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Biomedical subjects

K Y Ho

Publications and source records attributed to K Y Ho.

At least 91 records · Page 5Linked to original sources

[Contralateral hearing and tympanoplasty].

The contralateral hearing level of the operated ear is closely related to its preoperative hearing level, and is an important index to the success of tympanoplasty. We analysed 146 cases of chronic otitis media who had received tympanoplasty by the same surgeon at Kaohsiung Medical College Hospital. From the results of pure tone audiometry, we divided the hearing acuity into the following 5 categories: normal hearing, mild hearing loss, moderate hearing loss, severe hearing loss, and deafness. Referring to the categories of contralateral hearing, we discuss the preoperative hearing level of the operated ear, the occurrence of cholesteatoma, the type of the tympanoplasty, and the auditory gain of the operation. While 23.97% cases had moderate or severe loss of contralateral hearing, their hearing acuity of the operated ear was also poor. Most of cases with normal contralateral hearing received type I tympanoplasty. Compared to the above group, half of the cases with moderate or severe contralateral hearing loss received type III or type IV operations to reconstruct the ossicle chain. Though the type I cases had more hearing gains than the type III cases, those with moderate contralateral hearing loss had good results from the type III tympanoplasty. We also found the cases with cholesteatoma in the operated ear had better contralateral hearing in the contralateral ear than the cases without cholesteatoma. The decision to perform tympanoplasty in cases of the better hearing ear with poor contralateral hearing should be very carefully made so as to improve the postoperative social life of the patients.

Adult↗

Sleep apnea in acromegaly.

OBJECTIVE: To provide information on the nature, prevalence, and severity of sleep apnea in patients with acromegaly. DESIGN: Consecutive case series. SETTING: Tertiary referral hospital. PATIENTS: Fifty-three patients with acromegaly were consecutively referred: 33 patients were referred because of clinical suspicion of sleep apnea and 20 patients were referred without suspected apnea. MEASUREMENTS: Sleep studies as well as growth hormone and insulin-like growth factor 1 (IGF-1) measurements were done. MAIN RESULTS: Thirty-one patients (93%; 95% Cl, 85% to 100%) referred because of suspicion of sleep apnea had sleep apnea compared with 12 patients (60%; Cl, 37% to 83%) referred without suspected sleep apnea. Patients with sleep apnea did not have biochemical evidence of increased disease activity (random growth hormone, 12.7 +/- 4.4 micrograms/L; mean growth hormone at 24-hour sampling, 10.8 +/- 8.4 micrograms/L; IGF-1, 90.0 +/- 7.5 nmol/L) compared with patients without sleep apnea (random growth hormone, 14.2 +/- 4.9 micrograms/L, P greater than 0.2; mean growth hormone, 12.4 +/- 3.5 micrograms/L, P greater than 0.2; IGF-1, 90.0 +/- 10.0 nmol/L, P greater than 0.2). Central sleep apnea was the predominant type of apnea in 33% (Cl, 18% to 47%) of patients and was associated with higher random growth hormone and IGF-1 levels than was obstructive apnea (random growth hormone, 23.4 +/- 3.9 compared with 8.8 +/- 3.1 micrograms/L, P less than 0.001; IGF-1, 126 +/- 17.5 compared with 72.5 +/- 7.5 nmol/L, P less than 0.01). CONCLUSIONS: Sleep apnea is common in acromegaly. The rate of central sleep apnea was unexpectedly high in patients with acromegaly, and biochemical evidence of increased disease activity was associated with the presence of central apnea rather than with the degree of sleep apnea. Altered respiratory control is a possible mechanism producing sleep apnea in acromegaly.

Acromegaly↗

Circulating phospholipase A2 activity associated with sepsis and septic shock is indistinguishable from that associated with rheumatoid arthritis.

