SEARCH · PubMed Health

Results for “Subcutaneous”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed1993

[Subcutaneous venous reservoirs: comparative study of their efficacy in patients with AIDS versus oncology and hematology patients].

BACKGROUND: Chronic venous access may constitute a serious problem in some patients and the subcutaneous venous reservoirs have demonstrated to be a useful alternative. AIDS patients require intense pharmacologic treatment, thus the use of subcutaneous venous reservoirs may be specially useful. However, the prevalence of septic type complications following placement of the subcutaneous venous reservoirs in these patients is particularly high. AIMS: To know the efficacy of subcutaneous venous reservoirs in the AIDS population and compare the results in a non AIDS population. METHODS: All the subcutaneous venous reservoirs placed between January 1990 and December 1992 were prospectively studied with two groups being established: Group I: patients with positive serology for HIV and who achieved criteria of AIDS requiring placement of a subcutaneous venous reservoirs. Group II: All the remaining patients in whom a subcutaneous venous reservoirs was placed during the same period of time. RESULTS: The incidence of infection was higher in group I (AIDS) with respect to group II (0.1 versus 0.014 infections/100 catheters/day, p < 0.01) and the non septic complications were higher in group II (3.6% versus 12.7%, p < 0.0004). The catheters were most frequently used in group I with respect to group II (12.7 +/- 7.1 versus 3.3 +/- 4.9 punctures/month) but the period was use longer in group II (13.7 +/- 9.2 versus 4.3 +/- 3.1 months, p < 0.0001). CONCLUSIONS: The population of AIDS patients may benefit greatly from the systematic use of subcutaneous venous reservoir due to their clinical and therapeutic characteristics. Nonetheless greater risk of infection may occur in these patients because of the greater need for punctures with respect to the other indications for placement of these catheters.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Opposite nociceptive effects of the arginine/NO/cGMP pathway stimulation in dermal and subcutaneous tissues.

1. Nitric oxide has been described either as pronociceptive or antinociceptive. In this investigation, using an electronic pressure-metre, the intradermal and the subcutaneous effects of prostaglandin E(2) (PGE(2)) and agents that mimic or inhibit the arginine/NO/cGMP pathway were compared. 2. The hypernociceptive effect of the intradermal injection of PGE(2) (100 ng) was immediate, peaking within 15-30 min and returning to basal values in 45-60 min. The subcutaneous injection of PGE(2) induced a hypernociception with a delayed peak (3 h) plateauing for 4-6 h. 3. Intradermal administration of 3-morpholino-sydnonimine-hydrochloride (SIN-1) enhanced, while its subcutaneous administration inhibited, subcutaneous hypernociception induced by PGE(2). This inhibition was prevented by ODQ (8 micro g) but not by NG-monomethyl-L-arginine (L-NMMA) (50 micro g). 4. Intradermal but not subcutaneous administration of L-arginine (1-100 micro g), SIN-1 (1-100 micro g) and dibutyrylguanosine 3':5'-cyclic monophosphate (db cGMP) (0.1-100 micro g) induced an early (15-30 min) dose-dependent hypernociceptive effect. Intradermal pretreatment with NG-monomethyl-L-arginine (L-NMMA; 50 micro g) inhibited the hypernociception induced by L-Arg (10 micro g), but not that induced by SIN-1 (10 micro g) or db cGMP (10 micro g). 5. Intradermal injection of ODQ (8 micro g) antagonized the hypernociception induced by L-arginine and SIN-1, but not that induced by db cGMP. 6. Considering (a) the different time course of intradermal and subcutaneous PGE(2)-induced hypernociception, (b) the opposite nociceptive effect of intradermal and subcutaneous administration of SIN-1 (db cGMP) as well as the arginine/NO/cGMP pathway, the existence of different subsets of nociceptive primary sensory neurons in which the arginine/NO/cGMP pathway plays opposing roles is suggested. This hypothesis would explain the apparent contradictory observations described in the literature.

Animals↗

PubMed2005

Lipoatrophy induced by subcutaneous administration of octreotide in the treatment of acromegaly.

