Plasma cortisol levels were determined by a radioimmunological assay in three groups of ten psoriasis patients treated with 0.05% halometasone ointment, 0.05% halometasone cream and 0.025% fluocinolone acetonide ointment, without occlusive dressings, for 7 days. Fourteen grams of the corticoid topical was applied daily (7 g/b.i.d.) to the psoriasis plaques covering an average of 25% of the body surface. No significant differences with respect to plasma cortisol values at 8 a.m. before, during and after treatment were evident in any of the three treatment groups, nor did the treatment groups significantly differ from one another with regard to their effect on the plasma cortisol levels. No side-effects were observed.
The efficacy and acceptability of 0.25% and 0.05% desoxymethasone, 0.1% betamethasone valerate and 1% hydrocortisone creams were compared in patients with eczema. A double-blind parallel group multi-centre design was employed in which 96 patients were recruited by four centres. Patients used one cream for a 3-week period and follow-up assessment visits were made at weekly intervals. Efficacy variables were: erythema/redness, scaling, itching and extent of area affected. These variables were assessed by both the investigator and the patient. The 0.25% desoxymethasone was the most effective treatment, producing the greatest degree of improvement in all clinical parameters, hydrocortisone was the least effective and 0.05% desoxymethasone was of intermediate effectiveness. The 0.1% betamethasone produced similar results to 0.25% desoxymethasone for half the assessments; for the other half the results were similar to 0.05% desoxymethasone. No adverse effects were reported during the study. The results are discussed in terms of physical properties of the vehicles and corticosteroid potency.
This is a report of a non-comparative trial to assess the usefulness of a 0.05% halometasone and 1% triclosan combination in a cream base in the treatment of acute infected and infection-prone eczematous skin disorders. The trial was carried out in three centres. Of the 126 patients admitted to the trial, 25 were lost to follow-up. The remaining 101 patients utilized the cream as the only treatment during the 3-week duration of therapy. Medication was applied to the lesions twice daily without occlusive dressing. The cream gave either excellent or good results in 89% of cases. Infection, which was initially present in 38 cases, disappeared within 5 days from 27 (71%) of them and within 6-10 days from a further six (16%) cases. The therapeutic effect was first noted (in 43 cases) within a mean of 2.7 days (+/- 1.01). The cream did not give rise to any serious local unwanted effects. Systemic unwanted effects were suspected in an 8-month old infant with extensive atopic dermatitis. The findings in this study substantiate those of other investigators that this halometasone/triclosan preparation combines potent and rapid therapeutic effect with excellent local and systemic tolerability.
A randomized, investigator-blind, parallel-group trial was conducted to compare the safety and efficacy of 0.1% mometasone furoate cream applied once daily with that of 0.1% betamethasone valerate cream applied twice daily in patients (n = 69) with allergic contact dermatitis, atopic dermatitis and other steroid-responsive dermatoses. After 3 day's treatment improvement in conditions averaged 38.2% and 39.3%, respectively, in the mometasone and betamethasone treatment groups, and after 21 days average improvements were 93.6% and 96.5%, respectively. The physicians' global evaluation of overall change in disease status and the patients' evaluation of treatment also indicated that the two treatment regimens produced comparable, rapid and progressive improvements in the patients' conditions, and no local side-effects were reported. It is concluded that mometasone furoate was as effective as betamethasone valerate in the treatment of a variety of steroid-responsive dermatoses, although mometasone furoate was applied only half as frequently.
A multicentre general practice study was undertaken to compare the efficacy of two proprietary dithranol preparations, Psoradrate 0.1% and Dithrocream 0.1%, in the treatment of chronic psoriasis, using a single-blind, within-patient trial design.
A total of forty-nine patients entered the study and treatment lasted for 6 weeks. Psoradrate 0.1% produced a greater mean per cent clinical improvement in psoriasis than Dithrocream 0.1% at each stage of the trial, and this difference was statistically significant (p = 0.025) at 4 weeks. The evidence also suggested that Psoradrate 0.1% resulted in greater reductions in psoriatic scaling.
Most patients found that the Psoradrate 0.1% was more effective and a significant majority (p=0.01) thought that it worked faster than Dithrocream 0.1%. Although the increased effectiveness of the Psoradrate 0.1% was associated with a higher incidence of stinging/burning of the skin, this was not reflected in the patients' overall opinions of the treatments. Twenty-three patients preferred Psoradrate as against seventeen who preferred Dithrocream.
A randomized, double-blind, left-right study to compare the therapeutic efficacy and the cosmetic acceptability of the new hydrocortisone 17-butyrate (Locoid®) 0·1% fatty cream application form with desonide (Apolar®) 0·1% ointment was performed in thirty patients suffering from moderate to severe atopic dermatitis. The medications were applied to symmetrical, bilateral skin lesions twice daily for 4 weeks. Both treatments effected highly significant reductions of the score values for the severity of all clinical skin parameters assessed. Score reductions were, however, more pronounced on Locoid-treated sides than on Apolar-treated sides both after 2 and 4 weeks of therapy. It appeared further that clinical efficacy of treatment at completion of the study was also in favour of Locoid-treated sides, indicating that Locoid fatty cream is more effective than Apolar ointment. No serious side-effects were reported during the study.
