Biomedical subjects

L T Ho

Publications and source records attributed to L T Ho.

At least 19 recordsLinked to original sources

PubMed1992

Hyperemia of injured peripheral nerve: sensitivity to CGRP antagonism.

Intrinsic mechanisms of vasodilatation may prevent injury-related ischemia in peripheral nerve endoneurium. We examined local perfusion up to 10 days following local crush, partial injury or simple exposure of the rat sciatic nerve. By employing epineurial hCGRP(8-37), a receptor antagonist of CGRP, and serial hydrogen clearance measurements, we estimated the component of post-injury blood flow related to local CGRP action. Injury-related ischemia was not observed at any of the time points studied at or proximal to injury. Instead, endoneurial blood flow (EBF) increased at 24 h proximal to crush or partial injury, and at 48 h within the crush zone when compared to sham operated controls or to a pooled reference range of EBF. Composite blood flow (F) was also elevated at 48 h and 5 days within the crush zone suggesting hyperemia involving the epineurial plexus, perineurial vessels and AV shunts. hCGRP(8-37) constricted vasa nervorum at most time points but its effect on EBF was maximum and exceeded controls within the crush zone at 48 h. The findings indicate that certain types of nerve injury, including focal crush, are associated with hyperemia, not ischemia. CGRP vasodilatation may account for part of this response, implying a local peptidergic afferent fiber response to nerve trunk injury.

Animals↗

PubMed1992

Intraventricular endothelin-1 uncouples the blood flow: metabolism relationship in periventricular structures of the rat brain: involvement of L-type calcium channels.

Endothelin-1 (ET) produces contraction of cerebral resistance vessels in vitro and in situ, but also is neuroactive causing increases in tissue energy metabolism as measured by [14C]deoxyglucose autoradiography in the intact rat brain. ET may, therefore, disengage the normally tight linkage between cerebral blood flow and tissue metabolism. Using anatomically rigorous autoradiographic and imaging techniques to measure focal blood flow in anesthetized, ventilated rats, we found that intraventricular injection of 9 pmol of ET reduced rates of perfusion by an average of 29% (compared to a saline-injected condition) in 6 individual periventricular structures bordering the injected lateral ventricle. A significant vasoconstrictor effect (41% decrease in blood flow) also occurred in the ipsilateral choroid plexus after ET injection, despite its increased rate of glucose metabolism. We employed a hydrogen clearance method to monitor rates of blood flow serially within the periventricular margin of the caudate nucleus after intraventricular injection of the dihydropyridine calcium-channel antagonist, nimodipine (72 nmol), or 9 pmol ET, alone and in sequence. Nimodipine increased caudate blood flow (by 47%) and prevented the vasoconstriction produced by ET. The results indicate that ET causes vasoconstriction in penventricular brain structures and choroid plexus even in the presence of substantial increases in glucose metabolism. The simultaneous stimulation by intraventricular ET of tissue hypermetabolic and vascular constrictor mechanisms, leading to a net reduction of periventricular blood flow, is mediated, at least in part, by dihydropyridine-sensitive calcium L-channels.

Anesthesia↗

PubMed1992

Normal blood flow but lower oxygen tension in diabetes of young rats: microenvironment and the influence of sympathectomy.

Studies of rats with experimental streptozotocin (STZ)-induced diabetes at 4 months have identified sciatic nerve trunk oligemia and hypoxia, but it is uncertain how early these abnormalities develop or which develops first. We studied young (4-week-old) rats after 6 or 16 weeks of STZ-induced diabetes (or after citrate buffer injection in controls) by recording multi-fiber conduction in three different nerve territories and by measuring sciatic endoneurial blood flow (NBF) and oxygen tension (PnO2) at end point. To evaluate the impact of sympathectomy on this diabetic model, separate animal groups were treated for 5 weeks with guanethidine monosulfate given at the onset of diabetes (group 1, end point 6 weeks) or after 6 weeks of diabetes (group 2, end point 16 weeks). Diabetes was associated with deficits in sensory and motor caudal conduction and increased resistance to ischemic conduction failure (RICF). NBF was comparable to control animals at both time points and was within the published normal range of NBF. In contrast, oxygen tensions were shifted to lower values in diabetic animals. Sympathectomy was associated with blunting of the RICF increase in group 2 but worsened caudal sensory conduction despite evidence of modest improvement in sciatic nerve oxygenation. Our findings support the concept that neuropathy occurs early in diabetes and that hypoxia develops before oligemia. Sympathectomy did not benefit this diabetic model.

