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To assess whether a therapeutic, subcutaneous injection of insulin exerts hemodynamic effects in subjects with IDDM, 0.2 U/kg regular insulin was injected subcutaneously in 17 IDDM subjects: 6 without autonomic neuropathy, 7 with autonomic neuropathy and othostatic hypotension, and 4 with autonomic neuropathy but without orthostatic hypotension. Plasma glucose was maintained at approximately 8.5 mM throughout the studies. Mean blood pressure, plasma norepinephrine concentration, forearm vascular resistances, and calf venous volume were measured before and 120 min after subcutaneous insulin, in the supine position and 5 min after standing. Supine plasma volume ([125I]albumin and [131I]albumin) was measured before and after subcutaneous injection of insulin. In all three groups, subcutaneous insulin activated the sympathetic nervous system (approximately 30% increase in norepinephrine concentration). In subjects with IDDM but without autonomic neuropathy, standing forearm vascular resistance increased approximately 70% less after subcutaneous insulin, but supine or standing mean blood pressure did not decrease. In contrast, in subjects with IDDM with autonomic neuropathy and orthostatic hypotension, subcutaneous insulin decreased supine mean blood pressure (from 99 +/- 3 to 94 +/- 5 mmHg) and exaggerated the standing decrement in mean blood pressure (24 +/- 3 vs. 19 +/- 2 mmHg) (P < 0.05). This was associated with a decrease in forearm vascular resistance. Similarly, in subjects with IDDM with autonomic neuropathy without orthostatic hypotension, subcutaneously injected insulin decreased supine mean blood pressure (from 95 +/- 2 to 89 +/- 2 mmHg) and standing mean blood pressure by 8 +/- 1 mmHg (P < 0.05). Calf venous volume was not affected by subcutaneous insulin in any of the three groups. Plasma volume did not change after subcutaneous insulin in subjects with IDDM without autonomic neuropathy, whereas it decreased in those with autonomic neuropathy and orthostatic hypotension from 1.692 +/- 0.069 to 1.610 +/- 0.064 L/m2, without orthostatic hypotension from 1.631 +/- 0.027 to 1.593 +/- 0.024 L/m2, P < 0.05). No hemodynamic effects were observed when subjects with IDDM were restudied in a control experiment where placebo (distilled water), not insulin, was injected subcutaneously. In conclusion, therapeutic doses of subcutaneous insulin activate the sympathetic nervous system; decrease blood pressure in subjects with IDDM with autonomic neuropathy, but not in those without, primarily by decreasing arterial vascular resistances and plasma volume; and have no effects of capacitance vessels. Thus, in subjects with IDDM without autonomic neuropathy, greater activation of sympathetic nervous system after subcutaneous injection of insulin prevents orthostatic hypotension.(ABSTRACT TRUNCATED AT 400 WORDS)
OBJECTIVE: To determine if subcutaneous drain or closure of the subcutaneous layer decreases the incidence of wound complications in obese women undergoing cesarean delivery. STUDY DESIGN: Seventy-six obese women undergoing cesarean delivery and with at least 2 cm of subcutaneous fat were randomized to one of three groups: group 1 had suture closure of the subcutaneous tissue, group 2 had placement of a subcutaneous closed suction drain, and group 3 had neither suture closure nor drainage. RESULTS: Wound separation occurred in 12 (15.8%), seroma in 5 (6.6%) and infection in 3 (4%). There were no reports of wound hematoma. The overall incidence of any wound complication (infection, separation, seroma, hematoma) was higher in obese women who received neither subcutaneous suture nor drain as compared to obese women who received either subcutaneous suture closure or subcutaneous drain. The incidence of major wound complications (infection or separation) was also higher in obese women who received neither subcutaneous suture or drain compared to obese women who received either subcutaneous suture closure or subcutaneous drain. CONCLUSION: The use of closed suction drainage in the subcutaneous space may reduce the incidence of postoperative wound complications in obese women who have at least 2 cm of subcutaneous fat and undergo cesarean delivery.
