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Biomedical subjects

C M Dixon

Publications and source records attributed to C M Dixon.

At least 37 records · Page 2Linked to original sources
PubMed1992

Inhaled platelet-activating factor causes pulmonary neutrophil sequestration in normal humans.

Inhaled platelet-activating factor (PAF) causes bronchoconstriction and transient peripheral neutropenia in humans. We studied eight normal subjects to investigate whether inhaled PAF caused pulmonary neutrophil sequestration. All subjects received autologous 99mTc-red cells as a blood pool marker, seven received 111In-neutrophils, and one received 111In-platelets. Six subjects inhaled 48 micrograms of PAF. There was immediate pulmonary sequestration of 111In-neutrophils, maximal (218% baseline) at 6 min (p less than 0.001), returning to normal by 3 h. There was no change in circulating platelet count or pulmonary 111In-platelet transit. Methacholine inhalation caused equivalent bronchoconstriction to PAF, but it had no effect on neutrophil count or pulmonary 111In-neutrophil activity. We have demonstrated pulmonary neutrophil, but not platelet, sequestration after PAF. This supports a role for PAF as an inflammatory mediator in humans. This may be a useful model for exploring pulmonary neutrophil kinetics and preinflammatory processes.

Administration, Inhalation↗
PubMed1992

Surgical anatomy of the male and female urethra.

The urethra is lined by transitional and stratified columnar epithelium. The urethra can be divided into both anatomic (prostatic, membranous, bulbar, and pendulous) and functional (anterior and posterior) segments. In the male, the anterior urethra is contained within the corpus spongiosum and penis. The urethra in the male and female is located within the urogenital triangle and pierces the superficial and deep perineal spaces of the pelvic floor. The urethra is surrounded by perineal and pelvic musculature that provide support and also form the urethral sphincter mechanism. Cancers of the anterior urethra preferentially drain into superficial inguinal lymph node channels. Those of the posterior urethra (prostatic, membranous, and bulbar segments in the male and the proximal two thirds of the urethra in the female) generally drain into pelvic lymphatic channels. A thorough knowledge of urethral and regional anatomy allows for complete tumor excision, optimal reconstruction, and in selected cases, restoration of urinary tract function.

Female↗
PubMed1991

Clostridium difficile disease in a department of surgery. The significance of prophylactic antibiotics.

A clustering of Clostridium difficile-associated disease in a department of surgery prompted a program of infection control and the evaluation of contributing factors. Fifty patients had diarrhea and positive assays for C difficile cytotoxin during the study period. Twenty-one of the 36 cases that developed among patients admitted to the surgical services occurred on two adjacent general surgery wards that shared attending surgeons and house staff. Perioperative prophylactic antibiotics predated C difficile-associated disease in 20 patients, 12 of whom had short courses (less than 24 hours). Symptoms were typically nonspecific and early diagnosis may be difficult. Incidence remained high, despite infection control measures, until the coincidental closure of two surgical wards. Clostridium difficile-associated disease is a nosocomial infection that can be associated with short courses of prophylactic antibiotics. Recommendations regarding the use of perioperative prophylaxis should recognize C difficile-associated disease as a significant potential complication.

Adult↗
PubMed1991

Substance abuse-related spontaneous bladder rupture: report of 2 cases and review of the literature.

Spontaneous rupture of the normal bladder associated with alcohol abuse is rare, with only 20 cases reported in the English literature to which we add 2 cases. Heavy alcohol ingestion predisposes the bladder to rupture by the large volume of fluid intake, its diuretic effect and the mental obtusion it produces, clouding sensory cues to void. alpha-Sympathomimetic drugs, such as cocaine and methamphetamine, increase the resistance at the urethral sphincter and exacerbate the effects of alcohol. Cystography will be diagnostic, and prompt operative repair of intraperitoneal rupture is mandatory. Complete evaluation of the bladder, including urodynamic study, is important to eliminate underlying bladder pathological conditions. Substance abuse-related rupture demonstrates a typical constellation of clinical features that necessitate considering it a syndrome separate from other causes of spontaneous bladder rupture.

Adult↗
PubMed1991

Renal reconstruction after injury.

