A personalised medicine approach for ponatinib-resistant chronic myeloid leukaemia.

BACKGROUND: Chronic myeloid leukaemia (CML) is characterised by the presence of a fusion driver oncogene, BCR-ABL1, which is a constitutive tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the central treatment strategy for CML patients and have significantly improved survival rates, but the T315I mutation in the kinase domain of BCR-ABL1 confers resistance to all clinically approved TKIs, except ponatinib. However, compound mutations can mediate resistance even to ponatinib and remain a clinical challenge in CML therapy. Here, we investigated a ponatinib-resistant CML patient through whole-genome sequencing (WGS) to identify the cause of resistance and to find alternative therapeutic targets. PATIENTS AND METHODS: We carried out WGS on a ponatinib-resistant CML patient and demonstrated an effective combination therapy against the primary CML cells derived from this patient in vitro. RESULTS: Our findings demonstrate the emergence of compound mutations in the BCR-ABL1 kinase domain following ponatinib treatment, and chromosomal structural variation data predicted amplification of BCL2. The primary CD34(+) CML cells from this patient showed increased sensitivity to the combination of ponatinib and ABT-263, a BCL2 inhibitor with a negligible effect against the normal CD34(+) cells. CONCLUSION: Our results show the potential of personalised medicine approaches in TKI-resistant CML patients and provide a strategy that could improve clinical outcomes for these patients.

Signatures of the Z = 82 shell closure in α-decay process.

In recent experiments at the velocity filter Separator for Heavy Ion reaction Products (SHIP) (GSI, Darmstadt), an extended and improved set of α-decay data for more than 20 of the most neutron-deficient isotopes in the region from lead to thorium was obtained. The combined analysis of this newly available α-decay data, of which the (186)Po decay is reported here, allowed us for the first time to clearly show that crossing the Z = 82 shell to higher proton numbers strongly accelerates the α decay. From the experimental data, the α-particle formation probabilities are deduced following the Universal Decay Law approach. The formation probabilities are discussed in the framework of the pairing force acting among the protons and the neutrons forming the α particle. A striking resemblance between the phenomenological pairing gap deduced from experimental binding energies and the formation probabilities is noted. These findings support the conjecture that both the N = 126 and Z = 82 shell closures strongly influence the α-formation probability.

General surgery in patients with a bleeding diathesis: how we do it.

BACKGROUND: This study was undertaken to assess perioperative management, postoperative complications, and the adequacy of perioperative plasma factor levels in a regional hemophilia center. METHODS: A total of 113 consecutive patients (75 men, 38 women; median age 48 years, range 18-86 years) with bleeding disorders undergoing general surgical and endoscopic procedures (144 procedures: 15 urgent, 129 elective) were reviewed. The episodes were identified from a prospectively collected database at a regional hemophilia center from 1998 to the end of 2008. In all, 46% of the surgical patients had hemophilia A, 38% had von Willebrand disease, 6% had hemophilia B, 5% had factor XI deficiency, and 4% had other disorders. RESULTS: Procedures carried out were endoscopic in 40%, minor in 25%, and intermediate and major in 35%. There were two postoperative deaths, both in patients undergoing urgent major procedures. Postoperative complications occurred after 7.6% (4.0% hemorrhagic, 3.6% nonhemorrhagic) of the procedures. Four of six patients with postoperative hemorrhage required further operative intervention. The median dose of clotting factor for Hemophilia A patients was 2240 U for endoscopic procedures, 7500 U for minor procedures, and 23,500 U for intermediate/major procedures. In hemophiliacs, the mean preoperative plasma factor level attained was 129 IU/dl (SD 16) in patients who developed postoperative hemorrhagic complications and 125 IU/dl (SD 37) in those who did not have bleeding, indicating that in no case was hemorrhage attributable to inadequate factor replacement. CONCLUSIONS: General surgical and endoscopic procedures can be performed with low morbidity and mortality rates when there is appropriate factor replacement and good support from the hemophilia team.

A multi-institutional randomized controlled trial comparing first-generation transrectal high-resolution micro-ultrasound with conventional frequency transrectal ultrasound for prostate biopsy.

