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Biomedical subjects

C M Williams

Publications and source records attributed to C M Williams.

At least 145 records · Page 8Linked to original sources

Short-loop negative and positive feedback on ecdysone secretion by prothoracic gland in the tobacco hornworm, Manduca sexta.

Ecdysteroid production by the prothoracic glands of the tobacco hornworm, Manduca sexta was found to be under feedback control by the ecdysteroids in hemolymph using both culture in vivo in diapausing pupae lacking the brain-corpora cardiaca-corpora allata complex and the prothoracic glands and culture in vitro. Prothoracic glands having relatively high activity in larvae, prepupae, or developing pupae were inhibited by ecdysone or 20-hydroxyecdysone. By contrast, prothoracic glands with low activity from feeding larvae, day 1 non-diapausing pupae and diapausing pupae were activated by both ecdysone and 20-hydroxyecdysone in vivo and in vitro. Dose-response studies on diapausing pupal glands showed that ecdysone was the most effective activator. These findings suggest that prothoracic glands are either stimulated or inhibited by ecdysone or 20-hydroxyecdysone, depending on both the secretory activity of the gland and the effective level of ecdysteroids in hemolymph. Thus, when the glands are first activated, the ecdysteroids that are secreted show a positive feedback on the glands to increase ecdysteroid output. Then the activated glands are turned off by the increasing 20-hydroxyecdysone titer in the hemolymph leading to the rapid decrease in ecdysteroid titer at the end of the molt period.

Animals↗

The effect of a low-fat diet on luteal-phase prolactin and oestradiol concentrations and erythrocyte phospholipids in normal premenopausal women.

1. Fifteen normal premenopausal women followed a low-fat diet for a period of 2 months. 2. Daily fat intake was reduced from 81 g on their customary diet to 36 g on the low-fat diet. A significant reduction in total energy intake and an increase in the dietary polyunsaturated fat: saturated fat ratio was also observed. There was a significant decline in body-weight, percentage body fat and total serum cholesterol, but no significant change in high-density-lipoprotein-cholesterol. 3. Luteal-phase prolactin concentrations were not altered, but there was a significant decline in oestradiol concentrations on the low-fat diet. The proportion of erythrocyte inositol-phospholipid was increased on the low-fat diet and there was a significant increase in the 20:4 omega 6 (arachidonate) content of inositol-phospholipids. No significant changes in the content or fatty acid compositions of other phospholipid fractions were observed. 4. Further investigation of the effect of level and type of dietary fat on the content and fatty acid composition of membrane inositol-phospholipids are required. Long-term studies investigating the response of both prolactin and oestradiol to dietary fat reduction are also warranted.

Adolescent↗

The captopril glomerular filtration rate renogram in renovascular hypertension.

Administration of captopril to animals with two-kidney, one clip, renovascular hypertension (RH) lowers the glomerular filtration rate (GFR) in the clipped kidney. The authors therefore tested the hypothesis that a decrease in GFR after captopril administration would identify patients with RH. Total GFR was measured by the plasma disappearance of Tc-99m-diethylenetriaminepentaacetic acid (DTPA) after bolus injection and single-kidney GFR from renal uptake of DTPA assessed by renography. The authors studied six patients with arteriosclerotic RH who had strongly lateralizing renal vein renin levels and greater than 80% stenosis of the renal artery to that kidney. Results were contrasted with those of six patients with essential hypertension (EH) with a similar mean arterial blood pressure (MABP). Captopril (50 mg orally) increased total GFR (ml/min) in all patients with EH (102 +/- 8 to 120 +/- 12, P less than 0.005). However, GFR decreased in patients with RH (73 +/- 8 to 61 +/- 9, P less than 0.05) after captopril. Although the single-kidney GFR of patients with RH decreased in all six stenotic kidneys (27 +/- 4 to 21 +/- 5, P less than 0.02), it did not change consistently in the contralateral kidneys (45 +/- 8 to 40 +/- 6, N.S.). Clonidine (0.3 mg) also lowered MABP in patients with RH but, unlike captopril, it did not reduce total kidney GFR (75 +/- 10 to 79 +/- 11, N.S.). In conclusion, short-term captopril administration increases GFR in patients with EH, but decreases it in those with RH. This action is unrelated to its depressor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Improved detection of healed myocardial infarction by Fourier amplitude and phase imaging in two projections: validation with MRI.

