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PubMed2002

Allotype imbalance or microsatellite mutation in low-grade soft tissue sarcomas of the extremities in adults.

The ability to repair DNA double-strand breaks is essential to maintain chromosomal stability. Virtually all soft tissue sarcomas contain chromosomal instabilities, including clonal aberrations and cytogenetic aberrations. However, the relevance of DNA-dependent protein kinase (DNA-PK) in the pathogenesis of soft tissue sarcoma has not been clarified. The main aim of this work is to compare the prognostic impact of genotypic imbalance in low-grade soft tissue sarcomas of the extremities, and to correlate this with the translational level of DNA-PK. This study investigated 28 adult low-grade malignant spindle cell tumours of the extremities, predominantly fibrosarcomas, for loss of heterozygosity (LOH) and microsatellite mutation on flanking regions of each DNA-PK subunit, with identical immunophenotypes. Twelve different polymorphic markers flanking the specific loci of three subunits comprise the genetic map of DNA-PK, at 22q13, 2q35, and 8q11. Translational activity was also analysed by western blot and conventional immunohistochemistry. The overall sarcoma 5-year survival rate was 61.7%. LOH was identified in the specific coding region of DNA-PK in 39.29% for the DNA-PK catalytic subunit (cs), 17.86% for Ku70, and only 7.14% for Ku80. A positive LOH for DNA-PKcs was shown to be a significant factor for poor survival (log rank test p = 0.0160). Immunoreactivity and immunoblot results correlated with the loss of DNA-PKcs allotype in soft tissue sarcoma (Fisher's exact test p = 0.0037). Ku70 and DNA-PKcs were almost identical in terms of immunoreactivity. In conclusion, whereas microsatellite mutation seems an uncommon event during the evolution of low-grade fibrosarcoma of the extremities in adults, the loss of DNA-PKcs defines a biologically more aggressive subset.

Adolescent↗
PubMed1995

Purification, cloning, and sequencing of archaebacterial pyrophosphatase from the extreme thermoacidophile Sulfolobus acidocaldarius.

Cytoplasmic pyrophosphatases are indispensible for the function of cellular bioenergetics. From the extreme thermoacidophilic archaeon Sulfolobus acidocaldarius, situated at one of the lowest branches of the phylogenetic tree, a cytosolic pyrophosphatase has been isolated and purified 200-fold to electrophoretic homogeneity by combining ion-exchange and gel-exclusion chromatography. The native enzyme consists of a homotetramer of 71 kDa apparent molecular mass; the subunit displays an apparent molecular mass of 17 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has an absolute requirement for divalent cations (Mg2+) and a temperature optimum of 75 degrees C coinciding with the growth optimum of the organism; the apparent estimated activation energy is 79.5 kJ/mol. A large variety of cytosolic extracts from other archaebacteria has been probed with a polyclonal antiserum raised against the purified protein; surprisingly, except for an extremely weak signal with S. solfataricus none of the other organisms showed any cross-reactivity. Also, Escherichia coli PPase does not cross-react. Based on N-terminal sequencing the gene has been cloned and sequenced. It codes for a 173-amino-acid protein with a calculated molecular mass of 19,365 kDa. Alignment with known eucaryotic and procaryotic PPases reveals invariant conservation of all residues presently assumed to be involved in metal and substrate binding. Unexpectedly, the highest similarity is found with the enzyme from the phylogenetically extremely distant eubacterium E. coli, but immunological cross-reactivity is absent. Similarity to the only known other archaebacterial PPase is much weaker. Using the 3D structure of the Thermus thermophilus enzyme as a scaffold an energy-minimized structural model is presented, deviating only minimally from the former. The structural features are discussed. The enzyme provides an excellent model for studies of thermostability and folding dynamics since heterologous overexpression has been achieved and genetically mutated forms become accessible.

Amino Acid Sequence↗
PubMed1999

Acute lower extremity paralysis following radiation therapy for cervical cancer.

