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Biomedical subjects

R M Green

Publications and source records attributed to R M Green.

At least 91 records · Page 5Linked to original sources

A condemnation of subcutaneous fasciotomy.

Controversy exists regarding the indications and methods for lower-extremity fasciotomy. Two recent cases at our institution in which recurrent, acute limb-threatening ischemia occurred despite adequate fascial division have convinced us that in certain situations subcutaneous fasciotomy is clearly inadequate. In both patients, both of whom were young, intact healthy skin between the lower extent of the incision and the malleolus acted as a tourniquet, causing recurrent compartment syndrome as reperfusion edema occurred after initial repair. We believe that therapeutic fasciotomy in young patients with relatively noncompliant skin should include division of skin from the knee to the ankle on at least one side to prevent a tourniquet effect by intact skin at the ankle.

Adolescent↗

A co-twin study of the effect of calcium supplementation on bone density during adolescence.

The effect of calcium supplementation on bone mineral density (BMD) was evaluated in female twin pairs aged 10-17 years with a mean age of 14 years. Forty-two twin pairs (22 monozygotic, 20 dizygotic; (including one monozygotic pair from a set of triplets) completed at least 6 months of the intervention: 37 pairs to 12 months and 28 pairs to 18 months. BMD was measured by dual-energy X-ray absorptiometry (DXA). In a double-blind manner, one twin in each pair was randomly assigned to receive daily a 1000 mg effervescent calcium tablet (Sandocal 1000), and the other a placebo tablet similar in taste and appearance to the calcium supplement but containing no calcium. Compliance (at least 80% tablets consumed), as measured by tablet count, was 85% in the placebo group and 83% in the calcium group over the 18 months of the study, on average increasing dietary calcium to over 1600 mg/day. There was no within-pair difference in the change in height or weight. When the effect of calcium supplementation on BMD was compared with placebo at approximately 6, 12 and 18 months, it was found that there was a 0.015 +/- 0.007 g/ cm2 greater increase in BMD (1.62 +/- 0.84%) at the spine in those on calcium after 18 months. At the end of the first 6 months there was a significant within-pair difference of 1.53 +/- 0.56% at the spine and 1.27 +/- 0.50% at the hip. However, there were no significant differences in the changes in BMD after the initial effect over the first 6 months. Therefore, we found an increase in BMD at the spine with calcium supplementation in females with a mean age of 14 years. The greatest effect was seen in the first 6 months; thereafter the difference was maintained, but there was no accelerated increase in BMD associated with calcium supplementation. The continuance of the intervention until the attainment of peak bone mass and follow-up after cessation of calcium supplementation will be important in clarifying the optimal timing for increased dietary calcium and the sustained, long-term effects of this intervention.

Adolescent↗

Impact of inflow reconstruction on infrainguinal bypass.

PURPOSE: This study assessed whether multisegmental disease that is severe enough to require an inflow procedure adversely affects infrainguinal bypass patency, limb salvage, or patient survival rates. METHODS: The records of 495 patients who underwent 551 infrainguinal bypass grafting procedures were reviewed. Saphenous vein and prosthetic grafts were evaluated separately. Graft patency rates, patient limb salvage rates, and patient survival rates in those grafts that arose from a reconstructed inflow source were compared with those that arose from normal, nonreconstructed inflow sources. When grafts had either hemodynamic failure or occlusion, the cause of failure was identified. RESULTS: Four-year primary patency rates in vein grafts that arose from a reconstructed inflow sources were lower than those in grafts that arose from nonreconstructed inflow sources (41% vs 54%; p = 0.006). Assisted primary patency rates and secondary patency rates, however, were similar (62% vs 74% and 64% vs 77%, respectively). The 4-year primary patency rate (45% vs 55%), assisted primary patency rate (60% vs 60%), and secondary patency rate (60% vs 61%) in prosthetic grafts did not vary based on inflow source. The most common cause of graft failure was inflow failure, except in the vein grafts that did not require an inflow procedure, in which the most common cause of failure was graft failure. Inflow failure occurred in 24% and 22% of the vein and prosthetic grafts with multisegmental disease, respectively, but in only 7% (p < 0.001) and 10% (p < 0.05), respectively, of those that arose from normal nonreconstructed inflow. The presence of an inflow procedure did not affect limb salvage rates or patient survival rates, regardless of graft material. CONCLUSIONS: Long-term patency rates, patient limb salvage rates, and survival rates in patients with a reconstructed inflow source were similar to those of patients with a normal nonreconstructed inflow. A major cause of occlusion is inflow failure, and this occurs in a greater proportion of patients with multisegmental disease. These patients, in particular, may benefit from patient surveillance to screen for progression of their inflow disease and to allow for intervention before infrainguinal graft occlusion.

