A multicenter, randomized controlled trial comparing a single intra-articular injection of Gel-200, a new cross-linked formulation of hyaluronic acid, to phosphate buffered saline for treatment of osteoarthritis of the knee.

OBJECTIVE: To compare the safety and efficacy of a single intra-articular (IA) injection of a new cross-linked hyaluronic acid product, Gel-200, with phosphate buffered saline (PBS, control) in a multi-center randomized controlled trial in patients with symptomatic osteoarthritis (OA) of the knee. DESIGN: Patients were randomized 2:1 to receive a single injection of Gel-200 or PBS, after joint aspiration. The primary measure of effectiveness was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscores by 100-mm Visual Analog Scale (VAS); secondary outcomes included: total WOMAC, physical function, and stiffness subscores; patient and physician global assessments of disease activity, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) strict responders, as well as safety of Gel-200. RESULTS: Of 379 patients randomized, safety was evaluated in 377 and efficacy in 375 (98.9% randomized) in the intent-to-treat population. Effectiveness of Gel-200 by WOMAC pain subscores was statistically significant at week 13 (P=0.037). Mean improvements from baseline in WOMAC pain subscores consistently favored Gel-200 at each visit. Effectiveness of Gel-200 treatment was statistically significant over weeks 3-13 by WOMAC total score, physical function, and physician global evaluations (P<0.05). The number of "strict" OMERACT-OARSI responders was statistically significant from weeks 6 to 13 (P=0.022). Adverse events were not significantly different between treatment groups, including serious adverse events considered related to study treatment. CONCLUSIONS: This trial demonstrated that a single injection of Gel-200 was well tolerated and relieved pain associated with symptomatic OA of the knee over 13 weeks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NTC 00449696.

Effectiveness and Safety of a Multicenter Extension and Retreatment Trial of Gel-200 in Patients with Knee Osteoarthritis.

OBJECTIVE: To assess the continued effectiveness and safety of Gel-200 following observation and open-label retreatment in an extension protocol following a randomized, double-blind, phosphate buffered saline (PBS)-controlled trial (initial treatment trial). DESIGN: Patients who completed initial blinded treatment were allowed to enroll into this extension protocol that permitted retreatment with Gel-200 when eligibility criteria were met. Retreatment was administered with a Gel-200 injection, without knowledge of initial treatment assignment (Gel-200 or PBS). Retreated patients were followed for up to 13 weeks. In the extension phase, durability of response following the first injection was analyzed by time to retreatment eligibility. During separate extension and retreatment phases, responses were assessed by WOMAC pain, stiffness, and physical function subscores, total score, and global assessments of disease activity (patient, physician) as well as safety of Gel-200. RESULTS: In the extension phase, time-to-event analyses through 26 weeks following the initial injection showed statistically significantly longer times to retreatment in patients receiving Gel-200 compared with PBS (P < 0.05). Retreatment with Gel-200, e.g., a second injection, resulted in statistically significant improvements from retreatment baseline in all outcome measures (P < 0.0001). The incidence and type of adverse events after retreatment were comparable to those observed following initial injection of Gel-200 without allergic reactions, including "pseudosepsis" or unanticipated treatment-related serious adverse events. CONCLUSIONS: These data demonstrate that a single injection of Gel-200 resulted in durable effectiveness through 26 weeks and that repeated treatment with Gel-200 relieved symptomatic osteoarthritis with a favorable safety profile.

Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group.

A prospective, multicenter, randomized, double-blind, controlled trial was conducted in 226 patients with knee osteoarthritis to evaluate the safety and efficacy of intraarticular injections of sodium hyaluronate. Patients were randomized to three weekly injections of 30 mg sodium hyaluronate or physiologic saline (control) and were observed for an additional 25 weeks. In comparison with the control group, among patients who completed at least 15 weeks of the study and whose Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was less than 12 at baseline, sodium hyaluronate injection resulted in improvement in Western Ontario and McMaster Universities Osteoarthritis Index pain score, patient and investigator global assessments, and pain on standing from Weeks 7 to 27. Fifty-eight percent of patients treated with sodium hyaluronate achieved a 5-unit or greater improvement in mean pain score from Weeks 7 through 27, compared with 40% of control patients. In addition, nearly twice as many patients treated with sodium hyaluronate as with saline (30% versus 17%, respectively) achieved a net improvement of at least 7 units. In contrast to treatment with saline, Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was inversely related to the magnitude of improvement after treatment with sodium hyaluronate. Few side effects were attributed to treatment, and no differences between treatment groups were seen in this respect (sodium hyaluronate, nine [8%]; saline, 11 [10%]). The incidence of injection site reactions was low (sodium hyaluronate, 1.2 %; saline, 1.5%). The results indicate that sodium hyaluronate treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee osteoarthritis in whom pain in the contralateral knee is relatively modest.

