Search PubMed⌕ Search

Biomedical subjects

A G Harris

Publications and source records attributed to A G Harris.

At least 109 records · Page 6Linked to original sources
PubMed1992

SMS 201-995 and thyroid function in acromegaly: acute, intermediate and long-term effects.

The acute (TRH-stimulation test), intermediate (0-6 days administration), and long-term (0-30 months administration) effects of SMS 201-995 (octreotide) treatment on thyroid function were studied. Subcutaneous injection of 100 micrograms SMS 201-995 one hour before 200 micrograms TRH intravenously reduced serum TSH response area by more than 50% in 8 healthy volunteers. After 3 days of continuous subcutaneous infusion (CSI) of SMS 201-995 in 9 acromegalic patients (100 micrograms/24 h) a slight but significant decrease in serum total triiodothyronine (TT3) and a concomitant increase in serum TSH were demonstrated, indicating an initial inhibitory effect on peripheral deiodination of thyroxine. After a further 3 days treatment serum T3 and TSH had returned to prevalues. Six of the nine acromegalics were treated with SMS 201-995 (100-1500 micrograms/24 h) and admitted for diurnal hormone profiles on 13 occasions over 30 months. Apart from a barely significant increase in serum TSH, no changes in thyroid function were noted. The study was especially designed to detect minute changes over time in thyroid hormones. The only long-term effect of SMS 201-995 was the barely significant clinically irrelevant increase in serum TSH, possibly caused by a slight inhibition of peripheral deiodination of thyroxine.

Acromegaly↗
PubMed1992

Effects of octreotide on lipid metabolism in acromegaly.

Hypertriglyceridemia is the most frequent modification of lipid metabolism observed in acromegaly. The somatostatin analog, octreotide (Sandostatin), widely used in the treatment of acromegaly, is able to produce a decrease in levels of growth hormone (GH), insulin, and Insulin-like Growth Factor 1 (IGF1). We have attempted to evaluate the influence of this treatment on the lipid status of acromegalic patients. Seventeen patients with active acromegaly were treated with octreotide, 100 to 500 micrograms/injection subcutaneously three times daily. The levels of fasting serum triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL) cholesterol and IGF1, as well as mean plasma GH and insulin levels during a diurnal profile, were evaluated before and after three months of octreotide therapy. GH, insulin and IGF1 decreased by 61%, 42% and 36% respectively (p less than 0.05). Mean levels (+/- SEM) of TG and total cholesterol fell from 2.2 +/- 0.4 mmol/l to 1.6 +/- 0.3 mmol/l (p less than 0.05) and 6.4 +/- 0.39 mmol/l to 5.6 +/- 0.27 mmol/l (p greater than 0.05), respectively. There was no correlation between triglyceride decrease and hormonal changes or clinical status (BMI, age, sex). In conclusion, the administration of octreotide over a three month period to acromegalic patients is associated with a decrease in TG levels.

Acromegaly↗
PubMed1992

The sensitivity of growth hormone secretion to medical treatment in acromegalic patients: influence of age and sex.

OBJECTIVE: We investigated the relationship between age, sex, pituitary tumour volume, serum GH, PRL and IGF-I levels with the responsiveness of GH to TRH, bromocriptine and octreotide in patients with acromegaly. DESIGN: We performed a retrospective study. Correlations were determined between all variables using univariate regression analysis. PATIENTS: One hundred previously untreated acromegalic patients were studied (60 males (age 23-76; mean 49 years) and 40 females (age 25-83; mean 51 years)). MEASUREMENTS: We studied tumour volume, fasting morning circulating levels of GH, PRL and IGF-I, mean 24-hour circulating GH levels and the acute GH responses to TRH, bromocriptine and octreotide. RESULTS: Tumour size was related to serum and mean 24-hour GH levels, but not to IGF-I. Circulating IGF-I and GH levels were related only for the group of patients whose fasting and unsuppressed GH level was 80 mU/l (40 micrograms/l) or less. Older patients tended to have lower circulating GH and IGF-I levels. There was a close similarity in the responsiveness of tumorous GH secretion to TRH, bromocriptine and octreotide. An elevated serum PRL level predicted a stronger inhibitory response of bromocriptine on GH. The sensitivity of GH release to octreotide was highest in elderly (especially male) acromegalics, as well as in patients with lower IGF-I levels. CONCLUSIONS: Hormone secretion by GH secreting pituitary tumours, as well as circulating IGF-I levels, tend to be lower in elderly patients. These tumours are more sensitive to octreotide, especially in elderly male patients. This suggests that octreotide might be used especially successfully as a primary medical therapy in elderly, male acromegalics.

