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Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth factor beta--simultaneous application with basic fibroblast growth factor causes persistent fibrosis.

To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of transforming growth factor-beta by injection into subcutaneous tissue of newborn mice. Histological examination revealed that TGF-beta1, beta2, and beta3 induced granulation tissue formation after 3 days of injection, while these changes had disappeared after 7 days. The changes after 3 days of injection were more pronounced in the tissue injected with TGF-beta2 or beta3 than that with TGF-beta1. In situ hybridization analysis indicated that connective tissue growth factor mRNA was strongly expressed in the fibroblasts at the site of TGF-beta injection, which suggested that fibroblasts were activated by TGF-beta. Next, we investigated the cooperative effects of TGF-beta and other growth factors including basic fibroblast growth factor (bFGF). The simultaneous application of TGF-beta and bFGF caused apparent tissue fibrosis which persisted for at least 2 weeks, while bFGF alone caused slight fibrotic changes after 7 days of injection. Thus, we succeeded in establishing an animal model of skin fibrotic disorders by the exogenous addition of growth factors, and this animal will be useful for future studies in this area.

Animals↗

Subcutaneous tissue oximetry: implications for wound healing and monitoring critically ill patients.

Availability of oxygen and adequate blood flow to wounded tissues are important factors for the prevention of impaired wound healing. Oxygen is essential for the growth of new blood vessels, formation of collagen, and the prevention of infection. Subcutaneous tissue oximetry, an experimental technology for evaluating tissue oxygen and perfusion, is being researched for use in the evaluation of hypovolemia, hemorrhagic shock, sepsis, and would healing. This technology eventually may assist in the management of critically ill patients by promptly alerting physicians to decreased oxygen delivery and allowing for more timely intervention.

Critical Care↗

The distribution of aztreonam in serum, bile, skin and subcutaneous tissues in patients undergoing cholecystectomy.

The distribution of aztreonam was measured in patients undergoing elective cholecystectomy. In 14 patients 2 g aztreonam was injected preoperatively and the concentration of the antibiotic was assessed in the bile from the gall bladder and common bile duct, subcutaneous tissues and serum. Samples from bile and any wound discharge were cultured and sensitivities determined. The antibiotic reached bactericidal levels in the common bile duct within 30 min of injection and such levels were maintained in skin and gall bladder for at least 4 h after injection. Aztreonam was highly effective against the Gram-negative organisms that were cultured in bile but was less effective against Enterococcus faecalis.

Aztreonam↗

Carcinogenicity of airborne combustion products observed in subcutaneous tissue and lungs of laboratory rodents.

Most air pollution in West Germany is caused by combustion products. Particulate organic matter released by incomplete combustion is suspected to contribute to the "urban factor" of lung cancer frequency in urban-industrial centers. The carcinogenic potential of single components, groups of compounds and total source emissions of combustion processes was investigated in laboratory animals by subcutaneous injection, intratracheal instillation or inhalation. Tests by subcutaneous injection of condensates of automobile exhaust, extracts of coal furnace emissions and of airborne particles and different fractions of these extracts showed that the polycyclic aromatic hydrocarbons (PAH) with four to six benzene rings have the strongest experimental carcinogenicity. However, polar compounds (heterocyclic nitrogen-containing PAH, phenols, and others) also show remarkable carcinogenic potency. There were large differences between the dose-response relationships of several PAHs. In the subcutaneous tissue, benzo(a)pyrene and dibenz(a,h)anthracene are the most carcinogenic of the tested airborne PAHs. Furthermore, they can induce high tumor rates in the lung after subcutaneous injection in newborn mice and after intratracheal instillation of mice or hamsters. The tumor rate of benzo(a)pyrene did not further increase after simultaneous instillation of carbon black, but lead chloride may have a promoting effect. Far more than 100 PAHs are found in the urban atmosphere. However, because of the remarkable similarity of the PAH profiles in the examined samples, it may be sufficient to measure just a few stable PAHs in the urban air in order to facilitate an assessment of the carcinogenic potency of the PAH content in the atmosphere. To examine the carcinogenic or cocarcinogenic effects of gas and vapor emissions, studies with a two-phase model were carried out: phase 1 relates to the induction of a basic tumor rate in the lung by a well known carcinogen, while phase 2 is characterized by an inhalation of the substance under investigation. In an experiment with mice, the inhalation of a mixture of SO2 and NO2 seemed to increase the basic tumor rate induced by dibenz(a,h)anthracene. In a similar two-phase experiment conducted with hamsters, the inhalation of diesel exhaust (total exhaust as well as exhaust without particles) increased a basic tumor rate induced by diethyl nitrosamine. These experiments deserve confirmation before a detailed interpretation is attempted.

