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A comparative study of subcutaneous mastectomy with radical mastectomy.

The purpose of this study was to compare the results of 133 cases (131 patients) of subcutaneous mastectomy with axillary dissection between 1983 and 1999 and 910 cases of radical mastectomy during the same period. The median follow-up period of the subcutaneous mastectomy group and the radical mastectomy group were 66 months and 81 months, respectively. The age at operation was significantly (p<0.01) younger in the subcutaneous mastectomy group than in the radical mastectomy group and the clinical stage was significantly (p<0.01) earlier. Lymph node metastasis was significantly (p<0.01) higher in the radical mastectomy than in the subcutaneous mastectomy group. There was no difference in ER status between the two groups. There was local recurrence in 5 (3.8%) members of the subcutaneous mastectomy group and in 12 (1.3%) members of the radical mastectomy group. There was no difference in disease-free survival and overall survival between the two groups. Divided into two subgroups by lymph node status, there was no difference in disease-free survival and overall survival between the two groups. Local recurrence occurred more frequently (p<0.05) in the subcutaneous mastectomy group, however, than in the radical mastectomy group when no lymph node metastasis was found. Multivariate analysis using the Cox hazard model showed that operation method and lymph node status were independent prognostic factors for local recurrence, whereas, lymph node status and ER status were independent prognostic factors of disease-free survival. In conclusion, subcutaneous mastectomy presents a risk factor for local recurrence, but the survival rate of the subcutaneous mastectomy group is as favourable as the radical mastectomy group.

Adult↗

[Postoperative pain management using subcutaneous fentanyl and ketamine after abdominal gynecologic surgery].

BACKGROUND: Subcutaneous opioid is one way of managing postoperative pain in patients undergoing anticoagulant therapy. We have evaluated the safety and the efficacy of postoperative pain management using subcutaneous fentanyl and ketamine after abdominal gynecologic surgery. METHODS: Written informed consent was obtained from 50 ASA physical status 1 or 2 female patients aged between 20 and 65. Patients were randomized to one of 5 groups. Group 1, 2 and 3 received 25, 35 and 50 microg x h(-1) subcutaneous fentanyl infusion, respectively. Group 4 received 25 microg x h(-1) fentanyl and 2 mg x h(-1) ketamine subcutaneously; group 5 received 25 microg x h(-1) fentanyl and 4 mg x h(-1) ketamine subcutaneously. General anesthesia was administered to all patients. Two hours after induction, subcutaneous infusion of fentanyl and ketamine was started in the patients and discontinued 24 hours after the operation. All patients were assessed twice, at 4 hours and at 24 hours after operation. Blood gas analysis was performed. Number of analgesic administration required during the 24 hours after operation was recorded. Groups 1, 2, 3 and groups 1, 4, 5 were evaluated as one group, respectively. Group differences were analyzed by variance analysis. Differences of analgesic administration were analyzed with Kruskal-Wallis test. RESULTS: As to anesthetic requirement during the 24 hours after operation, there were no significant differences among treatment groups. With respect to blood gas analysis, only individuals receiving subcutaneous 25 microg x h(-1) fentanyl and 4 mg x h(-1) ketamine maintained high PaO2 4 hours after the operation (P<0.05). CONCLUSIONS: We recommend administration of 25 microg x h(-1) fentanyl and 4 mg x h(-1) ketamine subcutaneously, which maintains high Pao2 and requires less analgesic.

Adult↗

Patient preferences for migraine therapy: subcutaneous sumatriptan compared with other medications.

BACKGROUND: This study was conducted to identify, from the patient's perspective, the important attributes of a migraine therapy and to assess the performance of subcutaneous sumatriptan, aspirin, acetaminophen, and patients' usual therapies with respect to these attributes. METHODS: Six hundred forty-eight patients who had received subcutaneous sumatriptan (one or two doses, 6 mg per dose, for a single migraine episode) or placebo in a clinical trial completed questionnaires. RESULTS: According to patients, the four most important attributes of a migraine therapy are "how well it works," "how safe it is," "how fast it works," and "side effects." The least important attribute is "cost of drug." Subcutaneous sumatriptan received significantly more favorable scores than did aspirin, acetaminophen, or patients' usual therapies with respect to the attributes of how well it works, how fast it works, and number of doses needed to relieve pain. Subcutaneous sumatriptan was also rated more favorably than either aspirin or patients' usual therapies with respect to side effects. Acetaminophen and aspirin were rated significantly more favorably than subcutaneous sumatriptan on the attributes "easy to take" and "easy to buy." Asked which drug they would use again for migraine, more patients selected subcutaneous sumatriptan than any other single medication. More patients also ranked subcutaneous sumatriptan as the best overall performer compared with other migraine medications taken in the last 12 months. CONCLUSIONS: These data indicate that according to patients' preferences, subcutaneous sumatriptan possesses many of the attributes of an ideal migraine therapy.

