Intensive care management of patients with viral encephalitis.

Viral encephalitis is a severe syndrome that can lead to encephalopathy, seizures, focal deficits, and neurological sequelae and death. It is mainly caused by neurotropic herpes viruses (i.e., HSV and VZV), although other pathogens may be observed in specific geographic regions or conditions. Recent advances in neuroimaging and molecular biology (PCR, metagenomics) allow for faster and more accurate etiological diagnoses, although their benefits need to be confirmed to provide guidelines for their use and interpretation. Despite intravenous acyclovir therapy and supportive care, outcomes remain poor in about two-thirds of herpes encephalitis patients requiring ICU admission. Randomized clinical trials focusing on symptomatic measures (i.e. early ICU admission, fever control, and treatment of seizures/status epilepticus) or adjunctive immunomodulatory therapies (i.e. steroids, intravenous immunoglobulins) to improve neurologic outcomes have not been conducted in the ICU setting. Large prospective multicenter studies combining clinical, electrophysiological, and neuroimaging data are needed to improve current knowledge on care pathways, long-term outcomes, and prognostication.

3D reconstructions, 4D imaging and postprocessing with CT in musculoskeletal disorders: Past, present and future.

Three-dimensional (3D) imaging and post processing are common tasks used daily in many disciplines. The purpose of this article is to review the new postprocessing tools available. Although 3D imaging can be applied to all anatomical regions and used with all imaging techniques, its most varied and relevant applications are found with computed tomography (CT) data in musculoskeletal imaging. These new applications include global illumination rendering (GIR), unfolded rib reformations, subtracted CT angiography for bone analysis, dynamic studies, temporal subtraction and image fusion. In all of these tasks, registration and segmentation are two basic processes that affect the quality of the results. GIR simulates the complete interaction of photons with the scanned object, providing photorealistic volume rendering. Reformations to unfold the rib cage allow more accurate and faster diagnosis of rib lesions. Dynamic CT can be applied to cinematic joint evaluations a well as to perfusion and angiographic studies. Finally, more traditional techniques, such as minimum intensity projection, might find new applications for bone evaluation with the advent of ultra-high-resolution CT scanners. These tools can be used synergistically to provide morphologic, topographic and functional information and increase the versatility of CT.

Correction to: Functional outcomes in adult patients with herpes simplex encephalitis admitted to the ICU: a multicenter cohort study.

The original article unfortunately contained a mistake. Due to technical problems the study group was not tagged correctly. Please find the correct tagging down below. We apologize for the mistake.

Functional outcomes in adult patients with herpes simplex encephalitis admitted to the ICU: a multicenter cohort study.

PURPOSE: We aimed to study the association of body temperature and other admission factors with outcomes of herpes simplex encephalitis (HSE) adult patients requiring ICU admission. METHODS: We conducted a retrospective multicenter study on patients diagnosed with HSE in 47 ICUs in France, between 2007 and 2017. Fever was defined as a body temperature higher or equal to 38.3 °C. Multivariate logistic regression analysis was used to identify factors associated with poor outcome at 90 days, defined by a score of 3-6 (indicating moderate-to-severe disability or death) on the modified Rankin scale. RESULTS: Overall, 259 patients with a score on the Glasgow coma scale of 9 (6-12) and a body temperature of 38.7 (38.1-39.2) °C at admission were studied. At 90 days, 185 (71%) patients had a poor outcome, including 44 (17%) deaths. After adjusting for age, fever (OR = 2.21; 95% CI 1.18-4.16), mechanical ventilation (OR = 2.21; 95% CI 1.21-4.03), and MRI brain lesions > 3 lobes (OR = 3.04; 95% CI 1.35-6.81) were independently associated with poor outcome. By contrast, a direct ICU admission, as compared to initial admission to the hospital wards (i.e., indirect ICU admission), was protective (OR = 0.52; 95% CI 0.28-0.95). Sensitivity analyses performed after adjustment for functional status before admission and reason for ICU admission yielded similar results. CONCLUSIONS: In HSE adult patients requiring ICU admission, several admission factors are associated with an increased risk of poor functional outcome. The identification of potentially modifiable factors, namely, elevated admission body temperature and indirect ICU admission, provides an opportunity for testing further intervention strategies.

CT arthrography of the intra-articular long head of biceps tendon: Diagnostic performance outside the labral-bicipital complex.