The expressed patient preferences with respect to cosmetic acceptability of treatments were significantly in favour of Locoid fatty cream, indicating that patients preferred the use of this new galenic formulation over an ointment formulation. It is concluded that the new application form of Locoid, a fatty cream, is a useful and beneficial addition to topical corticosteroid therapy, which will promote patient compliance in a wide range of corticosteroid-responsive skin diseases.
A new preparation for treatment of psoriasis of the scalp, containing desoxymethasone 0.25%, salicylic acid 1% and polyol-fatty esters in ethanolic solution (Ibaril) was tested in patients with psoriasis of the scalp. In a double-blind study comprising forty patients there was a significant difference in favour of this solution in comparison with betamethasone valerate solution, 0.1% (Betnovat) after 2 weeks of treatment.
A crossover study was carried out in general practice to compare Slow Trasicor and Trasidrex (a fixed combination of Slow Trasicor 160 mg and Navidrex 0.25 mg) in the treatment of newly diagnosed hypertensive patients. Trasidrex produced a significantly lower systolic and diastolic pressure, but there were no obvious differences in the incidence of side-effects between the two treatments.
Sixty-two patients with hypertension who were treated with a free combination of Slow Trasicor or Trasicor and Navidrex K were transferred to a fixed combination tablet, Trasidrex (slow oxprenolol 160 mg + cyclopenthiazide 0.25 mg). Blood pressure control was marginally improved and there was no increase in side-effects.
This study evaluated the efficacy of tamsulosin in improving stent-related symptoms and quality of life in patients with in-dwelling double-J ureteral stents. A total of 42 patients (15 males and 27 females) with ureteral stent placement following ureteroscopy, percutaneous nephrolithotomy or balloon dilatation, were prospectively randomized into two groups of 21 patients. Group I received 0.4 mg tamsulosin once daily for 4 weeks and group II was a non-placebo, non-treatment control. All patients completed the International Prostate Symptom Score (IPSS) and SF-36 questionnaires at 2 and 4 weeks post-operatively. The IPSS scores for irritative and obstructive symptoms were significantly lower in group I than group II at both 2 and 4 weeks. Among the eight domains of SF-36, role limitation due to physical health and bodily pain was significantly better in group I at 2 and 4 weeks. General health was also significantly better in group I at 2 weeks. Tamsulosin improved both urinary symptoms and quality of life without causing serious side-effects.
This prospective, randomized, double-blind study compared the effects on thromboelastography (TEG) of pre-loading with two different colloid fluids prior to spinal anaesthesia for caesarean section. Healthy full-term parturients received either 500 ml 6% hydroxyethyl starch 130/0.4 (HES, n = 25) or 500 ml 4% succinylated gelatine (GEL, n = 25) prior to spinal anaesthesia. TEG parameters including reaction time (r-time), clot formation time (k-time), clot formation rate (α-angle) and maximum amplitude (MA) were measured immediately before and after pre-loading. Both groups had significantly shorter r-time and lower MA after pre-loading. The α-angle was significantly decreased after pre-loading with HES but not with GEL. No significant differences in k-time were induced pre-loading. In conclusion, pre-loading with HES or GEL was associated with a mild hypocoagulable effect in healthy parturients presenting for elective caesarean section; however, all TEG parameters in both groups remained within or very close to the normal range after pre-loading.
This pivotal, multicentre, double-blind, parallel-group study evaluated the efficacy and safety of cerivastatin 0.8 mg. Patients with primary hypercholesterolaemia were randomized, after 10 weeks' dietary stabilization on an American Heart Association (AHA) Step I diet, to treatment with cerivastatin 0.8 mg (n = 776), cerivastatin 0.4 mg (n = 195) or placebo (n = 199) once daily for 8 weeks. Cerivastatin 0.8 mg reduced mean low density lipoprotein-cholesterol (LDL-C) by 41.8% compared with cerivastatin 0.4 mg (-35.6%, P < 0.0001) or placebo. In 90% of patients receiving cerivastatin 0.8 mg LDL-C was reduced by 23.9 -58.4% (6th - 95th percentile). Overall attainment of the National Cholesterol Education Program (NCEP) goal was achieved by 84% of patients receiving cerivastatin 0.8 mg and by 59% of those with coronary heart disease (CHD). In the sub-population meeting the NCEP criteria for pharmacological therapy for LDL-C reduction, 74.6% of patients, including the 59% with CHD, reached the goal with cerivastatin 0.8 mg. Cerivastatin 0.8 mg also reduced mean total cholesterol by 29.9%, apolipoprotein B by 33.2% and median triglycerides by 22.9% (all P < 0.0001). Mean high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 were elevated 8.7% (P < 0.0001) and 4.5% (P < 0.0001), respectively, by cerivastatin 0.8 mg. Reductions of triglyceride and elevation in HDL-C were dependent upon triglyceride baseline levels; in patients having baseline triglyceride levels 250 - 400 mg/dl, cerivastatin 0.8 mg reduced median triglycerides by 29.5% and elevated HDL-C by 13.2%. Cerivastatin 0.8 mg was well tolerated. The most commonly reported adverse events included headache, pharyngitis and rhinitis (4 - 6%). Symptomatic creatine kinase elevations > 10 times upper limit of normal occurred in 0%, 1% and 0.9% of patients receiving placebo, cerivastatin 0.4 mg or cerivastatin 0.8 mg, respectively. Cerivastatin 0.8 mg is an effective and safe treatment for patients with primary hypercholesterolaemia who need aggressive LDL-C lowering in order to achieve NCEP-recommended levels.
