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Biomedical subjects

M D Brown

Publications and source records attributed to M D Brown.

At least 217 records · Page 12Linked to original sources
PubMed1989

Myocardial chronotropic and inotropic responsiveness in vitro after chronic alpha 1-adrenoreceptor blockade in the rat.

1. Positive chronotropic and inotropic myocardial responses to different adrenoreceptor agonists were studied using isolated right atria and left ventricular papillary muscles from rats treated orally for 5 weeks with prazosin, an alpha 1-antagonist, or vehicle (distilled water). 2. Chronotropic responses to the beta-adrenoreceptor agonists isoprenaline and salbutamol were similar in atria from both groups of rats, with no differences in their basal rates, maximum rate increases or pD2 values for either agonist. 3. Basal contractile force of field-stimulated papillary muscles was similar in both prazosin-treated (0.089 +/- 0.014 g mg-1) and control groups (0.104 +/- 0.035 g mg-1). In response to noradrenaline, force increased maximally by 145 +/- 30% and 131 +/- 30% above resting levels respectively, and pD2 values for this beta- and alpha-agonist showed no changes after chronic prazosin treatment. Inotropic responses to isoprenaline were also not different with maximum increases in force of 94.5 +/- 20.2% for prazosin-treated and 84.5 +/- 18.5% for controls, and similar pD2 values. 4. However, in response to the alpha 1-agonist phenylephrine (in the presence of propranolol), maximum increases in force were greater in relation to the noradrenaline maxima after prazosin treatment (48.8 +/- 4.2%) than in controls (32.0 +/- 4.3%, P less than 0.02). pD2 values for phenylephrine were also significantly higher after long-term alpha 1-blockade (5.71 +/- 0.10 vs 5.30 +/- 0.19 for controls, P less than 0.05). 5. Long-term alpha 1-blockade in the rat therefore led to supersensitivity of alpha 1-mediated inotropism in the heart, but both beta-mediated inotropic and chronotropic responses were unaffected. These results show selectivity of action of chronic prazosin treatment on alpha 1-receptors in the rat heart.

Adrenergic alpha-Antagonists↗
PubMed1989

Treatment of malignant fibrous histiocytoma and atypical fibrous xanthomas with micrographic surgery.

Fibrous tumors of the soft tissue are usually benign, but some fibrous neoplasms such as dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and malignant fibrohistiocytoma (MFH) can be very destructive locally with a high recurrence rate after local excision. On occasion, they can metastasize. Previous reports have confirmed the high success rate of Mohs micrographic surgery for the treatment of DFSP, but data have been lacking on the potential benefit of this surgical approach for MFH and AFX tumors. Over the past 6 years, we have treated 17 patients with MFH (20 tumors) and 5 patients with AFX with Mohs micrographic surgery. A retrospective analysis of the surgical results is presented. To date (average 3-year follow-up), all patients contacted are tumor free with only one recurrence; no patient has developed metastatic disease. Our results to date are very encouraging; they lend support to Mohs micrographic surgery as a desired surgical approach for these difficult-to-cure neoplasms.

Adolescent↗
PubMed1989

Laser vaporization: a novel treatment of botryomycosis.

Botryomycosis is an uncommon, chronic infection of the skin most often caused by Staphylococcus aureus. It has been successfully treated using carbon dioxide laser vaporization in a case in which antibiotic therapy failed, and surgical excision was not feasible.

Carbon Dioxide↗
PubMed1989

Beneficial effect of chronic bradycardial pacing on capillary growth and heart performance in volume overload heart hypertrophy.