Acromegaly↗
PubMed1992

Does the somatostatin analogue octreotide protect against ERCP induced pancreatitis?

This study evaluates the effect of the long acting somatostatin analogue octreotide on biochemical and clinical parameters of endoscopic retrograde cholangiopancreatography (ERCP) induced pancreatitis. Altogether 245 patients were randomised to receive either octreotide or isotonic saline. Octreotide (100 micrograms) was administered intravenously five minutes before ERCP and subcutaneously 45 minutes after ERCP. There were no significant differences in the median serum amylase and lipase activities at baseline, eight, and 24 hours after ERCP. Five patients (2%) developed clinical pancreatitis--three in the octreotide and two in the placebo groups. Excluding patients who developed pancreatitis, 43 (18%) developed abdominal pain after ERCP--21 in the octreotide and 23 in the placebo groups. There were no significant differences in the median serum amylase and lipase values between the treatment groups. None of the 52 patients who had therapeutic interventions developed pancreatitis. This study suggests that octreotide may not protect against ERCP induced pancreatitis.

Amylases↗
PubMed1992

A randomized comparison of intranasal and injectable octreotide administration in patients with acromegaly.

Fifteen acromegalic patients received four single doses of octreotide in random order (500 micrograms, 1000 micrograms, and 2000 micrograms applied intranasally and 100 micrograms given sc). Serum octreotide and GH data were subjected to pharmacokinetic analyses, and local nasal effects were evaluated by acoustic rhinometry. Average areas (+/- SEM) under the serum octreotide curves were: 2000 micrograms: 4597 +/- 536; 1000 micrograms: 1923 +/- 439; 500 micrograms: 957 +/- 168; and 100 micrograms sc: 896 +/- 81 micrograms.L-1.min (n = 13). The calculated relative availability was 27% +/- 0.03; 22% +/- 0.05; 22% +/- 0.03, respectively, for the three nasal doses. The rate of absorption after intranasally administered octreotide was greater than after sc application: t1/2 ka: 7.1 +/- 1.6; 7.9 +/- 1.6; 11.3 +/- 1.9, respectively, vs. 24.1 +/- 2.5 min, whereas the rates of disappearance were similar. GH suppression started immediately after application and reached minimum levels 1-2 h later. The average intervals during which serum GH was below 50% of preadministration values were: 2000 micrograms: 544 +/- 47; 1000 micrograms: 423 +/- 56; 500 micrograms: 289 +/- 52 vs. 351 +/- 34 min after sc injection of 100 micrograms. With 2000 micrograms intranasally all but one of the 15 patients attained constant suppression of serum GH below 5 micrograms/L for 273 to 680 min. Pharmacokinetic analysis demonstrated that 100 micrograms sc and 1000 micrograms intranasally induced the same GH suppressive effect and that 2000 micrograms intranasally approximately doubled the duration of action. Acoustic rhinometry was performed after nasal application of the largest dose of 2000 micrograms and after carrier (n = 9). A highly significant tumescence of the nasal mucosa was maximal after 10 min and gradually receded over the next 2 h. However, this was felt by the patients to be acceptable. The effect was caused by octreotide per se and was probably due to vasodilation.

Acromegaly↗
PubMed1991

Reduction in sella turcica volume. An effect of long-term treatment with the somatostatin analogue, SMS 201-995, in acromegalic patients.

Ten patients with acromegaly were treated with the long-acting somatostatin analogue, Sandostatin (SMS 201-995, octreotide) for more than one year. Computerized tomography was performed before and on 4 different occasions during the treatment. Sella turcica volumes were calculated in nine patients and showed a gradual decrease in all, averaging 32% +/- 14.6%, P less than 0.001 at the end of the study, which is probably indicative of a simultaneous reduction in adenoma size.

Acromegaly↗
PubMed1991

Pilot study of sandostatin (octreotide) therapy of refractory HIV-associated diarrhea.