We performed a single-blind, sequential-design study to investigate the effects of concomitant oral tamsulosin 0.8 mg/day on the pharmacokinetics and safety of intravenous theophylline 5 mg/kg in healthy subjects. Ten healthy volunteers aged 19-39 years received placebo on study days 0, 1, 2 and 10 and tamsulosin on days 3-9. Theophylline was administered intravenously on days 1 and 9. Theophylline and tamsulosin pharmacokinetic data were determined following administration of the drugs on days 1 and 9 and day 9, respectively. No differences were observed in theophylline pharmacokinetic parameters with and without concomitant tamsulosin, and there were no abnormalities in tamsulosin pharmacokinetic data. Some significant changes in vital signs and a number of mild adverse reactions were reported, but the overall safety profile of tamsulosin and theophylline was acceptable. The results of the study suggest that no dose adjustment in tamsulosin is necessary when it is administered concomitantly with theophylline.
The calcium intakes of 35,072 Italian schoolchildren aged 7-10 years were investigated as part of a nation-wide survey of nutritional patterns. The Friuli, Piedmont, Latium and Sicily regions of Italy were selected as representative of the nation's north-south and east-west socio-economic divisions. A food-frequency questionnaire was used to assess the nutritional intakes of the whole sample. The validity of the food-frequency questionnaire method was assessed in a sub-sample of children by traditional methods: 24-h dietary recall and a weighted food diary. The data indicate that the mean calcium intakes of girls were below the recommended daily intake of 800 mg in all of the regions except Sicily, and that the calcium intakes of boys were above the recommended daily intake in all of the regions except Friuli. These results suggest that there may be deficiencies in the calcium intakes of this age-group in the wider population, particularly in girls. Food-frequency questionnaires are potentially valuable as part of a multi-method approach in large-scale nutritional monitoring.
An investigation of the nutrient intake of a large-scale sample (n = 35,072), drawn from the Italian school-age population (7-10 years) was carried out in a nationwide survey of nutritional patterns. Friuli, the Piedmont, Latium and Sicily regions were selected as representative of the nation's north-south and east-west socio-economic divisions. A food frequency questionnaire was used to assess nutritional intake. Traditional methods of 24-h dietary recall and a weighted food diary were used in subsamples to assess the validity of the food frequency questionnaire. Our data suggest that the average diet of Italian schoolchildren is rich in protein (especially animal proteins) and lipids (prevalently saturated fatty acids), but that carbohydrate and fibre intakes remain generally low. The relatively low calcium intake among girls and a widespread, more than adequate iron intake are also noteworthy. The food and nutrient intakes assessed suggest a dietary pattern with several positive points, but also reveal potential hazards for a wider population spectrum. The type of large-scale nutritional monitoring with a multi-method approach can be used in Italy and elsewhere to describe the dietary trends of a school-age population.
In a double-blind randomized study, sixty-two patients suffering from psoriasis or eczema were treated, twice daily for three weeks, either with 0.05% betamethasone 17, 21-dipropionate cream or with 0.025% fluocinolone acetonide cream.
The results showed that both topical corticosteroid preparations were effective, well tolerated and cosmetically acceptable.
Fifty-seven per cent of the patients treated with betamethasone dipropionate were rated as being ‘much better’ in the overall assessment of response at the end of the trial period compared to only 25% of those in the fluocinolone acetonide group.
This was a double-blind, randomized, parallel-groups comparison of alclometasone dipropionate and desonide ointments (0.05%) applied twice daily without occlusion for 3 weeks by patients with moderate to severe psoriasis. Data from thirty-three patients in each group showed that both treatments produced rapid amelioration of erythema, induration, and, especially, scaling; substantial improvement was evident after 1 week and continued thereafter. Differences between the groups were not statistically significant, but trends consistently favoured alclometasone. No adverse drug reaction occurred.
A double-blind study, carried out at two centres, comparing once and twice a day application of betamethasone-17,21-dipropionate cream 0.05% (Diproderm), has shown that the efficacy in treating eczema is the same after 1 week.
Alclometasone dipropionate cream 0·05% was compared to hydrocortisone butyrate cream 0·1% in the treatment of atopic dermatitis in forty children, 5 to 11 years old. In this double-blind, parallel-group trial, the experimental creams were applied twice daily for 2 weeks, without occlusion, to the study areas. Efficacy was evaluated 1 and 2 weeks after the start of treatment.