Octreotide is the first somatostatin analogue to become available for clinical use in the treatment of acromegaly. To our knowledge, there are no reports describing lipoatrophy in patients treated with octreotide. Here, we report three patients who developed lipoatrophy after treatment with subcutaneous octreotide. Three patients (all women; 36, 43, and 50 years of age) with diagnosis of acromegaly due to pituitary macroadenoma who had undergone transsphenoidal surgery and radiotherapy received subcutaneos octreotide because of uncontrolled disease. The dose of octreotide was increased gradually in all patients. Lipoatrophy was noticed around the injection sites after about 6 years, 30 months, and 4 years of subcutaneous octreotide treatment in all patients. Thereafter, subcutaneous octreotide treatment was changed to intramuscular octreotide-LAR injection in all patients. In two of them, lipoatrophy around all injection sites did not regress after about 8 and 12 months of octreotide-LAR treatment, respectively. In the third patient, lipoatrophy around the injection sites regressed after 12 months of octreotide-LAR treatment. These cases highlight a potential for subcutaneous octreotide to induce lipoatrophy. The underlying mechanism is unknown but an immunological mechanism which is seen in lipoatrophy induced by insulin may be involved in the pathogenesis. Besides; simple trauma, personal susceptibility, mistakes in the administration of the drug, a problem in drug pH, or an idiosyncratic reaction of adipocytes to octreotide or additives in the drug may have caused lipoatrophy in our patients. Lipoatrophy in these cases was observed on long-term subcutaneous octreotide administration. Although intramuscular octreotide-LAR has largely replaced subcutaneous octreotide, we suggest close clinical follow-up for lipoatrophy in patients who are still on subcutaneous octreotide.

Acromegaly↗

PubMed2005

Sonographic measurement of the thickness of subcutaneous tissues in nonalcoholic fatty liver disease versus other chronic liver diseases.

PURPOSE: To measure an average subcutaneous tissue thickness in nonalcoholic fatty liver disease (NAFLD) and other liver diseases using bedside sonography and make comparisons of thickness between groups. The study also addressed whether a cut-off subcutaneous tissue thickness exists below which NAFLD is unlikely. METHODS: Sonograph was performed on 113 consecutive patients with chronic liver disease. Diagnosis was derived from serological data combined with liver biopsy in all cases. Distance was measured between the skin and the liver surface and was labeled the subcutaneous tissue thickness. RESULTS: Of the 113 patients, 16 were diagnosed with NAFLD, 56 were diagnosed with chronic hepatitis C, 17 were diagnosed with autoimmune liver disease, and 24 had miscellaneous diagnoses (hepatitis B, hemochromatosis, granulomatous hepatitis, and cryptogenic hepatitis). The subcutaneous tissue thickness was 25.6 mm +/- 5.6 mm in NAFLD versus 19.5 mm +/- 5.2 in the non-NAFLD patients (p < 0.001). The subcutaneous tissue thickness of the HCV group was 20.2 mm +/- 4.8, and although it was not different than all other patients, it was different from the NAFLD patients (p < 0.01). Fifteen out of sixteen of the NAFLD patients had a greater than average subcutaneous tissue thickness (20 mm). CONCLUSIONS: A sonographically measured subcutaneous tissue thickness of less than 20 mm makes the diagnosis of NAFLD unlikely.

Body Mass Index↗

PubMed1993

Subcutaneous heparin in postangioplasty management: comparative trial with intravenous heparin.

Abrupt closure of a coronary artery after successful angioplasty remains a problem for the interventionalist. Many laboratories continue to administer heparin intravenously for 12 to 24 hours in an attempt to alleviate this problem. But prolonged heparin therapy delays sheath removal and may lead to groin and vascular complications, and so prolong the hospital stay. To test the hypothesis that subcutaneous heparin was as efficacious as intravenous heparin in preventing acute closure while reducing the vascular complications associated with extended sheath placement, we prospectively randomized 151 patients to two groups. The intravenous group, 77 patients, received continuous intravenous heparin at 1000 units/hour for 12 to 18 hours; the subcutaneous group, 74 patients, received 12,500 units subcutaneously every 12 hours for three doses after sheath removal 2 to 3 hours after the angioplasty. The activated clotting time immediately after the angioplasty was 401 +/- 108 seconds in subcutaneous group, as compared with 368 +/- 67 seconds in the intravenous group (p = 0.028). Patients receiving subcutaneous heparin continued to show adequate anticoagulation, with a PTT of 85 +/- 21 seconds obtained approximately 12 hours after the procedure. The PTT at discharge was statistically greater in the subcutaneous group, at 49.2 +/- 21 seconds, versus 35.6 +/- 13 seconds in the intravenous group (p < 0.001). Abrupt occlusion was similar in both groups, but the hematomas and bleeding/oozing in the intravenous group was significantly higher when compared with that of the subcutaneous group, 16 versus 6 (p = 0.026) and 26 versus 7 (p < or = 0.002), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2004

Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis.

