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Comparison of aconitine-modified human heart (hH1) and rat skeletal (mu1) muscle Na+ channels: an important role for external Na+ ions.

Neurotoxins such as aconitine (AC) bind to receptor site 2 on voltage-gated sodium channels and modify channel kinetics. Although AC modification typically induces hyperpolarizing shifts in sodium channel activation, the effects on channel inactivation seem to vary depending on the tissue origin of the channel. In the present study, the alpha subunits of human heart (hH1) and rat skeletal muscle (mu1) sodium channels were transiently expressed in human embryonic kidney (HEK293t) cells. Whole-cell currents were examined before and after AC modification of the channels to determine whether the toxin had isoform-specific effects on channel kinetics. The magnitudes of the hyperpolarizing shifts in steady-state current activation and inactivation were similar for AC-modified hH1 and mu1 channels, and AC modification did not alter the voltage dependence of macroscopic current decay of either channel subtype. There were two notable differences between hH1 and mu1 channels after AC modification. First, the steady-state availability of AC-modified mu1 channels decreased by 5-10% after very negative conditioning pulses. Second, AC-modified mu1 channels inactivated completely at all voltages, whereas AC-modified hH1 channels exhibited sustained inward currents at voltages near the threshold of current activation. Interestingly, AC-modified hH1 channels inactivated completely if the external solution did not contain sodium ions. The data demonstrate that AC modification affects the activation of hH1 and mu1 channels similarly but affects inactivation of the two channels distinctly. The results also imply that the reduced inactivation of AC-modified hH1 channels at least partially depends on the presence of extracellular sodium.

Aconitine↗

Identification of Salmonella somatic and flagellar antigens by modified serological methods.

This report describes two modified methods for the identification of Salmonella somatic (O) and flagellar (H) antigens. Over a period of 2 years, both modified methods were found to be approximately three times less labor intensive than the standard methods while requiring no more technical skill. The modified methods were as accurate as the standard methods in identifying the O and H antigens of 350 Salmonella isolates. Furthermore, 43 O antisera reacted exclusively with organisms possessing homologous O antigens when the modified and two standard methods were used. At the antiserum dilutions used for H antigen identification, H antisera did not react with O antigens or heterologous H antigens by either the modified or the standard method. Compared with the standard method for H antigen identification, the modified method was approximately 20 times more economical with respect to antisera and usually generated a 1.5- to 4-fold higher titer. Since the antisera stored for use in the modified method for H antigen identification were usually 100-fold more dilute than the antisera stored for the standard method, an antibody-stabilizing buffer was incorporated in the diluted antisera, allowing these reagents to be used for at least 9 to 16 months.

Agglutination Tests↗

Outer membrane of Pseudomonas aeruginosa: heat- 2-mercaptoethanol-modifiable proteins.

A number of polyacrylamide gel systems and solubilization procedures were studied to define the number and nature of "major" polypeptide bands in the outer membrane of Pseudomonas aeruginosa. It was shown that five of the eight major outer membrane proteins were "heat modifiable" in that their mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was determined by the solubilization temperature. Four of these heat-modifiable proteins had characteristics similar to protein II of the Escherichia coli outer membrane. Addition of lipopolysaccharide subsequent to solubilization caused reversal of the heat modification. The other heat-modifiable protein, the porin protein F, was unusually stable to sodium dodecyl sulfate. Long periods of boiling in sodium dodecyl sulfate were required to cause conversion to the heat-modified form. This was demonstrated both with outer membrane-associated and purified lipopolysaccharide-depleted protein F. Furthermore, lipopolysaccharide treatment had no effect on the mobility of heat-modified protein F. Thus it is concluded that protein F represents a new class of heat-modifiable protein. It was further demonstrated that the electrophoretic mobility of protein F was modified by 2-mercaptoethanol and that the 2-mercaptoethanol and heat modification of mobility were independent of one another. The optimal conditions for the examination of the outer membrane proteins of P. aeruginosa by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis are discussed.

Bacterial Proteins↗

Prevention of cardiovascular diseases: focus on modifiable cardiovascular risk.