Both creams were effective treatments for atopic dermatitis; however, alclometasone dipropionate was judged slightly more efficacious. Improvement in erythema, induration, and pruritus averaged 76% for alclometasone dipropionate-treatedpatients and 70% for hydrocortisone butyrate-treated patients. At the end of treatment, the physician's global evaluation indicated nineteen of twenty patients in the alclometasone dipropionate group had between 51% and 100% improvement in disease signs and symptoms, compared with sixteen of twenty patients treated with hydrocortisone butyrate. Two patients in the alclometasone dipropionate-treated group and one in the hydrocortisone butyrate-treated group reported mild stinging.
In an open study of ten evaluable normal volunteers, 30 g of alclometasone dipropionate cream 0.05% was applied to 80% of body surface each morning and evening for 21 days. A plastic body suit effectively occluded the treated area for 12 hours/day. As demonstrated by continued normal levels of 8 a.m. plasma cortisol and 24-hour urinary 17-hydroxysteroid and free cortisol, no suppression of the hypothalamic-pituitary-adrenal axis occurred. Local adverse reactions were mild and transient.
These studies involved 1691 patients who applied either Diprosone or the comparative cream twice a day during the 3 wk trial period. The parameters evaluated were induration, inflammation, crusting, scaling, pruritus, excoriation and pain. It was found that Diprosone demonstrated superiority in terms of efficacy and tolerance over fluocinolone acetonide 0.025% (Synalar), flumethasone pivalate 0.02% (Locacorten), triamcinolone acetonide 0.1% (Kenacort), beclomethasone dipropionate 0.025% (Propaderm), betamethasone 17 valerate 0.1% (Betnovate), fluocortolone 0.25% (Ultralan), formocortal 0.025% (Fluderma) and fluprednidene acetate 0.1% (Decoderm) at the end of the three week trial period. While there were trends in favour of Diprosone over the other steroids during the first 7 days, differences were not statistically significant. The time of onset of action for all steroids tested was more or less the same being 4 days or less according to the particular sign or symptom evaluated. In examining the data beyond this period into the second and third weeks, the rate of continued successful response to treatment i.e., rapidity of improvement and 'cure' rate produced by Diprosone was found to be superior to that produced by other steroids. These results were statistically (p≤0.05) and clinically significant.
The implication of nosocomial infection due to Pseudomonas aeruginosa is demonstrated by comparing the bacteriological findings with the clinical picture of ten patients in a surgical intensive care unit. The occurrence of this organism and its resistance to beta-lactam-antibiotics and aminoglycosides is demonstrated. Ticarcillin was administered to ten patients following bacteriological and clinical evidence of infections due to P. aeruginosa. The pathogenicity of P. aeruginosa as an organism complicating the course of severely injured patients is discussed. Therapeutic consequences in regard to possible combination with other antibiotics are suggested.
As one of the main pathological changes of Parkinson's disease (PD), axonal degeneration was thought to be a passive process that is secondary to the apoptosis of dopaminergic neurons and, therefore, it has been overlooked for some time. Recent research, however, has indicated that axonal injury is the first location of damage in dopaminergic neurons in PD, and that the degree of injury in axonal degeneration is higher than in neural death. This study explored the relationship between apoptosis of dopaminergic neurons and their axonal degeneration by observing dopaminergic neuronal injury and axonal degeneration in the substantia nigra-striatum in different animal PD model and control groups. The results show that axonal degeneration plays a crucial role in the pathogenesis of PD and suggest that the process of axonal degeneration occurs independently of apoptosis and may even induce neuronal apoptosis. Thus, preventing axonal degeneration may be a potential new therapeutic strategy for PD.
In a three-week study of 10,000 general practice patients with depressive illness, a single dose of maprotiline 75 mg at night was effective therapy in three-quarters of the patients who completed the study.
At this dose the drug was well tolerated, and troublesome side-effects presented in only a small percentage of patients. Drowsiness was the most commonly reported side-effect, and the main reason for withdrawal of treatment.
The drug was acceptable to most physicians, and in this study was used in a wide range of patients and over a broad spectrum of depressive illness.
A post-marketing surveillance study of Euhypnos Forte (temazepam 20 mg) capsules for the treatment of insomnia in 10,057 patients previously unresponsive to other hypnotics given in conventional doses. Patients were prescribed a nightly dose of 40 or 60 mg, but 95% actually took 40 mg. At 2 weeks, 89% of patients found the treatment effective, as did 95% at 3 months. Hangover, severe enough to stop treatment, occurred in less than 3% of patients, and other adverse reactions such as headache, dreams, gastrointestinal disturbance and hangover symptoms were reported by only 6% of patients at 2 weeks and 4% at 3 months. The most common reason for stopping treatment was the patient having no further need for hypnotics. Euhypnos Forte was effective in 88% of 3,800 patients who had found nitrazepam unsatisfactory and 90% of 1,013 patients unresponsive to barbiturates.
