Creating new guidelines on how best to treat foot symptoms in people with EB.

Epidermolysis bullosa (EB) is a complex rare condition that affects the skin and many parts of the body. Those born with EB have skin so fragile they are called 'butterfly children', their skin is quite simply as fragile as the wing of a butterfly. In the UK it is estimated that there are more than 5,000 people living with EB and 500,000 worldwide. Little clinical guidance for care existed until DEBRA International started a programme to develop clinical practice guidelines (CPGs). There were no previous guidelines and few published studies on foot care in EB so treatment decisions were largely based on individual opinion and experience. The panel - made up of clinical experts and people living with EB representing Australia, the UK, and the USA - aimed to describe foot problems in people of all ages with EB, and summarise current evidence and management. The authors used a logical podiatric (foot) care literature review focussed on patients with EB. The authors found that the evidence in this area was limited but several interventions (treatments) currently practised by podiatrists show positive outcomes. The study allowed the group to make recommendations on how to treat foot and nail disorders in patients with EB. Furthermore, the authors concluded that further research is needed. This is a summary of the study: Foot care in epidermolysis bullosa: evidence-based guideline.

Foot care in epidermolysis bullosa: evidence-based guideline.

This guideline was designed to provide service providers and users with an evidence-based set of current best practice guidelines for people and their families and carers, living with epidermolysis bullosa (EB). A systematic literature review relating to the podiatric care of patients with EB was undertaken. Search terms were used, for which the most recent articles relating to podiatric treatment were identified from as early as 1979 to the present day, across seven electronic search engines: MEDLINE, Wiley Online Library, Google Scholar, Athens, ResearchGate, Net and PubFacts.com. The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used. The first guideline draft was analysed and discussed by clinical experts, methodologists and patients and their representatives at four panel meetings. The resulting document went through an external review process by a panel of experts, other healthcare professionals, patient representatives and lay reviewers. The final document will be piloted in three different centres in the U.K. and Australia. Following an EB community international survey the outcomes indicated six main areas that the community indicated as a priority to foot management. These include blistering and wound management, exploring the most suitable footwear and hosiery for EB, management of dystrophic nails, hyperkeratosis (callus), maintaining mobility and fusion of toes (pseudosyndactyly). The evidence here is limited but several interventions currently practised by podiatrists show positive outcomes.

Abaloparatide-SC improves trabecular microarchitecture as assessed by trabecular bone score (TBS): a 24-week randomized clinical trial.

In a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to one of three different doses of abaloparatide-SC, subcutaneous teriparatide, or placebo for 24 weeks, abaloparatide-SC resulted in improvements in skeletal microarchitecture as measured by the trabecular bone score. INTRODUCTION: Subcutaneous abaloparatide (abaloparatide-SC) increases total hip and lumbar spine bone mineral density and reduces vertebral and non-vertebral fractures. In this study, we analyzed the extent to which abaloparatide-SC improves skeletal microarchitecture, assessed indirectly by trabecular bone score (TBS). METHODS: This is a post hoc analysis of a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85 years randomized to abaloparatide-SC (20, 40, or 80 µg), subcutaneous teriparatide (20 µg), or placebo for 24 weeks. TBS was measured from lumbar spine dual X-ray absorptiometry (DXA) images in 138 women for whom the DXA device was TBS software compatible. Assessments were made at baseline, 12 and 24 weeks. Between-group differences were assessed by generalized estimating equations adjusted for relevant baseline characteristics, and a pre-determined least significant change analysis was performed. RESULTS: After 24 weeks, TBS increased significantly by 2.27, 3.14, and 4.21% versus baseline in participants on 20, 40, and 80 µg abaloparatide-SC daily, respectively, and by 2.21% in those on teriparatide (p < 0.05 for each). The TBS in the placebo group declined by 1.08%. The TBS increase in each treatment group was significantly higher than placebo at 24 weeks (p < 0.0001 for each) after adjustment for age, BMI, and baseline TBS. A dose-response was observed at 24 weeks across the three doses of abaloparatide-SC and placebo (p = 0.02). The increase in TBS in the abaloparatide-SC 80 µg group was significantly greater than TPTD (p < 0.03). CONCLUSIONS: These results are consistent with an effect of abaloparatide-SC to improve lumbar spine skeletal microarchitecture, as assessed by TBS.

The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI): grading disease severity and assessing responsiveness to clinical change in epidermolysis bullosa.