We have previously reported that chronic bradycardial pacing increases both capillary density/mm2 (CD) and maximal work output in normal rabbit hearts. This technique has now been applied to rabbits with volume-overload hypertrophy due to lesion of the aortic valve. Four groups of animals were studied: controls (C), paced (P), valve-lesioned (VL), and paced valve-lesioned (PVL). The aortic valve was lesioned 8 weeks before the acute experiments; pacing was started 4 weeks before the acute experiments, and thus, the PVL group had developed hypertrophy before pacing was started. The degree of hypertrophy was similar in VL hearts whether paced or not: heart wt/body wt ratio increased by 33.5 +/- 8.9% (mean +/- SEM) in VL and 25.2 +/- 8.2% in PVL versus control animals of similar body weight (p less than 0.001). The hearts of the PVL animals showed a higher CD (2,277 +/- 107) than VL hearts (1,383 +/- 43), CD in C hearts of similar weights being 1,595 +/- 103, and in P hearts 2,350 +/- 194. Thus, CD was lower by 14% in VL and higher by 43% in PVL than in C hearts. Valve-lesioning had a significant effect in reducing maximal cardiac minute work (p less than 0.001), whereas pacing significantly improved maximal cardiac minute work (p less than 0.001) to 2.467 +/- 0.206 J/g x 10(-4) in the P group versus 1.609 +/- 0.105 in the C group.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1989

Cardiac work and capillary density in normal and vascularly compromised hearts.

Capillary density and cardiac work were measured in several groups of rabbits, with normal hearts (controls) and hearts vascularly compromised by left ventricular volume-overload hypertrophy or subendocardial necrosis elicited by a high dose of noradrenaline. Measurements were also made in these same three groups after four weeks of atrial bradycardial pacing, and also in two groups treated for four weeks with coronary vasodilators (adenosine or a xanthine derivative HWA 285). Chronic bradycardial pacing, with decreased heart rate by about 50%, resulted in increased capillary density in both control and hypertrophied hearts. Increased capillary density was also induced by long-term i.v. infusion of adenosine or HWA 285. Since pacing or vasodilator infusion did not alter the heart weights or fibre diameters, the increase in capillary density can be interpreted as due to capillary growth. Increased capillary density was also found in noradrenaline-treated hearts--both unpaced and paced--and was due to a drastic reduction in fibre cross sectional area (and consequently reduced diffusion distances). Heart performance, estimated by maximal cardiac work, was increased in all paced hearts (control, hypertrophied, noradrenaline-damaged) and in hearts infused with HWA 285, but not with adenosine. Thus increased capillary density and shortening of diffusion distances do not guarantee improved heart performance. Since pacing of hypertrophied and noradrenaline-damaged hearts and infusion of HWA 285 increased subendo/subepicardial capillary density ratio, the importance of homogeneous transmural or preferential higher subendocardial capillary supply for cardiac work is discussed.

Adenosine↗
PubMed1989

Bone transplantation and human immunodeficiency virus. An estimate of risk of acquired immunodeficiency syndrome (AIDS).

The possibility of transplanting a bone allograft from a donor infected with human immunodeficiency virus (HIV) is remote, provided there is a combination of rigorous donor selection and exclusion, screening for the HIV antigen and antibody, and histopathologic studies of donor tissues. The chance of obtaining a bone allograft from an HIV-infected donor who failed to be excluded by the above techniques is calculated to be one in well over a million, using average estimates. On the other hand, if adequate precautions are not taken (for example, by testing only for antibodies to HIV), the risk might be as high as one in 161.

AIDS Serodiagnosis↗
PubMed1989

Therapy of dermatologic disease with cyclosporin A.

