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Biomedical subjects

A M Freedman

Publications and source records attributed to A M Freedman.

At least 37 records · Page 2Linked to original sources

Propranolol reduces anoxia/reoxygenation-mediated injury of adult myocytes through an anti-radical mechanism.

The effects of propranolol (PRO) and atenolol (ATE) on adult canine myocytes exposed to 30 min anoxia (A:95% N2/5% CO2) and subsequent reoxygenation (R:95% O2/5% CO2) for up to 20 min was investigated. In some studies, comparison of effects were made with that of superoxide dismutase (SOD). Although anoxia alone produced only minimal injury, reoxygenation in the absence of the beta-blockers or SOD was associated with significant losses of cellular viability, elevated release of cellular lactate dehydrogenase, and increased formation of lipid peroxidation products. Myocytes exposed to A/R in the presence of d,1-PRO (20, 200 microM) were afforded substantial, concentration-dependent protection during 20 min reoxygenation. Significant protection was also observed in the presence of 2 microM d-PRO (non-active beta-blocker), but only after a longer preincubation period (2 h). SOD (10 micrograms/ml) provided equi-potent protection to that of 200 microM d,1-PRO. By contrast, the more water-soluble beta-blocker, ATE (200 microM), offered only minor protection. Electron Spin Resonance spin trapping studies using alpha-phenyl-tert-butylnitrone (PBN) were also performed with A/R myocytes in the presence or absence of drug treatment. Short-term (10 min) exposure to d,1-PRO (200 microM) prior to A/R, or to SOD, resulted in a 71-84% reduction in total PBN lipid radical adduct formation (alkoxyl; alpha H = 2.0-2.5 G, alpha N = 13.5-13.75 G); long-term exposure (2 h) to 2 microM d-PRO resulted in a 51% reduction. These data suggest that the superoxide anion was an initiator of events leading to subsequent lipid radical formation and that the anti-peroxidative properties of PRO appear to be independent of beta-receptor blockade.

Adrenergic beta-Antagonists↗

Propranolol preserves ultrastructure in adult cardiocytes exposed to anoxia/reoxygenation: a morphometric analysis.

The protective effect of d,l-propranolol was studied using freshly isolated canine ventricular cardiocytes (1.5 x 10(6)/mL) exposed to 30 min anoxia (95% N2/5% CO2) and 0, 3, 20, and 45 min of reoxygenation (95% O2/5% CO2). In addition to preventing lipid peroxide formation, propranolol maintained cellular viability, and minimized ultrastructural alterations. In the absence of propranolol, the outer mitochondria become swollen and rounded up within the first few minutes of reoxygenation. The perinuclear mitochondrial area increased only slightly. We observed that the cellular injury process proceeded differentially from the exterior to the interior, with a mitochondrial area increase and outer membrane rupture. Sarcolemmal damage was also observed with prevalent blebbing and membrane loss. The Z-lines became wider and more diffuse with reoxygenation. Injury to the nuclear double membrane was observed. Incubation with propranolol showed significant protection during postanoxia reoxygenation. In contrast, the more water soluble beta-blocker atenolol only exhibited slight protection. In addition, d-propranolol (the non beta-blocking isomer) and the antioxidant enzymes, SOD and catalase, showed significant protection. These data support previous findings concerning the antioxidant properties of propranolol which appear to be independent of beta-receptor blockade.

Animals↗

Captopril protects against myocardial injury induced by magnesium deficiency.

We have previously reported that antioxidant drug intervention protects against magnesium deficiency-induced myocardial lesions. In the present study, Golden Syrian male hamsters were fed either a magnesium-deficient diet or a magnesium-supplemented diet. Animals from each group received sulfhydryl-containing angiotensin converting enzyme inhibitors: captopril, epi-captopril (a stereoisomer of captopril), and zofenopril* (arginine blend of zofenopril containing a free SH group); another group of animals received the non-sulfhydryl-containing angiotensin converting enzyme inhibitor enalaprilat. The animals were killed after 14 days, and their hearts were isolated for morphological and morphometric analyses. Hematoxylin and eosin-stained sections were examined by a computer image analysis system for a morphometric determination of the severity of myocardial injury. Captopril reduced both the density of lesions, from 0.32 to 0.08 lesions/(mm2) (p less than 0.01), and the area fraction of lesions, from 7.42 x 10(-4) to 2.03 x 10(-4) lesion area/(mm2) (p less than 0.01), as well as the degree of inflammatory infiltration around the blood vessels. Epi-captopril and zofenopril* were virtually equipotent to captopril, but enalaprilat afforded only slight (nonsignificant) protection. These results indicate that a significant component of the protective effect of captopril in this model was attributable to its sulfhydryl moiety, rather than solely due to the inhibition of the angiotensin converting enzyme. These data further support our previous findings of possible free radical participation in cardiomyopathy due to magnesium deficiency.