During an 11-year period 1,363 patients presented to our institution with renal trauma. Renal exploration was performed in 127 patients (133 renal units). Most patients had multiple organ injuries, as indicated by a mean blood loss of 4,160 ml. and a mean injury severity score of 25.8. Absolute indications for exploration were bleeding and pulsatile perirenal hematoma and relative indications included urinary extravasation, nonviable renal tissue and incomplete staging. Renal surgery was required in 2.4% of the blunt injuries, 45% of the stab wounds and 76% of the gunshot wounds. Salvage was successful in 88.7% of the kidneys explored and total nephrectomy was required in 11.3%. The success rate was based on early vascular control and reconstructive techniques of "renorrhaphy," partial nephrectomy, vascular repair and coverage with omental pedicle flaps. Complications occurred in 9.9% of the cases but none resulted in renal loss. When indicated, renal exploration after trauma is safe and in a high percentage of cases reconstruction will be successful.

Adult↗
PubMed1991

Salbutamol inhibits metabisulphite-induced bronchoconstriction.

The effect of salbutamol on bronchoconstriction induced by inhaled sodium metabisulphite has been studied in 12 atopic subjects. Salbutamol (200 micrograms, 3.5 x 10(-7) M) and matched placebo were administered by identical metered dose inhaler 15 min before a dose-response to sodium metabisulphite (1.25-100 mg ml-1) was performed. Geometric mean provocative dose of metabisulphite causing a 35% fall in sGaw after placebo pretreatment was 12.8 [5.75-28.1, 95% Cl] mumol, and after salbutamol was 75.9 [46.5-126] mumol. Mean maximum fall in sGaw after placebo pre-treatment was 47.4 [41-53.9]%. At the same metabisulphite concentration mean maximum fall in sGaw after salbutamol was 2.9 [-8.2-14.1]%.

Albuterol↗
PubMed1990

Heart rate response to peptide histidine valine in human subjects is not mediated through beta receptors.

Peptide histidine valine (PHV) is a 42 amino acid polypeptide closely related to the neuropeptides VIP, PHI and PHM. We have performed a placebo-controlled, double-blind study to assess the hypothesis that the cardiovascular response to PHV infusion may be mediated via the sympathetic nervous system. Four subjects received atenolol or matched placebo 90 min prior to a controlled incremental infusion of PHV, with monitoring of heart rate, blood pressure and skin temperature. Following placebo all subjects showed a dose-related increase in heart rate and skin temperature with no effect on blood pressure during PHV infusion. beta-Blockade had no effect on skin temperature response. Pre-treatment with atenolol reduced the resting blood pressure and the maximum heart rate achieved, but did not affect the percentage increase in heart rate during PHV infusion. This suggests that the action of PHV does not involve beta-receptors. The lack of effect of PHV infusion on blood pressure, despite tachycardia and marked cutaneous vasodilatation, implies that PHV has a different effect on the resistance vessels from that of other peptides such as VIP.

Adult↗
PubMed1990

Inhaled sodium metabisulphite induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate.

1. The effects of nedocromil sodium and sodium cromoglycate on bronchoconstriction induced by inhaled sodium metabisulphite have been studied in eight atopic subjects, three of whom had mild asthma. 2. Nedocromil sodium (4 mg, 7.8 X 10(-6) M), sodium cromoglycate (10 mg, 24.1 X 10(-6) M) and matched placebo were administered by identical metered dose inhalers 30 min before a dose-response to sodium metabisulphite (5-100 mg ml-1) was performed. 3. Maximum fall in sGaw after placebo pre-treatment was -43.9 +/- 3.3% baseline (mean +/- s.e. mean). At the same metabisulphite concentration maximum fall in sGaw after sodium cromoglycate was -13.0 +/- 3.6% and after nedocromil sodium was +4.3 +/- 6.8%. Nedocromil sodium prevented any significant fall in sGaw even after higher concentrations of metabisulphite. 4. Both nedocromil sodium, 4 mg, and sodium cromoglycate, 10 mg, inhibited sodium metabisulphite induced bronchoconstriction but nedocromil sodium was significantly more effective. Relative in vivo potency of the two drugs is broadly in line with other in vivo and in vitro studies.

Administration, Inhalation↗
PubMed1990

Ventilatory effects of substance P, vasoactive intestinal peptide, and nitroprusside in humans.