Seventeen AIDS patients were enrolled in a prospective open-label dose-finding study of octreotide (Sandostatin) therapy for refractory diarrhea. Five were nonevaluable due to progression of AIDS symptomatology, and one was excluded because of lack of confirmation of HIV infection. Five of 11 evaluable patients responded to therapy (45%); two each at 50 micrograms and 100 micrograms, and one at 250 micrograms thrice daily doses. A sixth patient demonstrated a moderate reduction in stool volume at 250 micrograms thrice daily, which, although deemed clinically relevant, did not meet the criteria for response. On discontinuation of therapy, diarrhea recurred in all patients within 1-12 days, and responded to reinitiation of octreotide in those five patients who resumed treatment. Only one of the three patients with concurrent cryptosporidial infection responded to treatment. The drug was well tolerated, with mild symptomatology in three patients. Long-term treatment at a stable dose was effective in three of five treated patients for periods for seven months in one (moderate responder) and one year in two. One patient required dose increases to control symptoms, but after one year of treatment developed severe nausea following injections, which required dose cessation. One patient had partial control of his diarrhea for only three months despite two dose increases. These data suggest that octreotide may be of useful therapeutic value in HIV-associated diarrhea and that further studies are indicated.

Adult↗
PubMed1991

Effects of antibodies against octreotide in two patients with acromegaly.

Two patients developed specific IgG antibodies against octreotide after 2-3 years' treatment for acromegaly with this long acting somatostatin analogue. The presence of these antibodies reduced the plasma disappearance rate of total extractable octreotide by 60 and 80% respectively. When compared to that of non-immune acromegalic patients, the plasma half-life of octreotide in these two patients was 300 and 450 vs 110 min in those with no detectable octreotide antibodies. The sole observed consequence of the immunization was a marked prolongation of the interval of maximum GH inhibition from a mean of 5 to 8 and 10 h in the two patients described after octreotide injection.

Acromegaly↗
PubMed1991

Effect of octreotide on 24-hour growth hormone and prolactin secretory patterns in acromegalics.

Four adult patients with active acromegaly underwent studies of their 24-hour secretory pattern of hGH and Prl prior to and at the end of 3 months of treatment with the octreotide (somatostatin analog SMS 201-995) 100 micrograms s.c. every 8 h. Blood was withdrawn at 30-min intervals with the aid of a constant withdrawal pump. The best fit cosinor method was used to define the following rhythm parameters: mesor, amplitude, acrophase and periodicity. Prior to treatment, hGH secretion was increased in all patients. The mean 24-hour ranged from 9-47 ng/ml with amplitude 5.2-23 and observed maximal pulse 41-95 ng/ml. Computed rhythms were circadian in 3 patients and ultradian in 1; in 2 patients the acrophases were shifted to daytime. hPrl secretion was altered in 3 of the patients. Two had elevated mean 24-hour of 17.7 and 22.2 ng/ml, while computed rhythms showed semicircadian periodicity in 1 of them and circadian periodicity with a shift of acrophase to daytime in the other. The third patient who had normal hPrl levels, showed ultradian 8-hour periodicity. At the end of treatment there was a marked reduction in hGH secretion in 1 patient and a lesser reduction in the other 3. The rhythm was influenced by the masking effect of the drug, to yield an 8-hour period with acrophases related to injection clock time having equal amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1991

Shrinkage of a primary thyrotropin-secreting pituitary adenoma treated with the long-acting somatostatin analogue octreotide (SMS 201-995).

The long-acting somatostatin agonist octreotide can control TSH hypersecretion from most thyrotropic adenomas. Octreotide therapy has even been shown to improve chiasmal dysfunction. We report another patient in whom octreotide therapy was associated with gradual suppression of TSH hypersecretion, which escaped partially, dramatic and very rapid and sustained improvement of chiasm compression, and dramatic and sustained shrinkage of an unresectable TSH-secreting pituitary tumour. Unusual and prolonged gastrointestinal adverse reactions eventually disappeared except for steatorrhea. In conclusion, octreotide may be considered as first line treatment in patients with unresectable thyrotropic adenomas.

Adenoma↗
PubMed1991

Octreotide treatment in acromegaly: a comparison between pen-treated and pump-treated patients in a cross-over study.

The effect of a schedule of three daily injections of 100 micrograms octreotide (pen treatment) compared with that of a continuous sc infusion of 300 micrograms/24 h on GH and IGF-I suppression, and other GH-dependent parameters was studied in 10 acromegalic patients in a cross-over study. Treatment was administered via a specially designed pen or a pump for 4 weeks. Following a washout period of a further 4 weeks, patients were switched to the other mode of delivery. Mean GH levels decreased from 26.2 +/- 4.7 to 9.9 +/- 3.1 mU/l (p = 0.007) during pen therapy and to 7.7 +/- 2.4 mU/l (p = 0.003) during pump treatment. IGF-I levels decreased from 75.6 +/- 9.5 to 42.0 +/- 9.3 nmol/l (p = 0.003) during pen treatment and to 32.5 +/- 2.5 nmol/l (p = 0.001) during pump treatment. There was a significant difference in IGF-I levels between pen and pump treatments (p = 0.03). In 7 patients the IGF-I levels normalized during pump treatment compared with 3 patients in the pen treatment group. There was no change in the free T4 index levels, but the free T3 index significantly decreased during therapy, without changes in plasma TSH. This study demonstrates that continuous infusion with octreotide results in a better control of GH oversecretion than the intermittent mode of delivery.