PURPOSE: The purpose of this study was to determine the performance of CT arthrography for the diagnosis of intra-articular long head of biceps (LHB) tendon intrinsic lesions using arthroscopy findings as standard of reference. MATERIAL AND METHODS: CT arthrography studies of 98 patients (55 men, 43 women; mean age 54.8±12.7 [SD] years [range: 16-77 years]) were retrospectively evaluated by two radiologists independently. Per operative arthroscopic images and surgical reports were retrospectively reviewed by a shoulder-specialist surgeon. Based on the analysis of arthroscopic images and the surgical reports, the LHB tendon was classified as normal (continuous with uniform tendon thickness), tendinopathy/partial rupture (focal change in tendon thickness and contour irregularities) and total rupture (total loss in tendon continuity). Imaging results were compared to those of surgery that served as standard of reference. Interobserver agreement was assessed. RESULTS: At arthroscopy, the LHB tendon was classified as normal in 38/98 (38.8%) patients, tendinopathic in 51/52 (52%) and totally ruptured in 9/98 (9.2%). The sensitivity and specificity of CT arthrography for the diagnosis of LHB tendinopathy were respectively 74% (95%CI: 60%-85%) and 93% (95%CI: 80%-99%) for reader 1 and 79% (95% CI: 67%-89%) and 95% (95% CI: 83%-99%) for reader 2. The sensitivity and specificity for the diagnosis of LHB tendon total ruptures were 100% (95%CI: 66%-100%) and 93% (95%CI: 86%-98%) for both readers. Interobserver agreements for the identification of the LHB tendon tendinopathy and total ruptures were excellent (kappa values of 0.94 and 0.96, respectively). CONCLUSION: CT arthrography demonstrates good sensitivity and excellent specificity for the detection of intra-articular LHB tendinopathy and tear.

Relevance of coexpression of somatostatin and dopamine D2 receptors in pituitary adenomas.

Dopamine and somatostatin are both involved in the negative control of normal pituitary cells. Dopamine subtype 2 receptor (D2DR) and somatostatin receptor (sst) agonists, mainly directed to sst2, are used in the treatment of pituitary adenomas. Nevertheless, a majority of corticotroph and gonadotroph adenomas and a third of somatotroph adenomas are still not sufficiently controlled by these treatments. D2DR and sst1, 2, 3 and 5 are present in most pituitary adenomas. These receptors may interact by heterodimerization as shown for sst1-sst5, sst5-D2DR, sst2-sst3 and sst2-D2DR suggesting possible additive effects. D2DR and sst2 agonist cotreatment showed limited additivity on GH secretion in acromegaly. Moreover, new chimeric compounds with sst2, D2DR and sst5 affinity have shown an increased control of secretion and/or proliferation of different types of pituitary adenomas in cell culture. Together with the multi-sst ligand drugs recently developed, these dopamine-somatostatin ligands represent a new opportunity in the combinatory treatment of pituitary adenomas.

Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease.

CONTEXT: Although transsphenoidal surgery remains the first-line treatment in Cushing's disease (CD), recurrence is observed in about 20% of cases. Adjunctive treatments each have specific drawbacks. Despite its inhibitory effects on steroidogenesis, the antifungal drug ketoconazole was only evaluated in series with few patients and/or short-term follow-up. OBJECTIVE: Analysis of long-term hormonal effects and tolerance of ketoconazole in CD. DESIGN: A total of 38 patients were retrospectively studied with a mean follow-up of 23 months (6-72). SETTING: All patients were treated at the same Department of Endocrinology in Marseille, France. PATIENTS: The 38 patients with CD, of whom 17 had previous transsphenoidal surgery. INTERVENTION: Ketoconazole was begun at 200-400 mg/day and titrated up to 1200 mg/day until biochemical remission. MAIN OUTCOME MEASURES: Patients were considered controlled if 24-h urinary free cortisol was normalized. RESULTS: Five patients stopped ketoconazole during the first week because of clinical or biological intolerance. On an intention to treat basis, 45% of the patients were controlled as were 51% of those treated long term. Initial hormonal levels were not statistically different between patients controlled or uncontrolled. Ketoconazole was similarly efficacious as a primary or postoperative treatment. Among 15 patients without visible adenoma at initial evaluation, subsequent follow-up allowed identification of the lesion in five cases. No adrenal insufficiency was observed. Adverse effects were rare in patients treated long term. CONCLUSIONS: Ketoconazole is a safe and efficacious treatment in CD, particularly in patients for whom surgery is contraindicated, or delayed because of the absence of image of adenoma on magnetic resonance imaging.