Elevation of circulating phospholipase A2 (PLA2) activity is associated with sepsis and septic shock. Elevated levels of PLA2 activity also are seen in association with chronic inflammatory disorders such as rheumatoid arthritis. The relationship between these phospholipases is unclear. We have developed a highly specific enzyme-linked immunosorbent assay (ELISA) capable of measuring human synovial PLA2 in plasma, using monoclonal antibodies raised to recombinant synovial PLA2. This ELISA has been used to quantitate circulating PLA2 levels in patients clinically diagnosed with sepsis. These elevated levels positively correlated with the elevation seen in plasma PLA2 enzyme activity. The antibodies also have been used to purify immunoreactive PLA2 from plasma of patients with sepsis, thus enabling characterization of the purified protein by amino-terminal sequence analysis. We conclude from this study that the increase in PLA2 activity seen in association with sepsis and septic shock results from a dramatic elevation in levels of a circulating PLA2 enzyme. This inflammatory PLA2 is indistinguishable, both immunologically and chemically, from that associated with rheumatoid arthritis. Therapeutic agents directed towards inhibition of this inflammatory PLA2 enzyme may have utility in the treatment of both chronic and acute inflammatory disease.

Adolescent↗

Role of growth hormone in fluid homeostasis.

Administration of human growth hormone (GH) is associated with clinically significant sodium retention. There is evidence that the antinatriuretic properties of GH are mediated by activation of the renin-angiotensin system, as well as a direct action on the kidney. The antinatriuretic properties of GH may be of pathophysiological significance in acromegaly, where increased body sodium and plasma volume occur, and may contribute to the development of hypertension in this condition.

Growth Hormone↗

[Sensorineural hearing loss in chronic otitis media].

In individuals with chronic otitis media-(COM), mixed hearing impairments are common, but it is unclear whether the raised bone conduction thresholds are a reflection of the pathologic process affecting the middle ear resulting in conductive defect. Charts of 65 patients with unilateral chronic otitis media were reviewed. These were three groups: 1) simple COM 2) COM with granulation, 3) COM with cholesteatoma. In them, the amount of sensorineural hearing loss in the third group was 20.3 dB, which was greater than the other two groups for pure-tone average. The amount of air conduction hearing loss was 66.8 dB, also the highest. In addition, the amount of sensorineural hearing loss was greater than that of normal contralateral ears in all of three groups. These findings suggest that more severe middle ear disease may result in sensorineural hearing loss. Raised bone conduction thresholds in chronic otitis media are considerably more likely to reflect the Carhart effect, rather than disease damage to the inner ear. However, for the majority of subjects, the amount of sensorineural hearing loss was judged not to be clinically significant.

Adolescent↗

Therapeutic efficacy of the somatostatin analog SMS 201-995 (octreotide) in acromegaly. Effects of dose and frequency and long-term safety.

STUDY OBJECTIVE: To determine the efficacy of stepwise incremental doses, to compare twice- with thrice-daily administration of the same total daily dosage of the long-acting somatostatin analog SMS 201-995 (octreotide, Sandoz Australia, Sydney, Australia), and to evaluate the risk for cholelithiasis after long-term therapy for acromegaly. DESIGN: Nonrandomized, controlled trial. SETTING: Tertiary care center at a medical research institute. PATIENTS: Sequential sample of 19 patients with active acromegaly. Twenty-five age-matched normal subjects were also studied to establish the normal range for growth hormone (GH) and insulin-like growth factor 1 (IGF-1). INTERVENTIONS: Eight patients (group 1) were treated with 100, 250, and 500 micrograms twice daily of octreotide, then switched to 333 micrograms three times daily, whereas 11 patients (group 2) were treated with 100, 200, 300, and 500 micrograms three times daily. Each treatment stage lasted 6 to 12 weeks. MEASUREMENTS AND MAIN RESULTS: Octreotide, 100 micrograms administered twice or thrice daily, significantly reduced mean 12-hour and nadir GH (P less than 0.01), IGF-1 (P less than 0.05), and hand volume (P less than 0.05). Dose increment to 500 micrograms in both groups did not further reduce mean 12-hour GH, nadir GH, or hand volume. Switching from 500 micrograms twice daily to 333 micrograms thrice daily resulted in significant (P less than 0.05) reduction of mean 12-hour GH, IGF-1, and hand volume. Normalization of mean 12-hour GH and IGF-1 occurred in 8 of 19 patients; 7 of the 8 patients had pretherapy mean 12-hour GH below 20 mIU/L. The pretherapy mean blood glucose was a significant negative predictor (r = -0.89) of the change in mean blood glucose during therapy. Gallstones were present in 9 of 18 patients after therapy. CONCLUSION: Thrice-daily was more effective than twice-daily administration of octreotide, and dose increments above 100 micrograms thrice daily did not confer additional benefit. Biochemical remission was achieved in 40% of patients and was dependent on the GH concentration at initiation of treatment. Cholelithiasis is a risk of octreotide therapy. Octreotide is effective and can be considered as a first-line therapy in patients with acromegaly with mean pretherapy GH concentrations below 20 mIU/L. In patients with mean GH over 20 mIU/L, octreotide may be used as an adjuvant to surgery or radiotherapy.