Analysis of Variance↗

Protective effects of sulfhydryl-containing angiotensin converting enzyme inhibitors against free radical injury in endothelial cells.

The effects of SH-containing (captopril, epi-captopril, and the free-SH form of zofenopril) and non-SH-containing (enalaprilat and lisinopril) angiotension converting enzyme (ACE) inhibitors on free radical injury in cultured endothelial cells were studied. When cultured endothelial cells were exposed to a superoxide and hydroxyl radical generating system (dihydroxyfumarate + Fe3(+)-ADP) for 30 min, lipid peroxidation [malondialdehyde (MDA) formation] occurred, and cellular viability (trypan blue exclusion) decreased to 41%; concomitantly, plasma membrane blebbing, assessed by scanning electron microscopy, occurred in 65% of the cells. Preincubation of the cells with each of the SH-agents before free radical addition resulted in an equipotent concentration-dependent (10-200 microM) inhibition (15-60%) of MDA formation; both losses in cellular viability and percent blebbed cells were reduced significantly (P less than 0.05) by concentrations as low as 10 microM of each SH-agent. However, neither of the non-SH agents up to 200 microM produced any major effect. When the effects on hydroxyl radical formation in the system were assessed by ESR spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), concentrations of 10 and 50 microM of the SH-agents reduced the intensity of the DMPO-OH adducts 20 and 50% respectively. Similar results were observed when the hydroxyl radical was generated from the Fenton-reagents (Fe2+ + H2O2), suggesting direct hydroxyl radical scavenging. Thus, these results demonstrate that the SH-containing ACE agents are capable of protecting the endothelial cells against free radical induced lipid peroxidation and cell injury; the mechanism may be due to direct hydroxyl radical scavenging.

Angiotensin-Converting Enzyme Inhibitors↗

Magnesium deficiency-induced cardiomyopathy: protection by vitamin E.

Syrian male hamsters weighing 80-100g were placed on either a magnesium deficient diet (MgD) or an identical diet supplemented with 100 mmols/Kg MgCl. Animals from each group received vitamin E 10, 15, and 25mg three-week slow release pellets, as subcutaneous implants. The animals were sacrificed after 14 days and their hearts isolated for morphological analysis. H&E stained sections were examined by a computer image analysis system for a morphometric determination of the severity of myocardial injury. Vitamin E significantly (p less than 0.01) reduced both the numerical density and the area fraction of MgD lesions. These data indicate possible free radical participation in the mechanism of injury.

Animals↗

Oxygen radical-mediated injury of myocytes-protection by propranolol.

UIe effects of propranolol and atenolol on free radical mediated injury in myocytes were examined. Freshly isolated adult canine myocytes were incubated with a superoxide generating (from dihydroxyfumarate) and Fe-catalyzed free radical system. Exposure of the myocytes to free radicals for 20 min resulted in more than a 5-fold increase in thiobarbituric acid reactant (peroxide) formation and elevated levels of lactate dehydrogenase (LDH) activity released into the media compared to controls. Ultrastructurally, severe sarcolemmal damage, mitochondrial and myofibril derangements were evident. At 40 min, cellular viability (trypan blue exclusion) in the samples exposed to free radicals decreased to about one-third of controls; concomitantly, major losses in total cellular phospholipids occurred. When the cells were pretreated with 200 microM propranolol before the addition of free radicals, both peroxide formation and increased LDH release were inhibited; in agreement, complete ultrastructural preservation was observed. In addition, the subsequent losses in cellular viability and phospholipids were prevented. For comparison, the more water soluble beta-blocker, atenolol at 200 microM was shown ineffective in providing significant protection against the induced injury. The results suggest that propranolol may provide antiperoxidative protection to myocytes when elevated levels of free radicals are present.

Animals↗

Full-thickness cheek and lip reconstruction with the radial forearm free flap.

The radial forearm free flap has proven versatility in head and neck reconstruction. It is superior to regional alternatives such as the pectoralis flap because it is thin, pliable, and predominantly hairless. A more recent application is the use of the folded forearm flap to replace both the skin and inner lining, simultaneously, in full-thickness cheek and lip defects. Nine such cases are presented in this report. Each patient had a recurrent lesion that had been reconstructed previously with local flaps, and all but one were treated with postoperative radiation therapy. The average size of the external defects after resection was 27 cm2, and of the intraoral defects, 18 cm2. All free flaps survived completely. The folded forearm flap solved the reconstructive problem for each patient in a single-stage procedure, providing good contour and a reasonable color match. The flap is easy to raise, has a long pedicle with large-diameter vessels, and has an acceptable donor site defect not associated with long-term morbidity.

