Search PubMed⌕ Search

Biomedical subjects

M A Adams

Publications and source records attributed to M A Adams.

At least 127 records · Page 7Linked to original sources
PubMed1989

Comparison of high- and low-diabetes-incidence NOD mouse strains.

The nonobese diabetic (NOD) mouse is a model of insulin-dependent diabetes mellitus. These mice develop insulinopenia and hyperglycemia secondary to beta-cell destruction, which is associated with insulitis and autoantibody production. We have two strains of NOD mice: a low-incidence strain (NOD/Wehi), in which less than 10% females and less than 1% males develop diabetes by 150 days despite intense insulitis, and a high-incidence strain (NOD/Lt), in which most females and many males develop diabetes by 150 days. This phenotypic difference has been maintained for 24 mo despite identical housing in our specific pathogen-free unit. Reciprocal skin grafting and allozyme electrophoresis have not identified a difference between the strains. Mixed-lymphocyte cultures were performed with splenic T-lymphocytes cultured with equal numbers of irradiated stimulator splenocytes for 3-6 days. NOD/Wehi mice demonstrated a heightened syngeneic mixed-lymphocyte response (SMLR), averaging 19% of the allogeneic response to CBA/CaHWehi cells. The response to NOD/Lt stimulator cells was not significantly different from the syngeneic response. In contrast, NOD/Lt mice had an SMLR similar to that of BALB/cAnBradleyWehi control mice, averaging 5% of the allogeneic response. NOD/Lt cells also responded similarly to NOD/Wehi stimulator cells and briskly to allogeneic cells. The heightened SMLR in NOD/Wehi mice may reflect active generation of suppressor function, and this may account for the low incidence of diabetes.

Alleles↗
PubMed1989

Biopharmaceutical comparison of two levothyroxine sodium products.

The relative bioavailability and therapeutic equivalence of two brands of levothyroxine sodium tablets, Levothroid and Synthroid, were compared in patients who had been receiving long-term levothyroxine replacement therapy. Eighteen patients with primary hypothyroidism were randomly assigned to receive therapeutic dosages of Levothroid or Synthroid for 43 days and then were switched to the opposite product for 43 more days. The pharmacokinetic profiles of the two drugs were evaluated on days 43 and 86 by analyzing blood samples drawn at various intervals after the final dose. Relative bioavailability was determined by comparing the absorption profiles and areas under the serum concentration-time curves (AUCs) of total and free serum thyroxine. In addition, the potency of the levothyroxine sodium tablets was determined by high-performance liquid chromatography. The time to reach maximum concentration and the maximum concentration of total thyroxine after treatment with Levothroid did not differ significantly from those after treatment with Synthroid. The mean +/- S.D. AUC of total thyroxine after Levothroid administration (2339 +/- 404 pg.hr/mL) was slightly but significantly higher (p = 0.047) than that following Synthroid (2169 +/- 422 pg.hr/mL). However, the main index of biological activity, thyrotropin concentration, did not differ significantly between the two products. All tablets tested were within the stated potency requirements of the USP. The AUC of total serum thyroxine and the serum thyrotropin concentration after long-term replacement therapy with Levothroid or Synthroid indicate that any differences in bioavailability between the two products are clinically unimportant and that the two products are therapeutically interchangeable.

Adult↗
PubMed1989

A community trial of ivermectin in the onchocerciasis focus of Asubende, Ghana. I. Effect on the microfilarial reservoir and the transmission of Onchocerca volvulus.

A community trial of the microfilaricide ivermectin was undertaken in an isolated focus of hyperendemic savanna onchocerciasis in Ghana. One of the objectives was to determine the effect of mass treatment on the microfilarial reservoir and on the transmission of Onchocerciasis volvulus. Since 1978 the focus has been under entomological surveillance. This was intensified from 1 September 1987 till 11 February 1988 with daily vector collection and dissection of over 30,000 flies. A total of 14,991 people were treated with ivermectin on 7-10 October 1987. Skin snip surveys were done pre-treatment, and at two and four months after treatment. The mean skin microfilarial load in treated persons had fallen by more than 96% two months after treatment. During the next two months there was an increase in microfilaria loads which appeared to be faster than reported in the clinical trials. The total reservoir of skin microfilariae available for transmission had been reduced by an estimated 68%-78% two months after treatment. This was consistent with the entomological results which indicated a reduction in transmission of 65%-85% during the first three post-treatment months. The present study has shown for the first time that mass chemotherapy can significantly reduce onchocerciasis transmission. However, the remaining level of transmission was still unacceptably high and further studies are required to predict the long term impact of repeated mass treatment.