Animal studies suggest that the neuropeptides, substance P and vasoactive intestinal peptide (VIP), may influence carotid body chemoreceptor activity and that substance P may take part in the carotid body response to hypoxia. The effects of these peptides on resting ventilation and on ventilatory responses to hypoxia and to hypercapnia have been investigated in six normal humans. Infusions of substance P (1 pmol.kg-1.min-1) and of VIP (6 pmol.kg-1.min-1) were compared with placebo and with nitroprusside (5 micrograms.kg-1.min-1) as a control for the hypotensive action of the peptides. Both peptides caused significantly less hypotension than nitroprusside. Substance P and nitroprusside caused significantly greater increases in ventilation and in the hypoxic ventilatory response than VIP. No changes were seen in hypercapnic sensitivity. The stimulation of ventilation and the differential effects on ventilatory chemosensitivity that accompanied hypotension are consistent either with stimulation of carotid body chemoreceptor activity or with an interaction with peripheral chemoreceptor input to the respiratory center, as is seen in animals. The similar cardiovascular but different ventilatory effects of the peptides suggest that substance P may also stimulate the carotid body in a manner independent of the effect of hypotension. This is consistent with a role of substance P in the hypoxic ventilatory response in humans.

Adult↗
PubMed1990

[The surgical treatment of renal trauma].

Over the past 12 years 1363 patients have been evaluated at our institution for renal trauma. Blunt trauma accounted for 1193 patients (88%), stab wounds 106 (8%) and gunshot injuries 64 (4%). Of 127 patients that underwent renal exploration, 6 had bilateral injuries resulting in a total of 133 kidneys that required surgical exploration. Overall, successful repair was achieved in 89% of renal units explored. Nephrectomy was required in 15 cases (11%) but never as a complication of renal exploration. The principles of successful operative management include early vascular control and a variety of surgical techniques. Renal salvage after major trauma can be safely and successfully performed.

Adolescent↗
PubMed1989

Bladder lymphoma: diagnosis and documentation of response by magnetic resonance imaging.

Invasion of the bladder by lymphoma rarely is encountered clinically. The characteristics on magnetic resonance imaging have not been described. We report a case of secondary nonHodgkin's lymphoma of the bladder in which we show the ability of magnetic resonance imaging to visualize the lymphomatous invasion and to monitor the response to chemotherapy.

Female↗
PubMed1989

Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate.

1. The effects of inhaled nedocromil sodium and sodium cromoglycate on bradykinin-induced bronchoconstriction have been studied in a double-blind, placebo controlled study, in eight mild asthmatic subjects. 2. The subjects attended on four occasions. Fifteen minutes after drug pre-treatment a bradykinin challenge was performed. Increasing concentrations were inhaled until a greater than 40% fall in expiratory flow at 30% of vital capacity from a partial flow volume manoeuvre (V p30) was demonstrated. 3. Inhaled bradykinin (0.06-8.0 mg ml-1) caused dose-related bronchoconstriction with the geometric mean cumulative dose causing a 40% fall in V p30 (PD40) of 0.035 (95% CI: 0.02-0.07) mumol, after placebo inhalation, which was similar to that measured before the trial (0.04: 0.02-0.09 mumol). 4. Both nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) gave significant protection (P less than 0.05) against bradykinin-induced bronchoconstriction (PD40 0.37: 0.19-0.72 mumol after nedocromil sodium and 0.22: 0.11-0.49 after sodium cromoglycate). 5. Since bradykinin-induced bronchoconstriction is probably neurally mediated we conclude that both nedocromil sodium and sodium cromoglycate have an action on neural pathways which may be useful in the control of asthma symptoms.

Adult↗
PubMed1989

The kinetics of 14C-GR43175 in rat and dog.

GR43175 is a selective 5-HT 1-like receptor agonist which is effective in the acute treatment of migraine. Rats and dogs were dosed intravenously (iv) and orally (po) with 1 mg 14C-GR43175 base (as succinate salt)/kg bodyweight. GR43175 is rapidly absorbed after oral dosing. In dog, 95-100% of the dose is absorbed, but less (25-30%) is absorbed by the rat. The bioavailability is greater than 54% in dog, but lower in rat. Except for the CNS, drug-related material is widely distributed after iv dosing, but is mainly concentrated in the gastrointestinal tract and excretory organs after oral dosing. GR43175 is eliminated from plasma by a combination of renal and metabolic clearance. Some first-pass metabolism occurs in both species. In dog the major route of excretion is in urine (78-83% of the dose) after either route of administration. In rat, urine is also the major route of excretion (71%) after iv dosing. After oral dosing to the rat the major route of excretion is in the faeces (83%). GR43175 is extensively metabolized, after either route of administration, in both species. GR49336, the indole acetic acid derivative of GR43175, is the major metabolite in dog and a major metabolite in rat.

