Reduced cancer mortality at high altitude: The role of glucose, lipids, iron and physical activity.

Residency at high altitude (HA) demands adaptation to challenging environmental conditions with hypobaric hypoxia being the most important one. Epidemiological and experimental data suggest that chronic exposure to HA reduces cancer mortality and lowers prevalence of metabolic disorders like diabetes and obesity implying that adaption to HA modifies a broad spectrum of physiological, metabolic and cellular programs with a generally beneficial outcome for humans. However, the complexity of multiple, potentially tumor-suppressive pathways at HA impedes the understanding of mechanisms leading to reduced cancer mortality. Many adaptive processes at HA are tightly interconnected and thus it cannot be ruled out that the entirety or at least some of the HA-related alterations act in concert to reduce cancer mortality. In this review we discuss tumor formation as a concept of competition between healthy and cancer cells with improved fitness - and therefore higher competitiveness - of healthy cells at high altitude. We discuss HA-related changes in glucose, lipid and iron metabolism that may have an impact on tumorigenesis. Additionally, we discuss two parameters with a strong impact on tumorigenesis, namely drug metabolism and physical activity, to underpin their potential contribution to HA-dependent reduced cancer mortality. Future studies are needed to unravel why cancer mortality is reduced at HA and how this knowledge might be used to prevent and to treat cancer patients.

Multiple drill-hole osteotomy in hand surgery - description of a novel application and proof of feasibility.

BACKGROUND: Malunion of phalangeal and metacarpal bones are often associated with impairment of hand function and pose a challenging task for treating surgeons in most cases. When applicable, corrective osteotomy is the treatment of choice, where the affected bone is cut to correct malalignment using chisels or saws. The use of these instruments is associated with several drawbacks especially in hand surgery. We aimed to determine whether a multiple drill-hole (MDH) osteotomy technique was suitable for performing corrective osteotomies of metacarpal and phalangeal bones. METHODS: This case series included 11 patients with malalignments or malunions of phalangeal or metacarpal bones. Corrective osteotomy was performed with the MDH technique. Follow-up examinations included clinical evaluations and radiography at frequent intervals, between 2 and 22 months postoperatively. RESULTS: In all cases, planned osteotomies were technically feasible with the MDH technique. Apart from one case of a broken drillbit, no intraoperative or postoperative complication was recorded. All performed osteotomies healed within a mean of 6 weeks to radiological consolidation. In all cases, satisfactory results were achieved. CONCLUSION: The present study was the first to test MDH osteotomy for hand surgery. We demonstrated that MDH was feasible for corrective osteotomies of metacarpal and phalangeal deformities. Advantages included excellent feasibility for osteotomies performed at varying angles, precise execution, reduced risk of collateral damage, and flexibility for performing intra-articular osteotomies.

Hexaminolevulinate-induced fluorescence colonoscopy versus white light endoscopy for diagnosis of neoplastic lesions in the colon.

BACKGROUND AND STUDY AIMS: To compare the rate of detection of colorectal neoplastic lesions using the selective photosensitizer precursor hexaminolevulinate (HAL) combined with a new fluorescence video endoscope system against that of standard white light endoscopy, and secondarily, to evaluate the safety profile of HAL-induced fluorescence colonoscopy. PATIENTS AND METHODS: This prospective phase II clinical pilot study from two hospital study centers included 25 patients with known or highly suspected colorectal neoplasia. They underwent sensitization with locally applied 500 ml HAL enemas at a concentration of 1.6 mmol/L. At 60 minutes after enteral HAL administration, fluorescence imaging was done using a special light source capable of delivering either white light or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. RESULTS: Using histology as the gold standard, 55 / 93 of neoplastic lesions were detected with white light endoscopy, 53 / 93 with both white and blue light, 38 / 93 with blue light and second-pass white light, and 27/93 with blue light only. Of all neoplastic lesions, 91 / 93 revealed red fluorescence under fluorescence imaging ( P < 0.0001). Fluorescence mode showed 38.7 % (36 / 93) more neoplasms than did white light endoscopy. An isolated slight elevation of bilirubin, by a factor of 1.5, was noted after the administration of HAL. CONCLUSIONS: Administration of HAL as enema induces selective lesion fluorescence and increases lesion detection rate in patients with colorectal neoplasia, especially of flat, nonvisible adenomas.

