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Biomedical subjects

P Simpson

Publications and source records attributed to P Simpson.

At least 109 records · Page 6Linked to original sources
PubMed1989

Peripheral somatic sensory neuropathy and skin galvanic response in the feet of patients with diabetes.

The relationship between abnormality in the peripheral sympathetic nervous system (skin galvanic response) and in the peripheral somatic sensory nerve fibers was studied in the lower extremities of 51 patients with diabetes. Deficits in temperature and pain sensations (the small sensory nerve fibers) were related to abnormal sympathetic nervous function (temperature sensation, p less than 0.001; pain sensation, p less than 0.05). The deficits in temperature sensation, in particular, predicted abnormal sympathetic nervous function reliably and vice versa. There was no relationship between deficits in touch and vibration sensations (the large sensory nerve fibers) and abnormal sympathetic nervous function. There was a relationship between skin galvanic response and RR-variation (p less than 0.01). However, abnormality in RR-variation was not related to the deficits in any of the four sensory modalities.

Adult↗
PubMed1987

The segment polarity gene costal-2 in Drosophila. I. The organization of both primary and secondary embryonic fields may be affected.

A series of loss of function alleles at the costal-2 locus is described. Embryos mutant for lethal alleles that are derived from a mutant female germ line display polarity defects on the larval segments. A posterior part of the segmental denticle belt is missing and in its place is a mirror-image duplication of the anterior part including the segment boundary. Maternally rescued embryos are lethal but have normal morphology. Hypomorphic alleles escape to adults that display pattern duplications on the wings and halteres. Dominant gain of function alleles at the Costal-1 locus are also described and data are presented that argue that these are neomorphic and act in trans to impair functioning of costal-2. Some wild-type isoalleles of costal-2 are particularly sensitive to interference from Costal-1 mutations and different combinations of these alleles with Costal-1 can lead to embryos in which the primary embryonic field is disrupted (bicaudal phenotype) and adults with pattern duplications on the anterior compartment of most body segments.

Abdomen↗
PubMed1987

The segment polarity gene costal-2 in Drosophila. II. The origin of imaginal pattern duplications.

Imaginal pattern duplications caused by hypomorphic expression of the segment polarity gene costal-2 are described. These affect the anteroposterior coordinate of the imaginal disc. A very small part of the pattern is deleted and a large number of additional pattern elements arise in a progressive order, anterior-most first followed by more and more posterior structures. Mosaic analyses show that the duplications arise nonautonomously in the larval stages but that the costal-2 gene is not required after early embryogenesis. Arguments that the duplications are the result of cell interactions and intercalary growth that themselves arise from an abnormal polarity of the embryonic segment are presented.

Abdomen↗
PubMed1987

An automated enzymic micromethod for the measurement of fat in human milk.

Most (98%) of the fat in human milk is present as triglycerides. This paper describes the use of a clarification procedure that enables the level of human milk fat to be determined by measurement of glycerol released by enzymic hydrolysis of triglycerides. The method requires only 10-50 microliters milk, thus presenting a possible technique for work with small mammals, and is suitable for use with autoanalysers, permitting rapid sample throughput.

Autoanalysis↗
PubMed1986

Dual trophic effects of the alpha 1-adrenergic receptor in cultured neonatal rat heart muscle cells.

The molecular signals regulating myocardial hypertrophy are unknown. We used a new model system to study this problem. Muscle cells from the neonatal rat ventricle were cultured in serum-free medium. Control cells did not change in size over time and did not show spontaneous contractile activity. Incubation with norepinephrine or epinephrine had two major trophic effects that developed over 1-2 days. The first was stimulation of muscle cell hypertrophy or increase in size. The second was induction of spontaneous contractile activity. The hypertrophic response was mediated through an alpha 1-adrenoceptor. The beating response required both alpha 1- and beta 1-adrenergic receptor stimulation. Alpha 1 stimulation alone produced enlarged cells that did not beat. Alpha 1 plus beta 1 stimulation induced contractile activity even when protein synthesis and hypertrophy were inhibited. Thus, the two alpha 1 responses could be dissociated, providing evidence for two independently-regulated cellular pathways for the dual alpha 1 trophic effects. One pathway leads to hypertrophy. The other, which requires concomitant beta 1 stimulation, controls the development of beating. Preliminary work raises the possibility that different products of inositol phospholipid hydrolysis might initiate the two alpha 1 trophic pathways. Other preliminary work suggests that the growth pathway is associated with the expression of specific genes and might reflect an action of the alpha 1-adrenoceptor on the cell nucleus. These studies define previously unsuspected trophic roles for the alpha 1-adrenergic receptor.

