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PubMed2002

Performance of twin central venous catheters: influence of the inversion of inlet and outlet on recirculation.

BACKGROUND: The use of a central venous catheter as a permanent vascular access is constantly growing. The recirculation rate in this type of vascular access varies depending on the site of insertion, the length of the catheter, the blood flow and the time elapsed since catheter insertion. When the in/out flow of the lumens of the catheter is reduced, it is sometimes necessary to inverse the arterial and venous lines of the catheter at the beginning or in the course of the dialysis session. The impact of such a practice on the recirculation rate has only been assessed by the low flow urea dilution method. METHODS: The blood recirculation rate was measured using the ultrasound dilution velocity method (Transonic system, Ithaca, N.Y.) in 14 patients (aged 64 +/- 15 years), with a right internal jugular (n = 9) or right subclavian (n = 5) central catheter (Twincath, Medcomp), used over a mean period of 16.3 (range 1-42) months. No clinical dysfunction of the catheter was apparently noted. The distance between the vein and the artery end of the catheter was 3.9 +/- 2.8 cm, measured on chest radiography. The recirculation rate was measured over a single dialysis session at increasing blood flows in the normal and inversed position of the catheter. RESULTS: The difference between the prescribed and effective blood flow was significant with an effective blood flow of 180 +/- 16 ml/min for 200 ml/min, 264 +/- 27 ml/min for 300 ml/min and 329 +/- 16 ml/min for 400 ml/min prescribed blood flow. There was no relationship between the recirculation rate and blood flow whatever the position of the lines on the catheter. There was also no relationship between the recirculation rate and the distance between the catheter ends. However, reversing the catheter ends significantly increased the recirculation rates from 2.9 +/- 5 to 12 +/- 9% whatever the blood flow. CONCLUSION: The use of central catheters in an inversed position can result in a higher recirculation rate. Reversing the lines of the central catheters may lead to less effective hemodialysis and it seems particularly important for the nursing staff to be aware of this phenomenon. Thus, measurement of the effective blood flow and recirculation by ultrasound velocity should be included in quality monitoring and maintenance.

Aged↗
PubMed1975

Isolated U wave-inversion in acute myocardial infarction.

Three patients are presented in whom an isolated inversion of the U wave preceded by several hours typical electrocardiographic changes of an acute myocardial infarction. The association of transient hypertension and an acute U-wave inversion during this period of myocardial ischemia is discussed. It is suggested that within the appropriate clinical context an isolated U-wave inversion may portend an acute myocardial infarction.

Action Potentials↗
PubMed1999

Low-density lipoprotein particle size is inversely related to plasminogen activator inhibitor-1 levels. The Insulin Resistance Atherosclerosis Study.

High levels of plasminogen activator inhibitor-1 (PAI-1) and preponderance of small dense low-density lipoproteins (LDL) have both been associated with atherosclerotic disease and with the insulin resistance syndrome (IRS). In vitro studies have shown a stimulatory effect of various lipoproteins on PAI-1 release from different cells, including endothelial cells and adipocytes. The authors sought to investigate the relation of PAI-1 to LDL particle size in a large tri-ethnic population (n=1549) across different states of glucose tolerance. LDL size was determined by gradient gel electrophoresis, and PAI-1 was measured by a 2-site immunoassay, sensitive to free PAI-1. PAI-1 was inversely related to LDL size in the overall population (r=-0.21, P<0.0001), independent of gender and ethnicity. However, the authors found a significant interaction with glucose tolerance status (P=0.035). In univariate analysis, the association between PAI-1 and LDL size was most pronounced in subjects with normal glucose tolerance (NGT, r=-0.22, P<0.0001) and weaker in impaired glucose tolerance (IGT, r=-0.12, P=0.03) and type-2 diabetes (r=-0.10, P=0.02). After adjustment for demographic variables and metabolic variables known to influence PAI-1 levels (triglyceride and insulin sensitivity), a significant inverse relation of LDL size to PAI-1 levels was only present in NGT (P=0. 023). In subjects with IGT or overt diabetes, who usually have elevated PAI-1 levels, additional factors other than LDL size seem to contribute more importantly to PAI-1 levels. The demonstrated inverse relation of LDL size and PAI-1 levels provides one possible explanation for the atherogeneity of small dense LDL particles.

Adipose Tissue↗
PubMed2000

Intravascular free tissue factor pathway inhibitor is inversely correlated with HDL cholesterol and postheparin lipoprotein lipase but proportional to apolipoprotein A-II.