Desmopressin test during petrosal sinus sampling: a valuable tool to discriminate pituitary or ectopic ACTH-dependent Cushing's syndrome.

UNLABELLED: Corticotropin-releasing hormone (CRH)-stimulated petrosal sinus sampling is currently the gold standard method for the differential diagnosis between pituitary and ectopic ACTH-dependent Cushing's syndrome. Our objective was to determine sensitivity and specificity of desmopressin test during petrosal sinus sampling. PATIENTS AND METHODS: Forty-three patients had petrosal sinus sampling because of the lack of visible adenoma on magnetic resonance imaging (MRI) and/or because of discordant cortisol response to high-dose dexamethasone suppression test. ACTH sampling was performed in an antecubital vein, right and left petrosal sinuses, then at each location 5 and 10 min after injection of desmopressin. Diagnosis was based on the ACTH ratio between petrosal sinus and humeral vein ACTH after desmopressin test. Diagnosis was confirmed after surgery. A receiver operating characteristics curve was used to determine optimal sensitivity and specificity. RESULTS: Thirty-six patients had Cushing's disease (CD) and seven had ectopic ACTH secretion. A ratio > 2 after desmopressin was found in 35 of the 36 cases of CD (sensitivity: 95%). A ratio < or = 2 was found in the seven patients with ectopic ACTH secretion (specificity: 100%). Sinus sampling was ineffective in determining the left or right localization of the adenoma (sensitivity = 50%). No major adverse effects were observed during or after the procedure. CONCLUSION: Desmopressin test during petrosal sinus sampling is a safe and effective diagnostic procedure in ACTH-dependent Cushing's syndrome. It thus represents a valuable alternative to CRH.

Prolactinoma surgery.

Surgery is generally used as second-line treatment in prolactinomas. For microprolactinomas, it may be indicated in cases of resistance or intolerance to dopamine agonists or where patients prefer definitive cure to lifelong drug treatment. In highly trained hands, selective adenomectomy results in normalization of prolactin levels in 75-90% of cases with little morbidity and no mortality. However, subsequent relapse is possible in up to 20% of cases. In macroprolactinoma, a definitive cure is unlikely due to the frequency of invasive tumor extension. A transsphenoidal or, less frequently, a transfrontal surgical approach is necessary in patients resistant to or intolerant of medical treatment, and also in rare cases such as pituitary apoplexy or cerebrospinal fluid rhinorrhea.

Gamma knife radiosurgery is a successful adjunctive treatment in Cushing's disease.

OBJECTIVE: Though transsphenoidal surgery remains the first-line treatment of Cushing's disease, recurrence occurs frequently. Conventional radiotherapy and anticortisolic drugs both have adverse effects. Stereotactic radiosurgery needs to be evaluated more precisely. The aim of this study was to determine long-term hormonal effects and tolerance of gamma knife (GK) radiosurgery in Cushing's disease. DESIGN: Forty patients with Cushing's disease treated by GK were prospectively studied over a decade, with a mean follow-up of 54.7 months. Eleven of them were treated with GK as a primary treatment. METHODS: Radiosurgery was performed at the Department of Functional Neurosurgery of Marseille, France, using the Leksell Gamma Unit B and C models. Median margin dose was 29.5 Gy. Patients were considered in remission if they had normalized 24-h free urinary cortisol and suppression of plasma cortisol after low-dose dexamethasone suppression test. RESULTS: Seventeen patients (42.5%) were in remission after a mean of 22 months (range 12-48 months). The two groups did not differ in terms of initial hormonal levels. Target volume was significantly higher in uncured than in remission group (909.8 vs 443 mm(3), P = 0.038). We found a significant difference between patients who were on or off anticortisolic drugs at the time of GK (20 vs 48% patients in remission respectively, P = 0.02). CONCLUSION: With 42% of patients in remission after a median follow-up of 54 months, GK stereotactic radiosurgery, especially as an adjunctive treatment to surgery, may represent an alternative to other therapeutic options in view of their adverse effects.

