Matched-pairs Signed-rank Test Research Articles

Single stage surgery combining transmucosal implant placement with guided bone regeneration and bioresorbable materials.

The aim of the present clinical study was to test whether peri-implant bone defects can successfully be filled with bone by applying bioresorbable materials for guided bone regeneration (GBR) procedures in conjunction with implants in the transmucosal healing position. Three women and 7 men ranging in age from 32 to 68 years (median 54.5) needed tooth replacement with dental implants. Eight to 14 weeks following careful tooth extraction, implants of the ITI Dental Implant System were placed at the extraction sites. At this time, all implants presented dehiscence defects of the alveolar bone partly exposing the rough titanium plasma sprayed (TPS) surfaces. GBR procedures were performed using deproteinized bovine bone mineral (Bio-Oss) as a membrane-supporting material and a bioresorbable collagen membrane (Bio-Gide) as a barrier. The membranes and the flaps were adjusted to fit around the necks of the implants, thus leaving the implants extending transmucosally into the oral cavity. Clinical measurements were taken at 6 sites around each implant (mesio-buccal, buccal, disto-buccal, disto-lingual, lingual, mesio-lingual) using a calibrated periodontal probe. These included: i) defect depth measured from the shoulder of the implant to the first bone-to-implant contact, ii) infrabony defect component measured from the bone crest to the first bone-to-implant contact, iii) defect width measured from the crest to the implant body in a direction perpendicular to the long axis of the implant. The Wilcoxon Matched Pairs Signed Rank Test was applied to detect differences over time. At baseline, the mean defect depth per patient amounted to 3.6 mm (Standard Deviation 1.6 mm, range 1.8-6.8 mm). The deepest extensions of the defects were located at the buccal aspects (mean 7.8 mm, SD 1.9 mm). At re-entry, the mean defect had decreased to 2.5 mm (SD 0.6 mm). This difference was statistically significant (P < 0.01). Initially, in 62% of sites the depth ranged from 0-3 mm, in 23% it ranged from 2-4 mm, and in 15% it amounted to more than 6 mm. Six to 7 months later, at re-entry, 95% of sites were 3 mm and less in depth and 5% ranged from 4-6 mm. Defect resolution, as assessed by the amount of coverage of the initially exposed rough implant surface, reached a mean value of 86% (SD 33%). One hundred percent resolution was accomplished at 8 out of 10 implants, 60% at one and 0% at another implant. The tissue at the latter implant showed signs of infection and inflammation during the healing phase. It is concluded that bioresorbable materials in GBR procedures at transmucosal implants can lead to successful bone regeneration into peri-implant defects.

The Effects of Sublingual Glyceryl Trinitrate on Walking Distance in Patients with Intermittent Claudication. A Randomised, Doubled-blind, Placebo-controlled, Crossover Study

SUMMARYBackground: Intermittent claudication (IC) is a common problem in older age. New work shows that the administration of glyceryl trinitrate (GTN) can reduce the fall in ankle brachial pressure index (ABPI) after exercise and can increase maximum walking distance by 19% on treadmill exercise. The aim of this study was to further define the clinical benefits of GTN in patients with PVD.Methods: The study is of a randomised, double-blind, placebo-controlled cross-over design. We studied 29 patients with intermittent claudication where the median age was 67.5 years (45-84). This included 20 males and nine females, and six of these patients were diabetics. To be selected, the patients had to have a history of IC with a resting ABPI of 1.0 or less, that fell by more than 0.1 on exercise. Patients were walked for 15 min on flat ground following GTN spray or placebo and total distances walked were measured. This was then followed by the crossover component of the trial.Results: Median walking distance with placebo was 825 m (100-1300 m) and with GTN was 900 m (240-1400 m). This is an increase of 9% (p = 0.02, using the Wilcoxon matched pairs signed ranks test).Conclusion: This study shows a statistically significant improvement in walking distance with GTN in patients with IC.