Animals↗
PubMed1989

Resistance control in hypertension.

In hypertension the small arteries undergo structural changes that increase vascular resistance, both in vivo and in vitro. The hallmark of a physiological vascular amplifier is that enhanced resistance responses must occur about the resting value. For this to happen, the average radius of the resistance vessels must be narrower than normal; increased wall thickness without narrowing does not result in this type of amplification. In primary hypertension in spontaneously hypertensive rats (SHR), the structural changes in the resistance vessels precede the elevation in blood pressure. This is consistent with the hypothesis that these changes cause hypertension. The role of the sympathetic nervous system in early vascular development is unclear, in view of the absence of regression of amplifier properties in the hindlimb vessels after extensive immunosympathectomy. However, short periods of enalapril treatment in young animals attenuate the development of hypertension and normalize hindlimb resistance properties, suggesting that the renin-angiotensin system may have a role in early vascular growth. Studies in tissue culture suggest that both systems could play a role in smooth muscle growth, in conjunction with growth factors such as platelet-derived growth factor (PDGF)-like peptides and endothelin. The early structural change that occurs in hypertension is probably a variant of normal development of the resistance vasculature, with greater secretion of 'normal' growth factors and/or enhanced responsiveness of the vascular smooth muscle.

Animals↗
PubMed1988

Commonly adopted postures and their effect on the lumbar spine.

The activity of the erector spinae muscles and the changes in lumbar curvature were measured in 11 subjects in a range of commonly adopted postures to see if there were any consistent trends. Surface electrodes were used to measure back muscle activity and lumbar curvature was measured using electronic inclinometers. The results showed that many commonly adopted postures reduced the lumbar lordosis when compared with erect standing or sitting, even at the expense of increasing the back muscle activity.

Adult↗
PubMed1988

The lumbar spine in backward bending.

Cadaveric lumbar motion segments were loaded to simulate backward bending (extension) movements of the lumbar spine. The motion segments' resistance was measured initially, and after the spinous processes and apophyseal joints had been cut through in turn. Compression tests were then performed on the discs while they were wedged in full extension. The results showed that extension is resisted mainly by the disc and spinous processes, and that, in hyperextension, damage usually occurs first in the spinous processes (or the soft tissue squashed between them). However, if the spinous processes are particularly widely spaced, then the apophyseal joints can become damaged first. The protection offered the disc by the neural arch is greater in young people, and after the disc height has been reduced by creep loading. The disc can be damaged in hyperextension if the spine is subjected to high compressive forces at the same time. A sudden application of compressive force can cause an anterior disc prolapse, while a cyclic (fatigue) compressive force can increase the posterior bulging of the lamellas in the posterior annulus.

Humans↗
PubMed1988

Effect of antihypertensive therapy on the cardiovascular amplifiers.

1. In established chronic hypertension the amplifier properties of vessels and heart contribute about 70% to the maintenance of the elevated blood pressure (BP). Recent studies in spontaneously hypertensive rats (SHR) suggest that the structural changes occur very early and their amplifier properties may be critical for the development of hypertension. 2. In patients with primary hypertension, the greater the regression of cardiac and vascular hypertrophy, the slower the subsequent redevelopment of hypertension. Following regression of hypertrophy, the antihypertensive action of moderate regular exercise can maintain BP in the normal range in a proportion of patients. 3. Early treatment of SHR with enalapril greatly reduces the subsequent 'steady-state' BP in SHR. This produces virtually complete regression of vascular hypertrophy, but somewhat lesser degrees of regression of cardiac hypertrophy. 4. These studies serve as models for primary and secondary prevention of hypertension. A strategy based on intermittent drug and non-pharmacological therapy in man may contribute to the secondary prevention of atherosclerosis, in view of the adverse effects on lipid profiles of many antihypertensive drugs.

Animals↗
PubMed1988

Time course of changes in baroreceptor reflex control of heart rate in conscious SHR and WKY: contribution of the cardiac vagus and sympathetic nerves.

