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Biomedical subjects

M Hales

Publications and source records attributed to M Hales.

15 recordsLinked to original sources

Epsilon-aminocaproic acid promotes the release of alpha2-antiplasmin during and after cardiopulmonary bypass.

This double-blind, randomized study compared the mechanisms by which low-dose aprotinin and epsilon-aminocaproic acid (EACA) inhibited fibrinolysis during cardiopulmonary bypass surgery. D-dimer levels during and after bypass were similar, indicating an equivalent inhibition of fibrinolysis. Effects on tissue plasminogen activator release were not associated with the inhibition of fibrinolysis by either drug. Treatment with EACA was associated with a substantial release of endogenous alpha2-antiplasmin, particularly 1 h after bypass. Compared with the aprotinin group, higher levels of the plasmin-alpha2-antiplasmin complex in the EACA group confirmed an increased inhibition of plasmin by alpha2-antiplasmin. In conclusion, it is hypothesized that EACA inhibited fibrinolysis by stimulating the release of the patients' own alpha2-antiplasmin.

Aminocaproic Acid↗

Endogenous circulating sympatholytic factor in orthostatic intolerance.

Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

Adrenergic alpha-1 Receptor Antagonists↗

Pulmonary vascular endothelial responses are differentially modulated after cardiopulmonary bypass.

The aim of this study was to characterize the mechanisms underlying pulmonary vascular dysfunction after cardiopulmonary bypass (CPB) by examining responses of isolated pulmonary arteries to selective endothelium-dependent and -independent activators in control and post-CPB dogs. Adult male mongrel dogs were placed on closed-chest, hypothermic CPB for 2.5 h, and then allowed to recover. Anatomically matched pulmonary arterial rings were isolated and suspended for isometric tension recording. Contractile responses to the alpha1-adrenergic agonist phenylephrine were similar in endothelium-containing arteries from control and CPB animals. Endothelium denudation increased contractions to phenylephrine to a similar extent in both groups. Endothelium-dependent relaxation to acetylcholine was decreased 4 days after CPB compared with controls. In contrast to acetylcholine, endothelium-dependent relaxation to bradykinin or to A23187 were not impaired 4 days after CPB. Inhibition of nitric oxide synthase (NOS) with L-NAME depressed the response to acetylcholine in control vessels, confirming that a component of the response to acetylcholine was nitric oxide (NO) dependent. At lower concentrations of acetylcholine, this component of the response was abolished after CPB. The residual relaxation evoked by acetylcholine in the presence of L-NAME also was impaired in CPB compared with control arteries. This suggests that the CPB-induced impairment of acetylcholine-evoked relaxation may not involve both an NO-mediated and an NO-independent component. L-NAME depressed the response to bradykinin to a similar degree in control and CPB arteries. Vascular smooth-muscle dilatation to the NO donor, SIN-1, or to the K+ATP-channel opener, cromakalim, were similar in endothelium-denuded arteries from CPB and control animals. These results suggest that CPB causes a selective impairment in endothelial dilator function without changing the vascular smooth-muscle response to vasodilator or vasoconstrictor stimuli.

Acetylcholine↗

The anemia of acute renal failure: association with oliguria and elevated blood urea.

Anemia is very frequent in patients with acute failure but the nature of the relationship between the two conditions has remained unclear. We studied all patients with well-documented acute renal failure seen in consultation by our nephrology division during 1991. Fifty-three of the 56 patients had at least mild anemia (hematocrit < 35%) at some point during their hospital stay. Forty-three of the patients had a hematocrit below 30% and 14 had a hematocrit below this level on admission. Twenty-four of the patients underwent major operations and all of these patients required blood transfusions. In this group there was a significant correlation between maximum serum urea and lowest hemoglobin (r = 0.4, p < .05) but no similar correlation between maximum creatinine and lowest hemoglobin. Oliguric patients had a mean lowest hemoglobin of 7.3 +/- 0.4 g/dL, which was significantly lower than the value for nonoliguric patients, 9.0 +/- 0.4 g/dL. This study confirms the presence of anemia in 91% of patients with acute renal failure and shows it to be related to rise in urea and presence of oliguria. Clearly, however, the anemia is multifactorial, since in one-quarter of the patients it precedes onset of renal failure.