Short-term durability and improvement of function in traumatic brain injury: a pilot study using the Paediatric Evaluation of Disability Inventory (PEDI) classification levels

Primary objective : To describe the short-term durability and improvement of functional outcomes for children and adolescents with traumatic brain injury (TBI) up to 6 months after discharge from inpatient rehabilitation. Research design : Retrospective, descriptive. Methods and procedures : Twenty-five (28.1%) of 89 children discharged from inpatient rehabilitation were available for outpatient follow-up within 6 months. The Paediatric Evaluation of Disability Inventory (PEDI) functional skill classification levels in the domains of self-care, mobility, and social function, recorded at discharge and follow-up, were examined using the Wilcoxon matched pairs signed rank test (two-tailed). Main outcomes and results : Most (64-80%) of the children sustained the outcome level achieved at hospital discharge in one or more of the three domains. Significant differences (p < 0.05) from discharge to follow-up were detected in mobility and social function levels. Differences between children with and without follow-up were non-significant in all but one variable (social function level at hospital discharge). Conclusions : The results of this study suggest that children after TBI sustain outcomes achieved during inpatient rehabilitation and make significant gains in mobility and social function skills within 6 months of returning home. More research is needed to predict those children who will continue to recover and to identify factors that facilitate recovery in the community setting.

Interfacing computerized biomechanical analysis in monitoring the motor development of children.

This research investigated the effectiveness of using kinematic analysis to monitor the motor development of children on three fundamental movement patterns. 12 children with specific motor delays were filmed before and after participation in the 2-hr. per week, 7-wk. program. The film was analyzed (60 frames per second) using a 2-dimensional analysis system. There were no significant differences when a Wilcoxon matched pairs signed-ranks test was applied to the galloping and skipping center of gravity and linear velocities of the ball data. Timing of the peak linear velocities of the upper body showed subjects increasingly exhibited the more advanced, sequential pattern and no longer exhibited the less advanced simultaneous pattern after the program. It was concluded the changes in timing were evidence of improvements in coordination.

Hemodynamic Effects of Noninvasive Bilevel Positive Airway Pressure on Patients With Chronic Congestive Heart Failure With Systolic Dysfunction

Noninvasive positive airway pressure may play a significant role in treating patients with congestive heart failure (CHF). We tested our hypothesis that noninvasive bilevel positive airway pressure improves left ventricular performance in patients with chronic CHF secondary to severe systolic dysfunction. To determine the cardiac performance of patients using bilevel positive airway pressure, and to describe the hemodynamic effects of bilevel positive airway pressure and its use as a therapeutic adjunct in these patients. Prospective, cohort, nonrandomized study. Outpatient medicine clinic. Fourteen patients (9 men and 5 women) with stable chronic CHF with left ventricular ejection fraction < or =35%; mean age was 60.6 years (range, 43 to 87 years). Bilevel positive airway pressure via nasal mask at an inspiratory pressure of 5 cm H(2)O and an expiratory pressure of 3 cm H(2)O on spontaneous mode at room air for 1 h. Myocardial performance and changes were measured using clinical and echocardiographic parameters. Baseline clinical and echocardiographic parameters were compared with the same parameters after 1 h of bilevel positive airway pressure. Statistically significant (p<0.05, Wilcoxon matched pair signed-rank test) decreases were noted in these mean values: systolic BP from 136.21 to 124.14 mm Hg (p = 0.008), heart rate from 85.07 to 74.71 beats/min (p = 0.002), respiratory rate from 23.07 to 15.43 breaths/min (p = 0.001), and systemic vascular resistance from 1671. 46 to 1236.27 dyne. s. cm(3) (p = 0.001). Statistically significant increases were noted in these mean values: cardiac output from 5.09 to 6.37 L/min (p = 0.004), ejection fraction from 28.71% to 34.36% (p = 0.001), and end-diastolic volume from 224.36 to 246.21 mL (p = 0.045). Bilevel positive airway pressure has excellent potential for improving left ventricular performance of patients with chronic CHF secondary to severe systolic dysfunction.