Role of myocardial temperature measurement in monitoring the adequacy of myocardial protection during cardiac surgery.

Inadequate myocardial protection continues to be encountered despite improved methods of cardioplegia delivery. Although myocardial temperature is commonly monitored to assess the adequacy of cardioplegia delivery, its relationship to the metabolic status of the myocardium has not been investigated. We prospectively reviewed patients who underwent valvular heart surgery with blood (n = 47) or crystalloid (n = 48) cardioplegia and continuous measurement of intraoperative myocardial tissue pH and temperature. We previously demonstrated a high correlation (r = 0.99) between extracellular myocardial pH, levels of intracellular hydrogen ion concentration, and a lowering of tissue ATP during coronary occlusion. Clinically, optimal metabolic protection was defined as the absence of myocardial tissue acidosis during the period of aortic occlusion as quantified by a temperature-corrected integrated mean pH of 6.8 or greater, which has been shown to be predictive of a favorable postoperative outcome. Age, bypass time, myocardial temperature, myocardial tissue pH at the onset of aortic occlusion, cross-clamp time, and volume of cardioplegia were not significantly different between blood and crystalloid groups. Linear regression analysis demonstrated no significant correlation between mean myocardial tissue pH and the corresponding mean myocardial temperature in either group during aortic occlusion. There was also no correlation between the mean myocardial tissue pH and volume of cardioplegia delivered in both groups. These data demonstrate wide intercardiac and intracardiac variability in the degree of regional tissue acidosis encountered during of hypothermic cardioplegia. Cardioplegia delivery guided by measurement of myocardial temperature or by standardized protocol did not prevent the occurrence of tissue acidosis and thus, did not ensure optimal metabolic protection of the heart. In 95 patients undergoing valvular heart surgery with cold blood or crystalloid cardioplegia, there was no correlation between myocardial tissue pH and mycardial temperature or between myocardial tissue pH and volume of cardioplegia administered. Temperature is a poor indicator of the metabolic state of the myocardium.

The impact of variable tint optics (Transitions Gray) on vision-related quality of life in normal volunteers: a randomized clinical comparison in a warm climate.

PURPOSE: A randomized crossover comparison of Transitions Gray variable tint optics (VTO) vs clear and fixed-tint lenses was undertaken to evaluate the impact of VTO on vision-related quality of life (VRQOL) in a warm climate. METHODS: Fifty-nine patients were randomized to one of four lens crossover groups: Transitions-->clear; clear-->Transitions; Transitions-->fixed-tint; fixed-tint-->Transitions. Each lens was worn for 30 days. VRQOL was measured using a newly developed and validated questionnaire instrument-the Transitions VRQOL. Changes in visual acuity were assessed by functional exam. RESULTS: Overall, Transitions was associated with the greatest improvement in VRQOL relative to clear and fixed-tint lenses without compromise in acuity. Transitions proved statistically superior to clear lenses, most notably in vision comfort both indoors and outdoors. Seventy percent of all patients selected Transitions as their primary lens at the end of the study. CONCLUSIONS: Transitions brand VTO offer patients significant and clinically meaningful improvements in VRQOL superior to clear lenses. VRQOL assessments provide clinicians with valuable information above and beyond visual acuity to help optimize lens product selection and enhance patient satisfaction.

The effectiveness of one-on-one nurse education on the outcomes of high-risk adult and pediatric patients with asthma.

