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Biomedical subjects

A J Hamilton

Publications and source records attributed to A J Hamilton.

At least 91 records · Page 5Linked to original sources
PubMed1988

Oxygen transport to exercising leg in chronic hypoxia.

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.

Acclimatization↗
PubMed1988

The fate of the circumsporozoite antigens during the exoerythrocytic stage of Plasmodium berghei.

There has been considerable interest in the circumsporozoite proteins due to their potential use in anti-malarial vaccines. Previous authors have shown that these proteins persist from the invading sporozoite throughout the growing exoerythrocytic or liver stage. We show that the different distributions of these proteins seen during the development of the exoerythrocytic parasite of Plasmodium berghei closely follow morphological changes, which can be recognized under the light microscope. At the end of the exoerythrocytic cycle, the majority of the remaining circumsporozoite proteins were associated with the spongy stroma in which the emerging exoerythrocytic merozoites lay. Cell-mediated immunity originally directed against sporozoites might recognize the stroma as a second target resulting in the indirect destruction of the exoerythrocytic merozoites.

Animals↗
PubMed1986

Neuropeptide investigations with an ovine surgical model.

An ovine surgical model for peptide investigations is presented. Techniques for exteriorization of the carotid artery, catheterization of the sagittal sinus, hypophysectomy via a transnasopharyngeal approach, and ventricular and cisternal cannulation in the sheep are employed within the model. Several experimental applications in neurosurgical research are presented.

Anesthesia↗
PubMed1986

High altitude cerebral edema.

Acute mountain sickness (AMS) is usually a benign and self-limited illness that befalls previously healthy individuals who ascend rapidly to high altitude without sufficient acclimatization. In its more severe forms, AMS can progress to a life-threatening condition in which pulmonary or cerebral edema can occur singly or in concert. High altitude cerebral edema (HACE) is a little-known clinical entity that manifests itself by a perplexing array of both generalized and localized neurological symptoms and signs. Furthermore, the development of HACE in climbers offers a unique experimental situation in which to examine the effects of hypoxia on the central nervous system. The epidemiology and clinical picture of HACE are reviewed. In addition, the pathology and predominant pathophysiological mechanisms postulated to explain HACE are examined, and the present recommendations for the prevention and treatment of this dangerous and unusual form of brain swelling are discussed.

Acclimatization↗
PubMed1986

Endotoxic shock elicits greater endorphin secretion than hemorrhage.

Opiopeptides may contribute to the pathophysiology of both endotoxic and hemorrhagic shock. To determine if endorphin secretion is similar in both types of shock, we divided 25 sheep into three groups: a saline control group (n = 10), an endotoxin-treated group (n = 9), and a hemorrhage group (n = 6). Each sheep had baseline determinations of mean arterial pressure (MAP) and plasma levels of beta-endorphin-like immunoreactivity (iB-EP). Experimental animals either received endotoxin (450 ng/kg intravenous) or underwent withdrawal of blood volume sufficient to diminish MAP by approximately one-third of baseline values. MAP and iB-EP levels were determined every 15 minutes thereafter for 5 hours. Individual data were averaged within each group and then compared between groups using analysis of variance. Both the endotoxin- and hemorrhage-treated groups showed a significant fall in MAP, which was significantly lower in the hemorrhage group than the endotoxin group. Endotoxin-treated animals displayed a mean peak iB-EP level 1,550% above baseline as compared to a mean peak iB-EP level of only 201% above baseline in the hemorrhage-treated group, despite a significantly greater degree of hypotension in the latter group; this difference in peak iB-EP response was significant. Mean peak iB-EP levels coincided with mean trough MAP values in the endotoxin-treated group while the mean peak iB-EP lagged the onset of mean trough MAP in the hemorrhage group. These results demonstrate that iB-EP secretory patterns differ in endotoxic versus hemorrhagic shock and suggest that distinct mechanisms of opiopeptide secretion accompany the two shock states.

Animals↗
PubMed1985

Contrasting actions of naloxone in experimental spinal cord trauma and cerebral ischemia: a review.