To elucidate the distribution and clinical implications of tissue factor pathway inhibitor (TFPI) concentrations, we measured TFPI levels consisting of preheparin free, lipoprotein-bound (Lp-bound), and endothelial cell-anchor pools in 156 patients with coronary artery disease (average age, 61.2+/-9.1 years; range, 32 to 78 years) by heparin infusion (50 IU/kg) and compared them with the preheparin TFPI levels of 229 healthy subjects (average age, 59. 6+/-9.4 years; range, 41 to 80 years). The patients had lower preheparin free TFPI and lower HDL cholesterol (HDL-C) levels than the healthy subjects with equivalent Lp-bound forms (free TFPI, 15. 9+/-6.5 versus 19.2+/-8.1 ng/mL). In a partial correlation analysis, the preheparin free TFPI levels were shown to be inversely correlated with the HDL-C concentrations in both the patients (r=-0. 454, P<0.001) and the healthy subjects (r=-0.136, P<0.05). As determined by comparison of preheparin and postheparin plasma, the patients generally showed preheparin free TFPI <10%, Lp-bound TFPI at 30%, and endothelial cell-anchor TFPI at 60%. When the patients were divided into 4 categories by their LDL cholesterol (LDL-C, 130 mg/dL) and HDL-C (40 mg/dL) levels to specify their coronary risks, the low-HDL-C groups had significantly increased preheparin and postheparin free TFPI levels and decreased postheparin LPL levels, whereas the high-LDL-C groups showed increased levels of Lp-bound TFPI. In a partial correlation analysis, we found a proportional relation between postheparin free TFPI and apolipoprotein A-II (r=0. 5327) and between HDL-C and LPL (r=0.4906), whereas postheparin free TFPI was inversely correlated with HDL-C (r=-0.4280) and postheparin LPL (r=-0.4791). The inverse relationship between TFPI and LPL suggests that increased free TFPI concentrations as a compensatory response of the endothelium to prevent atherothrombotic processes compete with and displace LPL on endothelial surface, resulting in reduced LPL and low HDL-C.

Adult↗
PubMed1997

Mechanisms for absence of inverse relationship between coupling intervals of premature impulses initiating reentrant ventricular tachycardia and intervals between premature and first tachycardia impulses.

BACKGROUND: During initiation of tachycardias by programmed stimulation (PES), an inverse relationship between the coupling interval of the premature impulse (V1V2) and the interval between the premature impulse and the first impulse of tachycardia (V2T1) has been proposed to be a specific indicator of reentry. However, an inverse relationship has not always been observed during initiation of clinical reentrant ventricular tachycardias (VTs). METHODS AND RESULTS: Reentrant VT was initiated by PES in twelve 4-day-old infarcted dog hearts. The relationship between V1V2 and V2T1 was always direct. Mapping of the epicardial border zone (EBZ) indicated that initiation of VT was secondary to functional orthodromic block of V2, propagation of V2 around the line of block, and antidromic propagation through the original location of the block. In 7 dogs, the line of orthodromic block and the pathway of orthodromic propagation were similar for different V1V2 coupling intervals. Orthodromic conduction time around the line to its distal side was longer at shorter V1V2 intervals, but a shorter antidromic delay in the area of unidirectional block for shorter V1V2 intervals, possibly reflecting small changes in the conduction pathway involving deeper layers of the EBZ, resulted in shorter V2T1 intervals. In the other 5 dogs, the orthodromic conduction pathway of V2 around the line of block changed markedly, with a shorter pathway for shorter V1V2 intervals resulting in shorter V2T1 intervals. CONCLUSIONS: An inverse relationship between V1V2 and V2T1 is not a specific indicator of functional reentry.

Animals↗
PubMed1998

Why faces may be special: evidence of the inversion effect in chimpanzees.

Five chimpanzees were tested on their ability to discriminate faces and automobiles presented in both their upright and inverted orientations. The face stimuli consisted of 30 black and white photographs, 10 each of unfamiliar chimpanzees (Pan troblodytes), brown capuchins (Cebus apella), and humans (Homo sapiens). Ten black and white photographs of automobiles were also used. The stimuli were presented in a sequential matching-to-sample (SMTS) format using a computerized joystick-testing apparatus. Subjects performed better on upright than inverted stimuli in all classes. Performance was significantly better on upright than inverted presentations of chimpanzee and human faces but not on capuchin monkey faces or automobiles. These data support previous studies in humans that suggest the inversion effect occurs for stimuli for which subjects have developed an expertise. Alternative explanations for the inversion effect based on the type of spatial frequency contained in the stimuli are also discussed. These data are the first to provide evidence for the inversion effect using several classes of face stimuli in a great ape species.