Acute Kidney Injury↗

Fluconazole for oropharyngeal candidiasis in anti-HIV positive haemophiliacs.

Candidiasis of the oropharynx and oesophagus is one of the most common problems encountered in patients with HIV disease. Fluconazole is a bis-triazole antifungal agent with a long serum half-life. Sixteen anti-HIV positive patients (15 haemophiliacs and one blood transfusion recipient) with a clinical diagnosis of oropharyngeal candidiasis were treated with 50 mg fluconazole daily for 14-28 days and then either 150 mg fluconazole or placebo weekly for 6 months in a prophylactic phase. Clinical cure occurred in all patients, and mycological cure occurred in 13/16 (81%) patients. In the prophylactic phase, there were 2/5 (40%) relapses in the placebo arm compared with 1/8 (12.5%) in the fluconazole arm, but this was not statistically significant by Fisher's one-sided exact test (P = 0.31). It is concluded that fluconazole is an effective treatment of oropharyngeal candidiasis and has potential for prophylactic use.

Adolescent↗

A study of the effect of ethamsylate (Dicynene) on the bleeding time, von Willebrand factor level and fibrinolysis in patients with von Willebrand's disease.

Nine patients with clinically moderate or severe Type I von Willebrand's disease were treated for 2 weeks with ethamsylate (2 g/day in four equal doses) and with a matched placebo in a randomised double-blind trial. Template bleeding time, von Willebrand factor activity (ristocetin co-factor) and antigen, euglobulin lysis time and type I tissue plasminogen activator inhibitor were determined before and at the end of each treatment period. None of these parameters showed any significant change attributable to ethamsylate. Thus, despite the fact that five patients thought subjectively that their bleeding symptoms improved during ethamsylate treatment compared to only one while on placebo, we obtained no evidence that the drug was of benefit to patients with von Willebrand's disease.

Adolescent↗

Diagnosis of Kaposi's sarcoma by fine-needle aspiration biopsy.

Fifteen cases of Kaposi's sarcoma diagnosed by fine-needle aspiration biopsy were reviewed. The diagnosis was confirmed by tissue biopsy in eight of the cases. All of the patients were homosexual males, and 13 had a previous diagnosis of AIDS. The aspirates were obtained from enlarged lymph nodes (five cases), soft-tissue masses (two cases), oral cavity lesions (seven cases), and an abdominal mass. The most characteristic cytologic features were intact tissue fragments composed of overlapping spindle cells with nuclear distortion and ill-defined cytoplasmic borders. Smaller groups of loosely cohesive spindle-shaped cells and individual spindle cells with cytoplasm were also helpful features. In the appropriate clinical setting, these cytologic features on FNAB are felt to be diagnostic of Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Aspiration cytology characterization of inflammatory masses.

Fine-needle aspiration biopsy smears are useful in the workup of patients with abscesses and inflammatory masses. We report 37 cases classified into three groups: group I, in which a causative organism was seen on the smear; group II, in which a causative organism was cultured from a smear where organisms were not seen microscopically, and group III, in which the organism was not seen or cultured, but the smear findings were useful in determining further workup.

Abscess↗

Carcinoma of the thyroid with a mixed medullary and follicular pattern: morphologic, immunohistochemical, and clinical laboratory studies.

We recently encountered an unusual carcinoma of the thyroid gland with a predominantly medullary pattern admixed with areas of follicular differentiation. Both patterns prevailed at the primary site and in bilateral cervical lymph node metastases. The tumor cells were stained for calcitonin by indirect immunofluorescence technique and were found to contain dense-core granules by electron microscopy. Calcitonin was demonstrated in tumor homogenates by radioimmunoassay and was elevated in the serum. Immunofluorescence staining also revealed thyroglobulin in the neoplastic cells. Moreover, following total thyroidectomy, the cervical node metastases concentrated radioactive iodine (131I), and serum thyroglobulin was increased at one stage of the disease when measured by radioimmunoassay. These findings are discussed in the light of the dual embryonic derivation of the thyroid gland.

Adult↗