bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenoleukodystrophy: Biochemical procedures in diagnosis, prevention and treatment
Authors: Watkins P. A. , Naidu S. , Moser H. W. 
Published: June 2005

AbstractThe childhood form of adrenoleukodystrophy is an X‐linked recessive disorder which is characterized biochemically by elevated concentrations of saturated very long chain fatty acids in tissues and plasma and impaired very long chain fatty acid oxidation in fibroblasts and leukocytes from adrenoleukodystrophy patients. The most consistently observed increase is that in hexacosanoic acid (C26:0); thus, measurement of plasma C26:0 concentration by gas‐liquid chromatography provides a rapid, sensitive method of diagnosis. Prenatal diagnosis of adrenoleukodystrophy can be made by measurement of C26:0 concentrations in amniocytes and chorionic villus cells. Heterozygote (carrier) detection has also been accomplished by biochemical measurement of C26:0 in plasma and skin fibroblasts. In a study of over 200 obligate heterozygotes, >90% showed abnormal concentrations of C26:0. Hybridization studies using the cloned DNA fragment St14 detects polymorphisms in the distal end of the long arm of the X chromosome (Xq27–28) and six informative kindreds have shown co‐segregation of adrenoleukodystrophy and the St14 marker through 65 meioses. Thus, such studies can supplement very long chain fatty acid concentrations in heterozygote detection. Therapeutic interventions for adrenoleukodystrophy, such as dietary restriction of very long chain fatty acids, administration of clofibrate or carnitine, immunosuppression and adrenal hormone replacement, have not been successful. Recently, a modification of the very long chain fatty acid‐restricted diet has been employed in which this diet is supplemented with synthetic glycerol trioleate. The rationale for this diet is that decreased very long chain fatty acid synthesis by fibroblasts from patients with adrenoleukodystrophy was observed when oleic acid was added to the culture medium. In a study of 14 patients on this diet from 2 to 11 months, there was a mean reduction in plasma C26:0 levels of 46%, with one patient achieving a normal plasma level. The effect of lowering plasma very long chain fatty acid concentrations on the neurologic status of patients with adrenoleukodystrophy and on the development of symptoms in asymptomatic individuals with elevated very long chain fatty acid concentrations remains to be established.
Morphological observations in skeletal muscle from patients with a mitochondrial myopathy
Authors: Stadhouders A. M. , Sengers R. C. A. 
Published: June 2005

AbstractMitochondrial metabolic dysfunction is considered to be the cause of certain congenital myopathies and a number of multisystem disorders in humans. The morphological hallmark of these diseases is the ‘ragged red’ fibre, which shows abnormally intensive oxidative enzyme reactions. Electron microscopy reveals that the numerically increased mitochondria in these fibres are often markedly enlarged and possess aberrant configurations of cristae. The mitochondrial matrix often contains lipid‐like inclusions or shows vacuolation. The most characteristic mitochondrial abnormality is the occurrence of highly ordered inclusions in the intracristal or intermembrane space. These inclusions appear to be true crystals, composed of proteinaceous material. It is argued that the activity of accumulation of proteins in the mitochondria is related to the nuclear and nucleolar hypertrophy noticeable in the ragged red fibres. Since protein crystals in mitochondria in particular occur when an increased capillary density around the ragged red fibres is present, it is suggested that oxygen free radicals and lipid peroxidation processes are involved in the ragged red fibre pathology.
Defects in oxidative phosphorylation. Biochemical investigations in skeletal muscle and expression of the lesion in other cells
Authors: Scholte H. R. , Busch H. F. M. , Luyt‐Houwen I. E. M. , Vaandrager‐Verduin M. H. M. , Przyrembel H. , Arts W. F. M. 
Published: June 2005