Action Potentials↗

PubMed1992

Acute endoneurial ischemia induced by epineurial endothelin in the rat sciatic nerve.

Endothelin (ET) is a potent vasoconstrictor peptide that may have pathophysiological roles in the microcirculation of the peripheral nervous system. We examined the local action of epineurial ET-1 on sciatic endoneurial blood flow using serial hydrogen clearance measurements in anesthetized, paralyzed, and ventilated Sprague-Dawley rats. In separate rats, we made serial measurements of sciatic motor multifiber conduction before and then after application of epineurial ET (saline on contralateral nerve) 2 and 24 h and 4 and 7 days later. Epineurial bathing solutions of ET increased microvascular resistance and reduced local endoneurial blood flow in a dose-responsive fashion with a half-maximum effective concentration of 10(-8) M. Maximum vasoconstriction at 10(-6) M ET was associated with a fall in endoneurial blood flow from 18.7 (pre-ET) to 7.2 ml x 100 g-1 x min-1. Epineurial norepinephrine (10(-7) to 10(-10) M) also resulted in vasoconstriction, but of lesser degree. Pretreatment with intraperitoneal nimodipine, a dihydropyridine Ca2+ channel antagonist, but not phentolamine, prevented the vasoconstrictive action of ET. Three of eight animals developed temporary but complete axonal conduction block at the site of ET administration (10(-5) M) and four others had partial conduction block. Contralateral saline-treated sciatic fibers were unaffected. Local ET action on extrinsic epineurial microvessels results in reversible ischemia of the underlying endoneurium that may be associated with conduction block. ET's action is more potent than norepinephrine and appears dependent on L-type voltage-gated Ca2+ channels.

Action Potentials↗

PubMed1992

Insulin-pen: preliminary report on its use for multiple injection regiment in insulin-dependent diabetic patients.

Insulin pens are pen-like devices for multiple injection of insulin. They can cut down the equipment necessary for a multidose regimen and thus make the therapy more convenient and flexible to help improve daily-life quality. It is of interest for us to known whether the average diabetic patients are motivated to achieve better metabolic control by means of insulin-pens. Seven insulin-dependent diabetic patients (male: 3, female: 4, age: 21-34 years) from the Veterans General Hospital participated in the study. None of them had diabetic proliferative retinopathy or proteinuria. They are initially treated with twice daily injection of mixtures of short- and intermediate-acting insulin (run-in period, 8 weeks). A multi-dose regimen with three premeal injections of short-acting insulin with insulin-pen plus one injection of long-acting insulin at bedtime was then used during the study period (12 weeks). Improved in metabolic control as assessed by HbAlc (7.6 +/- 0.9 vs 6.9 +/- 0.8%) and mean blood glucose (175.2 +/- 34 vs 152.3 +/- 28.1 mg/dl) in all patients was found. The frequency and severity of hypoglycemic episodes were not changed. In addition, all patients chose to continue multiple injection using insulin-pen, indicating a high acceptability of such device.

Adult↗

PubMed1992

Metabolic control and B cell function in patients with diabetes mellitus secondary to chronic pancreatitis.

