Search PubMed⌕ Search

Biomedical subjects

A G Harris

Publications and source records attributed to A G Harris.

At least 127 records · Page 7Linked to original sources
PubMed1990

Effect of the long-acting somatostatin analogue SMS 201-995 on growth rate and reduction of predicted adult height in ten tall adolescents.

Ten adolescents (four boys and six girls) aged 11.5 to 17 years, presenting with constitutionally tall stature were treated with twice daily subcutaneous injections of 250 micrograms of SMS 201-995 (Sandostatin). Results are reported after 6 and 12 months of therapy. Reduction of growth rate was obtained in 9 patients and correlated with the reduction of 24-hour growth hormone pulsatility and with the decrease of plasma Somatomedin-C values. Moreover, acceleration of bone maturation on SMS 201-995 therapy occurred in seven patients, and mean bone age increased from 13.3 years to 14.5 and 15.8 years after 6 and 12 months of SMS therapy. The mean reduction of predicted adult height was 4.9 cm at the last evaluation after 6 or 12 months of therapy. The dual effect of SMS 201-995 on growth rate and bone maturation suggests that it may be an alternative treatment to reduce adult height.

Adolescent↗
PubMed1990

Issues in the evaluation of a community psychogeriatric service.

The need for evaluation of community psychogeriatric programs is stressed. The results of the evaluation of an outpatient service, with a liaison component, based in a community general hospital are presented. The use of treatment outcome scales, user satisfaction surveys, and a study of cost effectiveness are discussed. The issues of needs assessment, service models, staffing, target population, and the role of the family physician are addressed. It is recommended that evaluation processes be initiated by psychogeriatric services and that program data collection be developed in a manner that allows for service comparability, the assessment of ongoing community needs and the determining of program effectiveness.

Aged↗
PubMed1990

A randomized study of SMS 201-995 versus bromocriptine treatment in acromegaly: clinical and biochemical effects.

Twenty-six acromegalic patients were randomized to treatment with either SMS 201-995 or bromocriptine in increasing doses and were investigated before treatment, after 2, 4, and 8 weeks of treatment, and 2 weeks after discontinuation of treatment. There were two dropouts from the bromocriptine group and one from the SMS 201-995 group. Amelioration of clinical signs and symptoms was seen in both groups during treatment. After 8 weeks mean 12-h GH concentrations had declined from 13.8 +/- 5.2 to 2.9 +/- 4.4 (mean +/- SEM) in SMS 201-995-treated and from 18.8 +/- 7.5 to 5.4 +/- 1.2 micrograms/L in bromocriptine-treated patients. Somatomedin-C concentrations fell from 3.04 +/- 0.36 to 1.43 +/- 0.36 in SMS 201-995-treated and from 2.93 +/- 0.40 to 2.13 +/- 0.27 U/mL in bromocriptine-treated patients. Size reduction of the pituitary tumor was seen in one patient receiving bromocriptine. Gastrointestinal glucose absorption was delayed, and insulin secretion suppressed during treatment with SMS 201-995. Hemoglobin-A1 concentrations remained unchanged in SMS 201-995-treated patients, but declined in the bromocriptine group. Side-effects were common, but usually tolerable, with both treatments. It is concluded that both drugs are of benefit in the treatment of acromegaly.

Acromegaly↗
PubMed1990

Long term effect of incremental doses of the somatostatin analog SMS 201-995 in 58 acromegalic patients. French SMS 201-995 approximately equal to Acromegaly Study Group.

Fifty-eight acromegalic patients were included in a multicenter prospective study of increasing doses (300-1500 micrograms) of SMS 201-995 (octreotide, Sandostatin) administered 3 times daily, sc, during 6 months to determine its effect on signs and symptoms of GH hypersecretion. Subsequently, 34 of the patients were maintained for 12-26 months on the minimal efficacious dose, determined from the previous dose-response study. Some adverse effects were frequently encountered, mostly at the initiation of treatment, and disappeared with time. Asymptomatic gallstones occurred in 5 patients. Minimal changes in carbohydrate tolerance, consisting of a rise in blood glucose and a transient decrease in plasma insulin level after meals, were noted. GH normalized in 22% of the patients, improved in 56%, and remained unchanged in 22% regardless of the dose. The optimal daily dose was 300 micrograms in 50% of the patients and 1500 micrograms in 20%. Pituitary tumor size reduction occurred in 47% of the patients harboring large tumors or tumor remnants. No additional improvement or escape from being controlled occurred with time. These data indicate that SMS 201-995 is an effective treatment for refractory acromegaly and for some de novo patients for whom surgical therapy is not advisable.