Aged↗

Fate of the proximal aortic cuff: implications for endovascular aneurysm repair.

PURPOSE: Long-term success of endoluminally placed grafts for exclusion of abdominal aortic aneurysms (AAAs) relies on secure fixation at the proximal and distal cuffs and, as such, assumes that the fixation sites will not dilate over time. Data regarding this issue, however, are not yet available. This study was performed to evaluate the region of the proximal anastomosis in patients many years after having undergone conventional AAA repair to determine the potential for late dilatation after placement of an endoluminal device. METHODS: Three hundred forty-six patients underwent repair of an infrarenal AAA at our institution between January 1985 and December 1990. Of 97 eligible living patients, 33 both had their original CT scans available and underwent repeat scanning at a mean of 88.6 +/- 23.8 months (mean +/- SD; range, 40 to 134 months) after repair. RESULTS: The overall 5-year survival rate was 73%. The mean preoperative infrarenal aortic cuff diameter by CT scan was 24.5 +/- 3.7 mm (range, 19 to 33 mm). At an average of 89 months after repair, the mean infrarenal aortic diameter increased 4.3 mm to 28.8 +/- 7.7 mm (range, 20 to 52 mm; p = 0.0004 by t test). The proximal cuff at this time measured 30 mm or more in 11 patients (33%), and as early as 6 years after operation three of the seven patients (43%) scanned within this time period had cuffs that were dilated to 30 mm or more. Late dilatation to 30 mm or more was rare (16%) in patients who had preoperative cuffs that measured 27 mm or less. The mean late iliac artery size was 16.9 +/- 8.9 mm (range, 10 to 52 mm), and 30% (10 of 33) measured 20 mm or more. CONCLUSIONS: One third of all patients who survive AAA repair experience significant dilatation of their proximal aortic cuff over time. Proximal dilatation is rare but not absent in patients who have smaller initial aortic cuff diameters. This dilatation rarely causes problems after conventional suture fixation, but the long-term implications of cuff dilatation after endoluminal repair are unclear. Our findings suggest that endovascular aortic prostheses that have the ability to continue to self-expand many years after implantation may be required and that endovascular prostheses may not be the best option for patients who have a long life expectancy or for those who have preoperative proximal cuffs greater than 27 mm.

Aorta, Abdominal↗

Prosthetic above-knee femoropopliteal bypass grafting: results of a multicenter randomized prospective trial. Above-Knee Femoropopliteal Study Group.

