Patients with premenstrual syndrome have decreased saccadic eye velocity compared to control subjects

BACKGROUND: Prior neurophysiological studies on patients with premenstrual syndrome (PMS) have revealed sleep electroencephalographic alterations in both cycle phases. We report on a study evaluating saccadic eye movements in PMS patients. METHODS: Saccadic eye movements were examined in 21 women with and 21 women without PMS on two occasions in the midfollicular and late luteal phase, respectively. On each occasion, plasma levels for estradiol, progesterone, and neuroactive progesterone metabolites were determined. RESULTS: PMS patients had decreased saccadic eye velocity (SEV) compared to control subjects. This finding was most evident in the luteal phase, whereas the difference between groups approached significance in the follicular phase. Saccade accuracy and saccade latency were not different between the two groups. Control subjects increased their SEV in the luteal phase compared to the follicular phase, whereas PMS patients did not. PMS patients rated themselves more sedated than control subjects on the testing days in both phases of the menstrual cycle. Plasma levels of gonadal hormones and neuroactive steroids did not differ between the study groups. CONCLUSIONS: The findings of a decreased SEV in PMS patients could be due to poor sleep and consequently increased sedation, but might also indicate that gamma-aminobutyric acidergic inhibition is different in patients with premenstrual syndrome.     

Ocular surface damage and tear lactoferrin in dry eye syndrome

Because falls are common among the elderly and are associated with high morbidity and mortality, community surveillance has been recommended. The purpose of this study was to characterize the impact of falls among the elderly on emergency medical transport services (EMS) and to explore the potential for community surveillance of falls through the use of computerized EMS data. Computerized EMS data and United States census data for 1990 for persons aged > or = 65 in Forsyth County, NC, were used to produce EMS transport rates for falls and to make comparisons by age, gender, race, and residence (nursing home vs community). A fall was reported as the cause for EMS summons in 15.1% (613 of 4,058) of cases. Transport rates in 1990 for falls were 7.8 per 1,000, 25.4 per 1,000, and 58.5 per 1,000 for the age groups of 65 to 74 years, 75 to 84 years, and 85 years and older. Rates were higher for females than for males (17.1 per 1,000 v 8.1 per 1,000) and higher for whites than for African-Americans (14.3 per 1,000 v 10.3 per 1,000). Rates for nursing home residents were four times that of community residents (70.6 per 1,000 v 16.0 per 1,000). Over 50% of nursing home fallers were transported between midnight and 0400 compared with 25% of community dwellers. EMS summons for older adults reporting a fall accounts for a significant portion (15%) of all transports in this county. Computerized EMS data demonstrated patterns of falls among the elderly that are consistent with known demographic factors. The potential for using computerized EMS data as a practical means of community surveillance should be further explored.     

Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B

OBJECTIVE: To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar. DESIGN: Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist. SETTING: General clinical research center of a university hospital inpatient unit. PATIENTS: Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study. MAIN OUTCOME MEASURES: Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression). RESULTS: Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment. CONCLUSIONS: Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases.     

Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle glaucoma or ocular hypertension

We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5% QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The study had a positive-controlled, double-masked, randomized, multicenter, 12-week, two-period (6 weeks each), crossover design. One hundred fifty-two patients with open-angle glaucoma or ocular hypertension were randomized to receive either timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed by a crossover to the alternate treatment. IOP and heart rate were measured at morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming solution QD was comparable to levobunolol BID in reducing IOP at peak and trough. Although the effects on peak heart rate were similar between the two medications, the effect on trough heart rate of timolol maleate gel-forming solution QD was significantly less than that of levobunolol BID (P = 0.001). The incidence of ocular burning and stinging was comparable between the two treatments. Patients experienced significantly more blurred vision when using timolol maleate gel-forming solution than when using levobunolol (P = 0.013). Overall, more patients experienced at least one adverse event when using timolol maleate gel-forming solution. Timolol maleate gel-forming solution QD is as efficacious in reducing IOP as levobunolol BID.     

Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group

BACKGROUND: Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. METHODS: 358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat. FINDINGS: The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group. INTERPRETATION: Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.     

Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes

OBJECTIVE: To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and metformin (2,000 or 2,500 mg/day in divided doses). RESEARCH DESIGN AND METHODS: This study had a multicenter randomized double-blind placebo-controlled parallel-group comparison design. The trial lasted 31 weeks and consisted of a 1-week screening period, a 6-week placebo pretreatment period, and a 24-week period of acarbose or placebo, with a forced titration from 25-50 mg t.i.d. and a titration of 50-100 mg tid that was based on glucose control. The primary efficacy variable was the mean change from baseline in HbA1c. Secondary efficacy variables included mean changes from baseline in fasting and postprandial plasma glucose, serum insulin, and triglyceride levels. RESULTS: The addition of acarbose to patients on background metformin and diet therapy showed a statistically significant reduction in mean HbA1c of 0.65%. There were statistically significant reductions in fasting and postprandial plasma glucose and serum insulin levels compared with placebo. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. No significant differences in liver transaminase elevations were observed between patients treated with acarbose and those treated with placebo. CONCLUSIONS: The results of this study demonstrate that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with metformin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and fasting and postprandial glucose and insulin levels.     

Efficacy and safety of acarbose in insulin-treated patients with type 2 diabetes

OBJECTIVE: To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and insulin. RESEARCH DESIGN AND METHODS: A multicenter randomized double-blind placebo-controlled parallel-group comparison study was conducted. The trial was 26 weeks with a 2-week screening period and a 24-week period of treatment with acarbose or placebo, with forced titration from 25 mg t.i.d. to 50 mg t.i.d. after 4 weeks, and titration of 50 mg t.i.d. to 100 mg t.i.d. after 12 weeks based on glucose control. The dosage of insulin was to remain stable. The primary efficacy variable was mean change from baseline in HbA1c, and secondary efficacy variables included mean changes in fasting and postprandial plasma glucose and triglyceride levels. RESULTS: The addition of acarbose to the treatment of patients receiving background insulin and diet therapy resulted in a statistically significant reduction in mean HbA1c of 0.69% compared with placebo. There were statistically significant reductions in postprandial plasma glucose and glucose area under the curve, and in postprandial serum triglyceride levels in the acarbose-treated patients. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. There were no significant differences in hypoglycemic events or liver transaminase elevations between groups. CONCLUSIONS: This study demonstrated that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with insulin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and postprandial glucose levels.     

Efficacy and safety of azelaic acid and glycolic acid combination therapy compared with tretinoin therapy for acne

We conducted a 12-week, multicenter, randomized, double-masked, parallel-group study of the efficacy, safety, and tolerability of azelaic acid 20% cream and glycolic acid lotion compared with tretinoin 0.025% cream and a vehicle lotion to treat mild-to-moderate facial acne vulgaris. Patients treated with azelaic/glycolic acid experienced a significantly greater reduction in the number of papules, as well as a greater reduction in the number of inflammatory lesions, than those treated with tretinoin. Overall global improvement was approximately 25% in both groups. In the physician evaluations, treatment with azelaic/glycolic acid was found to cause significantly less dryness, scaling, and erythema than tretinoin. Patients also reported significantly less dryness, redness, and peeling with azelaic/glycolic acid. Significantly more patients in the azelaic/glycolic acid group than the tretinoin group reported that they felt attractive. The combination of azelaic acid and glycolic acid is a useful alternative to tretinoin, being at least as efficacious as the latter, while offering a superior tolerability and patient approval profile.     

Efficacy and safety of total parenteral nutrition in pediatric patients

Pediatric patients differ from adult patients because of active musculoskeletal growth and development of visceral organs and because they have a proportionately smaller nutritional reserve, especially premature infants. Measures of outcome of effective nutritional support in pediatric patients who have experienced trauma or medical disease or who have undergone surgical procedures include weight gain, increased height and circumference of the head, increased hepatic synthesis of plasma proteins, immunocompetence, decreased morbidity, improved survival, and fast recovery. If a pediatric patient cannot eat or be tube-fed enterally after 3 days of recovery and support with fluids, parenteral nutrition is indicated. Examples in which this treatment has dramatically decreased morbidity include gastroschisis, short-bowel syndrome, necrotizing enterocolitis, and Hirschsprung's disease. Contraindications to its use include severe congenital (usually genetic) defects and terminal cancer, conditions in which life expectancy and quality of life are severely decreased. The team approach to parenteral and enteral nutrition in pediatric patients is preferred, and stable patients receiving long-term nutritional support, including infants, should be considered for home parenteral nutrition. When administered by protocol, parenteral nutrition is safe in pediatric patients. In properly selected pediatric patients, direct and indirect costs for such therapy may be significantly less than those in adults, and the cost-to-benefit ratio is appreciably higher when life expectancy, parental pleasure, and potential work productivity are considered. Ethical and social issues in initiating and discontinuing parenteral nutrition are best decided during thorough empathic discussions between physicians and parents.     

