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Biomedical subjects

M G Thomas

Publications and source records attributed to M G Thomas.

At least 145 records · Page 8Linked to original sources

Serum IgG, IgA, and IgM responses to pertussis toxin, filamentous hemagglutinin, and agglutinogens 2 and 3 after infection with Bordetella pertussis and immunization with whole-cell pertussis vaccine.

Class antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens 2 and 3 (Agg 2/3) were studied in 114 patients with pertussis, 49 family contacts of patients with pertussis, and 139 infants attending vaccination clinics. IgG responses to FHA and PT were similar in patients with pertussis and in infants immunized three times with whole-cell pertussis vaccine. IgA responses to FHA and PT were greater in patients with pertussis than in vaccines, and a serum log10 titer of IgA to PT greater than 1.9 was a useful discriminant of Bordetella pertussis infection. When compared with patients with pertussis, vaccinees had a greater IgG response to Agg 2/3 and an equivalent IgA response to Agg 2/3. Serologic responses to FHA, PT, and Agg 2/3 were common in family contacts but were smaller than the responses in patients with pertussis. Initial titers of IgG to FHA and IgA to FHA were significantly higher (P less than .005 and P less than .05, respectively) in family contacts aged 3-10 y than in patients with pertussis in an identical age group.

Agglutinins↗

Severe hypoxaemia in pertussis.

Overnight tape recordings of breathing movements, airflow, and arterial oxygen saturation from six infants aged 3 weeks to 7 months, who had cyanotic episodes associated with pertussis, were compared with recordings from 12 age matched healthy controls. In all patients clinically apparent apnoeic episodes were associated with the rapid onset and progression of central cyanosis. When overnight recordings were compared, patients with pertussis had a greater frequency of apnoeic pauses (particularly those greater than or equal to 12.0 seconds duration) and a greater frequency of episodes of hypoxaemia (oxygen saturation less than or equal to 80% for greater than or equal to 0.5 seconds) associated with apnoeic pauses. In addition to episodes of hypoxaemia associated with a prolonged absence of breathing movements, patients with pertussis had frequent dips in oxygen saturation in association with continued breathing movements with and without continued inspiratory airflow. These episodes of hypoxaemia during continued breathing movements were more common in patients with pertussis. These findings suggest that episodes of abnormal apnoea accompanied by evidence of a mismatch between ventilation and perfusion of the lungs may produce the rapid onset of severe hypoxaemia in infants with pertussis.

Apnea↗

Remission of mild to moderate hypertension after treatment with carteolol, a beta-adrenoceptor blocker with intrinsic sympathomimetic activity.

Previous studies have indicated that some hypertensive patients, following a period of effective treatment with certain antihypertensive drugs, may experience prolonged normotension after drug withdrawal. We have studied the ability of carteolol, a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, to produce such remissions of hypertension. Thirty-four patients whose diastolic blood pressure was controlled at 90 mm Hg or less with carteolol monotherapy (2.5 to 5.0 mg/d for an average of 328 days) were randomized to a nine-month, double-blind, placebo-controlled drug-withdrawal trial. Those patients randomized to continue carteolol therapy had initially responded to carteolol treatment with reduction in blood pressure from 151 +/- 4/99 +/- 2 to 132 +/- 4/80 +/- 2 mm Hg. Those randomized to treatment with placebo had initially responded with blood pressure reductions from 154 +/- 4/97 +/- 2 to 137 +/- 4/81 +/- 2 mm Hg. Changes in mean systolic and diastolic blood pressure (mm Hg +/- SEM) from baseline during carteolol therapy to the final visit at nine months were not different for patients receiving placebo (13 +/- 5/6 +/- 4 mm Hg, recumbent; 11 +/- 6/4 mm Hg, standing) or carteolol (11 +/- 5/7 +/- 3 mm Hg, recumbent; 12 +/- 6/7 +/- 3 mm Hg, standing). The final mean recumbent diastolic blood pressure (86.9 mm Hg) was the same in both groups. Prolonged normotension may follow a period of carteolol treatment, again suggesting the potential importance of periodic withdrawal of antihypertensive medication.

Blood Pressure↗

Survey of alpha-amylase activity and isoamylases in autopsy tissue.

We quantified total amylase and its isoenzymes in 22 different human tissues obtained at autopsy. Isoenzymes were separated by use of wheat-germ inhibition (WI) and electrophoresis on cellulose acetate (CA) and agarose (AG). Mean (+/- SD) total activity was highest in salivary glands (parotid 1710 +/- 897 U/g, submandibular 605 +/- 354 U/g), and pancreas (258 +/- 137 U/g). All other tissues contained 100- to 1000-fold less amylase. As assessed with WI, pancreas, jejunum, liver, placenta, testis, skeletal muscle, and spleen contained more than 90% pancreatic isoamylase. Salivary glands and thyroid contained more than 90% salivary isoamylase. All other tissues contained a mixture of the two isoenzymes. CA and AG often produced different results. For both CA and AG the most common pancreatic isoforms were P2 and S1. Salivary gland homogenates demonstrated a band migrating in the P3 position on CA. We conclude that both types of amylase isoenzymes can be found in tissues other than salivary gland and pancreas, but that their low total amylase concentrations diminish their clinical importance.