1. The aim of this study was to assess the vagal and sympathetic nerve contribution to the relationship between mean arterial pressure (MAP) and heart rate (HR) at 6, 9, 14 and 20 weeks of age in conscious Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with methoxamine- and nitroprusside-induced steady-state changes in blood pressure. 2. MAP increased with age in both strains but was 17-23% higher in SHR. 3. By contrast baroreflex parameters (HR range: difference between upper and lower HR plateaus, and gain: average slope between inflection points of the logistic MAP-HR relationship) decreased with age in SHR but increased in WKY. 4. After methylatropine, no differences in the cardiac sympathetic baroreflex range or gain parameters were observed between strains or ages. 5. It was concluded that older SHR have normal sympathetic but reduced vagal capacity to control HR in response to changes in MAP, but that this deficit was not dependent on the absolute level of blood pressure. 6. Because the differences were confined to one effector, SHR may have different central rather than arterial baroreceptor afferent mechanisms.

Animals↗
PubMed1988

Vascular smooth muscle polyploidy in the development and regression of hypertension.

1. Two groups of spontaneously hypertensive rats (SHR) were treated with enalapril (25-30 mg/kg per day): Group I received treatment from 4 to 14 weeks of age to inhibit development of hypertension and Group R received the drug from 14 to 20 weeks of age to reverse established hypertension. 2. Systolic blood pressure, ploidy of aortic smooth muscle cells (flow cytometric DNA analysis) and aortic hypertrophy (medial cross-sectional area) were determined at times both during and after enalapril treatment (up to 30 weeks). 3. Enalapril treatment normalized blood pressure to that of age-matched Wistar-Kyoto rats in both groups. Blood pressure rose again following cessation of treatment. 4. In untreated SHR the incidence of polyploid cells increased concomitantly with increasing pressure throughout the time studied, whereas in Group I the incidence remained low. In Group R, the incidence of polyploidy directly paralleled both the decrease (normalization) and the rise in blood pressure following cessation of treatment. 5. Hence, the incidence of vascular smooth muscle cell polyploidy is not simply a result of growth of the vessel with increasing age of the SHR, but parallels inhibition, reversal, and redevelopment of hypertension.

Aging↗
PubMed1987

Diurnal variations in the stresses on the lumbar spine.

Two complementary experiments were performed, the first on living people and the second on cadaveric spines. In the first experiment, electronic inclinometers were used to measure the range of lumbar flexion of 21 volunteers in the early morning and in the afternoon. The results showed that the range of movement increased by 5 degrees during the day. In the second experiment, cadaveric lumbar motion segments were creep loaded to simulate a day's activity and their bending properties were measured before and after creep. The results showed that creep loading reduces the spine's resistance to bending (the effect being particularly marked in the disc) and increases the range of lumbar flexion by 12.5 degrees. The results of the two experiments were combined to show that in life, forward bending movements subject the lumbar spine to higher bending stresses in the early morning compared with later in the day. The increase is about 300% for the discs and 80% for the ligaments of the neural arch. It is concluded that lumbar discs and ligaments are at greater risk of injury in the early morning.

Adolescent↗
PubMed1987

Ethanol-induced cardiac hypertrophy: effects of peripheral sympathectomy.

The development of cardiac hypertrophy was examined in rats that had undergone sympathectomy with 6-hydroxydopamine. After 4 days, the rats were given severely intoxicating doses of ethanol or isocalorically paired quantities of maltose-dextrin by intubation at 8-h intervals up to 48 h. The ethanol and sugar intubations were applied in a nutritionally adequate, liquid diet mix. The extent of the peripheral sympathectomy was evident from the absence of detectable quantities of noradrenaline in hearts of animals injected with the neurotoxin and in the reduced levels of excreted noradrenaline. The adrenal medullary catecholamine contents of sympathectomized rats were unchanged in the absence of ethanol; there were reduced quantities of adrenaline in the medullae of rats given ethanol. The adrenal glands of rats given ethanol were larger than those from control animals. Urine samples from sympathectomized and control rats, given ethanol, displayed equivalent increases in excreted adrenaline and noradrenaline. Increases in relative cardiac weight were evident in hearts from sympathectomized animals after 4 days of sympathectomy, and this change reached significance in the hearts from 6-hydroxydopamine-treated rats after a further 2 days on the control diet. Hearts from animals exposed to ethanol showed a marked, rapid development of cardiomegaly; after 24 h there was an increased mass of some 17%, which was sustained over the remaining 24-h period. The proportion of cardiac protein did not differ in the large hearts from ethanol-treated animals and those from their controls, hence myocardial oedema could not account for the increase in weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1987

The short-term effects of chymopapain on intervertebral discs.