To investigate the relationship between metabolic control and beta cell functions in chronic pancreatitis, 30 patients were selected for study, including 10 with diabetes mellitus in insulin-dependent state (group 1, Mean age 37.6), 10 with diabetes mellitus in non-insulin-dependent state (group 2, Mean age 47.8), and 10 with normal fasting glucose levels (group 3, Mean age 42.1). Each patient received urine routine, stool fat, renal function, biochemical study such as: serum lipid and glycosylated hemoglobin, eye fundi and X-ray examinations. Beta cell function was measured by C-peptide concentration six minutes after intravenous infusion of 1 mg glucagon. The results showed that the glycosylated hemoglobin concentrations were higher in group 1 than in group 2 or 3 patients (P less than 0.05), and were higher in group 2 than in group 3 patients (P less than 0.001) as well. The cholesterol and triglyceride levels were not significantly different among three groups. Furthermore, eight and two of group 1 and 2 patients manifested pancreatic calcification on abdomen X-ray examination (P less than 0.05). All and eight of group 1 and 2 patients received insulin injection respectively. In addition, group 1 patients were more likely to develop steatorrhea, other associated diseases and uncontrolled plasma glucose levels as compared with group 2 patients. In conclusion, insulin-dependent pancreatic diabetics had more advanced disease process and were therefore more likely to get other associated diseases than noninsulin-dependent pancreatic diabetics.

Adult↗

PubMed1992

The establishment of radioimmunoassay of cyclic AMP.

Succinyl cyclic AMP, coupled with human albumin, was injected into rabbit to elicit antibodies to the cyclic nucleotide hapten. The succinyl cyclic nucleotides were conjugated to human albumin through a carbodiimide coupling procedure. The radioligand was prepared essentially by the modified method of Hunter and Greenwood. The resulting radiolabeled 125-ScAMP-TME was subsequently purified by reverse phase chromatography on Seppak C18 cartridge and used as tracers. Free and bound form of labeled antigens in the assay system were separated according to their differences in adsorption to solid material, i.e., charcoal. The antisera in routine use had 8% cross-reactivity with cyclic GMP, but had no cross-reactivity with ADP, 5'-AMP or ATP. The sensitivity of the assay in standard was around 0.05 pmol/ml. The sequential saturation analysis system was superior to the equilibrium study in terms of its sensitivity in standard curve determination. The media dilution and recovery studies showed good parallelism with the standard curve. The intra-assay and inter-assay coefficient variations were 5% and 7%, respectively. It showed that a significant increase in tracer binding to the antibodies in equilibrium incubating system was obtained when they were incubated at 4 degrees C for up to 72 hours. When the standard curve was derived for Scatchard plot analysis, Kd of the curve decreased inversely with the increase of the antibodies diluted, the total binding capacity of the antibody would not alter. A thyroid-stimulating hormone produced a normal response of cyclic AMP concentrations in FRTL-5 tissue cultures.

Animals↗

PubMed1992

Arginine induced insulin release in patients with newly onset non-insulin-dependent diabetes mellitus.

To examine the release of insulin in response to oral glucose, intravenous glucagon and intravenous arginine, we measured the levels of plasma glucose, immuno-reactive insulin (IRI) and C-peptide levels on fasting and following an oral glucose loading (OGTT), intravenous glucagon (GON) and arginine (ARG) infusion test in nine newly diagnosed non-insulin dependent diabetics. Their ages ranged from 38 to 65. The fasting plasma glucose and hemoglobin A1c levels were 240 +/- 14 mg/dl (Mean +/- SEM) and 10.7 +/- 0.54%, respectively. Mean values of the peak C-peptide/fasting C-peptide ratio and peak IRI/fasting IRI ratio were significantly increased, as compared with the basal level (P < 0.05), but not significantly different from those of the OGTT, GON and ARG test. In conclusion, the effect of arginine-induced insulin secretion in non-insulin dependent diabetes mellitus is as good as those of glucose or glucagon.

Adult↗

PubMed1992

Diurnal variation of insulin sensitivity in NIDDM patients and normal subjects.

