Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study

Background  Intestinal immune infiltration contributes to symptoms in patients with irritable bowel syndrome (IBS).
Aim  To assesses the effect of mesalazine (mesalamine) on mucosal immune cells in patients with IBS, through a pilot study.
Methods  A randomized, double-blind, placebo-controlled trial in 20 patients with IBS in tertiary care setting. Patients were randomized to receive placebo or 800 mg mesalazine three times daily for 8 weeks. The primary endpoint was a significant reduction in total colonic immune cells on biopsies obtained at the end of treatment compared to baseline. Secondary endpoints included effects on subsets of immune cells, inflammatory mediators and symptom severity. Intention-to-treat analysis was performed.
Results  Mesalazine markedly reduced immune cells as compared with placebo ( P  = 0.0082); this effect was ascribed to a marked inhibition of mast cells ( P  = 0.0014). Mesalazine significantly increased general well-being ( P  = 0.038), but had no significant effects on abdominal pain ( P  = 0.084), bloating ( P  = 0.177) or bowel habits. No serious drug-related adverse events were reported during the study.
Conclusions  Mesalazine is an effective and safe approach to reduce mast cell infiltration and may improve general well-being in patients with IBS. These results support the hypothesis that immune mechanisms represent potential therapeutic targets in IBS.     

Reliability of a New Algorithm for Automatic Mode Switching from DDDR to DDIR Pacing Mode in Sinus Node Disease Patients with Chronotropic Incompetence and Recurrent Paroxysmal Atrial Fibrillation

To evaluate the safety and efficacy of a new algorithm for automatic mode switching (AMS) from DDD-DDDR to DDIR, 26 patients, 16 females and 10 males, mean age 73 ± 6 years of age, affected by sinus node disease, chronotropic incompetence, and recurrent paroxysmal atrial fibrillation (PAF) received the Medtronic Them DR pacemaker. The device continuously calculates, in ms, the running average of the intrinsic atrial rate (MAR) and compares the current atrial interval (CAI) with the stored MAR. When the CAI is greater than the MAR it increases by 8 ms, and when the CAI is less than the MAR, it decreases by 23 ms. When MAR ± 330 ms (182 beats/mm), tachycardia is detected and AMS is activated. All patients had clinical evaluation, 12-lead ECG, Holter monitoring, and exercise testing after implantation and every 3 months for 1 year. The results were compared with the data stored in the pacemaker memory: AMS episodes number; the histogram of the last 14 episodes; and atrial electrogram recording. Twenty-two Holier recordings in 13 patients showed PAF and in all of them AMS occurred simultaneously. AMS lasted between 10 seconds and 20 hours, and MAR ranged from 195–400 beats/mm. No episode of PAF and no AMS were recorded in 39 Holter recordings in 22 patients. Appropriate AMS was confirmed in five patients by stored atrial electrogram and in nine by 12-lead ECG and pacemaker event markers. Mean atrial sensing was 2.13 ± 1.04 mV during PAF and 3,18 ± 1.46 mV during sinus rhythm. No PAF episode and no AMS were recorded during exercise testing. In conclusion, this new algorithm was very reliable, sensitive, and specific.     

Longitudinal neuropsychological evaluation of HIV-infected intravenous drug users

The present study aimed to describe the cognitive status of a group of HIV-positive asymptomatic intravenous drug users (IVDU) and changes which occurred over a 12-month follow-up period. Forty-two HIV positive IVDU were selected and matched for age, sex, educational level and pattern of drug abuse with 39 seronegative IVDU controls. Baseline and follow-up evaluation included neuropsychological tests exploring attention, language, memory, logic and visuomotor abilities, biological markers and clinical parameters. About one-third of both seropositive and seronegative subjects showed at baseline slight cognitive deficits, ‘which did not change during the follow-up period.     

The long-term efficacy of interferon alfa in chronic hepatitis C patients: A critical review

With current therapeutic regimens, sustained responses occur in no more than 25% of patients with chronic hepatitis C who are treated with interferon. Relapses occur usually within 6 months from therapy suspension, but clinical and virologic recurrencies can be observed as late as after 3 years of follow up. The rate of long-term responses seems to depend on the dosage and the period of administration of interferon, but the best therapeutic protocol remains unknown. As a direct marker of permanent recovery is not available, indirect signs of disease resolution are: (i) continuously normal alanine aminotransferase levels; (ii) clearance of HCV-RNA; (iii) disappearance of anti-C100/NS4; and (iv) significant histological improvements assessed at least 2 years after therapy withdrawal. Known baseline predictive features of long-term response are the absence of cirrhosis, low viraemic levels and infection with HCV of type III or IV genotype (Okamoto's classification). According to recent reports, the lower the heterogeneity of the hypervariable region of the envelope 2 gene of HCV, the higher the chance of a sustained remission. There is not yet any consensus on the efficacy of a second therapeutic course of interferon in inducing a permanent response, and controlled trials are needed to clarify this issue.     