Animals↗
PubMed2003

Bronchoalveolar lavage fluid surfactant protein-A and surfactant protein-D are inversely related to inflammation in early cystic fibrosis.

The pulmonary collectins surfactant protein (SP)-A and SP-D play important roles in innate lung defense, enhancing opsonization of microbes and limiting lung inflammatory responses. To quantify relationships among collectins, bacteria, and inflammation in early cystic fibrosis (CF) airway secretions, bronchoalveolar lavage fluids (BALFs) were collected from children undergoing clinically indicated bronchoscopy. Quantitative bacteriology, differential cell counts, and ELISA for SP-A and SP-D were assessed. Significantly increased numbers of neutrophils relative to bacteria were noted in BALF from CF compared with non-CF subjects. Although SP-A levels tended to be lower in CF compared with non-CF, this was only significant in the presence of bacterial infection. Among CF patients, SP-A concentrations in BALF were inversely related to inflammation, bacterial colony-forming units per milliliter, and age. SP-D levels were significantly decreased in CF patients, and SP-D was rarely detectable in the presence of infection. Among CF patients, SP-D correlated inversely with inflammation and bacterial colony-forming units per milliliter, and there was decreased immunostaining of BALF cells for SP-D in CF. Immunohistochemistry of CF autopsy lung sections for SP-A and SP-D confirmed their paucity at sites of infection and inflammation. We conclude that relative collectin deficiency occurs early in CF airways and is inversely related to inflammation in CF airways.

Analysis of Variance↗
PubMed2006

Inverse association between pulmonary function and C-reactive protein in apparently healthy subjects.

RATIONALE: Increased levels of systemic markers of inflammation have been reported in patients with impaired lung function due to obstructive or restrictive lung disease. OBJECTIVE: We tested the hypothesis that a decline in lung function within the normal range may be associated with a systemic subclinical inflammation. METHODS: Pulmonary function tests, cardiorespiratory fitness, components of the metabolic syndrome, and high-sensitivity C-reactive protein (CRP) were determined in 1,131 subjects without known pulmonary disease. MEASUREMENTS AND MAIN RESULTS: Ninety-six of the study participants (8.5%) had FEV(1) of less than 80% of predicted values. There was a strong inverse association between CRP levels and quartiles of FEV(1). The median CRP levels in nonsmoking participants were 2.5, 1.8, 1.7, and 1.3 mg/L in the first, second, third, and forth FEV(1) quartiles, respectively (p < 0.0001). A similar inverse association was present in smoking subjects (median CRP levels were 3.8, 2.3, 2.0, and 1.9 mg/L in the first, second, third, and fourth FEV(1) quartiles, respectively; p < 0.0001). These associations remained highly significant after adjustment for age, sex, components of the metabolic syndrome, and fitness level (p = 0.0005). CONCLUSIONS: An inverse linear relationship exists between CRP concentrations and measures of pulmonary function in subjects without pulmonary disease and in never-smokers. These results indicate that systemic inflammation may be linked to early perturbations of pulmonary function.

Adult↗
PubMedDate not supplied

Application of inverse filtering for detecting laryngeal pathology.

Inverse filtering analysis was performed on acoustic speech samples of the vowel sound "ah" produced by ten selected patients and ten normal adults. The inverse filter output signal is the residue obtained by automatically extracting the effects of the supraglottal structure from the acoustic speech signal. For normal speakers, the residue consists of a series of rather sharp periodic spikes having low amplitude noise between periods. For pathological voices, the residue consists of lower amplitude, less sharp spikes having higher amplitude noise between periods. Comparisons between the acoustic speech waveforms and the residue signals illustrate the superiority of the residue signal for detecting irregularity, and thus suggests the feasibility of applying inverse filtering as an aid to laryngeal diagnostics.

Acoustics↗
PubMed1983

Inverse scattering solutions by a sinc basis, multiple source, moment method--Part I: Theory.