A modified insulin suppression test was adopted to assess the diurnal variation in insulin sensitivity and insulin clearance in 14 non-insulin-dependent diabetes mellitus (NIDDM) patients and eight age-, sex- and weight-matched normal subjects. The modified insulin suppression test was combined with an infusion of regular insulin, 30 mU/min x m2; glucose, 6 mg/kg x min; and somatostatin, 500 micrograms/h, for 120 minutes followed by only a somatostatin infusion for 60 minutes. Blood samplings were performed at appropriate times to obtain data on steady-state plasma insulin (SSPI), steady-state plasma glucose (SSPG as an index of insulin sensitivity), metabolic clearance and the half disappearance time (T1/2) of insulin. Blood specimens were also obtained during SSPI for measurement of erythrocyte insulin receptor binding. Each subject took the insulin suppression test twice. One test was started at 8 am and the other at 4 pm; each test was preceded by 16 hours of fasting. The order of the insulin suppression tests in each subject was randomized and balanced. In normal subjects, the SSPG level was lower in the morning than in the afternoon (118.0 +/- 43.6 vs 150.3 +/- 34.2 mg/dL, p less than 0.05). The NIDDM patients had a higher SSPG in the morning (217.7 +/- 51.4 vs 188.3 +/- 40.6 mg/dL, p less than 0.01). There was no diurnal difference in insulin clearance or the T1/2 in either normal subjects or NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

The influence of indomethacin and guanethidine on experimental streptozotocin diabetic neuropathy.

In diabetic animals, reduced endoneurial perfusion and oxygen content have been linked to neuropathic abnormalities and might be amenable to pharmacological manipulation. In streptozotocin-induced diabetic rats, we studied the influence of guanethidine adrenergic sympathectomy, indomethacin treatment and a combined strategy on: serial in vivo motor and sensory conduction, resistance to ischemic conduction failure, in vitro myelinated and unmyelinated conduction, endoneurial perfusion and endoneurial oxygen tension. Unlike previous work diabetic animals had normal endoneurial perfusion but lower endoneurial oxygen tensions after six months of hyperglycemia. Guanethidine worsened sensory conduction despite lower microvascular resistance and an improvement in endoneurial oxygen tension. In contrast, indomethacin improved motor and sensory conduction but not oxygen tension. These studies do not support a linkage between conduction deficits and early endoneurial microangiopathy in experimental diabetes. Indomethacin, or related agents may offer a new therapeutic approach toward diabetic neuropathy through a mechanism independent of the endoneurial microvasculature.

Animals↗

PubMed1991

Unique microvascular characteristics of the dorsal root ganglion in the rat.

Physiological characteristics of dorsal root ganglia microvessels have not been reported in detail. In this study we examined local blood flow and oxygen tension in the L4 dorsal root ganglion (DRG) of the rat. Under normal physiological conditions, local DRG blood flow measured 36.1 +/- 2.7 ml/100 g/min, over twice that within the endoneurium of the sciatic nerve. DRG blood flow was better maintained during hypotension than endoneurial blood flow suggesting partial autoregulation. Unlike endoneurium, there was relative constancy of flow between mean arterial pressures of 60 and 120 mm Hg. Hypercarbia with acidosis, and hypocarbia with alkalosis did not influence blood flow. The histogram of oxygen tensions within the dorsal root ganglion resembled that in brain but included more values at lower tensions than observed in published endoneurial histograms. Theses findings suggest that the DRG differ from endoneurium in ways that reflect the higher metabolic requirements of neural soma.

Acidosis↗

PubMed1991

Stimulation-induced peripheral nerve hyperemia: mediation by fibers innervating vasa nervorum?

We studied the influence of graded nerve trunk stimulation on endoneurial blood flow (NBF), oxygen tension and pH in the rat sciatic nerve. The purpose of the investigation was to explore changes in the in vivo microenvironment of axons which result from their metabolic activation. Using endoneurial microelectrodes, we made serial measurements before, during and after varying stimulation protocols in curarized animals. NBF was increased by stimulation and the effect was directly related to the frequency, length and intensity of the stimulation train. At an intensity designed to supramaximally recruit myelinated fibers, high frequency (50 and 100 Hz) and prolonged duration (5-15 min) stimulation increased NBF. The effect was partly blocked by infiltration of lidocaine at the stimulating site. High intensity stimulation, designed to also recruit unmyelinated fibers, was particularly effective in enhancing NBF and lowering microvascular resistance. Continuous measurements of endoneurial oxygen and pH tension failed to identify associated declines with stimulation irrespective of the protocol. Both oxygen tension and pH tended to rise with stimulation. These studies confirm the presence of stimulation-induced endoneurial hyperemia but provide no evidence that local hypoxia or acidosis are mechanisms. Stimulation recruitment of vasodilatory axons innervating vasa nervorum may be an alternative explanation.