Duplex-Doppler assessment of cirrhosis in patients with chronic compensated liver disease

Portal venous flow velocity (PFV) was measured with duplex-Doppler equipment in 50 normal subjects and in 117 patients with suspected chronic liver disease who showed no evidence of decompensation such as ascites, hepatic encephalopathy, jaundice or oesophageal bleeding. All the patients underwent percutaneous liver biopsy which demonstrated non-cirrhotic liver disease in 58 cases (CH-patients: steatosis 8, persistent chronic hepatitis 8, active chronic hepatitis 42) and liver cirrhosis in the other 59 cases (LC-patients). The normal subjects and the CH-patients had similar values of max-PFV and mean-PFV (max-PFV 26.7±3.2 and 25.7±3.4 cm/s respectively; mean-PFV 22.9±2.8 and 22.4±3.8 cm/s respectively). The LC-patients’ values (max-PFV 19.3±3.5; mean-PFV 16.9±2.9) were significantly lower than those of the normal subjects (P<0.001) and of the CH-patients (P<0.001). Considering the normal max-PFV to be in the range 20–33.1 cm/s (mean±2 s.d. of the normal subjects, 95% confidence limits), max-PFV was reduced in 0/50 normal subjects, 1/58 CH-patients and 39/59 LC-patients (66.1% sensitivity; 98.2% specificity). In conclusion, the duplex-Doppler measurement of PFV is of great interest in the diagnostic study of patients with suspected chronic compensated liver disease and in the early diagnosis of cirrhosis. A low max-PFV is a reliable pointer to liver cirrhosis, whereas a normal max-PFV indicates a non-cirrhotic liver disease but is less probative. Each centre should standardize normal PFV values in order to establish their own threshold value for diagnosing liver cirrhosis.     

An Implantable Intracardiac Accelerometer for Monitoring Myocardial Contractility

As the myocardium contracts isometrically, it generates vibrations that are transmitted throughout the heart. These vibrations can be measured with an implantable microaccelerometer located inside the tip of an otherwise conventional unipolar pacing lead. These vibrations are, in their audible component, responsible for the first heart sound. The aim of this study was to evaluate, in man, the clinical feasibility and reliability of intracavity sampling of Peak Endocardial Acceleration (PEA) of the first heart sound vibrations using an implantable tip mounted accelerometer. We used a unidirectional accelerometer located inside the stimulating tip of a standard unipolar pacing lead: the sensor has a frequency response of DC to 1 kHz and a sensitivity of 5 mV/G (G - 9.81 m/s^?2). The lead was connected to an external signal amplifier with a frequency range of 0.05–1,000 Hz and to a peak-to-peak detector synchronized with the endocardial R wave scanning the isovolumetric contraction phase. Following standard electro-physiological studies, sensor equipped leads were temporarily inserted in the RV of 15 patients (68 ± 15 years), with normal regional and global ventricular function, to record PEA at rest, during AAI pacing, during VVI pacing, and during dobutamine infusion (up to 20 |mg/kg per min). PEA at baseline was 1.1 G ± 0.5 (heart rate = 75 ± 14 beats/rain) and increased to 1.3 G ± 0.9 (P = NS vs baseline) during AAI pacing (heart rate = 140 beats/min) and to 1.4 G ± 0.5 (P = NS vs baseline) during VVI pacing (heart rate = 140 beats/min). Dobutamine infusion increased PEA to 3.7 G ± 1.1 (P < 0.001 vs baseline), with a heart rate of 121 ± 13 beats/min. In a subset of three patients, simultaneous hemodynamic RV monitoring was performed to obtain RV dP/dt_max, whose changes during dobutamine and pacing were linearly related to changes in PEA (r = 0.9; P < 0.001). In conclusion, the PEA recording can be consistently and safely obtained with an implantable device. Pharmacological inotropic stimulation, but not pacing induced chronotropic stimulation, increases PEA amplitude, in keeping with experimental studies, suggesting that PEA is an index ofmyocardial contractility. Acute variations in PEA are closely paralleled by changes in R V dP/dt_max, but are mainly determined by LV events. The clinical applicability of the method using RV endocardial leads and an implantable device offers potential for diagnostic applications in the long-term monitoring of myocardial function in man.     

Immune Lysis of Normal and AET-treated Lymphocytes: A Study by Transmission and Scanning Electron Microscopy

A morphologic study of normal andAET-treated lymphocytes exposed invitro to cytotoxic antibody and complement (C) has been carried out using bothtransmission and scanning electron microscopy. The abnormalities observed wereof the same kind for the two types ofcell, but they were more marked inAET-treated lymphocytes than in theiruntreated counterparts. These resultsconfirm the serologic finding that AET-treated lymphocytes possess a higherthan normal susceptibility to the damaging action of antibody and C in thelymphocytotoxicity reaction.

Submitted on March 1, 1971 Revised on June 4, 1971 Accepted on June 17, 1971     

An unusual congenital nail dystrophy ('soft nail disease')

An unusual, congenital, non-familial anomaly of all finger and toe nails was observed in a 33-year-old woman. The presence of an atrophic nail plate, which was very soft, has led us to call this condition ‘soft nail disease’. Histological and histochemical investigations have shown this to be an anatomical and functional defect of the nail matrix which is of unknown origin.     

Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis

1 Little information is available about the action of lamotrigine (LTG) on EEG paroxysmal abnormalities and background activity. On the contrary, several clinical trials have shown the therapeutic efficacy of the drug in preventing partial and generalized seizures.
2 We performed computerized EEG monitoring in 21 patients suffering from focal and generalized epilepsy before and 4 months after addition of LTG. The anticonvulsant modified the EEG ictal events by reducing their frequency and duration. A statistically significant decrease of the interictal spikes was observed. The decrease involved mainly the spreading component of the interictal events leading to a better spatial definition of the epileptic focus.
3 In the presence of LTG, generalized tonic-clonic attacks were completely controlled, whereas partial seizures were decreased.
4 The EEG background activity was not modified by the addition of the drug.
5 Our findings suggest a specific role for LTG in the generation and propagation processes of epileptiform activity without interfering with the EEG background activity.