Effectiveness and tolerance of Navoban (5HT3-receptor antagonist tropisetron) in prevention of cytostatic drug-induced nausea and vomiting in patients with breast carcinomas and gynecological malignancies

Efficacy and safety of the antiemetic agent Navoban (5HT3-receptor-antagonist Tropisetron) on cytostatic-induced emesis of breast cancers and gynecological cancers was tested in 28 female patients receiving a total of 127 chemotherapy courses containing high (cisplatin), moderate high (cyclophosphamid) or moderate (for example 5 FU) emetogenic cytostatic drugs. We studied antiemetic response rates of Navoban (5 mg/d) during the first 24 hours after administration of the chemotherapy as well as response rates of the "delayed nausea and emesis" (days 2-9 after chemotherapy). A complete response was observed in 103 chemotherapy courses (= 81.1%) during the first 24 hours after chemotherapy and in 93 courses (= 73.2%) for the "delayed emesis". Treatment failures (more than 5 vomiting episodes) during the first 24 hours were present in four courses and for the "delayed emesis" in 11 courses. The side effects of Navoban such as constipation, headache or tiredness were minimum. Therefore no patient refused to receive the necessary chemotherapy. Navoban is, with its single dose application, an effective therapeutic drug for the prevention of nausea and emesis in patients receiving a chemotherapy.     

Control of nausea and vomiting with ondansetron in patients treated with intensive non-cisplatin chemotherapy for acute myeloid leukaemia

18 consecutive patients with acute myeloid leukaemia (AML) treated with 34 cycles of intensive chemotherapy received ondansetron as antiemetic treatment. 14 patients were chemotherapy-naive, while 4 patients were treated for relapsed leukaemia. All patients received at least one cycle of chemotherapy, 11 patients (61%) received two cycles and 5 patients (28%) received three cycles. The remission induction regimen consisted of cytarabine 200 mg/m2 daily from day 1 to day 7, in combination with an anthracycline or amsacrine on 3 days. During the second and third cycle the dose of cytarabine was increased. Ondansetron was administered as follows: 8 mg intravenously before the start of chemotherapy, followed by 8 mg orally three times daily for 10 days. 50% of patients had no episodes of vomiting during the first cycle of chemotherapy and 78% had less than five episodes of vomiting over 10 days. 72% of patients had no or only mild nausea. These high response rates were maintained during the subsequent cycles. No side-effects due to ondansetron were registered. These data indicate that ondansetron is efficacious in preventing nausea and vomiting in patients with AML treated with intensive chemotherapy.     

Treatment of cisplatin-related nausea and vomiting with a combination of ondansetron and metoclopramide: a pilot study

Forty chemotherapy-naive patients receiving high-dose cisplatin were included in a pilot study of a combination of ondansetron plus metoclopramide as antiemetic therapy. Patients received ondansetron 16 mg plus metoclopramide 0.5 mg/kg in 250 cm3 of normal saline i.v. 15 min before cisplatin administration on day 1; then ondansetron 8 mg was given orally b.i.d. and metoclopramide 0.5 mg/kg was given intramuscularly t.i.d. for 4 days. This combination was given to all patients receiving the first cycle of chemotherapy. At the second cycle of chemotherapy all patients received the same antiemetic treatment as above plus methylprednisolone 125 mg i.v. on day 1 and the intramuscularly once a day for 4 days. There were 20 females and 20 males with a mean performance status of 1 (range 0-2) and a mean age of 58 years (range 36-68). Ten patients had ovarian carcinoma, eight patients had uterine adenocarcinoma and 22 and non-small cell lung carcinoma. The mean cisplatin dose was 96 mg/m2. All patients denied significant alcohol consumption. At cycle 1, complete protection against acute emesis was achieved in 22 patients (55%), major protection in 12 cases (30%), minor protection in four patients (10%) and failure in two cases (5%). On the other hand, the efficacy of this combination on delayed vomiting was not striking. For delayed vomiting, complete protection was observed in nine patients (23%), major protection in 13 cases (33%), minor protection in 10 patients (25%) and failure in eight cases (20%). At cycle 2, patients also received methylprednisolone showing complete protection from vomiting in 19 cases (47%) and major protection on 12 cases (30%). Results achieved with ondansetron plus metoclopramide are in the range reported for ondansetron alone in the medical literature. Although this study was not prospectively carried out in a randomized fashion, the results are not suggestive of a possible positive effect of metoclopramide addition to ondansetron. On the other hand, these results stress the role that corticosteroids may play in the control of delayed emesis. Toxicity was predictable and the frequency of side-effects was in the range reported in other studies with ondansetron.     

