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Biomedical subjects

N M Flynn

Publications and source records attributed to N M Flynn.

At least 19 recordsLinked to original sources

Megestrol acetate in patients with AIDS and cachexia.

OBJECTIVE: To study the effects of a megestrol acetate liquid formulation (800 mg/d) on body weight, body composition, caloric intake, and mental outlook in patients with the acquired immunodeficiency syndrome (AIDS) who had cachexia. DESIGN: Twelve-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Multiple clinical centers. PATIENTS: 100 patients with AIDS who had weight loss of 10% or more of ideal body weight were randomly assigned to placebo (n = 48) or megestrol acetate (n = 52). MEASUREMENTS: Caloric intake, body weight, body composition, and sense of well-being. RESULTS: Most patients receiving megestrol acetate had increased caloric intake resulting in body weight gain (mainly fat mass). From baseline to week 8, the megestrol acetate group increased their daily caloric intake by 608 calories, whereas the placebo group increased intake by 134 calories (difference, 474 calories; 95% CI, -68 to 880 calories). Body weight in the megestrol acetate group increased by 3.86 kg from baseline to week 8, although it decreased by 0.46 kg in the placebo group (difference, 4.32 kg; CI, 2.42 to 6.22 kg). At week 8 in the megestrol acetate group, patients gained 3.68 kg in fat mass and those in the placebo group lost 0.28 kg (difference, 3.96 kg; CI, 2.49 to 5.43 kg). Body water, lean mass, and patient survival were not statistically different between treatment groups. Patients treated with megestrol acetate had an increased sense of well-being when compared with patients who received placebo. CONCLUSIONS: This megestrol acetate liquid formulation is well tolerated, increases food intake, results in body weight gain, and improves the sense of well-being in cachectic patients with AIDS.

Acquired Immunodeficiency Syndrome

Decompression sickness in Ireland--a review.

In the last decade there has been an increase in the incidence of decompression sickness in Ireland. The modern diver, equipped with specially developed diving equipment, is exposed to abnormal physiological conditions. This has resulted in a spectrum of medical conditions, which need to be recognised, diagnosed and treated. The department of Underwater Medicine at University College Hospital, Galway, is the only referral centre in the Republic of Ireland for patients suffering from decompression sickness. Early recognition and referral for treatment dramatically improves patient outcome. A one year's review of patients referred for treatment is presented.

Adult

Tuberculous spondylitis as a complication of intravesical bacillus Calmette-Guerin therapy.

We report a case of tuberculous spondylitis following intravesical bacillus Calmette-Guerin (BCG) instillation. A 90-year-old male physician living in South Africa received an uncomplicated 6-week course of intravesical BCG (Japanese 172 strain) for high grade superficial bladder carcinoma. He experienced a sudden onset of debilitating lower back pain 16 months following this treatment. A lytic lesion involving the anterior T11 and T12 vertebral bodies was diagnosed and subsequently biopsied. An acid-fast organism was isolated after 3 weeks of incubation and was confirmed through deoxyribonucleic acid probe hybridization as a mycobacterium. High performance liquid chromatography analysis speciated the organism as Mycobacterium bovis BCG, proving that it was acquired through the intravesical therapy.

Aged

Enflurane, halothane, and isoflurane attenuate contractile responses to exogenous and endogenous norepinephrine in isolated small mesenteric veins of the rabbit.