Biplane Fourier amplitude and phase images from radionuclide ventriculograms were analyzed for the presence of regional wall motion abnormalities in 25 patients who had a total of 33 healed myocardial infarctions (nonviable scar tissue) documented by contrast ventriculography and ECG. This indirect evidence was validated by MRI, which permits direct visualization of healed myocardial infarction. The use of amplitude and phase images in both projections resulted in the detection of more healed myocardial infarctions (91%) than did the use of conventional radionuclide ventriculography with left anterior oblique images alone (67%), because inferior wall infarcts are more readily visualized in the left posterior oblique projection.

Adult↗

A controlled trial of sip-feed supplements in elderly orthopaedic patients.

The potential nutritional and clinical benefits of sip-feed supplements were investigated by means of a controlled trial in elderly female patients admitted for orthopaedic surgery. A nutritional risk assessment procedure (Nutritional Risk Questionnaire, NRQ) was used to identify patients who might benefit from supplementation. Patients identified as high risk who did not receive supplements showed significant losses in triceps skinfold thickness (TSF) and mid-upper arm muscle circumference (MUAMC) measurements during hospitalization. Such changes were not observed in high-risk supplemented patients, but significant losses of MUAMC were also recorded in a group of patients who failed to comply with the supplement. No differences in biochemical parameters, muscle function, or clinical outcome were observed between supplemented and unsupplemented and non-compliant patients. The problems of poor compliance to sip-feed supplements and failure to observe clinical benefit in supplemented patients are discussed.

Aged↗

Pectin delays gastric emptying and increases satiety in obese subjects.

As pectin delays gastric emptying in normal subjects and satiety may be linked to the rate of gastric emptying, we designed this study to evaluate, in a group of obese subjects, the effect of adding pectin to a meal on gastric emptying, sensation of satiety, and postprandial plasma cholecystokinin and pancreatic polypeptide levels. We studied gastric emptying of solids in 9 adult obese subjects on 2 separate days in a randomized fashion. On day 1, 15 g of pectin was added to the meal, and on day 2 15 g of methylcellulose was added and served as control. Satiety was evaluated by an analogue rating scale. Pectin significantly delayed gastric emptying time [t1/2 = 116 +/- 23 min vs. 71 +/- 17 min observed with methylcellulose (p less than 0.001)]. Pectin also significantly increased subjects' sensation of satiety [98 +/- 7 vs. 74 +/- 17 (p less than 0.001)]. Postprandial release of cholecystokinin and pancreatic polypeptide was not modified by pectin. As pectin induces satiety and delays gastric emptying in obese patients, it may be a useful adjuvant in the treatment of disorders of overeating.

Adult↗

Fetal growth, glucose tolerance and plasma insulin concentration in rats given a marginal-zinc diet in the latter stages of pregnancy.

1. Wistar rats were fed on a control semi-synthetic diet throughout pregnancy, or a control diet in the first 2 weeks and a marginal-zinc diet in the 3rd week of pregnancy. On day 20, after an overnight fast, half the animals in each group were given glucose by gavage and the 0-30 min rise in blood glucose measured in tail blood. After 60 min blood was taken by cardiac puncture for glucose and insulin assay. Maternal pancreases were removed and the Zn contents measured. Fetuses from each litter were combined for wet/dry weights, protein and DNA determinations. 2. Plasma insulin concentration was higher, and glucose concentration and pancreatic Zn content lower, in pregnant v. non-pregnant animals of similar age, fed on the same diet. Pancreatic Zn content was lowest in the marginal-Zn group of pregnant rats. Fetuses from mothers fed on the marginal-Zn diet during the last week of pregnancy were slightly heavier than controls and had a significantly higher protein: DNA ratio. The 0-30 min rise in blood glucose was significantly greater in the marginal-Zn animals. 3. In a second experiment, pregnant rats were given similar diets to those used in the first study, but the marginal-Zn diet was given for a shorter period (days 15-19 of pregnancy). On day 19 the rats were meal-fed and on day 20, after an overnight fast, an oral glucose dose was administered. Tail-blood was taken at timed intervals up to 60 min post-dosing for glucose assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diagnostic uses of angiotensin-converting enzyme inhibitors in renovascular hypertension.

The response to angiotensin-converting enzyme inhibitors (ACEIs) can be of considerable help in the diagnosis of human renovascular hypertension (RVH) in three settings. First, a particularly dramatic antihypertensive response or a decline in glomerular filtration rate (GFR), as indexed by a rise in serum creatinine or blood urea nitrogen concentrations, are useful clues to the presence of renovascular hypertension. Second, an exaggerated rise in plasma renin activity (PRA) after short-term captopril administration is a very promising screening test for this condition. Third, ACEI-induced changes in single-kidney hemodynamics (assessed by renography) may be helpful in confirming the diagnosis and offers the prospect of localizing the ischemic kidney.

