Effects of the opiate agonist loperamide on pituitary-adrenal function in patients with suspected hypercortisolism

In the present work the possible use of loperamide, an opiate agonist, in the dynamic evaluation of patients with suspected hypercortisolism was investigated. The effects of loperamide on plasma ACTH and cortisol levels were evaluated in normal subjects and in 58 patients with suspected Cushing's syndrome. The results were compared to those obtained after the overnight dexamethasone suppression test. In normal subjects plasma ACTH and cortisol levels were significantly (p less than 0.005) suppressed by both loperamide (16 mg po) and dexamethasone (1 mg po). In 17 patients, in whom the diagnosis of Cushing's syndrome was confirmed by subsequent investigations, neither loperamide or dexamethasone inhibited cortisol (from a baseline of 606 +/- 55 nmol/L) to a nadir of 502 +/- 43 nmol/L and 539 +/- 50 nmol/L, respectively) and ACTH concentration (from a basal level of 70.1 +/- 11.8 pg/ml to a nadir of 46.0 +/- 8.6 pg/ml and 54.3 +/- 7.5 pg/ml, respectively). In 34 patients, in whom the suspect of hypercortisolism was ruled out, either loperamide or dexamethasone suppressed the pituitary-adrenal axis: cortisol and ACTH levels significantly fell from 417 +/- 24 nmol/L and 28.3 +/- 3.5 pg/ml to 60 +/- 6 nmol/L and 14.4 +/- 1.4 pg/ml after loperamide and to 26 +/- 4 nmol and 16.4 +/- 1.7 pg/ml after dexamethasone. In 7 patients discordant responses were observed. In 3 patients treated with antiepileptic drugs ACTH and cortisol levels were inhibited by loperamide, but not by dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors affecting the transduction of pluripotent hematopoietic stem cells: long-term expression of a human adenosine deaminase gene in mice

An amphotropic retroviral vector, LgAL(delta Mo + PyF101) containing a human adenosine deaminase (ADA) cDNA was used to optimize procedures for the lasting genetic modification of the hematopoietic system of mice. The highest number of retrovirally infected cells in the hematopoietic tissues of long-term reconstituted mice was observed after transplantation of bone marrow (BM) cells that had been cocultured in the presence of both interleukin-1 alpha (IL-1 alpha) and IL-3. A significantly lower number was detected when IL-1 alpha was omitted from such cocultures. The yield of cells that generate spleen colony-forming cells (CFU-S) in the BM of lethally irradiated recipients (MRA-CFU-S) significantly improved on inclusion of the adherent cell fraction of cocultures in the transplant. Retroviral integration patterns in MRA-CFU-S-derived spleen colonies showed that an MRA-CFU-S can produce many CFU-S during BM regeneration. Expression of hADA was detected in the circulating white blood cells of long-term reconstituted animals, demonstrating that the LgAL(delta Mo + PyF101) vector is capable of directing the sustained expression of hADA, and in approximately 35% of the transduced MRA-CFU-S-derived spleen colonies. These results should facilitate the development of gene therapy protocols for the treatment of severe combined immunodeficiency caused by a lack of functional ADA.     

The treatment of carotid artery bifurcation stenoses with systematic stenting: experience of first 100 consecutive cardiological procedures