Clinicopathological features and surgical outcomes in patients with solid pseudopapillary neoplasm (SPN) of the pancreas were analysed.
Data regarding clinicopathological features, surgery and outcome for patients with SPN were retrospectively collected and analysed. Patients were followed-up by telephone interview.
The study included 102 patients (89 females/13 males), 99 of whom underwent surgical resection. A total of 89 patients (87.3%) were followed-up (mean duration 26.98 months, range 2-95 months); 86 (96.6%) had no relapse or metastasis.
Surgical resection is the primary therapy for SPN, and results in a good prognosis.
The myotonolytic activity of a new muscle-relaxant, DS 103-282, was compared with that of diazepam in a randomized double-blind study on thirty patients suffering from acute muscular spasm due to disorders of the cervical and lumbar segments of the spine. Fifteen patients received 4 mg DS 103-282 and fifteen received 5 mg diazepam on a three times daily regime for 7 days.
DS 103-282 was found to alleviate symptoms and improve mobility to a significant degree (p ≥ 0.05) in all parameters evaluated and was also significantly superior to diazepam in 5 of these. Onset of action was particularly rapid for DS 103-282. Both medications were well tolerated and there was no significant difference between them.
On the basis of these data DS 103-282 may be considered a more powerful and faster-acting myotonolytic agent than diazepam with which it was compared in similar clinical indications.
In a double-blind trial tizanidine (DS 103-282: S-Chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole), a new muscle relaxant, was compared with diazepam in twenty in-patients suffering from acute paravertebral muscle spasm. All the patients had suffered from degenerative spinal disease for some years. Ten patients received tizanidine and the other ten received diazepam. Both drugs were administered t.i.d. for a period of 7 days. Significant improvements were reported in eight of the sixteen variables. Tizanidine was significantly superior to diazepam for two of these variables (lateral flexion of the lumbar spine, right and left).
A centrally mediated blood-pressure-lowering effect was observed with both drugs. Tizanidine was generally better tolerated, only two patients reporting transient side-effects compared with five patients in the diazepam group. Like diazepam, tizanidine is a suitable drug for the treatment of acute paravertebral muscle spasm.
The effects of piroxicam, tenoxicam, diclofenac sodium, acetylsalicylic acid and tiaprofenic acid on the chemotaxis and random migration of human polymorphonuclear leukocytes were investigated, using zymosan-activated serum as chemo-attractant, with a modified Boyden chamber technique. All five compounds significantly reduced chemotaxis. The random migration of polymorphonuclear leukocytes was inhibited by piroxicam, diclofenac sodium and tiaprofenic acid but not by tenoxicam or acetylsalicylic acid. The inhibitory effect of these non-steroidal anti-inflammatory drugs on polymorphonuclear leukocyte chemotaxis and on random migration was generally dose-dependent. The results suggest that the drugs studied may have a direct effect on polymorphonuclear leukocyte chemotaxis and that this activity may contribute to their anti-inflammatory properties.
The effects of zolpidem, an imidazopyridine derivative, were studied in 107 patients suffering from insomnia, 60.9% of whom were over 60 years of age, in a 6-month, single-blind, flexible dose, general practitioner study. Comparison was made between baseline, last day of treatment and 10 days after the end of treatment to assess efficacy and rebound insomnia. An improvement in all efficacy parameters--time taken to fall asleep, total amount of nocturnal sleep and number of nocturnal awakenings--was reported by the investigator and the patients; the improvement was evident from the first evaluation day and was maintained throughout the trial. Improvement was also maintained during the washout period with a lack of rebound insomnia. There was no sign of withdrawal symptoms and tolerance to zolpidem did not develop over the 6-month treatment period. Adverse events were mild and infrequent, and tended to resolve with a dose reduction. It is concluded that 10 mg/day zolpidem is an appropriate starting dose and is effective and safe for the treatment of sleep disturbances of different origins.
Bone metastasis is a major complication of advanced breast cancer. The present prospective case-control study investigated the involvement of microRNA (miR)-10b in the development of bone metastasis arising from primary breast carcinoma.
Serum miR-10b concentrations were determined by quantitative real-time reverse transcription-polymerase chain reaction in 122 patients with breast cancer, with or without bone metastases, and 59 age-matched healthy control subjects.
Serum miR-10b concentrations were significantly higher in patients with bone metastases than in patients without bone metastases or control subjects. Serum miR-10b had an area under the receiver operating characteristic curve for the presence of bone metastases of 0.769, with 64.8% sensitivity and 69.5% specificity.
These results suggest that serum miR-10b may be a useful biomarker for the identification of bone metastatic breast cancer.
