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The evaluation of low dose pre-operative X-ray therapy in the management of operable rectal cancer; results of a randomly controlled trial.

824 patients with operable rectal carcinoma were randomly allocated to be treated by surgery alone, 2000 rad in 10 daily fractions and 500 rad as a single fraction. No difference has been demonstrated in the actuarial survival rates to 5 years. The local recurrence-free and metastasis-free rates are similar in all groups. There is also no evidence that the pre-operative radiotherapy benefited patients in subgroups by Dukes' stage. The complication rates were also similar in the three treatment groups.

Clinical Trials as Topic↗

Cyclosporin in cadaveric renal transplantation: one-year follow-up of a multicentre trial.

In a multicentre trial conducted in eight European centres, 232 recipients of cadaveric renal allografts were randomly allocated to receive either cyclosporin (117 patients) or azathioprine and steroids (115 patients) for immunosuppression. All patients have now been followed up for at least a year. 1-year graft survival was 72% in the cyclosporin group and 52% in the control group. 24 of the 84 patients in the cyclosporin group with functioning grafts at 1 year had been changed to azathioprine and steroids, and 1 patient had had prednisolone added to cyclosporin therapy; the other 59 patients were receiving cyclosporin as their sole immunosuppressive agent. 16 patients on cyclosporin treatment never received steroids. 1-year patient survival was 94% in the cyclosporin group and 92% in the control group. There was no difference between the two treatment groups in the prevalence of infection. Lymphoma did not develop in any patient. At 1 year post-transplantation, renal function was poorer in patients on cyclosporin than in those on conventional therapy. Thus the 1-year graft-survival rate is higher with cyclosporin alone as a first-line immunosuppressive agent than with azathioprine and steroids.

Adrenal Cortex Hormones↗

Long-term treatment with disodium cromoglycate does not alter bronchial hyperreactivity in patients with perennial bronchial asthma.

The purpose of this study was to examine whether a 3-month therapy with disodium cromoglycate (DSCG) is able to lower bronchial hyperreactivity in patients with perennial bronchial asthma and hyperreactive airways. Therefore, 24 patients with this condition (11 women, 13 men; age range from 16 to 41 years) were randomly allocated to either active treatment (20 mg DSCG four times daily) or to placebo in a prospectively designed, double-blind study. Bronchial hyperreactivity was assessed by acetylcholine-induced bronchoconstriction before and after 6 and 12 weeks of either DSCG or placebo treatment, respectively. As test values, the variations in FEV1 and oscillatory resistance (Ros) before and after inhaled acetylcholine was used. Despite the fact that DSCG significantly attenuated acetylcholine-induced acute bronchoconstriction in all patients studied, it did not exhibit a significant reduction in bronchial hyperreactivity in this patient population.

Adolescent↗

Factors affecting decision-making by young adults with intellectual disabilities.

Young adults with intellectual disabilities were placed into high and low learned helplessness groups based on their responses to a self-report questionnaire. Within each group participants were randomly allocated to one of three conditions for presentation of vignettes depicting decision-making situations: vignette only; vignette plus two options; and vignette plus the same two options, each with one positive and one negative consequence. Participants were asked to say what they would do in the situation and to give a reason. Responses were judged according to criteria based on theories of rational decision-making. Low learned helplessness participants obtained significantly higher decision-making scores. Additional information about options or options plus consequences was not beneficial for either group. Implications for providing training and experiences in decision-making are discussed.

Adult↗

Diabetic retinopathy after 3 years' treatment with continuous subcutaneous insulin infusion (CSII).

Twenty-four insulin-dependent juvenile diabetics with no or minimal background retinopathy were randomly allocated to conventional insulin therapy (CIT) or continuous sc insulin infusion (CSII) administrated by a portable pump. At the present 3 year follow-up, there was one drop-out in the CSII group. Although the metabolic control was significantly better in the CSII patients, both groups improved significantly in metabolic control during the observation period. After 3 years, the HbA lc level was 7.4% +/- 1.2 (+/- SD) in the CSII patients and 8.6% +/- 1.6 in the CIT patients (P less than 0.01). As compared to the status at the beginning of the study, a progression of diabetic retinopathy (criteria: development of more than 2 microaneurysms) was observed in 4 of 11 in the CSII group and in 5 of 12 in the CIT group (P greater than 0.05). None of the patients were seen to develop soft exudates or neovascularisations. This study confirms the impression gained from a previous one-year follow-up of similar progression of retinopathy in patients on CSII and CIT.