Animals↗
PubMed1986

Diverticular disease (adenomyomatosis) of the gallbladder: a radiological-pathological survey.

Seventy consecutive gallbladders removed at surgery were examined radiologically and pathologically. Fifteen (21%) of the operative specimens showed naked-eye changes of adenomyomatosis. The main conclusions drawn from this study are that this abnormality is present in a much higher proportion of gallbladders removed at surgery than is generally realised, and that the pathogenesis is primarily an abnormality of muscle contractions, with a strong similarity to diverticular disease of the colon. Diverticular disease of the gallbladder might well be the most appropriate name for this condition. The results of a post-operative clinical assessment of patients with diverticular disease are also presented. But this represents a small number of patients and larger, perhaps multicentre, surveys would be required in order to assess the clinical significance of this interesting abnormality.

Adult↗
PubMed1985

Stimulation of hypertrophy of cultured neonatal rat heart cells through an alpha 1-adrenergic receptor and induction of beating through an alpha 1- and beta 1-adrenergic receptor interaction. Evidence for independent regulation of growth and beating.

Catecholamines may be one of the molecular signals linking increased circulatory demand to myocardial hypertrophy, and I have found previously that norepinephrine stimulates hypertrophy of cultured neonatal rat heart muscle cells through an alpha 1-adrenergic receptor. Since catecholamine stimulation of contractility is believed to be under beta-adrenergic control, I asked whether these cultured heart cells had dual pathways regulating growth and contractility through alpha- and beta-adrenergic receptors, respectively. I examined the effect of adrenergic agents on hypertrophy and beating of myocytes in serum-free cultures. Hypertrophy was defined as an increase in myocyte surface area and in cell protein content, measured by a radioisotopic method, and chronotropic activity was examined visually. Norepinephrine and epinephrine were equipotent stimulants of hypertrophy and beating, increasing cell protein and area 1.5- to 2-fold, and the proportion of beating cells from 5% or less to 95%. Response maxima occurred 24-48 hours after exposure, and EC50 were 20-200 nM. Studies with other agonists (phenylephrine, methoxamine, clonidine, isoproterenol, dopamine) and antagonists (prazosin, terazosin, yohimbine, propranolol, betaxolol, ICI 118,551) indicated that hypertrophy was mediated through an alpha 1-adrenergic receptor, whereas the induction of beating required both alpha 1- and beta 1-receptor activation. Hypertrophied cells with minimal beating were produced by alpha-stimulation, alone. In contrast, alpha-plus beta-stimulation in the presence of cycloheximide to inhibit protein synthesis resulted in maximum beating but no hypertrophy. These findings imply that growth and beating can be regulated independently through separate cellular pathways.

Animals↗
PubMed1984

Failure of antihypertensive therapy with diuretic, beta-blocking and calcium channel-blocking drugs to consistently reverse left ventricular diastolic filling abnormalities.

The present protocol was designed to determine whether antihypertensive therapy with hydrochlorothiazide, propranolol or diltiazem, 3 agents with different mechanisms of action and potentially different effects on myocardial function, reverses left ventricular filling abnormalities. Twelve patients with essential hypertension and no evidence of associated cardiovascular disease, either clinically or with noninvasive testing, were evaluated while taking no medication and after 2 months of treatment with these agents. All 3 drugs produced equivalent control of blood pressure (BP), reducing sitting systolic BP by a mean of 20 to 24 mm Hg and diastolic BP by 14 to 16 mm Hg. LV ejection fraction and end-diastolic volume were normal in all but 1 subject (who was excluded from the analyses of LV diastolic filling) and were not altered by drug therapy. The peak LV filling rate and the first-third filling fraction were reduced in the patients with hypertension, but neither of these indexes nor the time to peak filling rate were significantly improved for the group as a whole by any of these medications. Nine of 10 patients whose BP was controlled by diltiazem had increases in their first-third filling fraction, but this change did not reach statistical significance. Our findings suggest that abnormalities of LV diastolic filling are not consistently affected by short-term therapy in patients with chronic, previously treated systemic hypertension.