Acromegaly↗
PubMed1990

Future medical prospects for Sandostatin.

Because of its widespread distribution within the nervous system and the gastro-enteropancreatic (GEP) system and its diverse physiological inhibitory actions on various gastrointestinal functions, including endocrine and exocrine secretion, motility, liver and splanchnic blood flow and absorption, native somatostatin has been viewed as a possible therapy for many diseases. However, its short duration of action and consequent limited clinical usefulness have been overcome with the availability of Sandostatin, a long-acting, synthetic octapeptide analogue of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of GH and TSH secreting pituitary tumours and GEP endocrine tumours (carcinoid tumour, VIPoma, glucagonoma, insulinoma, and gastrinoma). Preclinical in vitro and animal studies have shown the antineoplastic activity of the compound. Moreover, because of a possible direct effect on somatostatin receptor-positive endocrine tumour cells and indirect effect whereby Sandostatin lowers GH, IGF-1 and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labelling of somatostatin receptor-positive tumours with radiolabelled somatostatin analogues now allows localisation of such tumours and their metastases. Moreover, targeted irradiation of these tumours by beta particle emitting isotopes attached to such somatostatin analogues may become possible. The use of Sandostatin in acute oesophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal and pancreatic external fistulae, short bowel syndrome, dumping syndrome and AIDS-related refractory hypersecretory diarrhea has provided encouraging results. Preliminary reports indicate efficacy of Sandostatin in psoriasis, autonomic neuropathy (postprandial and orthostatic hypotension) and its ability to reduce height velocity in tall adolescents. The ultimate role of Sandostatin as a therapeutic agent in these disorders is being explored in prospective clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1990

Growth hormone suppression and nonproliferative diabetic retinopathy: a preliminary feasibility study.

We used the long acting somatostatin analogue SMS 201-995 in order to examine the feasibility and effect of medical suppression of growth hormone in nonproliferative diabetic retinopathy. Six insulin-dependent diabetic subjects with nonproliferative retinopathy were studied. After eight weeks of SMS 201-995 administration, 24-hour integrated plasma growth hormone concentrations had declined by 47.0 +/- 9.3% of pretreatment values (p less than 0.01), and insulin requirements fell from 40.7 +/- 6.7 units per day to 32.2 +/- 6.9 units per day (p less than 0.01). Plasma levels of somatomedin-C were low before SMS 201-995 (0.5 +/- 0.1 U/ml) and remained unchanged at eight weeks (0.6 +/- 0.1 U/ml; p = ns). During SMS 201-995 administration, best corrected visual acuity improved in both right eyes (53.8 +/- 2.57 to 59.8 +/- 0.7 letters, p less than 0.05) and left eyes (54.8 +/- 2.8 to 61.7 +/- 1.23 letters, p less than 0.03). Fluorescein angiography and stereo fundus photography demonstrated concurrent improvement in retinopathy level in only two subjects. Following cessation of SMS 201-995 treatment, visual acuity returned to pretreatment levels in both right eyes (54.5 +/- 2.4 letters, p = ns compared to baseline) and left eyes (55.8 +/- 2.6 letters, p = ns compared to baseline). These results demonstrate that growth hormone was only partially suppressed by SMS 201-995 in insulin-dependent diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Influenza viruses induce autoantibodies to a brain-specific 37-kDa protein in rabbit.

Immunization of rabbits with certain H1N1 influenza viruses, including the neurotropic strains NWS/33 and WSN/33 and the New Jersey/76 strain, resulted in the production of autoantibodies to a brain-specific protein of 37 kDa that is present in various species, including humans. Autoantibodies were produced to brain only; various other tissues tested were negative. These antibodies were not elicited by other influenza A or B viruses, including closely related recombinant strains, but were elicited by the isolated hemagglutinin of A/Bellamy/42 strain and by formaldehyde-fixed WSN virus--demonstrating that infection was not essential for the induction of autoantibodies. In histological studies, reaction with anti-viral antisera was specific to gray matter and was confined to sera that recognized the 37-kDa protein. Antibody binding was prominent in regions comprised of neuronal cell bodies in cellular layers of the dentate gyrus, hippocampus, cerebral cortex, and cerebellum and was undetectable in myelin-rich regions, such as the corpus callosum. The 37-kDa protein, therefore, appears to be a neuronal antigen. Antibodies directed against this protein may be involved in the pathogenesis of one or more of the neuropsychiatric disorders that occur after infection with influenza.

