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Biomedical subjects

D L Larson

Publications and source records attributed to D L Larson.

At least 91 records · Page 5Linked to original sources
PubMed1984

A perspective on chest wall resection in patients with breast cancer.

The morbidity from locally recurrent breast cancer or osteoradionecrosis and accompanying infection is substantial. The selective use of surgical resection offers good palliation. Extended full-thickness chest wall resection is facilitated by a variety of techniques available for closure and coverage including use of latissimus dorsi myocutaneous flap, rectus abdominus myocutaneous flap, pectoralis myocutaneous flap, breast flap, and omentum with skin graft. The experience with 43 consecutive chest wall resections in patients with breast cancer affords the opportunity to define indications and contraindications for such palliative procedures. Indications include local symptoms of pain and infection, tumor recurrence refractory to radiation therapy, and infection that precludes chemotherapy. Relative contraindications are pulmonary metastases, bone metastases, hepatic metastases, and malignant pleural effusions. Absolute contraindications are brain metastases, bone marrow involvement, bulky disease in two organs, and breakthrough on multiple chemotherapy regimens. Operative revision was only required in 4 of 43 patients. Minor wound complications occurred in 12 (28%). Three patients who underwent resection for local recurrence have survived 40 months or more free from disease. This procedure provides substantial palliation by relieving pain, controlling infection, removing a weeping wound, and allowing chemotherapy for metastatic disease. In the proper setting, chest wall resection is an important part of the armamentarium for palliation of the patient with breast cancer. It can markedly improve quality of life and occasionally may result in long-term survival.

Abscess↗
PubMed1984

Design and synthesis of naltrexone-derived affinity labels with nonequilibrium opioid agonist and antagonist activities. Evidence for the existence of different mu receptor subtypes in different tissues.

A series of beta-funaltrexamine (2, beta-FNA) analogues (3-14) were synthesized that contain a variety of electrophilic groups attached at the 6 beta-position of the opiate. The opioid agonist and antagonist activities of these ligands were evaluated in the guinea pig ileum (GPI) and mouse vas deferens (MVD) in vitro assays. Several of the compounds behaved like beta-FNA in that they exhibited reversible agonist activity at kappa opioid receptors and irreversible antagonist activity at mu opioid receptors. The rank order of irreversible antagonism for a series of related Michael acceptors did not parallel their intrinsic chemical reactivity, confirming that the degree of covalent binding is in part dependent on the spatial disposition of the electrophilic center relative to the receptor nucleophile (secondary recognition). The maleimidoacetamide 8 behaved very differently from beta-FNA in that it exhibited considerably greater irreversible mu antagonism in MVD relative to the mu blockage in the GPI. This suggests that different proportions of mu receptor subtypes exist in the two tissues. Several of the agents tested, including some nonreactive control compounds, displayed an unusual type of persistent kappa agonist activity in the GPI. This activity, which was reversed by addition of naloxone, reappeared upon washing. Receptor models have been presented to explain this effect. A few of the reactive ligands displayed a true nonreversible kappa agonist activity, suggesting a covalent association with the receptor. Of note in this regard was the propiolamide 6, which appeared to be an irreversible mixed agonist-antagonist at kappa and mu receptors.

Affinity Labels↗
PubMed1984

Musculocutaneous flap reconstruction of chest-wall defects: an experience with 50 patients.

Precepts derived from a review of 50 patients included (1) prior radiation of the vessel supplying the flap does not appear to have any effect on viability; (2) in an open, infected wound, use of synthetic materials adds significantly to the risk of infection and, in fact, appears to be unnecessary; (3) in full-thickness chest-wall defects, reconstruction can be accomplished in almost all cases by inset of the flap only, without need of support of fascia, ribs, or prosthetic material; and (4) in locally recurrent breast cancer, chest-wall resection is an adjunct to chemotherapy. A schematic outlining potential defects and appropriate musculocutaneous reconstruction is also presented.

Adult↗
PubMed1984

Does the diagnosis of depression in head and neck cancer mask organic brain disease?