Microleakage and SEM interfacial micromorphology of amalgam restorations using three adhesive systems

Objective: This study evaluated the microleakage and interfacial micromorphology of Class V cervical amalgam restorations lined with OptiBond, Ælitebond, or Panavia 21. Methods: Unlined amalgams served as control. Cavities were treated with each dentin bonding system according to the manufacturers’ instructions and restored with Tytin non-gamma 2 spherical amalgam. After one week of storage in tap water at 37°C, the specimens were thermocycled (1000 cycles, 6–60°C, 30 s dwell time). Microleakage was assessed by means of basic fuchsin dye penetration and recorded according to an ordinal scale. Results: None of the systems tested in this study completely eliminated microleakage. Kruskal–Wallis one-way ANOVA and Mann–Whitney U test found that on the occlusal wall, Panavia 21 and the control group had the least leakage ( P<0.05). No statistically significant differences were found at dentin margins ( P>0.05). Wilcoxon matched pairs signed rank test found that Panavia 21 and the control group had less leakage at the occlusal than at the dentin margins ( P<0.05); when Ælitebond and OptiBond groups were evaluated, microleakage at the enamel and at the dentin margins was similar for each group. With the adhesive systems, perhaps the hydrophilic bonding agents incorporated the dye during specimen immersion and/or sectioning. Conclusions: The use of adhesives may not be as worthy as resin cements for sealing and bonding amalgam restorations to enamel and dentin

A dobutamine test can disclose hepatosplanchnic hypoperfusion in septic patients.

In 36 hemodynamically stable septic patients, we explored whether changes in gastric mucosal-arterial PCO(2) gradient (PCO(2)gap) induced by a short-term dobutamine infusion may reveal hepatosplanchnic hypoperfusion. Hepatosplanchnic blood flow (HSBF) was determined by the continuous indocyanine green infusion technique and gastric mucosal PCO(2) (Pg(CO(2))) by saline tonometry. In each patient, hemodynamic measurements, blood samples, and Pg(CO(2)) determinations were performed three times: first at baseline (DOB 0), second during a dobutamine infusion at a dose of 5 microgram/kg/min (DOB 5), and third at a dose of 10 microgram/kg/min (DOB 10). The results were analyzed by Wilcoxon's matched-pairs signed rank test and are presented as medians with ranges. The PCO(2)gap decreased preferentially in groups of patients with inadequate hepatosplanchnic perfusion, i.e., with a low fractional HSBF (HSBF/CI), defined as the ratio of the HSBF to the simultaneous cardiac index, or a high gradient between the mixed venous blood and the suprahepatic blood O(2) saturations (DSvh(O(2))). In the 11 patients with a DSvh(O(2)) above 20% at baseline, PCO(2)gap decreased from 12.1 (6.3 to 19.5) mm Hg at DOB 0 to 6.2 (2.5 to 19. 3) mm Hg at DOB 5 (p < 0.001 versus DOB 0), and to 4.2 (0.1 to 35.9) mm Hg at DOB 10 (p < 0.05 versus DOB 5), whereas in the 25 patients with a DSvh(O(2)) below 20% at baseline, PCO(2)gap did not change significantly. At no time was the PCO(2)gap correlated with HSBF/CI or DSvh(O(2)). We conclude that although the PCO(2)gap does not correlate well with global indexes of gut oxygenation, such a simple dobutamine infusion test could identify patients with inadequate hepatosplanchnic perfusion.

Impact of the filling status of the bladder and rectum on their integral dose distribution and the movement of the uterus in the treatment planning of gynaecological cancer

Purpose: Determination of the impact of the filling status of the organs at risk (bladder and rectum) on the uterus mobility and on their integral dose distribution in radiotherapy of gynaecological cancer. Methods: In 29 women suffering from cervical or endometrial cancer two CT scans were carried out for treatment planning, one with an empty bladder and rectum, the second one with bladder and rectum filled. The volumes of the organs at risk were calculated and in 14 patients, receiving a definitive radiotherapy, the position of the uterus within the pelvis was shown using multiplanar reconstructions. After generation of a 3D treatment plan the dose volume histograms were compared for empty and filled organs at risk. Results: The mobility for the corpus uteri with/without bladder and rectum filling was in median 7 mm (95%-confidence interval: 3–15 mm) in cranial/caudal direction and 4 mm (0–9 mm) in posterior/anterior direction. Likewise, cervical mobility was observed to be 4 mm (−1–6 mm) mm in cranial/caudal direction. A full bladder led to a mean reduction in organ dose in median from 94–87% calculated for 50% of the bladder volume ( P<0.05, Wilcoxon's matched-pairs signed-ranks test). For 66% of the bladder volume the dose could be reduced in median from 78 to 61% ( P<0.005) and for the whole bladder from 42 to 39% ( P<0.005), respectively. No significant contribution of the filling status of the rectum to its integral dose burden was noticed. Conclusion: Due to the mobility of the uterus increased margins between CTV and PTV superiorly, inferiorly, anteriorly and posteriorly of 15, 6 and 9 mm each, respectively, should be used. A full bladder is the prerequisite for an integral dose reduction.