PURPOSE: To compare the efficacy and safety of subcutaneous insulin lispro with that of a standard low-dose intravenous infusion protocol of regular insulin in patients with uncomplicated diabetic ketoacidosis. METHODS: In this prospective, randomized open trial, 20 patients treated with subcutaneous insulin lispro were managed in regular medicine wards (n=10) or an intermediate care unit (n=10), while 20 patients treated with the intravenous protocol were managed in the intensive care unit. Patients treated with subcutaneous lispro received an initial injection of 0.3 unit/kg followed by 0.1 unit/kg/h until correction of hyperglycemia (blood glucose levels <250 mg/dL), followed by 0.05 to 0.1 unit/kg/h until resolution of diabetic ketoacidosis (pH > or =7.3, bicarbonate > or =18 mEq/L). Patients treated with intravenous regular insulin received an initial bolus of 0.1 unit/kg, followed by an infusion of 0.1 unit/kg/h until correction of hyperglycemia, then 0.05 to 0.1 unit/kg/h until resolution of diabetic ketoacidosis. RESULTS: Mean (+/- SD) admission biochemical parameters in patients treated with subcutaneous lispro (glucose: 674 +/- 154 mg/dL; bicarbonate: 9.2 +/- 4 mEq/L; pH: 7.17 +/- 0.10) were similar to values in patients treated with intravenous insulin (glucose: 611 +/- 264 mg/dL; bicarbonate: 10.6 +/- 4 mEq/L; pH: 7.19 +/- 0.08). The duration of treatment until correction of hyperglycemia (7 +/- 3 hours vs. 7 +/- 2 hours) and resolution of ketoacidosis (10 +/- 3 hours vs. 11 +/- 4 hours) in patients treated with subcutaneous lispro was not different than in patients treated with intravenous regular insulin. There were no deaths in either group, and there were no differences in the length of hospital stay, amount of insulin until resolution of diabetic ketoacidosis, or in the rate of hypoglycemia between treatment groups. Treatment of diabetic ketoacidosis in the intensive care unit was associated with 39% higher hospitalization charges than was treatment with subcutaneous lispro in a non-intensive care setting ($14,429 +/- $5243 vs. $8801 +/- $5549, P <0.01). CONCLUSION: Treatment of adult patients who have uncomplicated diabetic ketoacidosis with subcutaneous lispro every hour in a non-intensive care setting may be safe and more cost-effective than treatment with intravenous regular insulin in the intensive care unit.

3-Hydroxybutyric Acid↗

PubMed1998

Pharmacokinetics, cortisol release, and hemodynamics after intravenous and subcutaneous injection of human corticotropin-releasing factor in humans.

