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Biomedical subjects

D L Larson

Publications and source records attributed to D L Larson.

At least 19 recordsLinked to original sources
PubMed1992

Opioid agonist and antagonist activities of morphindoles related to naltrindole.

A series of naltrindole-related ligands (4-10) with an N-methyl,N-phenethyl,N-cinnamyl, or an unsubstituted basic nitrogen were synthesized and tested for opioid agonist and antagonist activity in smooth muscle preparations and in mice. The nor compounds (4 and 6) and the phenethyl derivatives (5 and 8) displayed full agonist activity (IC50 = 85-179 nM) in the mouse vas deferens preparation (MVD) while the other members of the series exhibited partial agonist or weak antagonist activity. In the guinea pig ileum preparation (GPI), all compounds except 8 were partial agonists. The ligands that were evaluated in mice were found to produce antinociception that was not selectively mediated via delta opioid receptors. However, two of these ligands (4 and 5) appeared to be delta-selective opioid receptor antagonists at subthreshold doses for antinociception. The finding that all of the compounds bind selectively to delta opioid receptors in guinea pig brain membranes together with the in vitro pharmacology and in vivo antagonist studies suggests that the lack of delta agonist selectivity in vivo may be due to a number of factors, including a basic difference between the delta receptor system in the MVD and in the mouse brain. Further, it is suggested that the constellation of message and address components in the morphindole nucleus may tend to stabilize delta receptors in the brain in antagonist state.

Analgesia↗
PubMed1992

Toxic shock syndrome following latissimus dorsi musculocutaneous flap breast reconstruction.

Acute toxic shock syndrome (TSS) not related to menstruation has comprised an increasing proportion of cases reported to the Center for Disease Control in recent years. We report a patient with TSS resulting from a postoperative donor site infection after bilateral breast reconstruction with latissimus dorsi musculocutaneous flaps. The diagnosis, management, and outcome of TSS are reviewed. The plastic surgeon should be aware of TSS as a potential postoperative complication of routine procedures in plastic surgery.

Adult↗
PubMed1992

Elimination of the vertical scar in reduction mammaplasty.

We describe a technique to eliminate the vertical portion of the inverted-T incision in patients who have combined enlargement of the breasts and moderate to severe ptosis. Initial preoperative markings are made, placing the new nipple site at the level of the transposed inframammary crease. The nipple-areola complex is then retained on a vascularized pedicle, with major reduction of the breast tissue being done in the medial and lateral quadrants. The nipple and breast tissue are then tucked underneath the superior skin segment and placed in this new position as one would do with the umbilicus in an abdominoplasty. Excess vertical skin is removed, and horizontal excess is collected at the midline as a small dog-ear. We have found that this dog-ear reduces markedly with time, rounding out the inferior portion of the breasts. The remaining small amount of excess skin can then be removed under local anesthetic at a later date. We have performed this procedure on 20 patients, with follow-up from 6 to 24 months.

Adolescent↗
PubMed1991

Persistent binding of fatty acyl derivatives of naltrexamine to opioid receptors.

A series of fatty acid derivatives of naltrexamine and naltrexhydrazine were synthesized and evaluated for their persistent binding to opioid receptors. Members of this series were found to require greater than five washes for removal from mouse brain membranes when the fatty acyl chain was saturated. The presence of unsaturation in the fatty acyl groups enhanced the persistent binding. In this regard the persistent binding increased as a function of the number of double bonds, with the unsaturated congeners requiring greater than 10 washes for removal of the ligand from the membranes. The results of this study are consistent with the apparently important role of polyunsaturated fatty acids in the binding of ligands to opioid receptors.

Animals↗
PubMed1991

Hyperbaric oxygen therapy in plastic surgery: a review article.

The most important effects of hyperbaric oxygen (HBO), for the surgeon, are the stimulation of leukocyte microbial killing, the enhancement of fibroblast replication, and increased collagen formation and neovascularization of ischemic tissue. Preoperative hyperbaric oxygen induces neovascularization in tissue with radionecrosis. Refractory osteomyelitis and necrotizing fasciitis appear to respond to adjunctive hyperbaric oxygen. Crush injury and compartment syndrome appear to benefit through preservation of ATP in cell membranes, which limits edema. Hyperbaric oxygen in burn injury permits shorter hospital stays, a reduced number of surgeries, and less fluid replacement. Skin grafts and flaps are reported to take more completely and more rapidly. The same mechanisms may apply in ischemic problem wounds such as infected diabetic extremities. Contraindications and side effects are described. Hyperbaric oxygen will not heal normal wounds more rapidly but may, under certain circumstances, induce problem wounds to heal more like normal ones.