Benzazepines↗
PubMed1984

Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide.

Fourteen hypertensive patients with a mean sitting systolic and diastolic blood pressure (BP) of 153 +/- 16/100 +/- 4 mm Hg were treated successively with hydrochlorothiazide and diltiazem for 8 weeks each. The BP response and changes in heart rate, left ventricular size and function, and plasma catecholamine concentrations and renin activity were monitored. The 2 drugs had comparable antihypertensive effects, with mean decreases of 14, 9 and 11 mm Hg for the sitting, standing and supine diastolic BP, respectively, during hydrochlorothiazide treatment and mean decreases of 16, 18 and 12 mm Hg during diltiazem treatment. Heart rate was unchanged, although plasma norepinephrine concentrations increased significantly during diltiazem treatment. Plasma renin activity increased slightly, from 0.6 to 0.9 ng/ml/hour during diltiazem treatment, but the change was not significant (p less than 0.10). Left ventricular ejection fraction and end-diastolic volume were not affected by either agent. In conclusion, diltiazem is an effective antihypertensive agent, which because of its benign side effect profile, may be useful as a step 1 agent.

Aged↗
PubMed1984

Monotherapy in mild to moderate hypertension: comparison of hydrochlorothiazide, propranolol and prazosin.

There has been recent interest in using nondiuretic drugs as initial antihypertensive therapy. Therefore, a study was designed to compare the efficacy and the effects on left ventricular function of hydrochlorothiazide, propranolol and prazosin in 13 patients with mild to moderate hypertension. After a 4-week washout period, patients were treated serially with each drug in a randomized order for 2 months each. Dosages were titrated until the patient showed a sitting diastolic blood pressure less than or equal to 90 mm Hg or to a maximum dosage of 100 mg/day of hydrochlorothiazide, 320 mg of propranolol and 20 mg of prazosin. Blood pressure was measured, plasma catecholamine concentrations were assayed and radionuclide determinations of rest and exercise left ventricular function and volume were made at the end of each period as well as after a second 1-month washout period at the end. In the sitting and standing positions, systolic and diastolic blood pressure control was equivalent for all 3 drugs. Goal blood pressure was achieved in 10 of 13 patients receiving hydrochlorothiazide, in 8 of 12 receiving propranolol and in 9 of 13 on prazosin. Importantly, 3 of 4 patients not controlled with prazosin, 5 of 6 uncontrolled with propranolol and 2 of 3 whose blood pressure was not reduced by hydrochlorothiazide were controlled when receiving 1 of the other medications. None of the drugs changed rest or exercise ejection fraction or volume, and side effects were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension.

This study was undertaken to determine the prevalence and significance of diastolic left ventricular (LV) dysfunction in mild to moderate systemic hypertension. Rest and exercise equilibrium blood pool scintigraphy was performed in 39 hypertensive subjects (mean systolic blood pressure [BP] 156 +/- 14 mm Hg [+/- standard deviation]; mean diastolic BP 103 +/- 5 mm Hg) and 11 normal control subjects. These studies were analyzed for ejection fraction (EF), segmental wall motion, peak filling rate (PFR), time to PFR and filling fraction in the first third of diastole normalized for cycle length (first-third filling fraction). EF at rest was similar in the hypertensive patients and control subjects (0.63 +/- 0.09 versus 0.65 +/- 0.07); only 2 patients had a reduced EF. The EF response to exercise was normal in every hypertensive patient (increasing to a mean of 0.74 +/- 0.08); only 1 patient had asynergy. In contrast, even when the 2 patients with abnormal systolic function were excluded, each index of diastolic filling was significantly different from the control group. PFR was lower (2.29 +/- 0.49 vs 2.63 +/- 0.39 end-diastolic volumes per second [EDV/s], p less than 0.05), time to PFR was longer (199 +/- 47 versus 158 +/- 17 ms/s), p less than 0.01) and first-third filling fraction was smaller (0.38 +/- 0.11 vs 0.60 +/- 0.07, p less than 0.001). The latter index fell below the lowest normal value in 84% of the hypertensive patients. The degree of diastolic filling abnormality was not related to the patients' age, heart rate, BP, duration of systemic hypertension or systolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Intrinsic and extrinsic control of growth in developing organs.