OBJECTIVE: To determine whether the use of a 20% absolute risk threshold for cardiovascular disease as recommended in current guidelines leads to exclusion of patients with a substantial modifiable risk (> or = 5%). METHODS: Data collected within the framework of a randomised controlled trial in three primary health care centres located in deprived neighbourhoods were analysed. The 10 year absolute risk and the modifiable part of risk were calculated by using the Framingham risk equation. Among patients with a modifiable risk reduction of > or = 5% (number needed to treat < or = 20) the characteristics and risk factors of patients with an absolute risk > or = 20% and those with an absolute risk < 20% were compared. RESULTS: 293 patients aged 30-70 years at risk of developing cardiovascular disease were included, of whom 66% were women and 36% were of Dutch origin. Of all patients, 33% had an absolute risk > or = 20% and 61% had a modifiable risk > or = 5%. Of those at > or = 20% absolute risk, a vast majority (98%) had a modifiable risk > or = 5%. Among those with an absolute risk < 20%, 43% had a modifiable risk > or = 5%; this group, who were relatively young and predominantly women, constituted 29% of the entire study population. CONCLUSIONS: Targeting preventive strategies at a 10 year absolute risk > or = 20% leads to exclusion of a large group of relatively young, predominantly female patients. In total, about one quarter had an absolute risk < 20% but a modifiable risk > or = 5% and should therefore benefit from intervention.

Adult↗

Diffusion-weighted MR imaging in closed head injury: high correlation with initial glasgow coma scale score and score on modified Rankin scale at discharge.

PURPOSE: To determine whether diffusion-weighted magnetic resonance (MR) imaging findings and conventional MR imaging findings correlate with initial Glasgow Coma Scale score and score on modified Rankin scale at discharge. MATERIALS AND METHODS: Twenty-six patients (18 male and eight female patients; mean age, 25.2 years; age range, 4-72 years) with diffuse axonal injury were examined with diffusion-weighted MR imaging and with fluid-attenuated inversion recovery, T2-weighted fast spin-echo, and T2*-weighted gradient-echo sequences. All images were evaluated by two neuroradiologists in consensus. Tissue volume with trauma-related signal-intensity abnormality on images from each sequence, number of lesions for each sequence, number of lesions for all sequences, and number of lesions with reduced apparent diffusion coefficient were correlated with scores on Glasgow Coma Scale and modified Rankin scale. Involvement of brainstem, deep gray matter, and corpus callosum were also correlated with clinical scores. Spearman rank correlation coefficients (r) were calculated. RESULTS: The strongest correlation was between signal-intensity abnormality volume on diffusion-weighted images and modified Rankin score (r = 0.772, P <.001). The strength of this correlation did not improve when only volume of lesions with decreased apparent diffusion coefficient was considered. For lesion number, the strongest correlation was between lesion number on images acquired with all sequences and modified Rankin score (r = 0.662, P <.001). For lesion location, the strongest correlation was between lesion location in the corpus callosum and modified Rankin score (r = 0.513, P =.007). CONCLUSION: Volume of lesions on diffusion-weighted MR images provides the strongest correlation with a score of subacute on modified Rankin scale at discharge. Total lesion number also correlates well with modified Rankin score. In future, diffusion-weighted images may be useful in determining treatment strategies for acute head injury.

Adolescent↗

Analysis of beta(2)-microglobulin kinetics in hemodialysis by a modified variable-volume one-compartment model.

It has been reported that deposition of beta(2)-microglobulin (BMG) is associated with the occurrence of dialysis-related amyloidosis (DRA) in long-term hemodialysis (HD) patients. Though reduction of the BMG burden is essential in preventing DRA, simple BMG kinetic models applicable to clinical practice have not been established. We have reported a modified variable-volume one-compartment model (1CM) for analyzing urea nitrogen (UN) kinetics, in which no specific parameters other than a modification factor are necessary. If there is a constant relation between the BMG concentration of the dialyzer arterial line and the mean BMG concentration in the body during HD, the modified 1CM may also be applied to BMG. As such, in order to verify its validity, we analyzed UN and BMG kinetics by the modified 1CM in 28 HD patients in whom polysulfone dialyzers were used, and compared the calculated and measured solute rebound. In 3 of the patients, the spent dialysate was collected in a tank, and the BMG removal mass, calculated by the modified 1CM, was compared with that recovered in the tank. The BMG rebound ratio (%), calculated by the modified 1CM, was not different from the measured one (36.3 +/- 9.9 vs. 36.5 +/- 11.5, p = 0.954), as in the case of UN (15.8 +/- 4.5 vs. 16.3 +/- 4.6, p = 0.541). The solute dilution in the blood circuit by solute disequilibrium and blood recirculations for BMG was estimated to be 74% stronger than that for UN. The normalized solute generation rate (mg/min/l) and the time-averaged solute concentration over a 1-week period (mg/l) were 0.142 +/- 0.023 and 448 +/- 68 for UN and 0.00578 +/- 0.00125 and 22.4 +/- 4.6 for BMG, respectively. The differences between these two solutes resulted in a Dilution index for BMG that was 23% lower than that for UN (2.62 +/- 0.44 vs. 3.21 +/- 0.39, p < 0.0001). The modified 1CM overestimated the BMG removal mass (mg) by about 20% compared with that recovered in the tank (195 +/- 22 vs. 162 +/- 17, p < 0.0001). One of the causes of this discrepancy was speculated to be adsorption of BMG by polysulfone dialyzers. It was concluded that, despite several problems in quantitative analysis, the modified 1CM would be a useful model for estimating the dialysis efficiency for BMG removal in clinical practice.

