Effect of various antithrombotic regimens (aspirin, aspirin plus dipyridamole, anticoagulants) on the functional status of patients and grafts one year after coronary artery bypass grafting

From 1987 until 1991 a large prospective randomized multicentre study was performed in The Netherlands, Germany and Switzerland entitled CABADAS (Prevention of Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study). The aim of CABADAS was to evaluate the relative efficacy of (1) aspirin, (2) aspirin plus dipyridamole, and (3) oral anticoagulants in the prevention of vein graft occlusion during the first year after aortocoronary bypass surgery. No significant difference was observed in the incidence of graft occlusion among the three treatment groups. In a subgroup of 127 CABADAS patients, studied in the Academic Medical Centre in Amsterdam, the relationship between treatment and clinical status (i.e. symptoms of angina pectoris and exercise capacity) was assessed, and the relationship between treatment and functional status of the vein grafts was determined by means of thallium-201 exercise scintigraphy. There were no differences in symptoms among the three treatment groups in the 127 patients studied. There were no significant differences either among the treatment groups, as regards exercise capacity and the number or intensity of perfusion defects, in the 81 patients who underwent thallium-201 exercise scintigraphy. The three antithrombotic treatment regimens had a similar effect on the clinical status of patients and on the functional status of venous bypass grafts one year after coronary bypass surgery. This finding underscores the CABADAS results in that aspirin may be the preferred treatment option in patients following venous bypass surgery.     

Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens

BACKGROUND: Long-term administration of cyclosporin carries a risk of renal toxicity, and immunosuppressants are associated with an increased rate of malignant disorders. We undertook an open randomised study of the risks and benefits of two long-term maintenance regimens of cyclosporin in kidney-allograft recipients. The primary endpoint was graft function; secondary endpoints were survival and occurrence of cancer and rejection. METHODS: 231 recipients of a first allograft with at most one previous rejection episode were randomised 1 year after transplantation. Most were receiving cyclosporin and azathioprine. One group received cyclosporin doses adjusted to yield trough blood concentrations of 75-125 ng/mL (low-dose group); the second received doses that yielded trough concentrations of 150-250 ng/mL (normal-dose group). Analysis was by intention to treat. FINDINGS: At 66 months' follow-up, the low-dose and normal-dose groups were similar in mean serum creatinine (182 [SD 160] vs 184 [157] micromol/L; p=0.9) and mean creatinine clearance (47.5 [25.1] vs 45.3 (22.5] mL/min; p=0.6). Nine of 116 patients in the low-dose group and one of 115 in the normal-dose group had symptoms of rejection (p<0.02). There was no difference between the low-dose and normal-dose groups in survival (95 vs 92%; p=0.7) or graft survival (89 vs 82%; p=0.17) at 6 years. 60 patients developed cancers, 37 in the normal-dose group and 23 in the low-dose group (p<0.034); 66% were skin cancers (26 vs 17; p<0.05). INTERPRETATION: We found no evidence that halving of trough blood cyclosporin concentrations significantly changes graft function or graft survival. The low-dose regimen was associated with fewer malignant disorders but more frequent rejection. The design of long-term maintenance protocols for transplant recipients based on powerful immunosuppressant combinations should take these potential risks into account.     

Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is thought to produce analgesic and possibly also antipruritic effects when applied topically. Capsaicin 0.05% was applied three times daily over a 5-day period to the same infrascapular region. The effects of the pretreatment upon the pruritogenic and wheal and flare reactions to subsequent histamine iontophoresis (20 mC) were evaluated on the following day. The antipruritic effects of the pretreatment were compared with the effects of placebo pretreatment and no pretreatment. Wheal and flare areas were evaluated planimetrically. Itch or pain were rated every minute over a 24-min period. The areas of alloknesis, i.e. the induction of perifocal itch sensation by usually nonitching (e.g. mechanical) stimuli, were also evaluated. In control subjects, but not in atopic eczema (AE) patients, capsaicin pretreatment significantly reduced the flare area. Compared with control subjects, AE patients showed a lack of alloknesis or significantly smaller areas of alloknesis in pretreated and nonpretreated skin. In control subjects, capsaicin pretreatment significantly reduced itch sensations compared with nonpretreated skin, whereas in AE patients no differences were seen. Itch sensations in capsaicin-pretreated skin were significantly lower in control subjects than in AE patients. We conclude that capsaicin does effectively suppress histamine-induced itching in healthy skin but has less effect in AE. The diminished itch sensations and the absence of alloknesis in atopic individuals indicate that histamine is not the key factor in itching in AE.     

Circadian rhythm of cutaneous hypersensitivity reactions in nocturnal asthma

Results of Gamma nail use in treatment for trochanteric fracture of the femur in 25 patients (15 females, 10 males) aged 45-91 years are presented. There were 12 type I, 9 type II, 3 type III and 1 type IV fracture according to Boyd-Griffin classification. Fracture healed 10-12 weeks after surgery in 24 cases; one patient died because of pulmonary embolism.     