OBJECTIVE: Two clinical trials investigated the pharmacokinetics of human corticotropin-releasing factor (hCRF), resulting cortisol release, and associated hemodynamic changes. METHODS: In a 3 x 3 Latin square design, subjects were randomized to receive a single dose of 5 microg x kg(-1) hCRF as a 10-minute intravenous infusion, a 180-minute infusion, and a subcutaneous injection in separate study sessions 7 days apart. Twelve additional subjects obtained a subcutaneous dose of either 300, 600, or 1200 microg hCRF on 3 consecutive days. Noncompartmental and compartmental pharmacokinetic analysis was performed. Hemodynamic response was characterized with use of pharmacodynamic models. RESULTS: The volume of distribution at steady state was 9.81 +/- 3.0 and 15.61 +/- 2.9, and the clearance was 256 +/- 40 mL x min(-1) and 345 +/- 90 mL x min(-1) for the 10-minute and 180-minute intravenous infusion, respectively (P < .05). Corresponding elimination half-life was 45 +/- 7 minutes and 37 +/- 10 minutes. Two-compartment and 1-compartment models adequately described the 10-minute and 180-minute infusions, respectively. The bioavailability of hCRF after subcutaneous administration was 67% +/- 17%. Apparent clearance remained unchanged for different subcutaneous doses. Peak plasma cortisol concentrations were similar after subcutaneous and intravenous administration of hCRF. Repetitive administration of hCRF did not result in accumulation but produced a reduced plasma cortisol response. A sigmoidal model related plasma hCRF concentrations to increase in heart rate (maximum, 39 beats x min(-1)). The relationship between the modest decrease in diastolic blood pressure and plasma hCRF concentrations was linear. CONCLUSION: The pharmacokinetics of intravenously administered hCRF were nonlinear, but apparent clearance was constant for various subcutaneous doses. An excellent bioavailability and preserved bioactivity make the subcutaneous route an attractive choice. Repetitive administration of hCRF probably caused tolerance of the cortisol response.

Adult↗

PubMed2000

Response to different measles vaccine strains given by aerosol and subcutaneous routes to schoolchildren: a randomised trial.

BACKGROUND: More than one dose of measles vaccine is necessary for the sustained control of measles. The aerosol route is thought to be more immunogenic for booster doses than traditional subcutaneous injections, so we did a randomised comparative trial of aerosol and subcutaneous measles vaccines in South African schoolchildren. METHODS: 4327 schoolchildren (aged 5-14 years), assigned by block randomisation of classrooms, received standard titre doses of either Schwarz or Edmonston-Zagreb measles vaccines subcutaneously or by aerosol. Blood samples for antibody assay were collected before vaccination, at 1 month, and 1 year after vaccination. The main endpoints (antibody titres at 1 month and 1 year) were compared between groups. FINDINGS: 992 children had antibody titre data available for all timepoints. 14 (3.6%) of 385 children who received Edmonston-Zagreb vaccine by aerosol were seronegative 1 year after vaccination, compared with 28 (8.6%) of 326 children who received Edmonston-Zagreb subcutaneous vaccine and 39 (13.9%) of 281 children who received Schwarz subcutaneous vaccine. At 1 month, 326 (84.7%) children who received aerosol Edmonston-Zagreb vaccine had seroconverted, compared with 257 (78.8%) who received subcutaneous Edmonston-Zagreb vaccine and 176 (62.6%) who received subcutaneous Schwarz vaccine. At 1 month, only 116 (22.7%) of 511 children in the Schwarz aerosol group had seroconverted; this aerosol vaccine had no detectable potency after 2 min of nebulisation. There were no serious side-effects: about 5% of children in each group had a rash within 2 weeks of vaccination. INTERPRETATION: An aerosol vaccination method that uses currently available devices and a suitably stable vaccine is effective and acceptable. This form of delivery is adaptable to mass campaigns, avoids the risks associated with injections, and could help measles eradication.

Administration, Inhalation↗

PubMed1999

Intranasal or subcutaneous co-administration of recombinant cholera toxin B subunit stimulates only a slight or no level of the specific IgE response in mice to tetanus toxoid.

Whether recombinant cholera toxin B subunit (rCTB) co-administered intranasally or subcutaneously with aluminium-non-adsorbed tetanus toxoid (nTT) can induce the production of tetanus toxoid (TT)-specific IgE antibodies in mice was investigated compared with aluminium-adsorbed tetanus toxoid (aTT) administered intranasally or subcutaneously. Mice immunized intranasally or subcutaneously with nTT together with rCTB showed a high level of TT-specific serum IgG antibody response and no or a slight level of TT-specific serum IgE antibody response. On the other hand, in mice vaccinated intranasally or subcutaneously with aTT alone, higher levels of TT-specific IgG and IgE antibodies were induced in comparison with intranasal or subcutaneous inoculation of nTT together with rCTB. These results suggest that intranasal or subcutaneous co-administration of rCTB with nTT is better than intranasal or subcutaneous administration of aTT to avoid IgE-mediated allergic reactions.