Adsorption↗

Multiple sclerosis, disease modifying treatments and depression: a critical methodological review.

BACKGROUND: Major depression affects one in two patients with multiple sclerosis (MS) during the course of their lifetime. This adds to the morbidity associated with the disorder and may contribute to an increased mortality rate because of suicide. Over the past few years, with the advent of disease modifying treatments for MS, a new concern with respect to mood has arisen, namely the possibility that some of these drugs may have depression as a clinically significant side effect. OBJECTIVE: To ascertain whether disease modifying treatments in MS are associated with the development of depression or the worsening of a depressive illness. METHODOLOGY: A MEDLINE and PSYCHLIT search focusing on depression and disease modifying treatments going back to 1993 (the publication date of the results of the first randomised, placebo controlled trial). The methodology pertaining to the assessment of depression is critically reviewed. Furthermore, a critical summary is provided of treatment modalities for the depressed MS patient. RESULTS: There are conflicting data that depression may occur with some disease modifying drugs, particularly interferon beta-1b. However, all studies reveal limitations with respect to the assessment of mood. Some reports, despite omitting details of how mentation was assessed, still comment on the presence or absence of depression. Others suffer from one or more of the following shortcomings: a failure to assess premorbid risk factors for mood disorder; a reliance on one question to assess depression; the utilisation of self report mood rating scales of questionable validity; neglecting to distinguish depression as a symptom from depression as a syndrome (i.e. major depression as defined by the DMS-1V). CONCLUSIONS: Given the many methodological pitfalls inherent in all studies to date, it is premature to conclude that disease modifying drugs are associated with depression. Evidence suggests that treatment of depression, irrespective of a putative association with a disease modifying agent, is frequently effective. This applies to pharmacotherapy or psychotherapy, although the former may be preferred should depression arise during a course of treatment with a disease modifying agent. Multiple Sclerosis (2000) 6 343 - 348

Major Depressive Disorder↗

Modified calcaneal index: a new screening tool for osteoporosis based on plain radiographs of the calcaneum.

PURPOSES: To assess osteoporosis using plain radiography of the calcaneum by studying the performance characteristics of the modified calcaneal index through inter- and intra-observer agreement. To study the correlation of the modified calcaneal index to quantitative ultrasound of the calcaneus and bone mineral density (BMD) of the femoral neck and distal radius. METHODS: Lateral calcaneal radiographs of 252 women who participated in a clinical trial for osteoporosis were reviewed. The BMD of the hip and distal radius was measured and the calcanea were assessed using ultrasound. The calcaneal radiographs were graded by 3 clinicians according to a previously described 5-grade calcaneal index. A modified 3-grade calcaneal index was then developed. RESULTS: The highest scores of intra- and inter-observer reliability of the modified calcaneal index were 0.45 and 0.40, respectively, which were higher than those of the 5-grade calcaneal index. The correlation of the modified calcaneal index with other measures was significant (hip BMD, r=0.31; distal radius BMD, r=0.28; calcaneal speed of sound, r=0.20; broadband ultrasound attenuation, r=0.36) [p<0.005]. There were significant differences in hip BMD, distal radial BMD, calcaneal speed of sound, and broadband ultrasound attenuation between the 3 grades of the modified calcaneal index (Kruskal-Wallis 1-way ANOVA; p<0.0001). CONCLUSION: The modified calcaneal index can be used to measure bone structure and skeletal strength and is a suitable screening tool for osteoporosis in places where advanced approaches to bone-status assessment are not available.