Objectives: To study high-frequency 29 MHz transrectal side-fire micro-ultrasound (micro-US) for the detection of clinically significant prostate cancer (csPCa) on prostate biopsy, and validate an image interpretation protocol for micro-US imaging of the prostate. Materials and methods: A prospective randomized clinical trial was performed where 1676 men with indications for prostate biopsy and without known prostate cancer were randomized 1:1 to micro-US vs conventional end-fire ultrasound (conv-US) transrectal-guided prostate biopsy across five sites in North America. The trial was split into two phases, before and after training on a micro-US image interpretation protocol that was developed during the trial using data from the pre-training micro-US arm. Investigators received a standardized training program mid-trial, and the post-training micro-US data were used to examine the training effect. Results: Detection of csPCa (the primary outcome) was no better with the first-generation micro-US system than with conv-US in the overall population (34.6% vs 36.6%, respectively, P = .21). Data from the first portion of the trial were, however, used to develop an image interpretation protocol termed PRI-MUS in order to address the lack of understanding of the appearance of cancer under micro-US. Micro-US sensitivity in the post-training group improved to 60.8% from 24.6% (P < .01), while specificity decreased (from 84.2% to 63.2%). Detection of csPCa in the micro-US arm increased by 7% after training (32% to 39%, P < .03), but training instituted mid-trial did not affect the overall results of the comparison between arms. Conclusion: Micro-US provided no clear benefit over conv-US for the detection of csPCa at biopsy. However, it became evident during the trial that training and increasing experience with this novel technology improved the performance of this first-generation system.

Barrier agents for adhesion prevention after gynaecological surgery.

BACKGROUND: Pelvic adhesion can form as a result of inflammation, endometriosis or surgical trauma. During pelvic surgery, strategies to reduce pelvic adhesion formation may include placing synthetic barrier agents such as oxidised regenerated cellulose, polytetrafluoroethylene or Fibrin sheets between the pelvic structures. OBJECTIVES: To assess the effect of physical barriers used during pelvic surgery in women of reproductive age on pregnancy rates, pelvic pain, or postoperative adhesion reformation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched September 2007) which is based on regular searches of MEDLINE, EMBASE, CINAHL, PsycINFO and CENTRAL, plus handsearching of 20 relevant journals and conference proceedings, and searches of several key grey literature sources. In addition, companies were contacted for unpublished trials. SELECTION CRITERIA: Any randomised controlled trials (RCTs) comparing the use of physical barriers versus no treatment or other physical barriers in the prevention of adhesions in women undergoing gynaecological surgery. DATA COLLECTION AND ANALYSIS: Review authors assessed trial eligibility and quality. MAIN RESULTS: Sixteen RCTs were included. Five trials randomised patients while the remainder randomised pelvic organs. Laparoscopy (six trials) and laparotomy (10 trials) were the primary surgical techniques. Indications for surgery included myomectomy (five trials), ovarian surgery (five trials), pelvic adhesions (four trials), endometriosis (one trial), and mixed (one trial). Eleven trials assessed Interceed versus no treatment, two assessed Interceed versus Gore-Tex, one trial assessed Gore-Tex versus no treatment, and one trial assessed Seprafilm versus no treatment. A single trial assessed Fibrin sheet versus no treatment. No studies reported pregnancy or reduction in pain as outcomes. The use of Interceed was associated with reduced incidence of pelvic adhesion formation, both new formation and reformation following laparoscopic surgery or laparotomy. However, this result should be interpreted with caution. Gore-Tex was more effective than no barrier or Interceed in preventing adhesion formation. There was only limited evidence that Seprafilm was effective in preventing adhesion formation following myomectomy and no evidence to support Fibrin sheet. AUTHORS' CONCLUSIONS: The absorbable adhesion barrier Interceed reduces the incidence of adhesion formation following laparoscopy and laparotomy, but there are insufficient data to support its use to improve pregnancy rates. Gore-Tex may be superior to Interceed in preventing adhesion formation but its usefulness is limited by the need for suturing and later removal. There was no evidence of effectiveness of Seprafilm and Fibrin sheet in preventing adhesion formation.

Characterisation of cytosolic phospholipase A2 as mediator of the enhanced arachidonic acid release from dimethyl sulphoxide differentiated U937 cells.

