Extra-Intestinal Manifestations of Familial Adenomatous Polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, which results from a germ line mutation in the APC (adenomatous polyposis coli) gene. FAP is characterized by the formation of hundreds to thousands of colorectal adenomatous polyps. Although the development of colorectal cancer stands out as the most prevalent complication, FAP is a multisystem disorder of growth. This means, it is comparable to other diseases such as the MEN syndromes, Von Hippel-Lindau disease and neurofibromatosis. However, the incidence of many of its clinical features is much lower. Therefore, a specialized multidisciplinary approach to optimize health care—common for other disorders—is not usually taken for FAP patients. Thus, clinicians that care for and counsel members of high-risk families should have familiarity with all the extra-intestinal manifestations of this syndrome. FAP-related complications, for which medical attention is essential, are not rare and their estimated lifetime risk presumably exceeds 30%. Affected individuals can develop thyroid and pancreatic cancer, hepatoblastomas, CNS tumors (especially medulloblastomas), and various benign tumors such as adrenal adenomas, osteomas, desmoid tumors and dental abnormalities. Due to improved longevity, as a result of better prevention of colorectal cancer, the risk of these clinical problems will further increase

Direct cardiac effects in isolated perfused rat hearts measured at increasing concentrations of morphine, alfentanil, fentanyl, ketamine, etomidate, thiopentone, midazolam and propofol

The direct cardiac effects of morphine, alfentanil, ketamine, etomidate, thiopentone, midazolam and propofol were measured in isolated Wistar rat hearts. Experiments were performed using a multiple columnar Langendorff apparatus and the hearts were perfused with a modified Tyrode solution under constant pressure. Each drug was applied from a different column in rising concentrations at 5-min intervals. Dose ranges were chosen to compare effects at subclinical, clinically relevant and more than clinical concentrations. Six rat hearts were chosen at random for each drug. Only thiopentone reduced contractile force at a clinically relevant concentration: measured as g contractility per g heart weight(-1) (mean+/-standard deviation), base-line contractility was 8.8+/-2.4, and contractility at 10(-4) mol litre(-1) thiopentone was 7.1+/-1.5 (P<0.01). Alfentanil was the only drug to have no significant effect on the isolated heart at any concentration. Propofol was not cardiodepressant at clinically relevant concentrations, but had a lower therapeutic range than the other drugs

Human albumin enriched St. Thomas Hospital cardioplegic solution increases reperfusion injury in isolated perfused rat hearts

In open heart surgery it is very important to protect the heart during the ischaemic period in terms of mortality and morbidity. Many different cardioplegic solutions are in clinical use without being tested experimentally. In this study we intended to investigate the effects of albumin addition to St. Thomas Hospital cardioplegic solution on cardiac protection to ischaemia. Rat hearts were isolated and perfused in Langendorff apparatus (n = 6 for each group). After the stabilisation period, the hearts in the control group were arrested with St. Thomas Hospital cardioplegic solution for 3 min then subjected to 30 min of global ischaemia in cardioplegic solution, this is followed by reperfusion for 10 min. In albumin groups, the experimental protocol was the same but 2.25%, 4.5% or 9% human albumin was added to the cardioplegic solution. All of the hearts were compared for their pre-ischaemic and post-ischaemic contractility, heart rate, coronary flow, LDH and CK enzyme leakage, and wet/dry weight ratio values. The contraction, heart rate (P < 0.01 for both), and coronary flow (only for the 9% albumin group, P < 0.05) values in the albumin group were less than the control group during the reperfusion period. There was no difference between groups in LDH, and CK leakage, and wet/dry weight ratio. The circulation of ischaemic hearts in the albumin group were diminished, possibly due to protein precipitation. This condition negatively affected the performance of the heart. The fact that there is no difference in enzyme leakage and wet/dry weight ratio, indicates that this event is not irreversible. (C) 1998 The Italian Pharmacological Society

THE INFLUENCE OF CHOLINE ASCORBATE ON THE BLOOD-LEVELS OF ASCORBIC-ACID IN HUMANS

Our study has clearly shown that the oral administration of choline ascorbate, which contains approximately 500 mg of ascorbic acid to the volunteers causes an increase in the blood levels of ascorbic acid. This increase is statistically significant (p < 0.01) compared with the basal level each time. In the control group, vitamin C tablet also causes an increase in the blood level of ascorbic acid. However, this increase is less than that of the test group. Our results indicate that ascorbic acid, as a part of choline ascorbate molecule, reaches the blood circulation without losing its activity

The role of isocolloidoosmotic synthetic colloid addition to St. Thomas Hospital cardioplegic solution for cardioprotection in isolated perfused rat hearts