Air Pollutants↗

Subcutaneous tissue distribution of vancomycin from a fibrin glue/Dacron graft carrier.

We investigated the tissue distribution of vancomycin (VCM) incorporated in fibrin glue (FG) in a rat model. One VCM-loaded FG Dacron graft (VCM-FG, VCM 0.6 mg/ graft) was implanted in the subcutaneous tissue of the anterior abdominal wall of each rat. VCM was injected intravenously at an equal dose (0.6 mg/rat) after implantation of one control graft (without VCM-FG). After the implantation and the iv injection of an equal dose of VCM (0.6 mg/rat), the tissue distribution of VCM for up to 24 h was determined through analysis of the implanted VCM-FG grafts, which released VCM over a 24 h period. The area under the VCM concentration-time curve (AUC) of the tissue was 89.58 micrograms.h/g after the implantation of the VCM-FG graft, and 7.40 micrograms.h/g after the iv injection of VCM, respectively. The targeting index of the tissue, defined as the ratio of AUC after the implantation of the VCM-FG graft to that after VCM iv injection, was 12.11. None of the six VCM-FG Dacron grafts after implantation became infected following inoculation with S. aureus ATCC 25923 (0.1 mL 10(8) CFU/mL). These results suggest that this VCM-FG Dacron graft delivery may be useful in preventing local infection by enhancing the delivery of VCM to the local areas of the implanted site in rats.

Animals↗

Monitoring skeletal muscle and subcutaneous tissue acid-base status and oxygenation during hemorrhagic shock and resuscitation.

Gastric tonometry correlates with the severity of blood loss during shock. However, tonometry is cumbersome, has a slow response time, and is not practical to apply in the acute resuscitation setting. We hypothesized that subcutaneous tissue (SC) and skeletal muscle (SM) pH, pCO2, and pO2 changes are comparable with changes seen in bowel tonometry during shock and resuscitation. Thirteen male mini-swine (25-35 kg; n = 4 control, n = 9 shock) underwent laparotomy and jejunal tonometry. A multisensor probe (Diametrics Medical, Roseville, MN) was placed in the carotid artery, the chest SC, and the adductor muscle of the leg (SM). PaCO2 was maintained between 40 and 45 mmHg. Shocked animals were hemorrhaged and kept at mean arterial pressure of 40 mmHg. Animals were bled until a reinfusion of >10% of the total shed blood was needed to maintain the mean arterial pressure at 40 mmHg. Animals were resuscitated with shed blood plus 2x shed volume in lactated Ringer's solution (20 min) and were observed for 3 h. The average blood loss was 47.2% +/- 8.7% of calculated blood volume. During the hemorrhagic phase, SM and SC displayed tissue acidosis (r2 = 0.951), tissue hypercapnea (r2 = 0.931), and tissue hypoxia (r2 = 0.748). Overall, pH displayed the best correlation between SM and SC during shock and resuscitation. PCO2 in the jejunum (tonometry), SM, and SC increased during decompensation. However, during resuscitation as tonometric pCO2 normalized, only SC pCO2 decreased to its baseline value, whereas the SM pCO2 decrease tended to lag behind. Bland-Altman analyses demonstrated that the variability of the tissue pH changes in SM and SC are predictable according to the phases of hemorrhage and resuscitation. Changes in tissue pH correlated during bleeding and during resuscitation among SC and SM, and these changes followed the trends in gut tonometry as well. Continuous pCO2 and pO2 monitoring in the SM and SC tissues had significant correlations during the induction of shock only. SM and SC continuous pH and pCO2 monitoring reflect bowel pCO2 values during hemorrhagic shock. The response of these indicators as potential surrogates of impaired tissue metabolism varies among tissues and according to the phases of hemorrhage or resuscitation.