A comparison of different density gradients and antibodies for enrichment of fetal erythroblasts by MACS

The enrichment of fetal cells, in particular fetal erythroblasts from the blood of pregnant women offers a promising non-invasive alternative for prenatal diagnosis. The purpose of this study was to compare the retrieval of erythroblasts by different density gradients and different antibodies against erythroid surface antigens, in both a model test system and in blood samples of pregnant women. We enriched erythroblasts from artificial mixtures of cord and adult blood (1:50) and from 16 ml of peripheral blood from pregnant women at a mean gestational age of 14+2 weeks. The yield of erythroblasts was calculated and compared using Wilcoxon's matched-pairs signed-rank test. In the artificial mixture most erythroblasts were retrieved using the heaviest density gradient (specific density of 1119) followed by antibody-labelled magnetic cell sorting (MACS). With anti-GPA the yield of erythroblasts from the artificial mixture was highest (9362.5 erythroblasts) compared with anti-CD36 (5164.3), anti-i (3455.2), anti-CD71 (3055.8) and HAE9 (2364.2). The difference between anti-GPA and anti-CD71, HAE9 and anti-i was significant (p=0.0277). The enrichment of erythroblasts from peripheral blood of pregnant women showed similar results. The yield of erythroblasts using anti-GPA was the highest. These results enable us to simplify our enrichment protocols to a single density gradient of 1119 specific density followed by MACS, with anti-GPA.

Vascular surgical society of great britain and ireland: prospective randomized double-blind placebo-controlled crossover study to assess the effect of sublingual glyceryl trinitrate in patients with intermittent claudication

BACKGROUND: The effect of sublingual glyceryl trinitrate (GTN) on the claudication distance (CD) and maximum walking distance (MWD) of patients with intermittent claudication was assessed. METHODS: Inclusion criteria were: history of intermittent claudication; resting ankle : brachial pressure index (ABPI) of 1.00 or less; fall in ABPI of more than 0.1 following exercise; and patient not taking nitrates. In the first study 22 patients (median age 69 (range 60-73) years, 16 men, five diabetic, median resting ABPI 0.57 (range 0.1-0.64)) had their CD and MWD measured on a treadmill set at 3.2 km h-1 and 10 per cent gradient. They were then randomized to either GTN or placebo spray, and the distances were remeasured. The crossover portion of the study was then completed. In the second study 28 patients (median age 68 (range 45-84) years, 20 men, six diabetic, median resting ABPI 0.57 (range 0.13-0.98)) were randomized to either GTN or placebo and walked at their own pace along a flat corridor for 15 min. Following a rest of 15 min, the crossover portion of the study was completed. Statistical analysis was by the Wilcoxon matched pairs signed rank test. RESULTS: CONCLUSION: GTN can increase the MWD by 19 per cent when patients with intermittent claudication are walked on a treadmill and by 9 per cent when walking at their own pace on a flat gradient.