Treatment of pancreatic stones with extracorporeal lithotripsy with sonographic localization

BACKGROUND: Pancreatic stones may be treated by endoscopic extraction or by surgery. Extracorporeal shock wave lithotripsy increased possibility of noninvasive steps to their elimination. The aim of this study was to describe our first experience with this method. METHOD AND RESULTS: 10 patients (6 men and 4 women) in average age 47 years (between 19 to 72 years) were treated. The lithotriptor MEDILIT with sonographic targeting was used for fragmentation of pancreatic stones. Fragmentation was achieved in 8 patients, in 4 cases we observed spontaneous disappearnace, in 3 cases an endoscopic extraction of fragments was necessary. In one case good fragmentation was observed at control ECRP, but the repeated Wirsungography showed a big pseudocyst which had not been diagnosed at the first examination and surgery was necessary. In 2 cases no fragmentation was achieved and in these cases surgery was also indicated. No serious side effects were observed, nor elevation of amylase values compared with the situation before the shock wave treatment. CONCLUSIONS: Extracorporeal shock wave lithotripsy of pancreatic stones revealed good fragmentation and disappearance stone from ductus Wirsungi without serious side effects on clinical course and surrounding soft tissues.     

Neuropeptide Y2 receptors on nerve endings from the rat neurohypophysis regulate vasopressin and oxytocin release

Cows from eight commercial dairies were randomly assigned to intrammamary infusions of cephapirin or cephapirin plus interleukin-2 at the end of lactation. During the first phase of the trial, interleukin-2 was administered to 159 cows at a dose of 1 mg per gland by intracisternal infusion immediately after 300 mg of cephapirin were administered. One hundred sixty-one cows received infusions of a placebo (phosphate-buffered saline; PBS) immediately after cephapirin. In the second phase of the trial, 70 cows received 2 mg of interleukin-2 per gland, and 78 cows received the placebo. Cows were observed daily by the participating farmer for 72 h after infusion and also during routine feeding and care during the dry period and at calving. Potential side effects from udder infusions, particularly gross abnormalities of the udder and signs of systemic side effects were monitored. During the first phase, cure rates for intramammary infections caused by Staphylococcus aureus that were present at the end of lactation were 33.3% for quarters treated with cephapirin and 53.6% for quarters treated with cephapirin and interleukin-2. Cure rates did not differ between treatment groups for all other pathogens or during the second phase of the trial. The incidence of new intramammary infections during the dry period was not affected by intramammary infusion of interleukin-2. Eighteen of 229 (7.9%) cows treated with interleukin-2 aborted within 49 d of treatment compared with 4 of 239 (1.7%) cows treated with PBS. Eleven of the 18 (61.1%) abortions by cows treated with interleukin-2 occurred 3 to 7 d after infusion; none of the abortions by cows treated with PBS occurred until wk 7 after infusion.     