Electrophoresis, Polyacrylamide Gel↗

Three methods compared for isoamylase separation in tissue homogenates.

Using homogenates of autopsy tissue, we compared three widely available techniques for separating amylase isoenzymes: wheat-germ inhibition (WI), and electrophoresis on cellulose acetate (CA) or agarose (AG). WI separated amylase into two isoforms, CA into seven (three pancreatic and four salivary), and AG into nine (five pancreatic and four salivary). CA and WI had similar isoamylase detection limits (8-10 U/L) and similar imprecision in measuring percent S-type vs P-type isoamylase (within-run SD 1-2%), and they demonstrated a linear response to added S or P isoamylase. In contrast, the AG method had higher detection limits (10-15 U/L), greater imprecision (within-run SD 3%), and showed a nonlinear response to added S or P isomylase. We conclude that CA and WI have essentially equivalent assay attributes, superior to AG, but that CA resolves more amylase isoforms than WI.

Electrophoresis, Agar Gel↗

Comparison of nitrendipine and hydrochlorothiazide for systemic hypertension.

Left ventricular (LV) hypertrophy with associated LV systolic and diastolic dysfunction is frequently found in patients with systemic hypertension, and is multifactorial in origin. Although a reduction in blood pressure (BP) often results in regression of hypertrophy, the pharmacologic profiles of the antihypertensive agents used may determine the probability of such regression despite similar levels of BP reduction. Thiazide diuretic drugs may actually result in increased LV hypertrophy; calcium channel antagonists may cause regression or no change. The effects of treatment with nitrendipine (20 mg/day) or hydrochlorothiazide (50 mg/day) were compared in an 8-week, double-blind study of 18 hypertensive subjects aged 50 years or older. BP was significantly reduced (p less than 0.05) by both nitrendipine (from 161 +/- 29/102 +/- 4 to 145 +/- 24/92 +/- 7 mm Hg; mean +/- standard deviation) and hydrochlorothiazide (from 162 +/- 15/105 +/- 6 to 143 +/- 20/95 +/- 7 mm Hg). Plasma norepinephrine increased in the nitrendipine group, from 202 +/- 110 to 332 +/- 220 pg/ml at 8 weeks of therapy and in the hydrochlorothiazide group, from 147 +/- 130 to 313 +/- 277. Plasma renin activity changed from 3.2 +/- 2.4 to 3.5 +/- 2.1 during nitrendipine treatment, but from 2.1 +/- 2.1 to 10.5 +/- 10.8 ng angiotensin l/ml/90 min (p less than 0.05) during treatment with hydrochlorothiazide. Left ventricular mass index did not change significantly with either therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Acute and short-term effects of clonidine in heart failure.

The authors performed a randomized, double-blind, placebo-controlled trial to assess the tolerance and effects of chronic oral clonidine administration on the clinical status, exercise tolerance, and ventricular function of 10 male patients with chronic heart failure. Patients were given either oral clonidine (400 micrograms/day) or matching placebo for twelve weeks and then tapered off medication over a two-week period. Results are summarized as follows: Profiles over time between groups were significantly different for resting heart rate (p = 0.0005), were different for arterial pressure (p = 0.04), were different for left ventricular ejection fraction (p less than 0.006), and were different for mean accumulated workload (p = 0.076). Exercise double product at 25 watts changed little in three patients and showed a decrease in 2 patients following six weeks of oral clonidine; after twelve weeks, it decreased in three patients, increased in 1, and changed little in another. After washout, double product returned toward baseline values. In the placebo groups, double product showed little change. Resting of the heart by decreasing heart rate, systemic arterial blood pressure, and venous tone are thought by the authors to be major contributing factors to the observed beneficial effect of chronic oral clonidine in chronic heart failure.

Administration, Oral↗

Alpha-adrenergic mechanisms in the pathophysiology of left ventricular heart failure--an analysis of their role in systolic and diastolic dysfunction.

