Failure of dopamine infusion to suppress the plasma prolactin response to sulpiride in normal and hyperprolactinemic subjects.

In eleven normal women dopamine infusion (5 microgram/Kg/min) significantly lowered plasma prolactin levels but failed to suppress the PRL response to sulpiride (10 or 100 mg i.v.), while the same dose of dopamine was effective in abolishing the PRL response to TRH (200 microgram i.v.). In four hyperprolactinemic women showing an impaired PRL response to sulpiride, dopamine infusion was effective both in lowering PRL circulating levels and in restoring an evident response to sulpiride. This finding suggests an impairment of endogenous dopamine activity in hyperprolactinemic amenorrhea.     

Plasma and urine cyclic nucleotide levels in patients with neoplastic diseases

Plasma and/or urine cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) levels were measured in 67 normal subjects, 55 patients with nonneoplastic diseases, and 324 patients with ten different types of cancer. There were no significant differences in plasma and urine cyclic nucleotide levels between normal subjects and patients with non-neoplastic diseases. In untreated cancer patients, plasma and urine cAMP levels were similar to those of normal subjects, whereas plasma and urine cGMP levels were markedly higher. This pattern was common to all the cancer groups studied. Chemotherapy per se did not seem to influence cyclic nucleotide levels in cancer patients. However, plasma and urine cGMP levels normalized in all patients who attained complete remission. Moreover, in acute leukemia patients who relapsed, plasma cGMP levels increased significantly with respect to the complete remission values, thus suggesting that this parameter may be useful in monitoring the response of cancer patients to treatment.     

Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly.

OBJECTIVE: Acromegaly is often associated with fasting and postprandial hyperinsulinemia, and the mechanisms involved are only partly understood. Hypersecretion of incretins such as glucose-dependent insulinotropic polypeptide (GIP) could play a role in determining hyperinsulinemia in acromegaly, but the available data are inconsistent. The aim of this study was to characterize the fasting and postprandial pattern of plasma GIP and insulin in a group of acromegalic patients. DESIGN AND METHODS: Eleven non-diabetic patients with newly diagnosed acromegaly and 11 sex- and age-matched healthy subjects were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal for growth hormone (GH), GIP and insulin measurements. RESULTS: Not only insulin, but also fasting and postprandial GIP levels were significantly higher in the patients with acromegaly than the healthy subjects (P<0.01). In the former group fasting GIP levels and the integrated GIP response to the meal correlated significantly with GH basal levels (r=0.83, P<0.01 and r=0.65, P<0.05, respectively). Moreover, multivariate linear regression analysis showed that the presence of acromegalic status was associated with higher fasting and postprandial GIP levels independently of sex, age, fasting and postprandial plasma glucose and insulin levels, and the occurrence of normal or impaired glucose tolerance. CONCLUSION: This study provides evidence that in patients with acromegaly fasting and postprandial GIP levels are abnormally high. GIP hypersecretion in turn might play a role in the pathogenesis of hyperinsulinemia that characterizes acromegaly.     

Human cobalamin deficiency: alterations in serum tumour necrosis factor-α and epidermal growth factor

OBJECTIVES: We have previously demonstrated that vitamin B12 (cobalamin)-deficient central neuropathy in the rat is associated with local overexpression of neurotoxic tumour necrosis factor (TNF)-alpha combined with locally decreased synthesis of neurotrophic epidermal growth factor (EGF). The aims of this study were to investigate whether a similar imbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficiency and whether it can be corrected by vitamin B12 replacement therapy. PATIENTS AND METHODS: We studied 34 adult patients with severe cobalamin deficiency, 12 patients with pure iron deficiency anaemia and 34 control subjects. Haematological markers of cobalamin deficiency and serum TNF-alpha and EGF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B12 treatment. RESULTS: TNF-alpha was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, but both were unchanged in patients with pure iron deficiency anaemia. In cobalamin-deficient patients the serum TNF-alpha levels correlated significantly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the treated patients TNF-alpha and EGF levels normalised concomitantly with clinical and haematological disease remission. CONCLUSIONS: In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-alpha and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF.     

Tuberculosis of the eye in Italy: a forgotten extrapulmonary localization

Purpose

Tuberculosis (TB) of the eye is a well-known extrapulmonary localization in high-incidence countries. Data on its relevance in developed countries are scanty. We aim to study the epidemiological and clinical pattern of ocular TB in a tertiary care institution of a western country.

Methods

From 2007 to 2010, consecutive patients with a diagnosis of isolated ocular TB or associated to extraocular TB were recruited. Patients with ophthalmological and clinical features of TB were treated with standard antitubercular therapy (ATT) and steroids in case of concomitant severe ocular inflammation.