METHYLNALTREXONE CHANGES GUT MOTILITY AND TRANSIT TIME IN CHRONIC METHADONE-MAINTAINED SUBJECTS*

S404 Constipation is the most common side effect of opioids and can be a severe problem in patients with chronic opioid pain therapy. [1] Methylnaltrexone (MNTX), a peripheral opioid receptor antagonist, offers the therapeutic potential of decreasing the side effects of opioids in the gut while preserving analgesia. [2] As a paradigm for cancer patients receiving chronic opioid therapy, we evaluated the effects of intravenous MNTX on subjects receiving chronic methadone therapy. METHODS: All protocols were approved by the IRB. In Study 1, the lactulose hydrogen breath test [3] was used to assess gastrointestinal transit time in 9 males and 10 females (mean age +/- SD 37.2 +/- 8.0 yr) who were chronically receiving methadone. Results of oral-cecal transit times were compared with results obtained from a previous study in healthy volunteers. Wilcoxon matched pairs signed rank test was used for statistical comparison. In Study 2, 4 subjects (2 males and 2 females) with opioid-induced constipation from chronic methadone therapy received placebo on day 1 and iv MNTX (0.05-0.45 mg/kg) twice daily for the rest of the week in a single-blind protocol. Oral-cecal transit time was recorded as well as laxation response based on the frequency and consistency of stools during the study period. Pharmacokinetic data were collected and analyzed. RESULTS: Constipation was experienced by 58% of our subjects. Mean oral-cecal transit time without MNTX was 159 +/- 49.2 min, significantly longer than the transit time in our previous study of volunteers (105 +/- 32 min, P < 0.01). These results suggest that chronic opioid use does not induce tolerance in the gut. In the second study, 2 subjects who received MNTX 0.45 mg/kg (a dose previously used in volunteers) showed immediate positive laxation with infusion. Of these, 1 subject had severe abdominal cramping but showed no other signs of systematic withdrawal such as lacrimation, diaphoresis, mydriasis, or hallucinations. In the remaining 2 subjects, MNTX was reduced to 0.05-0.15 mg/kg. They also had immediate laxation with mild abdominal cramping during and after medication. Stool frequency increased from 2-3 times/week before the study to 1.785 times/day during the treatment period. Gut transit times were reduced from 150 min (baseline) 5o 60 min for each subject by the end of the study. CONCLUSION: Tolerance to opioids does not appear to extend to gastrointestinal motility and transit. Low-dose MNTX transit time in chronic methadone subjects. Low-dose MNTX effectively reversed opioid-induced constipation and delay in gut transit time in chronic methadone subjects. We expect that cancer patients receiving opioids chronically also will have increased sensitivity to MNTX. Low-dose MNTX may have clinical utility in managing opioid-induced constipation. Supported in part by the IARS; Clinical Practice Enhancement & Anesthesia Research Foundation; grant M01 RR00055 from the U.S. Public Health Service General Clinical Research Center

A randomized, double-blind, placebo-controlled, crossover study to assess the immediate effect of sublingual glyceryl trinitrate on the ankle brachial pressure index, claudication, and maximum walking distance of patients with intermittent claudication

Purpose:The goal of the present study was to assess the immediate effect of sublingual glyceryl trinitrate (GTN) in patients with intermittent claudication. Methods: We conducted a randomized, double-blind, placebo-controlled crossover study. Inclusion criteria consisted of history of intermittent claudication, resting ankle brachial pressure index (ABPI) of 1.00 or less, a 20% or greater fall in ABPI after exercise, and maximum walking distance (MWD) of less than 250 m. Patients already receiving nitrates were excluded. In study 1, patients (n = 25) underwent a standard exercise test after randomization to receive either 800 μg of sublingual GTN or placebo. The postexercise ABPI was recorded. Then, the crossover portion of the study was performed. In study 2, patients (n = 22) had their claudication distance and MWD measured. They then were randomized to receive either GTN or placebo spray, and the exercise test was repeated, with the claudication distance and MWD recorded, followed by the crossover portion of the study. Statistical analysis was performed with the Wilcoxon matched pairs signed ranks test and the Mann-Whitney U test. Results:In study 1, the median postexercise ABPIs for placebo and GTN were 0.29 and 0.36 ( P = .0001). In study 2, the median claudication distance for both placebo and GTN groups was 70 m ( P = .59). The median MWD for the placebo and GTN groups was 105 and 125 m ( P = .0084) Conclusion: GTN can decrease the fall in ABPI after exercise and increase the MWD. (J Vasc Surg 1998;28:895-900.)

Evaluation of postsurgical crestal bone levels adjacent to non-submerged dental implants.