The effects of an asthma self-management program on asthma outcomes were evaluated in adult and pediatric patients with asthma who were considered at high risk (i.e., those who were not in control of their disease as determined by resource utilization, medication use, or lack of use). The program consisted of one-on-one nurse-to-patient ("nurse champion") education and subsequent assessment of asthma outcomes using the Asthma Quality Assessment System (AQAS) questionnaire, which measured asthma severity, patient quality of life, asthma awareness and knowledge, confidence in managing asthma, use of peak flow meters, asthma symptoms, medication use, lost work or school days, and affect of asthma. Over the course of six months, nurse champions educated 201 patients from four managed care plans and collected data at baseline and during four follow-up sessions. Adult patients and pediatric patient caregivers reported significant improvements in quality of life, and clinical and process measures. Significant increases in asthma knowledge were observed immediately after patient education, including greater than 89% increase in the proportion of patients who reported that they know "a lot" about the "things that cause asthma symptoms." Significant decreases were also found in work or school days missed, urgent care utilization, and hospital admission rates. Appropriate preventive care visits increased by more than 40%. These results indicate that the nurse champion program was associated with an improvement in asthma outcomes in high-risk adult and pediatric patients and warrant further evaluation in controlled studies. Incorporating one-on-one education programs into asthma management is an effective and rapid means of improving asthma outcomes.

Strategies to increase the use of autogenous arteriovenous fistula in end-stage renal disease.

The purpose of this retrospective study was to review our experience with a consecutive group of end-stage renal disease (ESRD) patients using simple strategies to increase the use of autogenous vascular access, and determine whether the current trend of using synthetic bridge-graft fistula (BGF) rather than autogenous arteriovenous fistula (AVF), could be reversed, despite an aging population and broadening criteria for hemodialysis. All patients for vascular access surgery had careful preoperative clinical examination of the arm veins with outflow occlusion to determine the venous anatomy and continuity. Where no veins were apparent or their continuity in doubt, selective preoperative venography was performed. Where veins were unsatisfactory for forearm AVF, new or modified surgical procedures to use both the basilic and cephalic veins in the upper arm were performed. Intraoperative angioscopy was used to monitor vein quality and surgical technique. Ninety-eight primary vascular access procedures were performed in 76 patients, 75 (76.5%) AVF (forearm, n = 41; upper arm, n = 34) and 23 (23.5%) BGF. Forty-one of 76 (54%) had already had at least one previous access procedure prior to this study. More than one access procedure was needed in 16 patients. Preoperative venography was performed in 22 (22.4%) and intraoperative angioscopy in 45 (45.9%) of the 98 procedures. The number of revisions required to maintain patency was significantly higher for BGF (37 revisions in 14/23) than AVF (16 revisions in 13/75) (p < 0.0001, Poisson test) with an annualized secondary revision rate of 1.168 for BGF and 0.173 for AVF (p < 0.0001, Poisson test). AVF had both longer primary (p = 0.0001, log rank test) and secondary patency (p = 0.038, log rank test) than BGF. AVF as the primary vascular access can be significantly increased and the current trend of using BGF reversed with the use of simple clinical strategies to evaluate the suitability of the arm veins for vascular access.

Topoisomerase II alpha expression in normal, inflammatory, and neoplastic conditions of the gastric and colonic mucosa.

Topoisomerase II alpha (TP) excises and reconnects double-stranded super-coiled DNA during the replicative cell cycle. We studied the localization of TP and Ki-67 in inflammatory and neoplastic mucosal lesions of the stomach and of TP in similar conditions of the colon. TP expression was correlated with tumor stage, grade, and survival time in the colonic tumors to evaluate its potential utility as a predictive marker for clinical outcome. Forty-three sections of chronic gastritis, lesions indefinite for dysplasia, low- and high-grade dysplasia, and gastric adenocarcinomas were immunostained with antibody against TP and Ki-67. For the colon, 71 sections of normal mucosa, chronic colitis, hyperplastic polyps, adenomas, and carcinomas were examined; fresh tissue was analyzed by flow cytometry. Expression of TP in non-neoplastic gastric mucosa was maximal in neck/foveolar cells and focal in surface and deep gland cells. Increased surface and deep gland positivity was found in low-grade dysplasia and a diffuse distribution of positive cells in high-grade dysplasia and carcinoma. The Ki-67 staining pattern was similar. TP in non-neoplastic colon was restricted to the lower crypt zone; it was greatly expanded in the surface/upper crypt region in adenomas and was diffuse in carcinomas. Flow cytometric analysis revealed TP expression mainly in the S and G2/M phase, with higher labeling index in tumors. There was no correlation of TP with stage, grade, or survival times in the colonic tumors. Staining for TP and Ki-67 might help in the distinction of inflammatory and neoplastic lesions of the stomach and colon.