CONTEXT: We studied behavior of the subcutaneously implanted pancreatic tumors and the process of metastasis using syngeneic Syrian golden hamsters. DESIGN: HaP-T1, a cell line derived from nitrosamine-induced pancreatic cancer in Syrian golden hamsters was used for this experiment. Thirty-five animals were divided into two groups: subcutaneous cell inoculation and subcutaneous tissue implantation. The tumor tissue was obtained from subcutaneously implanted cancer cells. One month after implantation, the tumors were resected and studied histopathologically. The animals were followed-up weekly by palpation of the peripheral lymph nodes in order to identify local recurrence. After death, necropsy was performed. Liver, lungs and pancreas specimens were taken for histopathogical study and detection of K-ras point mutation using the PCR/RFLP method. RESULTS: The mean survival time in the subcutaneous cell inoculation group was 151+/-17.5 days, and in the subcutaneous tissue implantation group was 137 +/-12.9 days. During the follow-up, 13 subcutaneously cell inoculated hamsters (86.7%) had right axillary lymph node metastasis while subcutaneously tissue implanted hamsters did not show any palpable lymph nodes. After necropsy, 10 of the 20 subcutaneously tissue implanted animals (50%) showed metastases in the lungs at the histopathological level. However, 16 of the 20 subcutaneously tissue implanted animals (80%) showed K-ras point mutation in the lung specimens. The lungs of the animals of the subcutaneous cell inoculation group did not show any metastases. No metastases were found in the liver or the pancreas in either group. CONCLUSION: This study suggests that homologous subcutaneous cell inoculation and subcutaneous tissue implantation models showed completely different patterns of metastasis. These models may aid further research to clarify the mechanisms of metastasis in pancreatic cancer.
BACKGROUND: Eczema-like infiltrated plaques at subcutaneous heparin injection sites are well-documented side effects of these anticoagulants. However, surgical interventions may be problematic if heparin is urgently needed in these patients. OBJECTIVE: The aims of this study were to perform extensive allergy skin testing in 24 patients, including a pregnant woman in whom subcutaneous infiltrated plaques developed after subcutaneous heparin injections, and to find safe therapeutic alternatives for this group of patients. METHODS: Patch, intradermal, and subcutaneous tests were performed with a panel of unfractionated heparins (UFHs), low-molecular-weight heparins (LMWHs), and heparinoids. Since 1997, we have also been performing allergy studies in 8 patients with lepirudin, a new recombinant heparinoid; tolerance of lepirudin was investigated by means of subcutaneous and intravenous injections. The allergy investigations in the pregnant woman were limited to patch tests with heparins and intradermal and subcutaneous tests with pentosanpolysulfate, which are not contraindicated during pregnancy. RESULTS: In our study population 19 of 23 patients were sensitized to all the UFHs and LMWHs tested when intracutaneous and subcutaneous test results were read at up to 96 hours. LMWH was found to be a possible substitute in 4 patients. Five patients were also sensitized to the heparinoid pentosanpolysulfate. Sensitization to the heparinoid danaparoid was observed in 12 of the 13 patients who were tested with this substance. The administration of an intravenous bolus containing a therapeutic dose of lepirudin after negative subcutaneous provocation was tolerated without any side effects in all 8 patients. The pregnant woman was sensitized to LMWH but tolerated subcutaneous pentosanpolysulfate without any side effects. CONCLUSION: Extensive allergy skin testing should be performed to find safe alternatives. With few exceptions, all patients react to both UFHs and LMWHs, as well as to danaparoid. The subcutaneous provocation test is the most reliable diagnostic measure. Intravenous lepirudin, and in some cases subcutaneous pentosanpolysulfate, appears to be a safe alternative in patients with eczema-like infiltrated plaques at subcutaneous heparin-injection sites.