Cyclosporin A is a potent immunosuppressive drug with almost a decade of clinical use. Due to its lack of bone marrow toxicity, it has assumed a leading role in organ transplant surgery. Likewise, it has shown remarkable efficacy in psoriasis and has shown potential usefulness in other dermatologic diseases, most of which are thought to have an autoimmune T-cell-mediated pathogenesis. There are many other inflammatory skin conditions in which T lymphocytes represent a majority of the cellular infiltrates, and theoretically such disorders may be responsive to CsA. Diseases such as lichen planus, allergic contact dermatitis, photoallergy, and vitiligo are potential areas of further study. The potential use of topical and intralesional CsA also warrants further clinical evaluation. There are reports of topical CsA showing effectiveness for alopecia areata and nickel contact sensitivity. Griffiths et al. treated six psoriatic patients with 2% CsA ointment twice daily for 4 weeks. The response to placebo or CsA at the end of the study was similar in all patients. Notably, there was no measured systemic absorption and no change in blood pressure or renal function. We had similar unimpressive results in several patients treated with a 10% solution of CsA; minimal to no response was seen. Of great benefit would be an effective topical preparation without systemic absorption or toxicity. Future studies will need to carefully evaluate the vehicle used and the strength of topical CsA employed. The role of CsA in dermatologic disease still needs much investigation, both at the clinical and basic science levels. The studies to date show dramatic and exciting results. Indeed, CsA may well represent a major advance in the understanding and treatment of psoriasis. However, the decision to use CsA for nonfatal diseases such as psoriasis will require a careful balance between efficacy and toxicity. If long-term side effects can be avoided or kept within reasonably safe, acceptable limits, CsA holds great promise for the treatment of psoriasis. It may at times be used as an acute intervention, with a relatively large, initial dose for a short period of time to quickly clear severe psoriasis. This could be followed by either a reduction to a lower and safer maintenance dose or a program of other treatments. Cyclosporin A may also prove useful alone in very low doses or in combination therapy, as with UVB or PUVA. Optimal dosing protocols are currently under investigation.

Cyclosporins↗
PubMed1989

Somatosensory-evoked potentials in lumbar nerve root decompression.

The adequacy of decompression of nerve roots is determined by direct visual observations and by correlation with roentgenograms of the pathological lesion. The usefulness of additional evidence of adequate neural decompression from intraoperative somatosensory-evoked potential (SEP) data was tested in 41 cases of a herniated intervertebral disc (27 patients) or spinal stenosis (14 patients). Postoperative observations at three weeks and three months were evaluated by intraoperative observation of decreased latency and/or increased amplitude of SEP recordings. In patients with unilateral or asymmetrical bilateral radiculopathy, the asymptomatic or less-affected leg acted as a control in the study. Successful function correlated significantly with intraoperative changes in latency toward normal in the more-affected leg, whether the lesion was herniated nucleus pulposus or spinal stenosis. Intraoperative physiological testing (SEP) is valuable for determining the adequacy of lumbar nerve root decompression and for the prediction of the successful relief of symptoms.

Evoked Potentials, Somatosensory↗
PubMed1988

Dexamethasone influences the lipid fluidity, lipid composition and glycosphingolipid glycosyltransferase activities of rat proximal-small-intestinal Golgi membranes.

Experiments were performed to examine the effects of subcutaneous administration of the synthetic glucocorticoid dexamethasone (100 micrograms/day per 100 g body wt.) on the lipid fluidity, lipid composition and glycosphingolipid glycosyltransferase activities of rat proximal-small-intestinal Golgi membranes. After 4 days of treatment, Golgi membranes and liposomes prepared from treated rats were found to possess a greater fluidity than their control (diluent or 0.9% NaCl) counterpart, as assessed by steady-state fluorescence-polarization techniques using three different fluorophores. Moreover, analysis of the effects of temperature on the anisotropy values of 1,6-diphenylhexa-1,3,5-triene, using Arrhenius plots, demonstrated that the mean break-point temperatures of treated preparations were 4-5 degrees C lower than those of control preparations. Changes in the fatty acyl saturation index and double-bond index of treated membranes, secondary to alterations in stearic acid, linoleic acid and arachidonic acid, at least in part, appeared to be responsible for the differences in fluidity noted between treated and control Golgi membranes. Concomitant with these fluidity and lipid-compositional alterations, treated membranes possessed higher specific activities of UDP-galactosyl-lactosylceramide galactosyltransferase and CMP-N-acetylneuraminic acid:lactosylceramide sialyltransferase than their control counterparts. Experiments utilizing benzyl alcohol, a known fluidizer, furthermore suggested that the fluidity alteration induced by dexamethasone may be responsible for the increased activity of the former, but not the latter, glycosphingolipid glycosyltransferase.