Association between sucrase-isomaltase and p53 expression in colorectal cancer.

BACKGROUND: Sucrase-isomaltase (SI) is a tissue-based phenotypic marker that is an independent prognostic factor in colorectal cancer (CRC). DF3 and galectin 3 are two other tissue-based markers that are upregulated during neoplastic transformation. Because p53 mutations are acquired during neoplastic progression, we reasoned that alterations in SI and p53 may be associated despite an apparent lack of biological interaction. METHODS: Paraffin sections from 183 patients who underwent surgery at New England Deaconess Hospital (NEDH) between 1965 and 1977 were analyzed first by immunohistochemistry (IHC) for the expression of the markers SI, DF3, and galectin 3, which were scored as absent or present. Paraffin sections from a second group of 59 patients who underwent surgery at NEDH between 1985 and 1992 were analyzed by IHC for the expression of p53 as well as SI, DF3, and galectin 3. p53 nuclear staining was scored as absent or present. Previous work has shown that p53 is mutated in all cells with nuclear staining and in 10% of tumors that are unstained. RESULTS: SI expression was not associated with the expression of either DF3 or galectin 3, and neither DF3 nor galectin 3 were prognostic factors in CRC. None of the phenotypic markers were associated with any of the clinicopathologic variables. However, 21 of 24 p53-positive cases (88%) expressed SI, whereas 15 of 35 p53-negative cases (43%) were also SI negative (p = 0.02, Fisher exact test). p53 expression was not associated with expression of DF3 or galectin 3. CONCLUSIONS: SI expression and p53 mutation are associated significantly in CRC. Although the mechanism underlying such an association in presently unknown, the association may define a subset of patients with a worse prognosis.

The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight.

This study investigated whether the addition of the high-intensity sweetener aspartame to a multidisciplinary weight-control program would improve weight loss and long-term control of body weight. One hundred sixty-three obese women were randomly assigned to consume or to abstain from aspartame-sweetened foods and beverages during 16 wk of a 19-wk weight-reduction program (active weight loss), a 1-y maintenance program, and a 2-y follow-up period. Women in both treatment groups lost approximately 10% of initial body weight (10 kg) during active weight loss. Among women assigned to the aspartame-treatment group, aspartame intake was positively correlated with percentage weight loss during active weight loss (r = 0.32, P < 0.01). During maintenance and follow-up, participants in the aspartame group experienced a 2.6% (2.6 kg) and 4.6% (4.6 kg) regain of initial body weight after 71 and 175 wk, respectively, whereas those in the no-aspartame group gained an average of 5.4% (5.4 kg) and 9.4% (9.4 kg), respectively. The aspartame group lost significantly more weight overall (P = 0.028) and regained significantly less weight during maintenance and follow-up (P = 0.046) than did the no-aspartame group. Percentage weight losses at 71 and 175 wk were also positively correlated with exercise (r = 0.32, P < 0.001; and r = 0.34, P < 0.01, respectively) and self-reported eating control (r = 0.37, P < 0.001; and r = 0.33, P < 0.01, respectively). These data suggest that participation in a multidisciplinary weight-control program that includes aspartame may facilitate the long-term maintenance of reduced body weight.

Assessment of dietary intakes of cadets at the US Military Academy at West Point.