Administration, Oral↗
PubMed1989

A muscarinic agonist inhibits reflex bronchoconstriction in normal but not in asthmatic subjects.

Muscarinic receptors of the M2 subtype, which inhibit acetylcholine release from cholinergic nerves (autoreceptors), have been described in animal and human bronchi in vitro. We investigated whether these receptors may be involved in feedback inhibition of cholinergic reflex bronchoconstriction induced by sulfur dioxide (SO2) in seven nonasthmatic atopic subjects and in six mild asthmatic subjects. In a control experiment, total respiratory resistance (Rrs) was increased by 30 +/- 5% in nonasthmatic and by 60 +/- 18% in asthmatic subjects. In nonasthmatic subjects, pilocarpine, an agonist of muscarinic M2-autoreceptors, increased Rrs by 15 +/- 5% and addition of SO2 increased Rrs to 21 +/- 5% above base line, which was not significantly greater than after pilocarpine alone. Histamine gave a comparable bronchoconstriction (25 +/- 3% increase in Rrs) and SO2 further increased Rrs to 39 +/- 6% above base line (P less than 0.05). Thus pilocarpine appears to inhibit SO2-induced bronchoconstriction in nonasthmatic subjects, and this effect is not explained by an increase in airway tone. In asthmatic subjects, pretreatment with pilocarpine increased Rrs by 31 +/- 8% and SO2 further increased Rrs to 88 +/- 17% above base line. SO2 alone gave a 60 +/- 18% increase in Rrs. Our results suggest that feedback inhibitory muscarinic receptors may be present on cholinergic nerves in normal airways and that there may be a dysfunction of this feedback mechanism in asthmatic airways. This might be contributory to exaggerated cholinergic reflex bronchoconstriction in asthma.

Adult↗
PubMed1989

Anticholinergic blockade of beta-blocker-induced bronchoconstriction.

The mechanism of propranolol-induced bronchoconstriction (PIB) remains unclear. Previous uncontrolled studies have suggested that atropine antagonizes PIB in asthma. We conducted a randomized, double-blind, placebo-controlled study of the effect of a new anticholinergic agent, oxitropium bromide, on bronchoconstriction induced by inhaled propranolol in seven subjects with mild asthma 24 to 39 yr of age. Inhaled propranolol induced long-lasting reduction in specific airway conductance (SGaw) in all subjects. This was associated with airway beta-adrenoceptor blockade as demonstrated by a shift in the isoproterenol dose-response curve. Propranolol was less potent than methacholine, with a geometric mean dose causing a 35% fall in SGaw of 4.7 mumol for propranolol compared with 0.48 mumol for methacholine. Pretreatment with oxitropium 200 micrograms completely inhibited the fall in SGaw in response to inhaled propranolol in all subjects. Oxitropium also revealed PIB. Cholinergic receptor blockade by oxitropium inhibits bronchoconstriction induced by inhaled propranolol, supporting involvement of cholinergic mechanisms in PIB.

Adult↗
PubMed1989

The metabolism of ondansetron.

The metabolism of ondansetron has been studied in rat, dog and man. In laboratory animals absorption of the compound across the gastrointestinal tract is rapid and extensive, but due to high first-pass metabolism, the oral systemic bioavailability is low (less than 10%). The high systemic clearance of ondansetron results in a very short half-life in rat and dog. The renal clearance of ondansetron is low, indicating that the major route of systemic clearance is by metabolism. Routes of excretion of drug-related material differ between laboratory animals and man - the major route in the rat and dog is via the bile, while in man the predominant route is via the urine. However, the routes of metabolism are qualitatively similar in all species, indicating that the species used in toxicological testing of ondansetron were appropriate.

Administration, Oral↗
PubMed1988

Reproducibility of heart rate changes following adenosine infusion in man.

The change in heart rate following infusion of adenosine in healthy human subjects was studied on two occasions. Adenosine produced a significant, dose-related increase in heart rate. Tachyphylaxis to this effect of the naturally occurring nucleoside did not occur. There was a tendency for prolonged infusion to cause a greater increase in heart rate, but this did not reach significance.

Adenosine↗