PURPOSE: There are excellent arguments in favor of the preferential use of prosthetic grafts above the knee for the treatment of infrainguinal occlusive disease. This approach has been popularized on the basis of the seemingly acceptable results when using polytetrafluoroethylene (PTFE). However, in many centers, knitted Dacron polyester has been used in these patients, and there are several studies that show equivalent and, in some, superior results with Dacron when compared with PTFE. The purpose of this study was to examine these results in a definitive way. METHODS: A randomized prospective trial in eight clinical academic centers in the United States and Canada was initiated in 1991. Two hundred forty-four patients eligible for such a study, by virtue of criteria extant in each institution at the time, were centrally randomized. They underwent placement of either a knitted Dacron polyester graft impregnated with collagen or a thin-wall expanded reenforced PTFE graft to the above-knee popliteal artery, usually from the common femoral artery. They were frequently observed by protocol for as long as 5 years by a physical examination noninvasive hemodynamic study, including duplex scanning in many instances. Continuing patency was noted, as were other potential adverse outcome events. The data were analyzed by the log-rank test for cumulative patency and expressed as Kaplan-Meier curves. Data were further analyzed with a Cox proportional hazards model. RESULTS: There were no differences in graft groups in demographic or comorbid factors. The procedural mortality rate was zero, and the morbidity rate was low (6.5%). The long-term patient survival rate was excellent (77% at 3 years). At the end of these years, no statistical significance in primary or secondary patency rates was observed between the two grafts (primary patency rate, 62% +/- 14.4% for Dacron; 57% +/- 15.5% for PTFE). No unexpected adverse outcomes on limb status were noted. Patency rates in both graft groups were inferior in patients who received small grafts (5 to 6 mm vs 7 to 8 mm; hazards ratio, 4.15) and younger (<65 years) smoking patients. CONCLUSIONS: The fact that these two prosthetic grafts performed in equivalent fashion in a controlled, well-conducted prospective study is not surprising in spite of the previous work that suggested differences. If the preferential use of synthetic bypass grafts above the knee is to be used, it should be restricted to older nonsmokers with favorable anatomy. In that instance, the choice of graft material will depend on handling characteristics and cost. Above-knee prostheses should be only selectively used in younger, smoking patients, and graft size should be carefully considered in patients who undergo this operation.

Arterial Occlusive Diseases↗

Primary fibrinolysis during supraceliac aortic clamping.

PURPOSE: An increased incidence of bleeding complications has been observed after supraceliac aortic clamping (SCC). This study was performed to identify possible hemostatic abnormalities that contribute to this problem. METHODS: A prospective cohort study over a 3-month period was performed by comparing hemostatic parameters in 10 consecutive patients who required elective SCC with those of eight concurrent randomly selected control subjects who required infrarenal clamping (IRC) for abdominal aortic reconstruction. Measures of coagulation, fibrinolysis, platelet function, temperature, hemodilution, and hepatic function were performed at selected times before, during, and after operation. RESULTS: Aneurysm size, fibrinogen, D-dimers, prothrombin, partial thromboplastin time, platelet counts, bleeding times, hemodilution, and temperature were comparable in both groups. Patients in the SCC group, however, consistently developed a primary fibrinolytic state within 20 minutes after supraceliac clamping, reflected by significantly decreased euglobulin clot lysis times (ECLT; p < 0.0001), elevated tissue plasminogen activator (t-PA) levels (p < 0.0006), elevated t-PA-to-plasminogen activator inhibitor-1 ratios (p < 0.0001), and reduced alpha 2-antiplasmin levels (p < 0.002). SCC produced hepatocellular injury documented by elevations in both aspartate transaminase (p < 0.0001) and lactate dehydrogenase (p < 0.009). CONCLUSIONS: SCC rapidly induces a primary fibrinolytic state manifested by increased circulating t-PA, reduced alpha 2-antiplasmin, and increased fibrinolytic activator-to-inhibitor ratios. These effects may be a result of hepatic hypoperfusion caused by SCC leading to insufficient clearance of t-PA. Antifibrinolytic agents may be of benefit if bleeding develops after aortic procedures that require supraceliac clamping.

Aged↗

Mobilization of predominantly Philadelphia chromosome-negative blood progenitors using cyclophosphamide and rHUG-CSF in early chronic-phase chronic myeloid leukaemia: correlation with Sokal prognostic index and haematological control.

Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m2 and rHUG-CSF 150 microg/m2 daily. This regimen was well tolerated with no major adverse events reported. More than 2 x 10(6)/kg CD34+ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0-25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score > or = 1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization (P = 0.006 and 0.02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poor-prognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.