Acromegaly↗
PubMed1991

Dynamics of the acute effects of octreotide, bromocriptine and both drugs in combination on growth hormone secretion in acromegaly.

The separate and combined GH-lowering effects of single doses of octreotide and bromocriptine were assessed in 51 acromegalic patients on 4 occasions each 2 days apart. Patients received sequentially: placebo sc (N = 51), 50 micrograms octreotide sc (N = 51), 2.5 mg bromocriptine po (N = 40) or a combination of both drugs (N = 25). With octreotide, in 28 patients (55%) GH levels were suppressed to less than 5 micrograms/l and 39 of them (76.5%) had a 50% or greater decrease of their basal GH level from 2 to 6 h. During bromocriptine, GH values were suppressed to below 5 micrograms/l in 11 patients (27.5%) and reduced by 50% or more in 21 (52.5%). The combination of both drugs acutely suppressed GH levels to less than 2 micrograms/l in 32%, to less than 5 micrograms/l in 56%, and by more than 50% in 84% of patients. Octreotide produced a stronger and faster suppression of GH levels than bromocriptine in most patients. The combination of both drugs had an additive effect on the lowering of GH levels, especially between 7 and 10 h after drug administration. These results suggest that chronic therapy with a combination of both drugs may be as effective as therapy with higher doses of either compound alone. Albeit transient, octreotide caused a rapid near total suppression of insulin release in the morning, 15 to 45 min after administration. Postprandial glucose rise, between 2 and 3.5 h after breakfast was significantly higher during octreotide than on the control day.

Acromegaly↗
PubMed1991

[Effects of biliary lithogenesis in acromegalic patients with long-term octreotide (SMS 201-995) treatment].

This study was performed to evaluate the risk of gallstone formation during long-term treatment with the long-acting somatostatin analog octreotide (SMS 201-995). Twelve patients (8 men, 4 women--mean age 43 years) treated with continuous subcutaneous octreotide infusion for acromegaly (mean duration 26.5 months, mean dose 541 micrograms/day) were included. Bile collection by duodenal intubation was performed before, during, and 45 days after octreotide treatment in 3, 12, and 8 patients, respectively. Abdominal ultrasonography and/or oral cholecystrography were also performed before (n = 9 patients), during (n = 12), and after treatment (n = 10). Bile examination was normal in the 3 patients controlled before treatment but showed that 58.3 percent of the treated patients had cholesterol monohydrate crystals. After discontinuation of octreotide only 25 percent of patients had cholesterol crystals. In 3 patients (25 percent) treated longer than 6 months, cholesterol crystals occurred prior to the occurrence of small radiolucent gallstones: one patient underwent cholecystectomy because of biliary colic, while in the two others, complete dissolution of stones was obtained after 10 months of treatment with ursodeoxycholic acid given in association with octreotide. None of the 9 other acromegalic patients (including 7 treated more than 20 months) developed stones. Cholesterol gallstone formation seems to be increased in acromegalic patients during long-term octreotide treatment but the exact incidence remains to be determined in larger series of patients.

Acromegaly↗
PubMed1991

Long-term treatment of 189 acromegalic patients with the somatostatin analog octreotide. Results of the International Multicenter Acromegaly Study Group.

BACKGROUND: We wanted to determine the clinical and biochemical effects of long-term therapy with the somatostatin analog octreotide in 189 acromegalic patients. METHODS: Patients were treated at 23 medical centers for 6 days to 231 weeks (median, 24.2 weeks) with varying octreotide dosages (100 to 1500 micrograms/d; median, 300 micrograms/d). Serum growth hormone and insulin-like growth factor I (IGF-I) concentrations before and at the end of the study were compared, and correlations between the response to treatment with total daily dosage and duration of treatment were sought. RESULTS: The clinical response rate was 88%, irrespective of dosage or treatment duration. Serum growth hormone levels decreased in 172 (94%) of 182 patients and IGF-I levels decreased in 91 (92%) of 99. The mean pretreatment growth hormone level was 39.4 +/- 4.4 micrograms/L and decreased to 12.2 +/- 1.5 micrograms/L. Growth hormone levels decreased to less than 5 micrograms/L in 82 (45%) of 182 patients. The pretreatment IGF-I level was 5.62 +/- 0.41 U/mL and decreased to 2.64 +/- 0.19 U/mL; suppression to 2 U/mL or lower occurred in 46 (46%) of 99 patients. The degree of growth hormone suppression was associated with longer treatment duration but not with the total octreotide dosage per day. In 34 patients studied prospectively, pituitary tumor size decreased by greater than 20% in 15 (44%). Side effects occurred in 37% of patients and were most commonly transient loose alcoholic stools, pain at the injection site, and abdominal discomfort; severity was mild to moderate. Glucose tolerance was unchanged or improved in 52% and declined in 48% of 25 patients evaluated. CONCLUSIONS: Octreotide is an effective treatment for acromegaly that may be used as primary therapy or after surgery and/or pituitary irradiation.

