral fractures.

INTRODUCTION: The purpose of this prospective study was to assess the Constant score and radiographic outcome in 66 patients (mean age 58.7 years/mean follow-up 51 months) with a minimally displaced and/or impacted fracture of the proximal humerus treated with early mobilization. METHOD: Special attention was paid to analyze the specific intrinsic parameters (age, gender, ASA grade and length of physiotherapy), injury-related parameters (classification, osteoporosis) and therapy-related parameters (initial fracture displacement, residual bony-deformity after healing, secondary fracture displacement during healing period, non-union, humeral head necrosis and omarthrosis) that may influence the final score. PATIENTS: There were 31 A (47%), 22 B (33%) and 13 C-fractures (19%). The median Constant score for the fractured shoulder was 89 points. RESULTS: All fractures healed without non-union. The radiological assessment showed in 80% a fracture-displacement with <15 degrees angulation and/or <5-mm displacement of the greater tuberosity. At time of follow-up, the residual bony-deformity was perfect and good in 88% of cases. There was a significant association between the final Constant score and the age, ASA classification, AO (ABC) classification and initial fracture displacement. CONCLUSION: Early physiotherapy, with a short period of immobilization is a sufficient therapy for management of minimally displaced and/or impacted fractures of the proximal humerus.