Scant attention has been paid to emotional changes as possible symptoms of impaired cerebral functioning in cancer patients. A retrospective study was conducted to determine the variety of organic brain syndromes (OBS) that presented with depressive symptoms in 20 head and neck cancer patients. The impressions of referring surgeons were in error in 16 patients (80%). Twelve (60%) had unsuspected OBS, with treatment resulting in reversal of symptoms in almost half. Of the eight patients with functional disorders, four received a final diagnosis of depression. Head and neck surgeons should be aware that (1) emotional changes in their patients frequently reflect OBS, some potentially reversible, (2) because of the ages of the patients, senile dementia may be a more common occurrence in head and neck cancer than suspected, and (3) because of the difficulties of evaluating changes in higher mental functions, more neuropsychiatric consultations may be warranted for head and neck patients.

Aged↗
PubMed1984

Inhibitory effect of sera from rheumatoid arthritis patients and enhancing effect of levamisole on total E-rosette levels of lymphoid cells from normal and RA subjects.

We determined the E-rosette levels (E-R) in rheumatoid arthritis patients (RA) and repeatedly tested a selected group with depressed E-R. We also evaluated, in vitro, the inhibitory effect of RA sera on normal E-R and the enhancing effect of levamisole (LV) on normal and RA E-R. Selection criteria and E-R protocol were those of Di Perri (1979). Mononuclear cells (MNC) from 23 normal donors had a mean E-R of 53 +/- 7% (X +/- SD) and this was unchanged after incubation with 32 microM LV. MNC from 31 RA displayed a value of 42 +/- 7% which was lower (p = 0.01) than the normal values and which increased to 47 +/- 9% after LV treatment (p = 0.02). Twenty of these RA did not show enhanced E-R after LV; the remaining 11 RA had E-R of 37 +/- 6% which were restored to 50 +/- 8% after incubation with LV (p = 0.001). We defined this latter group of RA as depressed responders (DR). Four DR were tested repeatedly over a four-month period and consistently remained depressed. Their sera had inhibitory activity on E-R of healthy donors. In vitro treatment of healthy MNC with these RA sera plus 3.2 microns LV abrogated the inhibitory effect. Both the IgG and the IgM fractions of the RA sera manifested this inhibitory effect. We conclude that RA can have depressed E-R which are not transient and can be corrected by in vitro incubation with an immunomodulator. Sera from these RA can inhibit E-R of normal MNC, and LV can abrogate the inhibitory activity of such sera.

Arthritis, Rheumatoid↗
PubMed1983

Major complications of radiotherapy in cancer of the oral cavity and oropharynx. A 10 year retrospective study.

In an attempt to determine the late effects and associated morbidity of radiotherapy on normal tissue, patients with squamous carcinoma of the oral cavity and oropharynx were retrospectively reviewed. Between 1964 and 1975, 569 patients with cancer of the floor of the mouth, oral tongue, tonsil, and retromolar trigone region of the anterior faucial pillar had their primary lesions treated by radiotherapy alone for cure. One hundred twenty-eight of the patients were evaluable for this study. Bone and soft tissue morbidity were graded according to the late radiation scoring scheme of the radiation therapy oncology group of the European Organization on Research and Treatment of Cancer, tallying only grade 4 changes. Patients were further classified according to site of tumor, age, sex, tumor stage, histologic grade, and dental status--none of which had a positive correlation with complications. Of 31 evaluable patients with cancer of the floor of the mouth (median follow-up 136 months), 71 percent (22 of 31 patients) had at least one complication involving bone (osteonecrosis, pathologic fracture) or mucus membrane (ulcer). Sixty-one percent (25 of 41 patients) with primary cancer of the oral tongue had grade 4 sequelae (median follow-up 112 months). In 26 patients with cancer of the tonsil, 13 (50 percent) had grade 4 sequelae (median follow-up 113 months). This included 11 patients with clinical and radiographic evidence of osteonecrosis, 6 of whom required mandibulectomy. Patients with cancer of the retromolar trigone region of the anterior faucial pillar fared the best (median follow-up 122 months). Late sequelae were noted in 40 percent (12 of 30 patients). The morbidity attendant to cure by radiotherapy included at least one significant complication of bone or soft tissue in 40 to 70 percent of the patients, depending on the location of the primary tumor. There was also a positive correlation with dose of radiation received.