A new method for solving the inverse scattering problem for the scalar, inhomogeneous, exact, Helmholtz wave equation is presented. No perturbation approximations are used and the method is applicable even for many cases where weak to moderate attenuation and moderate to strong refraction of incident fields occur. The ill-posed nature of the inverse scattering problem for a single monochromatic source is known. However, the use of multiple sources, the collection of redundant (i.e., overdetermined) data, and the constraining of the fields and complex refractive index to be spatially band limited constitutes a new problem. The cases we have tested by computer simulation indicate that the new problem is well posed, a unique solution, and is stable with noisy data. The method is an application of the well-known method of moments with sinc basis and delta testing functions to discretize the problem. The inverse scattering solution may be obtained by solving the resulting set of simultaneous, quadratic, multivariate equations. Several algorithms for solving these equations are given.

Electromagnetic Phenomena↗
PubMed1983

Inverse scattering solutions by a sinc basis, multiple source, moment method--Part II: Numerical evaluations.

In part I, we presented a method for solving the inverse scattering problem using multiple sources and detectors. Allowance for multiple angles of incident radiation improves the ill-posed nature of the inverse problem by improving the quality and quantity of information gathered at detector points. This paper describes implementation and numerical evaluation of the method. An 11 by 11 image reconstructed from noisy scattered field data is shown to closely match the original scattering object, and the improvement possible by constraining the reconstruction to be spatially band limited is demonstrated. Furthermore, for a somewhat simpler "pseudo-inverse problem," we give findings on the effects that detector radius, degree of over determination, noise, and object contrast have on reconstruction quality.

Mathematics↗
PubMed2005

First-time inversion ankle ligament trauma: the effects of sex, level of competition, and sport on the incidence of injury.

BACKGROUND: Inversion ankle trauma is disabling, yet little is known regarding the incidence rate of first-time ankle sprains and how it is influenced by factors including sex, level of competition, and sport. HYPOTHESIS: The incidence rates of first-time ankle ligament sprains are influenced by sex, level of competition (high school vs college), and type of sports participation (basketball, soccer, lacrosse, and field hockey). STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Between 1999 and 2003, high school and college athletes were evaluated before participation in their sports. Subjects were included in the study if they had not experienced a prior ankle or lower extremity injury and were then followed during participation in soccer, basketball, lacrosse, or field hockey to document their days of exposure to sport and injuries sustained. The relative risk associated with sex, level of competition, and sport was estimated by Cox regression. RESULTS: A total of 901 athletes had 50 680 person-days of exposure to sports, and 43 (4.8%) had an inversion injury that produced an ankle ligament sprain. Overall, the injury incidence rate was 0.85 sprains per 1000 person-days of exposure to sport. There were 0.68 and 0.97 ankle sprains per 1000 person-days of exposure to sport for the men and women, respectively. Although the risk of suffering an ankle sprain was higher for women than for men (relative risk, 1.51), the difference was not statistically significant (P = .21) and was owing to the increased risk in female basketball athletes compared to male basketball athletes (relative risk, 4.11; P = .045). Risk of injury was similar for the high school athletes in comparison to the college athletes (relative risk, 1.16). For the men, there was no difference in the risk of suffering an ankle sprain between the sports of basketball, soccer, and lacrosse, whereas for the women, the risk of suffering an ankle sprain was significantly greater during participation in basketball compared to lacrosse. CONCLUSION: In this study of first-time ankle sprains, for most sports, the incidence rate of inversion injury is less than 1 per 1000 days of exposure to sport, a value lower than previously reported. Among female athletes, ankle injury is associated with type of sport. Risk is highest for female basketball athletes, who are at significantly greater risk than male basketball athletes and female lacrosse athletes. The risk of first-time ankle injury is similar for high school and college-level athletes.

Adolescent↗
PubMed1994

A comprehensive study of pressure distribution in the ankle joint with inversion and eversion.

The understanding of load transfer characteristics is the baseline for biomechanics of the ankle joint. Changes in contact patterns of the articular cartilage from the norm may indicate pathologic conditions. Measurement of the contact in human cadaver ankles provides a direct measurement for this understanding. The force transfer characteristics of the three facets of the ankle joint were investigated. Five fresh-frozen cadaver lower extremities were tested in 12 positions under three axial loads of 490, 686, and 980 N. Fuji film served as the pressure transducer and the prints were analyzed by a computerized video digitizer. The results demonstrated that as the foot was moved into inversion or eversion with the ankle in neutral flexion or dorsiflexion, there was a decrease in total contact area and an increase in the average high pressure. In plantarflexion, the contact area was lower and the average high pressure was higher, indicating a greater force per unit area as compared with dorsiflexion and neutral flexion. In plantarflexion, however, little change was noted with inversion or eversion. In dorsiflexion, the total contact area was higher and the average high pressure slightly lower as compared with neutral flexion. With inversion, the contact area of the medial facet of the ankle increased and with eversion it increased on the lateral facet, especially in dorsiflexion. With an increase in loading, the pressure did not significantly increase but the contact area did increase. The centroid of the contact moved anteriorly to posteriorly on the talus as the joint moved from dorsiflexion to plantar-flexion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Inversely planned intensity modulated radiotherapy of the breast including the internal mammary chain: a plan comparison study.