Adult↗

One-stage repair of the anterior abdominal wall using bilateral rectus femoris myocutaneous flaps.

Total lower abdominal wall resection was required to remove a recurrent exophytic bladder carcinoma in a 36-year-old woman. The resulting 25 x 30-cm fascial defect was repaired with Marlex mesh. Bilateral rectus femoris myocutaneous flaps were rotated to close the 25 x 18-cm area of skin deficiency. These provided the advantages of robust cover of the lower abdominal wall in a single-stage procedure and primary closure of the donor sites.

Abdominal Muscles↗

Computer-analyzed EEG (CEEG) and dynamic brain mapping in AIDS and HIV related syndrome: a pilot study.

In a group of HIV positive young male patients without any significant neuropsychiatric signs, computer-analyzed EEG (CEEG) and Dynamic Brain Mapping evaluations were conducted. These patients, who only had micro-neuropsychiatric symptoms, demonstrated CEEG profiles that more closely resemble those of patients diagnosed as suffering from mild dementia than age-related normals from our CEEG data base. The CEEGs of patients diagnosed as having Acquired Immune Deficiency Syndrome (AIDS), compared to patients with HIV positive, showed greater similarity in CEEG patterns to severely demented patients than to normal control groups. The findings of this pilot study suggest that CEEG may be useful for early determination of the Central Nervous System's (CNS) involvement with the AIDS virus and monitoring the progress of the illness.

AIDS Dementia Complex↗

Soft-tissue sarcomas of the head and neck.

We reviewed the charts of 352 patients at the Mayo Clinic who were diagnosed and treated for primary soft-tissue sarcomas of the head and neck from 1962 to 1982. The age at diagnosis ranged from 6 weeks to 91 years; 28 percent were pediatric patients. Regional or distant metastases were present at the time of primary diagnosis in 8 percent of patients. Nonorbital rhabdomyosarcoma was the most common tumor type (17 percent), and neuroblastoma was the rarest (2 percent). In children, rhabdomyosarcomas were proportionally more common, as was overall involvement of the orbit. Surgical excision was the sole method of tumor control in 49 percent of patients; excision with adjuvant radiotherapy or chemotherapy was used in 33 percent. In those with localized disease, overall survival was 81 percent at 2 years, 68 percent at 5 years, and 60 percent at 10 years postoperatively. Patients with angiosarcoma and nonorbital rhabdomyosarcoma experienced the poorest survival rates.

Adolescent↗

Total scalp excision and auricular resurfacing for dermal cylindroma (turban tumor).

Dermal cylindroma is a benign neoplasm of the eccrine sweat glands, which presents in the head and neck area in 91% of cases. In its most florid presentation, the entire scalp can be involved, leading to the descriptive label turban tumor. We present the case of a 30-year-old woman with dermal cylindroma extensively involving her forehead and scalp and whose family was affected in three consecutive generations. She underwent total scalp and forehead excision with coverage by split-thickness skin grafts from the thigh. Seven years later, because of progressive external ear involvement, auricular resurfacing was performed. Her scalp and forehead have remained tumor free in the eight-year follow-up period and the auricles at one year. Total excision has led to a cosmetic and functional improvement, and the possibility of malignant degeneration is theoretically decreased.

Adult↗

Lymphoscintigraphy as a guide to treatment in malignant melanoma.

Regional node dissection is practiced as a measure of prophylaxis in patients with stage I and II malignant melanoma. Although the drainage pattern of the extremities is obvious, in the head and neck and trunk it may be ambiguous. We have used lymphoscintigraphy to assist in delineating the lymphatic drainage in 22 patients with primary malignant melanoma. Fourteen patients had melanoma in the head and neck region, and eight had melanoma in the trunk region. Based on Clark's classification there were ten level III melanomas, eight level IV melanomas, and two level V melanomas; the levels of the remaining two melanomas were unspecified. Seven melanomas were between 0.76 and 1.5-mm thick, eleven were between 1.51 and 4.0-mm thick, and two were over 4.0-mm thick (the remaining two were unspecified). Regional nodes were clinically negative in 18 patients. The scan distribution was unexpected in 13 patients (59%), and it influenced the surgical procedure in 11 patients (50%). No patient incurred an adverse effect from the scan. We conclude that lymphoscintigraphy may be of value in guiding prophylactic lymph node dissection in melanoma patients.

Adult↗

Failure of pentoxifylline to enhance skin flap survival in the rat.