Adult↗

Regulation of hepatocyte bile salt transporters during hepatic regeneration.

Bile formation is an essential liver-specific function, and the hepatic regeneration that occurs in response to hepatocellular injury is often associated with cholestasis. We have employed a partial hepatectomy model to examine the effect of hepatic regeneration on tissue-specific bile salt transporters and on Na(+)-K(+)-adenosinetriphosphatase (ATPase). Liver-specific sodium-dependent taurocholate uptake by basolateral plasma membrane vesicles was undetectable 24 h after hepatectomy. Basolateral membrane protein expression of the sodium-taurocholate cotransporter and gene expression of Ntcp were decreased by > 90% 24 h after partial hepatectomy. In vitro transcription assays demonstrated that Ntcp gene transcription was also markedly reduced. In contrast, hepatic Na(+)-K(+)-ATPase activity, protein expression, and gene expression were unaffected by partial hepatectomy. Similarly, protein and gene expression of the ectoATPase, a putative canalicular bile salt transporter, and canalicular ATP-dependent taurocholate uptake remained unchanged. Partial hepatectomy results in a marked reduction in the gene transcription and expression of the liver-specific Ntcp, as well as a decrease in protein expression and loss of transport activity. These changes provide a potential mechanism for the decrease in hepatocellular bile salt transport that is associated with hepatic regeneration.

Adenosine Triphosphatases↗

Effect of different diets on oral bacteria and caries activity in Sprague-Dawley rats.

The conventional rat model of dental caries has been used extensively to measure the contribution of various inoculated bacteria or diets to dental caries production. Only limited information is available on the effect of different diets on the oral bacterial community as a whole. In the present study, using selective and non-selective media, the oral bacterial populations of 21-day-old Sprague-Dawley rats fed diets with commercial rat and mouse cubes (control), high-starch (56%) and sucrose (56%) diets for 21 days were investigated. The high-starch diet did not significantly change the proportion of oral bacteria compared with the control group; the high-sucrose diet significantly enhanced the total cultivable bacteria, particularly Actinomyces naeslundii, Streptococcus rattus and Streptococcus suis-like bacteria. The order of diets with respect to the production of dental caries was sucrose > starch > normal. Thus the high-sucrose diet changed the oral bacterial population of Sprague-Dawley rats and these changes were reflected in the increased level of dental caries.

Actinomyces↗

Hepatic regeneration is associated with preservation of microsomal glucuronidation.

Significant controversy exists regarding the regulation of glucuronidation during the process of hepatic regeneration. We used a partial hepatectomy rat model to elucidate the effects of hepatic regeneration on the various components of the microsomal glucuronidation system. Hepatic microsomes were prepared by standard sucrose density centrifugation, coupled with a modified technique involving Percoll centrifugation. Microsomal uridine diphosphate (UDP)-glucuronosyltransferase (UGT) protein expression and UGT messenger RNA (mRNA) levels were measured by Western and Northern blotting. UGT enzyme activity was determined toward two prototypical aglycones, p-nitrophenol and estrone, in intact and digitonin-treated microsomes. Microsomal uptake of the cosubstrate for all glucuronidation reactions, UDP-glucuronic acid (UDP-GlcUA), was determined using a rapid-filtration assay. Microsomal enrichment after hepatectomy was preserved only when the Percoll method was used. Microsomal UGT protein expression and UGT mRNA levels were unaltered after hepatectomy. UGT enzyme activity toward estrone was unchanged 1 day posthepatectomy compared with sham laparotomy controls. Similarly, p-nitrophenol glucuronide formation was unaffected by hepatic regeneration 1, 2, and 5 days posthepatectomy when digitonin-treated microsomes were used. Glucuronidation of p-nitrophenol in intact microsomes was increased in partial hepatectomy compared with sham-operated controls at 1 and 2 days. This increase was not attributable to changes in microsomal UDP-GlcUA uptake, which was comparable in both groups. We conclude that microsomal glucuronidation, in contrast to other well characterized hepatic metabolic functions, is highly preserved during liver regeneration.