Angiotensin-Converting Enzyme Inhibitors↗

Activities of octopamine and synephrine stereoisomers on alpha-adrenoceptors.

1. The activities of the (-)- and (+)-forms of m- and p-octopamine and m- and p-synephrine on alpha 1-adrenoceptors from rat aorta and anococcygeus and alpha 2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA). 2. The rank order of potency of the (-)-forms on alpha 1-adrenoceptors from rat aorta and alpha 2-adrenoceptors was NA greater than m-octopamine = m-synephrine greater than p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on alpha 1-adrenoceptors from rat aorta and 150 fold less active on alpha 2-adrenoceptors. The two p- compounds were 1,000 fold less active than NA on both alpha 1-adrenoceptors from rat aorta and alpha 2-adrenoceptors. The rank order of potency of the (-)- forms on alpha 1-adrenoceptors from rat anococcygeus was NA = m-synephrine greater than m-octopamine greater than p-octopamine = p-synephrine. m-Octopamine was 4 fold less active than NA and (-)-m-synephrine. The two p- compounds were 30 fold less active than NA. 3. The rank order of potency of the (+)- forms was NA greater than m-octopamine greater than m-synephrine greater than p-octopamine greater than p-synephrine on both alpha 1- and alpha 2-adrenoceptors. The potency of each (+)- form was 1-2 orders of magnitude less than that of the (-) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both alpha 1- and alpha 2-adrenoceptors. 4. The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (-)-NA and (-)-m-octopamine-induced contractions in both preparations. Based upon the known selectivities of these isomers for alpha-adrenoceptor subtypes, it is concluded that the rat aorta contains only alpha 1-adrenoceptors while the rabbit saphenous vein possesses predominantly alpha 2-adrenoceptors. 5. Ligand binding data for the octopamine and synephrine stereoisomers at alpha 1- and alpha 2-binding sites from rat cerebral cortex was also obtained. (-)-Forms were more active than (+)-forms. The rank order of affinity of the (-)-forms for both alpha 1- and alpha 2-binding sites was NA greater than m-octopamine = m-synephrine greater than p-synephrine greater than p-octopamine. The relative affinities of the members of the series against alpha 1-binding sites were very similar to their relative functional activities on rat aorta. However, the affinities of both m- and p-compounds relative to that of ( -)-NA were much greater at the x2-binding sites than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (-)-octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. 6. The activities of m-octopamine and m-synephrine were not significantly different from each other on either a,-adrenoceptors from rat aorta or x2-adrenoceptors; however, m-synephrine is more active than m-octopamine on a,-adrenoceptors from rat anococcygeus. Both m-octopamine and msynephrine can be considered to be naturally occurring x,-selective amines. However, if m- and poctopamine are co-released with NA in amounts proportional to their concentration, it is concluded that their activities on m,- and x2-adrenoceptors are too low to be physiologically significant.

2-Hydroxyphenethylamine↗

Extracorporeal shock-wave lithotripsy: prevalence of renal stones 3-21 months after treatment.

One hundred and four (70%) of the first 148 patients who underwent extracorporeal shock-wave lithotripsy (ESWL) at the University of Florida were evaluated for persistent or recurrent renal stone disease. Radiographs obtained 3-21 months after treatment showed that 53 (50%) of 106 treated kidneys were free of stones. In 48 of the 53 kidneys that contained stones, the stones were residual fragments dating from the period immediately after ESWL. New stones had developed in only five kidneys. The 50% incidence of stone-free kidneys 3-21 months after ESWL is less than the 65-90% rate reported by other institutions in the United States and Europe. After stone removal by ESWL, new stone formation occurs at a rate of 5%, which is much lower than the expected recurrence rate of 37-50%.

Follow-Up Studies↗

Extracorporeal shock-wave lithotripsy: long-term complications.