AbstractMitochondria are very vulnerable to genetic and environmental damage. If a patient is suspected of having a mitochondrial disease, elevated blood lactate, lowered blood free carnitine, abnormal urinary organic acids and carnitine esters and tissue histopathology may help with the diagnosis. For biochemical assessment of the defect, muscle is the tissue of choice even when involvement of other organs like heart or brain is more prominent.We have studied isolated muscle mitochondria and homogenates from muscle biopsies in 250 patients, and have detected in more than one third mitochondrial defects in oxidative phosphorylation, dehydrogenases, non‐redox enzymes catalyzing synthesis of fuel molecules and in the carnitine system. Several patients showed more than one defect.We have selected eight patients to illustrate how a relatively simple series of investigations in both isolated mitochondria and homogenate can be used for the identification of defects in oxidative phosphorylation in a small amount of muscle (200 mg or more). Identification of the defect(s) is important since it may provide the basis for rational treatment. A minority of the patients recovered partly or completely, which is unique in treatment of inborn errors of subcellular organelles.An important aspect of mitochondrial dysfunction is the tissue specificity. The defect may be systemic but is often clinically expressed in only one or a few tissues. Rarely, tissue‐specific defects can be understood on the basis of tissue‐specificity of mitochondrial (iso‐)enzymes. Mitochondrial deficiencies of all biotin enzymes and most CoA‐linked enzymes are expressed in fibroblasts; most respiratory chain defects are not.When mitochondrial ATP synthesis has been compromised by a mitochondrial defect, secondary lesions may be generated by changes in mitochondrial protein synthesis, activated proteases and phospholipases, increased matrix CoA and resulting carnitine deficiency, decrease in Krebs cycle intermediates and increased free radical formation and lipid peroxidation.
A model for hyperphenylalaninaemia due to tetrahydrobiopterin deficiency
Authors: Cotton R. G. H. 
Published: June 2005

AbstractA model for tetrahydrobiopterin deficiency in mice is described. Elevated levels of phenylalanine produced in the model were shown to be dramatically reduced after injection of tetrahydrobiopterin. A comparison of several reduced pterins for their efficacy in the system is described. The unnatural S isomer of tetrahydrobiopterin was shown to be active in the system.
Enzyme activities and phospholipid storage patterns in brain and spleen samples from niemann‐pick disease variants: a comparison of neuropathic and non‐neuropathic forms
Authors: Besley G. T. N. , Elleder M. 
Published: June 2005

AbstractPhospholipid levels and enzyme activities were measured in brain and spleen samples from patients with the three major variants of Niemann‐Pick disease. Accumulations of sphingomyelin and bis(monoacylglycero)phosphate were demonstrated in spleen from types A and B and group C Niemann‐Pick disease, whereas only in type A Niemann‐Pick brain was the sphingomyelin concentration increased. Sphingomyelinase activity was markedly deficient in type A Niemann‐Pick brain and spleen but residual activity of approximately 12% of control was measured in type B Niemann‐Pick brain. Normal or raised sphingomyelinase and β‐glucosidase activities were measured in group C Niemann‐Pick brain and spleen. Significant (17% of control) residual β‐glucosidase activity was also measured in non‐neuropathic Gaucher brain. Normal levels of neutral sphingomyelinase activity were measured in brain samples from the three variants of Niemann‐Pick disease. Acid sphingomyelinase activity in group C Niemann‐Pick brain appeared normal with respect to enzyme extraction, pH optimum (pH5.0) and apparentKm (approximately 0.4 mmol/L). Isoelectric focusing of brain sphingomyelinase revealed a degree of heterogeneity with activity peaks between pI 4.5 and 6.5. No defect was observed in group C Niemann‐Pick brain and, although attenuated, all peaks were present in type B Niemann‐Pick brain.
Development of a protocol for newborn screening for disorders of the galactose metabolic pathway
Authors: Bowling F. G. , Brown A. R. D. 
Published: June 2005

AbstractThe protocol evaluated in this paper employs an enzymatic assay of galactose metabolites, thin layer chromatography, and an assay of galactose‐1‐phosphate uridyl transferase on a single sample of blood collected routinely for newborn screening. Its effectiveness was tested by a retrospective study of known galactosaemic blood samples, and also by a prospective study of 207 000 newborn samples from which 6 infants with severe transferase deficient galactosaemia and 2 infants with red cell epimerase deficiency were identified. The detection rate for severe transferase deficiency in the newborn population was 1:35 000. Advantages include low false positive rate, definitive diagnosis within 6 hours of sample receipt, and the use of technically simple and robust procedures. This protocol overcomes the difficulties encountered with previously described procedures.
Usefulness of an Estimation of Physiologic Ability and Surgical Stress (E‐PASS) Scoring System to Predict the Incidence of Postoperative Complications in Gastrointestinal Surgery
Authors: Oka Yoshio , Nishijima Junichi , Oku Kunihiko , Azuma Tatsuo , Inada Keiji , Miyazaki Satoru , Nakano Hiroshi , Nishida Yukihiro , Sakata Kazuya , Izukura Masaaki 
Published: June 2005