BACKGROUND: Volatile anesthetics exert both direct and indirect (neurally mediated) effects to produce splanchnic venodilation. These effects may result in clinically relevant hemodynamic changes. The present study examined the direct effects of isoflurane, halothane, and enflurane on rabbit mesenteric venous smooth muscle. METHODS: Changes in isometric tension, in response to exogenous and endogenous norepinephrine, were measured in isolated mesenteric vein rings before and during the administration of volatile anesthetics. RESULTS: Exogenous and electrically evoked endogenous norepinephrine produced an increase in tension with super-imposed rhythmic oscillations in tension. The exogenous norepinephrine-induced increase in tension was augmented in the presence of NG-nitro-L-arginine methyl ester (L-NAME, 5 x 10(-5) M). The oscillatory activity was not altered by L-NAME. The increase in isometric tension in response to electrical stimulation was inhibited by phentolamine (5 x 10(-6) M) and tetrodotoxin (3 x 10(-6) M). Equianesthetic (1 MAC) concentrations of isoflurane, halothane, and enflurane significantly attenuated contractile responses to exogenous and endogenous norepinephrine, with isoflurane demonstrating a more depressant effect than halothane or enflurane. Volatile anesthetics also suppressed the amplitude and frequency of oscillations in the control as well as L-NAME-treated veins. The inhibitory effects of volatile anesthetics on the oscillations were comparable to the effects of ryanodine, a specific blocker of calcium channels in sarcoplasmic reticulum. CONCLUSIONS: These results suggest that: 1) vascular endothelium, via endothelium-derived relaxing factor, modulates exogenous norepinephrine responses of the venous smooth muscle; 2) the oscillatory behavior of mesenteric veins may be attributed to calcium fluxes in the venous smooth muscle cells; and 3) the norepinephrine-dependent increases in contractile and oscillatory activity are attenuated more by isoflurane than halothane or enflurane. This indicates that volatile anesthetic-mediated splanchnic venodilation is, at least in part, due to a direct action on vascular smooth muscle as well as withdrawal of sympathetic tone.

Animals

Inhibition of neutral endopeptidase augments anaphylactic constriction of guinea pig tracheal smooth muscle.

To determine whether tachykinins participate in antigen-induced constriction of tracheal smooth muscle, we examined the effects of a neutral endopeptidase inhibitor, phosphoramidon, the tachykinin antagonist (D-Pro4, D-Trp7,9,10)-substance P(4-11), and capsaicin-induced tachykinin depletion on the responses to antigen in tracheal rings from ovalbumin-sensitized guinea pigs. In these preparations, the antigen (ovalbumin, 0.1 microgram/ml) produced reproducible and durable constriction of tracheal smooth muscle. Incubation with phosphoramidon (10 min, 10 microM) prior to antigen challenge significantly augmented the magnitude of ovalbumin-induced constriction by 22% after 30 min and by 31% after 45 min. The addition of phosphoramidon at the plateau level of antigen-induced constriction produced a similar, significant increase in the magnitude of the constriction. Following incubation with tachykinin antagonist (D-Pro4,D-Trp7,9,10)-substance P(4-11) (5 microM), the contractile response of the tracheal rings to the antigen was not altered. Furthermore, the addition of phosphoramidon (10 microM) did not significantly affect this contraction. Similarly, neither tachykinin antagonist nor phosphoramidon altered the ovalbumin-induced constriction of the tracheal rings from capsaicin-treated guinea pigs. Based on these findings, we hypothesize that tachykinins or similar broncho-constricting neutral endopeptidase substrates were released from tachykinin-containing nerve endings during immediate hypersensitivity reaction in airways, manifesting a modest and delayed constrictive effect. Following alteration of endopeptidase activity, these substances could modulate the anaphylactic constriction of the airway smooth muscle.

Anaphylaxis

Isoflurane produces endothelium-independent relaxation in canine middle cerebral arteries.

Although it is generally accepted that isoflurane can cause cerebral vasodilation, the sensitivity of the cerebral vessels to this anesthetic agent remains controversial. Furthermore, the mechanism by which isoflurane produces its direct effects on the cerebral vasculature remains unknown. The purpose of this study was to determine if isoflurane-induced relaxation of canine middle cerebral arteries is dose-dependent and/or endothelium-dependent. In an additional series of experiments, isoflurane-induced relaxation was studied in the presence of indomethacin to inhibit prostacyclin release, and endothelium-independent relaxation was examined with sodium nitroprusside. The response to isoflurane was examined in middle cerebral arteries prior to and following pretreatment with 300 microM NG-monomethyl-L-arginine (LnMMA), an inhibitor of endothelium-dependent vasodilation. Vascular rings (2.5 mm in length and 600-800 microns in diameter) were suspended in tissue baths and isometric tension recorded. The rings were constricted with either 0.2 microM 5-hydroxytryptamine or 5 microM prostaglandin F2 alpha and subsequently exposed to increasing concentrations of isoflurane (0.65-4.9%). In separate experiments the procedure was repeated in vessels with and without endothelium. Isoflurane produced a dose-dependent relaxation in all vessels. This relaxation was not inhibited by LnMMA and was unaffected by the absence of endothelium. The isoflurane response was independent of cyclooxygenase inhibition. These results demonstrate that isoflurane-induced relaxation of canine middle cerebral arteries: 1) is dose-dependent; 2) is not mediated by modulation of endothelium-derived relaxing factor or a release of prostacyclin; and 3) is endothelium-independent.