OBJECTIVE: A study was conducted at the US Military Academy, West Point, NY, to assess the nutritional adequacy of menus and dietary intakes of the cadets and to determine the effect of the optional weekday evening meal policy on nutrient intakes. METHODS: Dietary intakes were obtained over a 7-day period using a diary-interview technique. Volunteer cadets, 118 males and 86 females, recorded their own intakes and were interviewed by dietitians to verify food records. Cadets were categorized by gender and divided into three groups based on whether they consumed 0-1, 2-3, or 4-5 weekday evening meals in the Cadet Mess. RESULTS: Multivariate methods were used to assess compliance with Military Recommended Dietary Allowances (MRDA) and nutrient densities as well as the role of gender, number of weekday evening meals consumed in the West Point Cadet Mess, and the use of nutritional supplements during the study week. The number of weekday evening meals consumed in the Cadet Mess, was positively correlated with the nutrient intakes of the cadet groups. The female 0-1 group had the highest proportion of individuals with mean intakes providing < 70% MRDA for vitamin B6, folate, vitamin A, magnesium, or zinc. Snacks provided from 24% to 32% of the energy intakes of the female groups and were often substituted for meals, particularly by cadets who ate the fewest meals in the Cadet Mess. CONCLUSIONS: Diet counseling is recommended to help these cadets choose more nutritious meals and snacks. University and college students that choose not to purchase some of their meals from campus dining facilities could have similar dietary intake patterns and nutritional shortcomings.

The new era in breast cancer. Invasion, size, and nodal involvement dramatically decreasing as a result of mammographic screening.

OBJECTIVE: To describe the magnitude of changes and opportunities that may arise for simplified surgical procedures for women with breast cancer because of the decreasing size and lymph node involvement in invasive breast cancer and earlier presentation of noninvasive and invasive breast cancer. DESIGN AND MAIN OUTCOME ASSESSMENT: Cases (N=1001) of breast cancer from a tertiary and a community hospital between 1989 and 1993 were analyzed for invasion, size, nodal status, and change over time. RESULTS: Ductal carcinoma in situ constituted 14% and 18% of the cancers at the two hospitals. At the tertiary and community hospitals, the mean maximum diameters were 2.1 and 2.0 cm, respectively, and the median maximum diameters were 1.5 and 1.7 cm, respectively, for invasive breast cancer. Twenty-nine percent and 28%, respectively, were 1 cm or less in diameter. Axillary nodal metastases occurred in only 31% of the invasive cancers (tertiary hospital); only 10% had more than three nodal metastases. In the T1a and T1b cases, nodal metastases occurred in only 10% and 43% of the positive nodes were solitary; only 16% had more than three nodal metastases. The proportion of ductal carcinoma in situ, T1a and T1b, and node-negative cases increased significantly over time. CONCLUSIONS: Within the next decade, the proportion of all breast cancers that are ductal carcinoma in situ will approach 33%, and invasive cancers will approach 1 cm in median maximum diameter. Therapy simplification will be logical because of very small size, low risk of recurrence after breast conservation, and excellent prognosis, and might include increased breast conservation, avoidance of axillary nodal dissection, and omission of radiation therapy to conserve breasts. Adjuvant therapy will be based on the prognostic features of the primary cancer and findings from careful histologic examination of the sentinel lymph nodes.

Sucrase-isomaltase is an independent prognostic marker for colorectal carcinoma.

PURPOSE: Expression of disaccharidase sucrase-isomaltase (SI) is significantly enhanced during neoplastic transformation of colonic epithelium. Our study was designed to determine whether expression of SI within primary tumors was significantly associated with survival in patients with colorectal carcinoma (CRC). METHODS: SI expression was analyzed by immunohistochemistry in paraffin sections from 182 Stage I to III CRC that had been resected for cure at the New England Deaconess Hospital between 1965 and 1977. Expression was scored as absent or present in 1 to 50 percent or more than 50 percent of tumor cells. Associations were explored among SI expression, other clinical or pathologic variables, and overall survival. The data set is mature, with 91 (56 percent) patients who had died of CRC at a median follow-up of 96 months. RESULTS: Fifty-five percent of primary CRC expressed SI. When the multivariate Cox analysis was performed, nodal status, T stage, primary site, grade, and SI expression were independent covariates. SI expression was not associated with the expression of other clinicopathologic variables but increased the risk of death from colorectal carcinoma by 1.83-fold. DISCUSSION: These results indicate that SI is a prognostic marker for CRC that is independent of stage-related variables in patients who have undergone potentially curative resections.

Intense sweeteners use and weight change among women: a critique of the Stellman and Garfinkel study.

