Developmental and hormonal regulation of hepatocyte growth factor expression and action in the bovine ovarian follicle

BACKGROUND: Anorexia and cachexia are well-known sequelae of cancer that contribute to morbidity and mortality. In several studies in patients with non-hormone-sensitive tumors, synthetic progestogens were shown to exert beneficial effects on appetite and weight loss. The current study was undertaken to investigate the effects of medroxyprogesterone acetate (MPA) on food intake, body composition, and resting energy expenditure (REE). METHODS: Fifty-four patients with non-hormone-sensitive cancer, generally characterized by substantial weight loss and hypermetabolism, received either MPA, 500 mg, or placebo twice daily for 12 weeks (double-blind study). Food intake was measured by dietary history, body composition was assessed by deuterium dilution (fat mass, fat-free mass), and REE was obtained by indirect calorimetry. RESULTS: Compared with placebo, 12 weeks of MPA led to an increase in energy intake (between-group difference, 426 kcal/day; P = 0.01) that was significantly associated (r = 0.68, P = 0.003) with an increase in fat mass (between-group difference, 2.5 kg; P = 0.009). Fat-free mass was not significantly influenced. REE increased during MPA treatment: at 6 weeks, the between-group difference in change was 135 kcal/day (P = 0.009); after 12 weeks, this difference was 93 kcal/ day (P = 0.07). CONCLUSIONS: The authors conclude that MPA is able to stimulate increased food intake significantly and to reverse fat loss concomitantly in patients with non-hormone-sensitive cancer.     

Recombinant interferon-alpha therapy for acute hepatitis B: a randomized, double-blind, placebo-controlled trial

In spite of the availability of hepatitis B vaccine, acute hepatitis B continues to be a worldwide problem for which no specific therapy is available. We investigated the safety and the effectiveness of recombinant interferon-alpha2b (rIFN-alpha2b) in the treatment of acute hepatitis B by determining overall severity and duration of symptoms, time required to clear viral antigens and hepatitis B virus (HBV) DNA, and titre of antibodies to hepatitis B surface antigen (HBsAb), 24 weeks after the onset of therapy. One hundred patients were randomly assigned to treatment with either 3 million units (MU) (n = 34) or 10 MU (n = 33) rIFN-alpha2b or to placebo (n = 33), three times weekly for 3 weeks. Follow-up was for 24 weeks. A significantly shorter duration of the symptoms and signs of acute hepatitis was observed in patients who received 3 MU rIFN-alpha2b compared with those who received 10 MU rIFN-alpha2b or placebo. Twenty-one weeks post-therapy, patients treated with 10 MU rIFN-alpha2b showed a significantly higher geometric mean HBsAb titre than those treated with placebo (85.1 vs 35.5 IU l-1, P < 0.05). rIFN-alpha2b administration was well tolerated even in jaundiced patients. No serious side-effects were observed necessitating reduction in dose or discontinuation of the drug. The effect of rIFN-alpha2b on transition of HBV infection to chronicity could not be evaluated in this trial because such an unfavourable course was not seen in any of the treated or the control patients. In conclusion, rIFN-alpha2b was safe in acute hepatitis B, and at low dose was found to ameliorate symptoms and to shorten significantly the duration of illness.     

Imported Opisthorchis viverrini and parasite infections from Thai labourers in Taiwan