BACKGROUND: The lack of validated outcome measures for epidermolysis bullosa (EB) presents major barriers to evaluating disease severity and comparing the efficacy of therapies. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) was recently introduced as a valid and reliable instrument for EB; however, its interpretation for use in clinical practice and clinical trials is yet to be defined. OBJECTIVE: To assess the interpretability of the EBDASI in classifying patients according to disease severity and clinical response. METHODS: A total of 53 outpatients with EB at two interstate institutions were prospectively evaluated. At each visit, the principal dermatologist completed the EBDASI and global assessments of disease severity and change. Classifications for mild, moderate and severe disease using the EBDASI were determined using receiver operating characteristic curves. Minimal clinically important differences for the EBDASI activity subscale were calculated and compared with the standard error of measurement. RESULTS: Total EBDASI score ranges of 0-42, 43-106 and 107-506 corresponded to mild, moderate and severe disease respectively. Reduction in EBDASI activity scores of greater than 9 indicated clinically significant improvement. An increase of 3 in the activity score indicated deterioration. CONCLUSION: The EBDASI is a responsive tool and may be useful in characterizing disease severity and response. The cut-offs proposed in this study provide the first practical guide for interpreting the EBDASI, further supporting its use for longitudinal patient assessment and in clinical trials.

Differential expression of microRNAs during allograft rejection.

MicrorRNA are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes. In addition to being involved in many biologic processes, microRNAs are important regulators in innate and adaptive immune responses. Distinct sets of expressed microRNAs are found in different cell types and tissues and aberrant expression of microRNAs is associated with many disease states. MicroRNA expression was examined in a model of heterotopic heart transplantation by microarray analyses and a unique profile was detected in rejecting allogeneic transplants (BALB/c → C57BL/6) as compared to syngeneic transplants (C57BL/6 → C57BL/6). The microRNA miR-182 was significantly increased in rejecting cardiac allografts and in mononuclear cells that infiltrate the grafts. Forkhead box (FOX) proteins are a family of important transcription factors and FOXO1 is a target of miR-182. As miR-182 increases after transplant, there is a concomitant posttranscriptional decrease in FOXO1 expression in heart allografts that is localized to both the cardiomyocytes and CD3(+) T cells. The microRNA miR-182 is significantly increased in both peripheral blood mononuclear cells and plasma during graft rejection suggesting potential as a biomarker of graft status. Our results identify microRNAs that may regulate alloimmune responses and graft outcomes.

Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: Results from the ACTIVE phase 3 trial.

BACKGROUND: Abaloparatide is a 34-amino acid peptide that selectively binds to the RG conformation of the parathyroid hormone receptor type 1. It was developed for the treatment of women with postmenopausal osteoporosis at high risk of fracture. In ACTIVE, an 18-month phase 3 study (NCT01343004), abaloparatide increased bone mineral density (BMD), decreased the risk of vertebral and nonvertebral fractures compared with placebo, and decreased the risk of major osteoporotic fractures compared with placebo and teriparatide. Here, we report a prospective, exploratory BMD responder analysis from ACTIVE. METHODS: Proportions of patients experiencing BMD gains from baseline of >0%, >3%, and >6% at the total hip, femoral neck, and lumbar spine at 6, 12, and 18 months of treatment were compared among the placebo, abaloparatide, and teriparatide groups in ACTIVE. Responders were defined prospectively as patients experiencing BMD gains at all 3 anatomic sites. RESULTS: At months 6, 12, and 18, there were significantly more >3% BMD responders in the abaloparatide group compared with placebo and teriparatide: month 6, 19.1% vs 0.9% for placebo and 6.5% for teriparatide; month 12, 33.2% vs 1.5% and 19.8%; month 18, 44.5% vs 1.9% and 32.0% (P < 0.001 for all comparisons of abaloparatide to placebo and to teriparatide). Findings were similar for the >0% and >6% responder thresholds. CONCLUSIONS: In postmenopausal women with osteoporosis, a significantly greater proportion of patients treated with abaloparatide experienced increases in BMD than did those treated with placebo or teriparatide.

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.

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.

Initial and steady-state effects of diphenhydramine and loratadine on sedation, cognition, mood, and psychomotor performance.

BACKGROUND: The classic, first-generation histamine1-receptor antagonists used to treat allergic disorders frequently cause sedation. In contrast, sedation is reduced or absent after administration of recommended doses of second-generation histamine1-receptor antagonists. We measured the initial and steady-state effects of diphenhydramine, a first-generation antihistamine, and loratadine, a second-generation antihistamine, by means of a comprehensive battery of psychometric tests that mirror real-world tasks. METHODS: Healthy volunteers (N = 98) were randomly assigned in a double-blind fashion to receive loratadine (n = 33), diphenhydramine (n = 32), or placebo (n = 33). A computerized test battery was administered at baseline, on day 1 after administration of the initial dose, and on days 3 and 5. RESULTS: After the initial dose, subjects taking diphenhydramine demonstrated poorer cognitive performance than subjects taking loratadine or placebo on tasks of divided attention, working memory, speed, and vigilance. Subjects taking diphenhydramine also reported greater fatigue and sleepiness and lower levels of motivation, and rated the quality of their performance as lower than subjects taking loratadine or placebo. On day 3, subjects taking diphenhydramine continued to show more fatigue and lower motivation, and rated the quality of their test performance as poorer than subjects taking loratadine or placebo. There were no differences between loratadine and placebo after the initial dose or steady-state (day 5) dosing for any measure of cognitive or psychomotor test performance, mood, or sedation. CONCLUSIONS: Patients taking diphenhydramine may be at risk of lapses and significant errors that may lead to potential hazards and decreased work productivity.