Of 148 patients who had extracorporeal shock-wave lithotripsy (ESWL) for renal lithiasis in 1984, 21 (14%) returned after 17-21 months for renal function tests (21 patients) and blood pressure determination (20 patients). Quantitative radionuclide renography showed a statistically significant (p = .048) decrease in the percentage of effective renal plasma flow (ERPF) to the treated kidney. Two of these patients had developed hypertension requiring treatment but became normotensive when given medication. In the other patients there was a statistically significant increase in both systolic (p = .0002) and diastolic (p = .015) blood pressures. Information about blood pressure was also obtained from an additional 71 (48%) of the 148 patients; of the total 91 patients (61%) in whom blood pressures were obtained, seven (8%) had developed sufficiently severe hypertension to require treatment beginning within 21 months after ESWL. Side effects of ESWL for renal lithiasis include hemorrhage, edema, and acute tubular necrosis of the kidney. This form of renal trauma is associated with an immediate decrease in renal function of the treated kidney, and this decrease may be permanent. ESWL is also associated with the onset of hypertension, which may occur immediately or be delayed by several weeks or months. Although the pathogenesis remains unknown, hypertension is an important complication of ESWL in about 8% of patients.

Adult↗

In vivo binding in rat brain and radiopharmaceutical preparation of radioiodinated HEAT, an alpha-1 adrenoceptor ligand.

In vivo binding of [125I]-2-[beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl tetralone) ([125I]HEAT) to alpha-1 adrenoceptors in the rat brain was determined over 4 hr. Uptake in the thalamus and frontal cortex was approximately 0.1% injected dose per gram tissue. Thalamus/cerebellum ratios of 10:1 and frontal cortex/cerebellum ratios of 5:1 were found at 4 hr. Pretreatment with prazosin, an alpha-1 antagonist, completely inhibited the accumulation of [125I]HEAT in thalamus and frontal cortex; yet uptake of radioactivity was not significantly affected by antagonists and agonists for other receptors classes (propranolol, beta-1; apomorphine, D-1; spiperone, D-2). Binding of [125I]HEAT is saturable. At 4 hr, [125I]HEAT or [123I]HEAT was shown to be the only radioactive material in rat thalamus and frontal cortex. Iodine-123 HEAT and [125I]HEAT were synthesized as radiopharmaceuticals within 3 hr in 99% radiochemical purity.

Adrenergic alpha-Antagonists↗

Biodistribution and radiation dosimetry of radioiodinated-SCH 23982, a potential dopamine D-1 receptor imaging agent.

Radioiodinated-SCH 23982 is a potential agent for the imaging of dopamine D-1 receptors in the human brain. In vivo binding of [125I]SCH 23982 to D-1 receptors in rat brain was determined over 4 hr. The ratio of activity in striatum and frontal cortex to that in cerebellum increased over the first 2 hr to maximum values of 4.4:1 and 2.1:1, respectively. The percent injected dose in whole brain at 0.5 and 2 hr were 0.62 and 0.15, respectively. Administration of the antagonists propranolol (beta-1), prazosin (alpha-1), haloperidol (D-2) and ketanserin (5HT-2) did not significantly alter the striatum/cerebellum ratio; however, SCH 23390, a D-1 antagonist, totally blocked ligand uptake by striatum and frontal cortex. Biologic distribution data in the rat were determined after injection of 3 microCi of [125I]SCH 23982. 76% of the injected dose was excreted in 48 hr via the liver and kidneys. Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads and red bone marrow were calculated for humans using the physical decay data for 123I. The critical organ was found to be the lower large intestine which received 1.1 rad/mCi of the administered dose. The total-body dose was 63 mrad/mCi. The data indicate that [123I]SCH 23982 should be a suitable agent for imaging the D-1 dopamine receptor in the human brain by single photon emission computed tomography.

Animals↗

Iron and zinc status in multiple sclerosis patients with pressure sores.

Measurements of weighted dietary intakes and plasma determinations of albumin, iron, zinc, ascorbic acid and TIBC were carried out on twenty female multiple sclerosis patients in a long-stay hospital for disabled people. The group included ten patients with a recent history of pressure sores, closely matched with ten patients without pressure sores. Mean daily intake of carbohydrate was found to be higher in the non-pressure sore group whilst intake of zinc was lower in this group. Intakes of all other nutrients were comparable between the two groups. For both groups, intakes of energy, folate, vitamin D, iron and zinc were less than recommended values. Mean plasma levels of albumin and iron were towards the lower limit of the normal range, whilst that for zinc was considerably less than the normal range. Plasma TIBC was slightly above the normal range. Levels of plasma iron and zinc were significantly lower in the pressure sore group. The data indicate that severely disabled hospitalized patients with multiple sclerosis may be at risk of poor nutritional status. The results suggest that in the presence of pressure sores, there are increased requirements for specific nutrients, notably zinc and iron. Consideration is given to the possible value of supplementation of these individuals.

Aged↗