The aim of this paper is to evaluate the benefit of inversely planned intensity modulated radiotherapy (IMRT) in the adjuvant irradiation of breast cancer when internal mammary lymph nodes are included in the treatment volume. 20 patients treated with 3D-planned conventional radiotherapy (CRT) following breast conserving surgery were included in the study. We chose 10 patients with left-sided and 10 patients with right-sided tumors. All treatment volumes included the internal mammary chain. For plan comparison to the applied CRT plan an inverse IMRT-plan in, step-and-shoot'-technique was calculated. For all patients IMRT resulted in an improved conformity of dose distribution to the target volume compared to CRT (mean COIN95: 0.798 vs. 0.514 with COIN95 = C1 * C2 (C1= fraction of CTV that is covered by > 95% of the prescribed dose and C2 = volume of CTV that is covered by > 95% of the prescribed dose/total volume that is covered by > 95% of the prescribed dose). In all cases with matching adjacent beams, the homogeneity in the target volume was improved. The volume of the ipsilateral lung irradiated with a dose higher than 20 Gy was reduced with IMRT from 24.6% to 13.1% compared to CRT. For left-sided target volume the heart volume with a dose higher than 30 Gy was reduced from 6.2% to 0.2%. The presented plan comparison study for irradiation of the breast and the parasternal lymph nodes showed a substantial improvement of the dose distribution by inversely planned IMRT compared to CRT. This is visible for the target volume, the ipsilateral lung and, in case of left-sided target volume, the heart. Despite an increase in integral dose to the entire normal tissue, the application of IMRT might be clinically advantageous in cases where no satisfying dose distribution can be obtained by CRT.

Breast Neoplasms↗
PubMed2003

Enhanced spontaneous activity of the mu opioid receptor by cysteine mutations: characterization of a tool for inverse agonist screening.

BACKGROUND: The concept of spontaneous- or constitutive-activity has become widely accepted and verified for numerous G protein-coupled receptors and this ligand-independent activity is also acknowledged to play a role in some pathologies. Constitutive activity has been reported for the mu opioid receptor. In some cases the increase in receptor basal activity was induced by chronic morphine administration suggesting that constitutive activity may contribute to the development of drug tolerance and dependence. Constitutively active mutants represent excellent tools for gathering information about the mechanisms of receptor activation and the possible physiological relevance of spontaneous receptor activity. The high basal level of activity of these mutants also allows for easier identification of inverse agonists, defined as ligands able to suppress spontaneous receptor activity, and leads to a better comprehension of their modulatory effects as well as possible in vivo use. RESULTS: Cysteines 348 and 353 of the human mu opioid receptor (hMOR) were mutated into alanines and Ala348,353 hMOR was stably expressed in HEK 293 cells. [35S] GTPgammaS binding experiments revealed that Ala348,353 hMOR basal activity was significantly higher when compared to hMOR, suggesting that the mutant receptor is constitutively active. [35S] GTPgammaS binding was decreased by cyprodime or CTOP indicating that both ligands have inverse agonist properties. All tested agonists exhibited binding affinities higher for Ala348,353 hMOR than for hMOR, with the exception of endogenous opioid peptides. Antagonist affinity remained virtually unchanged except for CTOP and cyprodime that bound the double mutant with higher affinities. The agonists DAMGO and morphine showed enhanced potency for the Ala348,353 hMOR receptor in [35S] GTPgammaS experiments. Finally, pretreatment with the antagonists naloxone, cyprodime or CTOP significantly increased Ala348,353 hMOR expression. CONCLUSION: Taken together our data indicate that the double C348/353A mutation results in a constitutively active conformation of hMOR that is still activated by agonists. This is the first report of a stable CAM of hMOR with the potential to screen for inverse agonists.