Acromegaly↗

The antinatriuretic action of biosynthetic human growth hormone in man involves activation of the renin-angiotensin system.

Previous studies using human pituitary extracts have not resolved whether the sodium retaining effects of human growth hormone (hGH) are mediated in part by increased aldosterone secretion. We have studied the effects of an authentic biosynthetic GH (bio-hGH) preparation on sodium metabolism and on the activity of the renin-angiotensin system. Six young men were administered this preparation at 0.2 U/kg/d subcutaneously for five consecutive days. Twenty-four-hour urine collections were obtained for measurement of sodium excretion and osmolality and blood collected for quantitating changes in sodium, osmolality, plasma renin activity (PRA), aldosterone, and arginine vasopressin (AVP) concentrations. Bio-hGH administration resulted in a fall in 24-hour urinary sodium excretion (197 +/- 38 to 42 +/- 20 mmol, mean +/- SD, P less than .005), a reduction in urine volume (1,652 +/- 182 to 848 +/- 348 mL, P less than .05) but not osmolality. PRA increased significantly from 1,118 +/- 73 to 3,608 +/- 1,841 fmol angiotensin 1 L/s (P less than .005), which was associated with a sevenfold increase in plasma aldosterone concentration (52 +/- 12 to 402 +/- 99 pg/mL, P less than .001). Plasma osmolality and AVP concentrations did not change significantly. The results show that Bio-GH-induced retention of sodium involves the activation of the renin-angiotensin system. This mechanism may explain in part the occurrence of plasma volume expansion and hypertension in acromegaly and suggests a risk of fluid retention and possibly hypertension in subjects receiving supraphysiological doses of bio-hGH for treatment of short stature.

Adult↗

Secretory patterns of growth hormone according to sex and age.

Gender and age have distinct and interrelated effects on GH secretion in adults. GH secretion falls significantly with aging, particularly in women. The fall in GH release is amplitude- rather than frequency-modulated and appears to be related to estrogen status. Oral estrogen administration is unphysiological and causes a marked perturbation of the GH/insulin-like growth factor I axis. A nonparenteral route of administration is required for further investigations of the physiological role of estrogen in GH secretion.

Administration, Oral↗

Quantification of urinary growth hormone (GH) excretion by centrifugal ultrafiltration and radioimmunoassay: appraisal of the relationship between 24 h urinary GH and mean 24 h serum GH levels in normal and abnormal states of GH secretion.