A comparative study between sacral neuromodulation and intravesical botulinum toxin injection for patients with refractory overactive bladder.

OBJECTIVE: To compare the efficacy, safety, patient compliance and quality of life (QoL) (early and at 6 months after treatment), in a group of Iraqi female patients with refractory overactive bladder (OAB), treated with intradetrusor botulinum toxin A (BTX) injections vs sacral neuromodulation (SNM). PATIENTS AND METHODS: A prospective, clinical interventional study of 37 female patients assessed by history, physical examination, voiding diary, ultrasonography (US), and urodynamics. The patients were assigned to one of two groups: Group 1, treated with cystoscopic BTX injections; and Group 2, treated with SNM. Response to treatment was assessed by voiding diary, the Treatment Benefit Scale, a modified Quality of Life scale, urine culture, and abdominal US. RESULTS: The mean age of the patients in Group 1 (BTX) was 43.8 years and in Group 2 (SNM) was 37.2 years. OAB-wet was diagnosed in 11 patients in Group 1 and 10 in Group 2. At the 6-month follow-up there were 14/16 and 12/15 positive responders, in groups 1 and 2, respectively; with no major complications. All the responders had a significant improvement in their overall QoL after both types of treatment. CONCLUSIONS: Both BTX and SNM, in our experience, were safe and effective in managing our patients with refractory OAB after 6 months of follow-up, which was also reflected by an improvement in their QoL. ABBREVIATIONS: BTX: botulinum toxin A; IPG: implantable pulse generator; OAB: overactive bladder; PVR: post-void residual urine; QoL: quality of life; SNM: sacral neuromodulation; UDS, urodynamics; UI, urinary incontinence.

Time of appearance of ossification centers in carpal bones. A radiological retrospective study on Saudi children.

OBJECTIVES: To find reference data for the time of appearance of ossification centers in carpal bones and the lower ends of the radius and ulna in the Saudi population. In addition, to check the sequence of appearance of carpal bones and the relation of this sequence to the appearance of distal epiphyses of the radius and ulna. Methods: A retrospective radiological study was carried out between 2012 to 2020 at King Fahad Hospital of the University, Al-Khobar, Saudi Arabia. A sample of 279 hand/wrist plain radiographs of Saudi children was analyzed. RESULTS: The first bones at the wrist region to appear in Saudi children are the capitate, hamate, and distal epiphysis of the radius, and these appear during the first year of life. The other bones develop subsequently at yearly intervals, and the last one to appear is the pisiform, which arises at the end of the first decade of life. CONCLUSION: The sequence of appearance of carpal bones in the Saudi population is similar to what is described in the literature. However, the time of appearance of some of these bones is earlier than that in other populations.

Intermittent hypoxia increases exercise tolerance in patients at risk for or with mild COPD.

The effects of repeated short-term hypoxia on exercise tolerance in patients at risk for, or with mild COPD were investigated. Eighteen patients (10 males, 8 females; 33-72 years) were randomly assigned in a double-blind fashion to receive 15 sessions of intermittent hypoxia (FiO(2): 0.15-0.12) or normoxia within 3 weeks. Three weeks of intermittent hypoxia increased total haemoglobin mass (+4% vs. 0%, p<0.05), total exercise time (+9.7% vs. 0%, p<0.05) and the exercise time to the anaerobic threshold (+13% vs. -7.8%, p<0.05) compared to controls. Changes in the total exercise time were positively related to the changes in total haemoglobin mass (r=0.59, p<0.05) and changes in the time to the anaerobic threshold were positively related to the changes in the lung diffusion capacity for carbon monoxide (r=0.48, p<0.05). Intermittent hypoxia treatment may be a valuable addition to therapy designed to improve exercise tolerance in patients at risk for, or with mild COPD.

Repeated intramedullary stabilization following failed telescopic nail lengthening - An appropriate treatment strategy.