Adjuvants, Immunologic↗

PubMed2003

Changes in abdominal subcutaneous fat water content with rapid weight loss and long-term weight maintenance in abdominally obese men and women.

OBJECTIVE: Insulin resistance decreases blood flow and volume in fat tissue. We hypothesised that fat tissue nutritive blood flow and volume, and thereby water content, would increase during weight loss and weight maintenance in obese persons. DESIGN: Longitudinal clinical intervention with a 9-week very-low-calorie diet (VLCD) followed by one year of weight maintenance. SUBJECTS: Obese men (n=13) and women (n=14) with the metabolic syndrome. MEASUREMENTS: Water content of abdominal subcutaneous fat tissue as estimated by a sensor on the skin surface measuring the dielectric constant at 300 MHz. Anthropometric measures of fatness and fat distribution. Biochemical measures related to insulin resistance. RESULTS: Subjects lost 14.5+/-3.4% of body weight during the VLCD, and generally sustained this weight loss during weight maintenance. Insulin sensitivity as estimated by an index (qualitative insulin sensitivity check index) increased during the VLCD, and remained increased throughout weight maintenance. The dielectric constant increased from 23.3+/-2.3 to 25.0+/-2.1 (P<0.001) during the VLCD, and further to 27.8+/-1.9 (P<0.001) during weight maintenance, indicating an increase in the water content of subcutaneous fat. The increase in subcutaneous fat water content did not correlate with weight loss and other measures of adiposity during the VLCD, but there was an inverse correlation that strengthened in significance from baseline to 6, 9 and 12 mo (r=-0.32 to -0.64, P=0.079-0.002). Increases in subcutaneous fat water content also correlated with improvements in insulin sensitivity at 6, 9 and 12 months of weight maintenance (r=0.34-0.54, P=0.094-0.006). CONCLUSIONS: Water content of abdominal subcutaneous adipose tissue increases with weight loss in obese persons with the metabolic syndrome, and may reflect increased subcutaneous fat tissue nutritive blood flow. The increase in water content correlates with the increase in insulin sensitivity, suggesting that weight loss and consequent improved insulin sensitivity could mediate the increase in abdominal subcutaneous fat hydration.

Abdomen↗

PubMed2002

Pharmacokinetics of plasma enfuvirtide after subcutaneous administration to patients with human immunodeficiency virus: Inverse Gaussian density absorption and 2-compartment disposition.

OBJECTIVE: Enfuvirtide (T-20) is the first of a novel class of human immunodeficiency virus (HIV) drugs that block gp41-mediated viral fusion to host cells. The objectives of this study were to develop a structural pharmacokinetic model that would adequately characterize the absorption and disposition of enfuvirtide pharmacokinetics after both intravenous and subcutaneous administration and to evaluate the dose proportionality of enfuvirtide pharmacokinetic parameters at a subcutaneous dose higher than that currently used in phase III studies. METHODS: Twelve patients with HIV infection received 4 single doses of enfuvirtide separated by a 1-week washout period in an open-label, randomized, 4-way crossover fashion. The doses studied were 90 mg (intravenous) and 45 mg, 90 mg, and 180 mg (subcutaneous). Serial blood samples were collected up to 48 hours after each dose. Plasma enfuvirtide concentrations were measured with use of a validated liquid chromatography-tandem mass spectrometry method. RESULTS: Enfuvirtide plasma concentration-time data after subcutaneous administration were well described by an inverse Gaussian density function-input model linked to a 2-compartment open distribution model with first-order elimination from the central compartment. The model-derived mean pharmacokinetic parameters (+/-SD) were volume of distribution of the central compartment (3.8 +/- 0.8 L), volume of distribution of the peripheral compartment (1.7 +/- 0.6 L), total clearance (1.44 +/- 0.30 L/h), intercompartmental distribution (2.3 +/- 1.1 L/h), bioavailability (89% +/- 11%), and mean absorption time (7.26 hours, 8.65 hours, and 9.79 hours for the 45-mg, 90-mg, and 180-mg dose groups, respectively). The terminal half-life increased from 3.46 to 4.35 hours for the subcutaneous dose range from 45 to 180 mg. CONCLUSIONS: An inverse Gaussian density function-input model linked to a 2-compartment open distribution model with first-order elimination from the central compartment was appropriate to describe complex absorption and disposition kinetics of enfuvirtide plasma concentration-time data after subcutaneous administration to patients with HIV infection. Enfuvirtide was nearly completely absorbed from subcutaneous depot, and pharmacokinetic parameters were linear up to a dose of 180 mg in this study.