We have applied a simple method for the quantification of 24 h urinary GH excretion (24 h UGH), combining centrifugal ultrafiltration and radio-immunoassay (RIA), to an appraisal of the relationship between 24 h UGH and mean 24 h serum GH levels in normal and abnormal states of GH secretion. Forty-four subjects, comprising 13 normal adults, 12 short-statured subjects and 19 subjects with active acromegaly, underwent blood sampling at 20-min intervals and concurrent urine collection for 24 h. Mean 24 h serum GH and 24 h UGH were also determined in four post-menopausal women before and during cyclical oestrogen replacement therapy, and 24 h UGH was measured in six normal men prior to and following the subcutaneous administration of biosynthetic GH (0.2 IU/kg). Each subject's mean 24 h serum GH level was determined by assaying a 'pooled' sample, derived from equal aliquots of the 73 serum samples obtained during the 24 h study. The method for quantification of 24 h UGH employs centrifugal microconcentrators, and involves a 50-fold concentration of urine, followed by dialysis and RIA. Surface adsorptive hormone loss during sample collection and ultrafiltration is minimized by the prior addition of bovine serum albumin to the urine collection container. Immunoreactive GH in ultrafiltered urine dilutes in parallel with the RIA standard curve. GH is stable in urine stored at - 20 degrees C for at least 12 months. There was a highly significant correlation between 24 h UGH and mean 24 h serum GH values obtained from the combined population of normal adults (including the post-menopausal women during oestrogen therapy) and short-statured subjects (r = 0.69, P less than 0.0001). A significant correlation was also found in short-statured subjects alone (r = 0.63, P less than 0.05). In contrast, there was no significant correlation between 24 h UGH and mean 24 h serum GH in subjects with active acromegaly, and their 24 h UGH values were not distinguishable from those of the 'non-acromegalic' subjects. A significant increase in 24 h UGH occurred in the post-menopausal women given cyclical oestrogen replacement therapy (9.7 +/- 2.6 (mean +/- SE) to 24.6 +/- 1.0 muIU/mmol creatinine, P less than 0.02), reflecting the increase in their mean 24 h serum GH levels (0.8 +/- 0.3 to 5.3 +/- 0.7 mIU/l, P less than 0.01). Twenty-four hour UGH increased from 4.6 +/- 0.6 to 17.1 +/- 2.1 muIU/mmol creatinine (P less than 0.002) in the men given biosynthetic GH. Twenty-four hour UGH measurements reflect mean 24 h serum GH levels in normal adults and short-statured subjects. While the measurement of 24 h UGH shows promise as an investigative tool, our results cast doubt on its use in the diagnosis of acromegaly.

Acromegaly↗

The pharmacokinetics, safety and endocrine effects of authentic biosynthetic human growth hormone in normal subjects.

The pharmacokinetics, safety and endocrine effects of an authentic human growth hormone (bio-hGH), produced by the expression of genomic hGH in a mammalian cell line, were studied in six healthy young men who were administered 0.2 U/kg/day subcutaneously for five consecutive days. Changes in sodium balance and in thyroid function were studied during the week of bio-hGH administration and safety parameters were monitored over a 3-week period. Growth hormone levels reached a mean (+/- SD) peak of 106 +/- 10 mIU/l at 3.3 +/- 0.5 h following the first dose and resulted in a significant rise of somatomedin C. free fatty acids, fasting blood glucose and insulin concentrations. Bio-hGH administration resulted in a significant increase in body weight (80.0 +/- 4.5 to 81.1 +/- 4.3 kg; P less than 0.01) which was associated with a marked reduction in urinary sodium excretion (196 +/- 38 to 45 +/- 20 mmol/day; P less than 0.025). Serum T3 increased during bio-hGH administration and was associated with reciprocal changes in free thyroxine and TSH concentrations. Cardiac, hepatic, renal, biochemical, haematological, endocrinological and immunological functions remained normal throughout the study. No antibodies to hGH or to host cell protein developed during the study. The results show that bio-hGH is safe in the short term, well tolerated, possesses pharmacokinetic and biological properties similar to pituitary hGH, and has distinct effects on sodium balance and on thyroid function. This study stresses the need to monitor patients for effects on sodium retention, carbohydrate metabolism and thyroid function when using hGH doses of 1.0 U/kg/week (40 U/m2/week) or more in patients with GH responsive short stature.

Adult↗

Resolution of apparent growth hormone-dependent growth failure during puberty: a case report.

A prepubertal boy with apparent growth hormone (GH)-dependent growth failure displayed a marked increase in growth velocity, normal GH responses to arginine/insulin infusion and a fourfold increase in spontaneous 24-hour GH secretion following the onset of normal puberty. The case supports earlier observations of a transient form of GH insufficiency in some short prepubertal children, but represents the first evidence that puberty restores spontaneous as well as stimulated GH secretion in such patients.

Adolescent↗

Axon diameter distributions across the monkey's optic nerve.