Distal trisomy of 10q is a rare chromosomal abnormality. Distal deletions of the terminal long arm of chromosome 15 have rarely been described. We report on a male infant with low birth weight and microcephaly, a flat face with a spacious forehead, low-set ears, blepharophimosis, microphthalmia, a small nose, and a depressed nasal bridge. Microarray comparative genomic hybridization identified that he had the karyotype 46, XY, der (15) t (10;15) (q25.2;q26.2) pat, with chromosomal breakpoints at 10q25.2 and 15q26.2. This male neonatal case had an unbalanced translocation inherited from his father who was a balanced carrier with the karyotype 46, XY, t (10;15) (q25;q26). The neonate had a partial trisomy of the long arm of chromosome 10 with a partial monosomy of distal 15q. The clinical features were in agreement with previous descriptions and allowed us to propose a growth retardation phenotype for this neonate case.
This study evaluated interleukin (IL)-11 as an independent prognostic marker of mortality following intracerebral haemorrhage (ICH). Plasma IL-11 levels in patients with ICH were significantly higher than in healthy controls. Multivariate analysis indicated that plasma IL-11 level was an independent predictor for mortality within 1 week of ICH onset and was positively associated with haematoma volume. Receiver operating characteristic curve analysis identified that a baseline plasma IL-11 level > 20.9 pg/ml predicted mortality within 1 week of ICH onset with 81.2% sensitivity and 74.1% specificity. The area under the curve for IL-11 level was significantly smaller than that for the Glasgow Coma Scale score, but similar to that for haematoma volume. IL-11 did not, however, significantly improve the predictive value of the Glasgow Coma Scale or haematoma volume. Thus, IL-11 may be considered as a new independent prognostic marker of mortality and an additional valuable tool for risk stratification and decision-making in the acute phase of ICH.
In trials performed by the General Practitioner Clinical Research Group two rating scales have been employed extensively to measure depression. One includes some 17 target symptoms whilst the second is a shorter scale of 11 items. Although extensively used, neither scale has been validated against other measures of depression. An attempt was made to validate the 11-item scale, completed by the physician, against the Zung self-rating depression scale and the Wakefield Inventory, both patient-completed scales. Using thirty depressed patients the correlation between the 11-item scale and the Zung was 0.59 and between the 11-item scale and the Wakefield it was 0.5. Surprisingly, although the two scales are patient-completed and purport to measure the same thing, the correlation between the Zung and the Wakefield scales was only 0.69. All the correlations were statistically significant at the 1% level.
To observe sex determining region Y-box 11 (SOX11) gene expression in cutaneous malignant melanoma and its effect on tumour cell proliferation.
Clinicopathological data and tissue samples from patients with cutaneous malignant melanoma, together with tissue samples from healthy volunteers (controls), were retrospectively reviewed. Protein levels of SOX11 and the antigen identified by monoclonal antibody Ki-67 (Ki-67) in skin lesions were analysed using immunohistochemistry. The correlation between protein levels and clinipathological parameters was investigated.
Out of 40 patient samples, 25 (62.5%) were positive for SOX11 protein in malignant melanoma tissue. This was significantly higher than in 40 control tissue samples, in which no SOX11 protein was detected. Presence of SOX11 protein was positively related to the proliferation index of cutaneous malignant melanoma tumour cells. Presence of SOX11 protein in cutaneous malignant melanoma was related to tumour type, tumour location, lymph node metastasis and 5-year survival rate.
Human cutaneous malignant melanoma tissues expressed high levels of SOX11 compared with healthy controls, suggesting that SOX11 may be a new prognostic marker for malignant melanoma.
A phase I, double-blind, single-dose, randomized, two-period crossover study was conducted to investigate the effects of pimobendan on renal function to assess whether renal events were a contra-indication to its administration. Results in eight healthy volunteers indicated no significant adverse events on renal plasma flow, glomerular filtration rate, or laboratory safety screens; side-effects were also found to be minimal. Further studies are indicated to assess whether, in the proposed treatment group, i.e. patients with heart failure (in whom compromised renal function is common), pimobendan similarly elicits no serious adverse renal effects.
Unter Verabreichung einer Einzeldosis wurde eine randomisierte, über zwei Zeitspannen stattfindende gekreuzte Doppelblindstudie der Phase I durchgeführt, um die Effekte von Pimobendan auf die Nierenfunktion zu untersuchen. Diese Untersuchung diente der Beurteilung, ob eine gestörte Nierenfunktion als Gegenanzeige für die Verabreichung dieses Präparates zu bewerten ist. Die an acht gesunden Freiwilligen ermittelten Ergebnisse ließen keine signifikanten, unerwünschten Ereignisse auf den renalen Plasmafluß, auf die glomeruläre Filtrationsrate oder auf die Ergebnisse der im Labor durchgeführten Sicherheits-Screening-Tests erkennen. Darüber hinaus wurde auch festgestellt, daß die Nebenwirkungen geringgradig waren. Es sind weitere Studien angezeigt, um zu beurteilen, ob in der vorgeschlagenen Behandlungsgruppe, das heißt bei Patienten mit Herzversagen, bei denen eine gestörte Nierenfunktion häufig vorkommt, Pimobendan auf ganz ähnliche Weise keine schweren unerwünschten Effekte auf die Nieren hervorruft.