Studies were performed to characterise the phospholipase A2 (PLA2) responsible for the greatly increased capacity to release arachidonic acid (AA) of dimethyl sulphoxide (DMSO) differentiated U937 monocytic cells compared to undifferentiated cells (18-fold increase in response to Ca2+ ionophore A23187). Cytosolic PLA2 (cPLA2) activity could be measured in homogenates of differentiated cells, and the highly selective cPLA2 inhibitor arachidonic acid trifluoromethyl ketone reduced A23187 induced [3H]AA release from pre-labelled cells by at least 80%, with an IC50 (12.7 +/- 1.4 microM) not significantly different from that for inhibiting authentic cPLA2 (9.3 +/- 2.0 microM). On the other hand, type II PLA2 activity was not detected in cell homogenates, and [3H]AA release was not inhibited by heparin (1 mg/mL), which binds secreted type II PLA2 and reduces its ability to degrade membrane phospholipids. Stimulation of intact cells with A23187 plus phorbol myristate acetate (PMA) under conditions that released [3H]AA did not increase cPLA2 activity of the cell homogenate, and there was little difference between DMSO differentiated and undifferentiated cells in cPLA2 protein content, cPLA2 specific activity of homogenates, or distribution of cPLA2 between membrane and cytosol in the resting cell. Following stimulation with A23187 plus PMA, no increase in [33P] labelling of cPLA2 immunoprecipitates was seen in cells pre-labelled with [33P] orthophosphate, nor a change in electrophoretic mobility of cPLA2. It was concluded that cPLA2 releases the bulk of AA from stimulated, DMSO differentiated U937 cells. The failure to observe increased cPLA2 specific activity following cellular stimulation could be explained by increased [3H]AA release requiring the activation of only a small proportion of the cell pool of cPLA2 or, alternatively, by increased release reflecting greater Ca(2+)-dependent association of cPLA2 with membrane substrate rather than increased specific activity per se. There was no evidence that any such increased membrane association resulted from cPLA2 phosphorylation. The relative inability of undifferentiated cells to release AA was not due to the absence of cPLA2 or an altered distribution between membrane and cytosol, but suggested the presence of a repressor mechanism that prevents elevated Ca2+ from functionally activating the enzyme intracellularly.

Measurement of formaldehyde concentrations in a subatmospheric steam-formaldehyde autoclave.

A method has been developed for measuring formaldehyde concentrations in a subatmospheric steam-formaldehyde autoclave. Data obtained using this method indicate that the concentration of formaldehyde in the chamber atmosphere is not homogeneous and that it decreases rapidly with time. The penetration of formaldehyde vapour into narrow tubes has also been investigated and was shown to be dependent on the length-to-bore ratio of the tubes. The formaldehyde concentration within the tubes could be increased by using a lower vacuum in the air removal stage at the beginning of the cycle.

The prediction of ovulation: a comparison of the basal body temperature graph, cervical mucus score, and real-time pelvic ultrasonography.

Ninety-five menstrual cycles were studied in 20 women undergoing donor artificial insemination (AID). In 49 cycles basal body temperature (BBT) changes were charted daily and both daily cervical mucus scoring (modified Insler score) and daily realtime ultrasonography (USS) were performed from day 11 to ovulation. AID was performed only on the day of follicular rupture. A control group, not subjected to USS, were inseminated two to three times per cycle over 46 cycles in the periovulatory period. The Insler score was found to be a reliable indicator of follicular development and rupture. The BBT was found to be less reliable than the Insler score or USS. While USS may be used to confirm follicular development, the Insler score is reliable and less costly.

