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Biomedical subjects

M D Stone

Publications and source records attributed to M D Stone.

At least 19 recordsLinked to original sources

Use of clinical risk factors to identify postmenopausal women with vertebral fractures.

INTRODUCTION AND HYPOTHESIS: Previous studies have been unable to identify risk factors for prevalent vertebral fractures (VF), which are suitable for use in selection strategies intended to target high-risk sub-groups for diagnostic assessment. However, these studies generally consisted of large epidemiology surveys based on questionnaires and were only able to evaluate a limited number of risk factors. Here, we investigated whether a stronger relationship exists with prevalent VF when conventional risk factors are combined with additional information obtained from detailed one-to-one assessment. METHODS: Women aged 65-75 registered at four geographically distinct GP practices were invited to participate (n=1,518), of whom 540 attended for assessment as follows: a questionnaire asking about risk factors for osteoporosis such as height loss compared to age 25 and history of non-vertebral fracture (NVF), the get-up-and-go test, Margolis back pain score, measurement of wall-tragus and rib-pelvis distances, and BMD as measured by the distal forearm BMD. A lateral thoraco-lumbar spine X-ray was obtained, which was subsequently scored for the presence of significant vertebral deformities. RESULTS: Of the 509 subjects who underwent spinal radiographs, 37 (7.3%) were found to have one or more VF. Following logistic regression analysis, the four most predictive clinical risk factors for prevalent VF were: height loss (P=0.006), past NVF (P=0.004), history of back pain (P=0.075) and age (P=0.05). BMD was also significantly associated with prevalent VF (P=0.002), but its inclusion did not affect associations with other variables. Factors elicited from detailed one-to-one assessment were not related to the risk of one or more prevalent VFs. The area under ROC curves derived from these regressions, which suggested that models for prevalent VF had modest predictive accuracy, were as follows: 0.68 (BMD), 0.74 (four clinical risk factors above) and 0.78 (clinical risk factors + BMD). Analyses were repeated in relation to the subgroup of 13 patients with two or more VFs, which revealed that in this instance, the Margolis back pain score and rib-pelvis distance were associated with the presence of multiple VFs (P=0.022 and 0.026, respectively). Moreover, the predictive value as reflected by the ROC curve area was improved: 0.80 (BMD), 0.88 (the four most predictive clinical risk factors consisting of the height loss, past NVF, Margolis back pain score and rib-pelvis distance) and 0.91 (clinical risk factors + BMD). CONCLUSIONS: Evaluation of additional risk factors from detailed one-to-one assessment does not improve the predictive value of risk factors for one or more prevalent vertebral deformities in postmenopausal women. However, the use of factors such as the Margolis back pain score and rib-pelvis distance may be helpful in identifying postmenopausal women at high risk of multiple prevalent VFs.

Aged↗

Cost effectiveness analysis of using quantitative ultrasound as a selective pre-screen for bone densitometry.

It has been suggested that quantitative ultrasound (QUS) could be used as a selective population pre-screen, to maximise the cost effectiveness of referral for dual energy X-ray absorptiometry (DXA) assessment of bone mineral density (BMD). We set out to examine how such an approach might perform in the assessment of women who were referred by general practitioners for DXA via the open access service in Cardiff. In 115 women aged 40-80 (mean 69) years we used DXA to measure BMD at lumbar spine and hip, and QUS to measure broadband ultrasound attenuation (BUA) in the heel. A bottom-up approach was used to estimate the costs of DXA and QUS. We examined the cost effectiveness of using QUS as a pre-screen, only referring subjects for the more expensive DXA assessment if BUA were less than a pre-determined threshold. The unit costs of pencil-beam DXA and QUS were approximately 44 UK pounds and 16 UK pounds respectively. We identified a BUA threshold of 60 dB/MHz as the most cost effective, and calculated a sensitivity of 81% and specificity of 89% in identifying those subjects whom DXA assessment subsequently identified as having osteoporosis. At the BUA threshold of 60 dB/MHz, pre-screening saved 969 UK pounds at the expense of missing ten women with osteoporosis as diagnosed by DXA. Therefore the cost per additional woman with osteoporosis identified using DXA alone was only 97 UK pounds. QUS assessment does not appear to have a significant cost effective benefit as a pre-screen for DXA in the studied population. A QUS pre-screen would be cost effective only if this investigation could be performed at a substantially lower cost.