BACKGROUND: Acute lower extremity paralysis secondary to lumbosacral plexopathy is a rare but severe complication that may follow pelvic radiotherapy for cervical cancer. CASE: A 49-year-old female with newly diagnosed stage IIIB cervical cancer developed progressive bilateral lower extremity paralysis and pelvic pain only 10 weeks following completion of radiation therapy for cervical cancer with no evidence of metastasis or progression of disease. Her bladder and bowel function were not affected. Following extensive workup, the most likely etiology was presumed radiation-induced lumbosacral plexopathy. CONCLUSION: Although metastatic carcinoma is more commonly the reason for progressive lower extremity weakness with pelvic pain in women with advanced cervical cancer, radiation-induced lumbosacral plexopathy, a rare but devastating complication, may be the cause. Diagnosis is by exclusion.

Acute Disease↗
PubMed1996

Transcutaneous oxygen (TcPO2) estimates probability of healing in the ischemic extremity.

The severity of arterial ischemia is a major variable affecting healing of extremity wounds. By relating risk of failure to severity of ischemia, the probability of wound healing may be stratified along with assessment of general medical risks. Transcutaneous oxygen tension (TcPO2) arterial segmental pressure (ASP), and arterial segmental indices (ASI) were obtained in 204 ischemic lower extremity sites; 63% of the sites were in patients with diabetes mellitus (DM), 11% in patients with chronic renal failure (CRF), and 37% in patients with neither DM nor CRF (ND). Wounds included 126 amputations and 78 gangrenous ulcerations of the foot or toes. Healing (n = 112) was defined as complete wound closure, without regard to the time required. Failure (n = 92) was defined by the requirement for either arterial reconstruction (n = 45) or proximal amputation (n = 47). Stepwise multiple regression analysis was used to assess the relative contribution of each measurement and to predict the probability of healing; TcP02 was superior to ASP and ASI in all categories. TcP02 was the only test meeting the P < 0.05 entry criteria modeled by the regression. An accuracy of 83% was achieved. However, when each test was evaluated by univariate analysis, ASP and ASI did meet the criteria for the ND group. However, the accuracy was 68 and 72%, respectively. Predictive accuracy of TcP02 was unaffected by DM or CRF. ASP and ASI were satisfactory in the ND group, although of slightly reduced accuracy. ASP and ASI were misleading and inaccurate in DM and CRF. Thus, of the noninvasive tests, TcP02 alone is sufficient for objective risk stratification of arterial ischemia in the lower extremity.

Blood Gas Monitoring, Transcutaneous↗
PubMed1990

[Improved intraoperative leak control in cytostatic drug isolation perfusion of tumors of the extremities].

The success of extremity perfusion and the protection from systemic side effects largely depend upon the prevention of systemic drug leakage from the extremity circulation. The use of autologous 111-Indium labelled erythrocytes for leakage control allows a continuous exact surveillance and timely correction of the tourniquet position in case a major leak should occur. A total of 97 patients were studied. In 6 patients (= 6%) the perfusion had to be discontinued within the first 30 min due to an uncorrectable leak of greater than 20%. In 31 patients (= 32%), a major leak could be reduced by manipulation of the tourniquet. No systemic side-effects could be observed in any of our patients. Applying leakage control by means of 111-Indium labelled erythrocytes extremity perfusion has proved to be a safe procedure in patients with high risk or recurrent malignant melanoma and soft tissue sarcoma.

Adolescent↗
PubMed1992

Magnetic resonance imaging of tendon and ligament abnormalities: Part II. Pelvis and lower extremities.

Magnetic resonance imaging (MRI) has provided an ideal means, unmatched by other preexisting modalities, of examining musculoskeletal abnormalities, particularly those involving tendons and ligaments in the lower extremities. Lack of motion artifact, convenience of application of surface coil, and absence of overlying structures have made the lower extremities ideally suited to MRI. In addition, the abundance of adjacent adipose tissue provides a superb contrast background. Although evaluation of trauma remains the most common reason for MRI examination, many other conditions may also affect tendons and ligaments. As in other soft-tissue, chondral, and osteochondral lesions, MRI provides exquisite details of abnormalities in these structures. Part II of this review systematically reviews the abnormalities of tendons and ligaments in the pelvis and lower extremities.