PIP: This study was designed to compare the accuracy and reliability of the basal body temperature (BBT), cervical mucus, and daily real-time ultrasonography (USS) methods in the prediction of ovulation. A total of 95 menstrual cycles in 20 women undergoing donor artificial insemination were analyzed. In 49 cycles, BBT changes were charted daily and both daily cervical mucus scoring (modified Insler score) and USS were performed from day 11 until ovulation. Artificial insemination was performed only on the day of follicular rupture. A control group, not subjected to USS, was inseminated 2-3 times/cycle over 46 cycles in the periovulatory period. The Insler score was found to be a reliable indicator of follicular development and rupture. Follicular rupture occurred on the day of the maximal score in 31% of cycles. The maximal score was noted 24 hours before follicular rupture in 47.5%. The BBT was less reliable than the Insler score or USS. In 15% of 49 cycles, there was no clear change in thermal pattern despite USS-confirmed ovulation and a good Insler score. USS confirmation of ovulation was made 24 hours or more before the shift in 17.5% of cycles and 24 or more hours after the thermal shift in 69.5%. Of the 20 subjects, 2 became pregnant during USS-determined cycles and 5 in the absence of USS monitoring. While USS may be used to confirm follicular development, the Insler method is reliable and less costly. It is easily mastered, there is minimal individual variation between observers, and no technical or biochemical facilities are required. It is recommended that, in women undergoing artificial insemination with biphasic temperature graphs, the Insler score should be determined daily from day 11 until the maximal score is passed, with inseminations done daily when the score exceeds 10.

The effects of ovarian adhesive disease upon follicular development in cycles of controlled stimulation for in vitro fertilization.

This study was designed to determine the effect of periovarian adhesive disease upon follicular development. Forty-one clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin-stimulated cycles for in vitro fertilization and embryo transfer were studied. Each patient was assessed ultrasonographically before laparoscopic oocyte recovery. The number of follicles in each ovary greater than 1.2 cm was counted. By laparoscopy it was possible to determine the degree of periovarian adhesive disease. Sixteen patients had bilateral adhesion-free (AF) ovaries, 12 had bilateral adherent (A) ovaries, and 13 had one AF and one A ovary. In the 13 patients with one ovary AF and the other A, the mean number of follicles +/- 1 standard deviation (SD) was 3.4 +/- 1.4 and 1.2 +/- 1.1 (P less than 0.001), respectively. A total of 116 follicles was noted in 45 AF ovaries (mean +/- 1 SD, 2.6 +/- 1.3) and 59 follicles in 37 A ovaries (mean +/- 1 SD, 1.6 +/- 1) (P less than 0.001). From these data it was concluded that the presence of periovarian adhesive disease inhibits folliculogenesis by a yet undetermined mechanism.

Collagen membrane/fleece composite film reduces adhesions in the presence of bleeding in a rabbit uterine horn model.

OBJECTIVE: Determination of efficacy in presence of bleeding of CDS, a collagen/membrane fleece composite, in a rabbit uterine horn simple abrasion model. DESIGN: Randomized, controlled, and blinded study involving standard abrasion of the uterine horns with induction of moderate mesouterine bleeding. SETTING: Research laboratory. PATIENT(S): New Zealand White rabbits. INTERVENTION(S): No treatment (surgical control), CDS film, or INTERCEED barrier (negative reference control). MAIN OUTCOME MEASURE(S) AND RESULT(S): The extent (percent length uterine horn) with adhesions was assessed after 29 or 30 days. Adhesions formed in surgical controls to an extent (85.6% +/- 4.6%) consistent with historic data for this model. INTERCEED failed to reduce adhesions (78.1% +/- 7.7%) indicating that the test conditions of inadequate hemostasis were validated. CDS film, despite this inadequate hemostasis, reduced the extent of adhesions (31% +/- 7.4%; P<.01). Both the tenacity (P=.0008) and degree of uterine convolution (P=.000003) was reduced by CDS film but not by INTERCEED. CONCLUSION(S): Under conditions of inadequate hemostasis CDS effected a reduction in adhesion development. CDS may be useful adjuvant for procedures where hemostasis is difficult to achieve.

The rates of adhesion development and the effects of crystalloid solutions on adhesion development in pelvic surgery.