BACKGROUND: Neonatal diabetes mellitus can be extremely brittle. In this situation close glucose monitoring is essential for adequate insulin treatment. Continuous subcutaneous microdialysis is a promising approach for the babies to reduce the painful stress caused by diagnostic blood sampling. The goal of this study was to evaluate the feasibility of continuous subcutaneous microdialysis for glucose monitoring in a baby with neonatal diabetes and to assess the correlation between the blood and the subcutaneous glucose profile. PATIENT AND METHOD: During a period of seven days glucose monitoring was performed on a six month old infant with neonatal diabetes mellitus. In addition to frequent capillary blood glucose determinations, a continuous subcutaneous microdialysis device was used for the detection of the subcutaneous interstitial glucose concentration. RESULTS: Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to 23.8 mM. Variations in the adipose tissue glucose concentration closely paralleled changes in the capillary blood glucose. Based on 104 reference pairs there was a high overall correlation (r = 0.89) between the subcutaneous interstitial tissue (X) and the blood (Y) glucose concentration (Y = 1.1 X + 0.29). However the glucose profiles demonstrated a considerable variation of the time lag, up to one hour, between blood and subcutaneous interstitial glucose concentration. CONCLUSIONS: Continuous subcutaneous microdialysis helps the glucose monitoring of infants with diabetes mellitus by providing additional informations about the rise and fall of the glucose concentration. Further studies should focus on how to get a tighter link between blood glucose and the subcutaneous interstitial glucose concentration in the area around the microdialysis probe. Thus monitoring the subcutaneous interstitial glucose concentration will become a reliable procedure for real-time glucose monitoring.
In numerous patients with diabetes mellitus, a defect in the absorption of subcutaneously injected insulin has been suspected as an explanation for diabetic instability. The common clinical characteristic of these patients is poor metabolic control when insulin is injected subcutaneously, but good metabolic control when the insulin is infused intravenously. We have used three approaches to attempt to identify patients with "subcutaneous-insulin resistance." First, we performed a series of studies of subcutaneous-insulin absorption in 16 patients referred to us with a presumptive diagnosis of resistance to subcutaneous insulin; in none of these patients did we detect an abnormal response of blood glucose levels to insulin administered subcutaneously. Plasma free-insulin levels rose normally after injection. Second, we assayed insulin-degrading activity in subcutaneous biopsy specimens obtained from 25 patients throughout North America and Europe who had been diagnosed as resistant to subcutaneous insulin. In none of these patients did the insulin-degrading activity of subcutaneous tissue exceed the mean value (+/- 2 SD) of eight subcutaneous biopsy specimens obtained from control patients with diabetes. Third, we performed studies of tritiated-insulin absorption in three additional diabetic patients and three control patients with nonbrittle diabetes. These studies also suggested normal absorption of insulin. In none of the patients we studied were we able to confirm the clinical diagnosis of subcutaneous-insulin resistance. We therefore conclude that this syndrome is extremely rare and that misdiagnosis is common.
OBJECTIVE: The aim of this study was to determine the effect of the depth of subcutaneous tissue at the operative site and the closure of subcutaneous tissue on abdominal wound disruption after cesarean delivery. METHODS: 164 women divided into two groups: 70 with subcutaneous tissue thickness of at least 2 cm and 94 with subcutaneous tissue thickness more than 2 cm. These groups were randomized to closure of the subcutaneous fat tissue or no closure with cesarean delivery. RESULTS: In the 68 women with subcutaneous tissue thickness of at least 2 cm who completed the study, there was no difference between closure and no closure subgroups in terms of incidence of wound disruption. In 91 women with subcutaneous tissue thickness more than 2 cm who completed the study, the incidence of wound disruption was significantly higher in the no closure subgroup. In the no closure subgroup of 91 women with subcutaneous fat thickness more than 2 cm, the incidence of wound disruption was significantly higher than that of the 68 women with subcutaneous tissue thickness at least 2 cm. CONCLUSIONS: Subcutaneous tissue approximation with absorbable suture at closure of the abdominal incision during cesarean delivery appears to reduce the rate of postoperative wound disruption in patients with more than 2 cm of subcutaneous tissue.