Results

Seventeen cases of ocular and extraocular TB and 45 cases of isolated ocular TB were identified. The proportion of patients with ocular and extraocular TB in our local district was 8.1 %, with a proportion of 10.6 % for the isolated cases. In Cohort 1, only one patient was symptomatic for ocular impairment, and uveitis without inflammation was the most common presentation. On the contrary, in Cohort 2, all patients had visual impairment, mainly with bilateral involvement. 77.8 % of the patients showed an inflammatory pattern. ATT was administered for at least 9 months, in four cases with a short course of systemic corticosteroids. Eight cases in Cohort 2 showed recurrence after 1 year from diagnosis.

Conclusions

TB of the eye should not be forgotten, even in geographical areas not considered among endemic countries. Ocular evaluation is advisable in patients with pulmonary and extrapulmonary TB, as early detection may allow ATT to preserve visual acuity.     

Anticorpi antitiroidei e diabete mellito

Riassunto L'incidenza di anticorpi antitiroidei circolanti è stata studiata in 50 pazienti diabetici. Anticorpi anti-microsomi sono risultati presenti nel siero dei pazienti con diabete insulino-dipendente con frequenza significativamente superiore a quella dei soggetti di controllo. Viene quindi discusso il possibile intervento di processi autoimmuni nella genesi del diabete.

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Summary The incidence of circulating thyroid antibodies has been studied in 50 diabetics. The incidence of thyroid microsomal antibodies was significantly higher in insulin-dependent diabetics than in the normal controls. The possible role of autoimmune processes in the pathogenesis of diabetes mellitus is discussed.

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Zusammenfassung Bei 50 Diabetikern wurde die Anwesenheit von zirkulierenden Schilddrüsen-Antikörpern untersucht. Im Serum der insulinabhängigen Diabetiker wurden Mikrosomen-Antikörper signifikant häufiger gefunden als bei den Kontrollpersonen. Es wird die Möglichkeit des Mitwirkens autoimmuner Prozese in der Pathogenese des Diabetes besprochen.

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Resumen Se ha estudiado en 50 enfermos diabéticos la incidencia de anticuerpos antitiroideos en circulación. En el suero de los pacientes con diabetes insulino-dependiente, resulta la presencia de anticuerpos antimicrosomas con frecuencia significativamente superior a la de los individuos de control. A continuación se discute la posible intervención de procesos de autoinmunización en la génesis de la diabetes.

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Résumé L'incidence d'anticorps antithyroïdiens circulants a été étudiée chez 50 sujets diabétiques. Chez les diabétiques insulino-dépendant, la fréquence d'anticorps anti-microsomes dans le sérum était significativement plus haute que chez les sujets normaux. Le possible rôle de processus auto-immunitaires dans la genèse du diabète est discuté.

     

Gastric Emptying and Plasma Neurotensin Levels in Untreated Celiac Patients

Objective. To compare the effect of laparoscopic Nissen and Lind fundoplication on gastro-oesophageal reflux disease by means of a prospective randomized controlled trial. Material and methods. One hundred and twenty-one patients were randomized to undergo either Nissen (61) or Lind (60) fundoplication. Initial enrolment and subsequent clinical appointments were undertaken 1, 3, 6 and 12 months after the procedure using a standardized questionnaire. Ambulatory pH monitoring and manometry were undertaken both preoperatively and at approximately 3 months post-procedure. Results. The mean operating time was similar in both groups (44.8 versus 45 min). One operation in the Lind group was converted to open surgery. Postoperative dysphagia symptoms at 3 and 6 months were higher in the Nissen fundoplication group than in the Lind group (3 months p=0.003; 6 months p=0.020). The time taken to return to work was statistically longer in the Nissen group: at 1 month, 9 of 40 versus 2 of 45 patients had not returned to full activities (p=0.013). Three individuals required re-operation in the Nissen group and 4 individuals in the Lind group because of dysphagia caused by mechanical obstruction. Both procedures demonstrated good Visick scores at 12 months; the Nissen group having 33 (97%) patients with a Visick score of 1 or 2, and the Lind group having 38 (100%) patients with a Visick score of 1 or 2. Conclusions. Both operations provide good quantitative and qualitative control of gastro-oesophageal reflux. Operation time and postoperative comparators were similar in both groups. There were no statistically significant differences between the groups at 1 year.     