Absorptiometry, Photon↗

Leukotriene modifiers in pediatric asthma management.

Cysteinyl leukotrienes (Cys-LTs) are mediators released in asthma and virus-induced wheezing. Corticosteroids appear to have little or no effect on this release in vivo. Cys-LTs are both direct bronchoconstrictors and proinflammatory substances that mediate several steps in the pathophysiology of chronic asthma, including inflammatory cell recruitment, vascular leakage, and possibly airway remodeling. Blocking studies show that Cys-LTs are pivotal mediators in the pathophysiology of asthma. Cys-LTs are key components in the early and late allergic airway response and also contribute to bronchial obstruction after exercise and hyperventilation of cold, dry air in asthmatics. LT modifiers reduce airway eosinophil numbers and exhaled nitric oxide levels. Together these findings support an important role for the Cys-LTs in the asthma airway inflammation. Cys-LT receptor antagonists (Cys-LTRA) are generally well-tolerated. Phase III randomized, controlled clinical trials (RCT) show that LT modifiers are moderately effective, apparently with a particular between-patient variability in their clinical response. The clinical effects of LT modifiers are additive to those of beta-agonists and corticosteroids. The onset of action of LT modifiers is within 1 to several days, and not rapid enough to make them useful as rescue treatment. Although LT modifiers possess some antiinflammatory activity, they cannot substitute for corticosteroids for inflammation control. LT modifiers are alternatives to long-acting beta-agonists as complementary treatment to inhaled corticosteroids in pediatric asthma management because they provide bronchodilation and bronchoprotection without development of tolerance, and complement the antiinflammatory activity unchecked by steroids. In addition, the Cys-LTRA montelukast has been shown to ameliorate asthmatic symptoms and provide bronchoprotection in asthmatic preschool children from 2 years of age, which is of particular importance in this difficult-to-manage group of asthmatics. Given their efficacy, antiinflammatory activity, oral administration, and safety, LT modifiers will play an important role in the treatment of asthmatic children.

Acetates↗

Value and limitations of the von Reyn, Duke, and modified Duke criteria for the diagnosis of infective endocarditis in children.

OBJECTIVE: To compare the sensitivity of 3 different criteria-von Reyn, Duke, and modified Duke-in diagnosing infective endocarditis (IE) in children. STUDY DESIGN: Retrospective case study in a tertiary pediatric hospital. METHODS AND RESULTS: Between 1985 and 2001, 41 episodes of IE were documented in 40 children (median: 7 years old; range: 1 week to 18 years). The diagnosis was based on echocardiographic and microbiologic or pathologic findings. The initial echocardiogram suggested IE in 95% of the cases. Main findings were vegetations in 36, perivalvular abscess in 4, and/or new valvular leaks in 6 cases. In 31 (76%) of the 41 episodes, the causative organisms were identified directly by specimen bacteriology or blood cultures (BCs) or indirectly by polymerase chain reaction or serology. Sensitivities of the von Reyn, Duke, and modified Duke criteria in diagnosing IE were 63%, 81%, and 88%, respectively. In 10 cases (22%), the diagnosis of IE was "rejected" by the von Reyn criteria but was "definite or possible" by the Duke and modified Duke criteria. In 3 cases, the diagnosis of IE was "possible" by the Duke but "definite" by the modified Duke criteria: 2 of the 3 cases had 1 major and >or=3 minor symptoms, and 1 had Q fever. Five episodes (12%) were classified as "possible" IE by the modified Duke criteria: although major findings were present on echocardiography, no organism was identified on repeat BCs. Positive BC was the only criterion that differentiated "definite" from "possible" IE. CONCLUSIONS: The modified Duke classification was more sensitive in diagnosing IE in children than the von Reyn and Duke criteria. Still, 12% failed to be classified as "definite" IE by the modified Duke criteria. This illustrates the importance of positive BCs as a major IE criterion while significant echocardiographic findings are less considered by the presently used criteria.

Adolescent↗

Fluticasone is associated with lower asthma-related costs than leukotriene modifiers in a real-world analysis.