Effect of imipramine on mood and enumerative measures of immune status in depressed patients with HIV illness

OBJECTIVE: The authors' first objective was to ascertain whether imipramine is superior to placebo in treating axis I depressive disorders in the context of HIV illness. Supplementary questions were whether severity of immunodeficiency is associated with antidepressant response and whether patients with greater immunodeficiency can tolerate standard doses of imipramine. Second, the authors sought to determine whether imipramine treatment is associated with changes in immune status. METHOD: A double-blind, randomized placebo-controlled trial of imipramine was conducted in a university-affiliated research outpatient clinic. After 6 weeks of treatment, responders were maintained double-blind for another 6 weeks and nonresponders were removed from the study and treated openly. All patients were offered 26 weeks of treatment. Of the 97 patients who were randomly assigned to placebo or imipramine, 80 completed the 6-week phase. Main outcome measures included the Clinical Global Impression, the Hamilton Depression Rating Scale, the Brief Symptom Inventory, and CD4 cell count. RESULTS: Among study completers, 31 (39%) had AIDS. The response rate to imipramine was 74% and the response rate to placebo was 26%. There was no difference in depression response between patients with more or less severe immunodeficiency, nor was there a difference in medication dose or side effects. Neither type nor duration of treatment influenced CD4 cell count during the course of treatment. CONCLUSIONS: Depressed patients with HIV illness respond to imipramine at the same rate as medically healthy depressed patients. Severity of immunosuppression is not associated with imipramine treatment outcome. There is no evidence that imipramine has negative effects on enumerative measures of immune status.     

Treatment of rheumatoid arthritis of senile onset with methotrexate

Elderly onset rheumatoid arthritis is a not rare disease with relevant social implications. The most important question is represented by the therapeutic choice, in relation to the typical problems of the elderly patients and to the frequent coexistence of other diseases. In this work, we evaluated the practicability and the efficacy of methotrexate therapy, at the dose of 5 mg/week, in 27 patients affected by elderly onset rheumatoid arthritis (mean age 73.76 +/- 3.39 years, range 70-83). Low dose prednisone was associated in order to control painful symptoms. Also sulindac was allowed. Frequent clinical and hematochemical controls were made in order to precociously evaluate the appearance of side effects. All the 27 patients completed the first year of treatment; during this period there was no drop out. Sixteen patients finished the second year too; during this year one patient dropped out because of significant hypertransaminasemia and another patient did not respect the follow-up. Clinical and hematochemical parameters were monitored. A significant improvement of all data was observed from the third month. A further amelioration was recorded in the following months. Our data suggest the efficacy and the safety of low dose methotrexate in the treatment of elderly onset rheumatoid arthritis. A careful evaluation of side effects is obviously necessary.     

Azathioprine in patients with juvenile chronic arthritis: a longterm followup study

OBJECTIVE: To evaluate drug survival, efficacy, side effects, and longterm toxicity of azathioprine treatment in patients with juvenile chronic arthritis (JCA). METHODS: In an uncontrolled, prospective study we evaluated 129 consecutive patients with JCA refractory to therapy in whom azathioprine treatment was begun during 1980-1989. In the first 29 patients, a 2 year trial was planned, while for the remaining 100 patients the protocol was to continue until remission or dropout. The median treatment period was 13 months (range 3 days-8.5 yrs). Patients were assessed every 2 months for 2 years for efficacy, side effects, growth and need for glucocorticoids, and outcome evaluated in late 1996. RESULTS: Remission without drugs was attained in 19 patients (15%); in addition, temporary remission in patients continuing treatment was attained in 18 cases (14%). Treatment was discontinued due to side effects in 18 cases (14%); in two-thirds of these cases side effects occurred during the first 2 months. Of the total number of patients, 49 (38%) completed 2 years of treatment, with significant improvement in both clinical and laboratory indices of disease activity. Treatment had no noticeable effect on iridocyclitis. One patient died of cytomegalovirus infection during azathioprine treatment. CONCLUSION: Azathioprine is a useful drug in severe JCA, with a sustained effect and acceptable side effects. Even in cases of incomplete remission, its glucocorticoid sparing effect was noteworthy.     