Absorption↗

PubMed2005

Normal values and differences between intraperitoneal and subcutaneous microdialysis in patients after non-complicated gastrointestinal surgery.

OBJECTIVE: Visceral ischemia is an early event in the development of shock and organ failure. Microdialysis has been presented as a promising method for detection of visceral hypoxia and ischemia. The aim of this study was to investigate differences in the metabolic response measured by microdialysis between intraperitoneal and subcutaneous locations and to estimate normal values of lactate/pyruvate ratio, glucose and glycerol. MATERIAL AND METHODS: Intraperitoneal and subcutaneous metabolic responses were compared regarding lacate/pyruvate ratio, glucose and glycerol, during 45 postoperative hours in 33 patients undergoing various non-complicated elective major gastrointestinal surgery. RESULTS: Intraperitoneal lactate/pyruvate ratio started around 15 and decreased over time, while subcutaneous levels were stable around 9. Glucose levels were higher intraperitoneally and increased rapidly during the first 9 h to 8.6 mM, while the subcutaneous levels increased during 21 h to 7.5 mM. Intraperitoneal glycerol levels were stable around 100 microM, while subcutaneous values started around 230 microM and then increased. CONCLUSIONS: In a non-complicated postoperative course the lactate/pyruvate ratio and glucose levels are higher intraperitoneally, suggesting a higher postoperative intraperitoneal metabolism. Glycerol levels are higher and increase subcutaneously, suggesting increased postoperative energy demand, particularly in the visceral organs, as being responsible for the lipolysis seen in the subcutaneous tissue.

Adult↗

PubMed1997

The influence of peritoneal dialysis and the use of subcutaneous and intraperitoneal insulin on glucose metabolism and serum lipids in type 1 diabetic patients.

BACKGROUND: Intraperitoneally administered insulin is regarded as the most physiological replacement therapy, leading to lower peripheral insulin concentrations and equal or better glycaemic control than subcutaneous insulin. This two-part study was undertaken to evaluate the effect of CAPD, as well as the use of subcutaneous vs. intraperitoneal insulin on insulin sensitivity, glycaemic control and serum lipids in type 1 diabetes. METHODS: Eleven patients with type 1 diabetes mellitus and chronic renal failure participated the studies. Glycated haemoglobin (HbA1c), euglycaemic hyperin-sulinaemic clamp, serum lipids, and patient well-being were measured. During CAPD all patients were first treated with subcutaneous insulin and then with intraperitoneal insulin. The metabolic studies were repeated after both treatment periods for at least 3 months. Metabolic studies were performed on six of the patients also before initiation of CAPD. RESULTS: HbA1c rose after the initiation of CAPD from 8.85 +/- 0.54% to 9.58 +/- 0.66%, NS) and improved after changing from subcutaneous to intraperitoneally administered insulin (from 9.49 +/- 0.43% to 8.13 +/- 0.39%, P < 0.01). Insulin dose increased by 15% after initiation of CAPD and 128% after switching from subcutaneous to intraperitoneal insulin. Glucose disposal rate enhanced by 39% (P = 0.05) and 14% respectively (P < 0.01). Initiation of CAPD had no significant effects on serum lipids but intraperitoneally administered insulin reduced HDL cholesterol and increased LDL/HDL ratio significantly. CONCLUSIONS: Intraperitoneal insulin therapy offers better glycaemic control and insulin sensitivity than subcutaneous insulin. Deterioration of HbA1c after initiation of CAPD while patients remained on subcutaneous insulin may be partly due to absorbed energy from the dialysate. Intraperitoneal insulin therapy seems to have detrimental effects on serum lipids. The clinical significance in modifying the risk of atherosclerosis remains unclear.

Adult↗

PubMed1997

Intracerebral versus subcutaneous immunization with allogeneic fibroblasts genetically engineered to secrete interleukin-2 in the treatment of central nervous system glioma and melanoma.