[Diagnostic value of autoantibodies to MAG by ELISA Bühlmann in 117 immune-mediated peripheral neuropathies associated with monoclonal IgM to SGPG/SGLPG]. / Les autoanticorps IgM anti-MAG par Elisa Bühlmann: apport diagnostique dans 117 neuropathies périphériques auto-immunes associées à une IgM monoclonale à activité anti-SGPG/SGLPG.

The neuropathies associated with monoclonal IgM gammopathy reacted with glycoconjugated targets on a very antigenic epitope on the sulfated glucuronic glycolipids corresponding to SGPG and SGLPG (sulfoglucuronyl paragloboside and sulfoglucuronyl lactosaminyl paragloboside), myelin-associated glycoprotein (MAG) and sulfatide. Sometimes monoclonal IgM binds to a broad spectrum of gangliosides. The detection of targets of autoantibodies has considerable importance in the diagnosis and management of patients. It is not known whether the results of antibody tests are equally sensitive and specific for identification of involved auto-antigens. In this study we evaluated the results obtained using IgM reactivity against MAG by enzyme-linked immunosorbent assay (ELISA Bühlmann) with IgM reactivity against SGPG/SGLPG obtained by overlay thin-layer chromatography. We selected 117 patients with anti-SGPG/SGLPG monoclonal gammopathy and peripheral neuropathy and a control group of 102 peripheral neuropathies with 24 having IgM high titres of monoclonal IgM anti-ganglioside antibodies. The anti-MAG sensitivity was 0.97, specificity was 0.86. There is a crossreactivity between 8 (57%) monoclonal IgM antibodies anti-MAG and anti-ganglioside GM1 and 2 (28%) anti-disialylated gangliosides. These results indicate that in clinical practice, anti-MAG ELISA is useful for eliminating anti-MAG neuropathy, as well as for positive diagnosis for titres upper than 10,000 BTU. It is also alpha good test to appreciate clinical improvement after Rituximab treatment.

Consensus statement: medical management of acromegaly.

In November 2003, the Pituitary Society and the European Neuroendocrine Association sponsored a consensus workshop in Seville to address challenging issues in the medical management of acromegaly. Participants comprised 70 endocrinologists and neurosurgeons with international expertise in managing patients with acromegaly. All participants participated in the workshop proceedings, and the final document written by the scientific committee reflects the consensus opinion of the interactive deliberations. The meeting was supported by an unrestricted educational grant from Ipsen. No pharmaceutical representatives participated in the program planning or in the scientific deliberations.

New SRIF analogs in the control of human pituitary adenomas: perspectives.

SRIF receptor (sst) subtypes expressed on the different neuroendocrine tumors are the basis for treatment of such tumors with SRIF analogues. Although the drugs of reference, octreotide and lanreotide, are widely used in the treatment of acromegaly, their long-term administration allows an effective control of both GH hypersecretion and IGF-I levels in about 60% of the patients. This variable sensitivity is related to a significant loss of the sst subtype 2 (sst2) in the octreotide partial responder acromegalic patients. Such a decrease is rescued, in these tumors, by an overexpression of the sst5. Further, all GH-secreting adenomas coexpress the D2 dopamine receptor, which also mediates the inhibitory effect of dopamine agonists on GH secretion in acromegalic tumors. Such specific profiles of receptor expression in this class of neuroendocrine tumors led to the development of new ligand molecules directed towards sst2 + sst5 receptors, sst1 + sst2 + sst3 + sst5 receptors, or sst2 + dopamine D2 receptors. These bi- or multivalents ligands proved, in cell culture studies, more effective than their single components for inhibiting GH and PRL secretion. This review covers the data recently issued using such hybrid or chimeric compounds. The mechanism(s) by which such ligands may act are yet unknown. One possible explanation of their increased potency could be through their ability to induce oligodimerization of the receptors at the cell membrane level, and modify, in a ligands-specific manner, the subsequent trafficking and recycling of the receptors. New details from the literature are reviewed, supporting the importance of such ligands into the agonist-dependant control of G-protein-coupled receptors oligomerization.

Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy.