Animals↗
PubMed1989

Experience of a six-month treatment with sandostatin at increasing doses in acromegaly.

The French Sandostatin/Acromegaly Study Group performed a multicentric, prospective, open-label trial of incremental doses with the aim of obtaining the best antisecretory effect. Forty-two patients (24 women, 18 men) aged 22-71 years were involved, either after unsuccessful surgery and/or radiotherapy (30 patients), or as primary treatment (12 patients). Doses were increased from 3 x 100 to 3 x 500 micrograms/day, according to the results of hormonal investigations (GH profiles and Sm-C) performed each month and for each dose, and tolerability. Four patients dropped out because of major digestive troubles. Recurrent pain at the injection site and minor gastrointestinal disorders were noted in some patients. Asymptomatic gallstones appeared in 4 patients. Carbohydrate tolerance and insulin secretion (determined by diurnal plasma glucose and insulin profiles) were not significantly altered by the various SMS doses. Clinical improvement was determined by the scoring of the symptoms. Mean plasma GH concentrations were significantly reduced for each SMS dose, compared to pretreatment values. Fifteen patients obtained 75% of GH values less than or equal to 2 micrograms/l. In 9 patients the highest dose failed to bring GH below 10 micrograms/l. Sm-C normalized in 17/31 patients. After 6 months of treatment a tumor reduction of 20-50% was found in 7 patients and greater than 50% in 5 patients. We conclude that (1) the tolerability of SMS is compatible with long-term treatments; (2) clinical improvement and biological criteria of efficacy are obtained in 3/4 acromegalic patients treated by SMS, and that (3) some patients are resistant to SMS and the increase in the dose does not improve the result.

Acromegaly↗
PubMed1989

Long term effects of continuous subcutaneous infusion of the somatostatin analog octreotide in the treatment of acromegaly.

The marked pituitary tumor shrinkage achieved by continuous sc infusion (CSI) of the long-acting somatostatin analog octreotide in one acromegalic patient led us to treat 16 other acromegalic patients for up to 24 months by CSI. This therapy, given in doses ranging from 100-600 micrograms/day, resulted in normalization of the mean daily serum GH (mGH) and insulin-like growth factor I levels in 9 of the 17 patients (53%). In 7 patients, mean daily serum GH decreased but not to normal; 3 of these patients had hyperprolactinemia which was not influenced by octreotide. One patient was completely unresponsive. In contrast to the biochemical results, 80% of the patients had marked clinical improvement. Side-effects consisted of slightly impaired carbohydrate tolerance in 2 patients and cholelithiasis in 2 patients. Pituitary tumor size decreased in only 3 patients; in 1 of them visual field defects disappeared rapidly. These results suggest that octreotide treatment may prove beneficial before surgery in patients with macroadenomas, although its efficacy varies widely. Potential responsivity can usually be determined by a short course (24 h) of CSI of octreotide.

Acromegaly↗
PubMed1989

The effect of somatostatin analogue on chiasmal dysfunction from pituitary macroadenomas.

The long-acting somatostatin analogue SMS 201-995 has been shown to be efficient in the treatment of somatotropic and thyrotropic adenomas. In some cases, it can suppress adenoma secretion and lead to tumor shrinkage. Pituitary macroadenomas are often associated with a vision-threatening chiasmal syndrome. In this series, SMS 201-995 was administered subcutaneously to eight patients with pituitary macroadenomas of various types responsible for severe long-lasting visual defects. An obvious improvement of both visual fields and acuity occurred in six patients, in two of these during the first 4 to 6 hours of treatment; in two patients, gonadotropic adenomas were unresponsive. Maximal improvement (normalization of visual fields in three cases) occurred within 6 to 45 days and was sustained during the 1- to 12-month follow-up period. This effect seems independent of the type of adenoma since the adenomas secreting growth hormone (GH) and thyroid-stimulating hormone and silent corticotropic-secreting adenomas responded as well as did two of the non-functioning adenomas. In one acromegalic patient visual improvement was obtained while the abnormal GH secretion remained unaltered. In all cases but one, no tumor shrinkage could be demonstrated. These data demonstrate that SMS 201-995 can rapidly improve the chiasmal syndrome due to pituitary macroadenoma, and suggest that this effect might be independent of a reduction in tumor volume.