The growth rate and final size of developing organs is controlled by organ-intrinsic mechanisms as well as by hormones and growth factors that originate outside the target organ. Recent work on Drosophila imagined discs and other regenerating systems has led to the conclusion that the intrinsic growth-control mechanism that controls regenerative growth depends on position-specific interactions between cells and their neighbors, and that these interactions also control pattern formation. According to this interpretation, local growth by cell proliferation is stimulated when cells with disparate positional information are confronted as a result of grafting or wound healing. This local growth leads to intercalation of cells with intervening positional values until the positional information discontinuity is eliminated. When all discontinuities have been eliminated from a positional field, growth stops. In this article we consider the possibility that organ growth during normal development may be controlled by an intercalation mechanism similar to that proposed for regenerative growth. Studies of imaginal disc growth are consistent with this suggestion, and in addition they show that the cell interactions thought to control growth are independent of cell lineage. Developing organs of vertebrates also show intrinsic growth-control mechanisms, as demonstrated by the execution of normal growth programs by immature organs that are transplanted to fully grown hosts or to hosts with genetically different growth parameters. Furthermore, these organ-intrinsic mechanisms also appear to be based on position-specific cell interactions, as suggested by the growth stimulation seen after partial extirpation or rearrangement by grafting. In organs of most adult vertebrates, the organ-intrinsic growth-control system seems to be suppressed as shown by the loss of regenerative ability, although it is clearly retained in the limbs, tails and other organs of salamanders. The clearest example of an extrinsic growth regulator is growth hormone, which plays a dominant role along with insulin-like growth factors, thyroid hormone and sex hormones in supporting the growth of bones and other organs in postnatal mammals. These hormones do not appear to regulate prenatal growth, but other hormones and insulin-like growth factors may be important prenatally. The importance of other growth factors in regulating organ growth in vivo remains to be established. It is argued that both intrinsic and extrinsic factors control organ growth, and that there may be important interactions between the two types of control during development.

Ambystoma↗
PubMed1984

Effect of varying methods of upper limb occlusion on fibrinolytic activity in man.

Three techniques of intermittent venous occlusion (an oscillotonometer cuff, pneumatic leggings and an automatic arterial pressure monitoring cuff (Sentinel] were applied to one upper limb of seven healthy male volunteers. Fibrinolytic activity was assessed by the measurement of the euglobulin clot lysis time during a control period followed by 1 h of intermittent venous occlusion. Although no statistically significant differences were found with any of the methods, between the control and experimental periods, there was a trend towards fibrinolytic enhancement with intermittent pneumatic compression.

Adult↗
PubMed1983

A fatal case of lead poisoning due to a retained bullet.

Lead poisoning from a retained bullet or missile is rare and is usually dependent on the location of the missile in a bone or immediately adjacent to a joint. A review of the literature revealed only 14 cases in which there was adequate laboratory documentation of plumbism caused by a retained bullet or missile. Only one of these previously reported cases resulted in death. We report a second death due to lead poisoning from a retained bullet with elevated blood lead levels documented by toxicologic analysis.

Female↗
PubMed1983

Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response.

We have shown recently that norepinephrine stimulates muscle cell hypertrophy in primary cultures from the neonatal rat ventricle and that this stimulation is not blocked by the beta adrenergic antagonist propranolol. The present study was done to define the adrenergic specificity of the myocyte hypertrophic response to norepinephrine. 90% pure, single-cell cultures of nongrowing myocytes were maintained in serum-free medium 199 with transferin and insulin. Myocyte size was quantitated 48 h after addition of adrenergic agents, by measuring cell volume, cell surface area, and cell protein. L-norepinephrine increased myocyte size to a maximum 150% of control; half-maximum effect was obtained at a concentration of 0.2 microM. This increase in cell size was inhibited by the nonselective alpha adrenergic antagonist phentolamine and by the alpha 1 adrenergic antagonists prazosin and terazosin; it was not inhibited by propranolol or by the alpha 2 adrenergic antagonist yohimbine. The beta adrenergic agonist isoproterenol did not increase cell size. Thus, norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response.

Adrenergic alpha-Antagonists↗