Comparison of two regimens for ciprofloxacin treatment of enteric infections

An understanding of the functional significance of the newly identified estrogen receptor (ER beta) in the brain will require definition of its expression pattern and relationship to ER alpha. Using an antibody generated against the C-terminus of rat ER beta, we report the presence of ER beta immunoreactivity in the lateral septum, medial amygdala, hippocampus and paraventricular nucleus (PVN) of ovariectomized rats. Double labelling studies in the PVN revealed that approximately 35% of oxytocin neurons located principally in the medial and lateral parvocellular divisions of the caudal PVN were immunoreactive for ER beta while vasopressin, somatostatin and magnocellular oxytocin neurons exhibited no ER beta staining with this antibody. No ER alpha immunoreactive cells were identified in the caudal PVN. These observations provide direct evidence for the differential expression of ER sub-types within neurons and indicate that ER beta may be of physiological significance in the regulation of hypothalamic parvocellular oxytocin neurons by estrogen.     

Effect of octreotide pretreatment on surgical outcome in acromegaly

Pretreatment with octreotide (OCT) in acromegaly has been reported to improve surgical outcome. The objective of this study was to analyze retrospectively the effects of a 3- to 6-month presurgical treatment with OCT in acromegalics focusing on electrocardiographic (ECG) records, blood pressure levels, glucose and lipid profile, tumor size and consistency, easy tumor removal at surgery, and morphological findings at pathology. Fifty-nine patients with acromegaly who were undergoing surgical treatment were studied randomly before surgery; 37 patients were untreated, and 22 were treated with OCT at doses ranging 150-600 micrograms/day for 3-6 months. At study entry, untreated and OCT-treated patients had similar circulating GH and insulin-like growth factor I (IGF-I), glucose, and cholesterol levels as well as prevalence of overt diabetes mellitus, hypertension, and ECG abnormalities. In untreated and OCT-treated patients, respectively, radiological imaging documented microadenoma in 0 and 1, intrasellar macroadenoma in 10 and 6, intra- and suprasellar macroadenoma in 18 and 11, invasive macroadenoma in 9 and 4 patients. Before surgery, serum GH and IGF-I levels significantly decreased in the 22 OCT-treated acromegalics, and in 5 of them, a significant shrinkage was documented. ECG abnormalities disappeared in 7 of 11 (63.6%) OCT-treated patients. In 3 of the 7 patients with diabetes mellitus, treatment with OCT together with low carbohydrate intake normalized blood glucose levels, whereas in 2 patients, insulin could be replaced by oral antidiabetics, and in 2 patients, the insulin dose was reduced. Presurgical blood glucose, total cholesterol and triglyceride levels, as well as systolic (145.2 +/- 3.4 vs. 132.9 +/- 2.5 mm Hg; P < 0.01) and diastolic (94.3 +/- 1.7 vs. 84.3 +/- 1.6 mm Hg; P < 0.001) blood pressure levels were significantly higher in untreated than in OCT-treated patients. Two weeks after surgery, circulating GH and IGF-I levels were normalized in 11 untreated (29.7%) and 12 OCT-treated (54.5%) patients (P < 0.005, by chi 2 test). Macroscopically, no difference was found between untreated and OCT-treated adenomas, whereas at pathology, a significant increases in cellular atypia (31.6% vs. 19.2%; P < 0.05) was found in OCT-treated adenomas. One patients in the untreated group died from cardiorespiratory arrest during the early postoperative period. Finally, the average duration of hospitalization after operation was longer in untreated than in OCT-treated patients (8.6 +/- 0.7 vs. 5.6 +/- 0.5 days). We conclude that a 3- to 6-month treatment with OCT before surgery for GH-secreting adenoma improved clinical conditions and surgical outcome and reduced the duration of hospitalization after operation.     

Antibody-mediated basophil accumulations in cutaneous hypersensitivity reactions of guinea pigs