A post-marketing acceptability study was performed in 11,685 patients to assess the efficacy and acceptability of 10 mg timolol/2.5 mg bendrofluazide in patients with mild to moderate hypertension in general practice. The initial dose was 1 tablet/day. This was adjusted at weekly intervals up to a maximum of 4 tablets/day or until blood pressures of less than or equal to 95 mmHg diastolic or, in patients of greater than or equal to 60 years, less than or equal to 100 mmHg plus the patient's age (in years) systolic, were achieved. Stabilized patients were followed-up after 12, 24 and 48 weeks. Of the patients enrolled, 69% (8039) were successfully treated for at least 8 weeks, 26% (3033) were withdrawn and 5% (613) defaulted. One tablet/day was required by 61% of patients and 29% required 2 tablets/day to achieve stabilization. The mean reductions in systolic and diastolic blood pressures and pulse rate were 31 and 19 mmHg, and 11 beats/min, respectively. Over 60% of the patients enrolled were still taking timolol/bendrofluazide after 12 months' continuous therapy. The most frequently reported reason for withdrawal was an 'adverse event' which occurred in 15.4% (1805) of patients. Only 1.9% (217) failed to achieve target blood pressure on 4 tablets/day. This large study has shown timolol/bendrofluazide to be a highly effective and acceptable once daily therapy for mild to moderate hypertension in general practice.
One-hundred and eighteen patients with rheumatoid arthritis were treated for 4 weeks with flurbiprofen 300 mg/day (sixty patients) or naproxen 750 mg/day (fifty-eight patients) in a six-centre randomized trial. Flurbiprofen proved to be more effective than naproxen in reducing morning stiffness (p < 0·01), Ritchie articular index (p < 0·01) and number of swollen joints (p < 0·05) and in relieving night pain (p < 0·01).
The incidence and severity of side-effects, mainly gastric, were both low and similar with flurbiprofen (17%) and naproxen (19%).
Fortagesic was compared with Paramol 118 in a fourteen day single-blind crossover study in patients with moderate pain due to osteoarthritis. Both preparations were shown to be similarly effective. More side-effects were seen with Paramol 118 than with Fortagesic and more patients preferred Fortagesic. These differences were not statistically significant, but it is concluded that Fortagesic is a useful effective analgesic for standard use in moderate pain.
We evaluated the dose dependence of an oral adsorbent, AST-120, in 31 patients with early chronic renal failure (baseline serum creatinine: 1.2-3.0 mg/dl). Twenty-three patients were given AST-120 and eight patients were not. AST-120 was administered at three different maintenance doses, < 3.0 g, 3.0 g and 6.0 g/day, according to patients' ability to tolerate treatment. The treatment period was 12 months. The slope of the reciprocal of serum-creatinine concentration versus time was calculated to assess the progression of renal failure. This slope became significantly less steep after AST-120 treatment at 6.0 g/day, but did not change significantly at the other doses. These findings suggest that 6.0 g/day of AST-120 may delay the initiation of dialysis in patients with early chronic renal failure.
The oral adsorbent AST-120 has been widely used in Japan to delay the initiation of dialysis therapy in patients with chronic renal failure. This study evaluated the long-term effects of AST-120 in patients with chronic renal failure who had not previously undergone dialysis. One hundred out-patients were prospectively enrolled and prescribed 6 g/day oral AST-120 for >or= 1 year. The clinical effectiveness of AST-120 was evaluated by comparing changes in the slope of the reciprocal serum creatinine-time plot (1/sCr slope) before and after AST-120 administration. The 1/sCr slope improved significantly after >or= 1 year of AST-120 treatment and greatest improvement was observed in patients with the longest AST-120 administration period (> 30 months). The results suggest that long-term treatment with AST-120 may be beneficial for chronic renal failure patients in the pre-dialysis stage.
This preliminary communication reports on a non-randomized pilot type trial of 34 females with urgency after pelvic radiotherapy who were treated with flavoxate hydrochloride for 4 weeks. A dosage of 600 mg/day was given to 21 patients and 1200 mg/day to 13 patients. Clinically, both regimens achieved comparable results. Urodynamically (first desire volume, bladder capacity and pressure at capacity) treatment with 1200 mg/day was significantly superior to 600 mg/day. Both schedules were equally well tolerated by patients and no treatment interruption occurred. A randomized double-blind trial comparing 600 and 1200 mg/day flavoxate hydrochloride is currently underway the results of which will be reported in due course.
Flavoxate hydrochloride at a daily dosage of 600 mg was compared to a daily dosage of 1200 mg for the treatment of unstable bladder. Twenty-seven patients were treated for 4 weeks in a double-blind, randomized, parallel-group trial. Clinically, both schedules were equally successful. In urodynamic terms, however, particularly with respect to uninhibited detrusor contractions, 1200 mg/day was significantly superior to 600 mg/day. Tolerability was excellent for both regimens. The side-effect free treatment of urgency and urge incontinence is of paramount importance for a patient's quality of life.