AbstractSurgical intervention induces various host responses to maintain homeostasis. When postoperative inflammation is intense and persists for a long time, postoperative complications may occur, sometimes developing into multiple organ failure. Therefore, it is very important to assess surgical stress and predict the risk of morbidity and mortality. Using a new scoring system, an estimation of physiologic ability and surgical stress (E‐PASS) scoring system, surgical stress following gastrointestinal surgery was evaluated to assess the feasibility of this scoring system. This system comprises a preoperative risk score (PRS), a surgical stress score (SSS), and a comprehensive risk score (CRS) that is calculated from both the PRS and the SSS. The relationship of the E‐PASS score to the incidence of morbidity and mortality was examined. The relationship between the E‐PASS score and a sequential organ failure (SOFA) score was also evaluated. The CRS had a significant positive correlation between not only the incidence but also the grade of postoperative complications. Total maximum SOFA score in patients with a CRS of more than 1 was significantly higher than that in patients with a CRS of less than 1. In conclusion, the E‐PASS scoring system will be useful for predicting and recognizing the risk of postoperative complications. This scoring system is brief, simple, and reproducible and can be useful in all types of hospitals.
Groin Hernia Repair: Open Techniques
Authors: Amid Parviz K. 
Published: June 2005

AbstractSince the introduction of the Bassini method in 1887, more than 70 types of pure tissue repair have been reported in the surgical literature. An unacceptable recurrence rate and prolonged postoperative pain and recovery time after tissue repair along with our understanding of the metabolic origin of inguinal hernias led to the concept of tension‐free hernioplasty with mesh. Currently, the main categories of inguinal hernia repair are the open repairs and the laparoscopic repairs. In the open category, repair of the hernia is achieved by pure tissue approximation or by tension‐free mesh repair. The most commonly performed tissue repairs are those of Bassini, Shouldice, and to a lesser extent McVay. In the tension‐free mesh repair category, the mesh is placed in front of the transversalis fascia, such as with the Lichtenstein tension‐free hernioplasty, or behind the transversalis fascia in the preperitoneal space, such as during the Nyhus, Rives, Read, Stoppa, Wantz, and Kugel procedures. Numerous comparative randomized trials have clearly demonstrated the superiority of the tension‐free mesh repair over the traditional tissue approximation method. Placing mesh behind the transversalis fascia, although a sound concept, requires extensive dissection in the highly complex preperitoneal space and can lead to injury of the pelvic structures, major hematoma formation, or both. In addition, according to the prospective randomized comparative study of mesh placement in front of versus behind the transversalis fascia, the latter offers no advantage over the former, and it is more difficult to perform, learn, and teach. More importantly, preperitoneal mesh implantation (via open and laparoscopic procedure) leads to obliteration of the spaces of Retzius and Bogros, making certain vascular and urologic procedures, in particular radical prostatectomy and lymph node dissection, extremely difficult if not impossible. In conclusion, according to level A evidence from randomized comparative studies, (1) mesh repair is superior to pure tissue approximation repairs, and (2) mesh implantation in front of the transversalis fascia is superior, safer, and easier than open or laparoscopic mesh implantation behind the transversalis fascia.
Groin Hernia Repair: Anesthesia
Authors: Kehlet Henrik , Aasvang Eske 
Published: June 2005

AbstractThe choice of anesthesia for groin hernia repair is between general, regional (epidural or spinal), and local anesthesia. Existing data from large consecutive patient series and randomized studies have shown local anesthesia to be the method of choice because it can be performed by the surgeon, does not necessarily require an attending anesthesiologist, translates into the shortest recovery (bypassing the postanesthesia care unit), has the lowest cost, and has the lowest postoperative morbidity regarding risk of urinary retention. Spinal anesthesia has no documented benefits for this small operation and should be avoided owing to the risk of rare neurologic side effects and the high risk of urinary retention. General anesthesia with short‐acting agents may be a valid alternative when combined with local infiltration anesthesia, although an anesthesiologist is required. Despite sufficient scientific data to support the choice of anesthesia, large epidemiologic and nationwide information from databases show an undesirable high (about 10–20%) use of spinal anesthesia and low (about 10%) use of local infiltration anesthesia. Surgeons and anesthesiologists should therefore adjust their anesthesia practices to fit the available scientific evidence.
Incisional Hernia: Open Techniques
Authors: Klinge Uwe , Conze Joachim , Krones Carsten J. , Schumpelick Volker 
Published: June 2005