Endorphins have been implicated in the pathophysiology of both spinal cord injury and cerebral ischemia. This review examines the nature of the experimental evidence to support this hypothesis. Present studies suggest that naloxone administration improves neurological function and outcome in the setting of the spinal cord trauma by centrally inhibiting an opiate receptor-mediated diminution of spinal cord flow. In the setting of spinal shock, naloxone administration is associated with improvement in vital sign and cardiovascular parameters as measured by mean arterial pressure, cardiac output, body temperature, and ventilation. Experiments using a variety of animal stroke models similarly support the notion that naloxone improves neurological function in the setting of cerebral ischemia by a stereospecific opiate receptor-mediated effect, but this improvement does not seem to be accompanied by augmentation of blood flow to affected areas of the brain or by any improvement in vital signs or cardiovascular parameters as seen in spinal cord trauma. A variety of mechanisms are discussed to explain these observations. The therapeutic implications of administering opiate agonists and antagonists in the setting of neurological deficits are outlined for the neurosurgeon.

Animals↗
PubMed1983

Polytetrafluoroethylene grafts in the peripheral venous circulation of rabbits.

We demonstrated by venography that the patency of 3 mm PTFE grafts in the jugular veins of rabbits could be maintained by pretreating the animals with either an anticoagulant (warfarin sodium) or an antiplatelet agent (aspirin, dipyridamole, or both). Examination of the lining of the grafts up to 4 months after grafting by scanning electron microscopy or light microscopy showed that endothelial cells extended across the anastomosis for a short distance and that a neointima lined the remainder of the graft. This lining could hypertrophy to the point of almost occluding the graft unless the drugs were continued.

Animals↗
PubMed1980

Effects of current flow on pacemaker activity of the isolated kitten sinoatrial node.

The dynamic behavior of the cardiac pacemaker in response to single or to periodically repeated perturbations was studied using kitten sinoatrial (SA) nodal strips mounted in a sucrose gap. Sustained stepwise applications of current across the gap produce lasting variations in pacemaker cycle length that depend on current magnitude and polarity, but not on the phase of the pacemaker period at the time of the input. Brief current pulses, whether hyperpolarizing or depolarizing, may abbreviate or prolong the immediately affected cycle depending on their timing. These changes result in phase shifts of the subsequent discharges, but they do not alter the pacemaker period permanently. The phasic effects of brief current pulses can be described by a phase response curve (PRC), which is a plot of the phase shift as a function of the position of the stimulus in the pacemaker cycle. PRCs were constructed for inputs of different polarity and several strengths and durations. The behavior of the sinus nodal pacemaker when interacting with period perturbing inputs, such as vagal stimulation or electrotonic depolarization, can be predicted on the basis of the phase response curve.

Action Potentials↗
PubMed1980

Desensitization of the cholinergic receptor at the sinoatrial cell of the kitten.

The hyperpolarizing effects of long periods of vagal stimulation were studied in kitten sinoatrial node-vagus nerve preparations. Verapamil (2.2 x 10(-6) M) was used to arrest spontaneous pacemaker activity, thus permitting uninterrupted observation of the time course of cholinergically mediated hyperpolarizations. With progressively longer vagal trains the hyperpolarization was not maintained but decreased, rapidly at first, and then more gradually despite continuous vagal stimulation. Similar decay of the cholinergic effect was also observed during continuous iontophoretic application of acetylcholine (ACh) or carbamylcholine (CCh). The results show that, for the most part, the decay of the hyperpolarizing response cannot be due to "fatigue" of nerve terminals, to a gradual reduction in the driving force for K+, or to hydrolysis of ACh by cholinesterase. These experiments demonstrate the development of desensitization of the cholinergic receptor at the sinoatrial cell membrane. The data fit the "cyclic reaction" model proposed by Katz and Thelsleff (J. Physiol. London 138:63-80, 1957) for the neuromuscular junction.

Acetylcholine↗
PubMedDate not supplied

Preparation of murine monoclonal antibodies against the yeast phase of the dimorphic fungus Sporothrix schenckii.