Externally magnetic-controlled intramedullary telescopic nails for bone lengthening have recently gained popularity due to many advantages when compared to more traditional lengthening methods. Patients requiring lengthening often present with a clinical history of previous multiple surgeries increasing the risk for complications of further procedures. However, studies regarding the treatment of complications following implantation of these devices remain scarce in literature. Therefore, we report our experience with revision surgery after lengthening with a telescopic intramedullary lengthening nail. In 6 out of 20 cases (30%) of lower limb lengthening for leg length discrepancy revision surgery was necessary. Two revisions were necessary due to nail breakage while the other 4 cases required a secondary procedure for non-union. In all cases, revision surgery included standard intramedullary locking nailing with additional autologous bone grafting. The median interval between index and revision surgery was 11.5 months (range 2-15 months). Satisfying clinical results, the intended extend of lengthening and bony consolidation was observed in all 6 patients. We conclude that revision surgery using an intramedullary locking nail with autologous bone grafting after failed telescopic nail-based lengthening represents an useful salvage procedure in these cases.

Autonomic and cerebrovascular abnormalities in mild COPD are worsened by chronic smoking.

Patients with chronic obstructive pulmonary disease (COPD) may develop hypercapnia and hypoxia, two main determinants of cerebral blood flow. The current authors tested whether cerebrovascular regulation was altered in mild COPD, modified by manoeuvres acutely improving autonomic cardiovascular modulation or influenced by smoking habit. In 15 eucapnic normoxic mild COPD patients (eight smokers) and 28 age-matched controls (14 smokers), midcerebral artery blood flow velocity (MCFV), end-tidal carbon dioxide tension (P(ET,CO2)), arterial oxygen saturation (S(a,O2)), ECG and blood pressure at rest were monitored during progressive hypercapnic hyperoxia, isocapnic hypoxia, slow breathing and oxygen administration. MCFV, arterial baroreflex and dynamic MCFV-blood pressure relationships were compared by phase analysis. COPD and control smokers showed higher MCFV (when corrected for P(ET,CO2)), lower cerebrovascular resistance index and lower sensitivity to hypercapnia than nonsmokers, with equal sensitivity to S(a,O2) and similar phase analysis. Arterial baroreflex was depressed in all COPD patients. Slow breathing and oxygen administration improved baroreflex sensitivity and reduced MCFV in all COPD patients. Patients with mild chronic obstructive pulmonary disease show autonomic dysfunction. Chronic smoking induces cerebral vasodilation and impairs cerebrovascular control. All abnormalities can be partly corrected by improving the cardio- and cerebrovascular autonomic modulation, suggesting that functional autonomic abnormalities are already present at an early stage of disease.

Direct head injury caused by a tear gas cartridge. Questions on safety: A case report from Iraq and review of the literature.

INTRODUCTION AND BACKGROUND: Primary injuries from tear gas weapons include injuries to the visual and respiratory systems and skin. However, few studies have reported direct mechanical brain injuries from tear gas weapons. CASE REPORT: A 27-year-old male presented to the emergency department of a neurosurgery teaching hospital in Baghdad, Iraq, with a penetrating head injury of unknown source. DISCUSSION: Tear gas weapons are considered safe, but tear gas exposure causes severe complications. Traumatic brain injuries as a direct effect of tear gas bombs are rarely reported in the literature. Tear gas cartridge injuries should be managed in the same manner as any penetrating brain injury, with appropriate neuromonitoring. This monitoring is crucial for the detection and prevention of secondary brain insults. CONCLUSION: Emergency medicine specialists and neurosurgeons should be aware that tear gas weapons are not always safe, and they should anticipate chemical, thermal and mechanical side effects of tear gas weapons. The literature and our results suggest that these weapons should not be considered civil and harmless.

Fast simultaneous assessment of renal and liver function using polymethine dyes in animal models of chronic and acute organ injury.

Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.

New mechanical thrombectomy model in the rabbit: A feasibility study.

BACKGROUND AND PURPOSE: Thrombolytic therapy represented the gold standard for the treatment of ischemic stroke. Its drawbacks include increased bleeding risk and low recanalization rates. Mechanical thrombectomy is a new promising therapy option. Devices used for this procedure were substantially improved during recent years. New devices require extensive preclinical invivo testing. We therefore sought to translate the commonly used pig model to a simplified and cheaper rabbit model. MATERIALS AND METHODS: We performed thromboembolisation in eight intubated and sedated adult female New Zealand white rabbits. The thrombus was created by careful rotation of autologous blood in a silicone tube and addition of barium sulfate for radiopacity. We injected the artificial thrombus via a catheter through the cannulated femoral artery. After thromboembolisation, 2D-DSA was performed to evaluate location and thrombus dimensions. COMPARISON WITH EXISITING METHOD(S): None. RESULTS: No complications or mortality were observed in our series. In seven cases (87.5%) the location of the thromboembolism was the maxillary artery and in one case (12.5%) the thrombus reached the occipital artery. The radiopaque thrombus had a length of 7.0±4.55mm invivo. Vessel diameters in angiographic evaluation were 2.44±0.21mm for the common carotid artery and 2.1±0.16mm for the maxillary artery. CONCLUSIONS: The novel small animal model for mechanical thrombectomy in rabbit is technically feasible and cheap. It offers comparable vessel diameters to cranial arteries and closely mimics human coagulation system.

HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications.

Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated.

Effect of alterations in blood volume with bed rest on glucose tolerance.

Bed rest leads to rapid impairments in glucose tolerance. Plasma volume and thus dilution space for glucose are also reduced with bed rest, but the potential influence on glucose tolerance has not been investigated. Accordingly, the aim was to investigate whether bed rest-induced impairments in glucose tolerance are related to a concomitant reduction in plasma volume. This hypothesis was tested mechanistically by restoring plasma volume with albumin infusion after bed rest and parallel determination of glucose tolerance. Fifteen healthy volunteers (age 24 ± 3 yr, body mass index 23 ± 2 kg/m2, maximal oxygen uptake 44 ± 8 ml·min-1·kg-1; means ± SD) completed 4 days of strict bed rest. Glucose tolerance [oral glucose tolerance test (OGTT)] and plasma and blood volumes (carbon monoxide rebreathing) were assessed before and after 3 days of bed rest. On the fourth day of bed rest, plasma volume was restored by means of an albumin infusion prior to an OGTT. Plasma volume was reduced by 9.9 ± 3.0% on bed rest day 3 and area under the curve for OGTT was augmented by 55 ± 67%. However, no association (R2 = 0.09, P = 0.33) between these simultaneously occurring responses was found. While normalization of plasma volume by matched albumin administration (408 ± 104 ml) transiently decreased (P < 0.05) resting plasma glucose concentration (5.0 ± 0.4 to 4.8 ± 0.3 mmol/l), this did not restore glucose tolerance. Bed rest-induced alterations in dilution space may influence resting glucose values but do not affect area under the curve for OGTT.

Human pharmacokinetics of iodixanol.

The pharmacokinetic properties of the x-ray contrast medium, iodixanol, a new nonionic dimer, were investigated in a phase I study including 40 healthy male volunteers. Iodixanol (300 mg I/mL) was administered intravenously (i.v.) at four dose levels--0.3, 0.6, 0.9, and 1.2 g iodine (I)/kg body weight--and saline was given as a control. 51Cr-EDTA was given concomitantly with iodixanol at all dose levels to study renal excretion of iodixanol. Mean half-lives were 26 and 131 minutes in the distribution and elimination phase, respectively. Apparent volume of distribution was 0.28 1/kg body weight, indicating distribution to extracellular fluid only. Within 24 hours after injection, 97% of the dose was excreted unmetabolized in the urine via glomerular filtration. The excretion in feces was 1.2% of the dose. The parameters calculated were independent of the given dose. The pharmacokinetics of iodixanol are comparable with those reported for other intravascular contrast media.

Measurements of phantom scatter factors for small field sizes in high energy x rays.

An alternate method to measure the phantom scatter factor in small fields is provided for high energy photon beams. The measurement technique is based on the density scaling theorem described by O'Connor [Phys. Med. Biol. 1, 352-369 (1957)]. The phantom scatter factor (Sp) is measured in balsa and cedar wood to give effective field sizes in 3 x 3 to 0.5 x 0.5 cm2 water. The extrapolated zero area phantom scatter factor from the average data of balsa and cedar is 0.45. This indicates that the variation of output is largely due to a sharp decrease in the phantom scatter factor for small field sizes.

Differential scatter integration in regions of electronic non-equilibrium.

Dose calculation in regions of electronic non-equilibrium is usually achieved by Monte Carlo code systems or convolution techniques. Earlier primary and scatter dose calculation models are based on an assumption of electronic equilibrium. Therefore, dose in regions of non-equilibrium is not accurately calculated. We modified the primary and scatter dose model by introducing an electron perturbation factor to calculate dose in electronic non-equilibrium. All the parameters required for the model are derived experimentally and without the use of any Monte Carlo code systems. The detailed calculational method and experimental verification for 10 MX x-rays are provided.