AbstractEven with the routine use of mesh, repairing an incisional hernia is a challenge. Increasing evidence of impaired wound healing in these patients supports routine use of an open prefascial, retromuscular mesh repair. Basic pathophysiologic principles dictate that for a successful long‐term outcome and prevention of recurrence a wide overlap underneath healthy tissue is required. The extent of this overlap should be 5 cm in all directions: surrounding the wound closure, subxiphoidal underneath the ribs, below the arcuate line, and retropubic.
Incisional Hernia Repair: Laparoscopic Techniques
Authors: LeBlanc Karl A. 
Published: June 2005

AbstractRepair of incisional hernias using the laparoscopic technique has continued to evolve since its inception in 1991. An analysis of the current literature has revealed that hernias as large as 1600 cm2 have been successfully repaired with this method. The average size appears to be about 105 cm2. Several choices of a biomaterial are available today, differing in the type of synthetic product or products that are used to manufacture them. Others incorporate an absorbable component. The goal of all of them is to prevent adhesion formation. The fixation devices that can be used are also varied. The results of laparoscopic incisional hernia repair are described. The conversion rate of these procedures is an impressive 2.4% with an enterotomy rate of 1.8%. These results affirm the low risk of this operation. The recurrence rate of 4.2% confirms the permanence of the repair. This procedure may become the standard of care in the near future.
Can attitudes of stoicism and cautiousness explain observed age‐related variation in levels of self‐rated pain, mood disturbance and functional interference in chronic pain patients?
Authors: Yong Hua‐Hie 
Published: June 2005

AbstractThe aims of the present study were (a) to examine the relationship between age, attitudes and self‐reported pain and suffering in a sample of chronic pain patients and (b) to determine the extent to which attitudes of stoicism and cautiousness might mediate between age and chronic pain experience. Psychometric measures were administered to 338 chronic pain patients. The results indicate that there were significant relationships between both age and attitudes with measures of pain, mood disturbance and functional interference. Attitudes were found to provide either a full or partial mediation of the relationship between age and various measures of chronic pain experience, thus emphasizing the importance of including these cognitive variables for clinical assessment. It appears that attitudes of stoicism may be more important than age as a predictor of self‐reported pain severity. However, with respect to mood and functional disturbance, age and perhaps, other age‐related factors, remain important additional predictors.
Spironolactone and its main metabolite canrenoic acid block hKv1.5, Kv4.3 and Kv7.1+minK channels
Authors: Gómez Ricardo , Núñez Lucía , Caballero Ricardo , Vaquero Miguel , Tamargo Juan , Delpón Eva 
Published: June 2005

Both spironolactone (SP) and its main metabolite, canrenoic acid (CA), prolong cardiac action potential duration and decrease the Kv11.1 (HERG) current. We examined the effects of SP and CA on cardiac hKv1.5, Kv4.3 and Kv7.1+minK channels that generate the human IKur, Ito1 and IKs, which contribute to the control of human cardiac action potential duration.
hKv1.5 currents were recorded in stably transfected mouse fibroblasts and Kv4.3 and Kv7.1+minK in transiently transfected Chinese hamster ovary cells using the whole‐cell patch clamp.
SP (1 μM) and CA (1 nM) inhibited hKv1.5 currents by 23.2±3.2 and 18.9±2.7%, respectively, shifted the midpoint of the activation curve to more negative potentials and delayed the time course of tail deactivation.
SP (1 μM) and CA (1 nM) inhibited the total charge crossing the membrane through Kv4.3 channels at +50 mV by 27.1±6.4 and 27.4±5.7%, respectively, and accelerated the time course of current decay. CA, but not SP, shifted the inactivation curve to more hyperpolarised potentials (Vh−37.0±1.8 vs −40.8±1.6 mV, n=10, P<0.05).
SP (10 μM) and CA (1 nM) also inhibited Kv7.1+minK currents by 38.6±2.3 and 22.1±1.4%, respectively, without modifying the voltage dependence of channel activation. SP, but not CA, slowed the time course of tail current decay.
CA (1 nM) inhibited the IKur (29.2±5.5%) and the Ito1 (16.1±3.9%) recorded in mouse ventricular myocytes and the IK (21.8±6.9%) recorded in guinea‐pig ventricular myocytes.
A mathematical model of human atrial action potentials demonstrated that K+ blocking effects of CA resulted in a lengthening of action potential duration, both in normal and atrial fibrillation simulated conditions.
The results demonstrated that both SP and CA directly block hKv1.5, Kv4.3 and Kv7.1+minK channels, CA being more potent for these effects. Since peak free plasma concentrations of CA ranged between 3 and 16 nM, these results indicated that blockade of these human cardiac K+ channels can be observed after administration of therapeutic doses of SP.
Blockade of these cardiac K+ currents, together with the antagonism of the aldosterone proarrhythmic effects produced by SP, might be highly desirable for the treatment of supraventricular arrhythmias.