OBJECTIVES: Using a new fluorescence-quenching optode which, unlike earlier oximeters, neither consumes oxygen nor generates heat, we sought to determine the effects of hemorrhage and resuscitation on subcutaneous PO2. Additionally, we compared the effects of resuscitation with diaspirin crosslinked hemoglobin, an oxygen-carrying solution, on subcutaneous PO2 to that of traditional resuscitative fluids. We also compared mean arterial pressure and central venous oxygen saturation, indirect indices of perfusion, to subcutaneous PO2, a direct index of perfusion. DESIGN: Prospective trial, randomized for selection of treatment regimen. SETTING: Shock-trauma laboratory of a medical university. SUBJECTS: Male Sprague-Dawley rats, weighing 260 to 380 g. INTERVENTIONS: Rats were bled 22 mL/kg and resuscitated, 1 min later, with either 66 mL/kg of lactated Ringer's solution, 22 mL/kg of human serum albumin, 22 mL/kg of blood, or 22 mL/kg of diaspirin crosslinked hemoglobin. A fifth group of animals was not resuscitated after hemorrhage. Subcutaneous PO2 and mean arterial pressure were monitored continuously throughout the experiment, while central venous oxygen saturation was measured intermittently. MEASUREMENTS AND MAIN RESULTS: Subcutaneous PO2 decreased in response to hemorrhage and, although it did increase after resuscitation with each fluid, no treatment was able to restore subcutaneous PO2 to baseline within 2 hrs postresuscitation. Subcutaneous PO2 continued to decrease after hemorrhage in the unresuscitated animals. In contrast, mean arterial pressure was restored to baseline values in only blood- and diaspirin crosslinked hemoglobin-treated animals, although this effect was lost within 30 mins in the blood-treated group. Only blood restored the central venous oxygen saturation to baseline values in the early postresuscitation period. CONCLUSIONS: The fluorescence-quenching optode consistently followed changes in subcutaneous PO2 during hemorrhage and after resuscitation. Diaspirin crosslinked hemoglobin performed as well as blood in restoring peripheral perfusion, as measured by subcutaneous PO2, while both of these fluids were superior to either lactated Ringer's solution or albumin. Both whole blood and diaspirin crosslinked hemoglobin restored mean arterial pressure to baseline, although the effect of the latter was of a longer duration. The pressor effect of the crosslinked hemoglobin did not affect peripheral perfusion, as reflected by the values for subcutaneous PO2. Subcutaneous PO2 is a useful adjunct in assessment of the adequacy of peripheral perfusion and may help redefine targets for resuscitation.
BACKGROUND: The definition of the "subcutaneous cellular tissue" is still debated. METHODS: In order to establish the localisation and composition of this tissue, or, merely its existence, we interviewed French dermatologists and conducted a bibliographic study on the historical definitions of the so-called "subcutaneous cellular tissue". A questionnaire was sent to French professors of dermatology to assess their definition of the "subcutaneous cellular tissue". They were also asked to make a simple cartoon showing the anatomy of the skin and "subcutaneous cellular tissue". RESULTS: We obtained 37 answers which could be classified in three main categories: 1) "subcutaneous cellular tissue" and hypodermis are synonymous, 2) "subcutaneous cellular tissue" is an autonomous tissue which separates the hypodermis from the tissues below and 3) "subcutaneous cellular tissue" designates all structures located below the hypodermis. In an historic perspective, the "cellular system" was a macroscopic concept described in the eighteenth century as whitish fibrils delimitating "cells". It was renamed loose connective tissue in the twentieth century and thus "cellular" became obsolete. The definition of skin, and of "subcutaneous cellular tissue" in particular, has greatly changed over time. In the eighteenth century, only epidermis and dermis were considered as belonging to the skin, although some included the tela subcutanea. In the twentieth century, the "subcutaneous cellular tissue" is considered either as a part of the hypodermis, or as the hypodermis itself or as a tissue located between the hypodermis and the fascia. DISCUSSION: The difficulty in defining "subcutaneous cellular tissue" is the result of a French semantic problem. The "cellular tissue" became loose connective tissue. For French dermatologists, the skin is composed of epidermis, dermis and hypodermis and the hypodermis can therefore not be subcutaneous. In order to check whether an autonomous tissue could be evidenced under the skin, we conducted an histologic study, which is presented in a second article.