Adult↗

Effects of hypotension on cutaneous and subcutaneous blood flow in anaesthetized humans.

The aim of this study was to determine the effect of controlled hypotension on subcutaneous and cutaneous haemodynamics in humans. Moderate hypotension was achieved with nitroglycerin (NTG) and sodium nitroprusside (SNP) infusion during narconeuroleptanalgesia in seven patients. Subcutaneous and cutaneous blood flow were measured by a superficial and deep heat clearance (HC) technique. The mean arterial pressure (BPa) decreased by 23%-30% and heart rate (fc) increased but only during NTG infusion (+22%; P less than 0.02). Subcutaneous and cutaneous blood flows remained unchanged despite a significant decrease in calculated cutaneous resistance (NTG: -26%, P less than 0.01; SNP: -34%, P less than 0.02] and subcutaneous vascular resistance changed only with SNP (-31%, P less than 0.02). After hypotension was discontinued the subcutaneous blood flow decreased (-13%, P = 0.05), whereas subcutaneous vascular resistance returned to its control values. An inverse relationship was found between fc and BPa (NTG: r = -0.525, P less than 0.01; SNP: r = -0.622, P less than 0.01) as well as with subcutaneous blood flow (NTG: r = -0.653, P less than 0.001; SNP: r = -0.573, P less than 0.01). In addition, we found oscillatory changes in deep HC values which differed in magnitudes (NTG 0.22 (SEM 0.09) W.m-1.degree C-1 vs SNP 0.42 (SEM 0.1) W.m-1.degrees C-1, P less than 0.01) and frequencies (NTG 0.02 (SEM 0.006) Hz vs SNP 0.01 (SEM 0.002) Hz, P less than 0.01). Despite unchanged blood flow, the effects of controlled hypotension on cutaneous and subcutaneous haemodynamics were different depending on the type of drug. These differences may have been related to counterregulatory responses and/or to direct vascular effects.

Adult↗

Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance.

AIMS/HYPOTHESIS: Cross-sectional studies indicate that enlarged subcutaneous abdominal adipocyte size is associated with hyperinsulinaemia, insulin resistance and glucose intolerance. To further explore the pathophysiological significance of these associations, we examined prospectively whether enlarged subcutaneous abdominal adipocyte size predicts Type II (non-insulin-dependent) diabetes mellitus. METHODS: Body composition (hydrodensitometry), mean subcutaneous abdominal adipocyte size (fat biopsy), insulin sensitivity (hyperinsulinaemic clamp) and the acute insulin secretory response (25-g i.v. GTT) were assessed in 280 Pima Indians with either normal (NGT), impaired (IGT) or diabetic glucose tolerance (75-g OGTT). Subjects with NGT were then followed prospectively. RESULTS: After adjusting for age, sex and per cent body fat, mean subcutaneous abdominal adipocyte size was 19% and 11% higher in subjects with diabetes and IGT, compared with those with NGT (p < 0.001). Insulin sensitivity was inversely correlated with mean subcutaneous abdominal adipocyte size (r = -0.53, p < 0.0001), even after adjusting for per cent body fat (r = -0.31, p < 0.001). In 108 NGT subjects followed over 9.3 +/- 4.1 years (33 of whom developed diabetes), enlarged mean subcutaneous abdominal adipocyte size but not high per cent body fat, was an independent predictor of diabetes, in addition to a low insulin sensitivity and acute insulin secretory response [relative hazard 10th vs 90th centile (95% CI): 5.8 (1.7-19.6), p < 0.005]. In 28 NGT subjects with a 9% weight gain over 2.7 +/- 1.3 years, changes in insulin sensitivity were inversely and independently related to changes in mean subcutaneous abdominal adipocyte size and per cent body fat. CONCLUSION/INTERPRETATION: Although enlarged mean subcutaneous abdominal adipocyte size is associated with insulin resistance cross-sectionally, prospectively, both abnormalities are independent and additive predictors of Type II diabetes.