Acidosis↗

PubMed1991

Electropharmacological effects of sandostatin in human atrial fibers.

We studied the actions of sandostatin (0.1-1000 nM), an analogue of somatostatin, on human atrial tissues obtained from hearts of 20 patients undergoing corrective cardiac surgery. In 3 preparations showing fast response action potential in normal [K]0 Tyrode solution, sandostatin induced little effect, even at the highest concentration (1 microM). In 10 preparations showing a slow rate of phase-0 depolarization when atrial fibers were depolarized (maximum diastolic potential near -40 mV) in high [K]0 (27 mM), sandostatin at concentrations as low as 1 nM decreased significantly the velocity of the upstroke, and the amplitude of slow response of the action potential as well as the force of contraction. In 6 experiments on spontaneously active atrial fibers (maximum diastolic potential = -53.8 +/- 2.7 mV), sandostatin increased the spontaneous cycle length in a fashion dependent upon concentration. The decrease in spontaneous rate of firing was associated with an inhibition of the late diastolic slope, a change also induced by somatostatin. A longer period of washout, however, (30 min or longer) was required for complete recovery from the depressant effects. Sandostatin (0.1-100 nM) also depressed triggered activity induced by cardiotonic agents. The present findings indicate that sandostatin induces a prolonged action in human atrial cells. Sandostatin may depress abnormal automatic rhythms through an inhibition of transmembrane influx of calcium.

Action Potentials↗

PubMed1991

Influence of perivascular peptides on endoneurial blood flow and microvascular resistance in the sciatic nerve of the rat.

1. A variety of vasoactive peptides has been identified in the axon terminals innervating vasa nervorum but their function is unknown. In mesenteric arterioles, substance P (SP) and calcitonin gene-related peptide (CGRP) have been postulated to have a role in tonic vasodilatation. 2. We explored the effect of epineurial capsaicin, SP, CGRP, spantide (SP antagonist), and hCGRP (8-37) (CGRP antagonist) on blood flow (EBF) and microvascular resistance (EMR) in the endoneurial compartment of the rat sciatic nerve, as measured by hydrogen clearance. 3. Epineurial capsaicin induced a prompt, intense and prolonged increase in EBF and lowering of EMR as compared to epineurial application of the carrier alone in a separate animal group. The hyperaemic response was also confirmed by studying serial clearance curves in individual animals. 4. Multifibre sciatic-tibial motor conduction was not changed by epineurial capsaicin. 5. When co-administered with capsaicin, hCGRP (8-37) completely blocked the hyperaemic response and increased EMR above the pooled control range. Spantide also blocked the capsaicin response. 6. When administered alone, both epineurial hCGRP (8-37) and spantide lowered EBF below and increased EMR above the control measurements in the same animals. 7. At 10(-5) M epineurial CGRP, but not SP lowered EMR. Vasodilatation from intra-arterial administration of CGRP was much greater and was more prolonged compared with that induced by SP. hCGRP (8-37), but not spantide reduced the intra-arterial response to CGRP. 8. The findings suggest that epineurial peptidergic terminals mediate a vasodilatory response (particularly through CGRP) that increases blood flow in the 'downstream' endoneurial compartment. Physiological peptide release (blocked by SP and CGRP receptor antagonism) may be important in maintaining tonic vasodilatation.

Animals↗

PubMed1991

Abnormal thyroid hormone levels in critical nonthyroidal illness.

Low levels of thyroid hormone in the absence of clinical hypothyroidism often happen to patients with critical non-thyroidal illnesses (NTI). Low thyroid hormone concentrations in serum do not necessarily mean hypofunction of the thyroid gland; rather it is a helpful adaptation of the human body to the underlying diseases. We collected 133 hospitalized cases of critical NTI and analyzed the incidence of this phenomenon. Fifty-three per cent of the patients had T3 level lower than 60 ng/dl (normal:85-165 ng/dl) and 60% had T4 level lower than 6 ug/dl (normal:6-12 ug/dl). The lowest levels were observed in patients who had sepsis, were aged over 70 or died in this admission. Free T4 and TSH levels were within normal range in most cases. There is a strong negative correlation between the prognosis and the level of T4 in these patients. Those patients with markedly low levels of T3 and T4 should be treated more sophisticatedly.

