GSTP1, GSTM1, and GSTT1 genetic polymorphisms in patients with cryptogenic liver cirrhosis

We investigated glutathione S-transferase (GST) P1I le (105) Val, T1, and M1 polymorphisms in 45 patients with documented cryptogenic cirrhosis and 56 healthy control subjects. Polymerase chain reaction-based procedures were performed in the studied populations to confirm the genotypes of GSTT1, M1, and P1. Ile/Val and Val/Val GSTP1 genotypes were more frequent in the patients with cirrhosis (n = 39, 87%) than in the control subjects (n = 10; 18%) (odds ratio [OR] 34.04; 95% confidence interval [CI] 10.70 to 108.31, P < 0.001). Among these patients with cirrhosis, 16 were heterozygous and 23 were homozygous, whereas only one person in the control group was homozygous. The GSTM1 null genotype was also more prevalent in cirrhotic patients than in healthy control subjects (OR 6.83, 95% CI 2.53 to 18.42, P < 0.001). The rate of GSTT1 deletion did not show a significant difference between the two groups (OR 2.35, 95% CI 0.76 to 7.28, P = 0.111). To our knowledge, this is the first evidence that GSTP1 and GSTM1 polymorphisms may be related to the development of cirrhosis by unknown mechanisms. The significant association of cryptogenic cirrhosis with Val/Val GSTP1 genotype encoding a low detoxification activity protein implicates this polymorphism as a risk factor for the occurrence of the disease. Presented as an abstract at the Forty-Fourth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Florida, May 19–22, 2003 (Poster of Distinction).     

Accuracy of computed tomography in assessing thoracic pedicle screw malposition

OBJECTIVE: Transpedicular instrumentation of the thoracic spine is potentially dangerous because of the close proximity of vital structures and the morphologic variability seen. Computed tomography has become the gold standard in evaluating the position of thoracic pedicle screws in vivo. Unfortunately, despite its common use, the accuracy of computed tomography has not been adequately investigated. The objective of this work was to evaluate the accuracy of computed tomography in evaluating the position of thoracic pedicle screws. METHODS: One hundred ninety-four thoracic pedicles in nine cadaveric specimens were instrumented and evaluated postoperatively with computed tomography and open dissection. Computed tomography films were assessed by three blinded observers who noted the position of each pedicle screw on two separate occasions. These data were subsequently compared with the open dissection data. RESULTS: Computed tomography was found to be 76 +/- 16% sensitive and 75 +/- 13% specific when compared with open dissection. Overall accuracy was 76 +/- 8%. Intraobserver accuracy was 79 +/- 5% in assessing thoracic pedicle screws by computed tomography. Fair to moderate degree of agreement was demonstrated for both interobserver and intraobserver data using kappa values. CONCLUSIONS: Computed tomography was found to be relatively insensitive in assessing thoracic pedicle screw position. In the face of postoperative complications, surgical exploration and hardware removal may still be necessary despite negative computed tomography.     

Spontaneous regression and complete disappearance of the vein of Galen aneurysmal malformation

Introduction

Thrombosis is frequently observed in Galen malformation, but propagation of thrombosis resulting in the disappearance of the aneurysmal malformation is a very rare clinical condition.

Case report

A rare case of spontaneous regression and disappearance of the vein of Galen aneurysmal malformation (VoGAM) in a pediatric patient with repeated generalized seizure, increased head circumference, and congestive heart failure is recorded. The course of regression from infancy to 8 years of age has been depicted. Radiological studies initially demonstrated VoGAM complicated by an intra-cerebral hemorrhage and hydrocephalus, which later underwent spontaneous regression. Long-term clinical and radiological follow-up is presented.

Discussion

Different conditions including hemodynamic alteration, compression of adjacent hematoma, and narrowing of related vascular structures have been described to cause thrombosis of VoGAM. The relevant literature to address possible mechanism is reviewed.

     

Polyphloretin phosphate, an antagonist of thyrotropin action: evidence for an interaction with the hormone rather than the receptor