OBJECTIVE: To establish the efficacy and acceptability of combined continuous low-dose oestrogen and low-dose progestogen therapy, to determine whether any of three commercially available progestogens had any advantages or disadvantages in these circumstances and whether use of the lowest clinically effective oestrogen dose affected other outcomes being measured. DESIGN: A 12-month, prospective, open label, single centre, randomised trial. PATIENTS AND METHODS: Seventy-five postmenopausal women already receiving hormone replacement therapy in the form of conjugated equine oestrogens (CEE) (0.625 mg daily) and cyclical medroxyprogesterone acetate (10 mg) and experiencing withdrawal bleeding were changed to a continuous daily regimen of 0.3 mg CEE and a random allocation of one of three low-dose progestogens (medroxyprogesterone acetate 2.5 mg, levonorgestrel 30 micrograms or norethisterone 350 micrograms). Return to a dose of 0.625 mg CEE was permitted if required to control menopausal symptoms with separate analysis of this group when appropriate. OUTCOMES MEASURED: Menopausal symptom score, clinical bleeding pattern, endometrial biopsy results, forearm bone density and content, serum lipids and side effects. RESULTS: Fifteen women withdrew from the trial, five because of irregular bleeding. In the remainder, amenorrhoea was achieved in 53% by three months, in 67% by six months and in 93% by 12 months. Endometrial biopsy showed atrophic endometrium by 12 months in all but one patient, in whom minimal proliferative activity was seen. Twenty-seven women chose to return to a dose of 0.625 mg CEE. In all groups, final control of menopausal symptoms improved. All regimens were bone sparing and the lipid profile was unchanged. Minimal side effects were experienced by the patients. There was little difference in outcome between the three progestogens except that norethisterone therapy was associated with a greater prevalence of amenorrhoea at six months than was seen in the levonorgestrel and medroxyprogesterone acetate groups. CONCLUSIONS: These low-dose continuous oestrogen and progestogen regimens appear an appropriate option for the postmenopausal woman wishing to eliminate withdrawal bleeding and reduce both hormonal side effects and menopausal symptoms. The long term benefits of these regimens with regard to the prevention of osteoporotic fractures, cardiovascular disease and endometrial cancer need to be further assessed over time.     

Lubeluzole treatment of acute ischemic stroke. The US and Canadian Lubeluzole Ischemic Stroke Study Group

BACKGROUND AND PURPOSE: Lubeluzole is a novel benzothiazole compound that has shown neuroprotective activity in preclinical models of ischemic stroke. The present multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of lubeluzole in the treatment of ischemic stroke. METHODS: Seven hundred twenty-one patients with clinical symptoms of acute ischemic stroke were randomized to receive either lubeluzole (7.5 mg over 1 hour, followed by a continuous daily infusion of 10 mg for up to 5 days) or placebo. Treatment was initiated within 6 hours of symptom onset. Mortality at 12 weeks was the primary efficacy end point. Secondary efficacy end points included neurological recovery (based on the National Institutes of Health Stroke Scale [NIHSS]), functional status (based on the Barthel Index), and level of disability (based on the Rankin Scale). Safety assessments included standard and continuous electrocardiographic monitoring, physical examination, measurements of vital signs, clinical laboratory evaluation, and adverse events reports. RESULTS: The overall mortality rate at 12 weeks for lubeluzole-treated patients was 20.7% compared to 25.2% for placebo-treated patients (NS). Controlling for relevant covariates, the degree of neurological recovery (NIHSS) at week 12 significantly favored lubeluzole over placebo (P = .033). Lubeluzole treatment similarly resulted in significantly greater improvements in functional status (Barthel Index) (P = .038) and overall disability (Rankin Scale) (P = .034) after 12 weeks. A global test statistic confirmed that lubeluzole-treated patients had a more favorable clinical outcome at 12 weeks (P = .041). The safety profile of lubeluzole resembled that of placebo. CONCLUSIONS: Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns.     