In most of the studies on long-term radiographic evaluations of crestal bone levels adjacent to dental implants, no baseline radiographs taken immediately postsurgically had been obtained. The aim of this study was to test the reproducibility of a simple radiographic method for linear measurements of changes in bone levels and to evaluate changes in crestal bone levels adjacent to non-submerged ITI implants 1 year following the surgical procedure. From 128 patients enrolled in a clinical and radiographic longitudinal study 40 patients also had radiographs taken immediately postsurgically. They were, however, not obtained as "identical" images. The radiographs were mounted onto slides and projected on a screen. Mesially and distally from 57 implants triplicate linear measurements of the distance implant shoulder to bone crest were taken, using known dimensions of the implants as internal reference distances. The median difference of 213 (out of 228 possible) duplicate measurements was 0.00 mm (ranging from -1.72 mm to +1.47 mm when comparing the second to the third reading). Some 81% of the double measurements were within +/- 0.5 mm and the precision was 0.30 mm. In the immediate postoperative radiographs the median mesial bone level was located at 2.07 mm (distally 2.19 mm) from the implant shoulder. A statistically significant amount of bone loss in the first year was observed mesially (median = -0.78 mm) and distally (-0.85 mm) (Wilcoxon matched pairs signed rank test P < or = 0.001). No statistically significant influence of the implant location, the implant length, type of the implant (screw; cylinder) was observed (Kruskal-Wallis P > 0.05). The age of the patients was not correlated significantly to the amount of bone loss observed. In conclusion, methodological limitations existed when evaluating linear bone changes in non-identical radiographs using reference dimensions of the implants. The amount of postsurgical bone loss estimated in other studies was confirmed when using an immediate postoperative radiograph as a baseline.

Effect of superimposed infections on viral replication in human immunodeficiency virus type 1-infected children.

Effect of superimposed infections on viral replication in human immunodeficiency virus type 1-infected children.

A Case-Control Study of Metabolic Therapy for Fibromyalgia

ABSTRACT The long-term effectiveness of metabolic therapy for fibromyalgia syndrome (FMS) involving the use of exogenous thyroid honnone was evaluated. Twenty treated FMS patients were compared with 20 matched evaluated but non-treated FMS patients. Treated patients successfully underwent metabolic therapy and were released as significantly improved or recovered between 1991 and 1995. Untreated patients were evaluated during this same time frame, but were not able to undergo treatment because of insufficient or absent insurance coverage. Patients were contacted by mail; they each filled out and returned a questionnaire with forms used to evaluate FMS status. Treated patients were matched with untreated patients based on time since initial evaluation, sex, and thyroid status. In each group, 10 (50%) patients had been classified as euthyroid, 6 (30%) as primary hypothy-roid, and 4 (20%) as central hypothyroid. Of treated patients, all but 1 euthyroid patient used T3, and all but 1 hypothyroid patient used T4. Both groups were compared at baseline and follow-up using chi square analysis for discontinuous variables. These included age, employment, thyroid status, duration of illness, and use of medications and other forms of treatment. Groups were also compared using analysis of variance for continuous variables at baseline and follow-up. These included pain distribution by the percentage and the ACR methods, mean symptom intensity, and scores on the Fibromyalgia Impact Questionnaire (FIQ) and Zung's Self-Rating Depression Scale (Zung's). Because some patients were not available for physical examination at follow-up, mean algometer scores of tender points for the two groups were compared only for the initial evaluation. There were no significant differences at baseline between treated and untreated groups. At follow-up, Wilcoxon Matched Pairs Signed Rank Test showed that treated patients had decreased their use of antidepressants and NSAIDS; untreated patients had increased their use of antidepressants and anxiolytics. Comparison of baseline measures with follow-up measures for each group by r-tests showed that treated patients improved on all FMS measures, while untreated patients improved on none. Multivariate analysis of variance showed significant differences between the two groups on FMS measures (F < 0.0005). Univariate analysis of variance revealed that at follow-up, compared to the untreated group, the treated group significantly improved specifically in pain distribution via the ACR method (F= 0.0002) and in pain distribution via the percentage method, mean symptom intensity, FIQ, and Zung's (F< 0.00005). We conclude that at l-to-5 year follow-up, the FMS status of euthyroid and hypothyroid patients who underwent metabolic therapy, including the use of exogenous thyroid hormone, significantly improved compared to matched untreated FMS patients (see Table 1). The continuation of improved FMS status for l-to-5 years effectively rules out a placebo effect as the mechanism of improvement.