Topical clobetasol propionate compared with placebo in the treatment of unretractable foreskin

OBJECTIVE: To assess whether it is the steroid alone or the gentle physical retraction combined with ointment that is responsible for the excellent results observed with topical steroid treatment of unretractable foreskin. DESIGN: Prospective, randomised, double-blind study. SETTING: University hospital, Sweden. SUBJECTS: 30 Boys randomised to be treated with clobetasol propionate (n = 15) or placebo (n = 15). INTERVENTIONS: The boys were examined 1, 2 and 6 months, respectively, after treatment. MAIN OUTCOME MEASURES: Comparison between the effects of clobetasol propionate and placebo. RESULTS: Two patients in the steroid group and one in the placebo group withdrew from the study. 10 Boys in the steroid group showed an improvement within 2 months. The remaining 3 boys had no effect and were circumcised. Histopathological examination showed lichen sclerosus et atrophicus. Seven boys in the placebo group improved. The 7 non-responders were prescribed clobetasol propionate ointment, and all 7 improved. CONCLUSION: 17 of 27 boys referred with "phimosis" were successfully treated with an ointment and gentle traction. When clobetasol propionate was given the non-responders success rate was increased to 24/27 (89%).     

Efficacy of lodoxamide 0.1% versus N-acetyl aspartyl glutamic acid 6% ophthalmic solutions in patients with vernal keratoconjunctivitis

The purpose of this study was to investigate environmental lead exposure in the general Taiwanese population. A total of 8828 Taiwanese adults selected by a multistage sampling method were investigated. Characteristics of the participants were ascertained by questionnaire and 10 ml venous blood was drawn by public health nurses. The blood specimens were distributed to six laboratories for blood lead level (BLL) measurement. A quality control program was applied during the analysis of the BLLs in order to improve precision and accuracy. The arithmetic mean BLL of the 8828 Taiwanese adults was 7.70 +/- 5.23 micrograms/dl, with a maximal level of 69.1 micrograms/dl. The median was 6.5 micrograms/dl and the 90th percentile was 14.0 micrograms/dl. After logarithmic transformation, the geometric mean was 1.84 +/- 0.67 microgram/dl. This study also found that elevated BLLs were associated with certain personal characteristics, i.e., gender, ethnic group, and education level; life-style factors, such as smoking, alcohol consumption, Chinese herbal drug consumption, milk consumption, and sources of drinking water; residential location, i.e., level of urbanization; and occupational history of lead exposure. However, age, floor level of residence, distance from house to road, and betel nut consumption were not associated with elevated BLLs. These results showed that BLLs in the Taiwanese population were not higher than those in developed and developing countries. Most of the influencing factors were also found in other studies; however, local factors such as ethnic group, Chinese herbal drug consumption, and sources of drinking water are important considerations in Taiwan when examining ways to prevent overexposure to lead in the general population.     

Efficacy and safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy

PURPOSE: A retrospective analysis of the MUSE clinical trial was performed to evaluate the efficacy and safety of transurethral alprostadil in patients with erectile dysfunction after radical prostatectomy. MATERIALS AND METHODS: Patients received doses of transurethral alprostadil in the clinic and those for whom a suitable dose was determined were treated at home with active drug or placebo for 3 months. Patients had undergone radical prostatectomy no less than 3 months before study entry. RESULTS: Of the 384 patients in whom radical prostatectomy was identified as a cause of erectile dysfunction 70.3% had an erection believed sufficient for intercourse in the clinic and 57.1% on active medication had sexual intercourse at least once at home. The product of clinic and home success rates (70.3 x 57.1%) was an overall success rate (the likelihood of active treatment to lead to intercourse at home) of 40.1%. The frequency of most adverse effects of radical prostatectomy was comparable to that of other organic etiologies of erectile dysfunction (1,127 patients). The percentage of patients with hypotension in the clinic was lower after radical prostatectomy compared to other erectile dysfunction etiologies (0.8 versus 4.2%, p < 0.001) but the percentage of patients with urethral pain/burning was higher (18.3 versus 10.4%, p = 0.027). No urinary tract infection, fibrosis or priapism occurred in the post-radical prostatectomy patients. CONCLUSIONS: Transurethral alprostadil is a well tolerated and efficacious method of treating erectile dysfunction after radical prostatectomy, although psychological changes associated with cancer and surgery may limit home response. The severe neurovascular deficit associated with prostatectomy neither limits the efficacy of transurethral alprostadil nor increases the risks.     