Absorptiometry, Photon↗

Effect of adding dopexamine to intraoperative volume expansion in patients undergoing major elective abdominal surgery.

BACKGROUND: The contribution of low-dose dopexamine to outcome, when given to increase cardiac output in patients already treated with fluids during major abdominal surgery, is not yet known. METHOD: We carried out a randomized double-blind placebo-controlled trial. All 100 patients studied were given fluid infusions during surgery guided by stroke volume measurements made with an oesophageal Doppler probe. Patients were randomized to receive dopexamine at the rate of 0.25 microg kg(-1) min(-1) or saline 0.9% (control) for the first 24 h after the start of surgery. The primary outcome measure was the incidence of postoperative morbidity. RESULTS: There were no statistically significant differences between groups in the incidence of postoperative complications, the length of hospital stay, the incidence of morbidity and the use of critical care facilities. The patients randomized to receive dopexamine had significantly more pre-existing disease than the control patients. Mortality in both groups was significantly less than predicted by the POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) risk prediction score. CONCLUSION: We could not demonstrate an advantage to using low-dose dopexamine in high-risk patients during major abdominal surgery.

Abdomen↗

Surgical resident research in New England.

HYPOTHESIS: This study sought to determine the attitudes of general surgery residents in New England toward research and the factors that affect their research participation and productivity. DESIGN: Survey. SETTING: Eighteen of the 20 general surgery residency programs in New England. PARTICIPANTS: Four hundred fifty-nine surgical residents taking the American Board of Surgery In-Training Examination in 1999. MAIN OUTCOME MEASURES: Rationale for and amount of time spent in research and the number of publications. RESULTS: A majority of residents (61%) participated in research. Rationales for research participation included initiating an academic career (82%) and enhancing fellowship application prospects (83%). Personal debt was substantial, but had little influence on decisions regarding research. Gender was not a factor in the decision to participate in research, although women were more likely to cite a break from residency as a positive influence in their decision for doing research. Residents from larger programs (>25 residents) were more likely to participate in research, spend more time in research, and to publish an article than those from programs with fewer than 25 residents. CONCLUSIONS: Most surgical residents in New England plan to or participate in research and publish their work. Significant differences in the type, duration, and productivity of research exist between larger and smaller programs, and may reflect differing priorities among residents, or differences in the variety of research opportunities available.

Adult↗

Effect of resident call status on ABSITE performance. American Board of Surgery In-Training Examination.

BACKGROUND: Long work hours that result in fatigue may adversely affect cognitive function. Chronically sleep-deprived surgical residents fear that being on call the night before sitting for a standardized test puts them at a potential disadvantage. We examined American Board of Surgery In-Training Examination (ABSITE) scores to assess the effect of call status on exam performance. METHODS: Results of the 1994 ABSITE for 424 residents in 15 New England general surgery programs were collected. We compared standard scores of residents for the total test, clinical management, and basic science components with resident call status (on/off) for the night before the exam. RESULTS: Differences were apparent in total test scores (mean: off, 496.1; on, 466.0; P <.03) and clinical management scores (mean: off, 504.3; on, 470.6; P <.02) (t test, Mann-Whitney U test). Multivariate analyses revealed that differences in postgraduate year level and training track were significant contributors to differences in scores in all test components (analysis of covariance). Call status was not a significant factor in score variation after adjusting for these 2 factors. CONCLUSIONS: Differences in ABSITE scores of residents were related to postgraduate year level and training track. Call status had no significant effect on ABSITE performance.