STUDY OBJECTIVE: To compare the impact of fluticasone propionate versus three leukotriene modifiers-montelukast, zafirlukast, and zileuton-on the cost of asthma within a managed care organization. DESIGN: Retrospective quasi-experimental comparison. SETTING: Managed care organization with approximately 350,000 enrollees. PATIENTS: Three hundred forty-seven patients with asthma who received at least two prescriptions for either fluticasone or a leukotriene modifier. Patients receiving both fluticasone and a leukotriene modifier were excluded. MEASUREMENTS AND MAIN RESULTS: Multivariate analysis was used to compare total asthma-related costs between treatment groups. A significant difference in total asthma-related costs was found between patients receiving fluticasone (adjusted mean cost $511) compared with those receiving a leukotriene modifier ($1,092; p=0.0001). Other significant predictors of postindex asthma-related costs were pre-index asthma-related costs, a severity adjustment score, and the diagnosis of chronic obstructive pulmonary disease. Patients taking a leukotriene modifier obtained more short-acting beta-agonists than patients receiving fluticasone (6.49 +/- 4.05 vs 4.30 +/- 3.41, p < 0.0001). A survival analysis of time to receive any additional controller therapy revealed that patients receiving fluticasone were significantly less likely to receive another controller than were those receiving a leukotriene modifier (p=0.0014). CONCLUSION: These results suggest that fluticasone is associated with lower asthma-related costs than leukotriene modifiers.

Adult↗

Rotational stability of a modified step-cut for use in intercalary allografts.

BACKGROUND: Intercalary allografts are used for the reconstruction of major skeletal defects. Step-cuts help to provide rotational stability when intramedullary fixation is used. A modified step-cut is proposed to reduce rotation at the interface. This study compares the rotational stability of conventional and modified step-cuts. METHODS: In Phase I, seven pairs of human cadaveric femora were divided into a conventional step-cut group (left femora) and a modified step-cut group (right femora). All femora were cut transversely at the mid-diaphysis. In the conventional group, a 1-cm step-cut was created in the exact midsagittal plane in both the proximal and distal segments. In the modified group, a 1-cm step-cut was created in the parasagittal plane, leaving 2 mm of additional bone on both the proximal and the distal fragment. Phase II was identical except that in the modified step-cut group only 1 mm of additional bone was left. Smooth femoral nails were then placed after standard reaming. Specimens were tested by fixing the proximal segment and applying +/-2 N-m (17.7 in-lb) of torque to the distal segments with ten oscillation cycles. Maximum rotation was measured. The data were analyzed with the paired Student t test. RESULTS: The average rotation in Phase I was 23.3 degrees for the conventional step-cut group and 3.0 degrees for the 2-mm modified step-cut group; the difference was significant (p < 0.001). Four femora sustained an incomplete fracture during nail insertion. The average rotation in Phase II was 20.6 degrees for the conventional step-cut group and 0.5 degrees for the 1-mm modified step-cut group without any fractures; the difference was significant (p < 0.001). CONCLUSIONS: Step-cut modification that leaves more bone in the sagittal plane provides rigid fixation and significantly more stability than the conventional step-cut technique.

Biomechanical Phenomena↗

Cost effectiveness of leukotriene modifiers in adults with asthma.

Asthma is the most common chronic disorder in industrialised nations, with over 100 million people worldwide affected. Leukotrienes are chemical mediators released from mast cells, eosinophils and basophils. They cause bronchoconstriction, an increase in mucous secretions and activation of inflammatory cells. Leukotriene modifiers are a long-term controller medication used to treat asthma. They function by selectively competing for the leukotriene receptor sites, thereby blocking their action, or by inhibiting 5-lipoxygenase and thus preventing leukotriene formation. Both current US and Global Initiative for Asthma treatment guidelines have clarified the role of leukotriene modifiers in the management of asthma in adults and children. Leukotriene modifiers have two distinct roles: to replace inhaled corticosteroids in milder asthma and as an add-on therapy to inhaled corticosteroids in more severe asthma. While efficacy is certainly an important issue, economic considerations are also important in a disease such as asthma where there are a variety of treatment options and the severity of the disease varies widely. This review examined published studies to better understand the cost effectiveness of leukotriene modifiers in adults with asthma. Fifteen articles were found that analysed the cost effectiveness of leukotriene modifiers, with almost all performed in the US. The vast majority of the studies were retrospective claims analyses, but three randomised controlled trials incorporating economic outcomes have been reported. The majority of the articles found that for both monotherapy in mild persistent asthma and add-on therapy in moderate persistent asthma, leukotriene modifiers were less cost effective than inhaled corticosteroids with or without a long-acting beta2-adrenoceptor agonist. However, these results must be viewed cautiously as in several studies there were methodological issues such as comparisons of unequal treatment groups or inappropriate use of leukotriene modifiers in stepwise treatment.

