Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

Purpose

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m²) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

Nuclear cardiology in the UK 1994: activity relative to Europe, USA, and British Cardiac Society targets

Objective—To survey practice in nuclear cardiology in the UK in 1994.
Design—A questionnaire was sent to 219 centres performing nuclear imaging asking for details of current practice in nuclear cardiology. Replies were received from 192 centres (88%).
Main outcome measures—Activity in performance of myocardial perfusion imaging (MPI) and radionuclide ventriculography (RNV), anticipated changes in activity, differences between regional and district hospitals, technical imaging parameters, and referral sources.
Results—Of the responding centres, 125 (65%) performed nuclear cardiology procedures. More regional than district hospitals performed nuclear cardiology procedures (85% v 55%, p < 0.0003) and regional centres performed a higher proportion (62% v 24%, p < 0.001) of nuclear cardiology activity. Nuclear cardiology activity was 0.82 scans per 1000 population per year (MPI 0.56, RNV 0.26). There has been a significant increase (24%) in nuclear cardiology since 1988. There has been a pronounced rise in MPI (350%) while RNV has fallen by 47%. Myocardial perfusion activity in the UK remains very low (25% and 5% in regional and district hospitals, respectively) compared with the 1994 figures of 2.2/1000/year for Europe or 10.8/1000/year for the USA.
Conclusions—MPI has increased on average by 23%/annum (compound rate) since 1988, but in 1994 was still only 32% of the British Cardiac Society target of 2.6/1000/year. Proper resources for capital expenditure on new equipment and new staff will be important to maintain momentum in closing the gap. Also important is improved clinical understanding, as already implemented by including nuclear cardiology in guidelines for specialist cardiology training.

Keywords: survey;  nuclear cardiology;  myocardial perfusion imaging;  radionuclide ventriculography;  guidelines;  British Cardiac Society     

Dipyridamole is superior to dobutamine for thallium stress imaging: a randomised crossover study.

OBJECTIVE--To assess the value of dobutamine over dipyridamole as a pharmacological stressing agent in myocardial perfusion imaging with thallium-201. DESIGN--Stress and redistribution tomographic images were taken in a group of patients in a randomised crossover study of both agents. The scans were scored to give a value for the stress and redistribution images and a reversibility score (redistribution--stress). All patients had coronary angiography that was also scored. Differences between the two agents were compared by a paired t test. PATIENTS--30 patients aged 51-70 years with chest pain thought to be caused by myocardial ischaemia. 11 had had previously myocardial infarction. RESULTS--Dipyridamole caused adverse symptoms in six patients whereas dobutamine caused symptoms in 21 patients (chi 2 = 15.15, p < 0.0001). Dobutamine stress took considerably longer than dipyridamole (31 v 6 minutes) and cost more (17 pounds v 1.50 pounds). There were no significant differences between the agents in terms of total stress or redistribution scores, but regional analysis showed that dipyridamole showed significantly more defects during stress at the apex and lateral wall (p < 0.05), with no significant difference at redistribution. Dipyridamole stress also caused significantly more reversible defects at the apex (p < 0.05) and gave a better correlation than dobutamine with coronary score (dipyridamole r = 0.80, p < 0.001 v dobutamine r = 0.64, p < 0.001). In six patients who had continued to take beta blockers the results of dobutamine stress did not correlate with coronary score, r = 0.34 (NS), whereas dipyridamole studies were not affected. CONCLUSION--Compared with dobutamine, dipyridamole was as effective in producing overall perfusion defects and more effective in provoking defects at the apex and lateral segment. The dipyridamole study correlated better with coronary score and was not affected by concurrent beta blocker treatment. It was also better tolerated by the patients, was less time consuming, and was much cheaper.     

Early changes in scores of chronic damage on transplant kidney protocol biopsies reflect donor characteristics,but not future graft function

The amount of irreversible injury on renal allograft biopsy predicts function, but little is known about the early evolution of this damage. In a single‐center cohort, we examined the relationship between donor‐, recipient‐, and transplantation‐associated factors and change in a morphometric index of chronic damage (ICD) between protocol biopsies performed at implantation and at 2–3 months. We then investigated whether early delta ICD predicted subsequent biochemical outcomes. We found little evidence to support differences between the study group, who had undergone serial biopsies, and a contemporaneous control group, who had not. In allografts with serial biopsies (n = 162), there was an increase in ICD between implantation (median: 2%, IQR:0–8) and 2–3 months post‐transplant (median 8% IQR:4–15; p < 0.0001). Donation from younger or live donors was independently associated with smaller early post‐transplant increases in ICD. There was no evidence for a difference in delta ICD between donation after cardiac death vs. donation after brain death, nor association with length of cold ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD after three months did not predict allograft function at one yr. These findings suggest that graft damage develops shortly after transplantation and reflects donor factors, but does not predict future biochemical outcomes.     

Treatment of postoperative peritonitis of small-bowel origin with continuous enteral nutrition and succus entericus reinfusion

HYPOTHESIS: Proximal intestinal stomas established by the exteriorization of leaking anastomosis in the presence of peritonitis can be used to reinfuse succus entericus and provide adequate enteral nutrition. DESIGN: Retrospective analysis of prospectively gathered data from a cohort of consecutive patients admitted between January 1993 and December 1999 for postoperative peritonitis requiring laparotomy and the construction of one or more small-bowel stomas. SETTING: Tertiary referral center with a surgical intensive care unit experienced in the treatment of intra-abdominal sepsis and succus entericus reinfusion. PATIENTS: Twenty-one consecutive patients with postoperative peritonitis originating from a jejunal or ileal leak. We excluded patients with established enterocutaneous fistulae, abscesses amenable to percutaneous drainage or other conservative treatments, and postoperative peritonitis caused by ileocolic or ileorectal anastomosis. INTERVENTIONS: Early laparotomy with exteriorization of small-bowel leak(s), and continuous enteral nutrition (CEN) and succus entericus reinfusion (SER) via the distal portion of the stoma until gastrointestinal continuity was restored. MAIN OUTCOME MEASURES: Feasibility of CEN and SER with temporary, diverting small-bowel stomas and their associated postoperative morbidity and mortality rates. RESULTS: One patient died, and 14 experienced complications. For technical reasons, CEN and SER were discontinued early on in 7 patients. The mean duration of CEN and SER was 58 days and 61 days, respectively. Enteral feedings allowed the suppression of central venous access after a median of 28 days, with 82 days as a median time to restoration of intestinal continuity. CONCLUSIONS: Although the exteriorization of small-bowel leaks with CEN and SER is generally feasible and effective in the treatment of critically ill patients with peritonitis secondary to small-bowel leaks, it is associated with significant morbidity and mortality, in part relating to patients' underlying diseases.     

CCK2 gastrin receptor as a potential target for therapy in leukaemia cell lines

The gastrin CCK2 pathway has been implicated in the development of various cancers including leukaemia. An autocrine or intracrine pathway may exist in the leukaemia cell that is involved in stimulating proliferation. We tested four leukaemia cell lines, KU812, ML-1, MOLT-4 and U937 for the existence of the CCK2 receptor and gastrin precursor protein using immunoblotting. We also assessed the effect of CCK2 antagonist PD 135 and both gastrin 17 and glycine-extended gastrin on the proliferation of the cell lines. We found immunoreactive CCK2 and gastrin precursors present in all 4 cell lines. We also observed a stimulatory effect on proliferation by gastrin and glycine-extended gastrin on 2 and 3 of the cell lines respectively and an inhibitory effect of PD 135 on all 4 cell lines. These results demonstrate that the gastrin-gastrin receptor axis is a potential target for new therapeutic strategies.