British Journal of Pharmacology (2005) 146, 146–161. doi:10.1038/sj.bjp.0706302
Sympathetic and Hemodynamic Effects of Moderate and Deep Sedation with Propofol in Humans
Authors: Ebert Thomas J. 
Published: June 2005

Background
The objective of this study was to determine the mechanisms involved in the hypotension associated with sedative doses of propofol in humans.

Methods
Ten healthy volunteers (aged 21-37 yr) participated on two occasions and in random order received placebo or propofol infusions. Standard monitoring and radial artery blood pressure were combined with measurement of forearm blood flow (plethysmography) and derivation of forearm vascular resistance, recording of peroneal nerve sympathetic activity, and blood sampling for norepinephrine concentrations. A computer-controlled infusion pump delivered placebo or two concentrations of propofol, adjusted to achieve moderate and deep sedation based on the Observer Assessment of Alertness/Sedation score (responsiveness component) of 4 and 3. Level of sedation was quantitated using bispectral analysis of the electroencephalogram. Baroreflexes were assessed with a hypotensive challenge via administration of sodium nitroprusside.

Results
Baseline neurocirculatory and respiratory parameters did not differ between sessions. Progressive infusions to achieve moderate and deep sedation resulted in average Bispectral Index values of 70 and 54, respectively. Propofol significantly reduced sympathetic nerve activity at both levels of sedation and decreased norepinephrine and forearm vascular resistance at deep sedation. These effects resulted in significant decreases in mean blood pressure of 9% and 18% at moderate and deep sedation, respectively. Propofol also reduced reflex increases in sympathetic nerve activity.

Conclusions
These data from healthy subjects indicate that sedation doses of propofol, which did not compromise respiratory function, had substantial inhibitory effects on sympathetic nerve activity and reflex responses to hypotension resulting in vasodilation and significant decreases in mean blood pressure.
Management of the Difficult Airway
Authors: Peterson Gene N. , Domino Karen B. , Caplan Robert A. , Posner Karen L. , Lee Lorri A. , Cheney Frederick W. 
Published: June 2005

Background
The purpose of this study was to identify the patterns of liability associated with malpractice claims arising from management of the difficult airway.

Methods
Using the American Society of Anesthesiologists Closed Claims database, the authors examined 179 claims for difficult airway management between 1985 and 1999 where a supplemental data collection tool was used and focused on airway management, outcomes, and the role of the 1993 Difficult Airway Guidelines in litigation. Chi-square tests and multiple logistic regression analysis compared risk factors for death or brain damage (death/BD) from two time periods: 1985-1992 and 1993-1999.

Results
Difficult airway claims arose throughout the perioperative period: 67% upon induction, 15% during surgery, 12% at extubation, and 5% during recovery. Death/BD with induction of anesthesia decreased in 1993-1999 (35%) compared with 1985-1992 (62%; P < 0.05; odds ratio, 0.26; 95% confidence interval, 0.11-0.63; P = 0.003). In contrast, death/BD associated with other phases of anesthesia did not significantly change over the time periods. The odds of death/BD were increased by the development of an airway emergency (odds ratio, 14.98; 95% confidence interval, 6.37-35.27; P < 0.001). During airway emergencies, persistent intubation attempts were associated with death/BD (P < 0.05). Since 1993, the Airway Guidelines were used to defend care (8%) and criticize care (3%).

Conclusions
Death/BD in claims from difficult airway management associated with induction of anesthesia but not other phases of anesthesia decreased in 1993-1999 compared with 1985-1992. Development of additional management strategies for difficult airways encountered during maintenance, emergence, or recovery from anesthesia may improve patient safety.