Abdomen↗

Starvation depresses acylglycerol biosynthesis in bovine subcutaneous but not intramuscular adipose tissue homogenates.

The primary objective of this study was to document the effects of starvation on acylglycerol biosynthesis in homogenates of intramuscular and subcutaneous adipose tissues. Adipose tissue samples were obtained from 8th-13th thoracic rib sections from 12 Angus cattle (six steers plus six heifers). Three steers and three heifers were starved for 72 h prior to slaughter while the remainder were slaughtered 4 h after food was withheld. Fat-free 700 x g centrifugal fractions were used to measure the esterification of radiolabeled sn-glycerol 3-phosphate (G-3-P) into acylglycerols at 1.0 mM palmitic or stearic acid, or 0.2 mM oleic, linoleic, or alpha-linolenic acid. There were significant tissue x fatty acid interactions for rates of incorporation into diacylglycerols and triacylglycerols; in subcutaneous, but not intramuscular homogenates, palmitic > stearic = oleic = linoleic = alpha-linolenic acid. Subcutaneous homogenates incorporated a greater percentage of G-3-P into triacylglycerols, and a lesser percentage into phospholipid, than intramuscular homogenates (P < 0.05). In intramuscular homogenates, the primary product of G-3-P esterification to saturated fatty acids was phospholipids. When unsaturated fatty acid served as substrates, triacylglycerols and phospholipids were produced in equal proportions in intramuscular homogenates, and triacylglycerols were the predominant product in subcutaneous homogenates. Intramuscular adipose tissue homogenates exhibited no response to starvation, whereas triacylglycerol and diacylglycerol synthesis was depressed by approximately 50% in subcutaneous adipose tissue homogenates. Similarly, phosphatidic phosphohydrolase activity, initially greater in subcutaneous than in intramuscular adipose tissue, was decreased by approximately 50% by starvation in subcutaneous adipose tissue, but not in intramuscular adipose tissue. We conclude that differences in rates of diacylglycerol and triacylglycerol biosynthesis, and response to starvation, between intramuscular and subcutaneous adipose tissues were due to dissimilarities in the activity of phosphatidic phosphohydrolase.

Adipose Tissue↗

Infiltrative subcutaneous malignant fibrous histiocytoma: a comparative study with deep malignant fibrous histiocytoma and an observation of biologic behavior.

Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas of adulthood. Although it is usually intramuscular and pseudocapsulated, we have recently observed MFHs with extremely infiltrative growth margins, which are predominantly located in the subcutis. These lesions are often associated with incomplete primary surgical excision, the subsequent need for additional surgery or adjuvant therapy, and an increased risk for local recurrence. To further analyze the growth pattern and clinical implication of the subcutaneous infiltrative MFHs, we reviewed a series of 24 subcutis and 21 intramuscular MFHs of the extremities. Morphologically, we defined "infiltrative" as tumor extension along normal tissue planes for a minimum measurable distance of 2 mm from the edge of the main mass. Radiographic findings were correlated with pathologic findings. Of the 24 subcutis MFHs, 83% showed an infiltrative growth pattern, involving 5% to 90% (mean, 51%) of the evaluable margin. Fifty percent of patients with subcutaneous MFH had both an infiltrative growth pattern and positive surgical resection margin on initial resection. Only 25% noninfiltrative subcutaneous MFHs had a positive initial surgical resection margin. Of the 21 intramuscular MFHs, only 5 (24%) had an infiltrative growth pattern that involved 5% to 90% (mean, 40%) of the evaluable margin. One of the five tumors had 90% margin infiltration with multiple positive surgical resection margins. Of 16 noninfiltrative intramuscular MFHs, 3 (19%) had positive resection margins. Magnetic resonance imaging (MRI) and/or computed tomography (CT) scan correctly identified the growth pattern in 87% of subcutaneous and 88% of intramuscular MFHs. Patient follow-up evaluation showed that four (17%) patients with subcutaneous MFHs had resection-proven recurrences, 6 to 57 months after diagnosis. All four of these tumors had infiltrative growth patterns and positive margins on the original surgical resection. There were no local recurrences of the intramuscular MFHs. Two patients of 20 in the infiltrative subcutaneous MFH group and two patients of four in the well-circumscribed subcutaneous MFH group had biopsy-proven metastases, which developed within 5 years after diagnosis. Six patients had metastases in the intramuscular MFH group. A group of MFHs, predominantly subcutaneous, have an extremely infiltrative growth pattern. This growth pattern, documented by radiographic methods and/or light microscopic examination of biopsy specimens, should indicate that a wider margin on initial resection is necessary to entirely excise the lesion. The presence or absence of an infiltrative growth pattern is not predictive of the tumor's metastatic potential.