OBJECTIVE: The purpose of this study was to evaluate the work of Stellman and Garfinkel who speculated, based on epidemiologic data, that users of intense sweeteners are more likely than nonusers to gain weight. METHODOLOGY: We analyzed the study's design and statistical analysis to determine whether the conclusions of Stellman and Garfinkel were supported by the data. RESULTS: Several methodological flaws and inappropriate statistical analyses were identified. These included: use of data from an unrelated study for which they were not intended; failure to correct for bias due to convenience sampling; use of data from a subpopulation without validation; and stratification of subjects by outcome data. CONCLUSION: Our analysis indicates that the data from the study in question do not allow one to draw conclusions about a relationship between use of intense sweeteners and weight change. Furthermore, data from well-designed clinical trials have shown that aspartame is not associated with weight gain, and when used as part of a balanced deficit diet, can facilitate weight loss.

Role of angioscopy in reoperation for the failing or failed infrainguinal vein bypass graft.

The purpose of this retrospective study is to review our ongoing experience with the use of angioscopy during reoperation for failed or failing infrainguinal vein bypass grafts and define the role of angioscopy in the management of this clinically demanding patient group. All hospital records, arteriograms, and intraoperative angioscopic video recordings of 79 consecutive failed or failing grafts (76 patients) examined with angioscopy during reoperation between 1987 and 1993 were reviewed. Clinical and intraoperative data, comparison of the preoperative arteriogram and intraoperative angioscopic findings, and surgical decisions or interventions resulting from the additional angioscopic findings were collated and analyzed according to a predetermined protocol. Sixty-six additional angioscopic findings were noted during the 79 reoperations and resulted in 61 additional interventions and surgical decisions with salvage of all or part of the graft in 90.9% in the early (< 30 day) failed (group 1), 84.6% in the late (> 30 day) failed (group 2), and 90.3% in the late (> 30 day) failing grafts (group 3). The amount of residual thrombus within the graft, as assessed by angioscopy after all interventions, was the critical determinant for overall early graft patency (p < 0.001) and long-term patency for all the subgroups after reoperation (group 1, p < 0.001; group 2, p = 0.0016; and group 3, p = 0.0194). Intraoperative angioscopy has an important role in these challenging procedures. It provides additional and useful information that not only influences the conduct and extent of the reoperative surgery but may provide insights into the pathogenesis of graft failure.

Expression of colorectal carcinoma-associated antigens in colonic polyps.

Immunohistologic techniques were used to study the expression of colorectal carcinoma-associated antigens in colonic polyps and to compare this with expression in the normal colonic epithelium. Forty-nine polyps were studied using monoclonal antibodies to 16 different blood group and differentiation antigens and carcinoembryonic antigen epitopes. With the Lewis(a) antigen and the two epitopes of CEA recognized by 3D6 and COL-4 expression in polyp tissue was the same as that in the normal colon. Five types of alteration of antigen expression in polyps were seen. The blood group antigens A, B, and Lewis(b), which are expressed only on the right side of the normal adult colon, were detected in both neoplastic and nonneoplastic polyps from the distal colon. The Lewis(x) antigen and the antigen epitopes detected by the antibodies COL-12, CA19-9, ME491, and GA73.3 showed an increased frequency of expression in all types of polyps in comparison with the normal colonic epithelium, while H-type 2, ND4, and the antigen epitope detected by CO29.11 showed a slightly decreased frequency of expression in polyp tissue. The X-like antigen which was expressed in only 7% of normal colon specimens showed increased frequency of expression in polyp tissue with significantly greater expression in neoplastic than hyperplastic lesions (P = 0.003). The TAG-72 antigen was detected only in adenomas with severe dysplasia (P = 0.01), correlating well with premalignant histology. These findings have helped us clarify the variation of antigen expression in colonic polyps and allowed us to define which antigens are worthy of further investigation as markers of possible malignant transformation.

Angioscopically directed interventions improve arm vein bypass grafts.