BACKGROUND: A reliable method for direct measurement of both subcutaneous and visceral fat volume is the measurement of fat tissue area from tomographic pictures by CT or by MR imaging. However, these are not widely usable because of high cost and/or exposure to radiation. METHODS: We compared sonographic subcutaneous and visceral fat indices with fat distribution by serial-slice MR imaging in 17 subjects. Sonographic subcutaneous or visceral fat index is standardized thickness of subcutaneous fat tissue or the intra-abdominal depth at the level of umbilicus by height. RESULTS: Sonographic visceral fat index and intra-abdominal depth were significantly correlated with visceral fat volume by serial-slice MR imaging (r = 0.746, r = 0.726, respectively). Similarly, sonographic subcutaneous fat index and subcutaneous fat thickness were significantly correlated with subcutaneous fat volume by serial-slice MR imaging (r = 0.825, r = 0.816, respectively). The ratio of sonographic visceral fat index and sonographic subcutaneous fat index was closely correlated with the ratio of the visceral fat volume and the subcutaneous fat volume by single-slice MR imaging, which proves to be related to cardiovascular disease risk (r = 0.722). CONCLUSION: Sonographic subcutaneous or visceral fat index could be an easily measured and inexpensive indicator for the assessment of fat distribution instead of CT or MR imaging.
The pharmacokinetics of sulphadoxine-trimethoprim was studied in 6 pre-ruminant calves using two different products. Product A, which contained 200 mg sulphadoxine and 40 mg trimethoprim per mL, was administered intravenously or subcutaneously at a dosage of 25 mg sulphadoxine and 5 mg trimethoprim.kg-1 bodyweight. Product B, containing 62.5 mg sulphadoxine and 12.5 mg trimethoprim per mL plus lidocaine (1 mg.mL-1), was given subcutaneously at the same dosage. After intravenous administration of product A the mean time of half-life of elimination phase (t1/2) for sulphadoxine was 12.9 h, steady-state volume of distribution (Vd(ss)) was 0.44 L.kg-1 and clearance was 0.024 L.kg-1.h-1. Respective values for trimethoprim were 1.9 h, 2.0 L.kg-1 and 0.9 L.kg-1.h-1. After subcutaneous administration, the bioavailability of sulphadoxine was 96% and 98% and the time to reach a maximum concentration was 6.3 and 8.0 h for products A and B, respectively. The Cmax for trimethoprim was higher for product A (0.49 microgram.mL-1) than for product B (0.32 microgram.mL-1) (p = 0.014). Slow absorption from the injection site appeared to delay the elimination of trimethoprim after subcutaneous administration when compared to that after intravenous administration: apparent elimination t1/2 for trimethoprim after intravenous administration of product A was 1.9 h compared to 3.9 h and 3.6 h after subcutaneous administration of products A and B, respectively. The difference between intravenous and subcutaneous administrations was statistically significant (p < 0.05). Also the mean residence time was significantly shorter (p < 0.05) after intravenous administration (2.4 h) than that after subcutaneous administration of product A (6.9 h) and B (7.1 h). The bioavailability of trimethoprim was lower than that of sulphadoxine: 76% and 74% for products A and B, respectively. All 6 calves showed pain after subcutaneous administration of product A and the injection sites were warm and showed soft oedematous reactions 5-8 cm in diameter. Three of the calves also showed some pain after subcutaneous administration of product B; the local reactions were less severe. A marked increase was seen in creatine kinase activity after subcutaneous administration of both products. Product A caused a more pronounced increase but the difference was not statistically significant. We suggest 30 mg.kg-1 at 24-h intervals or alternatively 15 mg.kg-1 at 12-h intervals as the minimum dosage of sulphadoxine-trimethoprim combination for pre-ruminant calves. Extravascular routes of administration should be avoided due to marked tissue irritation at the injection site.
