Effect of calcitonin on gall-bladder volume in man

The effect of increasing intravenous doses of synthetic salmon calcitonin (0.0044, 0.0088, 0.0175, and 0.0350 iu/kg per min) versus placebo on the fasted gall-bladder volume was assessed in seven normal subjects according to a double-blind study protocol. In addition, the action of calcitonin on meal-induced gall-bladder emptying was examined. Gall-bladder volumes were measured by means of real-time ultrasonography. Calcitonin evoked a dose-dependent relaxation of the fasted gall-bladder. A statistically significant increase of the fasted gall-bladder volume was observed with 0.0175 (23.4 +/- 5.5 cm3 placebo versus 33.9 +/- 7.7 cm3 calcitonin, P less than 0.001) and 0.0350 (21.4 +/- 4.6 cm3 placebo versus 36.1 +/- 8.4 cm3 calcitonin, P less than 0.01) iu/kg per min calcitonin, whereas a mean increase of the gall-bladder volume amounted to 32.1% and 46.5%, respectively. A significant delay of the gall-bladder emptying after calcitonin was reflected by a decrease of the ejection fraction: 23.2 +/- 8.3% calcitonin versus 57.8 +/- 6.9% placebo (P less than 0.02) at 20 min, and 40.5 +/- 8.8% calcitonin versus 67.2 +/- 3.8% placebo (P less than 0.02) at 30 min after the test meal. Calcitonin is concluded to have a potent relaxing effect on the human gall-bladder.     

Mouse model of gastric infection with cytotoxin-expressing strain of Helicobacter pylori in studying of pathogenesis of chronic gastric ulcer

Abstract Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori infection in gastric pathology are limited due to lack of convenient models resembling H. pylori infection in humans. We studied the effects of inoculation of conventional BALB/c mice with a toxigenic (cytotoxin associated gene A (cagA)+ and vacuolating cytotoxin gene A (vacA+) H. pylori strain on the course of healing of gastric ulcers. Following inoculation of toxigenic H. pylori or vehicle, gastric ulcers were produced in mice, which were then killed either at day 0 or after 2, 4, 7, 14 or 28 days and ulcer area and gastric blood flow (GBF) were determined. Gastric secretions from mice with chronic gastric fistulae were studied before and after inoculation with toxigenic H. pylori or vehicle (saline). The area (7 mm²) of ulcers in control mice decreased gradually and disappeared almost completely after 14 or 28 days. The ulcers in H. pylori-infected mice were present at all test days, showing a larger area than in vehicle control animals. The GBF in control mice rose gradually with decreasing ulcer size, being significantly higher at the ulcer margin than the ulcer crater. In contrast, the GBF in H. pylori-infected mice was significantly lower at the ulcer area than that in the vehicle controls but, again, the GBF at the ulcer margin was always higher than at the ulcer crater. Gastric acid output was reduced by more than 50% immediately after H. pylori inoculation and was accompanied by a significant increase in plasma gastrin release and a fall in gastric luminal somatostatin content. These secretory changes persisted at all test days. Oedema/congestion of surface epithelium appeared after 7 days and mucosal inflammatory infiltration appeared after 14 days, to further increase after 28 days, upon the induction of ulcer. Plasma interleukin (IL)-Iß and IL-12 were significantly elevated above the initial values compared with controls. Conventional mice with gastric ulcers can be successfully infected with an H. pylori strain expressing cagA and vacA cytotoxin and this infection markedly delays healing of the ulcers, probably due to the fall in GBF in the ulcer area, mucosal inflammation, cytokine release and impairment of the gastrin-somatostatin link.     

Autologous Cultured Melanocytes in Vitiligo Treatment

BACKGROUND: Surgical treatment of vitiligo is indicated when lesions are localized in poorly responding areas. OBJECTIVES: The objectives were: (1) to establish the melanocyte culture obtained from the epidermis of vitiligo patients for future treatment; (2) to estimate the influence of selected factors on the formation of suction blisters and the results of culture; and (3) to compare the results of treatment of vitiliginous macules localized in the dorsum of the hands and lower limbs by transplantation of cultured autologous melanocytes plus psoralen and ultraviolet A (PUVA) therapy (CMP), suction blister transplantation plus PUVA therapy (SBP), cryotherapy plus PUVA-therapy (CP), and only PUVA therapy (OP). METHODS: Forty patients were qualified for the study. The roofs of the suction blisters were used as a melanocyte source for culture establishment or were directly transplanted. RESULTS: The CMP procedure was successfully performed on only 10 of 20 patients because of the difficulties in cell culture establishment. The SBP method was carried out on all 20 patients. A total lack of effectiveness was found in CP and OP methods. CONCLUSIONS: The effectiveness of culture depends on time of suction blister forming, phototype, and previous PUVA therapy. This study demonstrated the advantage of the SBP over the CMP method.     