Effects of short-term pre-operative tamoxifen on steroid receptor and Ki-67 expression in primary breast cancer: an immunocytochemical study.

The effects of the short-term pre-operative administration of tamoxifen (TAM, 20 mg once daily) on the tumor levels of steroid receptors and the nuclear proliferation Ki-67 antigen, were investigated in 32 elderly patients with hormone-sensitive, operable primary breast cancer by means of fine-needle aspiration biopsy (FNAB). The FNAB smears before (pre-TAM) and after six weeks of treatment (post-TAM) were stained immunocytochemically in order to obtain an H-score for steroid receptors, and the percentage of cellular nuclei containing Ki-67. The mean oestrogen receptor (ER) score between the pre- and post-TAM specimens fell from 181.2 9.7 ( SEM) to 148.1 7.9 (Wilcoxon's matched-pairs signed-rank test, p=0. 01) and there was also a significant decrease in both the mean progesterone receptor (PgR) score (178.4 10.6 vs 148.5 10.6; p=0.01) and mean Ki-67 index (8.2% 1.2 vs 4.9% 0.9; p=0.0002). The reliability of FNAB as a sampling method was checked by comparing the results of the immunocytochemical assay (ICA) of the post-TAM biopsies with those of the immunohistochemical assay (IHA) of the corresponding excised tumors. There was a positive correlation between the ICA and IHA scores: ER (Spearman's correlation coefficient, rho=0.66, p<0.001), PgR (rho=0.84, p<0.001) and Ki-67 (rho=0.96, p<0.001). We conclude that the sequential use of FNAB is a reliable means of assessing the behaviour of within-tumor biomarkers during endocrine therapy.

CHANGES IN GUT MOTILITY AND TRANSIT IN SUBJECTS MAINTAINED ON METHADONE

S50 Constipation is the most common side effect of opioids and can be a severe problem in those patients taking opioids chronically for pain therapy. We studied the gut motility and transit time in methadone-maintained addicts and in normal subjects by measuring oral-cecal transit time. Methods: With approval from the IRB, 9 males and 10 females who had been in a methadone maintenance program for at least 1 month were enrolled in this study. Their mean age +/- SD (range) was 37.2 +/- 8.0 (26-56) years. The subjects were admitted in the morning for a study which lasted approximately 5 hr. Gastrointestinal transit time was assessed by the lactulose hydrogen breath test. Subjects were also asked to complete a questionnaire regarding their bowel activity. Oral-cecal transit times in the subjects were compared to transit times recorded previously in two studies of non-addict volunteers. The Wilcoxon matched pairs signed rank test was used for statistical analysis. Results: Mean oral-cecal transit time +/- SD of the methadone-maintained subjects was 159 +/- 49.2 min, significantly longer than the transit time recorded in two previous studies of non-addicted subjects (105 +/- 31 min and 114 +/- 37 min, respectively; P < 0.01) (Figure 1) None of the subjects taking methadone reported constipation problems before usage of illicit drugs. During chronic methadone therapy, 58% of subjects experienced some degree of constipation, and two of the 19 subjects reported that constipation was a very serious problem.Figure 1Conclusion: Our results indicate that tolerance to opioids does not appear to extend to gastrointestinal motility and transit. It has been shown that constipation is the most common side effect of chronic opioid pain medication in patients with metastatic malignancy. Before proceeding to treat chronically ill cancer patients with methylnaltrexone, a peripheral opioid receptor antagonist, we intend to evaluate its effects in subjects undergoing methadone therapy.

Prognostic significance of MIB-1 proliferative activity in thin melanomas and immunohistochemical analysis of MIB-1 proliferative activity in melanocytic tumors.