Apomorphine, a short-acting dopamine D1 and D2 receptor agonist, was the first dopamine receptor agonist used to treat Parkinson's disease. Subcutaneous apomorphine is currently used for the management of sudden, unexpected and refractory levodopa-induced 'off' states in fluctuating Parkinson's disease either as intermittent rescue injections or continuous infusions. Other indications include the challenge test for determining the dopaminergic responsiveness and finding the appropriate dose of the drug in intermittent subcutaneous administration. Except for a rapid on- and offset of the antiparkinsonian response with subcutaneous apomorphine, the magnitude and pattern of the motor response to single dose of subcutaneously administered apomorphine is qualitatively comparable to that of oral levodopa. Seventy-five percent of patients achieve a clinically significant improvement with a dose of apomorphine 4mg. The efficacy of intermittent subcutaneous apomorphine injections as an add-on to levodopa therapy in advanced Parkinson's disease was explored in one short-term, randomised, double-blind, placebo-controlled trial, one short-term and six long-term, open-label, uncontrolled studies, including a total of 195 patients. These studies provide evidence that this mode of administration was successful in aborting 'off' periods and improving Parkinson's disease motor scores, but tended to increase dyskinesias. No levodopa-sparing effect was observed. Eleven long-term, open-label, uncontrolled studies, including a total of 233 patients evaluated the efficacy of continuous subcutaneous apomorphine infusions in monotherapy or as an add-on to levodopa therapy in advanced Parkinson's disease. These studies proved that subcutaneous apomorphine infusions are successful in aborting 'off' periods, reducing dyskinesias and improving Parkinson's disease motor scores with the added benefit of a substantial levodopa-sparing effect. The apomorphine challenge test has at least 80% overall predictive ability to clinically diagnose Parkinson's disease across the different stages of the disease and parkinsonian syndromes. Similarly, those data also indicate that the apomorphine challenge test has a >80% ability to predict dopaminergic responsiveness across all stages of Parkinson's disease. Adverse events are usually mild and consist predominantly of cutaneous reactions and neuropsychiatric adverse effects. The incidence of adverse effects is higher in patients receiving continuous infusion than in those receiving intermittent pulsatile administration. Based on the results of these studies it is recommended that subcutaneous apomorphine either as intermittent injections or continuous infusions should be offered to any suitable Parkinson's disease patient who has difficulties in his/her management with conventional therapy. Low-dose levodopa therapy in combination with waking-day hours subcutaneous apomorphine infusion would probably be the most efficient treatment. Continuous subcutaneous apomorphine infusions should be evaluated before more invasive measures or neurosurgical interventions are contemplated.
Refinement of continuous subcutaneous insulin infusion for diabetes therapy requires improved knowledge of subcutaneous insulin absorption kinetics. We have used kinetic modelling to quantitate systemic insulin delivery produced by subcutaneously-infused insulin (i.e. simulated meal and basal delivery). Profiles were studied in normal subjects, with endogenous insulin suppressed. Paired studies of intravenous insulin infusion enabled systemic insulin delivery to be quantitated. High rate subcutaneous delivery (10 U in 5 min) resulted in a systemic delivery of approximately 8 U in 4 h. Increasing infused insulin concentration delayed systemic delivery (p less than 0.025). Both continuous and pulsatile low-rate infusions (2.4 U/h) gave similar slow increases in systemic delivery to 1 U after 4 h. Computer fitting to a two-pool model of the subcutaneous space suggested a low rate of insulin degradation for all profiles (rate constant less than 10%/h). We conclude that: systemic insulin delivery following subcutaneous infusion conforms reasonably to a two-pool model, subcutaneous insulin degradation is low regardless of input profile, a long delay in basal systemic delivery should be taken into account when initiating or resuming interrupted subcutaneous insulin infusion. Kinetic modelling of subcutaneous insulin absorption should be useful to predict the impact of programming strategies for continuous subcutaneous insulin infusion therapy.