Cutaneous basophil hypersensitivity (CBH) was studied in guinea pigs by using simplified histologic techniques. Animals immunized with oxazolone or picryl conjugates of keyhole limpet hemocyanin (KLH) emulsified with complete (CFA) or incomplete Freund's adjunvant (IFA) were found to have hapten-specific cutaneous basophil reactions when skin tested at 1 week with oxazolone or picryl chloride contant painting or intradermal injection of oxazolone or picryl-conjugated human serum albumin, respectively. Thus, hapten-specific cutaneous basophil reactions were present in guinea pigs immunized with CFA for classical delayed hypersensitivity, and in animals immunized with IFA for Jones-Mote reactions. Hapten-specific 24-hr cutaneous basophil reactions were passively transferred with immune serum from donors sensitized with conjugates of oxazolone or picryl-KLH in CFA or IFA, and with serum from oxazolone contact-sensitized animals as well. As little as 0.5 ml sera obtained from donors 1 week after immunization could systemically transfer cutaneous basophil reactions. It is likely that hapten-specific cutaneous basophil reactions are mediated by small quantities of serum antibodies. We conclude that antibody-mediated cutaneous basophil reactions may be distinctive hypersensitivity responses that can be distinguished from classical anaphylactic, Arthus, and delayed hypersensitivities. It is suggested that CBH reactions are heterogeneous and that antibody products of B lymphocytes, and factors probably derived from T lymphocytes, play a role in basophil accumulations at cutaneous hypersensitivity reactions.     

Effect of Y-24180, an antagonist at platelet-activating factor (PAF) receptors, on IgE-mediated cutaneous reactions in mice

OBJECTIVE AND DESIGN: We examined the effect of Y-24180, a potent platelet-activating factor (PAF) antagonist, on IgE-mediated cutaneous reactions in mice. MATERIALS: Female BALB/c mice were used. TREATMENT: Drugs were orally administered 1 h before a dinitrofluorobenzene (DNFB) challenge or 1 h before and 12 h after the challenge. METHODS: Biphasic increase in ear thickness, with peak responses at 1 h (immediate phase reaction, IPR) and 24 h (late phase reaction, LPR) after the DNFB challenge, were induced in mice which had been passively sensitized with monoclonal anti-dinitrophenyl IgE antibody 24 h before the DNFB challenge. Ear thickness was measured with a dial thickness gauge. RESULTS: Y-24180, WEB2086, ketotifen, and suplatast suppressed the IPR. Y-24180 also suppressed the LPR when administered once at 10 mg/kg or twice at 1 to 10 mg/kg. WEB2086 suppressed the LPR only when administered twice. However, ketotifen and suplatast did not suppress the LPR even when administered twice. Single administration of prednisolone significantly suppressed both the IPR and LPR. CONCLUSIONS: These results indicate that PAF may be involved in the induction of biphasic cutaneous reactions mediated by IgE, and Y-24180 is more effective compared with WEB2086 in this model. It is possible that the difference in the effectiveness between Y-24180 and WEB2086 depends on the persistence of those activities.     

Effect of immunosuppressive drug regimens on acute and chronic murine toxoplasmosis

This study was undertaken to quantify salivary gland parenchymal damage after radioiodine treatment with a standard protective regimen of ascorbic acid. Altogether, 106 patients underwent quantitative salivary gland scintigraphy with 99Tcm-pertechnetate prior to and 3 months after radioiodine therapy. Parenchymal function was quantified by calculating 99Tcm-pertechnetate uptake 13 min post-injection. Patients received 131I doses ranging from 400 MBq to 24 GBq (cumulative). Among the patients who received large doses of 131I, severe parenchymal destruction could be visually analysed as well as quantitatively evaluated. In contrast, after low-dose radioiodine treatment, mild parenchymal impairment was demonstrated by quantitative evaluation only. In conclusion, standardized quantitative salivary gland scintigraphy is essential for the reliable detection of mild parenchymal malfunction. Despite the standard protection regimen using ascorbic acid as a sialogogue, radioiodine therapy induces loss of salivary gland parenchymal function even with low doses of 131I.     

Gentamicin therapy in preterms: a comparison of two dosage regimens

OBJECTIVE: To compare the pharmacokinetic profile of gentamicin given as a once daily dose as against the conventional twelve hourly dose in preterm neonates. DESIGN: Randomized double blind study. SETTING: Tertiary level Neonatal Intensive Care Unit. SUBJECTS: Eighteen preterms admitted during the period January 1994 to May 1994. METHODS: The babies were randomly assigned to receive either the once daily (plan O, 4 mg/kg Q 24 h) or the conventional (plan C, 2.5 mg/kg Q 12 h) gentamicin dosage regimen. Blood was collected for the first peak level one hour after the first dose of gentamicin. Trough and peak-2 levels were collected before and one hour after the dose due at 48 hours, respectively. Assays were done using fluorescence immunoassay and the pharmacokinetic estimations were calculated using the three measured levels on a simplified one-compartment open model. Serum concentration time curves were plotted using the computerized Bayesian forecasting. Student 't' and Mann-Whitney U tests were applied as required. MAIN OUTCOME MEASURES: Initial peak levels and steady state trough and peak levels in both groups. RESULTS: Optimum therapeutic peak level after the first dose was achieved only with the once daily gentamicin regimen (mean level 5.88 vs 3.88 micrograms/ml p = 0.000). Mean trough levels remained over 2 micrograms/ml in the conventional regimen (2.76 vs 1.96 micrograms/ml p = 0.019) group. Mean peak levels at the steady state were not significantly different in either regimen (6.65 vs 5.45 micrograms/ml in conventional p = 0.177). None of the neonates showed nephrotoxicity. CONCLUSION: Once daily dose (4 mg/kg) of gentamicin has logistic and monetary benefits in addition to the obvious pharmacokinetic advantage.     