Cognition↗

Bone density, body composition, and inflammatory status in cystic fibrosis.

Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores </= 2.5 SD (n = 13) or </= 1 SD (n = 7) at least at one site. They had increased bone collagen breakdown, greatest in those with a reduced FFM. BMD was related to FEV(1) (r = 0.44), IL-6 (r = -0.60), and TNF-alpha-soluble receptors (r = -0.42, r = -0.50). Patients with a low FFM had greater concentrations of IL-6, which suppressed less after antibiotic treatment than in those with a normal FFM. Those with a low FFM were more catabolic and less active than those with a normal FFM. The association between altered body composition, catabolic status, and circulating inflammatory mediators suggests that chronic pulmonary infection in adults with CF may be a contributory factor in the long-term complications of low weight and bone disease.

Adult↗

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE: To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA: Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS: Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS: Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS: Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Carcinoembryonic Antigen↗

Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection, and intraoperative radiation therapy.

PURPOSE: To determine the impact of intraoperative radiation therapy (IORT) combined with preoperative external beam irradiation and surgical resection in patients with locally advanced, unresectable rectal carcinoma. METHODS AND MATERIALS: Between 1982 and 1993, 40 patients with locally advanced colorectal cancer unresectable at initial presentation were treated with preoperative external beam radiation therapy (median dose 50.4 Gy). Thirty patients received concurrent 5-fluorouracil. Twenty-seven patients had primary tumors and 13 had recurrent disease; 1 patient had a solitary hepatic metastasis at the time of surgery. Four to 6 weeks after radiation, surgical resection was undertaken, and if microscopic or gross residual disease was encountered, IORT was delivered to the tumor bed. Patients with an unevaluable or high-risk margin were also considered for IORT. IORT was delivered through a dedicated 300-kVp orthovoltage unit. The median dose of IORT was 12.5 Gy (range 8-20). The dose was typically prescribed to a depth of 1-2 cm. The median follow-up was 33 months (range 5-100). RESULTS: Thirty-three patients were able to undergo a curative resection (83%). Five patients had gross residual disease despite aggressive surgery. Seven patients did not receive IORT: six because of clear margins, and one with gross disease that could not be treated for technical reasons. The remainder of the patients (26) received IORT to the site of pelvic adherence. The crude local control rates for patients following complete resection with negative margins were 92% for patients treated with IORT and 33% for patients without IORT. IORT was ineffective for gross residual disease. Pelvic control was none of four in this setting. The crude local control rate of patients with primary cancer was 73% (16 of 22), as opposed to 27% (3 of 11) for these with recurrent cancer. The 5-year actuarial overall survival and local control rates for patients undergoing gross complete resection and IORT were 64% and 75%, respectively. Seventeen of the 26 patients (65%) who received IORT experienced pelvic complications, as opposed to two patients (28%) who did not receive IORT. The incidence of complications was similar in the patients with primary versus recurrent disease. All cases were successfully treated with the placement of a posterior thigh myocutaneous flap. Of note, no pelvic osteoradionecrosis was seen in this series. CONCLUSION: Patients with locally advanced carcinoma of the rectum were aggressively treated with combined modality therapy consisting of preoperative external beam radiotherapy, surgery, and IORT. The pelvic control rate was 82% for patients with minimal residual disease. IORT failed to control gross residual disease. The incidence of pelvic wound healing problems was 65% in this series; however, a reconstructive procedure which replaced irradiated tissue with a vascularized myocutaneous flap was successful in treating this complication. We believe that IORT has therapeutic merit in the treatment of locally advanced rectal cancer, particularly in the setting of minimal residual disease.

Adult↗

The effect of ankle oedema on bone ultrasound assessment at the heel.