Polyphloretin phosphate (PPP) is known to be an inhibitor of bovine TSH (bTSH)-induced stimulation of the thyroid in both in vivo and in vitro assays. The present studies were undertaken to delineate the mechanism of these effects. A high molecular weight PPP preparation strongly inhibited both the binding of 125I-labeled bTSH [( 125I]bTSH) to human thyroid membranes and the stimulation of adenylate cyclase evoked by bTSH therein. Inhibition of bTSH-induced adenylate cyclase activity by PPP was evident both in the absence and the presence of NaCl (150 mM) in the incubation medium. Incubation of membranes with PPP, followed by its removal, did not affect subsequent binding of [125I]bTSH, indicating that PPP did not bind firmly to or damage the TSH receptor. Gel chromatography on Sephadex G-100 revealed that [125I]bTSH incubated with PPP eluted earlier than [125I]bTSH alone, indicating that PPP had formed a higher molecular weight complex with [125I]bTSH. This effect could be prevented by the addition of an excess of unlabeled bTSH to the incubation mixture. Binding of [125I] bTSH in the higher molecular weight peak generated by incubation with PPP was less than half that in control specimens of [125I]bTSH. Studies with PPP were also conducted in a highly sensitive assay that employs cultured porcine thyroid cells and measures the cAMP response induced by bTSH. The inhibitory effect of PPP on bTSH-induced cAMP accumulation was also evident in this assay. However, the presence of divalent cations Ca++ and Mg++ in the assay medium greatly diminished the inhibitory effect of PPP. Similarly, addition of Ca++ and Mg++ to the incubation medium greatly reduced or abolished the inhibitory effect of PPP on [125I]bTSH binding. Both effects of these salts to lessen the inhibitory response to PPP were overcome by increasing the PPP concentration. Gel chromatographic studies revealed that Ca++ and Mg++ acted by inhibiting the formation of the high molecular weight complex of bTSH and PPP. From these findings, we conclude that PPP exerts its inhibitory effect on TSH-induced stimulatory responses in the thyroid, in vivo as well as in vitro, by forming a complex with the hormone. The complex either does not bind to TSH receptors or does so with much lower affinity.     

The active principles of plant extracts with antithyrotropic activity: oxidation products of derivatives of 3,4-dihydroxycinnamic acid

We have recently reported that freeze-dried extracts (FDE) of certain plants form high molecular weight adducts with bovine TSH (bTSH), preventing it from binding to and stimulating adenylate cyclase in human thyroid membranes. We have now studied 34 pure compounds identical or structurally related to compounds present in FDE from Lycopus or Lithospermum, 2 of the 3 species of active plants studied previously. In studies conducted at 4 C in 20 mM Tris-HCl-0.5% BSA buffer, pH 7.45, eight 3,4-dihydroxylated compounds, all structurally related to cinnamic acid, inhibited the binding of [125I] bTSH to human thyroid membranes. Of these, 4 (caffeic, rosmarinic, chlorogenic, and ellagic acids) are present in the plants, and 4 (3,4-dihydroxyphenylacetic acid, deoxyepinephrine, adenochrome, and nordihydroguaretic acid) are structurally related thereto. These compounds were inactive when tested directly but became active when allowed to undergo auto-oxidation. With all 8 compounds, half-maximum inhibition of [125I]bTSH binding required quantities of oxidized product equivalent to 20-80 micrograms/ml (60-195 microM) of the original compound. Half-maximum inhibitory concentrations of oxidized caffeic and ellagic acids were increased 2- to 4-fold when experiments were performed at 37 C in medium containing 50 mM NaCl. Preincubation of membranes with active oxidation products in concentrations up to 100 micrograms/ml, followed by washing, had no effect on the subsequent binding of [125I]bTSH. As has been shown in the case of FDE, when [125I]bTSH was preincubated with oxidation products of caffeic and ellagic acids and was then chromatographed on Sephadex G-100, its elution pattern was advanced from an apparent mol wt of 30,000 to the void volume, and [125I]bTSH in the early eluting fractions displayed greatly reduced binding to thyroid membrane preparations. Addition of a large excess of unlabeled bTSH during preincubation prevented the shift in the elution pattern of [125I]bTSH produced by these oxidation products. To ascertain whether FDE and active compounds interact with the protein or carbohydrate moieties of bTSH, studies of their effects on the binding and chromatographic behavior of 125I-deglycosylated-bTSH (dg-bTSH) were also performed. Effects were similar to those observed for intact bTSH, suggesting that they do not interact with the carbohydrate moiety of TSH. Preincubation of both bTSH and dg-bTSH with either active FDE or oxidation products of caffeic or rosmarinic acid also greatly decreased their activity in the McKenzie mouse assay.(ABSTRACT TRUNCATED AT 400 WORDS)     

Accuracy of in situ neck-shaft angle and shortening measurements of the anatomically reduced,varus malreduced and shortened proximal femur: Can we believe what we see on the postoperative films?

ObjectivesMeasuring the neck-shaft angle (NSA) and amount of shortening of the femoral neck on the anterior to posterior (AP) X-ray is important when treating proximal femur fractures. To compensate for proximal femoral external rotation, the X-rays need to be taken with the leg internally rotated, an act that cannot always be performed or verified. This study aims to define the utility of in situ AP X-ray in NSA and shortening measurements.MethodsComputed tomography (CT) scans of 50 patients undergoing abdominal CT scans were assessed for the in situ rotation of the femoral neck relative to the AP beam. Three proximal femur fracture Sawbones models were made and AP X-rays of the models were taken with changing proximal femur rotation. NSA and shortening were measured on all X-rays.ResultsIn situ femoral neck rotation averaged 25.4 ± 10.6° of external rotation (range, 0.9–51.8°, 80% of measurements less than 35°). NSA measurements varied less than 5° with less than 35° of rotation in all models, and were always greater than the true value. Femoral neck vertical length (VL) measurement was independent of proximal femur rotation whereas the horizontal length component was found to be highly dependent on the same.ConclusionsNSA measured on AP X-ray will be accurate to within 5° in 80% of patients with the hip left in situ and in 100% of the patients if the hip is internally rotated 15°. Measurement of significant varus or loss of VL of the femoral neck can be considered accurate regardless of leg rotation at the time of X-rays being taken.     