Poorer survival of nulliparous women with endometrial carcinoma

BACKGROUND: Several epidemiologic studies have shown an inverse relationship between parity and the incidence of endometrial carcinoma. A prognostic influence of reproductive factors has been reported for carcinomas of the breast and uterine cervix; but no such independent influence has been reported for endometrial carcinoma, to the authors' knowledge. Therefore, the authors investigated the prognostic importance of parity in an unselected group of patients. METHODS: Clinical and histopathologic data on all 316 patients treated for endometrial carcinoma during the period 1981-1990 in Hordaland County, Norway, were related to cause specific death in univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression model) analyses. The median follow-up for the survivors was 9 years (range, 4-16 years). No patients were lost due to insufficient follow-up information. RESULTS: Nulliparous women had a poorer 5-year survival rate compared with patients who had had 1 or more deliveries (57% vs. 81%, P = 0.0001), and they were significantly older and had more advanced disease at the time of primary surgery than the parous women. After adjustment for traditional risk factors, a hazard ratio of 2.81 (95% confidence interval, 1.55-5.06) was found for nulliparous versus parous women. International Federation of Gynecology and Obstetrics stage, curative treatment, and tumor differentiation grade were also identified as independent prognostic factors, whereas age and menopausal status had prognostic significance in the univariate analysis only. CONCLUSIONS: The decreased survival among nulliparous women reported herein may reflect biologic differences between parous and nulliparous endometrial carcinoma patients. It may also be due in part to a greater delay in diagnosing the women in the nulliparous group.     

Combined versus sequential hormonal replacement therapy: a double-blind, placebo-controlled study on quality of life-related outcome measures

BACKGROUND: To compare combined and sequential hormonal replacement therapies to each other as well as placebo in patients suffering from the postmenopausal syndrome. Clinical outcomes were measured concerning both the specific postmenopausal symptoms (using the Kupperman scale) and health or well-being dimensions (using subscales of the General Health Questionnaire and specific depression and anxiety scales). METHODS: A prospective randomized double-blind study over 12 months of 105 normal early postmenopausal women in the setting of a general hospital. RESULTS: Both hormone replacement therapies were superior to placebo on the Kupperman scale (sweating, hot flushing, myalgia and vertigo). The psychic symptoms on the Kupperman scale were psychometrically invalid. However, psychic symptoms as measured by the Beck Depression Inventory and the General Health Questionnaire were significantly improved by the hormonal replacement therapies. No differences were observed when combined therapy was compared to sequential therapy. CONCLUSION: One-year treatment with hormonal replacement therapy is superior to placebo in measuring the somatic and psychic symptoms of the menopausal syndrome. No differences were found in this respect between combined and sequential replacement therapy.     

Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma

OBJECTIVE: To compare the efficacy and safety of inhaled salmeterol xinafoate, a long-acting beta 2-adrenoceptor agonist, with that of albuterol, a short-acting inhaled beta 2-agonist, in the treatment of asthma. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Eleven outpatient clinical centers. SUBJECTS: A total of 322 male and female patients at least 12 years of age with chronic symptomatic asthma requiring daily therapy. INTERVENTION: Patients were treated with salmeterol xinafoate (42 micrograms inhaled twice daily), albuterol (180 micrograms inhaled four times daily), or placebo (four times a day) for 12 weeks; patients in all three groups could use inhaled albuterol as backup medication for breakthrough symptoms. MAIN OUTCOME MEASURES: Serial 12-hour forced expiratory flow in 1 second (FEV1), peak expiratory flow (PEF), asthma symptoms, nocturnal awakenings due to asthma, episodes of asthma exacerbations, and electrocardiography. RESULTS: The mean area under the curve for FEV1 throughout each 12-hour period was consistently greater after a single dose of salmeterol than after two doses of albuterol administered 6 hours apart (P < .001), with the difference ranging from 3.1 to 4.3 L.h. Salmeterol produced an average increase in morning and evening PEF of 26 and 29 L/min, respectively, over pretreatment values compared with decreases of -13 and -3 L/min, respectively, in the albuterol group and -2 L/min both in the morning and evening in the placebo group (P < .001). Patients in the salmeterol group had significantly fewer days and nights with symptoms than did either the albuterol or placebo group (P < .001). Responses to salmeterol were similar at day 1 and at week 12. Adverse events in all treatment groups were equally infrequent, and no clinically significant change in cardiac rhythm was observed with salmeterol treatment. CONCLUSION: Salmeterol inhaled twice daily is more effective than albuterol inhaled four times a day (or as needed) in patients with asthma requiring maintenance therapy. No deterioration of asthma control was observed with the use of salmeterol over a 3-month period.     