OBJECTIVE: The purpose of this study was to determine the optimal route of delivery of gene therapy for an intracerebral (IC) tumor. In previous studies, treatment of an IC tumor with the IC administration of a cellular vaccine consisting of allogeneic fibroblasts genetically engineered to secrete cytokines prolonged survival. Systemic delivery of gene therapy is of significant clinical interest. METHODS: In this study, allogeneic fibroblasts engineered to secrete interleukin (IL)-2 (LM-IL-2 cells) were administered either subcutaneously or intracerebrally to C57BL/6 mice with IC glioma. In addition, fibroblasts genetically engineered to express (antibody-defined) melanoma-associated antigens and to secrete IL-2 (RLBA-IL-2) were injected either intracerebrally or subcutaneously into mice bearing IC melanoma. RESULTS: The results indicate a significant prolongation of survival in mice with IC glioma treated intracerebrally with LM-IL-2 cells, relative to the survival of mice with IC glioma treated subcutaneously with LM-IL-2 cells or untreated mice with glioma. The specific release of isotope from 51Cr-labeled glioma cells coincubated with spleen cells from animals treated either subcutaneously or intracerebrally with LM-IL-2 cells was significantly greater than the release of isotope from glioma cells coincubated with spleen cells from nonimmunized mice. In a similar fashion, the survival of mice with IC B16 melanoma immunized intracerebrally with RLBA-IL-2 cells was significantly longer than nonimmunized mice injected with B16 cells alone. In contrast, the survival of mice with IC melanoma treated by subcutaneous injection with RLBA-IL-2 cells was not significantly different than that of untreated mice. Using a 51Cr-release assay, the specific release of isotope from labeled B16 cells coincubated with spleen cells from mice immunized either intracerebrally or subcutaneously with RLBA-IL-2 cells was significantly higher than that of B16 cells coincubated with cells from nonimmunized mice. CONCLUSIONS: Direct IC administration of fibroblasts genetically engineered to secrete IL-2 was more effective in prolonging survival than peripheral subcutaneous administration in the treatment of mice with IC glioma or melanoma.

Animals↗

PubMed2004

Subcutaneous tumor implantation after laparoscopic procedures in women with malignant disease.

OBJECTIVE: To describe the incidence of clinically detected laparoscopy-related subcutaneous tumor implantation in women with malignant disease who were treated by a gynecologic oncology service. METHODS: We reviewed all cases of primary or metastatic malignancy who underwent a transperitoneal laparoscopy. Open laparoscopy technique was used in all cases with the Hasson trocar, usually placed near the umbilicus. A carbon dioxide pneumoperitoneum was used in all cases, with maximum intraabdominal pressure set at 15 mm Hg. All trocar sites more than 5 mm were closed at the fascia level. Identifying subcutaneous implantation was performed by a detailed review of all available medical records and by review of a prospectively maintained comprehensive complications database. RESULTS: In a 12-year period (July 1991 to July 2003), 2,593 laparoscopic procedures were performed, including 1,335 transperitoneal laparoscopies in 1,288 women with malignant disease. Malignant disease sites included adnexa/peritoneum (584), uterine corpus (355), uterine cervix (100), and other (249). There were no "isolated" trocar-related subcutaneous tumor implantations during the study period. Subcutaneous tumor implantations (n = 13, 0.97%) usually occurred with carcinomatosis, with synchronous metastases to other sites, and in the setting where the preceding laparoscopy was performed in the presence of advanced or recurrent abdominopelvic disease. CONCLUSION: Laparoscopy-related subcutaneous tumor implantation is rare (0.97%) in women undergoing transperitoneal laparoscopy with malignant disease. Subcutaneous implantation appears to occur in patients with known metastatic disease and is detected in the setting of synchronous advanced intraabdominal or pelvic metastasis and progression of carcinomatosis. The risk of subcutaneous tumor implantation should not be used as an argument against laparoscopy in the majority of women with gynecologic malignancies managed by gynecologic oncologists. LEVEL OF EVIDENCE: II-2

Adolescent↗

PubMed1979

Evidence that protease inhibitors reduce the degradation of parathyroid hormone and calcitonin injected subcutaneously.