Burns↗
PubMed1990

Long-acting agonist and antagonist activities of naltrexamine bivalent ligands in mice.

A series of naltrexamine bivalent ligands, compounds with two naltrexamine pharmacophores separated by a spacer which contains a variable number of glycyl units flanking a succinyl group, were synthesized and evaluated in vivo in mice. These compounds possessed long-acting agonist and especially antagonist activities. The bivalent ligands, 2 and 3 displayed antinociceptive activity that lasted greater than 4 h. Compound 1, a bivalent ligand and 4, the monomer, antagonized the antinociceptive effect of morphine for a week after a single injection i.c.v. The long duration of action may be due to entrapment of these ligands in the central nervous system. These compounds may give future insights into the design of long-acting agonists and antagonists.

Analgesics↗
PubMed1990

Long-term effects of radiotherapy in childhood and adolescence.

The records of 50 selected pediatric patients who were treated and followed at M. D. Anderson Cancer Center were reviewed to study the late effects of nonsurgical treatment of cancer in children. There were 26 girls and 24 boys ranging in age between 2 months and 16 years. Patients with head and neck cancer received chemotherapy and radiotherapy for rhabdomyosarcoma (n = 27), retinoblastoma (n = 8), or nasopharynx cancer (n = 2). Median follow-up was 13 years. The most severe side effects were noted in the fields of radiation and included hypoplasia of the jaw, orbit, or hemi-face with varying degrees of atrophy of the overlying soft tissues. A wide range of endocrine, dental, and psychologic abnormalities was also documented. Since 1 in every 1,000 adults older than 20 years today is likely to be a survivor of childhood cancer, recommendations are made for this "new" class of patients whom the head and neck surgeon will be seeing in the future.

Adolescent↗
PubMed1990

Long-term survival after chest-wall reconstruction with musculocutaneous flaps.

Reconstruction of chest-wall defects with musculocutaneous flaps permits resection of advanced chest-wall tumors and of tissues severely damaged by radiotherapy in patients who in a previous era were not surgically treatable. To determine the long-term outcome from this surgery, the records of 96 patients who had undergone chest-wall resection with musculocutaneous flap reconstruction were reviewed. Median survival for the entire group was 20.5 months, but a more accurate prediction of outcome could be obtained by dividing the patients into three groups. In group I, patients free of known malignancy and undergoing resection of radionecrotic tissues, median survival was 60.0 months. In group II, patients with resectable disease and free of tumor following surgery, median survival was 31.1 months. In group III, patients incompletely resected or known to have metastatic disease following surgery, median survival was only 12.5 months. Even in group III, however, some individuals achieved prolonged survival and lasting benefits from the surgery, so these data should not be used to exclude patients from undergoing necessary palliative procedures.

Analysis of Variance↗
PubMed1990

Alterations in wound healing secondary to infusion injury.

Though uncommon, the occurrence of an extravasation of a tissue-toxic drug can be a very disconcerting event in the physician's practice. A wound specialist, such as a plastic surgeon, is frequently consulted. The author reviews the "state of the art" approach to these challenging wounds.

Doxorubicin↗
PubMed1989

Prevalence of gallstone disease in Hispanic populations in the United States.

The 1982-1984 Hispanic Health and Nutrition Examination Survey used ultrasonography to investigate the epidemiology of gallstone disease. Mexican American, Cuban American, and Puerto Rican men and women, aged 20-74 yr, were selected from household samples in Texas, New Mexico, Arizona, Colorado, California, Connecticut, New Jersey, New York, and Florida. Ultrasonography was performed on 2299 persons. The age-adjusted prevalence of gallstone disease (gallstones + cholecystectomy) among Mexican American men (7.2%) was 1.7 times that of Cuban American men and 1.8 times that of Puerto Rican men. The prevalence for Mexican American women (23.2%) was 1.5 times that of Cuban American women and 1.7 times that of Puerto Rican women. Rates were about three times higher among women than men and increased with age in both sexes and all ethnic groups except older Puerto Rican women. Among Mexican American women aged 60-74 yr, the prevalence of gallstone disease reached 44.1%. These results support the hypothesis that Mexican Americans are at increased risk of gallstone disease.