Clastogenic effects of radiofrequency radiations on chromosomes of Tradescantia.

The clastogenicity of electromagnetic fields (EMF) has so far been studied only under laboratory conditions. We used the Tradescantia-micronucleus (Trad-MCN) bioassay in an in situ experiment to find out whether short-wave electromagnetic fields used for broadcasting (10-21 MHz) may show genotoxic effects. Plant cuttings bearing young flower buds were exposed (30 h) on both sides of a slewable curtain antenna (300/500 kW, 40-170 V/m) and 15 m (90 V/m) and 30 m (70 V/m) distant from a vertical cage antenna (100 kW) as well as at the neighbors living near the broadcasting station (200 m, 1-3 V/m). The exposure at both sides of the slewable curtain antenna was performed simultaneously within cages, one of the Faraday type shielding the field and one non-shielding mesh cage. Laboratory controls were maintained for comparison. Higher MCN frequencies than in laboratory controls were found for all exposure sites in the immediate vicinity of the antennae, where the exposure standards of the electric field strength of the International Radiation Protection Association (IRPA) were exceeded. The results at all exposure sites except one were statistically significant. Since the parallel exposure in a non-shielding and a shielding cage also revealed significant differences in MCN frequencies (the latter showing no significant differences from laboratory controls), the clastogenic effects are clearly attributable to the short-wave radiation from the antennae.

The Mount Sinai Hospital clinicalpathological conference: a 45-year-old man with Pompe's disease and dilated cardiomyopathy.

This is an unusual case of a 45-year-old man, born in Ecuador, with evidence of profound left ventricular dysfunction, dilated cardiomyopathy and marked myocardial hypertrophy. Preceding events were advanced atrioventricular block (necessitating pacemaker implantation) and atrial flutter. The diagnosis of Pompe's disease was established by endomyocardial biopsy and appropriate staining, which indicated abnormal glycogen storage.

Comparison between the efficacy of dimeric and monomeric non-ionic contrast media (iodixanol vs iopromide) in urography in patients with mild to moderate renal insufficiency.

Non-ionic dimers induce less diuresis than non-ionic monomers, resulting in increased opacification of the urinary tract in intravenous (i.v.) urography. This double blind, comparative, randomized, parallel trial compared the efficacy of iodixanol (non-ionic dimer) and iopromide (non-ionic monomer) in 100 patients with mild to moderate renal insufficiency (serum creatinine of 135 to 265 mumol l-1) who underwent i.v. urography. A total dose of 600 mgI kg-1 bw of iodixanol (320 mgI ml-1) or iopromide (300 mgI ml-1) was injected. Radiographs were blindly evaluated by three radiologists who analysed different parameters (renal border visualization, nephrogram density, calyceal filling and density, papillary blush detection, delineation of collecting ducts, renal pelvis opacification, visualization of ureters, bladder density, bladder distention). Densitometric evaluation on the renal pelvis and bladder was also performed. Iodixanol showed better filling and density of the calyces (p = 0.004), more frequent detection of papillary blush (p = 0.003) and better opacification of the renal pelvis (p = 0.006). No significant differences between the two contrast media were found in regard to other parameters. In conclusion, the results confirmed theoretical expectations. The non-ionic dimer iodixanol is to be preferred to a non-ionic monomer such as iopromide in i.v. urography on patients with impaired renal function.

Safety and toleration of the non-ionic contrast medium iopentol. An intravenous phase I trial.

The safety and toleration of iopentol, a new non-ionic contrast medium for intravascular use, were evaluated. In the intravenous phase I study, 24 volunteers were allocated to 3 dose groups corresponding to 0.3, 0.6 or 1.2 g I/kg body weight, respectively. Injection of saline was used as control in the highest dose group. Adverse events, hemodynamic parameters, and clinical chemical parameters in the blood and urine were recorded. No severe or unexpected adverse events occurred. All findings were transient and included a sensation of warmth, a small increase in heart rate, a dilution effect on blood parameters, and enzymuria. The deviations in clinical chemical parameters fell mostly within reference ranges and were clinically insignificant. Thus, iopentol may safely be advanced to clinical trials in patients for comparative studies.