Clinical, endocrine, and metabolic effects of two doses of gestrinone in treatment of pelvic endometriosis

AIM: To study the effect of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome. PATIENTS AND METHODS: Ninety-six patients were randomly assigned to treatment with either cisapride 5 mg three times daily or placebo three times daily for a period of 12 weeks. The dosage could be doubled after 4 weeks. Presence of the target symptoms abdominal pain, constipation and abdominal bloating was an obligatory criterion for inclusion in the study. RESULTS: After 12 weeks of treatment, 31%, 56% and 27% of the cisapride treated patients were found to be without the three target symptoms (P < 0.05). The corresponding percentages for the placebo-treated patients were 31%, 58% and 19%, respectively, (P < 0.05). The visual analogue scale (VAS) symptom scores assessed by the patients for global rating of bowel disease, general well-being and frequency of stool passage improved significantly within each treatment group (P < 0.05). Evaluation of efficacy parameters using intention-to-treat analysis showed no statistically significant differences between the groups. Using efficacy analysis, the difficulty of stool passage showed a significantly higher improvement with cisapride (P < or = 0.05). CONCLUSIONS: These results indicate that cisapride is not superior to placebo in the treatment of constipation and abdominal discomfort as components of irritable bowel syndrome. It may, however, be of use in improving the difficulty of stool passage.     

Potential neuroprotective therapy for glaucomatous optic neuropathy

Although mexiletine, an antiarrhythmic with local anesthetic properties, has been reported to relieve discomfort in diabetic neuropathy, its usefulness in the treatment of HIV-related painful peripheral neuropathy (PPN) has not been determined. The tolerance and effectiveness of mexiletine in HIV-related PPN were assessed in 22 patients who were randomized to receive mexiletine (maximum dose, 600 mg/day) or placebo for 6 weeks, followed by the alternative intervention for 6 weeks after a 1-week washout period. The daily pain response was assessed using a visual analogue scale card in 19 patients who received at least 2 weeks of the drug, 16 of whom were crossed-over to receive the alternate agent. No statistically significant difference was found between the mean daily pain scores for patients receiving mexiletine versus placebo, irrespective of the order in which the agents were received. Comparing the mean individual daily pain scores for each phase of study, 5 patients (31%) had significantly less pain while receiving mexiletine compared with their response to placebo, 5 patients (31%) had significantly less pain while receiving placebo, and no difference was noted in 6 patients (38%). Crossover and multivariate analyses for repeated measures showed no apparent difference in the response to mexiletine versus placebo. Dose-limiting adverse events occurred in 39% of those receiving mexiletine, but only 1 patient (5%) discontinued placebo. Mexiletine was only modestly well tolerated despite its relatively brief period of administration, and no evidence was found to support its benefit in HIV-related PPN. Although a first-drug effect was not demonstrated, a powerful placebo effect was seen in some patients.     

Expression of collagenase and stromelysin in skin fibroblasts from recessive dystrophic epidermolysis bullosa

OBJECTIVE: To compare the effects of felodipine and placebo in patients with New York Heart Association functional class II or III and stable congestive heart failure despite treatment with an angiotensin converting enzyme inhibitor, diuretic, or digoxin, or any combination of these three drugs. PATIENTS AND DESIGN: 252 patients were randomised in a double blind, parallel group study after a 2-4 week placebo run-in to oral treatment with either felodipine extended release formulation or placebo 2.5-10 mg twice daily given in addition to existing background medication for a further 12 weeks. METHODS: Patients aged 18-75 years of either sex with chronic congestive heart failure due to ischaemic heart disease, hypertensive heart disease, or dilated cardiomyopathy with or without secondary mitral insufficiency that was stable during the preceding two months were included in the study. Treadmill exercise tests according to the modified Naughton protocol were performed at baseline, and after six, 11, and 12 weeks of treatment. Signs and symptoms of heart failure were assessed at every visit. Physical examination was performed and left ventricular ejection fraction measured at baseline and after 12 weeks. RESULTS: Mean (SD) baseline exercise test times increased from 434 (162) s and 480 (157) s for felodipine and placebo groups respectively to 541 (217) s and 591 (218) s at 12 weeks or the last visit. The change in exercise from baseline to last visit was 107 (141) s for patients given felodipine and 112 (128) s for those given placebo (P > 0.20). There was also no difference between treatments with respect to the other efficacy variables. There were few deaths in the study (felodipine n = 3, placebo n = 2). More patients who received felodipine were withdrawn from treatment (n = 29) than those who received placebo (n = 17). The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo. Patients withdrawn from the study due to increased need for non-study heart failure treatment rapidly stabilised and recovered. CONCLUSION: Felodipine has not been shown to be of benefit in patients with mild to moderate heart failure.     