Acromegaly↗
PubMed1990

Cardiovascular effects of the somatostatin analog octreotide in acromegaly.

OBJECTIVE: To determine the cardiovascular effects of the somatostatin analog octreotide in patients with acromegaly. DESIGN: Prospective nonrandomized study. SETTING: Referral-based endocrinology clinic. PATIENTS: Seven patients with active acromegaly, three of whom had refractory congestive heart failure. The other four patients were free of symptoms associated with heart failure. INTERVENTIONS: All patients were treated with octreotide, 100 to 500 micrograms subcutaneously three times daily. The three patients with heart failure continued to receive cardiovascular therapy (angiotensin converting enzyme inhibitors, digitalis, diuretics). MEASUREMENTS AND MAIN RESULTS: During octreotide therapy, patients showed a rapid decrease in growth hormone and insulin-like growth factor 1 (IGF-1): Mean levels (+/- SD) fell from 28.1 +/- 32.7 micrograms/L to 5.2 +/- 8.3 micrograms/L and 740 +/- 126 micrograms/L to 372 +/- 64 micrograms/L, respectively (P less than 0.025). Plasma volume returned to normal and heart rate decreased significantly. In the four patients without heart failure, right-heart catheterization done before and after 3 months of octreotide therapy showed an 18.3% +/- 11% reduction in stroke volume and a return to normal of the cardiac index. The three patients with congestive heart failure, evaluated before and after 40 days and up to 2 years of therapy, showed a dramatic clinical improvement that was associated with an increase in stroke volume (by 24% to 51%). In these patients, the cardiac index remained in the normal range, filling pressures were markedly decreased, and pulmonary wedge pressure returned to normal. This improvement was sustained for up to 3 years in the two patients with heart failure who were receiving long-term treatment. CONCLUSION: The rapid and sustained cardiac improvement seen in our patients shows that octreotide therapy for patients with acromegaly may be highly beneficial, even in those patients with advanced cardiac failure.

Acromegaly↗
PubMed1990

Future medical prospects for Sandostatin.

Because of its widespread distribution within the nervous system and gastroenteropancreatic (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 (octreotide, Sandoz Ltd), a long-acting, synthetic octapeptide analog of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of growth hormone (GH) and thyrotropin (TSH)-secreting pituitary tumors and GEP endocrine tumors (carcinoid tumor, 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 tumor cells and an indirect effect whereby Sandostatin lowers GH, insulin-like growth factor type 1 (IGF-1), and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labeling of somatostatin receptor-positive tumors with radiolabeled somatostatin analogs now allows localization of such tumors and their metastases. In addition, targeted irradiation of these tumors by beta particle-emitting isotopes attached to such somatostatin analogs may become possible. The use of Sandostatin in acute esophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal, and pancreatic external fistulae, short bowel syndrome, dumping syndrome and acquired immunodeficiency syndrome (AIDS)-related refractory hypersecretory diarrhea has provided encouraging results.(ABSTRACT TRUNCATED AT 250 WORDS)

Forecasting↗
PubMed1990

Clinical and biochemical effects of incremental doses of the long-acting somatostatin analogue SMS 201-995 in ten acromegalic patients.

Ten patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open-label prospective trial of 3 daily subcutaneous injections of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201-995 doses were increased in a stepwise fashion from 100 micrograms every 8 h (three times daily) to 200, 300 and finally 500 micrograms three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12-h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 micrograms t.i.d. in 7/10 patients. Somatomedin-C (SM-C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201-995 up to 500 micrograms three times daily did not produce further clinically relevant GH or SM-C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side-effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 micrograms/day and one patient on 600 micrograms/day after 6-12 months treatment. This dose-finding study shows that 100 micrograms three times daily SMS 201-995 is an effective therapy for most of the acromegalic patients we treated.

Acromegaly↗