Three murine monoclonal antibodies (Mabs) were raised against a cytoplasmic antigen of the yeast phase of the pathogenic fungus Sporothrix schenckii using a modification of standard hybridoma technology incorporating the immunosuppressive drug cyclophosphamide. When tested for species-specificity within the pathogenic dimorphic fungi one of these Mabs (S5) showed little cross-reactivity by enzyme-linked immunosorbent assay and Western blot, though there was some recognition of Paracoccidioides brasiliensis antigen. This Mab recognized a 70-75 kDa molecule on reduced Western blots of S. schenckii antigen. The other two Mabs (S12 and S15) showed cross-reactivity with all dimorphic fungal antigens tested, though they appeared to recognize a molecule of similar molecular weight. This is the first report of any attempt to raise species-specific Mabs against this important causative agent of dermatological disease.

Animals↗
PubMedDate not supplied

Preparation of monoclonal antibodies that differentiate between Histoplasma capsulatum variant capsulatum and H. capsulatum variant duboisii.

The immunosuppressive drug cyclophosphamide was used to facilitate the production of monoclonal antibodies (Mabs) which differentiated between the yeast phase of the two variants of the dimorphic fungus Histoplasma capsulatum by both enzyme-linked immunosorbent assay and Western blot. Two Mabs are described, identifying epitopes on a 70-75 kDa molecule, which are specific to H. capsulatum var. capsulatum and which do not identify epitopes of H. capsulatum var. duboisii. These Mabs have potential use in the epidemiology and serodiagnosis of histoplasmosis in areas where both classical and African forms of the disease occur.

Animals↗
PubMedDate not supplied

Murine monoclonal antibodies recognizing a non-capsular antigen that distinguishes between Cryptococcus neoformans var. neoformans and C. neoformans var. gattii.

A panel of 4 monoclonal antibodies (mabs) of the IgG1 subclass have been made against a cytoplasmic antigen of Cryptococcus neoformans. Mab 4E2 recognized isolates of C. neoformans var. gatti by enzyme-linked immunosorbent assay (ELISA), whilst the other antibodies did not recognize these antigens. By Western blot 4E2 recognized determinants at 110-125, 65-70, 45-50 and 36-38 kDa. Mabs 9E6, 7C7 and 5D9 recognized bands at 36-38 and approximately 30 kDa. All 4 mabs (4E2, 9E6, 7C7 and 5D9) recognized both non-encapsulated and encapsulated isolates of C. neoformans var. neoformans by ELISA, and in addition showed reactivity to only the cytoplasm and cell membrane of yeasts by immunofluorescence. Mab 7C7 recognized antigens of the closely related fungus Trichosporon beigelii by ELISA but did not recognize any other fungal antigens. The other 3 mabs showed no recognition of T. beigelii or any other fungal pathogens tested.

Animals↗
PubMedDate not supplied

Isolation and partial characterization of a Paracoccidioides brasiliensis 58 kDa extracellular glycoprotein which is recognized by human immune sera.

A novel 58 kDa antigenic determinant of the fungus Paracoccidioides brasiliensis was identified by enzyme-linked immunosorbent assay using a panel of species-specific murine monoclonal antibodies (MAbs). Western immunoblot analysis, deglycosylation studies and isoelectric focusing indicated that this 58 kDa antigen is a glycoprotein, with a pI of approximately 5.2. The molecule was purified from P. brasiliensis culture filtrate and yeast cytoplasmic antigens by membrane ultrafiltration, liquid isoelectric focusing and gel filtration; N-terminal amino acid sequence data revealed no substantial homology with known proteins. The presence of the antigen in the cytoplasm of both yeast and mycelial forms of the fungus was demonstrated when these MAbs were used as markers in immunofluorescence, immunoperoxidase and immunoalkaline phosphatase techniques to label P. brasiliensis in cryostat sections. These MAbs also recognized the cytoplasm of P. brasiliensis yeast forms in paraffin-embedded pathological specimens from human cases. A preparation of the 58 kDa component from yeast cytoplasmic antigen was reacted by Western immunoblotting with 26 different serum samples from paracoccidioidomycosis patients, and 81% of them recognized it.

Adult↗
PubMedDate not supplied

Exposure to Cryptococcus neoformans var. gattii--a seroepidemiological study.