Adult↗

Growth of visceral fat, subcutaneous abdominal fat, and total body fat in children.

OBJECTIVE: To examine the patterns of growth of visceral fat, subcutaneous abdominal fat, and total body fat over a 3- to 5-year period in white and African American children. RESEARCH METHODS AND PROCEDURES: Children (mean age: 8.1 +/- 1.6 years at baseline) were recruited from Birmingham, Alabama, and those with three or more repeated annual measurements were included in the analysis (N = 138 children and 601 observations). Abdominal adipose tissue (visceral and subcutaneous) was measured using computed tomography. Total body fat and lean tissue mass were measured by DXA. Random growth curve modeling was performed to estimate growth rates of the different body fat compartments. RESULTS: Visceral fat and total body fat both exhibited significant growth effects before and after adjusting for subcutaneous abdominal fat and lean tissue mass, respectively, and for gender, race, and baseline age (5.2 +/- 2.2 cm(2)/yr and 1.9 +/- 0.8 kg/yr, respectively). After adjusting for total body fat, the growth of subcutaneous abdominal fat was not significant. Whites showed a higher visceral fat growth than did African Americans (difference: 1.9 +/- 0.8 cm(2)/yr), but there was no ethnic difference for growth of subcutaneous abdominal fat or total body fat. There were no gender differences found for any of the growth rates. DISCUSSION: Growth of visceral fat remained significant after adjusting for growth of subcutaneous abdominal fat, implying that the acquisition of the two abdominal fat compartments may involve different physiologic mechanisms. In contrast, growth of subcutaneous abdominal fat was explained by growth in total body fat, suggesting that subcutaneous fat may not be preferentially deposited in the abdominal area during this phase of growth. Finally, significantly higher growth of visceral fat in white compared with African American children is consistent with cross-sectional findings.

Abdomen↗

Effects of sex on the change in visceral, subcutaneous adipose tissue and skeletal muscle in response to weight loss.

OBJECTIVE: To examine the influence of sex on whole body and regional subcutaneous, visceral, total adipose tissue (AT), skeletal muscle (SM), and lean tissue in response to weight loss induced by diet alone (DO) or the combination of diet and aerobic (DA) or resistance exercise (DR). DESIGN: Sixty upper-body obese men and women were randomly assigned to one of three treatments: DO, DA, or DR. All tissues were measured using a whole body, magnetic resonance imaging protocol. RESULTS: Within each group reductions were observed for body weight ( approximately 11 kg), subcutaneous and visceral AT (P<0.01). After controlling for pretreatment differences in tissue size, reductions in total adiposity, total and regional subcutaneous and visceral adipose tissue were not different between sexes (P>0.1). Independent of sex, the reduction in visceral AT was greater than subcutaneous AT (P<0.05) in response to DO and DA. With the exception of DA women, the reduction in abdominal subcutaneous AT was greater (P<0.05) than lower-body subcutaneous AT in response to diet and exercise, but not diet alone, in both sexes (P>0.05). Independent of sex, skeletal muscle mass was preserved within the exercise groups (P>0.05) but not diet alone (P<0.05). Peak VO2 (l/min) improved in the DA groups as did muscular strength in the DR groups (P<0.01). CONCLUSIONS: These findings indicate that in response to diet or diet and exercise-induced weight loss, reductions in total adiposity, subcutaneous and visceral adipose tissue distribution are not different in obese men and women. Independent of sex, the combination of diet and exercise results in a preservation of skeletal muscle mass, a preferential reduction of abdominal subcutaneous AT, and improved functional capacity by comparison to diet alone.