Histopathological responses in the CNS following inoculation with a non-neurovirulent mutant (1716) of herpes simplex virus type 1 (HSV 1): relevance for gene and cancer therapy

OBJECTIVE: To determine the efficacy of intranasally administered immunoglobulin in preventing symptoms of rhinitis in children. METHODS: Forty children ages 1 to 4 years who attended day-care centers in Turku, Finland, were enrolled in the double blind, placebo-controlled study. The children were randomly assigned to receive treatment with immunoglobulin, composed mainly of immunoglobulin A, or placebo, both administered as nasal sprays twice daily for 8 weeks. During this medication period and an additional 8-week follow-up period, the parents recorded the symptoms of the children daily in the diaries provided. One child who met an exclusion criterion was withdrawn from the study after a few days of medication. RESULTS: During the 8-week medication period the 19 children in the immunoglobulin group had 42% fewer days with rhinitis than the 20 children receiving placebo (mean, 10.8 vs. 18.7 days; P=0.004). The total numbers of episodes of rhinitis in the immunoglobulin and placebo groups were 33 and 51, respectively. No significant differences were observed between the groups during the postmedication follow-up period. CONCLUSIONS: Intranasal administration of immunoglobulin appears to be an effective method to prevent symptoms of rhinitis in children, and further studies of this approach are needed.     

Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study

Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening.     

Combating hyperthermia in acute stroke: a significant clinical concern

OBJECTIVE: There is only limited evidence from adequately controlled clinical trials to support high-dose methylprednisolone therapy for attacks of multiple sclerosis (MS) and none supporting oral administration. We assessed the effect of oral high-dose methylprednisolone therapy in attacks of MS. METHODS: Twenty-five patients with an attack of MS lasting less than 4 weeks were randomized to placebo treatment. Twenty-six patients received oral methylprednisolone (500 mg once a day for 5 days with a 10-day tapering period). The patients received scores on the Scripps Neurological Rating Scale (NRS) and Kurtzke Expanded Disability Status Scale. The symptoms were scored on a visual analog scale (VAS) before treatment and after 1, 3, and 8 weeks of treatment. Primary efficacy measures were NRS and VAS scores in the first 3 weeks and changes in NRS score and answers to an efficacy questionnaire administered after 8 weeks of treatment. RESULTS: Changes in NRS scores among methylprednisolone- and placebo-treated patients differed significantly in the first 3 weeks and after 8 weeks (p = 0.005 and p = 0.0007). VAS scores the first 3 weeks and treatment efficacy after 8 weeks also favored a beneficial effect of methylprednisolone treatment (p = 0.02 and p = 0.05). After 1, 3, and 8 weeks, 4%, 24%, and 32% in the placebo group and 31%, 54%, and 65% in the methylprednisolone group had improved one point on the Expanded Disability Status Scale score (all p < 0.05). No serious adverse events were seen. CONCLUSION: Oral high-dose methylprednisolone is recommended for managing attacks of MS.     

Results of a pilot study with high-dose medroxyprogesterone acetate in the treatment of metastasizing breast carcinoma

Nineteen patients with advanced breast cancer were treated with 1 g medroxyprogesterone acetate (MPA) i.m. daily for 4 weeks. The therapy was well tolerated. The measurable tumor lesions showed a regression of more than 50% in 6 cases; the mean duration of remission was 12 months. In 12 patients the treatment led to a marked subjective improvement. On the basis of these data the authors feel that high-dosage MPA warrants further investigation in the treatment of metastatic breast cancer.     