Surgery as an Effective Nonpharmacological Mode of Treatment of Atrial Fibrillation Resistant to Standard Therapy

There are two surgical methods for atrial fibrillation (AF) treatment: Maze and corridoring procedures. The first one prevents AF occurrence by performing multiple atriotomies. During the second procedure a corridor between a sino-atrial and the AV node is created together with an electrical isolation of the atria. During 1992 and 1993 seven patients, aged 27–55, mean 43-years-old, with recurrent, resistant to standard therapy AF were referred for surgical treatment to our department. Additional diagnoses include: concealed WPW syndrome in 1 patient, atrial septal defect (ASD) in 3 patients, coronary artery disease in 1 patient. Maze procedure was performed solely in 1 patient, in another together with 2 accessory pathways ablation, in 3 patients with ASD closure and in 1 patient with 2 bypass grafts. In one patient corridoring procedure was performed. Normal sinus rhythm was restored in every patient from 7 to 26 days after the procedure, No surgical complications were noted during the postoperative period. Mechanical function of the atria was documented with echo Doppler 2–6 weeks after the operation. No evidence for AF recurrence was noted within 3–14 months (mean 5 months) of follow-up. The preliminary results of Maze and corridoring procedures are encouraging.     

Variable Effects of Physical Training of Heart Rate Variability, Heart Rate Recovery, and Heart Rate Turbulence in Chronic Heart Failure

Background: Heart rate variability (HRV), heart rate turbulence (HRT), and heart rate recovery (HRR), indices that reflect autonomic nervous system (ANS) activity, are outcome predictors in patients with chronic heart failure (CHF). It is not clear, however, whether they reflect the same components of ANS activity. No study has examined the effects of physical training (PT) training on HRV, HRT, and HRR in CHF.
Study Objective: To examine the responses of HRV, HRT, and HRR to a PT program in patients presenting with CHF.
Methods: In 41 patients (mean age = 58.7 ± 10.2 years) in New York Heart Association CHF functional classes II or III, and with a left ventricular ejection fraction <40%, HRV, HRT, and HRR were measured before and after 8 weeks of PT.
Results: The training was clinically effective in all patients. Before versus after PT, standard deviation of all normal RR intervals increased from 107 ± 30 to 114 ± 32 ms (P = 0.047), high frequency increased from 210 ± 227 to 414 ± 586 ms²/Hz (P = 0.02), and the low/high frequency ratio decreased from 1.8 ± 1.55 to 1.1 ± 1.2 (P = 0.002). HRT and HRR did not change significantly after PT.
Conclusions: In patients with CHF, the positive effects of PT were limited to HRV indices, which reflect parasympathetic activity, without significantly changing HRR and HRT. These observations indicate that different mechanisms modulate HRV, HRR, and HRT, which provide complementary information regarding ANS activity. The 8-week PT program failed to completely normalize ANS function.     

LEPROMIN RESPONSES IN RECIPIENTS OE A CANDIDATE ANTILEPROSY BACTERIN VACCINE (WHO-IMMLEP MYCOBACTERIUM LEPRAE KILLED PREPARATION) IN THE USA

Background. Identification of the nine-banded armadillo as a potential source of massive numbers of Mycobacterium leprae led to the development of a candidate bacterin vaccine for possible immunoprophylaxis. Methods. Volunteers were from a leprosy-hypoendemic, nonBCG-using area (USA). They had been vaccinated intradermally 3 years earlier with a candidate antileprosy bacterin vaccine of irradiated and autoclaved Mycobacterium leprae obtained from experimental nine-banded armadillos. They were tested for dermal responsiveness to standard lepromin A. Results. Values for induration and erythema appeared slightly greater for the vaccinated group; however, the differences were not statistically significant, indicating no appreciable ‘anamnestic’ effect on either Fernandez (early) or Mitsuda (late) reactions after 3 years. Conclusions. Because previous studies had demonstrated that administration of this bacterin produced no humoral changes, it now appears less probable that laboratory methods will be of much help in assessing even possible effectiveness of such vaccination.     

Peptic proteolysis of esterified β-casein and β-lactoglobulin

Moderate esterification induces slight secondary structure changes in two major milk proteins, β-lactoglobulin and β-casein. Esterification of β-lactoglobulin prompts its tertiary structure‘melting′, opening it to peptic cleavage. Twenty-two new cleavage sites were characterised in β-lactoglobulin and five in β-casein. Some of them are due to esterification-improved peptide bond accessibility, some to the bias of pepsin specificity by glutamate and aspartate esters. The resulting fragmentation yields original and partially amphiphilic peptide populations.     

Triple-Site Versus Standard Cardiac Resynchronization Therapy Study (TRUST CRT): Clinical Rationale, Design, and Implementation

Background: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF), lowered LV ejection fraction, and wide QRS. However, many patients (≤40%) do not respond to this form of pacing. TRUST CRT is a prospective, single-center, randomized, single-blind, parallel, and controlled study that has been designed to treat patients with moderate to severe HF (NYHA III-IV), QRS ≥120 ms, sinus rhythm, LV dysfunction (EF ≤ 35%), and signs of mechanical dyssynchrony.
Objective: The primary objective will evaluate the 6-month's combined endpoint of alive status, freedom from hospitalization for HF or heart transplantation, relative ≥10% increase in LV ejection fraction, ≥10% in peak oxygen consumption, and ≥10% in 6-minute walking distance.
Methods: Patients with HF receiving optimal pharmacotherapy, with LV dysfunction, mechanical dyssynchrony, wide QRS and sinus rhythm will be randomized in a 1: 1 fashion to standard or triple-site CRT-D. Patients will be followed for 1 week, 1, 3, and 6 months during a blind phase, then every 6 months until study completion. One hundred patients will be enrolled by the study center.
Conclusions: TRUST CRT is a randomized, clinical trial in CRT candidates to evaluate the effectiveness of triple-site pacing versus standard resynchronization in patients with HF.