Prevention of emesis by tropisetron in children receiving combined chemotherapy with cisplatin

We evaluated the antiemetic efficacy of tropisetron, a 5-HT3 receptor antagonist, during its use in 15 children with malignant disease who received cisplatin (CDDP) either alone (1/15) or in combination (14/15) with other cytostatic drugs. Tropisetron was given to 15 children (8 boys and 7 girls, ranging from 6 months to 17 years of age) with miscellaneous neoplasms. Generally, tropisetron (5 mg/m2/day, maximum 5 mg/day) was administered intravenously the first day of CDDP-based chemotherapy and orally for 4 subsequent days of chemotherapy. The dose of tropisetron was reduced to 0.2 mg/kg/day in children less than 1 year of age and/or those weighing less than 10 kg. Vomiting and nausea were controlled completely in 8 of 15 (53.3%) children on day 1 with a single intravenous infusion of tropisetron. Partial control was observed in 40% of patients on day 1. Complete control of delayed nausea and vomiting ranged between 40% and 80% in patients over days 2 to 5. The results obtained during administration of tropisetron confirm that it is a valid, safe, and manageable antiemetic for the treatment of malignant disease in pediatric patients.     

Lowered antioxidant status of red blood cells in post-parturient haemoglobinuria of buffaloes

Vaccination against tick-borne encephalitis with FSME-Immun vaccine was started in the Department of Infectious Diseases, University Medical School of Bia?ystok, Poland, in 1992. No serious adverse reactions after vaccine administration were observed. Post-vaccine side effects were reported in 242 (11.3%) persons after the first dose (n = 2,135) and only in 14 patients (1.2%) after the second one (n = 1,183). These effects were mild and transitory. No relationship was observed between the frequency of adverse reactions, general or local, and the initial anti-TBE virus antibody titres or the age of the immunized individuals. Post-vaccine side effects were reported significantly more frequently among people not bitten by ticks.     

Levonantradol, a new antiemetic with a high rate of side-effects for the prevention of nausea and vomiting in patients receiving cancer chemotherapy

Levonantradol, a new antiemetic compound pharmacologically related to the cannabinoids, was given to 17 patients who had experienced severe and protracted nausea and vomiting during previous courses of cancer chemotherapy, and to six patients receiving a first course of strongly emetic cytostatic treatment. Eight patients were partially protected from acute gastrointestinal disturbances. Of the 23 patients, 21 exhibited some toxicity, with six patients exhibiting major affective side-effects and 13 patients complaining of pain at the injection site. Levonantradol is an active antiemetic compound. Due to the rate of side-effects observed in our study however, we would not recommend use of this agent as an antiemetic drug.     

Repeated doses of combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine

The combination of lysine acetylsalicylate and metoclopramide is effective in the treatment of migraine attacks. It was unknown whether repeated doses could improve efficacy. The aim of this open trial was to evaluate the effects of a second, and eventually a third dose of lysine acetylsalicylate and metoclopramide when a first dose of the treatment was ineffective. Patients were asked to take a second dose 2 hours after a first dose when they thought that the first dose was ineffective. They were allowed to take a third dose or their rescue medication 2 hours after the second dose when they judged that the treatment remained ineffective. Two hundred ninety-two patients were included in the study; 262 of the 292 patients treated 517 attacks. Headache relief (reduction in headache severity from grade 3 or 2 to grade 1 or 0) was observed in 54.8% of attacks after one dose, in 48.1% of attacks after a second dose, and in 40.3% of attacks after a third dose. Complete headache relief without recurrence and without use of a rescue medication was reported in 37% of the total attacks. The patients judged their treatment as good or excellent in 78% of attacks treated with one dose, in 41% of those treated with two doses, and in 19% of those treated with three doses. Tolerance, as judged by the patients, was considered good in 92% of treated attacks. Minor side effects occurred in 6% of attacks after a first dose, in 4.5% of attacks after a second dose, in 1.5% of attacks after a third dose, in 2% after unspecified delay, and in 14% overall. In conclusion, the efficacy of lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks can be improved by repeated doses. It is well tolerated.     