Alpha-adrenoceptor (alpha-AR) mechanisms may contribute to systolic and diastolic dysfunction of the left ventricle. Centrally acting alpha 2-AR agonist drugs, including methyldopa, clonidine, and guanabenz, activate brainstem alpha 2-AR and this activation results in a decrease in overall sympathetic tone and an increase in parasympathetic tone. Peripherally acting alpha 1-AR antagonists, such as prazosin, inhibit the actions of catecholamines at post-synaptic receptor sites. Heart failure is characterized by hyperactivity of sympathetic pathways and parasympathetic withdrawal. In this situation, alpha 2-agonists reduce sympathetic activity and improve hemodynamic parameters of cardiac function; both acute and chronic administration of alpha 2-AR have been demonstrated to reduce serum catecholamine levels, heart rate, and arterial blood pressure, and to improve exercise performance. Diastolic dysfunction of the left ventricle is characterized by a marked decrease in ventricular compliance, often a result of hypertension and left ventricular hypertrophy; the end result is an increase in left ventricular filling pressure and pulmonary venous pressure. Treatment with alpha 2-AR, by decreasing sympathetic tone and blood pressure, and alpha 1-AR antagonists, by reducing blood pressure and by directly inhibiting the actions of catecholamines at alpha 1-AR, may produce a reduction in the degree of ventricular hypertrophy and improve diastolic performance of the left ventricle. Thus, therapeutic intervention in heart failure with either alpha 2-AR agonists or alpha 1-AR antagonists may favorably modulate these alterations in sympathetic tone and improve ventricular function.

Adrenergic alpha-Antagonists↗

Comparative in-vitro activity of antibiotics incorporated in acrylic bone cement.

We compared the persistence of antibacterial activity around antibiotic-impregnated acrylic bone cement discs which were serially transferred on seeded agar plates. On plates inoculated with Staphylococcus aureus ATCC 25923, CMW1 discs containing 2.5% by dry weight of cephalothin, coumermycin or fusidic acid (as diethanolamine fusidate) produced zones of inhibition for four to eight weeks when transferred daily. In contrast, ceftriaxone, cotrimoxazole, rifampicin and vancomycin ceased to be inhibitory within a week. Discs made of 'Palacos-R with Garamycin,' which contains gentamicin 1.25%, had an intermediate duration of activity. When Escherichia coli ATCC 25922 was used as the test organism, ceftriaxone and 'Palacos-R with Garamycin' showed activity for almost three weeks, cephalothin and cotrimoxazole were briefly inhibitory and the remainder not at all. When discs were transferred each week instead of daily, the ranking of antibiotics was similar but antibacterial activity persisted for longer. A combination of gentamicin plus fusidic acid in CMW1 was active for a much shorter time than either fusidic acid alone or 'Palacos-R with Garamycin'. We conclude that coumermycin is a promising new agent for incorporation in acrylic cement.

Acrylates↗

In-vitro activity of coumermycin against methicillin-resistant staphylococci: a comparison with six other agents.

The in-vitro activity of coumermycin was compared with that of vancomycin, rifampicin, fusidic acid, trimethoprim-sulphamethoxazole, norfloxacin and cefamandole against seven isolates of methicillin-resistant Staphylococcus aureus and 97 isolates of methicillin-resistant coagulase negative staphylococci. Apart from one strain of methicillin-resistant S. aureus all isolates were inhibited by less than or equal to 0.06 mg/l of coumermycin. Cefamandole was more active against strains of S. epidermidis than against other coagulase negative staphylococci.

Aminocoumarins↗

Antianginal effects of clonidine.

The effects of clonidine, a central alpha-adrenoceptor agonist, were studied in 12 patients with chronic stable effort angina pectoris in an 18-week randomized, double-blind, two-period (6 weeks each) crossover study with a 3-week inter-period washout phase. Clonidine (200 micrograms as a single dose) produced a decrease in rate-pressure product at rest and during exercise and an increase in exercise tolerance, at 1 and 2 h after administration. Chronic administration of clonidine produced a decrease in rate-pressure product at rest and during exercise and an increase in exercise tolerance after 3 weeks (200 micrograms twice a day) and 6 weeks (400 micrograms twice a day) of treatment.

Angina Pectoris↗

Antimicrobial spectrum of Ro 15-8074/001, a new oral cephalosporin.

The activity of Ro 15-8074/001 was compared with that of cefaclor, amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, norfloxacin, and ceftriaxone against 225 clinical isolates. It was more active than cefaclor, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole against members of the family Enterobacteriaceae and Haemophilus influenzae and had activity similar to that of cefaclor against nonenterococcal streptococci. It was not usefully active against Pseudomonas aeruginosa, Streptococcus faecalis, or most isolates of staphylococci.

Anti-Bacterial Agents↗

Intravascular cannula-related sepsis: two years experience.

Thirteen episodes of intravascular cannula-related sepsis were seen during a two year period. Staphylococcus aureus was the most common pathogen. Fungaemia occurred in four patients all receiving total parenteral nutrition. Culture of the cannula tip and swabs of the insertion site were useful in confirming the diagnosis. Three patients with infection due to S aureus died while receiving treatment for their infections. Care with insertion and maintenance of intravascular cannulae should reduce the frequency of this iatrogenic infection.

Aged↗