Metastasis from thin melanomas is rare and unpredictable. In order to assess the prognostic value of the proliferation marker, MIB-1, immunohistochemical staining was evaluated in a retrospective case-control study of 11 thin melanomas with documented metastasis and 11 control tumors that failed to metastasize. Tumors selected were < 1-mm thick and were individually matched for tumor thickness, date of excision, and patient age and sex. Analysis of MIB-1 expression as both a mean and a maximum level for the case and control groups revealed no association with metastasis. Wilcoxon's matched-pairs signed-rank test had p-values of 0.45 for the maximum values and 0.79 for the mean values. For the 11 thin melanomas that metastasized, there was a weak, yet statistically insignificant, correlation between the proportion of cells positive for MIB-1 and the length of the relapse-free period [Spearman's correlation coefficient = 0.20 for the maximum level (p = 0.56) and 0.19 for the mean level (p = 0.58)]. These results suggest that MIB-1 expression may be of limited value as a prognostic marker for increased risk of metastasis in patients with thin melanomas. MIB-1 immunohistochemistry was also performed on 25 benign and 70 malignant paraffin-embedded melanocytic tumors to evaluate the level of MIB-1 expression at different stages of tumor progression. A progressive increase in MIB-1 expression was seen from benign tumors through to primary melanomas, with the highest level seen in metastatic melanomas. Within the group of primary melanomas, the MIB-1 score was shown to correlate significantly with tumor thickness and Clark's level of invasion (Spearman's correlation coefficient = 0.71 for level and 0.77 for thickness).

Investigation of Topical Ciprofloxacin Ototoxicity in Guinea Pigs

Antibiotic eardrops mostly contain potentially ototoxic aminoglycosides. Ciprofloxacin is an alternative, and there is limited experience in its topical use. To investigate the topical ototoxicity of ciprofloxacin, 11 guinea pigs have been operated on. Transbullae silicone drug delivery tubes were placed to both ears of the animals. After the operation the guinea pigs were divided into two groups. The first group of animals received 0.2 ml of 4% gentamicin in one ear and 0.2 ml of 0.9% sodium chloride solution in the other. The second group received 0.2 ml of 0.2% ciprofloxacin in the test ear and 0.2 ml of 0.9% sodium chloride solution in the control ear. All drugs were given once a day on 7 consecutive days. Auditory brainstem response thresholds were recorded using click, 4 and 8 kHz logon stimuli before and after the operation, and after topical drug application. Results were statistically compared using Wilcoxon matched pairs signed-ranks test. Comparison of the thresholds before and after the operation, physiological saline application, as well as ciprofloxacin application yielded no statistically significant differences, whereas application of gentamicin resulted in total hearing loss. The results indicate that topical use of 0.2% ciprofloxacin is not ototoxic in guinea pigs.

Prostanoid production in the umbilicoplacental arterial tree relative to impaired glucose tolerance

The purpose of this study was to investigate prostanoid synthesis in different segments of the umbilicoplacental vascular tree and its relationship to impaired maternal glucose tolerance. Segments from the umbilical artery and vein, allantochorionic artery branches, and the cotyledon artery from 21 women with diabetes or impaired glucose toleranc and 10 healthy women were studied. Production of prostacyclin (PGI 2) and thromboxane (TxA 2) metabolites was determined. The Mann-Whitney U test, Wilcoxon signed-ranks matched-pairs test, Kruskal-Wallis test, analysis of variance, and simple linear regression analysis were used. A two-tailed P value of < 0.05 was considered statistically significant. From the umbilical artery distal to the cotyledon artery, the PGI 2 synthesis decreased and the TxA 2 synthesis increased gradually towards the periphery in normal pregnancy. The PGI 2 TxA 2 ratio was more than 200 times higher in the umbilical artery than in the cotyledon artery. The TxA 2 production tended in general to be higher in the diabetic group than in the control group, resulting in significantly lower PGI 2 TxA 2 ratios in some vessels. The prostanoid production was not significantly correlated to maternal HbA 1c or cord C-peptide concentrations. The balance between vascular prostacyclin and thromboxane synthesis in the umbilicoplacental arterial tree changed gradually towards the periphery: the more peripheral, the lower the prostacyclin and the higher the thromboxane production. The physiological role of this phenomenon is unknown, but may be of importance for the equilibration of vascular tone between arteries of different calibers. The altered prostanoid balance found in diabetic pregnancy was not directly attributable to the degree of maternal glycemic control, but may reflect increased free radical activity and peroxide production in diabetes.