Adolescent↗
PubMed1992

[Doppler ultrasound measurements of blood circulation of the lower extremity in man. II. Hemodynamics after trauma and operation].

A duplex ultrasound system was used to examine the blood flow of the common femoral artery in ten young patients with fractures of the lower extremities. Two patients had fractures of both legs. In eight patients the blood flow in the injured leg was comparable with that in the not injured leg. The flow alterations were measured on 3-7 different days over a period of 6-224 days after trauma. All patients showed a significant (to twice or three times that before injury) increase in blood flow in the injured leg a few days after trauma and/or operation, whereas the blood flow in the uninjured leg remained the same or even decreased a little. In the case of undisturbed fracture healing the change in blood flow disappeared within 8-12 weeks, corresponding to fracture consolidation. When fracture healing was delayed and/or further operations on the injured leg were necessary, the blood flow was increased for much longer. The hemodynamics of an injured extremity are compared with those reported elsewhere in the literature. The increased demand for oxygen or energy can explain the changes only in part. Another function of the reflective increase in blood flow could be the temperature increase in the extremity.

Adult↗
PubMed1975

[The effect of acetylsalicylic acid, extremely restricted movement and a cholesterol-rich diet on atheromatosis of the rabbit aorta: comparative investigations (author's transl)].

A multifactorial model for demonstrating the pathogenesis of the diet-induced atheromatosis of the rabbit is described. We examined the effect of various diets (atherogenetic, rich in fibre, mixed, normal) and of extreme restriction of movement, with and without doses of acetylsalicylic acid. The aorta showed uniforms morphological findings; 1. Acetylsalicilic acid no influence on the cholesterol-induced atheromatosis of the rabbit; 2. An atherogenic diet and a diet rich in raw fibre caused different degrees of sclerosis of the aorta; this was related to the cholesterol content of the mixed diet, which was 50% less than the cholesterol content of the atherogenic diet; 3. Macro- and microscopic examination showed that extreme restriction of movement alone has no demonstrable effect on the aorta of the rabbit; 4. The cholesterol-induced atheromatosis showed significantly less involvement of the aorta when there was extreme restriction of movement in addition to the diet; 5. In none of the test groups could we demonstrate any effect of PAT I on platelet adhesiveness; 6. The test conditions did not result in an activation of the contact phase of the haemocoagulation system.

Animals↗
PubMed1983

[Technic of isolated perfusion of the extremities. Experience with 171 cases].

In 171 cases of isolated perfusion of the extremities for treatment of melanomas and soft tissue sarcomas, standardized operation techniques were perfected. The arterial double cannulation makes an iliac cannulation feasible also in cases of second and third perfusion. Cytostatics are dosed per liter of perfused extremity. Cis-Platinum and dacarbacine were recently introduced in isolation perfusion treatment. So-called preheating of the extremity before adding the drugs allows administration of cytostatics besides tumortoxic hyperthermia.

Arm↗
PubMed1995

Free and total thyroid hormones in humans at extreme altitude.

Alterations in circulatory levels of total T4 (TT4), total T3 (TT3), free T4 (FT4), free T3 (FT3), thyrotropin (TSH) and T3 uptake (T3U) were studied in male and female sea-level residents (SLR) at sea level, in Armed forces personnel staying at high altitude (3750 m) for prolonged duration (acclimatized low-landers, ALL) and in high-altitude natives (HAN). Identical studies were also performed on male ALL who trekked to an extreme altitude of 5080 m and stayed at an altitude of more than 6300 m for about 6 months. The total as well as free thyroid hormones were found to be significantly higher in ALL and HAN as compared to SLR values. Both male as well as female HAN had higher levels of thyroid hormones. The rise in hormone levels in different ALL ethnic groups drawn from amongst the southern and northern parts of the country was more or less identical. In both HAN and ALL a decline in FT3 and FT4 occurred when these subjects trekked at subzero temperatures to extreme altitude of 5080 m but the levels were found to be higher in ALL who stayed at 6300 m for a prolonged duration. Plasma TSH did not show any appreciable change at lower altitudes but was found to be decreased at extreme altitude. The increase in thyroid hormones at high altitude was not due to an increase in hormone binding proteins, since T3U was found to be higher at high altitudes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
PubMed1994

Distal arterial reconstruction using Esmarch's bandage technique to salvage upper extremity function in thoracic outlet syndrome caused by cervical ribs: a report of two cases.