Adult↗

Comparison of fat-suppressed T2-weighted fast spin-echo sequence and modified STIR sequence in the evaluation of the rotator cuff tendon.

OBJECTIVE: This study was performed to determine whether a modified version of the classic STIR sequence provides similar information about the integrity of the rotator cuff tendon as the commonly used fat-suppressed T2-weighted fast spin-echo sequence. SUBJECTS AND METHODS: Sixty-one consecutive MRI examinations of the shoulder in 57 patients were performed using a coronal oblique T1-weighted spin-echo sequence, a modified version of the STIR sequence, and a fat-suppressed T2-weighted fast spin-echo sequence. Three reviewers independently assessed the rotator cuff tendon using the coronal oblique modified inversion recovery sequence and T1-weighted spin-echo sequence. After a minimum of 4 weeks, reviewers assessed the rotator cuff tendon using the fat-suppressed T2-weighted fast spin-echo sequence and T1-weighted spin-echo sequence. The kappa statistic was used to measure the degree of concordance between interpretations when each sequence was used independently. The conditional probability that a full- and a partial-thickness tear would be diagnosed on both sequences was calculated. Image quality was assessed in a side-by-side comparison. RESULTS: The overall weighted kappa score was 0.82, which indicates excellent concordance between the two sequences. If a full-thickness tear of the rotator cuff tendon was found on the fat-suppressed T2-weighted fast spin-echo sequence, there was a 94.1% probability that the same conclusion would be reached using the modified inversion recovery sequence. If a partial-thickness tear was found on the fat-suppressed T2-weighted fast spin-echo sequence, there was an 80.3% probability that the same conclusion would be reached with the modified inversion recovery sequence. Fat suppression in the modified inversion recovery sequence was superior to that in the T2-weighted fast spin-echo sequence in 26-39% of the examinations. CONCLUSION: The modified inversion recovery sequence and fat-suppressed T2-weighted fast spin-echo sequence provide similar information about the integrity of the rotator cuff tendon.

Adult↗

[Modified Rives technic in the treatment of recurrent inguinal hernia].

After the introduction of prosthetic material in hernia surgery the fundamental changes in operative strategy occurred. This is because the coverage of myopectineal orifitium with non-absorbable prosthesis decreases the incidence of recurrences. Because of the appearance of lateral re-recurrences after the classical Rives procedure, we modified the operative technique. The modified Rives technique consists of the following: always polypropilen mesh 15x10 cm; creation of the new internal inguinal ring between Poupart's ligament and mesh; no lateral notching the mesh and anchoring mesh 2-3 cm from the medial, inferior, lateral and superior edge. During the period January 2001-December 2003, 34 cases of recurrent hernias were operated on 7th dept. of I Surgical Clinic of CCS. The recurrences were managed by classical (10/34) or modified Rives technique through direct inguinal approach (22/34), less frequently Lichtenstein procedure (1/34) and McVay (1/34) technique. Among 10 patients with recurrent inguinal hernias managed by classical Rives technique 2 re-recurrences appeared (indirect and interstitial) and 2 cases of infection (immediately after the operation or 7 months after the operation), and in the group of 22 cases with recurrent inguinal hernias managed by modified Rives technique the aim complications didn't appear. Using the modified Rives technique we managed the primary hernias in 56 cases without recurrences and infections. The modified Rives technique, because of the way of mesh fixation (all around), no lateral notching of mesh and remaining hem in all directions secures abdominal wall protection 2-3 cm from the line of fixation and prevents any movement of the mesh. This procedure enables management of all inguinal hernias regardless to their size and full protection of the medial, femoral and lateral inguinal triangle. The modified Rives technique is the technique of choice for big multiple defects (giant inguino-scrotal and re-recurrences), especially among patients with increased intra-abdominal pressure when other techniques may be insufficient because of mesh protrusion.

Digestive System Surgical Procedures↗

Native and modified LDL activate extracellular signal-regulated kinases in mesangial cells.