Adult↗

[Tetravalent diphtheria, tetanus, pertussis and inactivated poliomyelitis vaccine].

Two hundred forty-nine infants were immunized after being randomly allocated to the classical Tetracoq vaccine or to inactivated poliomyelitis vaccines prepared on monkey kidney cells or on Vero-type continuous cell lines either mixed with DPT or placed in a 2-compartment syringe separating (by-pass) the polio vaccine from the DPT. The 3 preparations were well tolerated and led to a good immune response: the first after 3 injections, the second and third after the second injection.

Clinical Protocols↗

Writer's cramp: a controlled trial of habit reversal treatment.

In uncontrolled studies, several behavioural methods, including habit reversal, were said to be useful in writer's cramp. In this controlled study, 23 subjects with writer's cramp recruited from a neurology clinic were randomly allocated to five sessions over four weeks of either habit reversal training or a control treatment of relaxation training. Three subjects dropped out. Twenty patients (9 habit reversers, 11 controls) completed the trial up to three months follow-up. Outcome measures included observation of writing within the session, assessment of writing tasks completed at home, and blind ratings by an independent assessor. The results showed that habit reversal was no better than relaxation. Taking both treatments together, patients improved to three months follow-up on seven of nine measures, but remained substantially handicapped.

Adult↗

Randomised, controlled trial of faecal occult blood screening for colorectal cancer. Results for first 107,349 subjects.

To assess the effectiveness of screening by faecal occult blood tests, 107,349 people without symptoms of colorectal disease identified from general practitioner records have been randomly allocated to test and control groups. 53,464 test subjects were invited to carry out the screening test; 27,651 (53%) of the 52,258 who received the tests did so. Further investigation of the 618 (2.3%) with positive tests showed 63 cancers (52% stage A) and 367 adenomas (266 subjects). Rescreening of subjects with negative results every 2 years (9510 first rescreen, 3639 second) has shown a significant fall in the rate of positive results (1.7% of 7344; 0.3% of 2906). Cancers have also been diagnosed in 20 subjects presenting in the interval between a negative test and rescreening, and in 83 non-responders. The incidence of cancer in the control group (123 subjects; 10.6% stage A) was 0.72 per 1000 person-years. Cancers detected by screening were at a less advanced pathological stage, but it is too early to show any effect of screening on mortality from colorectal cancer.

Adenocarcinoma↗

The influence of isoflurane on blood flow in coronary bypass grafts.

The effects of isoflurane on graft blood flow, central hemodynamics and ECG were evaluated in 20 patients during coronary artery surgery in the period immediately after cardiopulmonary bypass (CPB). Intravenous anesthesia with thiopentone, diazepam, fentanyl (continuous infusion), droperidol and pancuronium supplemented with nitrous oxide was used before, and thiopentone and fentanyl were used during CPB. A first measurement of graft flow was performed during fentanyl infusion and the patients were randomly allocated to a control (n = 10) and a study (n = 10) group. In the study group isoflurane was administered in a dose that reduced systolic arterial blood pressure (SAP) to approximately 100 mmHg (13.3 kPa) (inspired concentration 0.5-1.5%) and a second measurement was performed after 30 min. In the control group the infusion of fentanyl was continued. Isoflurane reduced graft blood flow from 52 +/- 5 (mean and s.e. mean) to 40 +/- 5 ml . min-1 (P less than 0.01) concomitant with reductions in SAP, cardiac index, stroke index, left ventricular stroke work index and power index, while these parameters as well as graft flow remained unchanged in the control group. Isoflurane did not produce any change in the degree of ischemia as judged from the ECG. A high blood flow in recently established coronary artery bypass grafts is essential for the prevention of early graft occlusion; therefore the graft-flow-reducing effect of isoflurane has to be taken into consideration when evaluating different anesthetic regimens in the period after CPB.