We present herein the cases of two patients with thoracic outlet syndrome (TOS) who required arterial reconstruction due to gangrene of the fingers and/or hand. In both patients, the cervical ribs had produced intimal injury of the subclavian arteries, and the successive distal arterial embolism brought about severe ischemia of the affected upper extremity. To treat the TOS, the cervical ribs were resected through a supraclavicular incision. In the first patient, arterial reconstruction was performed from the subclavian artery to the radial collateral artery, a branch of the deep brachial artery, which resulted in minimizing amputation of the gangrenous hand. In the second patient, resection and direct anastomosis of the injured subclavian artery were performed, and bypass surgery from a brachial artery to an interosseous artery was carried out, preserving finger function. Reversed saphenous vein grafts were utilized and Esmarch's bandage technique was applied as a substitute for a vascular clamp in both patients. Following these case reports, we discuss the technique of performing distal bypass in the upper extremities and comment on the usefulness of Esmarch's bandage technique for preserving upper extremity function.

Adult↗
PubMed1991

DNA-strand breaks limit survival in extreme dryness.

The inactivation of the anhydrobiotic organisms Bacillus subtilis (spores) and Deinococcus radiodurans during long-term exposure (up to several weeks) to extreme dryness (especially vacuum) is correlated with an increase in the number of DNA-strand breaks and other DNA lesions. Survival finally depends on the repair of DNA damages. Exposure of anhydrobiotic organisms to extreme dryness (e.g. on Mars or in space) for geological times will lead to so extended DNA lesions that recovery is extremely unlikely.

Bacillus subtilis↗
PubMed1996

Is hyperbaric oxygen a useful adjunct in the management of problem lower extremity wounds?

Hyperbaric oxygen (HBO) is currently being used in the treatment of nonhealing or "problem" wounds of the lower extremities. In an attempt to evaluate the efficacy of HBO in problem wounds, a retrospective study of the HBO experience at Orlando Regional Medical Center was conducted. From 1989 to 1994, fifty-four patients with nonhealing lower extremity wounds resulting from underlying peripheral vascular disease and/or diabetes mellitus were treated with HBO. Wounds were grouped into the following five categories: (1) diabetic ulcers (n = 17 [31%]); (2) arterial insufficiency (n = 8 [15%]); (3) gangrenous lesions (n = 6 [11%]); (4) nonhealing amputation stumps (n = 13 [24%]); and (5) nonhealing operative wounds (n = 10 [19%]). Each patient received an average of 30 treatments. Outcomes for all 54 patients treated with HBO in this study were dismal. None of the patients experienced complete healing, six (11%) showed some improvement, 43 (80%) showed no improvement, and in five cases (9%) results were inconclusive because these patients underwent concomitant revascularization or amputation. Thirty-eight of the 43 patients who showed no improvement (88%) ultimately required at least one surgical procedure to treat their wounds. Thirty-four patients (63%) developed complications, most commonly barotrauma to the ears, which occurred in 23 patients (43%). The average cost of 30 HBO treatments was $14,000 excluding daily inpatient charges. Based on the experience with HBO therapy at Orlando Regional Medical Center and the paucity of good supporting literature, it is difficult to justify such an expensive, ineffective complication-prone treatment modality for problem extremity wounds.

Amputation Stumps↗
PubMed1991

Late upper extremity embolic complications of occluded axillofemoral grafts.

The use of axillary femoral grafting in the treatment of patients at high risk for aortoiliac reconstruction has become a widely accepted treatment modality. Ischemia and even loss of the donor upper extremity have been reported to occur early after graft occlusion. This report describes three patients who developed emboli to the upper extremity at nine, 15, and 34 months following occlusion of their axillary femoral graft. Based on our experience, we consider an occluded axillofemoral graft a permanent threat to the viability of the donor upper extremity. Anatomic changes suggestive of potential ischemia include: presence of a blind pouch in the graft stump, or "Y" elongation of the artery with proliferative changes in the intima.