The reliability and validity of outcome measures for atopic dermatitis in patients with pigmented skin: A grey area.

BACKGROUND: Outcome measures for atopic dermatitis (AD) patients with pigmented skin have neither been developed nor validated. OBJECTIVE: To compare the reliability and validity of four common AD outcome measures in patients with various levels of skin darkness. METHOD: The inter- and intra-rater reliability and construct validity of the EASI (Eczema Area and Severity Index), objective-SCORing Atopic Dermatitis (oSCORAD), Three Items Severity index (TIS) and Six Areas, Six Sites Atopic Dermatitis (SASSAD) were evaluated in 18 patients of various levels of skin darkness, using their full body photographs, by five trained clinicians. RESULTS: The inter-rater reliability intraclass coefficient (ICCs) and 95% confidence intervals were poor for highly pigmented patients: EASI -.054(-.200 to .657), oSCORAD -.089(-.206 to .598), TIS -.21(-.24 to .147), SASSAD -.071(-.200 to .631); fair for mildly pigmented patients: EASI .464(.140-.839), oSCORAD .588(.265-.89), TIS.524(.200-.865), SASSAD .41(.045-.775); and fair to good for non-pigmented patients: EASI .64(.330-.908), oSCORAD .586(.263-.889), TIS .403(.09-.809), SASSAD .667(.358-.916). Erythema likely contributed to the inter-rater variability. Construct validity had significant correlations across all measures in non-pigmented patients, but no correlations in highly pigmented patients. CONCLUSION: AD outcome measures have poor reliability and validity in highly pigmented patients, with variations in erythema perception being a contributor.

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.

Morphological effects of octreotide on growth hormone-producing pituitary adenomas.

The SRIH analog octreotide is a potent GH-inhibiting agent that has been used to effectively treat patients with acromegaly. To investigate the morphological changes induced by octreotide on GH-producing pituitary tumors, we examined 86 adenomas from acromegalic patients who participated in a multicenter study. GH- producing pituitary adenomas removed from 43 patients treated preoperatively with octreotide for 4 months were compared to those obtained from 43 untreated acromegalic patients. Tissue samples were studied by histology, immunohistochemistry, and transmission electron microscopy as well as light microscopic and ultrastructural morphometry. The morphological appearance of some tumors was unaltered by octreotide treatment. Necrotic changes were not apparent in any. Acidophilia and GH immunoreactivity were more pronounced in the octreotide-treated tumors. Perivascular and interstitial fibrosis was more prevalent in the octreotide group (72% vs. 42%). An increase in hormone granularity was obvious in 4 of 15 densely granulated and 2 of 9 sparsely granulated (SG) tumors from treated patients. A decrease in cell size was conspicuous in 4 of 15 densely granulated and 2 of 10 SG adenomas. There was a slight downward trend in the cell and cytoplasmic size in all treated tumors and a slight upward trend in secretory granule size in treated SG adenomas. Only 2 of 9 SG adenomas in the octreotide group, however, demonstrated a statistically significant reduction in cell and cytoplasmic size. There was no statistically significant change in the size of nuclei, secretory granules, or lysosomes between the 2 groups. Decreased cell size and increased granularity were not linked, however. We conclude that there are no striking morphological alterations in GH pituitary adenomas that can be consistently associated with octreotide treatment.

Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients.

This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.

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.

The impact of continuous subcutaneous infusion of octreotide on gallstone formation in acromegalic patients.

Treatment of acromegaly with intermittent sc injections of octreotide is associated with an increased incidence of cholelithiasis. We investigated the incidence of gallstone formation, the occurrence of gallbladder disease, and the response of gallstones to ursodeoxycholic acid in 30 acromegalic patients who were treated with a continuous sc infusion of octreotide at doses between 200 and 800 micrograms/day for 3-70 months. Of the 30 patients, 28 had pretretment ultrasonography of the biliary tree performed, and all had frequent follow-ups. Nine patients underwent pre- and posttreatment bile sampling. No patient treated for less than 6 months and 18.5% of patients treated for more than 6 months developed new gallstones. No patient developed symptomatic cholelithiasis while receiving octreotide therapy. Of six patients who developed gallstones, four were treated with ursodeoxycholic acid, which dissolved all gallstones. One patient with gallstones experienced an episode of biliary colic when octreotide was withdrawn; however, no cholecystitis was found at subsequent cholecystectomy. Bile sampling showed that 8 (75%) of the 12 patients who were assessed demonstrated microcrystals, whereas in 3 (50%) of 6 patients who were closely analyzed thereafter, microcrystals disappeared once octreotide therapy was stopped. Our results show that continuous sc infusion octreotide therapy increases the incidence of cholelithiasis over normal values, as is the case with intermittent sc injections. Although higher octreotide levels are sustained with continuous sc infusion, this is not associated with an increased risk of gallstone formation compared with intermittent sc octreotide therapy.

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.

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.

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.