Effects of 12 weeks of ramipril treatment on the quality of life in patients with moderate congestive heart failure: results of a placebo-controlled trial. Ramipril Study Group

The assessment of quality of life (QoL) has become recognized as an important tool for evaluating heart failure therapy. The angiotensin-converting enzyme inhibitor ramipril (mean dose 8 mg) was evaluated in 223 patients with moderate chronic congestive heart failure at 24 centers in 4 Nordic countries following a randomized, double-blind, placebo-controlled, parallel group design. The follow-up period was 12 weeks. QoL was evaluated using a questionnaire with 47 items, including the disease-specific Severe Heart Failure Questionnaire, the Sleep Dysfunction Scale, and the Psychological General Well-Being Index. In both treatment groups the total score increased from baseline to 12 weeks for both the Severe Heart Failure Questionnaire and for the Psychological Well-Being Index, reflecting relief of symptoms and improved well-being. However, no significant differences between the placebo and ramipril groups could be detected. Only a trend toward improvement in sleep on ramipril compared with placebo therapy was observed. In conclusion, in this placebo-controlled trial no significant effects of 12-week ramipril treatment of QoL could be demonstrated in patients with moderate congestive heart failure.     

Do multiple measurements employing different ultrasonic techniques improve the accuracy of amniotic fluid volume assessment?

BACKGROUND: To determine the results of standardized ulcer treatment regimes and effects of the oral thromboxane A2 antagonist Ifetroban (250 mg daily) on healing of chronic lower-extremity venous stasis ulcers. METHODS: In a prospective, randomized, double blind, placebo-controlled multicenter study, 165 patients were randomized to Ifetroban (n = 83) versus placebo (n = 82) for a period of 12 weeks. Both groups were treated with sustained graduated compression and hydrocolloid. Ulcer size was measured weekly by tracings and computerized planimetry. A total of 150 patients completed the study. RESULTS: Complete ulcer healing was achieved after 12 weeks in 55% of patients receiving Ifetroban and in 54% of those taking a placebo with no significant differences; 84% of ulcers in both groups achieved greater than 50% area reduction in size. CONCLUSIONS: These results are likely to be useful as a benchmark for comparison with other treatment protocols concerning the care of chronic lower-extremity stasis ulcers.     

What alters physicians'' decisions to admit to the coronary care unit?

OBJECTIVES: To determine the endometrial response and bleeding patterns in post-menopausal women who were given a sequential hormone replacement regimen with estradiol 2 mg and dydrogesterone 10 mg. METHODS: One-hundred-and-eighty-eight (188) post-menopausal women with amenorrhea of 6 months or longer, with FSH/estradiol (E2) levels in the post-menopausal range and normal endometrium were entered in the study. All patients received a daily dose of 2 mg E2 during day 1-14 of each 28 day cycle and 2 mg E2 combined with 10 mg dydrogesterone during cycle day 15-28. The total duration of treatment was 12 months (13 cycles of 28 days). RESULTS: The rate of adequate progestational response (secretory or atrophic) in the 146 patients who remained in the study for at least 356 days with 90% study medication compliance and received an endometrial biopsy after 13 cycles of study medication was 97.2%. Three patients had proliferative endometrium and one simple hyperplasia. Cyclic bleedings in the 153 women who remained on study medication for at least 76 days occurred in over 85% of all cycles; the day of onset occurring regularly on day 13 or 14 of the combined period; the mean duration of bleeding per cycle was approximately 5 days with most patients having (very) slight bleeding. Sixty percent of patients had no intermittent bleedings over the whole 12-month study period. The average incidence of intermittent bleeding in the remaining patients was only 2.7 and generally of very slight quantities and of short duration. Per evaluable cycle the percentage of patients with an intermittent bleeding varies from 4.6 to 9.8%. Only two patients discontinued therapy because of bleeding problems. A clear decrease in the incidence of typical menopausal symptoms, i.e. hot flushes and night sweats was observed by the first visit after 6 weeks of treatment. CONCLUSIONS: The endometrial safety of 2 mg E2 sequentially combined with 10 mg dydrogesterone is very good as determined by the histologic response of the endometrium. The incidence of cyclic bleedings with this combination therapy is very high as is the regularity of day of onset and duration of bleeding. Blood loss during intermittent bleedings was mild and of short duration.     

Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia

The effects of the administration of 50 mg of guggulipid or placebo capsules twice daily for 24 weeks were compared as adjuncts to a fruit- and vegetable-enriched prudent diet in the management of 61 patients with hypercholesterolemia (31 in the guggulipid group and 30 in the placebo group) in a randomized, double-blind fashion. Guggulipid decreased the total cholesterol level by 11.7%, the low density lipoprotein cholesterol (LDL) by 12.5%, triglycerides by 12.0%, and the total cholesterol/high density lipoprotein (HDL) cholesterol ratio by 11.1% from the postdiet levels, whereas the levels were unchanged in the placebo group. The HDL cholesterol level showed no changes in the two groups. The lipid peroxides, indicating oxidative stress, declined 33.3% in the guggulipid group without any decrease in the placebo group. The compliance of patients was greater than 96%. The combined effect of diet and guggulipid at 36 weeks was as great as the reported lipid-lowering effect of modern drugs. After a washout period of another 12 weeks, changes in blood lipoproteins were reversed in the guggulipid group without such changes in the placebo group. Side effects of guggulipid were headache, mild nausea, eructation, and hiccup in a few patients.     

Preseasonal intranasal immunotherapy in birch-alder allergic rhinitis. A double-blind study

A double-blind, placebo-controlled study was carried out to test the clinical efficacy and safety of local nasal immunotherapy (LNIT) in powder form. Twenty-two patients suffering from allergic rhinitis strictly associated with early spring symptoms, with positive skin prick tests and RAST for birch-alder, all responders to a specific nasal provocation test (NPT), received randomly active or placebo treatment for 4 months. Immunotherapy consisted of administration of a set of capsules containing progressively increasing amounts of birch (Betula pendula) and speckled alder (Alnus incana) allergens in powder form with controlled granulometry. The active (birch-alder) and placebo (lactose) group completed the treatment according to a similar schedule. During the pollen season (March-April), the patients who took the active treatment reported less sneezing and rhinorrhea than the placebo group, on the basis of a symptoms score, and the differences were statistically significant; the need for drugs (terfenadine) was also significantly reduced. These findings agreed well with the results of specific NPT after the treatment; only patients in the active group had a higher threshold dose of nasal specific reactivity to birch-alder allergens than in tests before the LNIT.     

Multivariate changes in coordination of postural control following spaceflight

BACKGROUND: Bright light therapy is the recommended treatment for winter seasonal affective disorder (SAD). However, the studies with the best placebo controls have not been able to demonstrate that light treatment has a benefit beyond its placebo effect. METHODS: Ninety-six patients with SAD completed the study. Patients were randomly assigned to 1 of 3 treatments for 4 weeks, each 1.5 hours per day: morning light (average start time about 6 AM), evening light (average start about 9 PM), or morning placebo (average start about 6 AM). The bright light (approximately 6000 lux) was produced by light boxes, and the placebos were sham negative-ion generators. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) were performed weekly. RESULTS: There were no differences among the 3 groups in expectation ratings or mean depression scores after 4 weeks of treatment. However, strict response criteria revealed statistically significant differences; after 3 weeks of treatment morning light produced more of the complete or almost complete remissions than placebo. By 1 criterion (24-item SIGH-SAD score <50% of baseline and < or =8), 61% of the patients responded to morning light, 50% to evening light, and 32% to placebo after 4 weeks of treatment. CONCLUSIONS: Bright light therapy had a specific antidepressant effect beyond its placebo effect, but it took at least 3 weeks for a significant effect to develop. The benefit of light over placebo was in producing more of the full remissions.