An enzyme-linked immunosorbent assay was developed to study prevalence of immunoglobulin G (IgG) antibody to non-capsular Cryptococcus neoformans var. gattii antigen in a population of healthy Papua New Guinea (PNG) controls and patients. Patients with acute C. neoformans var. gattii meningitis had elevated levels of IgG which declined significantly following treatment (P = 0.034). Levels in the sera of convalescent patients were significantly higher than those in PNG controls (P < 0.001), which in turn were significantly higher than in a UK control group (P < 0.001). Clear differences were observed amongst the PNG controls. Adults had significantly higher levels than children (P = 0.002) and men had significantly higher levels than women (P = 0.047). No difference was observed between levels in patient-related and unrelated controls. IgG responses in PNG controls mirror the prevalence of disease in this population. It is postulated that exposure to C. neoformans var. gattii is less common in children and women due to some as yet unidentified behavioural difference and that exposure occurs away from the home environment.

Adolescent↗
PubMedDate not supplied

Comparison of high-dose epinephrine versus standard-dose epinephrine in adult cardiac arrest in the prehospital setting.

OBJECTIVE: To compare the efficacy of high-dose epinephrine (HDE) with standard-dose epinephrine (SDE) in the management of cardiac arrest in adults in the prehospital setting. HYPOTHESIS: The use of HDE will improve the outcome of adult patients in cardiac arrest. METHODS: In a general population of 700,000 persons, in a mixed geographical area of 2,200 square miles, a 12-month retrospective study of SDE and a 12-month prospective trial of HDE were conducted involving adult patients in cardiac arrest in the prehospital setting. Treatment was provided by paramedic-level clinicians. In the control group, patients were treated according to existing American Heart Association cardiac resuscitation guidelines using SDE (defined as 1.0 mg boluses to a maximum dose of 4 mg). In the test group, the same guidelines were revised to use HDE (defined as a rapid sequence of 5, 10, and 15 mg boluses to a total dose of 30 mg). RESULTS: The control group included 594 patients; the test group consisted of 580 patients. The overall survival rate to hospital admission in the control group was 14.5% (84 patients) and in the test group 15.3% (89 patients). The survival rate to hospital discharge in the control group was 4.9% (29 patients) versus 4.8% (28 patients) in the test group. For patients whose initial rhythms were ventricular fibrillation, survival to admission in the control group was 20.4% (39 patients) versus 24.4% (43 patients) in the test group. Survival to discharge for patients with ventricular fibrillation in the control group was 8.9% (17 patients) versus 10.8% (19 patients) in the test group. CONCLUSION: There was no statistically significant difference in overall rate of survival to hospital admission or discharge between patients treated with SDE and those treated with HDE, regardless of the initial rhythm.

Adult↗
PubMedDate not supplied

Partial purification and characterization of a 235,000M(r) extracellular proteinase from Trichophyton rubrum.

An extracellular proteinase has been partially purified from culture filtrates of Trichophyton rubrum by ultrafiltration, isoelectric focusing and gel filtration chromatography. The enzyme has a non-reduced molecular weight of 235,000 by substrate SDS-PAGE. It has a pH optimum of 8.5 using azocasein and azoalbumin as substrates and a pI of 3.6-3.8. The metalloproteinase inhibitors EDTA and 1,10-phenanthroline, together with the chymotrypsin inhibitor chymostatin, strongly inhibited its activity. The serine proteinase inhibitors phenylmethanesulphonyl fluoride and diisopropylfluorophosphate showed weak inhibitory activity. The proteinase exhibited broad substrate activity against azocoll, azoalbumin, azocasein, laminin and fibronectin. It exhibited weak activity against elastin and keratin. Observations on the occurrence of this proteinase together with previously described lower molecular weight proteinases suggests that the former is the first to appear in minimal medium cultures. Freeze/thaw cycling of the partially purified 235,000 M(r) proteinase was found to generate low molecular weight proteinases, particularly at 53,000, 27,000 and 25,000 M(r), indicating that the latter may originate from the larger molecule.

Culture Media↗