Animals↗
PubMed1988

S-adenosyl-L-methionine modulates Na+ + K+-ATPase activity in rat colonic basolateral membranes.

Rat colonic basolateral membranes were incubated with S-adenosyl-L-[methyl-3H]methionine (0.3 mM) at 37 degrees C for 2 h at pH 9.0. This resulted in an increase in the specific activity of Na+ + K+-ATPase by 60%. Kinetic parameter analysis revealed a 2-fold increase in the Vmax. of this enzymatic activity, whereas the Km for ATP was unchanged. The methylation inhibitor S-adenosyl-L-homocysteine (2 mM) significantly reduced these S-adenosyl-L-methionine-stimulated increases in specific activity and the Vmax. of Na+ + K+-ATPase. S-Adenosyl-L-methionine treatment of basolateral membranes was also found to significantly increase the fluidity of these preparations, as assessed by steady-state fluorescence polarization techniques using the fluorophore 1,6-diphenyl-1,3,5-hexatriene; S-adenosyl-L-homocysteine (2 mM) again markedly reduced this S-adenosyl-L-methionine-induced increase in fluidity. While transmethylation reactions involving phospholipids, non-polar lipids and proteins were all found to exist in rat colonic basolateral membranes, based on a number of observations, the results of the present studies suggest that transmethylation of membrane phospholipids, but not membrane non-polar lipids or proteins, influenced the fluidity of basolateral membranes which, in turn, modified Na+ + K+-ATPase activity in these membranes.

Animals↗
PubMed1988

Capillary density and fine structure in rabbit papillary muscles after a high dose of norepinephrine.

Two days after an iv infusion of norepinephrine (NE) (4 micrograms.kg-1.min-1 X 60 min) in rabbits, patchy myocardial damage in frozen cross sections of right and left papillary muscles was associated with loss of staining for alkaline phosphatase (ALP), an enzyme present in normal capillary endothelium, whereas a regular pattern of staining was observed in control normal muscles. Semithin cross sections of the same muscles after resin embedment gave comparable estimates of capillary density in control muscles and undamaged regions of norepinephrine-treated muscles. In damaged regions the complete absence of ALP staining corresponded with an apparent reduction in number, but not absence, of capillaries identifiable in semithin sections with light microscopy. Electron microscopy, however, revealed capillaries present in these regions in numbers similar to control undamaged tissue. Around 90% of these capillaries exhibited marked morphological abnormalities, with an 18% increase in endothelial cell volume density and a corresponding reduction in luminal volume density. These changes are similar to those reported after ischemia in cardiac and skeletal muscle. Myocardial damage induced by a high dose of NE is therefore associated 48 hr later with loss of ALP staining and endothelial cell disruption and edema, which may impair capillary perfusion and contribute to limited working cardiac performance observed previously.

Alkaline Phosphatase↗
PubMed1988

Genital tumors: their management by micrographic surgery.