Animals

Differential relaxant effect of high concentrations of intravenous anesthetics on endothelin-constricted proximal and distal canine coronary arteries.

This study determined the direct effect of three intravenous anesthetics on isolated canine coronary arteries constricted with the potent endogenous vasoconstrictor endothelin. Arteries were divided into groups of large (1.3-2.5 mm) and small (250-500 microns) vessels, and arterial rings were suspended in tissue baths. The rings were stretched to an optimal resting tension and then preconstricted with an EC50 concentration of endothelin that was equivalent for both groups. Incremental concentrations (5 x 10(-6) M to 1.6 x 10(-2) M) of thiopental, ketamine, and propofol were added to the baths, and the relaxant responses were recorded. Small arteries demonstrated greater vasodilation at equivalent drug concentrations than did large arteries. These results demonstrate antagonism of the vasoconstrictor endothelin by intravenous anesthetics. Distal vessels are more sensitive than proximal vessels to the relaxant effects of the intravenous anesthetics studied. Direct effects on coronary vascular tone, however, are only apparent at concentrations above those seen clinically. Despite the potential for a differential effect on proximal and distal coronary arteries, we conclude that thiopental, ketamine, and propofol do not possess a direct effect on the tone of large or small canine coronary arteries at concentrations seen in routine clinical practice.

Anesthetics

Effects of isoflurane on K+ and Ca2+ conductance in isolated smooth muscle cells of canine cerebral arteries.

Although isoflurane is a known cerebral vasodilator, the mechanism of isoflurane-induced vasodilation is not clear. The purpose of this study was to investigate the effects of 2.6% isoflurane (1.2 mM) on macroscopic calcium and potassium channel currents in voltage-clamped canine middle cerebral artery cells. Cells were dialyzed with K(+)-glutamate solution and superfused with Tyrode's solution for measurement of potassium current (n = 20). Stepwise depolarization from a holding potential of -60 mV to beyond -30 mV elicited an outward, slowly inactivating potassium current that was reduced 50% +/- 2% and 81% +/- 3% (mean +/- SEM) in the presence of 1 mM 4-aminopyridine and 30 mM tetraethylammonium, respectively. Calcium ionophore (A23187, 10 microM) increased the potassium current by 76% +/- 3%, suggesting calcium dependency. Isoflurane reduced the amplitude of the potassium current by 35% +/- 4%. Calcium current was measured in cells dialyzed with solution containing 130 mM Cs(+)-glutamate and superfused with solution containing 10 mM BaCl2 and 135 mM tetraethylammonium to pharmacologically isolate the calcium current (n = 13). Under these conditions, progressive depolarizing steps from -60 mV elicited an inward current that was maximally activated at +20 mV and essentially eliminated by 1 microM nifedipine. This current, resembling a long-lasting (L-type) Ca2+ channel current, was reduced 40% +/- 4% by isoflurane. The results of this study suggest that isoflurane acts directly at the vascular muscle membrane to suppress transmembrane calcium and potassium currents. The decrease in calcium current would cause vasodilation; however, the concomitant decrease in potassium current may partially antagonize the depressant effect of isoflurane mediated through calcium current reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Endothelium-dependent vasodilation of canine coronary collateral vessels.

The objective of this study was to determine whether endothelium-mediated relaxation occurs in canine coronary collateral vessels. Responses to endothelium-dependent vasodilators in coronary collateral vessels (250-350 microns) were compared with those obtained in normal native coronary arteries of similar size. Rings of small arteries and collateral vessels were suspended in baths, and tension was recorded. All rings were constricted with prostaglandin F2 alpha (3 microM) and subsequently exposed to cumulative concentrations of acetylcholine or bradykinin. In separate experiments, the procedure was repeated in the presence of 300 microM NG-monomethyl-L-arginine (L-NMMA) to inhibit endothelium-mediated vasodilation. Endothelium-dependent relaxation was further studied in the presence of indomethacin, and endothelium-independent relaxation was examined with sodium nitroprusside. Acetylcholine and bradykinin relaxed both normal native and collateral rings. In preconstricted small arteries and collateral vessels the concentration at 50% of maximal response of acetylcholine was 85.5 +/- 19.5 and 61.0 +/- 14.0 microns, and bradykinin was 11.9 +/- 7.4 and 10.7 +/- 2.1 microns, respectively. L-NMMA attenuated the response to acetylcholine and bradykinin in both groups. The results indicate that endothelium is present and functional in canine coronary collateral vessels. Both small coronary arteries and collateral vessels are equally responsive to endothelium-dependent vasodilators and inhibition of endothelium-dependent relaxing factor.