Heparin has a short half-life (8 to 12 hours) and therefore must be administered by continuous infusion or by intermittent subcutaneous injection. Intermittent subcutaneous injection may lead to fluctuation in the levels of anticoagulation attained. In correcting this deficiency, the programmable automated subcutaneous infusion pump in conjunction with weekly home nursing visits has been used. Eight pregnant women with documented deep venous thrombosis or embolic events before pregnancy who received such therapy were studied. Eight similar subjects who received intermittent subcutaneous injection, matched for age, parity, site of deep venous thrombosis, and days on a regimen of heparin therapy, served as the control group. The mean daily dose of heparin by subcutaneous infusion pump was higher (29,445 vs 13,822 U), resulting in smoother, more therapeutic heparinization (mean partial thromboplastin time, 20.6 vs 10.4 seconds above control) when compared with the intermittent subcutaneous injection group (p less than 0.05, p less than 0.007). There were two complications (hematoma, site infection) in the intermittent subcutaneous injection group while none occurred in the subcutaneous infusion pump group. When used in concert with weekly home visits, the subcutaneous infusion pump method of administration allowed more even control of anticoagulation, appeared to result in fewer complications (although not statistically significant), and subjectively was better received by patients than the intermittent subcutaneous injection technique.
In the current study subcutaneous glucose kinetics were investigated in tissue fluid collected with a percutaneous device (PD). PDs containing a subcutaneous tissue chamber were implanted subcutaneously in New Zealand white rabbits. Sintered titanium fiber mesh sheets were used for subcutaneous anchorage of the PD. The bottom of the subcutaneous tissue chamber was either covered with a titanium fiber mesh sheet, a cellulose acetate membrane, or left uncovered. Subcutaneous glucose kinetics were determined after injection of octreotide and glucagon. The tissue reaction to the implants was evaluated histologically. No dynamic relationship was observed between glycaemia and subcutaneous tissue fluid glucose for all membrane covered devices. Histological evaluation showed that the presence of a seroma cavity in combination with obstruction of the membrane prevented adjustment of the subcutaneous glucose concentration in response to changes in glycaemia. In the uncovered devices, on the other hand, changes in glycaemia were reflected in subcutaneous tissue fluid. Our results prove that it is possible to measure changes in the glucose concentration in subcutaneous tissue fluid collected with a percutaneous device. Therefore, we conclude that a percutaneous device has an application as model to study the in vivo performance of implantable glucose sensors. The use of porous membranes in such devices has to be avoided.
PURPOSE: We hypothesized that the clinical benefit of elastic compression stockings (ECS) is at least in part due to an increase in subcutaneous pressure that may promote resorption of extracellular fluids, providing more efficient diffusion of oxygen and nutrients from the microcirculation to the skin and subcutaneous tissues. METHODS: To test this hypothesis we designed and standardized a device for measuring subcutaneous pressure in patients. We then measured the supine perimalleolar subcutaneous pressure from a single limb in four groups: group 1 consisted of control subjects (n = 8); group 2 consisted of patients with varicose veins and superficial venous insufficiency without lipodermatosclerosis or edema (n = 5); group 3 consisted of patients with deep venous insufficiency and lipodermatosclerosis but without edema (n = 8); and group 4 consisted of patients with deep venous insufficiency, lipodermatosclerosis, and clinically evident edema (n = 8). Measurements were made at baseline and after application of 20 to 30 mm Hg and 30 to 40 mm Hg ECS. RESULTS: There was no significant difference in the baseline subcutaneous pressure between the three groups without clinical edema (p > 0.05). Baseline perimalleolar pressure was elevated, however, in group 4 patients compared with groups 1, 2, and 3 (p < 0.05). All three groups with chronic venous insufficiency (CVI) (groups 2, 3, 4) demonstrated increases in subcutaneous pressure with application of ECS, which was statistically significant in groups 3 and 4. There was no difference between the increase in perimalleolar subcutaneous pressure induced by 20 to 30 mm Hg or 30 to 40 mm Hg ECS in groups 3 and 4. CONCLUSIONS: Patients with CVI and edema have significant elevations in supine resting perimalleolar subcutaneous pressure compared with control subjects and patients with CVI without edema. Twenty to 30 mm Hg and 30 to 40 mm Hg ECS increased measured perimalleolar subcutaneous pressure in patients with CVI with and without clinical edema but not in control patients. These results suggest the mechanism of benefit of ECS in patients with CVI is due at least in part to an increase in subcutaneous pressure that may act to promote more efficient absorption of perimalleolar extracellular fluid.