Aging↗

An investigation of immunological subclass function in burned adults.

The serum concentrations of the immunoglobulin subclasses and their functional activity against pneumococcal polysaccharide (PPS) and E. coli antigens have been studied for 15 days in 12 adult burned patients, of whom six were randomly allocated to receive biosynthetic human growth hormone (somatropin) and six to form a control group. The concentrations of the major subclasses, IgG1 and IgG2, fell below their normal ranges as a result of injury by burning but had recovered significantly by the eleventh day of the study. There were no significant changes in the concentrations of the IgG3 and IgG4 subclasses, however, the relative proportions of the four subclasses remained unchanged and were comparable to those found in normal man. Significantly reduced functional activities, compared with normal volunteers, were observed in all the subclasses except IgG1. The activities of the major subclasses during the study were correlated with their serum concentrations and when corrected for their concentrations were comparable to those of normal blood donors. There were no significant increases in concentrations or activity of the subclasses as a result of somatropin administration. It is concluded that patients with moderately sized burns have reduced immunoglobulin function which results from the changes in serum concentration rather than from any qualitative change and that somatropin administration results in no improvement in immunoglobulin function.

Adolescent↗

Which intravenous induction agent for day surgery? A comparison of propofol, thiopentone, methohexitone and etomidate.

Eighty day patients for the vaginal termination of pregnancy were randomly allocated to receive thiopentone, propofol, methohexitone or etomidate as intravenous induction agents. The same anaesthetist administered the anaesthesia and all the observers were blind to the agents used. The results show that thiopentone and propofol produced the least sequelae at induction and in recovery. Furthermore, both agents produced a high quality of induction and recovery. All patients were discharged home 2 hours postoperatively and there was no obvious delay in recovery. This study has altered clinical practice in our Day Surgery Unit.

Abortion, Induced↗

The reflex dystrophy syndrome response to treatment with systemic corticosteroids.

Twenty-three patients with reflex dystrophy syndrome were randomly allocated to medication with oral prednisone, 10 mg thrice daily, or placebo, previous reports having indicated effect of systemic corticosteroids. The medication was continued until clinical remission, maximally 12 weeks. The diagnosis was based on fulfillment of at least four of seven criteria which included clinical, radiological and circulatory changes. All 13 patients in the prednisone-treated group showed more than 75% clinical improvement within the twelve-week period. Of the ten patients who received placebo, only two reported improvement. Prednisone appears to be superior to other treatment in reflex dystrophy syndrome, although the mode of action is not known.

Administration, Oral↗

Buccal morphine--a new route for analgesia?

The analgesic effects of buccal and intramuscular morphine were compared in a prospective, double-blind, double-dummy study in forty patients who experienced pain after elective orthopaedic operations. Each patient simultaneously received a buccal tablet and an intramuscular injection, only one of which contained morphine sulphate (13.3 mg); the patients were randomly allocated to two equal groups so twenty patients received each active preparation. The two preparations produced a similar degree of postoperative analgesia, assessed by the mean reduction in pain score and the pain relief score. Peak plasma morphine concentrations were slightly lower after buccal than after intramuscular administration but they declined more slowly; consequently, the drug's bioavailability was 40-50% greater after buccal than after intramuscular administration. The adverse effects of buccal morphine were generally less than those of intramuscular morphine.

Administration, Oral↗

Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.

Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Orally administered grass pollen.

In 1900 it was claimed that oral administration of ragweed could be used for the hyposensitization of hay fever patients. Several uncontrolled trials have been published, all showing an effect of oral hyposensitization. Only one study was controlled and showed no effect of oral hyposensitization. It was decided to undertake controlled clinical trials to determine the safety and effectiveness of orally administered enteric-coated grass pollen tablets in patients with hay fever. The actual grass pollen dose in the first trial was 30 times the dose that is normally recommended for preseasonal oral pollen hyposensitization using pollen aqueous solution or pollen powder. The safety study will be described here. Twelve young adults with a history of grass pollen hay fever positive skin prick test and positive nasal provocation test with extracts of timothy grass pollen were randomly allocated to one of the treatment groups with four patients in each group taking enteric-coated Conjuvac Timothy tablets or enteric-coated Whole Timothy pollen tablets or enteric-coated placebo tablets. The study was double blind. Preseasonally, the patients received 342,500 PNU and in total they received 4,500,000 PNU during 6 months. The patients receiving active treatment did not have any side effects. No significant changes were shown in the skin and nasal reactivity to grass pollen during the study. Neither were there any changes in timothy-specific IgE, IgG, total IgE nor histamine liberation from basophils.