Animals↗

Retired elite female ballet dancers and nonathletic controls have similar bone mineral density at weightbearing sites.

Elite female ballet dancers exhibit several risk factors for osteoporosis during their performing years. To study the long-term effect of this lifestyle, we compared the bone mineral density (BMD) of 101 retired elite female ballet dancers (mean age 51 years, SD = 14 years) and 101 normal controls, derived from a twin study, matched hierarchically for age, height, weight, and menopausal status. The dancers, who had been retired for a mean of 25.6 years (range 1-53 years) reported a greater prevalence of previous menstrual disturbance, greater lifetime alcohol intake and smoking, and a lower dietary milk intake in adolescence than controls (all p < 0.05). However, current exercise in the dancers was twice that of the controls (p < 0.01). The BMD of retired dancers did not differ from that of the controls at weightbearing sites. The mean +/- SE difference in BMD (dancers minus controls) was 0.009 +/- 0.013 at the total body, -0.009 +/- 0.018 at the total hip, 0.005 +/- 0.017 at the femoral neck, 0.014 +/- 0.018 at the femoral trochanter, 0.036 +/- 0.022 at the femoral intertrochanter and -0.017 +/- 0.021 at the lumbar spine. Retired dancers had lower mean (+/- SE) BMD at the nonweightbearing sites: ultradistal radius (-0.029 +/- 0.008) (p < 0.01) and at the midthird radius (-0.019 +/- 0.011) (p < 0.05). There was no difference in the proportion in each of the World Health Organization (WHO) categories of osteopenia (t score -1.0 to -2.5) and osteoporosis (t score < -2.5) at any of the measured sites. Regression analysis revealed that menstrual disturbance was negatively associated with BMD at the lumbar spine and the ultradistal radial sites, but not at the weightbearing femoral sites. This sample of retired elite ballet dancers who had multiple historical risk factors does not appear to have an increased risk for future hip or vertebral fracture based on WHO standards.

Absorptiometry, Photon↗

Measurement of carotid bifurcation pressure gradients using the Bernoulli principle.

Current randomized prospective studies suggest that the degree of carotid stenosis is a critical element in deciding whether surgical or medical treatment is appropriate. Of potential interest is the actual pressure drop caused by the blockage, but no direct non-invasive means of quantifying the hemodynamic consequences of carotid artery stenoses currently exists. The present prospective study examined whether preoperative pulsed-Doppler duplex ultrasonographic velocity (v) measurements could be used to predict pressure gradients (delta P) caused by carotid artery stenoses, and whether such measurements could be used to predict angiographic percent diameter reduction. Preoperative Doppler velocity and intraoperative direct pressure measurements were obtained, and per cent diameter angiographic stenosis measured in 76 consecutive patients who underwent 77 elective carotid endarterectomies. Using the Bernoulli principle (delta P = 4v(2), pressure gradients across the stenoses were calculated. The predicted delta P, as well as absolute velocities and internal carotid artery/common carotid velocity ratios were compared with the actual delta P measured intraoperatively and with preoperative angiography and oculopneumoplethysmography (OPG) results. An end-diastolic velocity of > or = 1 m/s and an end-diastolic internal carotid artery/common carotid artery velocity ratio of > or = 10 predicted a 50% diameter angiographic stenosis with 100% specificity. Although statistical significance was reached, preoperative pressure gradients derived from the Bernoulli equation could not predict actual individual intraoperative pressure gradients with enough accuracy to allow decision making on an individual basis. Velocity measurements were as specific and more sensitive than OPG results. Delta P as predicted by the Bernoulli equation is not sufficiently accurate at the carotid bifurcation to be useful for clinical decision making on an individual basis. However, end-diastolic velocities alone as well as internal carotid artery/ common carotid artery velocity ratios are highly specific in the prediction of clinically significant carotid stenoses. An end-diastolic velocity of > or = 1 m/s accurately identifies a 50% or greater diameter stenosis, and thus may in some cases be sufficient for operation.