Carotid endarterectomy still represents the gold standard treatment of carotid artery bifurcation stenosis but percutaneous angioplasty with stenting is rapidly growing as a non-invasive alternative. In this paper we report the results of systematic application of carotid stenting performed in a cardiological setting, particularly as regards clinical management of patients and technical approach. One-hundred (100) procedures of carotid artery stenting (CAS) on 94 consecutive patients, both symptomatic and asymptomatic, with a carotid stenosis > 70%, were performed over a period of 30 months. The technical approach was directly derived from coronary angioplasty with use of large lumen guiding catheters, 0.014 in. intravascular guidewires and distal protection devices usually employed in coronary interventions. In 3 cases, a post-carotid endarterectomy restenosis and in 97 cases, a de-novo lesion, were treated respectively; in 71 cases, the degree of stenosis was 71-89% and in 29 cases, 90-99%. Cerebral protection was obtained with a distal to the lesion endovascular filter in 63 cases. Immediate technical success, i.e. residual stenosis of the treated vessel < 30% and no significant pathologic acceleration of blood flow (< 1.5 m/sec) at the Doppler ultrasound evaluation, was achieved in all procedures (100%). Ninety-six (96) procedures were totally uncomplicated; in-hospital cerebral complications were 1 TIA, 2 minor and 1 major strokes; at 30-day follow-up one additional major stroke occurred. Despite a particularly high incidence of comorbidities, neither unfavorable cardiological complications nor neurologic deaths were reported. Systematic CAS is a feasible treatment of the carotid artery bifurcation stenosis with high procedural success and low perioperative and short term complications. Its performance in a cardiological setting can combine satisfying procedural results and potentially successful handling of cardiovascular complications.     

Incidence of new diabetic patients on dialysis in Piedmont,Italy: Major changes recorded over a 10-year period

Different incidence rates of new diabetic patients on dialysis are reported in various settings; although prevalence of this disease is often considered a marker of acceptance policy, rates are thought to be influenced also by genetic, epidemiological and other characteristics of a population (genetic composition, age distribution, lifestyle). Moreover, since features of a general population are often not stable (as in the setting analysed) changes at this level may have important reflections in the incidence of diabetics with end-stage renal disease (ESRD). In the region studied (Piedmont, northern Italy, about 4400 000 inhabitants, 20 dialysis centres, open acceptance since the mid-1970s, yearly information on 100% of patients, gathered by a Dialysis and Transplantation Registry) the incidence of diabetic patients with ESRD (389 cases recorded 1981–1990: 222 males, 167 females: mean age at start increasing from 55.5 years in 1981–1985 to 58.7 years in 1986–1990) differs according to age and sex. Incidence was higher in males, and rose from 6.23/year patients per million population (p.m.p.) in 1981–1982 to 12.88/year p.m.p. in 1989–1990, with a peak at age 60–69 (from 18.46/year p.m.p. in 1981–1982, to 46.12/year p.m.p. in 1989–1990). While relatively stable in the younger age groups from 1981 to 1990, incidence increased in the elderly (males age 70–79: 7.12/year p.m.p. in 1981–1982, 26.08/year p.m.p. in 1989–1990). As regards clinical and metabolic patterns, at the first update, in 1986–1990, 88.3% of diabetic patients were hypertensive or taking hypotensive drugs; albumin levels were below the normal range (<3.5 g/dl) in 30.3%; cholesterol levels were below the normal range (<150 mg/dl) in 16.15%. As regards entry criteria, creatinine clearances ranged from <1 to 14 ml/min (mean values at first update: 3.45±2.76 ml/min). In conclusion, presentation of diabetic patients with ESRD is changing. The stability of incidence in the younger age groups confirms the appropriateness of an open acceptance policy, at least for these ages. The increase in the elderly probably reflects the longer lifespan of diabetic patients in the overall population, while the influence of a hidden preselection must be further assessed. Since this cohort increasingly requires in-hospital high-tolerance treatment, future provision of dialysis needs must take into account the trend towards an increase in this high-risk elderly population.     

Role of bile acids and metabolic activity of colonic bacteria in increased risk of colon cancer after cholecystectomy

Since the metabolic activity of the colonic flora plays a definite role in colon cancer and an increased incidence of this disease is reported after cholecystectomy, we studied the metabolic activity of the colonic flora in a group of postcholecystectomy patients and matched controls by measuring, as representative end products of the bacterial metabolism, their fecal bile acids (BA), fecal 3-methylindole (SK) and indole (IN), and respiratory methane and hydrogen. Patients had significantly higher SK and lower IN, and, among BA, higher lithocholic (LCA) and chenodeoxycholic acid concentrations and LCA/deoxycholic acid ratio in the stools than controls. Similar differences from controls were reported for colon cancer. Comparable bacterial metabolic activities are thus operative in the large bowel of postcholecystectomized and colon cancer patients. This supports the biological plausibility of the association of cholecystectomy and colon cancer.     