The distribution of axons according to diameter has been examined in the optic nerve of old world monkeys. Axon diameters were measured from electron micrographs, and histograms were constructed at regular intervals across a section through the optic nerve to reveal the local axon diameter distribution. The total axon diameter distribution was also estimated. Fine-calibre optic axons (less than 2.0 micron in diameter) are found at all locations across the optic nerve. They are most frequent centrotemporally, where very few coarse optic axons can be found, but also make up the majority at the optic nerve's periphery. Coarse optic axons (greater than 2.0 microns in diameter) are increasingly common at progressively peripheral positions in the nerve. Around the nerve's circumference, these coarse optic axons are least numerous temporally, and most common dorsonasally. The axon diameter distribution peaks around 1.25 microns at most locations across the optic nerve, but there are more, slightly larger (1.5-2.0 microns), optic axons dorsally than ventrally. The estimated total axon diameter distribution is unimodal, peaking at 1.0-1.25 microns, with an extended tail towards larger diameters. This centroperipheral gradient of increasing axon diameters across the optic nerve is not substantial enough to account for the partial segregation of axons by size in the monkey's optic tract: there, coarse optic axons form a conspicuously greater proportion of the local axon diameter distribution along the tract's superficial (sub-pial) border, and fine optic axons are the only axons present near the tract's deep border. Hence, the fibre distribution in the optic tract cannot be formed by a simple combination of the fibre distributions of the two respective half-nerves, as described in the classic neuro-ophthalmologic literature. Rather, the present results, in conjunction with previous results from the optic tract, demonstrate that there must be a reorganization of axons by size in or near the optic chiasm.

Animals↗

Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man.

Studies in man have shown that the episodic release of growth hormone (GH) is infrequent and erratic, and unlike that in the rat does not appear to have discernible ultradian periodicities. However, these observations in nonfasted subjects may be invalid since mixed nutrients have unpredictable effects on GH release. Moreover, in the fed state basal GH levels are frequently undetectable, thus rendering the identification of low amplitude pulses unreliable. Accordingly, the 24-h pulsatile pattern of GH secretion obtained from repetitive venous sampling in six normal adult male subjects was examined during a control fed day and during the first and fifth days of a 5-d fast. The GH data were analyzed using two distinct methods: a discrete pulse detection algorithm (Cluster analysis) and Fourier expansion time-series, which allows fixed periodicities of secretory activity to be resolved. The 5-d fast resulted in a significant increase in discrete GH pulse frequency (5.8 +/- 0.7 vs. 9.9 +/- 0.7 pulses/24 h, P = 0.028), 24 h integrated GH concentration (2.82 +/- 0.50 vs. 8.75 +/- 0.82 micrograms.min/ml; P = 0.0002), and maximal pulse amplitude (5.9 +/- 1.1 vs. 12.3 +/- 1.6 ng/ml, P less than 0.005). While multiple low-amplitude sinusoidal periodicities were present on the control fed day, time-series analysis revealed enhancement of circadian and ultradian cycles on the first and fifth days of fasting. Concomitantly, fasting resulted in a decline (day 1 vs. day 5) in serum concentrations of somatomedin C (1.31 +/- 0.22 vs. 0.77 +/- 0.18 U/ml) and glucose (4.9 +/- 0.2 vs. 3.2 +/- 0.2 mmol/liter), and a marked rise in free fatty acid (0.43 +/- 0.12 vs. 1.55 +/- 0.35 mmol/liter) and acetoacetate (35 +/- 6 vs. 507 +/- 80 nmol/liter). We conclude that the acute nutritional status is an important determinant of spontaneous pulsatile GH secretion in man. Fast-induced enhancement of GH release is achieved through combined frequency (discrete pulses) and amplitude (sinusoidal periodicities) modulation. Such alterations in somatotropic hormone release may play an important role in substrate homeostasis during starvation.

Acetoacetates↗

Effects of gonadal steroids on somatotroph function in the rat: analysis by the reverse hemolytic plaque assay.