Aged↗
PubMed1989

Reactivity of glutathione with alpha, beta-unsaturated ketone flavouring substances.

The relative reactivities of a number of alpha, beta-unsaturated ketones used as flavourings were determined using glutathione as the nucleophile. Monosubstitution at the beta-position of the alpha, beta-unsaturated system impeded nucleophilic addition by approximately 1000 times. Beta-Disubstitution reduced reactivity by more than 100,000 times. Endocyclic alpha, beta-unsaturated ketones were generally less reactive than alicyclic analogues. By way of comparison, the most reactive flavouring investigated, 2-octene-4-one, was consumed by glutathione about 700 times less rapidly than was methylvinyl ketone. Methylvinyl ketone was found to condense with guanylic acid 240,000 times more slowly than with glutathione. It is concluded that alpha, beta-unsaturated ketones used as flavourings generally possess low electrophilicity.

Butanones↗
PubMed1989

Opioid agonist and antagonist activities of peripherally selective derivatives of naltrexamine and oxymorphamine.

A series of beta-naltrexamine and beta-oxymorphamine derivatives that contain ionizable moieties coupled to the 6 beta-amino group were synthesized in an effort to develop antagonists and agonists that have negligible access into the central nervous system (CNS). Among the beta-naltrexamine derivatives 1-7, all displayed partial agonism on the guinea pig ileal longitudinal muscle preparation except for aspartyl derivative 6, which was a full agonist with activity in the range of morphine. The beta-oxymorphamine derivatives 8-12 were all full agonists with potencies ranging from 1.5 to 6.1 times that of morphine. Among the compounds evaluated in mice for antinociceptive or opioid antagonist activities, aspartyl derivative 6 possessed the greatest difference between peripheral (po or iv) and icv equiactive antagonist doses. Compared to naltrexone, 6 was greater than 100 times more potent by the icv route, but 6000-10,000 times less potent when administered po or icv. The present study suggests that zwitterionic groups are highly effective in preventing penetration of ligands into the CNS. Such ligands may be useful pharmacologic tools for investigation of peripheral opioid mechanisms. Moreover, they could find clinical applications when the central actions are unwanted.

Animals↗
PubMed1987

Hybrid bivalent ligands with opiate and enkephalin pharmacophores.

Bivalent ligands consisting of oxymorphamine and [D-Glu2]enkephalin pharmacophores linked through a spacer attached to the 6-amino group of the former and D-Glu of the latter were synthesized in an effort to investigate the possible coexistence of mu and delta recognition sites in the same opioid receptor complex. Of the two bivalent ligands (1,2) synthesized, only 1 had substantially greater antinociceptive potency in mice than its monovalent analogues (1a, 1b). Testing of 1, 1a, and 1b in the guinea pig ileum preparation (GPI) revealed a potency profile similar to that found in vivo, whereas no correlation was observed in the mouse vas deferens (MVD). Binding data indicated the same rank-order affinities at delta receptors as the opioid activities in the GPI and in mice. However, mu binding exhibited no relationship with activity. These results are consistent with the simultaneous occupation of mu and delta by a single bivalent ligand 1, but they are also in harmony with the interaction of 1 with an opioid receptor and an accessory binding site.

Analgesics↗
PubMed1979

Chloroxymorphamine, and opioid receptor site-directed alkylating agent having narcotic agonist activity.

Chloroxymorphamine, the 6beta-N,N-bis(2-chloroethyl) derivative of oxymorphone, is a potent nonequilibrium narcotic agonist in the longitudinal muscle preparation of guinea pig ileum. The corresponding naltrexone analog,chlornaltrexamine, is a potent nonequilibrium antagonist of morphine. These receptor sitedirected alkylating agents possess considerable potenial as pharmacologic and biochemical probes of apoid receptors.

Alkylating Agents↗
PubMed1979

Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties.

Chlornaltrexamine (CNA) produces ultralong-lasting (3--6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.

Alkylating Agents↗