Cardiac transplantation is a prominent development in the treatment of patients with severe cardiac diseases. If it is not possible to transplant the heart immediately after removing it from the donor, procedures for preparing, protecting, storing and transferring of the heart constitute a major portion of this study. Selecting the best method among those used for cardioprotection is still been debated. This experimental study investigated whether isocolloidoosmotic solution in addition to St. Thomas Hospital cardioplegic solution would give better cardioprotection. Wistar rat hearts were isolated and perfused by the Langendorff method (n = 6 for each group). In the control group after stabilisation, the hearts were arrested while perfused with St. Thomas Hospital cardioplegic solution for 3 min, then they were placed in cardioplegic solution at 4 degrees C for 6 h. Afterwards the hearts were reperfused. In the experimental groups, modified gelatin fluid (30 g/l) or HES 200/0.5 (50 g/l) or dextran 70 (25 g/l) was added to the cardioplegic solution. Maximum contractility, +dF/dt(max), -dF/dt(max), heart rate, contractility rate product, coronary flow and lactate dehydrogenase, creatine phosphokinase enzyme leakage were measured in all groups during pre-ischemic and post-ischemic periods (10 min after reperfusion). At the end of each experiment, the hearts were weighted and tissue levels of lipid peroxide, expressed in terms of thiobarbituric acid reactive substances, malondialdehyde, glutathione (an important intracellular antioxidant) and ATP were measured. Non-ischemic tissue levels of malondialdehyde, glutathione and ATP were also measured in another group (n = 6). There was no statistically significant difference among the simultaneous experimental and control groups in any criteria evaluated (P > 0.05). The addition of synthetic colloids to the standard cardioplegic solution did not provide further protection except for the gelatin group in which recovered contractile force was not significantly different from the group's initial values. This effect may be explained by its degradation to amino acids which may play a substrate role. (C) 1997 The Italian Pharmacological Society

EFFECT OF THEOPHYLLINE IN CHRONIC OBSTRUCTIVE LUNG-DISEASE

The bronchodilator, respiratory center and respiratory muscle effects of oral sustained release theophylline are investigated with a placebo controlled double-blind study in 34 patients with chronic obstructive lung disease (COLD). The first 3 days were a theophylline washout period and the patients did not receive theophylline and on the 4th day, serum theophylline concentration was negligible. Initial pulmonary function tests were performed. Twenty-four of the patients took 350 mg oral sustained release theophylline twice a day. Ten of the patients were given placebo. On day 7, serum theophylline concentrations of the study group were in therapeutic doses and the tests were repeated. Bronchodilator effect was assessed by spirometry, flow-volume loops and measuring airway resistance (R(aw)). Respiratory muscle function was assessed by measuring maximal inspiratory (P(Imax)) and expiratory pressures (P(Emax)) and the effect on respiratory center was evaluated by minute ventilation, mouth occlusion pressure index and inspiratory duty ratio. Forced vital capacity in one second (p <0.001), maximal mid expiratory flow rate (p <0.05), maximal expiratory flow at 50 percent of vital capacity (p <0.001), maximal inspiratory pressure (p <0.01) increased, while airway resistance (p <0.05) decreased significantly. Mouth occlusion pressure and minute ventilation mouth occlusion pressure index did not change after theophylline therapy. In placebo group, there was no significant change in airway obstruction assessed by spirometry and flow volume loops or in respiratory muscle function assessed by maximal respiratory pressures. It is therefore, concluded that oral sustained release theophylline has a bronchodilator effect in irreversible chronic obstructive lung disease, increases respiratory muscle function, but in therapeutic doses has no effect on respiratory cente

Venous blood histamine levels and effect of terfenadine in patients with bronchial hyperreactivity

Twenty-two subjects complaining of cough, chest tightness and/or shortness of breath with normal chest radiograph and normal pulmonary function test results were challenged with methacoline. Venous histamine levels were measured before and just after methacoline challenge. For comparison, a single blood sample was obtained from 10 normal subjects. Blood histamine levels were significantly higher in subjects with respiratory symptoms regardless of methacoline challenge being positive or negative (p<0.001). After methacoline challenge, blood histamine increased significantly in methacoline challenge positive group (p <0.05). Thereafter, terfenadine, a H1 antagonist, 120 mg/day were given to patients for one month. After terfenadine therapy, there was a subjective improvement of symptoms, methacoline provocation dose (PD20) increased and there was no significant change in blood histamine level. It is concluded that nonspecific challenge increases blood histamine levels and blood histamine levels seems to be a sensitive index of bronchial hyperreactivity in subjects with respiratory symptoms of unknown origin and that terfenadine is effective in the treatment of bronchial hyperreactivity

Comparative tear concentrations of topically applied ciprofloxacin, ofloxacin, and norfloxacin in human eyes

The tear pharmacokinetic profiles of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.3% norfloxacin ophthalmic solutions after a single drop topically administrations in the eyes of 30 healthy volunteers were evaluated. Tear samples collected at 30, 120, 180, and 240 minutes, were analyzed for drug concentrations by high performance liquid chromatography (HPLC) with fluorometric detection. Topically applied ciprofloxacin, ofloxacin, and norfloxacin achieved the mean tear concentrations (mean +/- SD) of 11.28 +/- 6.98, 6.52 +/- 4.06, and 13.28 +/- 8.78 mu g/g at 30 min, and then fell to 3.52 +/- 1.30, 4.82 +/- 1.80, and 5.79 +/- 4.80 mu g/g at 240 min, respectively. Topical norfloxacin achieved mean tear level significantly higher than ofloxacin at 30 min (p=0.031). There were no statistically significant differences in the mean tear levels of ciprofloxacin versus ofloxacin (at 30, 120, 180, and 240 min), ciprofloxacin versus norfloxacin (at 30, 120, 180, and 240 min) and ofloxacin versus norfloxacin (at 120, 180, and 240 min). However, the mean tear levels, 240 min after dosing ciprofloxacin and norfloxacin, fell to the statistically significant concentrations (p=0.02 and p=0.01, respectively). But, it is concluded that concentrations of ciprofloxacin, ofloxacin, and norfloxacin in tears were still significantly greater than the minumum inhibitory concentrations for the most sensitive organisms, 240 min after a single drop application