Alanine↗
PubMed2006

Inverse association of antioxidant and phytoestrogen nutrient intake with adult glioma in the San Francisco Bay Area: a case-control study.

BACKGROUND: Increasing evidence from epidemiologic studies suggest that oxidative stress may play a role in adult glioma. In addition to dietary antioxidants, antioxidant and weak estrogenic properties of dietary phytoestrogens may attenuate oxidative stress. Our hypothesis is that long-term consumption of dietary antioxidants and phytoestrogens such as genistein, daidzein, biochanin A, formononetin, matairesinol, secoisolariciresinol and coumestrol, may reduce the risk of adult glioma. METHODS: Using unconditional logistic regression models, we compared quartiles of consumption for several specific antioxidants and phytoestrogens among 802 adult glioma cases and 846 controls from two study series from the San Francisco Bay Area Adult Glioma Study, 1991-2000, controlling for vitamin supplement usage, age, socioeconomic status, gender, ethnicity and total daily calories. For cases, dietary information was either self-reported or reported by a proxy. For controls, dietary information was self-reported. Gender- and series-specific quartiles of average daily nutrient intake, estimated from food-frequency questionnaires, were computed from controls. RESULTS: Significant p-values (trend test) were evaluated using significance levels of either 0.05 or 0.003 (the Bonferroni corrected significance level equivalent to 0.05 adjusting for 16 comparisons). For all cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.003), carotenoids (alpha- and beta-carotene combined, p < 0.05), daidzein (p = 0.003), matairesinol (p < 0.05), secoisolariciresinol (p < 0.003), and coumestrol (p < 0.003). For self-reported cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.05) and daidzein (p < 0.05). CONCLUSION: Our results support inverse associations of glioma with higher dietary antioxidant index and with higher intake of certain phytoestrogens, especially daidzein.

Adult↗
PubMed2006

Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment.

BACKGROUND: Presenting the initial clinical results in the treatment of complex shaped adenoid cystic carcinomas (ACC) of the head and neck region by inverse planned stereotactic IMRT. MATERIALS: 25 patients with huge ACC in different areas of the head and neck were treated. At the time of radiotherapy two patients already suffered from distant metastases. A complete resection of the tumor was possible in only 4 patients. The remaining patients were incompletely resected (R2: 20; R1: 1). 21 patients received an integrated boost IMRT (IBRT), which allow the use of different single doses for different target volumes in one fraction. All patients were treated after inverse treatment planning and stereotactic target point localization. RESULTS: The mean follow-up was 22.8 months (91-1490 days). According to Kaplan Meier the three year overall survival rate was 72%. 4 patients died caused by a systemic progression of the disease. The three-year recurrence free survival was according to Kaplan Meier in this group of patients 38%. 3 patients developed an in-field recurrence and 3 patient showed a metastasis in an adjacent lymph node of the head and neck region. One patient with an in-field recurrence and a patient with the lymph node recurrence could be re-treated by radiotherapy. Both patients are now controlled. Acute side effects >Grade II did only appear so far in a small number of patients. CONCLUSION: The inverse planned stereotactic IMRT is feasible in the treatment of ACC. By using IMRT, high control rates and low side effects could by achieved. Further evaluation concerning the long term follow-up is needed. Due to the technical advantage of IMRT this treatment modality should be used if a particle therapy is not available.

Adult↗
PubMed2006

Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis.

Mutations of mitochondrial DNA (mtDNA) are an important cause of genetic disease, yet rarely present in the neonatal period. Here we report the clinical, biochemical, and molecular genetic findings of an infant who died at the age of 1 mo with marked biventricular hypertrophy, aortic coarctation, and severe lactic acidosis due to a previously described but unusual mtDNA mutation, a 7-bp intragenic inversion within the mitochondrial gene encoding ND1 protein of complex I (MTND1). In direct contrast to the previous case, an adult with exercise intolerance who only harbored the mutation in muscle, the MTND1 inversion in our patient was present at high levels in several tissues including the heart, muscle, liver, and cultured skin fibroblasts. There was no evidence of the mutation or respiratory complex I defect in a muscle biopsy from the patient's mother. Transmitochondrial cytoplasmic hybrids (cybrids) containing high mutant loads of the inversion expressed the biochemical defect but apparently normal levels of the assembled complex. Our report highlights the enormous phenotypic diversity that exists among pathogenic mtDNA mutations and reemphasizes the need for appropriate genetic counseling for families affected by mtDNA disease.

Acidosis, Lactic↗