PURPOSE: Our purpose was to determine the incidence and segmental distribution of intraluminal disease in the arm veins of patients in whom saphenous vein was unavailable or inadequate for bypass, determine whether angioscopic evaluation and directed interventions can upgrade the quality of arm vein conduit and improve early graft patency, and describe the angioscopic technique of in situ retrograde arm vein inspection. METHODS: Retrospective review of 109 infrainguinal arm vein bypass grafts in 104 patients performed with intraoperative angioscopic vein preparation and monitoring between August 1989 and March 1992 was undertaken. Four additional arm veins harvested were discarded because of diffuse disease. RESULTS: Intraluminal disease was noted in 71 (62.8%) of 113 arm veins, "webs" in 61 (54%), vein sclerosis in 25 (22.1%), localized stenosis in 11 (9.7%), and thrombus in 7 (6.2%). Intraluminal disease was most common in the cephalic (forearm 49.2%; arm 35.1%) and median cubital (33.3%) veins and least common in the basilic vein (11.7%). Eighty-three angioscopically directed interventions in 68 of 71 abnormal arm veins resulted in upgraded vein conduit quality in 47 (66.1%) of 71. Primary patency (< 30 days) was 99 (90.8%) of the 109 grafts, 85 (95.5%) of 89 grafts with normal or upgraded quality conduits, and 14 (70%) of 20 inferior-quality grafts (p = 0.0024). These differences persisted through 1 year by life-table analysis, (p < 0.001). CONCLUSIONS: Not only is the routine use of the angioscope in arm vein bypass grafting a sensitive technique to detect the intraluminal diseases so prevalent in arm veins but it can also direct endoluminal and surgical interventions that upgrade the quality of the vein conduit and improve early graft patency.

Efficacy and tolerability of a combination of enalapril and hydrochlorothiazide in the treatment of hypertension measured manually and with an ambulatory blood pressure monitor.

The efficacy and tolerability of an enalapril maleate-hydrochlorothiazide combination (EM-HCTZ) were evaluated in a prospective, open-label study in 26 patients with uncomplicated essential hypertension (mean baseline sitting systolic/diastolic blood pressure: 153/103 mmHg) requiring two agents to reduce sitting diastolic blood pressure (SDBP) below 90 mmHg. Their mean age was 52 years. Patients received enalapril 5 mg daily, which was increased to 10 mg if SDBP was not reduced to < 90 mmHg during a 5-week titration period following washout. If blood pressure did not reach that goal, 25 mg hydrochlorothiazide was added. Only patients who required enalapril 10 mg and hydrochlorothiazide 25 mg for control (SDBP < 90 mmHg) at the end of titration received open-label EM-HCTZ as maintenance therapy for 6 weeks. The SDBP of 19 of the 26 patients (73%) who began titration was controlled at the end of titration, and they received maintenance therapy. During maintenance, the mean SDBP decreased from baseline 13.2 mmHg at week 2, 13.3 mmHg at week 4, and 10.1 mmHg at week 6. All changes from baseline were significant. At the end of the maintenance period, SDBP was controlled in 8 (42%) of 19 patients enrolled. One patient was withdrawn from the study because blood pressure was poorly controlled. Ambulatory blood pressure (ABP) was monitored, average outcome was computed for each patient during the 24-hour interval, and with a paired comparison, baseline and follow-up data were compared with the data measured manually. The mean baseline ABP was 9 mmHg lower than the baseline SDBP measured manually (r = 0.58, P = 0.01). Following treatment with EM-HCTZ, mean diastolic blood pressure fell 10 mmHg and mean systolic blood pressure fell 15 mmHg. In summary, EM-HCTZ was highly effective and generally well-tolerated in a substantial proportion of participants whose SDBP remained > 90 mmHg on enalapril 10 mg. Important differences between blood pressure measured manually and with a monitor were also demonstrated.

Using autoregressive and random walk models to detect trends and shifts in unequally spaced tumour biomarker data.

Continuous time autoregressive (CAR(1)) and random walk models of time series data are provided for detecting non-random shifts and trends of tumour markers in breast cancer patients following resection for cure. The continuous time random walk model with observation error is extended to the case of multiple patient time series. These models can be used to monitor large numbers of patients with time series with few sampling events that are serially correlated and unequally spaced. Further, the methodologies can be used to recommend appropriate testing intervals. A Kalman filter recursive algorithm is used to calculate the likelihood functions arising from the CAR(1) and random walk models and to calculate recursive residuals, which are monitored by Shewhart-cusum schemes.