Adipose Tissue↗

Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue: a study of 15 patients.

Extranodal low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type occurs in the gastrointestinal tract, salivary gland, thyroid, orbit, lung, and breast. We report 15 patients with MALT-type lymphomas involving skin and subcutaneous tissue. All patients had tumors with histologic features of low-grade B-cell lymphoma of MALT type, including marginal zone cells (15 of 15 cases), plasmacytic differentiation (10 of 15 cases), Dutcher bodies (three of 15 cases), and reactive germinal centers (10 of 15 cases). All expressed pan B-cell antigens and monotypic immunoglobulin. Seven patients (five women, two men) aged 29 to 86 years (median, 53 years) had primary MALT-type lymphoma of skin (6) or subcutaneous tissue (1). One patient had persistent disease, and four patients had relapses involving skin, subcutaneous tissue, breast, orbit, and lymph node. At last follow-up (11-121 months; median, 36 months), one patient was alive with disease, and six patients had no evidence of disease. Three patients (two women, one man) aged 36 to 67 years (median, 57 years) had concurrent MALT-type lymphoma involving both subcutaneous tissue and extracutaneous sites at primary diagnosis, including lung, breast, orbit, lymph node, and bone marrow. One patient responded to treatment but relapsed with lymphoma of the skin and breast. The other two patients had persistent disease despite treatment. One patient died of disease at 25 months, and, at last follow-up (7 and 46 months), two patients were alive with disease. Five patients (four women and one man) aged 29 to 72 years (median, 63 years) had secondary skin or subcutaneous involvement by MALT-type lymphoma with primary tumors of ocular adnexa (3) or parotid gland (2). All five patients had relapses, which involved skin or subcutaneous tissue, parotid gland, lacrimal gland, breast, and lymph node. At last follow-up (61-137 months), two patients were alive with disease and three were alive with no evidence of disease. Low-grade B-cell lymphomas of MALT type may arise in or secondarily involve the skin and subcutaneous tissue and have a tendency to affect middle-aged to older women. These tumors are characterized by multiple extranodal relapses and are associated with long patient survival. Patients with primary MALT-type lymphoma of skin or subcutaneous tissue without extracutaneous involvement at diagnosis were more likely to experience prolonged disease-free survival than patients with extracutaneous spread at presentation (p < 0.03).

Adult↗

Semiquantitative culture of subcutaneous segment for conservative diagnosis of intravascular catheter-related infection.

BACKGROUND: Sensitivity and negative predictive values of combined surface cultures (skin and hub) are high in the presumptive diagnosis of catheter-related infection, but specificity and PPVs are poor. The purpose of the study was to evaluate the yield of the semiquantitative culture of the subcutaneous segment in the diagnosis of colonization of the catheter tip without removal of the catheter. METHODS: A prospective study was performed in 124 nontunneled central venous catheters that were removed because of suspected infection or the end of therapy. Catheter colonization was considered if >15 colony-forming units (CFU) in the roll procedure or > 1,000 CFU in the quantitative Cleri procedure were recovered from the tip cultures ("gold standard"). Before removing the catheter, a semiquantitative culture of skin surrounding the point of insertion, a semiquantitative culture of the subcutaneous segment (after removing the catheter only 2 cm), a semiquantitative cultures of the hub, and a pareated quantitative blood culture were performed. Receiver operating characteristic curves were calculated to estimate the cutoff points, and a culture was considered positive when CFUs were > or =15, > or =15, and > or =5 for skin, hub, and subcutaneous segment cultures, respectively. RESULTS: Catheter colonization was detected in 51 catheters. The mean duration of catheterization was 14 +/- 8 days, and the rates of incidence of tip colonization and bacteremia were 2.9 per 100 catheter days and 1.2 per 100 catheter days, respectively. Sensitivity of skin, subcutaneous, and hub cultures analyzed individually were < or =61%; however, specificity and positive predictive values (PPVs) of subcutaneous segment cultures were significantly higher than skin cultures (94% and 88.5% vs 71.6% (p = .001) and 62% (p = .014), respectively). Sensitivity of the combined skin and hub cultures and of the combined subcutaneous segment and hub cultures were similar: 86.2% and 84.3%, respectively; however, specificity and PPVs of this latter combination were significantly higher than former: 82% and 78.1% vs 59.7% (p = .008) and 61.9% (p = .07), respectively. The likelihood ratio of a positive test for the combined subcutaneous segment and hub culture was 4.68, and only 2.13 for the combined skin and hub culture. CONCLUSIONS: These results indicate that the combined subcutaneous segment and hub culture constitutes an easy, effective procedure for the conservative diagnosis of catheter colonization.