Humans↗

PubMed1991

Insulin treatment improved glucose-induced insulin release in elderly non-insulin-dependent diabetes mellitus, secondary failure to oral hypoglycemic agents.

In order to observe whether the improvement of diabetic control would promote insulin release of elder non-insulin-dependent diabetics, we performed oral glucose tolerance test and glucagon infusion in eight patients before and after fasting plasma glucose normalized with insulin therapy for three weeks. The levels of plasma glucose and C-peptide both on fasting and following intravenous glucagon infusion and oral glucose loading were measured. Their ages ranged from 60 to 72 years old. The initial fasting plasma glucose levels were 261 +/- 18 mg/dl (Mean +/- SEM). After insulin therapy for three weeks, the fasting plasma glucose levels dropped to 130 +/- 8 mg/dl (Mean +/- SEM, P less than 0.001). The fasting C-peptide/glucose ratio showed no difference before and after therapy. On the other hand, the C-peptidogenic index was markedly improved following insulin therapy, as compared with the value before therapy (P less than 0.05). These results suggested that greater C-peptide response was found in non-insulin dependent elderly diabetics following oral glucose after plasma glucose normalized with insulin therapy.

Administration, Oral↗

PubMed1991

Recombinant DNA produced somatropin in the treatment of prepubertal growth hormone deficient children.

The safety and efficacy of recombinant DNA produced human growth hormone in the treatment of growth failure in prepubertal children with idiopathic or organic deficiency of pituitary GH has been assessed. Five patients entered this clinical trial. They had never been treated with hGH, anabolic steroids or any medicine that affected GH and all of them were healthy without any chronic disease; except patient 1, who took a surgical operation for cerebellar astrocytoma at the age of 3. Each patient was treated with subcutaneous injection of recombinant somatropin (SAIZEN) at a dosage of 0.2 IU/Kg +/- 10% three times per week in the evening for 1 year. Typical catch up growth was observed. The height increased by between 6.3 and 15.1 cm and their mean growth velocity of 3.7 cm/yr prior to therapy increased to 11.1 cm/yr during one year of treatment. The annual change in bone age during the treatment with SAIZEN was 2.0 +/- 0.6 years in four patients, except patient 2 who showed different bone age (right hand 3.5 years, left hand 6.0 years). Anti-hGH antibodies were observed in patient 1, but the binding capacity was low (1:10), and no clinical symptoms or growth attenuation occurred. No side effects or laboratory abnormalities were noted throughout the clinical trial. In conclusion, recombinant somatropin has a growth promoting effect and low immunogenicity, and it is shown to be safe and effective during the first year of therapy in children with GH deficiency.

Body Height↗

PubMed1990

Endoneurial microenvironment and acute nerve crush injury in the rat sciatic nerve.

In severe peripheral nerve ischemia in the rat, serial nerve blood flow (NBF) measurements have identified evidence of 'no reflow', a mechanism of continued fiber damage during reperfusion. It has been postulated that 'no reflow' also occurs in nerve compression due to direct mechanical or ischemic (if compression is prolonged) injury of microvessels, resulting in continuing nerve fiber damage. To address this question, we measured endoneurial blood flow (NBF), oxygen tension and pH at the site of an acute nerve crush injury. In further sets of experiments, NBF and endoneurial oxygen tension were examined before and after prolonged epochs of crush. NBF and MR (microvascular resistance) were not appreciably different than values obtained in control animals without intervening brief nerve crush. NBF was slightly higher and MR slightly lower 2 h after injury, but the difference was not statistically significant. No evidence of significant endoneurial hypoxia or acidosis was observed. Similarly, after more prolonged crush there was no significant oligemia or hypoxia. The studies provide no evidence that 'no reflow' occurs in crush injury even if the injury is maintained for a period of time known to induce 'no reflow' with severe ischemia. We suggest that nerve damage in crush, and possibly compression, more likely arises from direct mechanical injury of fibers.

Animals↗