Aged↗
PubMed1980

Chronic vascular disease of the upper extremity: radiologic and clinical features.

The major chronic vascular diseases of the upper extremity are (1) subclavian artery occlusions, (2) thoracic outlet syndrome, and (3) angiospastic disease of the hand. Central subclavian artery lesions ease of the hand. Central subclavian artery lesions can have either hemodynamic consequences (subclavian steal syndrome) or, by peripheral embolization, can provoke ischemic symptoms of the hand. Costoclavicular narrowing can cause functional or fixed stenosis of the subclavian artery and can also involve the vein or brachial plexus. Symptoms due to pressure on the brachial plexus are most frequent, but embolization to the peripheral vessels may also occur. Angiospastic disease, the most frequent lesion of upper extremity vessels, comprises three types: Raynaud's disease, in which there are intermittent attacks of coldness and discoloration without evidence of occlusion on the angiogram; asphyxia manus et digitorum in which the attacks are also intermittent but there is morphologic evidence of occlusion; and digitus moriens or mortuus, in which there is a painful, permanent discoloration. All investigations of chronic vascular disease of the upper extremity should begin with arch aortography and then proceed to a selective catheterization of the vessels that are presumed to be involved.

Adolescent↗
PubMedDate not supplied

Arteriographic study of variant arterial anatomy of the upper extremities.

Anatomic variations in the major arteries of the upper extremities have been reported in 11-24.4% of individuals. In a review of 100 upper extremity arteriograms, we found an overall incidence of 9%. High origin of the radial artery from the brachial artery was the most frequently encountered anomaly occurring in 7% of individuals and accounting for 78% of all anatomic variations. Origin of the radial and ulnar arteries from the axillary artery was an infrequent finding occurring in only 2% of extremities.

Adult↗
PubMedDate not supplied

Subcutaneous emphysema of the lower extremity of gastrointestinal origin.

Two cases of subcutaneous emphysema of the left lower extremity secondary to perforations of the rectum ,nd sigmoid colon are presented. Although this is an extremely rare syndrome, the true incidence is probably higher, as some cases will be misdiagnosed as gas gangrene unless careful clinical and postmortem examinations are performed. Only rapid recognition of the probable origin of the gas, coupled with aggressive, definitive therapy, can prevent the usually fatal course of this condition. In the absence of trauma to the chest or infection in a previously normal leg, subcutaneous emphysema of a limb should alert the physician to the possibility of a gastrointestinal perforation as a source of the gas. Perforations of the gastrointestinal tract into the subcutaneous tissue can occur anywhere from the neck to the lower extremities.

Aged↗
PubMed1997

Extreme arterial blood pressure differentials in a patient with Takayasu's arteritis.

PURPOSE: To describe the extreme arterial blood pressure differentials in a patient with Takayasu's arteritis and its implications for the preservation of cerebral perfusion during anaesthesia. CLINICAL FEATURES: A 26-yr-old woman with Type III Takayasu's arteritis presented with a tentative diagnosis of mesenteric ischaemia. Determination of systolic arterial blood pressure assisted by oximetry revealed pressures of 114 mmHg in the left and 90 mmHg in the right arm while direct arterial line pressure monitoring of the left posterior tibial artery showed a pressure of 322/113 mmHg. Following induction of anaesthesia with thiopentone and succinylcholine and maintenance with N2O, isoflurane and fentanyl, posterior tibial arterial pressures were maintained (low of 213/96 mmHg) to maintain cerebral blood flow despite surgical requests to lower blood pressure. Epidural local anaesthesia was not considered for intra- or postoperative management due to the regional differences in blood pressure and the effect that sympatholysis may have had on cerebral perfusion. CONCLUSION: In patients with Takayasu's arteritis, extreme arterial blood pressure differentials may exist which may affect regional blood flow, and monitoring of both upper and lower extremity arterial blood pressure should be considered.

Adult↗