Adolescent↗
PubMed1983

Importance of C-6 chirality in conferring irreversible opioid antagonism to naltrexone-derived affinity labels.

A series of five epimeric pairs of naltrexone derivatives that contain an electrophilic substituent at the 6 alpha- or 6 beta-position was synthesized and tested on the guinea pig ileal longitudinal muscle (GPI) and mouse vas deferens (MVD) preparations in order to determine if the orientation of the electrophile is important for covalent bonding to opioid receptors. In the GPI all compounds were pharmacologically active as reversible agonists, but only the 6 beta-isomers of the fumaramate ester 2b (beta-FNA) and isothiocyanate 6b exhibited covalent reactivity, involving a selective irreversible antagonism of the mu agonist, morphine, without affecting kappa agonists. The 6 alpha-isomer 2a (alpha-FNA) was itself nonalkylating but was able to protect the GPI against alkylation by its epimer, beta-FNA, indicating that the two epimers bind to the same receptor. These results suggest that the proper orientation of the electrophilic substituent is required for covalent bonding with a proximal nucleophile in the case of mu receptor blockade. Moreover, the lack of covalent bonding to kappa receptors by these or other ligands in this series indicates the possible absence of sufficiently reactive nucleophiles on this recognition site. In the MVD, 2b, but not 2a, irreversibly antagonized morphine (as in GPI), whereas neither epimer exhibited irreversible antagonism toward the delta agonist, [D-Ala2,D-Leu5]enkephalin (DADLE). In contrast, both of the isothiocyanate epimers (6a,b) irreversibly blocked mu and delta receptors. Evidence suggesting differences between mu receptors in the MVD and GPI was obtained with the beta-iodoacetamide 5b, which was an irreversible blocker of morphine only in the MVD. When analyzed together with those of previous studies with the nitrogen mustard analogues, alpha- and beta-chlornaltrexamine, the data suggest that the receptor-alkylating ability of each isomer in an epimeric pair differs most when the electrophile possesses a narrow spectrum of reactivity.

Affinity Labels↗
PubMed1983

Appropriate timing for breast reconstruction.

Once a chest-wall recurrence is diagnosed, it should be treated by modalities effective for both local and systemic disease, since it is a cutaneous marker of distant metastases. If the chest-wall recurrence can be controlled, short-term prognosis is much improved, although all patients in this study eventually died of systemic breast cancer. The results of this retrospective study suggest that appropriate timing of breast reconstruction depends on the pathologic status of the axillary nodes and completion of adjunctive therapy. A patient with stage I breast cancer can undergo a subpectoral or musculocutaneous flap reconstruction of the breast without fear of masking a local chest-wall recurrence.

Axilla↗
PubMed1982

Treatment of tissue extravasation by antitumor agents.

Infiltration of antitumor agents into subcutaneous tissues may either result in a local area of self-resolving inflammation, or progress to full-thickness loss of skin and underlying vital structures. The immediate treatment of 50 extravasations occurring over a 20-month period resulted in our developing a protocol of appropriate care. Once extravasation is suspected, the intravenous line is removed, ice is applied intermittently for three days, and the wound is observed closely. No drugs are even given locally. If local pain persists or skin changes progress, the area of involvement is debrided and, a skin graft is applied two to three days later. As a result of this conservative approach, only 12 of 50 patients have required surgery. This method of treatment has minimized patient mortality, hospitalizations, and loss of synchronization of chemotherapy.

Aged↗
PubMed1982

Major chest wall reconstruction after chest wall irradiation.