OBJECTIVE: To document rates of adhesion development after abdomino-pelvic surgery, stratified by adhesion type, access method, and use of crystalloid solution instillates. DESIGN: Reports from a MEDLINE search (1/1/1966-12/18/1996) detailing rates of adhesion development and meeting the inclusion criteria were subjected to meta-analysis. SETTING: Meta-analysis. PATIENT(S): Patients undergoing abdomino-pelvic surgery. INTERVENTION(S): Intraperitoneal crystalloid solution instillates. MAIN OUTCOME MEASURE(S): Percentage adhesion-free outcome in patients ("patients") or surgical sites ("sites"). RESULT(S): Adhesion-free outcome (sites) was lowest for reformed (26.3% laparotomy; 14.3% laparoscopy), higher for de novo 1b (direct trauma) (45.2% laparotomy, 37.2% laparoscopy), and highest for de novo 1a (indirect trauma) adhesions (82.4% laparoscopy). Crystalloid solution instillates reduced adhesion-free outcome at sites (45.2% versus 20% de novo 1b adhesions in laparotomy) and in patients (43.5% versus 19.9% reformed, laparotomy; 71.7% versus 25% de novo 1b, laparoscopy). CONCLUSION(S): Adhesion-free outcome was lowest for reformed, higher for de novo 1b, and highest for de novo 1a adhesions. Surprisingly, it was lower in laparoscopy than in laparotomy for de novo 1b and reformed adhesions. Crystalloid instillates did not increase adhesion-free outcome. Although limited by the retrospective and heterogeneous nature of the data, these conclusions nonetheless provide a basis on which to formulate future hypotheses.

A randomized clinical trial of oxidized regenerated cellulose adhesion barrier (Interceed, TC7) alone or in combination with heparin.

OBJECTIVE: To compare the efficacy of heparin-saturated oxidized regenerated cellulose absorbable adhesion barrier, Interceed (TC7; Johnson and Johnson Medical Inc., New Brunswick, NJ) to oxidized regenerated cellulose alone for the prevention of postoperative adhesions. DESIGN: Clinical trial. By random assignment, one ovary was wrapped in oxidized regenerated cellulose, and the contralateral ovary was wrapped in oxidized regenerated cellulose saturated with a heparin solution (1,000 U/mL). PATIENT(S): Forty women with defects on both ovaries due to adhesiolysis and/or ovarian cystectomy. MAIN OUTCOME MEASURE: Adhesion formation and raw ovarian surface area were assessed at second-look laparoscopy 10 days to 16 weeks later. RESULT(S): At the second-look laparascopy-adhesions were present on 52.5% (21/40) of the ovaries treated with oxidized regenerated cellulose plus heparin and in 65% (26/40) of the contralateral ovaries treated with oxidized regenerated cellulose alone. For ovaries treated with oxidized regenerated cellulose plus heparin, the raw surface area was reduced from 9.41 +/- 1.27 cm2 (mean +/- SE) at laparotomy to 1.33 +/- 0.52 cm2 at second-look laparoscopy. The corresponding figures for ovaries treated with oxidized regenerated cellulose alone were from 10.24 +/- 1.08 to 1.92 +/- 0.54 cm2, respectively. The mean difference between the reductions in raw surface area (85.9% for oxidized regenerated cellulose plus heparin; 81.3% for oxidized regenerated cellulose alone) was not significantly different from zero (difference = - 0.24 cm2; 95% confidence interval = -2.56 to 3.04). CONCLUSION(S): Adding heparin did not enhance significantly the adhesion-reducing capacity of oxidized regenerated cellulose adhesion barrier when applied to ovarian surfaces after cystectomy and/or ovariolysis at laparotomy. This conclusion is subject to the possibility of a type II error.

Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice.

The transdermal nicotine patch has proved an effective aid to smoking cessation. The ease of securing good compliance gives it a potential advantage over nicotine gum as an adjunct to brief advice and support in primary care settings where the major public health impact is obtained. In a preliminary report of half the sample of a randomized placebo controlled trial, we showed the patch to be effective in a general practice setting. We report here the definitive results of the full sample, including dose effects, predictors of outcome and other issues of theoretical and practical interest. A total of 1200 heavy smokers (> or = 15 per day), attending 30 general practices in 15 English counties received brief GP advice, a booklet and 16 hours per day patch treatment for 18 weeks. Dose increase and abrupt vs. gradual reduction of patch dosage were also randomized and follow-ups conducted at 1, 3, 6, 12, 26 and 52 weeks. Outcome was measured by self-reported complete abstinence from week 3 to 52 with biochemical validation at all follow-up points. Nicotine patch treatment doubled the rate of continuous abstinence up to 1 year (nicotine 9.6%, placebo 4.8%, p < 0.01); it most likely worked by reducing withdrawal symptoms. It enhanced cessation during the first week and reduced relapse during the second week. The dose increase after week 1 produced no sustained increase in cessation. Gradual reduction was no better at preventing relapse than abrupt withdrawal of patches after week 12. Whether relapse would have increased by ending treatment at some point between weeks 3 and 12 was not tested. Although pre-treatment dependence on cigarettes was prognostic of failure, the patches were equally helpful to both highly and less dependent smokers. Patches were particularly helpful to smokers with pre-treatment subclinical dysthymic symptoms. All but one of the 96 subjects eventually achieving long-term abstinence in the study quit during the first week of cessation.