Administration, Oral↗

Physical training and occupational rehabilitation after aortic valve replacement.

Forty-four patients were tested 2, 6 and 12 months after an isolated aortic valve implantation in order to evaluate the influence of training and vocational assistance on physical work capacity and the rate of reemployment. They were randomly allocated to a training group (A) or a control group (B). Training was carried out from the eighth to the twelfth week after operation and the socio-occupational status was evaluated. Training increased physical work capacity, expressed as cumulated work (CW), by 58 per cent (P less than 0.001), decreased the rate-pressure product (RPP) by 13 per cent (P less than 0.001) and the rate of perceived exertion (RPE) by 13 per cent (P less than 0.001) at the highest comparable work load. The CW was 38 per cent higher in the training than the control group after 6 (P less than 0.02) and 37 per cent after 12 months (P less than 0.025). After one year 81 per cent in group A and 65 per cent in group B were working (NS). Reemployment correlated significantly with the CW and inversely with the duration of sick leave prior to operation. Thus, physical training shortly after aortic valve operation rapidly and persistently improves physical work capacity while return to work is less influenced by training and socio vocational assistance.

Adult↗

Continuous oestrogen-progestogen treatment and bone metabolism in post-menopausal women.

The suggestion that norethisterone acetate (NETA) stimulates bone formation prompted us to investigate calcium and bone metabolism in post-menopausal women treated with a continuous combination of oestrogen and NETA. The study included 49 healthy post-menopausal women. After an initial examination the women were randomly allocated to 2 yr of treatment with either hormones or placebo; 43 women completed the study. Within the first year of treatment the hormone group showed a slight, but significant, increase in bone mineral content in the forearms (single photon absorptiometry) and in the total skeleton (dual photon absorptiometry). After this initial increase the bone mass remained constant throughout the trial. Bone mineral density of the spine (dual photon absorptiometry) showed a significant increase of more than 5% in the hormone group. There were significant decreases of 4-7% in bone mass in the placebo group over 2 yr. Biochemical estimates of bone turnover (plasma bone Gla protein, serum alkaline phosphatase, fasting urinary calcium and fasting urinary hydroxyproline) fell significantly in the hormone group, but remained unchanged in the placebo group. We conclude that continuous administration of NETA in combination with oestrogen provides effective prophylaxis against post-menopausal bone loss, although it does not produce a persistent positive calcium balance in early post-menopausal women.

Alkaline Phosphatase↗

A comparison of the gastric and central nervous system effects of two substituted benzamides in normal volunteers.

Eight healthy male volunteers participated in a single-blind, random allocation, crossover, comparison of intravenous metoclopramide (10 mg), the peripherally acting, gastrointestinal stimulant BRL 20627 (10 mg) and saline. The central nervous system effects were assessed by quantitative electroencephalography (EEG) and by visual analogue scales. Gastric motility and emptying were assessed by epigastric impedance. Metoclopramide increased the EEG amplitude by 10.4% (a statistically significant, P less than 0.05, effect) and increased frequencies above 22 Hz, whereas both BRL 20627 and placebo had only minor effect on the EEG frequencies and slightly decreased the EEG amplitude. Ratings on visual analogue scales showed that metoclopramide caused statistically significant (P less than 0.01 difference from placebo) restlessness and slight but significantly less (P less than 0.05 difference from placebo) feeling of happiness. Epigastic impedance changes indicated that both metoclopramide and BRL 20627 increased gastric contractile activity, but the rate of gastric emptying was not significantly altered by either drug although it tended to be shortened following metoclopramide but not BRL 20627 treatment. It is concluded that since the published animal data show that BRL 20627 has only weak dopamine antagonistic properties this study further implicates dopamine receptor blockade in the akathisia but not in the gastric effect of metoclopramide.

Adult↗