Adenoma↗
PubMed1988

Spectroscopic studies of quinonoid species from pyridoxal 5'-phosphate.

To establish the state of protonation of quinonoid species formed nonenzymically from pyridoxal phosphate (PLP) and diethyl aminomalonate, we have studied absorption spectra of the rapidly established steady-state mixture of species. We have evaluated the formation constant and the spectrum of the mixture of Schiff base and quinonoid species. For N-methyl-PLP a singly protonated species with a peak at 464 nm is formed from the unprotonated aldehyde and the conjugate acid of diethyl aminomalonate with a formation constant Kf of 240 M-1. The very intense absorption band with characteristic vibrational structure (most evident as a shoulder at 435 nm) is accompanied by a weaker, structured band at about 380 nm and a weak, broad band at 330 nm. We suggest that the 380-nm band may represent a tautomeric form of the quinonoid compound. Protonation of the phosphate group appears to affect the spectrum only slightly. The corresponding mixture of Schiff base and quinonoid species formed from PLP has a very similar spectrum at pH 6-7. It has a formation constant Kf of 230 M-1 and a pKa of 7.8, which must be attributed to the ring nitrogen atom. The dissociated species, which may be largely carbanionic, has a strong structured absorption band at 430 nm and a weaker one, again possibly a tautomer, in the 330-nm region. The analysis establishes that in all species a proton remains on either the phenolic oxygen or the imine nitrogen. Proton NMR spectroscopy, under some conditions, reveals only two components: free PLP and what appears to be Schiff base. However, we suggest that the latter may, in fact, be a quinonoid form, either alone or in rapid equilibrium with the Schiff base. Absorption spectra of quinonoid species formed in enzymes are analyzed and compared with the spectra of the nonenzymic species.

Chemical Phenomena↗
PubMed1987

Continuous subcutaneous pump infusion of somatostatin analogue SMS 201-995 versus subcutaneous injection schedule in acromegalic patients.

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 micrograms/24 h. Subcutaneous injections (33 micrograms) induced impressive suppression of serum GH lasting 3-6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 ng/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4-102 ng/ml) implying either that adequate suppression by the SMS 201-995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201-995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201-995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin-C immunoreactivity (all patients) decreased from 496 +/- 129 (mean +/- SD) to 385 +/- 100 ng/ml (P less than 0.003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 +/- 76 ng/ml). The normal adult mean is 179 +/- 40 ng/ml. Computer tomographic (CT) scans of the sellar region were performed in all patients before and after the experimental week. Two patients had extracellular tumours whose size decreased from 8.2 to 4.1 cm3 and from 12.6 to 10.5 cm3. The results demonstrate that superior and stable suppression of GH secretion is obtained during continuous s.c. pump infusion of SMS 201-995.

Acromegaly↗
PubMed1987

Shrinking of a growth hormone-producing pituitary tumor by continuous subcutaneous infusion of the somatostatin analog SMS 201-995.

SMS 201-995, a long-acting somatostatin analog, was given as the initial treatment to an acromegalic patient. SMS 201-995 (200 micrograms, sc, three times daily) reduced, but did not normalize, serum GH levels. Complete and prolonged control of GH secretion was obtained with a 600-micrograms daily continuous sc infusion (CSI), and the patient was treated in this way for 6 months. Rapid improvement of clinical signs and symptoms of acromegaly occurred, as did major tumor shrinkage. The other pituitary functions did not change. After 6 months, the daily SMS 201-995 dose was progressively reduced; GH secretion remained suppressed. After 12 months of treatment, GH secretion was controlled with a CSI of 100 micrograms SMS 201-995 daily, but not with two daily sc 100-micrograms injections. Further significant reduction in tumor size occurred. We conclude that CSI of SMS 201-995 resulted in constant GH normalization and marked clinical and morphological improvement. This form of treatment should be considered as an alternative to ablative treatment of acromegaly.

Adult↗
PubMed1987

Long-acting somatostatin analogue (Sandostatin) reduces late night insulinopenic ketogenesis in diabetic teenagers.