Iliopsoas bursitis and tendinitis. A review.

This review examines the diagnosis and management of iliopsoas bursitis and/or tendinitis. It is a relatively uncommon and unrecognised cause of anterior hip pain and anterior snapping hip. In view of its pathology, iliopsoas bursitis might be better referred to as iliopsoas syndrome. It can usually be diagnosed by history and physical examination, though real time ultrasound may be useful in confirming the diagnosis. Magnetic resonance and computerised tomography imaging have limited roles in its diagnosis, but may identify other pathology or surgical lesions. Nonoperative management has not been well established. Surgical management does not guarantee treatment success. There is a need for further research into both diagnostic and treatment options for those patients with iliopsoas bursitis/tendinitis.

Human parvovirus infection and aplastic crisis in hereditary spherocytosis.

This report records an episode of parvovirus-induced bone-marrow aplasia in a child with hereditary spherocytosis and arising during a local outbreak of erythema infectiosum (fifth disease or 'slapped-cheek syndrome'). Inapparent infection was found in two haematologically normal family contacts.

Hyperbaric oxygen in the treatment of burns.

This article presents the rationale and methods used to employ hyperbaric oxygen (HBO) treatment for patients with burns at the Sherman Oaks Community Hospital. It is based upon an expanded concept of burn injury formation and healing. We believe that new knowledge of oxygen transport and storage in the tissues in the presence of HBO will alter our understanding of the process of wound healing and the application of HBO in treatment.

Barrier agents for preventing adhesions after surgery for subfertility.

BACKGROUND: Pelvic adhesions can be the result of inflamation, endometriosis or surgical trauma. Prevention of postoperative adhesions (either new or reoccurance) has been postulated by using barriers to prevent two surfaces being in contact. When pelvic surgery is being undertaken strategies to reduce pelvic adhesions occurring may be undertaken and these include barrier agents which are placed between the pelvic structures. Two synthetic barriers with differential characteristics are commercially available: oxidised regenerated cellulose (Interceed) and polytetrafluoroethylene (PTFC) (GoreTex). OBJECTIVES: The objective of this review was to assess the effect of mechanical barriers (materials interposed between pelvic structures to prevent adherence of serosal surfaces) used during pelvic surgery in women of reproductive age on pregnancy rates, pelvic pain, or postoperative adhesion reformation. SEARCH STRATEGY: The Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled clinical trials was undertaken. In addition, companies were contacted for unpublished trials. SELECTION CRITERIA: Randomised controlled trials or controlled clinical trials of barriers versus no treatment or other barriers in women undergoing fertility preserving pelvic surgery. DATA COLLECTION AND ANALYSIS: Reviewers assessed eligibility and trial quality. MAIN RESULTS: 15 randomised controlled trials were included. Five trials randomised patients while the remainder randomised pelvic organs. Laparoscopy was the primary surgical technique in six trials while the remaining trials were laparotomy. Indications for surgery included myomectomy (five trials), ovarian surgery (four trials), pelvic adhesions (six trials), endometriosis (two trials) and mixed (one trial). Thirteen trials assessed Interceed versus no treatment, two assessed Interceed versus Gore-Tex, one trial assessed Gore-Tex versus no treatment, and one trial assessed Seprafilm versus no treatment. No study reported pregnancy or reduction in pain as an outcome. The use of Interceed in women was associated with reduced incidence of pelvic adhesion formation, both new formation and re-formation following laparoscopic surgery and after laparotomy. Gore-Tex was more effective than no barrier or Interceed in preventing adhesion formation. There was limited evidence that Seprafilm was effective in preventing adhesion formation in women following myomectomy. REVIEWER'S CONCLUSIONS: The absorbable adhesion barrier Interceed reduces the incidence of adhesion formation, both new formation and re-formation, at laparoscopy and laparotomy, but there are insufficient data to support its use to improve pregnancy rates. Gore-Tex may be superior to Interceed in preventing adhesion formation but its usefulness is limited by the need for suturing and later removal. There was no evidence of effectiveness of Seprafilm in preventing adhesion formation.