Influence of Caloric Intake on Gastric Emptying of Solids Assessed by 13C-Octanoic Acid Breath Test

Background: The 13C-octanoic breath test (13C-OBT), a recently developed technique to evaluate gastric emptying of solids, has been validated in comparison to scintigraphy with low caloric meals (250 kcal). However, there is consensus that for clinical studies total caloric load should be in excess of 300 kcal, but studies comparing 13C-OBT results after low and medium caloric meals are lacking. Methods: Ten healthy subjects were given a 250-kcal and a 550-kcal meal in randomized order. Gastric emptying was assessed simultaneously by ultrasonography and 13C-OBT. Breath samples were taken according to both classic (21 samples over 5 h) and simplified (11 samples) schedules. Results: Increasing the meal energy content resulted in significantly longer half emptying time (T½) estimates by both ultrasonography (P &lt; 0.01, Wilcoxon test) and 13C-OBT (P &lt; 0.05). T½ estimates by the two methods significantly correlated for both the 250 (r s = 0.733, P = 0.018) and the 550 (r s = 0.637, P = 0.035) kcal meal. However, differences between T½ estimates by 13C-OBT and ultrasonography were greater after the 550- than the 250-kcal meal (median 172.5 versus 76.5 min, P &lt; 0.05). Interindividual variability was also 2-fold greater for indexes estimated by 13C-OBT with the 550-kcal meal compared with the 250-kcal meal. For both meals 13C-OBT yielded similar results with the classic and simplified schedules. Conclusions: In healthy subjects caloric intake is a major determinant of gastric emptying rate. However, after a medium caloric meal 13C-OBT shows some inaccuracy, which raises questions about its routine clinical application. Nevertheless, when using 13C-OBT one must take into account that the simplified schedule is just as effective as the classic one, and is far lower in cost.     

Unusually aggressive type 1 gastric carcinoid: a case report with a review of the literature

Gastric carcinoids are rare tumors of the stomach. Gastric carcinoid type 1 is associated with chronic atrophic gastritis, and because of a low metastatic potential, is the most benign type. Death from metastatic disease has been reported in only three patients in a review including 724 cases. The present report refers to a 60-year-old man who was affected by type 2 diabetes mellitus and pernicious anemia and died from metastatic gastric carcinoid type 1. In 1998, a well-differentiated 1.2 cm gastric neuroendocrine tumor, immunoreactive for chromogranin A, with a Ki-67 index less than 2% and with infiltration to the submucosal layer was diagnosed and enucleated. In 2002, a new well-differentiated gastric endocrine tumor 6 mm in size with a Ki-67 of approximately 2% was detected, and endoscopic ultrasound confirmed it to be limited to the submucosal layer. The patient refused antrectomy and started long-acting somatostatin analog (lanreotide) in 2005 when the Ki-67 index was 7%, but he stopped the treatment after 4 months. In 2007, despite previous endoscopic stability, endoscopic ultrasound showed an infiltrating gastric lesion of 7 cm. At surgery, the disease appeared to be extended to the liver and to the peritoneum (well-differentiated endocrine carcinoma, Ki-67 40%) with both hepatic and massive peritoneal metastases. A regimen of somatostatin analog was soon restarted; however, the disease continued to spread, and the patient died 6 months later. Overall, despite their generally benign course, type 1 gastric carcinoids may have malignant potential, a finding that should be considered when planning the medical workup of these patients.     

Use of intrinsic binding energy for catalysis by an RNA enzyme

The contribution of several individual ribozymesubstrate base pairs to binding and catalysis has been investigated using hammerhead ribozyme substrates that were truncated at their 3′ or 5′ ends. The base pairs at positions 1.1–2.1 and 15.2–16.2, which flank the conserved core, each contribute 10⁴-fold in the chemical step, without affecting substrate binding. In contrast, base pairs distal to the core contribute to substrate binding but have no effect on the chemical step. These results suggest a “fraying model” in which each ribozymesubstrate helix can exist in either an unpaired (“open”) state or a helical (“closed”) state, with the closed state required for catalysis. The base pairs directly adjacent to the conserved core contribute to catalysis by allowing the closed state to form. Once the number of base pairs is sufficient to ensure that the closed helical state predominates, additional residues provide stabilization of the helix, and therefore increase binding, but have no further effect on the chemical step. Remarkably, the >5 kcal/mol free energy contribution to catalysis from each of the internal base pairs is considerably greater than the free energy expected for formation of a base pair. It is suggested that this unusually large energetic contribution arises because free energy that is typically lost in constraining residues within a base pair is expressed in the transition state, where it is used for positioning. This extends the concept of “intrinsic binding energy” from protein to RNA enzymes, suggesting that intrinsic binding energy is a fundamental feature of biological catalysis.