Activity of two doses of rifampin against Mycobacterium leprae

In the course of a clinical trial designed to re-examine the bactericidal efficiency of 600-mg doses of rifampin (RMP) against Mycobacterium leprae, two doses of RMP, either 600 mg or 1200 mg, were administered 28 days apart to 29 previously untreated patients with lepromatous or borderline leprosy. Seven, 28, and 35 days after the start of the trial, skin biopsies were performed and immunologically normal mice were inoculated with 5 x 10(3) or 10(4) M. leprae in each hind foot pad. The patients assigned to the two regimens did not differ significantly in terms of sex, age, disease classification, bacterial index, or the concentration of M. leprae in the skin lesion biopsied for the inoculation of mice. The concentrations of organisms in the skin-biopsy specimens did not change significantly over the course of the trial among the patients, whether they were being treated by the first or the second regimen. The M. leprae recovered from specimens obtained from 21 of the patients, before beginning treatment, multiplied in a majority of the mice inoculated. The results of mouse inoculation confirmed the rapid bactericidal effects of RMP against M. leprae: a single dose of RMP rendered the organisms obtained from all but two of the patients incapable of multiplying in mice. No significant difference was demonstrated between the two regimens, nor was an additional effect of the second dose of RMP observed.     

Anti-ischemic effects of first and second dose of 20 mg isosorbide dinitrate administered 5 hours apart: attenuation of effects despite rising plasma concentration

Based on evidence that there may be early tolerance development even within the first daily cycle of treatment, this study was undertaken to evaluate the duration and extent of the antiischemic effects of two 20 mg doses of isosorbide dinitrate as used in a well-established regimen documented to maintain effectiveness during long-term treatment. Ischemia parameters were analyzed at 2 and 4 1/2 hours after the first dose as well as at 2 and 7 hours after the second dose given 5 hours later. The studies were performed in 10 male patients with documented coronary artery disease using bicycle ergometry and a double-blind, randomized, placebo-controlled, crossover protocol. ST-segment depression was reduced by 59% (p < 0.0005) at 2 hours and by 42% (p < 0.01) at 4 1/2 hours after the first tablet and by 38% (p < 0.005) at 2 hours and by 15% (p < 0.05) at 7 hours after the second tablet. Increments in ischemia-free workload capacity amounted to 112% (p < 0.005) and to 41% (p < 0.05) after the first tablet and 68% (p < 0.05) and 38% (p < 0.05) at 2 and 7 hours after the second tablet. At 2 and 4 1/2 hours after the first tablet, plasma concentrations of isosorbide dinitrate were 8.4 and 5.9 ng/ml, and those of isosorbide-5-mononitrate were 166.6 and 130.3 ng/ml. At 2 and 7 hours after the second tablet, the concentrations of isosorbide dinitrate were 9.1 and 5.9 ng/ml, and those of isosorbide-5-mononitrate were 224.5 and 148.1 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical study on temporal bone of autopsy cases with Mycobacterium leprae infection

Three temporal bones were obtained en bloc from autopsy cases with lepromatous leprosy from the middle cranial fossa side after removing the brain. After fixation with 10% formalin followed by sufficient decalcification, the specimens were embedded in paraffin en bloc and cut serially to stain every 10th section with hematoxylin and eosin (H&E) for anatomical orientation. An immunohistochemical study with anti-neurofilament, anti-MBP (myelin basic protein), anti-BCG (Bacillus Calmette-Gue'rin) and anti-PGL (Mycobacterium leprae-specific antiphenolic glycolipid-I) antibodies were performed to vestibular, cochlear and facial nerves, respectively, on the basis of anatomical orientation of the adjacent H&E sections. In one of three cases, positive staining by anti-PGL antibodies was recognized only in the facial nerve both in its internal auditory meatal and tympanic portions. However, even in this case, no neural damage was observed either by anti-neurofilament nor anti-MBP stainings. This finding supports the possibility of central neural infection by Mycobacterium leprae.     