Acetylcholine

Intradermal inoculation with Heptavax-B. Immune response and histologic evaluation of injection sites.

The high cost of hepatitis B vaccine has limited its widespread use. Low-dose, intradermal injections of vaccine represent one option for reducing the cost. In this study, 92 nonimmune medical students were given three 0.1-mL intradermal injections of Heptavax-B containing 2 micrograms of hepatitis B surface antigen (HBsAg) at 0, 1, and 6 months. By 6 months, 90% of the subjects had developed protective levels of antibody to HBsAg (greater than or equal to 10 mIU/mL). Follow-up at 1 year showed a geometric mean concentration of antibodies to HBsAg of 396 mIU/mL for the group, and 95% had levels of antibody to HBsAg greater than or equal to 10 mIU/mL. A level of antibody to HBsAg of greater than 100 mIU/mL also was observed in more than 75% of subjects. Side effects included induration of the inoculation site in 18% at 6 months, which disappeared by 12 months, and macules that persisted at 1 year in 63%. The administration of hepatitis B vaccine intradermally is an attractive, low-cost alternative in the United States, where universal vaccination of preschool children or adolescents is being contemplated, and where booster doses are being considered.

Adult

Multilumen catheter sepsis and an educational program to combat it.

Catheter-related sepsis is a problem with many variables. A process of elimination may eventually identify the actual cause(s) of this phenomenon. We began our problem-solving approach by observing personnel inserting and caring for central lines, which showed a lack of compliance with existing protocols. A program was designed to provide the correct procedural activities. This study plans to test whether ongoing educational programs and an infection control department that maintains a high degree of visibility are effective in reducing nosocomial line-related infections.

Catheterization, Central Venous

Treatment of fungal infections with semisynthetic derivatives of amphotericin B alpha.

AME appeared to be as effective as AmB in the treatment of mycoses in humans. AME was much less nephrotoxic than AmB, and was better tolerated in terms of rapid onset and reversible adverse reactions. AME may be more ototoxic than AmB. AME, even as AmB and OAME, may cause neurotoxicity and leukoencephalopathy, particularly when high doses are given for long periods.

Adult

Absence of HIV antibody among dental professionals exposed to infected patients.

Dental professionals have relatively frequent skin contact with saliva and small amounts of blood of patients infected with the human immunodeficiency virus (HIV). Despite this exposure, none of 255 dentists, hygienists and chairside assistants had the antibody to HIV following an estimated 189 or more exposures. These data provide further evidence that casual contact with the saliva of HIV-infected persons, such as may occur in households, the workplace or in public places, is unlikely to result in transmission of HIV to uninfected persons. Because of the small sample size in this study, however, and the relatively high frequency of exposure of HIV-infected patients that we found, we recommend that dental care professionals increase their use of disposable gloves and adhere to the Centers for Disease Control's guidelines for infection control practices for dentistry until more is known about the transmission of this virus.

Acquired Immunodeficiency Syndrome

Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis.

Five patients with laboratory evidence of latent or neurosyphilis were treated orally with doxycycline (200 mg) twice a day for 21 days. After the seventh dose, the mean level of doxycycline in serum was 5.8 micrograms/ml, with a mean drug level in cerebrospinal fluid of 1.3 micrograms/ml. The mean penetration into cerebrospinal fluid was 26%. These preliminary findings suggest that doxycycline, administered orally at a dose of 200 mg twice a day, reaches a sufficient concentration in cerebrospinal fluid to be worthy of further evaluation as an alternative regimen to penicillin therapy for latent or neurosyphilis.

Administration, Oral