The effect of pentoxifylline, a hemorheological agent that increases erythrocyte flexibility and augments capillary blood flow, on the survival of the dorsal skin flap of the rat was studied. An experimental group received intraperitoneal injections of pentoxifylline twice daily, 50 mg/kg/day, and a control group was given identical volumes of saline. Standard McFarlane flaps sized 4 x 9 cm (n = 22) and narrower 2 x 6-cm flaps (n = 18) were constructed 14 days later. After a postoperative observation period of 7 days, no significant difference in tissue survival between the pentoxifylline-treated animals and the controls was found in either flap model. Fourteen days preoperative treatment with pentoxifylline appeared to have no effect on flap survival.

Animals↗

Arteriovenous shunts in free vascularized tissue transfer for extremity reconstruction.

Local vessels are occasionally unsatisfactory donor choices for vascularized tissue transfer in extremity reconstruction. Construction of a temporary arteriovenous loop facilitates not only tension-free anastomoses outside the zone of injury but also affords vascular distention at physiological pressures, an opportunity to verify vein graft patency before tissue transfer, and presumably a decrease in the ischemia time of the vein graft itself. We reviewed the cases of 25 consecutive patients who underwent upper and lower extremity reconstruction facilitated by temporary arteriovenous shunts. In single-stage procedures, greater or lesser saphenous veins were used; the venous end was left in situ in its bed in 17 patients and the entire vein harvested freely in 8. The most common destination was the leg (11), followed by the thigh (7), foot (2), sacrum (2), knee (1), arm (1), and forearm (1). There were three (12%) failures. We conclude that construction of temporary arteriovenous shunts using vein grafts is a productive adjunctive technique in vascularized tissue transfer where additional pedicle length is needed.

Adult↗

Infections in breast implants.

Infection following breast implants is an uncommon event. This is somewhat surprising, since the human breast is not a sterile anatomical structure. The flora found in the breast are derived from the nipple ducts and closely resemble those of normal skin. These organisms, predominantly S. epidermidis, may in some cases be responsible for firmness secondary to capsular contracture. Treatment of the periprosthetic infection usually involves implant removal, but salvage by systemic antibiotics is sometimes possible. Atypical mycobacteria are very rarely the cause of infection, but can be extremely difficult to eradicate when involved. Toxic shock syndrome has been reported to occur following breast implants and is a life-threatening problem requiring immediate removal of the implant. It may be significant that in some cases with effusion and infection occurring many months or years after implant placement, there has been a preceding event such as a laryngitis or flu-like illness. This suggests the possibility of a bacteremia being involved in the causation of the infection. If this were the case, then these patients should be handled in a fashion similar to those with prosthetic heart valves. Accordingly, in our own practice, we advise that penicillin "V" be given beforehand when a patient with breast implants is to have any dental procedure. It must be stressed that there is no statistical or scientific proof at the present time that this is of any value. In conclusion, when dealing with these large foreign bodies, absolute sterility is essential, and excellent surgical technique to obviate hematoma and the occurrence of tissue ischemia is mandatory. Evidence of severe infection necessitates implant removal, but in less severe cases a trial of intravenous antibiotics is permissible. Having removed an implant, further insertion should be deferred, preferably for 6 months. If the new implant can be placed in a different plane, that is, submuscular, this is desirable. Exposed implants can be salvaged but this requires considerable judgment and one should be prepared for re-exposure or frank infection.

Bacterial Infections↗

Angioleiomyomas of the extremities: report of a case and review of the Mayo Clinic experience.

Angioleiomyomas are rare smooth-muscle tumors that occur anywhere in the body. We present the case of a 46-year-old woman with a 3-year history of a painless angioleiomyoma in the right-hand fourth web space with the typical histologic features of tortuous vascular channels and thick muscular walls. In the 39 cases of angioleiomyoma of an extremity treated at the Mayo Clinic, we found a male-to-female ratio of 1:2.2, a mean age of 52 years, and pain as the presenting symptom in 67 percent of the patients. The lesions usually were less than 1 cm in diameter, and they decreased significantly in size with increasing patient age. Simple excision was curative. Angioleiomyoma should be considered in all patients with nodular lesions of an extremity.

Age Factors↗

Cosmetic surgery and criminal rehabilitation.

The contribution of physical appearance to criminal behavior has long been a matter of general interest. We investigated the influence of cosmetic surgery on recidivism rates in the Texas state prison system. The baseline prison population recidivism rates have been 14%, 32%, and 36% at one, two, and three years, respectively. The study group consisted of 253 inmates who had cosmetic procedures between 1982 and 1984 and who were released from prison between the time of operation and the end of 1986. The recidivism rates, calculated by life table analysis, were 8% at one year, 17% at two years, and 25% at three years. All were significantly less than baseline (P less than .01, P less than .001, P less than .01). The rates for those who had been incarcerated for violent crimes were 3.3%, 7.7%, and 15.0% (all P less than .001). We conclude that a positive relationship exists between cosmetic surgery and criminal rehabilitation, as measured by a decrease in recidivism.

Actuarial Analysis↗