The mechanism by which gonadal steroids modulate GH secretion is not known. We have used the reverse hemolytic plaque assay to examine whether gonadal steroid-induced modulation of GH secretion is effected by changes in the population of somatotrophs and/or alterations in their secretory properties. Two groups of Sprague-Dawley rats were studied: group 1 (n = 6) comprised male (M), castrate (Cx), and testosterone-replaced castrate male (Cx + T) rats and group 2 (n = 5) consisted of male (M), female (F), and 17 beta-estradiol-replaced castrate male (Cx + E) rats. The number of plaque-forming cells (expressed as both absolute number and a percentage of all cells) was determined, and secretory status was assessed by measuring plaque areas in response to 0, 0.01, 0.1, 1, 10, and 100 nM GHRH. While mean basal GH plaque areas were similar among the treatment groups of group 1, the maximal GH plaque area was significantly decreased in Cx [16.8 +/- 2.4 vs. 26.4 +/- 3.9 X 10(6) microns2 (mean +/- SEM); P less than 0.05], but not in Cx + T (27.5 +/- 4.1 microns2) rats. The GHRH EC50 was unaffected by castration or T replacement. The percentage and absolute population of somatotrophs were reduced in Cx, but not in Cx + T, rats, while the numbers of lactotrophs remained unchanged in these treatment groups. For group 2, the mean peak GH plaque area was reduced in Cx + E (16.5 +/- 2.9 microns2; P less than 0.001) compared to that in M rats (36.2 +/- 2.3 microns2), but was not significantly different from that in F (13.0 +/- 1.5 microns2) rats. The EC50 was significantly (P less than 0.025) greater in Cx + E (10.9 +/- 2.3 nM) and F (7.9 +/- 1.6 nM) compared to M rats (2.8 +/- 0.7 nM). The absolute somatotroph and lactotroph populations were increased in Cx + E compared to M and F rats, as were the populations of other pituitary cell types. Testosterone enhances GH secretion by increasing the secretory capacity, but not the sensitivity, of somatotrophs to GHRH and by recruiting the function of a subpopulation of somatotrophs. Estradiol reduces the secretory capacity and sensitivity of somatotrophs to GHRH, but increases the population of somatotrophs, lactotrophs, and non-GH- and non-PRL-secreting cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Therapeutic applications of bromocriptine in endocrine and neurological diseases.

Bromocriptine, or 2-bromo-alpha-ergocryptine, is a semisynthetic ergot alkaloid. The basis of its therapeutic application in endocrine and neurological diseases is its action as a potent dopamine agonist. Its ability to inhibit prolactin secretion has led to its successful use in suppression of puerperal lactation and in the treatment of pathological hyperprolactinaemia causing galactorrhoea, infertility or hypogonadism. It has been shown to be safe in pregnancy. The ability of bromocriptine to reduce the size of large prolactin-secreting pituitary tumours has resulted in the recovery of pituitary function and correction of visual field defects. Bromocriptine is less effective in acromegaly but is useful as adjuvant therapy to radiotherapy and/or surgery which has been the standard mode of treatment. It has been shown to be efficacious either alone or in combination with levodopa in the treatment of Parkinson's disease. Therapy with low doses appears to be effective and is associated with a significantly reduced incidence of side effects. The successful use of bromocriptine has also been reported for the treatment of non-functioning pituitary tumours, premenstrual syndrome, cyclical mastalgia, luteal phase insufficiency and portal-systemic encephalopathy, although its role in the treatment of these latter disorders remains uncertain until more extensive and adequately controlled trials have been conducted.

Bromocriptine↗

Impact of intensive venous sampling on characterization of pulsatile GH release.

The effect of sampling intensity on quantitative properties of pulsatile growth hormone (GH) release was tested using an objective, statistically based pulse detection algorithm (Cluster). Seven normal young men had blood withdrawn at 5-min intervals for 24 h. The number of GH peaks/24 h (mean +/- SE) detected in the 5-min series (5.93 +/- 0.66) was significantly greater than the number of peaks documented in the constituent 10-min (3.45 +/- 0.28), 15-min (2.79 +/- 0.31), 20-min (2.86 +/- 0.64), 30-min (2.5 +/- 0.36), 45-min (2.21 +/- 0.21), and 60-min (1.93 +/- 0.23) series. The increased number of peaks detected with 5-min sampling reflected high-frequency pulsatile GH release occurring within the major GH secretory episodes. Both the mean widths and areas associated with peaks identified in the 5-min series were smaller than those documented with less intensive sampling. Peak amplitude did not change with sampling intensity. These data suggest that the major secretory episodes of GH release in normal young men encompass high-frequency GH secretory activity. That these high-frequency GH secretory events have not previously been described probably reflects the relatively infrequent sampling paradigms (e.g., every 20-30 min) commonly used in the past.

Adult↗