Ultrasound catheter placement for deep posterior compartment pressure measurements in chronic compartment syndrome.

Medial shin pain, often referred to as shin splints, is a common but difficult to diagnose entity in many athletes. Chronic deep posterior compartment syndrome as a cause of medial leg pain is still controversial. The problems of deep posterior compartment pressure measurement contribute to this controversy. These problems include safety of catheter insertion and the possibility that the patient has more than one deep posterior compartment. In this paper, we present a new technique for catheter placement in which continuous ultrasound guidance is used. This technique allows for the safe placement of the catheter into the deep posterior compartment and for documentation of catheter tip location.

Effect of different barriers of oxidized regenerated cellulose (ORC) on cecal and sidewall adhesions in the presence and absence of bleeding.

Adhesion formation after bowel surgery is a significant problem. The objective of this study was to evaluate two adhesion barriers composed of oxidized regenerated cellulose (ORC) in a model of bowel surgery, with and without bleeding. Ceca of female New Zealand White rabbits were abraded with gauze and a 3 x 5 cm patch of peritoneum and underlying muscle was excised from the right sidewall. Animals were randomized to receive no treatment, INTERCEED Barrier (Ethicon, Inc.), or neutralized INTERCEED (nTC7). ORC fabrics were applied to the excision site. Seven days later the percentage of the site and length of cecum with adhesions were estimated. The study was replicated in the presence of blood by nicking small vessels near the site sufficient to saturate the fabrics with blood. With hemostasis, the percentage of the sidewall with adhesions was reduced (p < .01) from 63.2 +/- 14.7% in controls (n = 6) to 4 +/- 2.7% with INTERCEED Barrier (n = 6) and 3 +/- 1.2% (n = 5) with nTC7. With bleeding, however, control (n = 5) levels of adhesions (67 +/- 17.5%) were reduced significantly with nTC7 (5.5 +/- 4%, n = 4; p < .01), but not INTERCEED Barrier (34.2 +/- 18.4%, n = 4). Similar trends were observed when the extent of adherent cecum was examined, since the cecum was the main site of adherence to the sidewall. However in the presence of blood, there was no effect of INTERCEED Barrier on cecal adhesions. We conclude that with hemostasis, both absorbable fabrics of ORC reduced adhesion formation between the injured cecum and abdominal sidewall. The effectiveness of INTERCEED Barrier, but not nTC7, was reduced but not eliminated in the presence of bleeding. This confirms similar observations in models of gynecologic surgery.

Time-dependent effect of tolmetin sodium in a rabbit uterine adhesion model.

Tolmetin is a nonsteroidal anti-inflammatory drug (NSAID) that reduces adhesion formation in several animal models after a single intraperitoneal (i.p.) dose delivered at the time of surgery. We set out to determine the period during which tolmetin could prevent adhesions. Adhesions were induced in New Zealand White rabbits (2-3 kg) by abrading the uterine horns and removing their mesouterine vasculature. Tolmetin sodium (1 mg/5 ml saline) was given at various times relative to the start of surgery as a single dose i.p. One week later adhesions were assessed using a standard scoring system (0 = no adhesions; 1 = light adhesions involving both uterine horns; 2 = more tenacious adhesions to bowel or bladder; 3 = tenacious adhesions to bowel and bladder partly immobilizing the uterus; 4 = completely fixed horns adherent to bowel and bladder). Scores were arranged in ascending rank order. Mean rank positions were calculated for each group and compared against controls (Dunnett's multiple comparison). Tolmetin sodium was most effective when administered within 1 hour of surgery. Mild effects could still be observed after 4 hours and the effect diminished after 24 hours. When these effects are compared to the temporal biochemical and cellular effects of tolmetin obtained in related studies, the data support the hypothesis that tolmetin reduces adhesions at least in part by modulating fibrinolytic activity of resident macrophages and macrophages present in the early postsurgical period.