In the last year, 12 patients have undergone extensive chest wall resection. Eight patients had recurrent cancer after prior resection and irradiation with an average defect of 160 square centimeters, usually including ribs and a portion of the sternum; four had radionecrosis of soft tissue and/or bone. Methods of reconstruction included latissimus dorsi musculocutaneous (MC) flap (five patients), pectoralis major MC flap (seven patients), and omental flap and skin graft (one patient). The donor site was usually closed primarily. All flaps survived providing good wound coverage. The only complication was partial loss of a latissimus dorsi MC flap related to an infected wound; this reconstruction was salvaged with a pectoralis major MC flap. The hospital stay ranged from 10-25 days with a median stay of 11 days. Use of the MC flap is a valuable tool which can be used to significantly decrease morbidity, hospital stay, and patient discomfort related to the difficult problem of chest wall reconstruction after radiation therapy.

Adult↗
PubMed1982

Preservation of the orbital contents in cancer of the maxillary sinus.

Tumor invasion of the periorbita, posterior ethmoid cells, or orbital apex is considered an absolute indication for orbital exenteration. Preservation of the orbital contents in selected cases can be applied safely to the treatment of primary maxillary sinus cancer. Patient complaints relating to the preserved eye were more commonly associated with radiation therapy than the method of reconstruction used. Reconstruction of the orbital floor with a skin graft, even when combined with radiation therapy, gave a functional eye in the majority of cases while not compromising the oncologic safety or the procedure.

Eye↗
PubMed1982

Clinical effects of closed suction drainage on wound healing in patients with head and neck cancer.

This study was undertaken to determine what optimal levels of suction pressure were necessary to provide good drainage volume and obliteration of any dead space and also to determine the prevalence of clotting and complications secondary to various levels of suction pressure. The patients were grouped by their degree of nutritional depletion, prior radiation exposure, the types of surgical procedures undergone, and the results of tests using four levels of suction pressure. Three of the suction pressure values were obtained with a wall suction and one was obtained using a portable closed system. All wall suction pressure levels were certainly comparable with the portable unit. However, the portable unit provided continuous suction pressure when the patients were ambulatory and was not associated with any statistically significant increase in wound complications or equipment failure.

Head and Neck Neoplasms↗
PubMed1982

An analysis of piroxicam in rodent models of arthritis.

Piroxicam, a potent, long acting non-steroidal anti-inflammatory drug, was tested in several rodent models of arthritis to assess further the possible mechanisms underlying its anti-inflammatory action. Piroxicam inhibited rat adjuvant disease and its associated manifestations, which include erosion of bone and cartilage (as evidenced by X-ray examination), soft tissue swelling and disease-induced weight loss. Piroxicam also inhibited the edema, the total leukocyte infiltration and the mononuclear cell infiltration into the carrageenan-injected pleural cavity of the rat. The possible relationship of these effects to the clinical activity of piroxicam is discussed.

Animals↗
PubMed1982

Synthesis, X-ray crystallographic determination, and opioid activity of erythro-5-methylmethadone enantiomers. Evidence which suggests that mu and delta opioid receptors possess different stereochemical requirements.

Enantiomers of erythro-5-methylmethadone (3) were synthesized from optical antipodes of erythro-3-(dimethyl-amino)-2-butanol. X-ray crystallographic analysis of (-)-3 perchlorate revealed that it possesses the 5S,6S absolute configuration. It was found that (-)-3 is substantially more potent than its enantiomer (+)-3 as an opioid agonist in vivo and in vitro. In vitro tests (guinea pig ileal longitudinal muscle and mouse vas deferens preparations) suggest that (-)-3 mediates its effect chiefly through mu opioid receptors. On the other hand, (+)-3 and the more potent enantiomers of methadone, (-)-1, and isomethadone, (-)-2, appear to have less mu-receptor selectivity and interact with a greater fraction of delta receptors than does (-)-3. The fact that the solid-state conformation of (-)-3 differs from that of (-)-1 and (-)-2, which show great similarity in conformational features, suggests that mu and delta receptors have different conformational requirements. The possibility of different modes of interaction with a single opioid receptor population also is discussed.

Animals↗