Animals↗

Axillary osmidrosis treated by partial removal of the skin and subcutaneous tissue en bloc and apocrine gland subcision.

BACKGROUND: Axillary osmidrosis can be treated with many methods, but local surgery is the treatment of choice. METHODS: Forty-three patients (32 females and 11 males, average age 20.3 years) were treated by partial removal of the skin and subcutaneous tissue en bloc and follicular clipping of the adjacent area. All operations were performed with local anesthesia in an outpatient setting. RESULTS: Follow-up ranged from 2 to 47 months (mean: 13.4 months). Forty-one patients (95%) had good results, two (5%) were fair, and none were poor. No recurrences were seen. The wound complication rate was 3.5% for axillae and 7% for patients. There were no scar contractures or limitations of arm abduction. CONCLUSION: This combined surgical method can eliminate malodor and has a low wound complication and recurrence rate. Though the transient and conspicuous scar is the chief drawback of this method, it is a simple, safe, effective and inexpensive method for treating axillary osmidrosis.

Adolescent↗

Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth factor beta-simultaneous application with basic fibroblast growth factor causes persistent fibrosis.

To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of transforming growth factor-beta by injection into subcutaneous tissue of newborn mice. Histological examination revealed that TGF-beta1, beta2, and beta3 induced granulation tissue formation after 3 days of injection, while these changes had disappeared after 7 days. The changes after 3 days of injection were more pronounced in the tissue injected with TGF-beta2 or beta3 than that with TGF-beta1. In situ hybridization analysis indicated that connective tissue growth factor mRNA was strongly expressed in the fibroblasts at the site of TGF-beta injection, which suggested that fibroblasts were activated by TGF-beta. Next, we investigated the cooperative effects of TGF-beta and other growth factors including basic fibroblast growth factor (bFGF). The simultaneous application of TGF-beta and bFGF caused apparent tissue fibrosis which persisted for at least 2 weeks, while bFGF alone caused slight fibrotic changes after 7 days of injection. Thus, we succeeded in establishing an animal model of skin fibrotic disorders by the exogenous addition of growth factors, and this animal model will be useful for future studies in this area.

Animals↗

Lymphatic flow in humans as indicated by the clearance of 125I-labeled albumin from the subcutaneous tissue of the leg.

Since the removal of albumin from the extracellular space and its return to the vascular compartment is the essential function of the lymphatic system, the rate at which it is removed from the interstitial tissue may be regarded as a means of estimating lymphatic efficiency. An objective measure of lymphatic function can be obtained by monitoring the rate of clearance following injection of 125I-labeled albumin (RIHSA) from the subcutaneous tissue of a limb. The clearance of 125I-RIHSA from lower limb was monitored in a group of patients with normal limbs, patients with unilateral edema due to deep vein thrombosis, and patients with bilateral edema due to hypoproteinemia. The mean T1/2 in normal legs was 32.7 hr, compared to 23.7 hr in edematous limbs due to deep vein thrombosis and 19.4 in edematous limbs due to hypoproteinemia. There is a clear-cut difference in clearance rate between edematous and nonedematous limbs. This suggests that lymphatic flow is increased in edema due to venous obstruction and hypoproteinemia.

Adult↗

Subcutaneous tissue oxygen pressure: a reliable index of peripheral perfusion in humans after injury.