Cadaveric lumbar discs were injected with chymopapain and subjected to a series of mechanical tests over a period of up to 19 hours. Discs from the same spine injected with saline were used as controls. The results showed that chymopapain had no measurable effect on the mechanical properties of the disc apart from the increased height and stiffening caused by fluid injection. Another series of tests on isolated pieces of disc material showed that chymopapain could reduce the size of prolapsed nuclear material by 24% in one hour and by 80% in 48 hours. It is concluded that, in the short-term, chymopapain has a negligible effect on the mechanics of a disc but it can reduce the size of any prolapsed nuclear material with which it comes in contact.

Adult↗
PubMed1986

Nasal trigeminal chemoreception: responses to n-aliphatic alcohols.

Odorant molecules can stimulate nasal trigeminal receptors, but the properties of such molecules which make them effective stimuli are largely unknown. In the present study, we obtained integrated multiunit responses from the ethmoid branch of the rat trigeminal nerve to a homologous series of aliphatic alcohols. Our aim was to determine whether lipid solubility might correlate with stimulus efficacy. Response thresholds (ranging from 3000 ppm for methanol to 3 ppm for octanol) decreased with increasing carbon chain length, suggesting that lipid solubility is important for stimulus effectiveness. One plausible explanation for the importance of lipophilicity is that the more lipid soluble a substance, the more easily it can penetrate epithelial layers to reach chemoreceptive trigeminal nerve endings. Since all stimuli at vapor saturation elicited responses within 0.5 s, and because diffusion of stimulus molecules through epithelium is slow, we speculate that trigeminal nerve endings lie closer to the epithelial surface than previously thought.

Alcohols↗
PubMed1986

Ethanol-induced cardiac hypertrophy: correlation between development and the excretion of adrenal catecholamines.

The progression of cardiac hypertrophy and the effects on adrenal medullary catecholamine content and release were determined in rats given ethanol, in conjunction with a supplementary diet, by gavage, every eight hours for periods up to 96 hours. Ethanol caused a marked depletion of adrenal medullary adrenaline content which fell to about 25 percent of control after the full time course. During this time, there were two- to fourfold increases in urinary noradrenaline content and five- to tenfold increases in urinary adrenaline. Cardiac hypertrophy, with increases in protein content and tissue weight of both ventricles, was evident at 24 hours of intoxication. By 96 hours of treatment these markers had increased more than 20% over control values. Proportional heart weight increases per day correlated significantly with daily urinary catecholamine excretion, providing support for the hypothesis that ethanol induced cardiac hypertrophy in the rat results from catecholaminergic stimulation, primarily of adrenal medullary origin.

Adrenal Glands↗
PubMed1986

The influence of adrenal medullectomy on the development of ethanol-induced cardiac hypertrophy.

Cardiac hypertrophy was assessed in adrenal medullectomized and sham control rats given ethanol in a liquid diet mixture, intragastrically, in severely intoxicating doses at 8-h intervals for 48 and 96 h. The ethanol treatments produced increases of some 20% in wet and dry proportional heart weights in the control animals, but this rapid development of hypertrophy was less apparent in the medullectomized rats. Hearts of the medullectomized animals given ethanol were heavier than those of pair-matched controls given isocaloric maltose-dextrin in the diet mix. These increases were not statistically significant. The ethanol treatments produced, in addition, equivalent increases in the weight of the adrenal glands of both medullectomized and control animals. Medullectomy was evaluated by analysis of adrenal glands and urine samples for catecholamines. The majority of adrenals from the demedullated group had nondetectable amounts of catecholamines and minimal quantities were found in the remainder. Adrenaline was not detected generally in urine samples from this group. The adrenaline contents of adrenals from sham controls given ethanol were markedly reduced by the ethanol treatments, whereas the quantities in urine were many times greater than those from rats given maltose-dextrin. Urinary noradrenaline levels were increased in both control and medullectomized rats given ethanol. The results of this study identify that adrenal medullary catecholamines participate in the rapid development of cardiac hypertrophy that results from severe, continuing ethanol intoxication in the rat.

Adrenal Glands↗