Bacteriological Techniques↗

Modified subcutaneous tissue with neovascularization is useful as the site for pancreatic islet transplantation.

The success rate of subcutaneous transplantation of pancreatic islets has been extremely low. Insufficient oxygen supply to the grafted islets is one possible major obstacle to the preservation of graft function. This study attempted to use basic fibroblast growth factor (bFGF) in subcutaneous transplantation to induce neovascularization and a sufficient blood flow around the space formed for grafted islets in the subcutaneous tissues. A bFGF-releasing device was designed enclosing bFGF in a polyethylene terephthalate mesh bag coated with polyvinylalcohol hydrogel. In the vascularized group (n = 5), two bFGF-releasing devices were implanted bilaterally into the subcutaneous tissue of the back of streptozotocin-induced diabetic Lewis rats. One week after implantation, isolated rat islets (5000) were syngeneically transplanted subcutaneously after the removal of the devices. In the control group (n = 5), no devices were implanted and the same number of rat islets was transplanted directly. One week after the implantation of the devices into the test animals, a thick, well-vascularized capsule was observed in the subcutaneous site. All vascularized recipient rats showed significant decreases in nonfasting blood glucose and maintained normoglycemia for more than 1 month after islet transplantation. However, in the control group, all rats failed to achieve normoglycemia after transplantation. This study provides evidence that the subcutaneous tissue is a promising site for pancreatic islet transplantation, offering convincing advantages in acceptability for diabetic recipients. Establishment of this subcutaneous islet transplantation technique will afford some new perspectives on successful clinical islet transplantation.

Animals↗

Glucose monitoring with long-term subcutaneous microdialysis in neonates.

BACKGROUND: Microdialysis is a new approach for continuous monitoring of small molecules in the extracellular space, and hypoglycemia is a common problem in neonatal intensive care. The objective of this study was to evaluate subcutaneous microdialysis for long-term glucose monitoring in neonatal intensive care. We determined the relative recovery of the microdialysis system in vitro and in vivo, the stability of the relative recovery in vivo during long-term microdialysis, and the correlation between blood and dialysate concentrations of glucose and urea. Furthermore, we evaluated the sensitivity and specificy of subcutaneous microdialysis for the diagnosis of hypoglycemia. PATIENT AND METHODS: Thirteen infants (10 neonates) with gestational ages of 30.2 to 45.6 weeks were investigated by microdialysis of subcutaneous adipose tissue and blood sampling. Subcutaneous microdialysis was performed for a median (range) duration of 9 (4-16) days. RESULTS: The application was safe, even in extremely low birth weight infants (<1000 g) with scanty subcutaneous adipose tissue. The mean +/- standard deviation of the relative recovery in vitro was 101 +/- 3% for glucose and 100 +/- 2% for urea. Using urea as the internal standard, the mean relative recovery in vivo was 96.4 +/- 12.7% at the beginning and remained constant up to 16 days. The correlation between microdialysate and blood was significant for glucose (r = 0.88) and urea (r = 0.98). Subcutaneous microdialysis allowed the detection of asymptomatic hypoglycemias. The diagnostic sensitivity of a dialysate glucose </=2.9 mM to predict a blood glucose level </=2.8 mM was 92.3%, with 88.1% specificy. The positive predictive value with a 13.4% prevalence of a blood glucose </=2.8 mM was 54.5%, with a negative predictive value of 98.7% and an accuracy of 88.7%. CONCLUSIONS: Subcutaneous microdialysis is a safe method, well suited for long-term glucose monitoring in neonates during intensive care. Subcutaneous microdialysis can be used to reduce blood loss and painful stress resulting from diagnostic blood sampling in high-risk neonates.

Blood Glucose↗

Glucose concentration in subcutaneous extracellular space.