Genital tumors represent a special group requiring effective and curative treatment while functional and cosmetic demands require tissue sparing techniques. For these reasons, micrographic surgery is indicated. Over the past 5 years we have treated 24 such patients utilizing standard techniques for micrographic surgery. The patient population included twenty male and four female patients with ages ranging from 27 to 80 years. Histologically confirmed diagnoses included squamous cell carcinoma, Bowen's disease, verrucous carcinoma, basal cell carcinoma, Paget's disease, and leiomyosarcoma. These were located on the penis, scrotum, perineum, and buttocks. Seven of these patients were considered to have recurrent tumors. Preexisting conditions existed in 6 patients, including balantis xerotica obliterans, trauma, decubitus ulcer, and hidradenitis suppurativa. All surgery was performed under local anesthesia in the cutaneous surgery unit. Average pretreatment tumor size was 2.0 X 1.9 cm. Average postoperative defect size was 4.5 X 3.7 cm. Tumors were excised with an average of three stages and 18 sections. Most defects (65%) were allowed to heal by secondary intention, five (21%) were closed primarily, and three were referred for closure. After surgery five patients developed metastases in their regional lymphatic system. No patients developed local recurrence. Micrographic surgery is a most useful treatment modality in patients with genital tumors for control of local disease. However, patients with squamous cell carcinoma should be considered for elective regional lymph node biopsy and/or dissection in conjunction with micrographically controlled excision of the primary tumor.

Adult↗
PubMed1988

Protective effects of long-term bradycardial pacing against catecholamine-induced myocardial damage in rabbit hearts.

A high intravenous dose of norepinephrine (4 micrograms/kg/min for 60 minutes) to New Zealand Red rabbits produced patchy subendocardial damage (estimated stereologically in frozen sections) of about 5% of the heart volume 2 days after application. The damaged areas showed loss of staining for alkaline phosphatase, an enzyme present in normal capillary endothelium. Heart performance (cardiac output index, cardiac work [i.e., cardiac output X mean blood pressure], and dP/dtmax) were significantly lower than in control hearts. Capillary density distribution estimated in nondamaged areas of the left ventricular free wall was inhomogeneous favoring subepicardial regions, while homogeneous transmural distribution was found in control hearts. Bradycardial pacing (reduction of heart rate to 50% of normal) performed for 3-4 weeks prior to norepinephrine administration showed a protective effect against catecholamine damage manifested in a smaller extent of necrosis, in the maintenance of homogeneous transmural capillary distribution in nondamaged areas, and, most importantly, in the maintenance of normal cardiac pump performance at rest and during maximal work in response to acutely administered norepinephrine.

Animals↗
PubMed1988

Epidural anesthesia for lumbar spine surgery.

A retrospective review of the hospital records of 80 patients undergoing elective lumbar spine surgery was performed, in order to determine the effect of anesthetic technique on various clinical parameters. Forty patients receiving epidural bupivacaine anesthesia were matched with 40 patients receiving general endotracheal anesthesia; these two groups were homogeneous based on age, sex, type of operative procedure, and number of spinal levels operated upon. Significant results included lower injectable narcotic requirements (p less than 0.001), lower incidence of postoperative urinary retention (p less than 0.01), and lower operative blood loss (p less than 0.1) for patients receiving epidural anesthesia. Epidural bupivacaine provided satisfactory anesthesia, and allowed intraoperative testing of lower extremity motor function. In a follow-up surgery, 38 of 40 patients who received epidural anesthesia were satisfied with the technique. For patients undergoing decompressive lumbar spine surgery, epidural bupivacaine anesthesia is an effective, well tolerated technique with several potential advantages, and an acceptable incidence of complications, as compared with general endotracheal anesthesia.

Anesthesia, Epidural↗
PubMed1988

Rapid occurrence of nodular cutaneous T-lymphocyte infiltrates with cyclosporine therapy.

Cyclosporine, a potent immunosuppressive agent, has been successfully used in the treatment of several dermatologic conditions including psoriasis. However, the drug does have an array of toxic side effects that need to be carefully considered when determining the risk-benefit ratio for the treatment of skin disease. We present another potential adverse effect of cyclosporine, namely, a benign lymphocytic infiltrate. This eruption developed in a patient with psoriasis after only ten days of cyclosporine therapy. The exact mechanism by which cyclosporine induced the lymphocytic infiltrate is unknown, but it is postulated that cyclosporine caused an imbalance of T-cell regulatory systems, thus resulting in an expanded T-cell subpopulation and the clinical manifestation of erythematous papules and nodules.

Biopsy↗