The usual initial life-threatening effect of injury is hypovolemic shock. In the hierarchical physiologic response to hypovolemia, perfusion of peripheral tissues is sacrificed early and restored late. But the usual hemodynamic and metabolic measurements of blood pressure, urine output, and base deficit are not reliable indices of peripheral perfusion. Although the Clark electrode can quantitate tissue oxygen pressure and thereby serve as an index of perfusion, its use is compromised by several technical deficiencies. Recently, an optical method (optode) using fluorescent technology has been developed for measurement of oxygen tension in subcutaneous tissue (P sgO2). Our studies compared this device with the Clark electrode in the laboratory and tested its value in both animal and clinical studies of hypovolemic shock. The results of these several studies demonstrated that: (1) the new oximeter tracked a rapid fall or rapid rise of oxygen tension between room air (150 mm Hg) and 0 mm Hg ( a glucose oxidase/catalase solution) as well as the Clark electrode without encountering its technical problems; (2) with an acute hemorrhage to 20% of base line, the PsgO2 was found to decline rapidly in parallel with the decline of mean arterial pressure (MAP). Although the MAP rapidly returned to normal after immediate complete return of all shed blood, the PsgO2 did not reach normal levels for at least 2 hours, suggesting persistent peripheral vasoconstriction. (3) Studies in progress suggest that between 35 and 78% of trauma patients (n = 18) adequately resuscitated for hypovolemia b customary criteria have a decreased level of PsgO2 for as long as 60 hours after resuscitation for injury. If care is taken to prevent other causes of catecholamine induced vasoconstriction such as pain, fear, cold, and arterial hypoxia, these several results suggest that a certain number of injured patients are inadequately resuscitated despite the return to normal of conventional hemodynamic measurements. The serial analysis of PsgO2 may assist in managing patients and promote better understanding of the responses to injury.

Animals↗

Role of subcutaneous tissue endotoxin in the production of prostanoid-induced lung injury: comparison with intravenous endotoxin response.

Local injection of endotoxin into soft tissues of the flank results in hypoxia and pulmonary hypertension. Our purpose was to determine whether this was caused by tissue prostanoid production or production by the lung as is seen with endotoxemia. Twenty-six sheep were prepared with lung and flank tissue lymph fistulae. Thirteen sheep were given 2 micrograms/kg Escherichia coli endotoxin into the flank soft tissue, six of which were pretreated with ibuprofen, 12.5 mg/kg. Thirteen sheep were given intravenous endotoxin, 2 micrograms/kg, with six pretreated with ibuprofen. An early hypertensive phase was noted with both insults characterized by pulmonary hypertension, hypoxia, and increased lung lymph flow (QL). With subcutaneous tissue endotoxin, there was a significant increase in tissue lymph TxB2 and 6-keto-PGF1 alpha when compared to lung lymph and increased values in venous plasma compared to arterial plasma, indicating tissue to be the source. With intravenous endotoxin, lung lymph and aortic plasma levels were significantly higher than tissue lymph and venous plasma, respectively. The hypoxia, hypertension and increased prostanoids were prevented using ibuprofen. An increased lung permeability phase was noted with intravenous endotoxin but not with tissue endotoxin. As expected, this phase was not inhibited with ibuprofen and, therefore, not prostanoid-induced.

6-Ketoprostaglandin F1 alpha↗

Case report: serous atrophy of bone marrow and subcutaneous tissue enhancement associated with recurrent rectal carcinoma: MR appearances.

We report a case of serous atrophy of bone marrow associated with recurrent rectal carcinoma detected by MR images. Bone marrow of vault, clivus and femur showed waterlike signal patterns in T1- and T2-weighted images. Postcontrast T1-weighted images revealed no enhancement of bone marrow, while subcutaneous tissue showed decreased signal intensity and enhancement consistent with an increase in connective tissue with fat atrophy. Gadolinium-enhanced MR imaging was useful for differentiating the serous atrophy of marrow from bone metastasis in this carcinoma patient.

Aged↗

Immune selection for antigenic drift of major outer membrane protein P2 of Haemophilus influenzae during persistence in subcutaneous tissue cages in rabbits.