A non-comparative multicentre trial was conducted by 156 general practitioners with 1218 patients in eight European countries to assess the efficacy and toleration of once daily doses of piroxicam in the treatment of osteoarthrosis (degenerative joint disease). Drug was taken for an average of 2.5 months with more than 75% on piroxicam for 7 weeks or more. The maintenance dose in 81% of all patients was the same as the recommended starting dose of 20 mg, taken once daily after breakfast. Although more than 40% of patients received concurrent analgesic/anti-inflammatory drug(s) at the beginning of the trial, only 10% to 15% took such therapy by the end of their treatment period.
Most patients had moderate or severe involvement in one or more of knee, spine, hip, digit, or shoulder joints. From 75% to 80% of patients reported marked or moderate improvement in ability to move and use joints and their general overall feeling (‘quality of life’ measurement). Patients' self-assessment of joint pain and stiffness showed from 25% to 30% reduction after 2 weeks on drug and up to 60% reduction by the end of the treatment period. Onset of morning pain at baseline occurred within 1 to 2 hours after waking, but by final evaluation, the average time had risen to 6 hours in those patients still experiencing pain. Side-effects definitely attributed to piroxicam were reported by 13% of all patients; there were sixty discontinuations (5%) due to drug. The majority of side-effects were upper gastro-intestinal in origin, primarily epigastric distress, nausea, and indigestion. Most side-effects were mild or moderate and were experienced without incident within the first three weeks on drug.
In their global evaluation, investigators judged the efficacy of piroxicam as marked or moderate in 82% of patients while toleration was considered excellent or good in 92% of cases. In comparison to a patient's prior therapy, investigators considered piroxicam better in its overall effect in 72% of the cases. In summary, the data show that once-daily doses of piroxicam, mostly 20 mg, can provide very favourable efficacy and toleration in the treatment of osteoarthritis in general practice.
This study aimed to define the correlation between microRNA-122 (miR-122) expression and hepatectomy-induced liver injury in patients with hepatocellular carcinoma (HCC).
Plasma miR-122 expression in patients with HCC and healthy age-matched controls was determined, and correlated with plasma alanine transaminase activity (ALT) and bilirubin levels preoperatively and on days 1 and 7 postoperation. Correlations between plasma miR-122 and clinicopathological characteristics at 1 day postoperation were also determined.
This study included 80 patients with HCC and 80 controls. Baseline expression of miR-122 mRNA and ALT in patients with HCC was significantly higher than in controls. MiR-122 expression correlated with ALT and bilirubin levels preoperatively and on days 1 and 7 postoperatively. In patients with HCC who received a block of the first hepatic portal during surgery and those with excised tumour size >5 cm, plasma miR-122 expression was significantly increased on day 1 postoperatively, compared with expression levels in those who did not receive a block and those with smaller tumours.
Plasma miR-122 expression is correlated with hepatectomy-induced liver injury in patients with HCC. Increase in miR-122 expression could be used as an index of such injury before and after hepatectomy in these patients.
Iodine-123-metaiodobenzylguanidine [123I-MIBG] has been used to evaluate the cardiac sympathetic nervous system. We evaluated the effect of pulmonary hypertension on the sympathetic neuronal function of the left ventricle in patients with pulmonary hypertension. We studied 20 patients with either chronic lung disease or pulmonary vascular disease. The patients were divided into a pulmonary hypertensive group and a control group. Single photon emission tomography was performed in the resting state 15 min and 4 h after administration of 123I-MIBG. Regions of interest (ROI) were set in the left ventricular (LV) free wall, the interventricular septum (IVS) and outside the LV free wall on short-axis images. The washout rate and the ROI/LV uptake ratio were calculated in each ROI. The IVS:LV uptake ratio was significantly lower in the pulmonary hypertensive group than in the control group. Our results suggest that left heart sympathetic neuronal dysfunction initially occurs in the IVS before it involves the LV free wall subsequently.
The objective of this study was to evaluate whether or not right ventricle (RV) uptake of iodine-123-labelled-beta-methyliodophenylpentadecanoic acid ([123I]-BMIPP) correlated with the degree of right ventricular pressure overload (RVPO). Myocardial scintigraphy of [123I]-BMIPP and thallium-201 (201Tl) was performed on 46 patients with RVPO. We determined the right ventricle (RV)/left ventricle (LV) ratio = (radioactivities of RV)/(radioactivities of LV), and the RV metabolic index (RVMI) = (RV/LV ratio of [123I]-BMIPP)/(RV/LV ratio of 201Tl). We also evaluated the correlation between RVMI and mean pulmonary arterial pressure (mPAP), and between RVMI and total pulmonary resistance (TPR). Significant correlations were found between the RV/LV ratio of [123I]-BMIPP and mPAP and between the RV/LV ratio of [123I]-BMIPP and TPR. In addition, a significant negative correlation was observed between RVMI and mPAP and between RVMI and TPR. RVMI declined as RVPO increased, suggesting the presence of a fatty-acid metabolism disorder of the RV. Moreover, [123I]-BMIPP myocardial scintigraphy could be useful for evaluating a disorder of the fatty-acid metabolism of the RV with RVPO.