OBJECTIVE: To compare the subcutaneous glucose sensor measurements with two reference methods. Previous studies provide conflicting findings about the real glucose concentrations in subcutaneous tissue. Some suggest substantially lower concentration, whereas others measure proportionally higher glucose concentrations compared with the blood compartment. Before these results can be taken seriously as an expression of the real glucose concentration in the extracellular space, the measurements must be validated by an independent method. RESEARCH DESIGN AND METHODS: We applied a microdialysis-based enzyme sensor to measure glucose concentration in subcutaneous tissue. We also developed two reference methods: subcutaneous filtrate collection and an equilibration method using ultrafiltration membranes to support the earlier findings. We provided an anatomical model to explain the results. RESULTS: The mean overall intercellular filtrate glucose concentration, sampled with the filtrate collector and taken after a 6-h stabilization time, including the values during the glucose clamp period, was 46 +/- 9%. The mean subcutaneous glucose concentration measured with the glucose sensor, calibrated in vitro, was 44 +/- 8% of the mean venous blood glucose concentration. Mean overall intercellular equilibrate glucose concentration, i.e., the mean glucose concentration in the subcutaneous extracellular space, taken after a 4-h stabilization time, was 46 +/- 15% of the mean venous blood glucose concentration. CONCLUSIONS: The close agreement between the mean values of subcutaneous glucose concentrations, obtained with three independent methods--filtration, equilibration, and dialysis (sensor)--shows the real glucose concentration in subcutaneous interstitial fluid is approximately 50% the blood glucose value in normal humans. Our results clarify some of the conflicting evidence presented in previous studies.

Adult↗

Subcutaneous glucose concentration in humans. Real estimation and continuous monitoring.

OBJECTIVE: To determine the real subcutaneous glucose concentration in healthy volunteers to help in the development of new calibration methods for subcutaneous glucosensors. RESEARCH DESIGN AND METHODS: We developed a new method to estimate the real subcutaneous glucose concentration based on the recirculation of phosphate-buffered saline (PBS) in a microdialysis probe inserted into the subcutaneous tissue. Tissue glucose diffuses into the probe until complete equilibration between the glucose concentration outside and inside the microdialysis probe is achieved. Later, the glucose content of the recirculated PBS is assessed in vitro. We applied the method in 10 healthy volunteers under fasting state and during a hyperglycemic clamp. In addition, we monitored the subcutaneous glucose with an enzymatic-amperometric glucosensor combined with a microdialysis probe. RESULTS: The subcutaneous glucose concentration measured by the recirculation method was 72 +/- 6 and 78 +/- 6% of the blood glucose measured in the fasting state and during the hyperglycemic clamps, respectively. On the other hand, the glucosensor's signal correlated significantly with the blood glucose. CONCLUSION: The recirculation method estimated the real subcutaneous glucose concentration, opening the way to develop new calibration procedures for subcutaneous glucosensors. However, a suitable calibration procedure is still lacking.

Adult↗

Open-flow microperfusion of subcutaneous adipose tissue for on-line continuous ex vivo measurement of glucose concentration.

OBJECTIVE: To evaluate a novel technique for on-line continuous glucose measurement in subcutaneous adipose tissue, and to investigate its accuracy for detection of hypoglycemia. RESEARCH DESIGN AND METHODS: The method combined an open-flow microperfusion of subcutaneous adipose tissue using a double lumen catheter and an extracorporeal sensor cell. An isotonic ion-free solution was perfused through the inner lumen of the catheter, equilibrated with the subcutaneous tissue fluid, and sampled through the outer lumen. The recovery was continuously monitored as the ratio between the measured sampled fluid conductivity and the subcutaneous tissue fluid conductivity (assumed to have a constant value of 1.28 S/m at 25 degrees C). Glucose concentration was calculated on-line from the measured glucose in the sampled fluid and the measured recovery in healthy volunteers during hyperglycemic glucose loads (n = 8), hypoglycemic hyperinsulinemic clamp (n = 6), and a 24-h monitoring period (n = 7). RESULTS: Subcutaneous glucose concentrations in the fasting state were 94% of the plasma glucose concentrations in arterialized venous samples. According to the error grid analysis, 96.9% of the on-line measured subcutaneous glucose concentrations during hyperglycemia and 96.3% during hypoglycemia were in accurate or acceptable zones. The mean differences between the measured subcutaneous glucose and the actual plasma glucose concentration were -0.06-3.3 mmol/l (hyperglycemia), and -0.6-1.1 mmol/l (hypoglycemia). CONCLUSIONS: By combining open-flow microperfusion, glucose sensor, and conductivity measurement, glucose concentration in the subcutaneous adipose tissue can be monitored on-line, extracorporeally, and continuously without any in vivo calibration, and gives accurate measurements during hyper- and hypoglycemia.