During persistence of nonencapsulated Haemophilus influenzae in the respiratory tracts of patients with chronic bronchitis, the major outer membrane proteins (MOMPs) P2 and P5 show antigenic drift. The hypothesis that appearance of antigenic variants is the consequence of antibody-dependent selection was tested in a rabbit model. Persistence of H. influenzae d1 was achieved in subcutaneous tissue cages for up to 948 days. During persistence in the rabbits, similar changes in MOMP P2 of H. influenzae occurred, as observed in isolates from chronic bronchitis patients. In rabbits vaccinated with strain d3 and in nonvaccinated rabbits, antigenic drift occurred later than in rabbits vaccinated with strain d1. High titers of antibodies against H. influenzae were measured in tissue cage fluid and serum. Vaccination of the rabbits with H. influenzae d1 or d3, an antigenic variant of strain d1, resulted neither in eradication of H. influenzae d1 nor in increased antibody titers in serum and tissue cage fluid. The sera of nonvaccinated rabbits during persistence had no strain d1-specific bactericidal activity in the presence of complement. Vaccination with H. influenzae d1 induced serum bactericidal activity against strain d1 in the presence of complement. However, a variant of strain d1 appearing in the tissue cages was not killed by this serum bactericidal activity. We conclude that immunological pressure leads to the selection of MOMP variants of H. influenzae and that these variants escape the antibody-mediated strain-specific bactericidal activity against H. influenzae.

Amino Acid Sequence↗

An unusual presentation of extramedullary plasmacytoma occurring sequentially in the testis, subcutaneous tissue, and heart.

Extramedullary plasmacytoma (EMP) is a rare neoplasm of soft tissue that usually arises in the respiratory tract, nasal cavity, sinuses, and nasopharynx. It is even more uncommon for it to arise either in the testis or heart. We report the presentation of a case where plasmacytomas were found sequentially in the testis, subcutaneous tissue, and heart. EMP usually has a good prognosis except when it involves the heart. Our patient survived for only 15 months post autologous hematopoietic stem cell transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

Two-stage correction of depressed glabella and nasal root scar contracture utilizing subcutaneous tissue advancement flaps and a layered soft tissue/procerus muscle transposition flap.

BACKGROUND: A postoperative nasal root and glabellar forehead deformity comprised both vertical and horizontal elements, with scar contracture and fixation across the left medial nose base, extending into the adjacent superior canthal region. METHODS: A two-stage reconstruction was performed, initially correcting the vertical centrally placed forehead depression by dual subcutaneous flaps advanced centrally and joined. The horizontal nasal root contracture was repaired at a second stage utilizing a procerus muscle transposition flap elevated on the ipsilateral deep contracture side, imbricated in serpentine fashion on itself and sutured into the depression over the scar base. RESULT: Significant improvement followed. CONCLUSION: The careful and precise placement of subcutaneous tissue and muscle can serve to assist in filling certain deep defects and in elevating scar lines.

Aged↗

Effects of synthetic leukotriene D-4 on the local regulation of blood flow in human subcutaneous tissue.

Prostaglandin E-1 and E-2 acts as vasodilators partly through inhibition of sympathetic nerves and partly through a direct action on smooth muscle. To elucidate the mechanisms of LTD-4 induced vasodilation, the vascular smooth muscle dependent auto-regulation of blood flow and the sympathetic reflex mechanism of the "vasoconstrictor reflex" was investigated in humans. Blood flow was measured in subcutaneous tissue after injection of 133-Xenon 1) alone, 2) mixed with lidocaine 20 mg/ml for sympathetic blockade, 3) mixed with PGE-2 0.1 ug/ml and 4) mixed with LTD-4 in concentrations of 5 and 20 microM. Blood flow was kept constant during elevation by 20 cm above heart level (preserved autoregulation) except after injection of PGE-2 and LTD-4 20 microM where a significant decrease was observed (defective smooth muscle function). During lowering by 45 cm, a decrease in blood flow by 50% was observed in experiment 1. This response was blocked by lidocaine and PGE-2, partially blocked by LTD-4 20 microM but unaffected by LTD 5 microM. LTD-4 affects vascular smooth muscle function but does not affect sympathetic reflexes in concentrations which does not have a direct smooth muscle action.

Adult↗