Blood Flow Velocity↗

Determinants of hip axis length in women aged 10-89 years: a twin study.

Hip axis length (HAL), a measure of femoral geometry, has been shown to predict hip fracture in white women over the age of 67 years, independently of bone mineral density at the femoral neck. A cross-sectional study of 304 pairs of female twins [176 monozygous (MZ) and 128 dizygous (DZ)], aged between 10 and 89 years, was performed to examine the influence of age, constitutional, lifestyle, and genetic factors on HAL. HAL was calculated from dual energy X-ray absorptiometry scans of the proximal femur using an automated technique with an Hologic QDR-1000W. Lean mass, fat mass, height, and weight were also measured. Maximum mean HAL was achieved by the age of 15 years. After this age there was no discernible dependency of mean HAL on age. Using within-pair differences, after adjusting for height there were no other independent constitutional or lifestyle predictors. Cross-sectionally, after adjustment for height, MZ and DZ correlations were 0.79 (95% CI: 0.73-0.84) and 0.54 (95% CI: 0.39-0.68), respectively, and independent of age. The MZ correlation exceeded the DZ correlation (p < 0.001). The best-fitting model apportioned 79% (SE 7%) of variation in height-adjusted HAL to additive genetic factors. There was marginal evidence that an environmental influence shared by twins explained 31% (SE 16%) of height-adjusted variance (p = 0.07), in which case the genetic variance was reduced to 51% (SE 15%). Adjustment for height had reduced the magnitude of total variance by 26%, and 95% of this reduction was in the additive genetic component. Applying a previously described theoretical model, approximately 10% of the increased risk of hip fracture associated with a maternal history of hip fracture could be attributed to the genetic factors determining HAL. We conclude that, in women, adult HAL is achieved by midadolescence. After adjustment for height, which is itself largely under genetic influence, other genetic factors appear to play the predominant role in explaining variation in HAL.

Adolescent↗

Activated protein C resistance: prevalence and implications in peripheral vascular disease.

PURPOSE: Activated protein C (APC) is a naturally occurring anticoagulant that interacts with factors V and VIII to inhibit the clotting cascade. Resistance to APC (APC-R), hypothesized to occur as a result of an abnormal factor V, has been documented in up to 40% of patients with venous thrombotic events, but its prevalence in patients with arterial disease remains ill defined. METHODS: With an assay of APC resistance that expresses the ratio of the activated partial thromboplastin time with and without the addition of exogenous APC, APC resistance ratios were quantitated in 200 individuals comprising 177 patients with vascular disease and 23 control subjects. An abnormal activated partial thromboplastin time was present in four patients who were excluded from analysis. The 173 remaining patients formed the study population and were divided into diagnostic subgroups on the basis of the most symptomatic problem. RESULTS: APC resistance was documented in 20 individuals, representing 11.6% of the study group. The highest prevalence of APC resistance was observed in patients with lower extremity occlusive disease, with the APC-R ratio below 2.0 in 13.7%. Within the subgroup of individuals with lower extremity disease, 76 patients (10 with APC-R, 13.2%) underwent infrainguinal bypass and were monitored a mean of 47 +/- 8 months. Occlusion of the arterial reconstruction occurred in 22 patients (29%). Six (60%) of the patients with APC-R had failed reconstructions, versus 16 (24%) of 66 patients without APC-R (p = 0.02). CONCLUSIONS: These findings suggest that APC-R is relatively common in patients with peripheral vascular disease, especially in those with lower extremity occlusive disease. APC-R appears to be a risk factor for failure of infrainguinal bypass. These observations suggest that screening for APC-R may be useful in patients with peripheral vascular disease, providing the opportunity to restore the normal thrombogenic balance with anticoagulant therapy in susceptible individuals.

Aged↗