Relatively inexpensive, portable bone ultrasound systems are of particular relevance to disabled or elderly subjects, who may have problems with access to other forms of densitometry. The effects of local soft tissues on ultrasound measurements are poorly understood and, as ankle oedema is common in such subjects, we examined its consequences for bone ultrasound readings at the heel. Eleven elderly subjects (mean age 81 years) with below-knee pitting oedema were assessed using a direct-contact bone ultrasound system (CUBA Clinical). We made a total of 16 series of readings, 6 unilateral and 5 bilateral. In each series an initial reading was followed by repeated pressure over the measurement site to disperse oedema; subsequent readings were thus subject to a progressively lessening degree of local oedema, until a steady state was eventually reached in which no further oedema could be displaced. Heel width fell by a mean of 6.3 mm between initial and steady-state readings; consistent with the clinical appearance of moderate oedema, pitting to a mean depth of only 3.15 mm. Measurements in the presence of oedema were compared with those after its elimination, and oedema was shown to cause a mean reduction of 23.9 m/s in velocity of sound (VOS) and of 5.5 dB/MHz in broadband ultrasound attenuation (BUA). Both changes were equivalent to a fall by a quarter of one standard deviation of the reference range, and were significant at p < 0.05 on paired t-test. As the severity of oedema will vary through the day, and from day to day, measurement protocols for bone ultrasound should pay attention to the confounding effects of oedema.

Aged↗

Reliability of parathyroid hormone measurements in the period immediately following hip fracture.

AIM: As it is unclear whether parathyroid hormone (PTH) measurements performed immediately after hip fracture are reliable indicators of pre-fracture metabolic status, we set out to define how PTH levels are affected by hip fracture and its surgical repair. METHOD: In two longitudinal projects, we studied 12 patients presenting with hip fracture and eight patients undergoing elective hip replacement. PTH, calcium and 25-hydroxyvitamin D (25OHD) levels were measured on admission, 2 days and 1 week later and after recovery at least 2 months after initial admission. FINDINGS: In the subjects presenting with hip fracture, PTH levels during inpatient care were no different from those subsequently measured during the recovery period. In subjects undergoing elective hip surgery, PTH levels did not change following surgery and again remained unchanged into the recovery period. CONCLUSIONS: Measurements of PTH performed during inpatient care of those with hip fracture appear sufficiently reliable for use in assessment of metabolic status.

Aged↗

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.

Adult↗

Comparison of methods of assessing response of Paget's disease to bisphosphonate therapy.

Bisphosphonates have been shown to be effective in suppressing the elevated bone turnover found in Paget's disease of bone. In theory, the major determinants of post-treatment bone turnover are the initial disease activity and the rate of decline in bone turnover with therapy. In the present study, we examined the rate of decrease of alkaline phosphatase and hydroxyproline (expressed as a half-life) and showed this to be superior to percentage changes in bone turnover as a marker of response. The combination of pre-treatment alkaline phosphatase and the alkaline phosphatase half-life and pre-treatment hydroxyproline and the hydroxyproline half-life were the best models to predict post-treatment bone turnover (multiple r = 0.75, r2 = 0.56, p < 0.0001; and r = 0.71, r2 = 0.51, p < 0.0001, respectively). In addition, measurement of the half-lives of these markers of bone turnover may allow prospective changes to be made during treatment so that maximal disease suppression can be achieved.

Alkaline Phosphatase↗

Shifting proportions of gastric adenocarcinomas.