OBJECTIVE: This study compared the potency of a somatostatin receptor (sstr)2-sstr5 analog, BIM-23244, of an sstr2-dopamine D2 receptor (sstr2-DAD2) molecule, BIM-23A387 and of new somatostatin-dopamine chimeric molecules with differing, enhanced affinities for sstr2, sstr5 and DAD2, BIM-23A758, BIM-23A760 and BIM-23A761, to suppress GH and prolactin (PRL) from 18 human GH adenomas that are partially responsive to octreotide or lanreotide. MATERIALS AND METHODS: The sstr2, sstr5 and DAD2 mRNA levels were determined by RT-PCR. The effect of drugs was tested in cell cultures at various concentrations. RESULTS: In all tumors, the sstr2, sstr5 and DAD2 mRNA levels were coexpressed (mean levels+/-s.e.m. 0.4+/-0.1, 5.3+/-1.9 and 2.0+/-0.4 copy/copy beta-glucuronidase). In 13 tumors, the maximal suppression of GH secretion produced by BIM-23A387 (30+/-3%) and BIM-23244 (28+/-3%) was greater than that produced by octreotide (23+/-3%). In six out of 13 tumors, BIM-23A758, BIM-23A760 and BIM- 23A761 produced greater maximal suppression of GH secretion than octreotide (33+/-5, 38+/-2 and 41+/-2 vs 24+/-2%). Their EC(50) values were 10, 2 and 4 pmol/l. BIM-23A761 was more effective than BIM-23A387 in GH suppression (41+/-2 vs 32+/-4%). The new chimeric molecules produced maximal PRL suppression greater than octreotide (62+/-8 to 74+/-5 vs 46+/-11%). CONCLUSIONS: Novel dopamine-somatostatin chimeric molecules with differing, enhanced activity at sstr2, sstr5 and DAD2, consistently produced significatly greater suppression of GH and PRL than either octreotide or single-receptor-interacting ligands in tumors from patients classified as only partially responsive to octreotide therapy. The higher efficacy of the chimeric compounds was, at least partially, linked to their high affinity for sstr2 (IC50 1-10 pmol/l). The other mechanisms by which such molecules produce an enhanced inhibition of GH remain to be elucidated.

BIM-23A760, a chimeric molecule directed towards somatostatin and dopamine receptors, vs universal somatostatin receptors ligands in GH-secreting pituitary adenomas partial responders to octreotide.

We report the comparative efficacy of a somatostatin receptor 1 and 5 subtypes (SSTR2 and SSTR5), and dopamine D2 (DAD2) compound, BIM-23A760, in suppressing GH secretion, in cell culture from human GH-secreting tumors, from patients partially responsive to long-term treatments with octreotide or lanreotide. In 18 tumors tested, the SSTR2, SSTR5, and DAD2 mRNAs were coexpressed. The SSTR2-selective analog, BIM-23197, the SSTR5-selective analog, BIM-23268, and the dopamine (DA) analog, BIM-53097, produced a mean maximal suppression of GH secretion (24 +/- 3, 20 +/- 3, and 20 +/- 3%, respectively) that was similar to that obtained with octreotide (23 +/- 3%). Nevertheless, based on individual responses, 60% of the tumors were mostly sensitive to the SSTR2 analog while 19 and 21% of the tumors were mainly responsive to the SSTR5 analog and to the DA analog, respectively. Among a series of new chimeric compounds that bind the SSTR2, SSTR5, and DAD2 receptors with variable affinities, BIM-23A760 produced greater maximal suppression of GH secretion than octreotide (38 +/- 2 vs 24 +/- 2%; p<0.03). The EC50 for BIM-23A760 was 2 pmol/l. In the presence of sulpride, the dose response inhibition of GH secretion by the trihybrid molecule, BIM-23A760, was partially reversed. The trihybrid produced also a maximal suppression of PRL greater than octreotide (74 +/- 5 vs 46 +/- 11%). When SSTRs pan inhibitors such as BIM-23A779 (binding affinity for SSTR1, SSTR2, SSTR3, SSTR5, respectively: 2.5, 0.3, 0.6, 0.6 nmol/l) or SOM230 were tested for their suppressive effects on GH secretion, they were less potent than the previous dopastatin hybrid molecule. After a brief exposure to a SSTR2-selective analog, BIM-23197, or to a DA analog, BIM-53097, the maximal GH suppression was achieved during 12 h. Under exposure to BIM-23A760, in the same conditions, maximal suppression of GH secretion lasted for 24 h. Such a longer biological effect, yet not explained, probably participates in the higher efficacy of BIM-23A760. The higher efficacy of BIM-23A760 is, at least partially, linked to its high affinity for the SSTR2 receptor subtype (IC50: 3 pmol/l). As compared to the dopastatin compound, the lower efficacy of the universal somatostatin ligands in the inhibition of GH secretion of GH-secreting tumors argues for the use of drugs targeted, according to specific receptors expression and functionality which may vary among the various classes of tumors.