The Efficacy of Steroid Injection in the Treatment of Trigger Finger

Background

Trigger finger is one of the most common reasons for referral to a hand specialist clinic. The purpose of this study is to investigate the efficacy of steroid injections for treating trigger digits.

Methods

Ninety digits were investigated with at least a year follow up. The study mainly focused on the efficacy of the injections, as well as co-morbidities, presence of a nodule, actual digit injected and the severity at presentation using Green''s classification.

Results

The study found that 66% of trigger digits were effectively treated using steroid injections. There was a difference between the efficacy of the injection in the different digits, with a statistical significance between the thumb and the fingers. The results also showed that there was no statistical relationship between the severity of the condition, the presence of a nodule or co-morbidities and the efficacy of the steroid injections.

Conclusions

The study found that steroid injections are an effective first-line intervention for the treatment of trigger digit. It also found an increased efficacy for treating the thumb compared to other digits. Both the severity of the condition at presentation and the presence of a nodule had no significant impact on the efficacy of the injections.     

Anterior cervical interbody constructs: effect of a repetitive compressive force on the endplate

Graft subsidence following anterior cervical reconstruction can result in the loss of sagittal balance and recurring foraminal stenosis. This study examined the implant–endplate interface using a cyclic fatigue loading protocol in an attempt to model the subsidence seen in vivo. The superior endplate from 30 cervical vertebrae (C3 to T1) were harvested and biomechanically tested in axial compression with one of three implants: Fibular allograft; titanium mesh cage packed with cancellous chips; and trabecular metal. Each construct was cyclically loaded from 50 to 250 N for 10,000 cycles. Nondestructive cyclic loading of the cervical endplate–implant construct resulted in a stiffer construct independent of the type of the interbody implant tested. The trabecular metal construct demonstrated significantly more axial stability and significantly less subsidence in comparison to the titanium mesh construct. Although the allograft construct resulted in more subsidence than the trabecular metal construct, the difference was not significant and no difference was found when comparing axial stability. For all constructs, the majority of the subsidence during the cyclic testing occurred during the first 500 cycles and was followed by a more gradual settling in the remaining 9,500 cycles. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:587–592, 2012     

Results of routine shunting and patch closure during carotid endarterectomy

BackgroundThe role of shunting and patching during carotid endarterectomy remains controversial.MethodsThis is a retrospective case series evaluating consecutive patients undergoing carotid endarterectomy with routine shunting and patching. The primary endpoints were perioperative stroke, arterial injury, and lesion recurrence by duplex.ResultsOf the 220 operations performed, 43% were for symptomatic disease. Successful shunt placement occurred in 98%, with no shunt-related injuries. There was 1 minor perioperative stroke and no major strokes. At a mean follow-up of 24 months (median = 12 months), there was 1 restenosis potentially related to shunt placement. The incidence of asymptomatic >50% stenosis in the patched segment was 8%.ConclusionsA combined policy of routine shunting and patching simplifies intraoperative decision making with results that rival or exceed those of trials in which their use was not standardized. Shunts need not be avoided because of concern of arterial injury.     

Tensile bond strength of sealants following Er:YAG laser etching compared to acid etching in permanent teeth

The aim of this in vitro study was to assess the effect of Er:YAG laser surface treatment on the tensile bond strength of a sealant in permanent teeth. A total of 30 sound third molars were selected and embedded in cold-cure acrylic resin. The enamel surfaces were flattened by a grinding. The teeth were randomly divided into three groups and pretreated as follows: (1) 37% phosphoric acid; (2) Er:YAG laser (1.5 ml/min water spray, 100 mJ energy output, 10 Hz frequency, focal distance 17 mm); (3) Er:YAG laser + 37% phosphoric acid. The treated surfaces were isolated by double adhesive Sellotape and after insertion of a split Teflon matrix at an isolated site, sealant was applied. The specimens were thermocycled and stored at 37°C in distilled water for 72 h, then subjected to a tensile bond strength test (50 kgf at 0.5 mm/min). The mean tensile bond strengths (±SD, in megapascals) were: 18.51±5.68 in group 1, 8.06±2.69 in group 2, and 17.33±5.04 in group 3. Data were submitted to analysis of variance and the Tukey test. No significant difference were found between groups 1 (37% phosphoric acid) and group 3 (Er:YAG laser + 37% phosphoric acid) but treatment with the Er:YAG laser alone (group 2) resulted in significantly lower tensile bond strength than seen in the other groups. In this setting, the Er:YAG laser prepared the enamel surface for sealing but did not eliminate the need for acid etching before sealant application.