Glycation and/or oxidation of LDL may promote diabetic nephropathy. The mitogen-activated protein kinase (MAPK) cascade, which includes extracellular signal-regulated protein kinases (ERKs), modulates cell function. Therefore, we examined the effects of LDL on ERK phosphorylation in cultured rat mesangial cells. In cells exposed to 100 microg/ml native LDL or LDL modified by glycation, and/or mild or marked (copper-mediated) oxidation, ERK activation peaked at 5 min. Five minutes of exposure to 10-100 microg/ml native or modified LDL produced a concentration-dependent (up to sevenfold) increase in ERK activity. Also, 10 microg/ml native LDL and mildly modified LDL (glycated and/or mildly oxidized) produced significantly greater ERK activation than that induced by copper-oxidized LDL +/- glycation (P < 0.05). Pretreatment of cells with Src kinase and MAPK kinase inhibitors blocked ERK activation by 50-80% (P < 0.05). Native and mildly modified LDL, which are recognized by the native LDL receptor, induced a transient spike of intracellular calcium. Copper-oxidized (+/- glycation) LDL, recognized by the scavenger receptor, induced a sustained rise in intracellular calcium. The intracellular calcium chelator (EGTA/AM) further increased ERK activation by native and mildly modified LDL (P < 0.05). These findings demonstrate that native and modified LDL activate ERKs 1 and 2, an early mitogenic signal, in mesangial cells and provide evidence for a potential link between modified LDL and the development of glomerular injury in diabetes.

Animals↗

Comparison of absorptive capacities of original and modified Schirmer tear test strips in dogs.

OBJECTIVE: To compare in vitro and in vivo absorptive capacities of modified Schirmer tear test strips with those of original strips, and to establish reference values for use with the modified strips. DESIGN: Prospective study. ANIMALS: 100 dogs. PROCEDURE: In vitro absorptive capacity was determined by immersing strips in an irrigating solution for 15 seconds and recording amount of wetting. In vivo absorptive capacity was determined by placing an original Schirmer tear test strip in 1 eye and a modified strip in the other eye of 50 dogs with normal or abnormal tear production. Time required to wet 10 mm of each strip was recorded. Measurements were repeated 30 minutes later after reversing which strip was placed in the left or right eye. Reference values (mean +/- SD) were determined by recording the time required to wet 10 mm of the modified strip in 50 healthy dogs. RESULTS: Amount of wetting was significantly less and time required to wet 10 mm was significantly greater for the modified strip, compared with the original strip. Reference values determined for the modified strip were 32 +/- 11 seconds in the right eye, 33 +/- 11 seconds in the left eye, and 32 +/- 10 seconds in both eyes. CONCLUSIONS AND CLINICAL RELEVANCE: Absorptive capacities of the original and modified Schirmer tear test strips were significantly different. Reference values determined for 1 strip should not be used for the other strip.

Absorption↗

A modified procedure for simultaneous extraction and subsequent assay of calcium-dependent and lysosomal protease systems from a skeletal muscle biopsy.

An extraction and assay system was developed for quantifying endogenous muscle proteases from a single 5-g sample. A single extraction buffer was developed for simultaneous extraction of both calcium-dependent proteases (CDP) and cathepsins. Protease activity determined by the modified procedure was compared to standard procedures currently used in our laboratory. The successful use of the modified procedure on muscle biopsies was verified. Activities per gram of ovine longissimus muscle of CDP system components for 50-g standard and 5-g modified procedures were not different (P greater than .05) for CDP-I (1.16 vs 1.08), CDP-II (.89 vs 1.03), or CDP inhibitor (2.34 vs 2.32), respectively. Activities of cathepsins per gram of muscle for standard and modified procedures were higher (P less than .05) for the modified procedure (cathepsins B + L, 202.0 vs 309.8), but not different (P greater than .05) for cathepsin B (76.6 vs 98.8). Cystatin-like activity was not different (P greater than .05; 3.4 vs 3.2). To test the effect of location within the longissimus muscle on protease activities, 5 g of longissimus muscle was removed immediately postmortem from each of six locations from each side of three steer carcasses. Location within the longissimus muscle had no effect (P greater than .05) on the protease activities measured. Protease activities determined on bovine longissimus muscle biopsies with the modified procedure were similar to immediate postmortem activities. These data verify that the modified procedure was as able to quantify endogenous muscle proteases as the standard procedures and could be used on muscle biopsies. This procedure should be useful in studying the role of endogenous muscle proteases in muscle growth and postmortem proteolysis.

Animals↗