Efficacy and safety of prophylactic cranial irradiation in patients with small cell lung cancer

In this review we examine the complex interactions between lipoprotein metabolism, immunosuppressive drug therapy, and inflammation and the potential benefits of lipid-lowering drug therapy after heart transplantation. The newer formulations of cyclosporine, Neoral (Novartis Pharmaceuticals; Basle, Switzerland), and other newer agents such as tacrolimus may have advantages in regard to lipid metabolism as compared with traditional triple-drug immunosuppression. Lipoprotein levels may influence both the toxicity and efficacy of cyclosporine. Dyslipidemia may adversely influence inflammation and rejection in the allograft. Two recent clinical trials have shown that lipid-lowering therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor alone or in combination with low-density lipoprotein apheresis may confer significant benefits toward preventing transplant coronary artery disease.     

Compliance with and typical usage of artificial tears in dry eye conditions

BACKGROUND: Although the literature on dry eye is extensive, little has been written about the typical use of tear supplements among the clinical population. METHODS: This study consisted of chart reviews and telephone surveys. Self-reported use of tear supplements was evaluated. RESULTS: At the time of the survey, 63% of those recommended to use artificial tear solutions (114 of 229) continued to do so. The discontinuation rate was higher for ointments, with 53% (47 of 89) having stopped using a recommended ointment. The majority of those continuing to use drops will use one or two drops per day (30 gtts/30 days, +/- 89). In addition to the extreme amount of variability in the number of artificial tears used by any individual, a great deal of day-to-day variability is seen within any individual. CONCLUSIONS: Patients appear to titrate dosage to symptoms on any given day. Given this, there may be little reason to prescribe a specific dosage regimen for the majority of persons using tears. Researchers who are looking at the effectiveness of tear supplements need to take into account the individual variability of use in tear supplements. When prescribing artificial tears, patient education regarding purpose for treatment, specific agent, and dosage used may improve relatively low compliance rates.     

Diltiazem compared with placebo in the prevention of myocardial ischemia during non-cardiac surgery

OBJECTIVE: Because eosinophils likely play important roles in the pathophysiology of allergic diseases, specific inhibitors of eosinophils may be desirable to treat such diseases. To evaluate the capacity of a novel compound, sulochrin, as an inhibitor of eosinophilic inflammation, we examined the effects of this compound on various effector functions of eosinophils. MATERIALS AND METHODS: We examined the effects of sulochrin on degranulation of human eosinophils stimulated with platelet-activating factor (PAF) or Sepharose 4B beads coated with secretory IgA (sIgA) or IgG. The effects of sulochrin on other effector functions of human eosinophils, including superoxide anion (O2-) production, leukotriene (LT) C4 release, and interleukin (IL)-8 production induced by sIgA-beads were also studied. Finally, using PAF and LTB4 as chemoattractants, we evaluated the potency of sulochrin to inhibit eosinophil migration in vitro and in vivo. RESULTS: Sulochrin inhibited EDN release by eosinophils stimulated with sIgA-beads. IgG-beads and PAF in a concentration-dependent manner; IC50 values were 0.75 microM, 0.30 microM and 0.03 microM. Eosinophil O2- production, LTC4 release, and IL-8 production were also inhibited by sulochrin. Furthermore, PAF-induced chemotaxis of human eosinophils and LTB4-induced chemotaxis of guinea pig eosinophils were abolished by 1 microM of sulochrin. Finally, sulochrin potently inhibited LTB4-induced infiltration of eosinophils into the skin of guinea-pig in vivo. CONCLUSIONS: These results suggest that sulochrin is a potent inhibitor of various effector functions of eosinophils. Sulochrin and its derivatives may be useful in the development of therapeutic approaches for patients with allergic diseases.     

Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation

OBJECTIVES: This multicenter study compared the efficacy and safety of ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation. BACKGROUND: Ibutilide fumarate is an intravenous (IV) class III antiarrhythmic agent that has been shown to be significantly more effective than placebo in the pharmacologic conversion of atrial flutter and fibrillation to sinus rhythm. Procainamide is commonly used for conversion of recent-onset atrial fibrillation to normal sinus rhythm. METHODS: One hundred twenty-seven patients (age range 22 to 92 years) with atrial flutter or fibrillation of 3 h to 90 days' (mean 21 days) duration were randomized to receive either two 10-min IV infusions of 1 mg of ibutilide fumarate, separated by a 10-min infusion of 5% dextrose in sterile water, or three successive 10-min IV infusions of 400 mg of procainamide hydrochloride. RESULTS: Of the 127 patients, 120 were evaluated for efficacy: 35 (58.3%) of 60 in the ibutilide group compared with 11 (18.3%) of 60 in the procainamide group had successful termination within 1.5 h of treatment (p < 0.0001). Seven patients were found to have violated the protocol and were not included in the final evaluation. In the patients with atrial flutter, ibutilide had a significantly higher success rate than procainamide (76% [13 of 17] vs. 14% [3 of 22], p=0.001). Similarly, in the atrial fibrillation group, ibutilide had a significantly higher success rate than procainamide (51% [22 of 43] vs. 21% [8 of 38], p=0.005). One patient who received ibutilide, which was found to be a protocol violation, had sustained polymorphic ventricular tachycardia requiring direct current cardioversion. Seven patients who received procainamide became hypotensive. CONCLUSIONS: This study establishes the superior efficacy of ibutilide over procainamide when administered to patients to convert either atrial fibrillation or atrial flutter to sinus rhythm. Hypotension was the major adverse effect seen with procainamide. A low incidence of serious proarrhythmia was seen with the administration of ibutilide occurring at the end of infusion.     

Tropisetron or ondansetron compared with placebo for prevention of postoperative nausea and vomiting

In a prospective, randomized, double-blind, placebo-controlled, multicentre study, the efficacy of prophylactic tropisetron (2 mg) or ondansetron (4 mg) for the prevention of post-operative nausea and vomiting after abdominal or non-abdominal surgery with general balanced anaesthesia was studied in 842 ASA I-III patients. In patients undergoing abdominal surgery, ondansetron and tropisetron reduced the frequency of emetic episodes compared with the placebo (29%, 30% vs. 42% respectively). In men, neither tropisetron nor ondansetron had an effect different from the placebo, whereas in women both drugs led to lower rates of emetic episodes and nausea. In comparison with abdominal surgery, fewer patients in the non-abdominal surgery subgroup had emetic episodes (42% vs. 23% in the placebo group). However, neither tropisetron nor ondansetron was significantly different from the placebo in this patient subgroup. In conclusion, for patients at increased risk of post-operative nausea and vomiting, a prophylactic therapy at the lowest effective dose with tropisetron or ondansetron may be useful.     

Immunotherapy using the anti-endotoxin antibody HA-1A in patients with sepsis syndrome; good results in relation to treatment with placebo

Passive immunization with a human anti-endotoxin monoclonal IgM antibody (Centoxin, HA-1A) was recently studied in patients with suspected Gram-negative sepsis. Comparison of the results obtained in the Amsterdam subpopulation with those in a larger international study population of which the Amsterdam patient group was a part, showed that it had been possible to select a patient population in which HA-1A has an 'intention-to-treat' effect based upon clinical criteria (a decrease in mortality compared with placebo by 42% (p = 0.04) and in the larger study by 9% (p = 0.24). Until a clinically useful test becomes available, identification of patients who have a high likelihood of Gram-negative sepsis and who would benefit from anti-endotoxin immunotherapy with HA-1A should be based upon the history and evaluation of underlying disease, infection status, severity and progression of the disease. The severely ill patients thus selected should receive treatment as early as possible.     

The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone

OBJECTIVE: To compare the therapeutic effects of the alpha-glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone. RESEARCH DESIGN AND METHODS: After a 4-week placebo run-in period, 201 patients in 18 centers in 4 countries were randomized in a double-blind manner to miglitol (50 mg t.i.d., followed by 100 mg t.i.d.), glibenclamide (3.5 mg q.d/b.i.d.), or placebo for 24 weeks. Efficacy criteria were changes from baseline of HbA1c, fasting and postprandial blood glucose and insulin levels, body weight, and serum triglycerides. RESULTS: Efficacy was assessed in 119 patients who completed the full protocol, and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis. Compared with placebo, mean baseline-adjusted HbA1c decreased by 0.75% (P = 0.0021) and 1.01% (P = 0.0001) in the miglitol and glibenclamide treatment groups, respectively. Blood glucose decreased slightly in the fasting state and considerably in the postprandial state in both treatment groups but not in the placebo group. Fasting insulin levels increased slightly (NS) in all treatment groups; however, postprandial insulin levels decreased with miglitol, while increasing markedly with glibenclamide (P = 0.0001 between all treatment groups). Gastrointestinal side effects (flatulence and diarrhea) occurred mostly in the miglitol-treated patients, while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia. CONCLUSIONS: Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.