Ten diabetic teenagers were admitted into our hospital for two nights, separated by one week. In a double-blind cross-over randomized study they received either 50 micrograms of the new long-acting somatostatin analogue Sandostatin sc or placebo. All patients were between 12 and 16 years of age, C-peptide negative with a duration of diabetes of at least four years. They had either conventional therapy or insulin pump therapy. Insulin doses and diets were kept unchanged. Blood samples were taken half hourly from 17.00 h until 09.30 h the next morning from an indwelling venous catheter. Hormonal and metabolic profiles on the two nights were evaluated by means of a distribution free time sequential co-movement analysis and by the paired Wilcoxon's signed rank test. After Sandostatin was given at 22.00 h, GH levels were significantly suppressed during 4 h. During that period blood glucose was slightly but significantly lower than after placebo. The free-insulin profiles from both nights were very comparable. Co-movement analysis showed a significant correlation between glucose and free insulin variations with a 30-min backward shift of the glucose curve. However, after Sandostatin administration this relation was lost in the period between 22.00 and 07.00 h, indicating a different effect of insulin on glucose levels during the nights Sandostatin was given. Early morning glucose rises were associated with free insulin levels below 20 mU/l. This association was not altered during the Sandostatin nights. Glucagon was not suppressed by Sandostatin except at 120 min after injection, and remained unchanged during the rest of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1987

The effect of subcutaneous infusion versus subcutaneous injections of a somatostatin analogue (SMS 201-995) on the diurnal GH profile in acromegaly.

Multiple sc injections of a long-acting somatostatin analogue (SMS 201-995) are currently used in the treatment of acromegaly. However, plasma GH concentration often reaches a pathological level (less than 5 micrograms/l) between two injections. In seven patients with active acromegaly we compared, in a short-term trial, the effect of SMS 201-995 administered by continuous sc infusion (50 micrograms and 100 micrograms a day) and by three sc injections (100 micrograms each). In six patients, plasma GH levels were significantly reduced regardless of the mode and dose of treatment (P less than 0.05). However, comparing diurnal profiles, 100 micrograms continuous sc infusion was more effective than discontinuous administration in reducing the number of GH levels above 5 micrograms/l (P less than 0.01). In two patients, continuous infusion was the only way to decrease all plasma GH values below 5 micrograms/l during the diurnal profile determination. Moreover, even when, in a long-term study, the dose of multiple injections was progressively increased to 500 micrograms three times a day, GH levels remained consistently elevated in one of these patients. Thus, in some acromegalic patients continuous sc injection seems currently the most efficient way of treatment with SMS 201-995.

Acromegaly↗
PubMed1985

Purification and immunological characterisation of two calcium-activated neutral proteinases from rabbit skeletal muscle.

Two Ca2+-activated neutral proteinases have been prepared to a high degree of purity from rabbit skeletal muscle. One, calpain I, is optimally activated by 100 microM Ca2+ and the other, calpain II, by 1 to 2 mM Ca2+. Both enzymes have two subunits of molecular weight 80 000 and 28 000. Antibodies have been raised against the native forms of both enzyme. It was found that the antibody to native calpain I reacted only with calpain I and not with calpain II, and similarly the antibody to native calpain II reacted only to calpain II. This suggested that the epitopes in the two enzymes are located in regions that are structurally different. However, immunoblotting of the denatured calpains after SDS-polyacrylamide-gel electrophoresis revealed cross-reaction between the two subunits for both enzymes. Therefore, although the denatured enzymes have common antigenic sites it would appear that these are not exposed equally in the native proteins.

Animals↗
PubMed1975

Anaesthesia for posterior cervical osteotomy.

We have studied 22 consecutive cases of posterior cervical osteotomy done at the Toronto East General Hospital between October 1967 and November 1973. The anaesthetic management is discussed in some detail and consists of psychological preparation of the patient, and neuroleptanalgesia with infiltration with local anaesthetic by the surgeon. The reasons for this choice of technique have been discussed in some detail. There were no deaths during operation, but one patient suffered collapse on the table, which was thought to be due to air embolism. One patient died three weeks post-operatively of pulmonary embolism. Experience in anaesthetizing patients who require operation after previous posterior cervical osteotomy is mentioned briefly and techniques are recommended for successful management of such cases.

Adult↗