Multicenter registry to evaluate the efficacy of the NIROYAL stent in de novo or restenotic coronary stenosis

The purpose of this registry was to document the safety and efficacy of elective deployment of the NIROYAL stent (Boston Scientific SCIMED, Maple Grove, Minnesota) in coronary arteries. This was a prospective, multi-center international registry. NIROYAL stents (9, 16, 25 and 32 mm-long) were manually crimped onto coronary balloons and deployed in de novo or restenotic lesions in 165 male and female patients with angina pectoris and a reference vessel diameter of 2.0-4.5 mm. Stent deployment was successful in 98.8% of the lesions. Mean percent diameter stenosis decreased from 83.5+/-10.8% to 2.7+/- 6.2% after intervention. The interventional procedure of the treatment site was successful in 97.6% of patients. At six-month clinical follow-up, 88.5% had event-free survival [i.e., did not experience a major adverse cardiac event (MACE)] and 95.2% had no anginal symptoms. Furthermore, 87.3% of the patients were free of target vessel failure (defined as a composite of acute procedural failure, target vessel revascularization, myocardial infarction or death at six months). Only three MACE were observed within the first 30 days after stent implantation. A low left ventricular ejection fraction and the percentage stenosis pre-procedure were identified as statistically significant (p<0.05) predictive factors for MACE. The incidences of MACE and target vessel failure after six months follow-up were lower than that seen in other studies, and target lesion revascularization rates were low.     

Coronary angioplasty of chronic occlusions: factors predictive of procedural success.

In a retrospective study of 365 chronic total occlusions that were submitted for angioplasty, we studied the influence of 27 clinical, morphologic, and procedural variables as possible predictors of successful outcomes. Success rate was shown to be significantly influenced by the following variables: operator experience (41% in early patients, first 6 months; 73% in late patients, last 6 months of entire series; p less than 0.001), duration of occlusion (less than or equal to 1 month, 89%; 1 to 3 months 87%; greater than or equal to 3 months 45%; unknown 60%; p less than 0.001), morphology of occlusion (tapered, 83%; abrupt, 51%), length of occlusion (less than or equal to 15 mm, 71%; greater than 15 mm, 60%; p less than 0.001), and bridging collaterals (present, 29%; absent, 67%; p less than 0.001). None of the other clinical, angiographic, or procedural variables correlated with the success rate of coronary angioplasty. The calculated probability for an experienced operator (greater than 100 occlusions attempted) to successfully open an occlusion with favorable morphology (less than or equal to 1 month old, short, tapered, without bridging collaterals) is 99%. An attempt by the same operator to open an occlusion with unfavorable structure (greater than or equal to 3 months old, long, untapered) has only 47% probability of success. The probability increases to 84% when the occlusion is tapered. We concluded that in addition to the duration and the length of occlusion, tapered morphology, bridging collaterals, and operator experience can predict successful angioplasty in chronic total coronary occlusion.     

Synthesis of glucose in human thrombocytes

Net synthesis of carbohydrates could be demonstrated at a rate of $\text{12 μ}\text{mole/hr}\text{10}{}^{11}$ cells by incubating human thrombocytes in a buffered solution in the presence of 20 mM pyruvate and 2.5 mM ATP. Moreover, incorporation of isotopic carbon from pyruvate-2-¹⁴C into carbohydrates was measured to occur at a rate of $\text{0.7 μ}\text{mole/hr}\text{10}{}^{11}$ cells in the absence of added ATP and of $\text{2.2 μ}\text{mole/hr}\text{10}{}^{11}$ cells in the presence of 7.5 mM ATP. The addition of 20 mM pyruvate and of increasing amounts of ATP (up to 7.5 mM) were shown to have a sparing effect on carbohydrate utilization. On the other hand, increasing the cell concentration from 3.3 × 10⁸ to 16.5 × 10⁸ cells/ml in the incubation medium resulted in an increase of glucose uptake from the medium. It is concluded that thrombocytes are capable of synthesizing carbohydrates from pyruvate.