A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants

BACKGROUND: Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. METHODS: We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 g) who had respiratory index scores (mean airway pressure x the fraction of inspired oxygen) of 52.4 at two weeks of age. One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory-index score of > or =2.4 on treatment day 14) or additional placebo for two weeks. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose was then tapered. RESULTS: The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks' postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P< 0.001) in both groups. CONCLUSIONS: Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of ages.     

Effect of aspirin in coronary artery bypass grafting

OBJECTIVES: To evaluate the effect of aspirin (ASA) therapy on postoperative blood loss, transfusion requirements, reoperation for bleeding, duration of stay in the intensive care unit and in the hospital in a selected population undergoing a first coronary artery bypass grafting (CABG) surgery. DESIGN: Prospective observational study in consecutive patients during a 3-month period. SETTING: A teaching cardiothoracic center. PARTICIPANTS: Two hundred forty consecutive patients undergoing elective coronary artery bypass grafting surgery for the first time. INTERVENTIONS: Two hundred forty consecutive patients admitted for a first CABG the day before surgery were visited. patients with an abnormal routine coagulation screen or taking drugs that might have affected their coagulation mechanisms were prospectively excluded (n = 96). The date of the last dose of ASA was recorded in the 144 remaining patients, and data were acquired prospectively. MEASUREMENTS AND MAIN RESULTS: Total mediastinal blood drainage, blood products usage, reopening, and duration of intensive care unit and hospital stay were recorded. Patients were grouped by days free of ASA. There were no significant differences detected between groups. CONCLUSIONS: In patients undergoing a first CABG and with no known factors affecting their coagulation, ASA therapy did not appear to increase blood loss, reopening for bleeding, or blood products usage requirements during the hospital stay. ASA therapy did not influence the duration of stay in intensive care or in the hospital.     

Clinical study of using aspirin at various times to reduce adverse reactions of alpha-IFN

The prevalence of problem drinking among medical and surgical in-patients in a general hospital was studied using the CAGE questionnaire. Almost a quarter (23.3%) of the in-patients had associated drinking problems which were more among medical than surgical in-patients. In a large majority of these patients, the associated problem drinking was not recognised by the treating medical professionals. Routine administration of instruments like CAGE which are brief and easy to use would contribute to the early detection and management of alcohol problems in the general hospital setting.     

粉末预处理对钨坩埚应用性能的影响

利用不同原料粉末制备钨坩埚样品,并于高温环境下进行应用模拟实验.结果表明,射流分级预处理有助于提升钨坩埚组织均匀性及整体性能;以费氏粒度3.0～3.5μm的钨粉为原料,经射流分级、压制、烧结等工艺,可制得密度较高(18.770 g·cm-3)、维氏硬度较高(HV0.3372.15)的钨制品;将该钨坩埚置于高温环境下进行...     

Comparison of two cyclophosphamide treatment regimens in nephrotic patients with chronic glomerulonephritis

AIM: Comparison of two cyclophosphamide (CPA) treatment regimens in chronic glomerulonephritis (CGN) patients: oral daily CPA versus intravenous CPA pulses (IV-CPA) MATERIALS AND METHODS: 31 nephrotic patients entered the trial: 12, 16 and 3 with membraneous, mesangial proliferative and mesangiocapillary CGN, respectively. The patients were randomized into two groups. 13 patients of group 1 received oral CPA (1.5-2.0 mg/kg/day for 6 months, while 18 patients of group 2 received IV-CPA pulses (20 mg/kg/monthly, at least 6 pulses) combined with oral prednisolone (40-6-mg/day during 1.5 mo with subsequent tapering). At entry, no statistical differences (p > 0.05) were found between groups 1 and 2 by age, gender, duration of the renal disease, serum creatinine levels, frequency of arterial hypertension. Mean duration of follow-up was 27.6 and 22.6 mo (p > 0.05) for group 1 and 2, respectively. RESULTS: After 6 months of follow-up there was no difference in the rate of complete and partial remission between the groups (69 and 83% for group 1 and 2, respectively). The rate of renal function deterioration was also similar. Side effects occurred 3 times more frequently in group 1 than group 2. The mean cumulative course dose of CPA per 1 patient in group 1 was 35.6 g, in group 2--5.6 g. CONCLUSION: The effectiveness of methods was similar irrespective of CGN morphological form, but in spite of similar rates of remission of nephrotic syndrome, pulse CPA is preferable being more safe as to possible complications.