1 Agents known to delay absorption from a subcutaneous site were tested in chicks for their ability to prolong the hypercalcaemic response to parathyroid hormone (PTH). 2 Polyvinylpyrrolidone was found to enhance the response but gelatine greatly reduced the 2 h hypercalcaemia. 3 The reduction by gelatine was reversed when the protease inhibitor aprotinin was added to the injection vehicle, and hypercalcaemia then persisted for more than 8 h. 4 Of other protease inhibitors studied, epsilon-aminocaproic acid was also found to enhance the hypercalcaemic response to subcutaneous PTH and its fragments but, unlike aprotinin, it was ineffective in the presence of gelatine. 5 By radioimmunoassay and bioassay respectively, it was confirmed that aprotinin raised circulating levels of PTH and also of another peptide hormone, calcitonin, injected subcutaneously. 6 Addition of calcium to the solutions injected subcutaneously abolished the hypercalcaemic response to PTH while injection of calcium and PTH simultaneously but at separate sites left the response unaltered. 7 The two protease inhibitors, epsilon-aminocaproic acid and aprotinin, each restored the response to subcutaneous PTH despite the presence of calcium at the injection site. 8 It was concluded that protease inhibitors injected subcutaneously with PTH and calcitonin in the chick reduced the rate of degradation of these hormones and that the proteases responsible for hormone degradation at the subcutaneous injection site may be released or activated by calcium ions.

Animals↗

PubMed2002

Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: a double-blind randomized placebo-controlled trial.

Methylnaltrexone, the first peripheral opioid receptor antagonist, has the potential to prevent or reverse opioid-induced peripherally mediated side effects without affecting analgesia. In previous human trials, we demonstrated that intravenous methylnaltrexone prevented morphine-induced delay in gastrointestinal transit time. We also observed that the compound decreased some of the morphine-induced troublesome subjective effects. However, the effects of subcutaneous methylnaltrexone, a more convenient route of administration, have not been evaluated. In this controlled trial, we evaluated the efficacy of subcutanous methylnaltrexone in antagonizing morphine-induced delay in oral-cecal transit time. In addition, opioid-induced unpleasant subjective effects and pharmacokinetics were studied. We observed that in the first group (n = 6) morphine (0.05 mg/kg intravenously) increased the transit time from a baseline level of 85 +/- 20.5 min to 155 +/- 27.9 min (mean +/- S.D., P < 0.01). After 0.1 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 110 +/- 41.0 min. In the second group (n = 6), morphine increased the transit time from a baseline level of 98 +/- 49.1 min to 140 +/- 58.2 min (P < 0.01). After 0.3 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 108 +/- 59.6 min (P < 0.05 compared with placebo plus morphine). In addition, subcutaneous methylnaltrexone significantly decreased morphine-induced subjective rating changes. Pharmacokinetic data after subcutaneous drug injection were compared to the data obtained from previous intravenous and oral administrations. Our results suggest that subcutaneous methylnaltrexone may have clinical utility in treating opioid-induced constipation and reducing opioid-induced unpleasant subjective symptoms.

Administration, Oral↗

PubMed1991

Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice.

The therapeutic effects of subcutaneously administered sedecamycin on experimental Treponema hyodysenteriae infection in mice were evaluated. Sedecamycin was more active than tiamulin and lincomycin. The efficacy of sedecamycin upon subcutaneous administration was similar to that upon oral administration. Sedecamycin given subcutaneously provided similar degrees of protection in bile duct-ligated and intact mice. Pharmacokinetic studies utilizing a liquid chromatographic technique were carried out to determine the concentration of sedecamycin in the cecum, the site of T. hyodysenteriae infection in mice. Little sedecamycin was found; however, lankacidinol, a major metabolite of sedecamycin, was found in the cecal contents of intact mice after subcutaneous or oral administration of sedecamycin. Lankacidinol was also found in the cecal contents of bile duct-ligated mice, although the concentration found after subcutaneous administration of sedecamycin was much lower than that found after subcutaneous or oral administration to intact mice. These results indicate that sedecamycin is excreted directly into the intestinal tract as an active metabolite by a route other than the bile duct. It is suggested that this intestinal excretion plays an important role in the efficacy of subcutaneously administered sedecamycin against cecal infection of mice by T. hyodysenteriae.

Animals↗