Novel modalities of somatostatin actions.

The first part of this contribution reviews the current knowledge about endocrine and neuromodulatory actions of somatostatin. These biological actions are exerted according to endocrine, paracrine and autocrine modes of action and involve five distinct types of membrane receptors belonging to the 'super-family' of G-protein-coupled receptors. A new concept concerning a juxtacrine mode of action has recently been introduced to refer to the intervention of cytokines and growth factors in direct, cell-to-cell communication. The evidence in favor of juxtacrine actions of somatostatin will be presented in the second part of this review and illustrated by our own results on macrophage-lymphocyte T interactions in the immune system and spermatogonia-Sertoli cell interactions in mammalian testis. Another phenomenon such as ligand-induced somatostatin receptor homo- and hetero-dimerization resulting in 'poly'-receptors (with characteristics different from those of each of the two receptors forming the complex) is also at the origin of a novel mode of somatostatin action. The latter will be illustrated by the data obtained on human pituitary adenomas with somatostatin analogs specific for either 'poly'-receptor or relevant individual receptors. The arguments in favor of the analogous mode of actions among different families of chemical messengers such as peptides, cytokines and growth factors are discussed in the concluding section. The emerging unifying concepts on such functional analogies might provide a useful basis for the development of synthetic analogs not only for bioactive peptides but also for other types of chemical messengers.

Diagnosis and treatment of acromegaly complications.

The Pituitary Society in conjunction with the European Neuroendocrine Association held a consensus workshop to develop guidelines for diagnosis and treatment of the co-morbid complications of acromegaly. Fifty nine pituitary specialists (endocrinologists, neurosurgeons and cardiologists) assessed the current published literature on acromegaly complications in light of recent advances in maintaining tight therapeutic control of GH hypersecretion. The impact of elevated GH levels on cardiovascular disease, hypertension, diabetes, sleep apnea, colon polyps, bone disease, reproductive disorders, and neuropsychologic complications were considered. Guidelines are proposed for effective management of these complications in the context of overall acromegaly control. When appropriate, requirements for prospective evidence-based studies and surveillance database development are enunciated. Effective management of co-morbid acromegaly complications will lead to improved morbidity and mortality in acromegaly.

Demonstration of enhanced potency of a chimeric somatostatin-dopamine molecule, BIM-23A387, in suppressing growth hormone and prolactin secretion from human pituitary somatotroph adenoma cells.

In acromegaly, the combination of somatostatin (SS) and dopamine (DA) agonists has been shown to enhance suppression of GH secretion. In the present study, a new chimeric molecule, BIM-23A387, which selectively binds to the SS subtype 2 receptor (sst(2); K(i) = 0.10 nM) and to the DA D2 receptor (D2DR; K(i) = 22.1 nM) was tested in cultures prepared from 11 human GH-secreting tumors for its ability to suppress GH and prolactin (PRL) secretion. The chimeric compound was compared with individual sst(2) and D2DR agonists of comparable activity at the individual receptors. All tumors expressed both sst(2) and D2DR mRNAs (0.8 +/- 0.2 and 4.7 +/- 0.7 copy/copy beta-glucuronidase mRNA, respectively). In cell cultures from seven octreotide-sensitive tumors, the maximal inhibition of GH release induced by the individual sst(2) and D2DR analogs and by BIM-23A387 was similar. However, the mean EC(50) for GH suppression by BIM-23A387 (0.2 pM) was 50 times lower than that of the individual sst(2) and D2DR analogs, either used individually or combined. Similar data were obtained in four tumors that were only partially responsive to octreotide. The inhibition of GH release by BIM-23A387 was only partially reversed by the D2R2 antagonist, sulpiride, or by the sst(2) antagonist, BIM-23454. Only when both antagonists were combined was the GH suppressive effect of BIM-23A387 totally reversed. Finally, BIM-23A387 produced a mean 73 +/- 6% inhibition of PRL in six mixed GH plus PRL tumors. These data demonstrate an enhanced potency of the chimeric molecule, BIM-23A387, in suppressing GH and PRL secretion from acromegalic tumors, which cannot be explained merely on the basis of binding affinity for SS and/or DA receptors.