Familial inv(X) (p22q22): ovarian dysgenesis in two sisters with del Xq and fertility in one male carrier

PURPOSE: To evaluate the antiemetic efficacy and safety of adding the dopamine antagonist prochlorperazine to the combination of granisetron and dexamethasone in the prevention of acute nausea and vomiting following high-dose cisplatin. PATIENTS AND METHODS: Sixty patients receiving cisplatin (> or = 75 mg/m2) (median dose = 100 mg/m2) were enrolled at three sites. Patients received prochlorperazine spansule 15 mg orally, 60 minutes prior to and 12 hours after cisplatin; dexamethasone 20 mg intravenously, 45 minutes prior to cisplatin, and 10 mg intravenously or orally, 12 hours after cisplatin; and granisetron 10 micrograms/kg intravenously, 30 minutes prior to cisplatin. Efficacy was assessed during the 24-hour period after cisplatin using complete antiemetic response (no emetic episodes and no rescue antiemetics) and patient assessment of nausea and satisfaction using 100-mm visual analog scales (nausea: 0 = none, 100 = nausea as bad as it can be; satisfaction: 0 = not at all satisfied, 100 = satisfied as can be). RESULTS: Complete response (0 emetic episodes) was noted in 84% (49/58) of patients. Forty-two patients (72%) experienced no nausea. The mean change in posttreatment nausea visual analog scales from baseline was 8.9 mm. Forty-eight patients (83%) were completely satisfied with their antiemetic treatment. The mean posttreatment patient satisfaction score was 92 mm. Treatment was well tolerated, with infrequent and minor adverse events. CONCLUSIONS: This three-drug antiemetic regimen is well tolerated and highly effective in the prevention of acute nausea and vomiting arising from high-dose cisplatin. Further studies evaluating this regimen are warranted.     

On-demand treatment of gastro-oesophageal reflux symptoms: a comparison of ranitidine 75 mg with cimetidine 200 mg or placebo

AIM: To compare the effects of ranitidine 75 mg with those of either cimetidine 200 mg or placebo given on demand for relief of typical symptoms of gastro-oesophageal reflux disease during a 15-day period. METHODS: A total of 1336 patients (aged > or = 18 years) with heartburn episodes were recruited and randomly assigned to a ranitidine 75 mg, cimetidine 200 mg or placebo group. Depending on the occurrence or persistence of heartburn, treatment was administered as required up to three times daily, with at least 2 h between drug doses. Antacids were allowed as rescue medication if symptoms persisted for at least 2 h after the third medication on any given day. The primary end-point was defined as the proportion of patients with relief of at least 75% of heartburn episodes during the study period (i.e. relief occurring within 2 h after drug ingestion and lasting for at least 5 h). RESULTS: Analysis was performed in an intention-to-treat population comprising 504 subjects in the ranitidine group, 515 in the cimetidine group and 270 in the placebo group. Primary end-point success rates were 41, 38 and 28%, respectively, for the three groups (P < 0.001 for ranitidine vs. placebo, P = 0.274 for ranitidine vs. cimetidine). Ranitidine 75 mg was significantly more effective than placebo in providing overall heartburn relief (P < 0.001). The differences between the ranitidine and cimetidine groups were not significant, except for a greater reduction in heartburn frequency in the ranitidine group at the end of the study period (P < 0.05). Drug dose was lower and less rescue medication was used in the ranitidine group than the placebo group. The three treatment groups did not differ in terms of tolerability. CONCLUSION: On-demand ranitidine 75 mg or cimetidine 200 mg are safe and effective treatment for reflux-related symptoms.     