OBJECTIVES: To substantiate reports of increasing proportions of gastric adenocarcinoma of diffuse histologic type and in the proximal portion of the stomach, to better understand the prognostic features that govern survival, and to determine whether alterations of operative strategy might improve the surgical results. DESIGN: Retrospective analysis of 289 consecutive patients with gastric adenocarcinoma operated on by general surgeons over a 26-year period. Records were reviewed for location, histologic type, resection, operative mortality, lymph node status, and outcome. SETTING: The Section of Surgical Oncology, the New England Deaconess Hospital, Boston, Mass. MAIN OUTCOME MEASURES: Survival rate, length of life of the patients who died, and operative mortality. RESULTS: A marked and significant shift of gastric adenocarcinoma to a proximal location (54% between 1985 and 1990) occurred over 26 years (P = .0075) with a significant stage improvement at presentation (P = .0235). Percentages of cancers that were of the diffuse, poorly differentiated histologic type increased to 48%. More curative operations were performed in the last period (61%), and this upward trend from 37% was significant. Proximal gastric cancers had a poorer prognosis with more operative deaths, more lymph node metastases, and worse survival rates than distal cancers. Poor survival rates occurred even when comparing patients with negative lymph nodes or favorable histologic features with patients with similar distal cancers. CONCLUSIONS: Despite significant increases in the proportion of proximal cancers, survival rates have improved only slightly. Nodal status plays a less prognostic role than does location or histologic type but does provide prognostic information for individual locations. Survival rates for diffuse histologic cancer were consistently worse than those for intestinal histologic cancer, which emphasizes the underlying disease biology controlling outcome. Radical lymphadenectomy for gastric adenocarcinoma would not improve surgical outcome in the United States.

Actuarial Analysis↗

Intraoperative ultrasound imaging of the liver at the time of colorectal cancer resection.

OBJECTIVES: To evaluate the accuracy of intraoperative ultrasound (IOUS) liver imaging at the time of primary colorectal cancer resection, which might eliminate incurable patients from adjuvant chemotherapy trials or permit earlier resection of curable metastases. DESIGN: A prospective trial of routine IOUS liver imaging during resections of primary colorectal cancer. The rate of detection of occult metastases by IOUS imaging alone and the false-negative rate over 22.7 months of follow-up were determined. SETTING: A tertiary care referral center in Boston, Mass. PATIENTS: Fifty-five patients undergoing 56 operations for colorectal carcinoma between May 1990 and June 1992. MAIN OUTCOME MEASURES: The rate of detection, by IOUS imaging alone, of otherwise occult hepatic metastases, the total number of patients with metastases detected at any time during follow-up, and the rate of false-negative findings on IOUS imaging and direct examination. RESULTS: Occult hepatic metastases were detected by IOUS imaging alone in 5% of patients. Restriction of IOUS imaging to patients with T3 or T4 lesions or recurrent cancers would have identified all metastases and increased the detection rate to 10%. Occult metastases were detected by IOUS imaging alone in 12.5% of patients with T3, N0 lesions. The rate of false-negative findings on IOUS imaging was 13% overall, 0% for patients with T1 or T2 lesions, 3% for patients with node-negative findings, and 7% for patients with T3, N0 lesions. CONCLUSIONS: The small increment in the detection of occult metastases by IOUS liver imaging does not warrant its use in all patients with colorectal cancer. Selective use in patients with T3 or T4 lesions or recurrent cancers increased the incremental gain in detection. The observed frequency of occult metastases in patients with T3, N0 lesions is sufficient to impact on results of adjuvant chemotherapy trials. Longer follow-up in more patients is needed to determine whether a negative IOUS study is an additional favorable prognosticator in patients with T1 and T2 lesions and node-negative findings.

Adult↗

Continuing trends in the prevalence of right-sided lesions among colorectal carcinomas.

The shift of colorectal carcinoma location toward the proximal colon has been reported. This study documents that this statistically significant trend has continued through 1992. An increase in transverse and descending colon cancers is now apparent also. Only 59% of all large-bowel cancers occurred distal to the descending colon between 1978 and 1992. Both right-sided and distal large-bowel cancers have significantly decreased in size, yet the incidence and frequency of lymph node metastases have not changed over a 65-year interval (from 1928 to 1992). This constant proportion of lymph node metastases may suggest distinct biological subsets of cancers (lymph node avid vs lymph node avoidance). The progression from small size with fewer metastases to large size with more lymph node metastases occurs only in some of the smallest distal colorectal cancers.

Boston↗