Adipose Tissue↗

Utility of subcutaneous fat aspiration for diagnosing amyloidosis in patients with isolated peripheral neuropathy.

OBJECTIVE: To determine the value of subcutaneous fat aspiration in patients with sensorimotor peripheral neuropathy. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all patients undergoing subcutaneous fat aspiration for suspected amyloidosis from January 1, 1994, through December 31,1999. We classified patients undergoing subcutaneous fat aspiration due to peripheral neuropathy into 2 groups: (A) those with isolated peripheral neuropathy and (B) those with any family history and laboratory or clinical findings typically associated with systemic amyloidosis. RESULTS: The study population consisted of 450 patients with peripheral neuropathy in whom fat aspiration was performed for suspected amyloidosis. This constituted 56% of all fat aspirations performed during the study period. Group A had 143 patients, and group B had 307 patients. None of the patients in group A had a positive subcutaneous fat aspirate, whereas 17 patients (6%) in group B had a positive subcutaneous fat aspirate (P=.002, Fisher exact test). The subcutaneous fat aspirate was most commonly positive in patients with a monoclonal protein or other clinical findings associated with amyloidosis. CONCLUSIONS: The yield of a subcutaneous fat aspirate in patients with isolated peripheral neuropathy and no other associated family history, signs, or symptoms of amyloidosis is low. Subcutaneous fat aspiration should be reserved for evaluating patients with peripheral neuropathy who also have findings associated with systemic amyloidosis.

Adipose Tissue↗

Reduced alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes as a modulator of fasting and postprandial triglyceride levels in men.

This study examined the postprandial lipemia of two groups of men displaying similar age, body weight, and regional fat distribution, but characterized by either low (n = 11) or high (n = 15) alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes. In addition to fat cell lipolysis, adipose tissue lipoprotein lipase (AT-LPL) as well as postheparin plasma LPL activities were measured in the fasting state. Fasting AT-LPL and PH-LPL activities were similar in both groups. Maximal adipose cell lipolysis induced by isoproterenol (beta-adrenergic agonist) as well as the beta-adrenergic sensitivity did not differ between both groups of men. The selective alpha(2)-adrenergic agonist UK-14304 promoted a similar antilipolytic response in subcutaneous abdominal adipocytes from both groups. However, the alpha(2)-adrenergic sensitivity, defined as the dose of UK-14304 that produced half-maximal inhibition of lipolysis (IC(50)), was significantly different between groups (P < 0.0001). Men with low versus high subcutaneous abdominal fat cell alpha(2)-adrenergic sensitivity showed higher fasting TG levels. In the whole group, a positive relationship was observed between log-transformed IC(50) UK-14304 values of subcutaneous adipocytes and fasting TG levels (r = 0.39, P < 0.05), suggesting that a low abdominal adipose cell alpha(2)-adrenergic sensitivity is associated with high TG levels. After the consumption of a high-fat meal, subjects with low subcutaneous abdominal adipose cell alpha(2)-adrenergic sensitivity showed higher TG levels in total, medium, and small triglyceride-rich lipoprotein (TRL) fractions at 0- to 6-h time points than men with high adipocyte alpha(2)-adrenergic sensitivity (P values ranging from 0.01 to 0.05). Stepwise regression analysis showed that the fasting TG concentration was the only variable retained as a significant predictor of the area under the curve of TG levels in total TRL fractions (73% of variance) among independent variables such as body weight, percent body fat, visceral and subcutaneous abdominal adipose tissue accumulation measured by CT, as well as subcutaneous abdominal fat cell alpha(2)-adrenoceptor sensitivity. Taken together, these results indicate that a reduced antilipolytic sensitivity of subcutaneous abdominal adipocytes to catecholamines may increase fasting TG levels, which in turn play a role in the etiology of an impaired postprandial TRL clearance in men.

Abdomen↗