Treatment of neonatal respiratory distress syndrome with Alveofact--results of a prospective observational study

AIM: After registration of the bovine Surfactant Alveofact (Fa. Thomae) for treatment of neonatal respiratory distress syndrome (RDS) an observational study was performed in 47 german neonatal departments to register indication, effectivity, mode of administration and unexpected side effects. METHODS: 680 ventilated preterm infants (gestational weeks 29.5 +/- 2.9; birth weight 1359 +/- 507 g) were enrolled in an uncontrolled clinical study with study-protocol, prospectively defined outcomes and covariates, manual of operation, central control system, biometrical control. RESULTS: Surfactant was applicated at a postnatal age of 2 hours 56 minutes (median). Only 2.9% of newborn infants got the first surfactant doses < 6 min postnatally, 19.4% between 6 ... 60 min and 77.7% > 60 min postnatally. Following 1338 instillations in 76% an improved lung function, in 21% no change and in 3% a worsening was observed. During the study the total dose of surfactant increased. Safety considerations determined by the rate of pulmonary and extrapulmonary complications were similar to data of the literature: pneumothorax 12%, pulmonary interstitial emphysema 11.6%, secondary pneumonia 20.4%, broncho-pulmonary dysplasia 27%, pulmonary hemorrhage 2.1%, peri/intraventricular hemorrhage (degree III/IV) 27.9%, ductus arteriosus persistens 24.4%, sepsis/meningitis 12.4%. During the study the mortality reduces from 31% (first period) to 18% (third period) the mean was 20%. In 44 infants (6.5%) a disturbed ventilation (airway obstruction, overdystension of pulmonary areas, atelectasis) after surfactant administration was observed. CONCLUSION: In RDS the surfactant Alveofact is preferably used therapeutically (rescue mode), it is effective but not free of risk. Its administration needs for a clear indication. New unknown side effects of Alveofact were not observed.     

A dose-ranging study of the use of cyclical dydrogesterone with continuous 17 beta oestradiol

OBJECTIVE: To establish the lowest dose of cyclical dydrogesterone that protects against endometrial hyperplasia induced by continuous 2 mg 17 beta oestradiol, and to study the dose effect on vaginal bleeding and side effects. DESIGN: Double-blind, prospectively randomised dose-ranging study. SETTING: Menopause clinics in the UK and The Netherlands. SUBJECTS: Three hundred and seventy-one postmenopausal women with intact uteri, aged 40 to 60. INTERVENTIONS: Administration of six 28-day treatment cycles of continuous daily micronised 17 beta oestradiol with a randomly allocated dose of 5 to 20 mg of dydrogesterone added for the last 14 days of each. MAIN OUTCOME MEASURES: Histological assessment of adequate progestational endometrial response, bleeding patterns and adverse effects. RESULTS: The study was completed by 320 subjects (86%). Endometrial transformation occurred in over 94% of those taking 5 mg of dydrogesterone, and in over 97% of those on higher doses, without significant differences between the 10, 15 and 20 mg groups. Acceptable bleeding patterns were found at all doses, with the incidence of withdrawal bleeding rising with increasing dose. The day of onset of bleeding was predictable from cycle to cycle, and occurred later in the 20 mg group than in the others. The incidence of noncyclic bleeding was about 6% at all doses. Withdrawal occurred in 3.3% due to unacceptable bleeding and in 5.4% due to side effects. There was no relation with dose. CONCLUSIONS: A dydrogesterone-17 beta oestradiol combination hormone replacement therapy confers endometrial protection with an acceptable bleeding pattern and few side effects At least 10 mg of dydrogesterone for 14 days is required for acceptable endometrial protection.     

Extent and severity of periodontal destruction based on partial clinical assessments

OBJECTIVES: To evaluate the postoperative analgesic efficacy, side effects and acceptance by patients and nurses of intravenous "patient-controlled analgesia" (PCA) with morphine, metamizole and buprenorphine. MATERIAL AND METHODS: In this randomized double blind prospective study of 150 patients in three groups receiving morphine (group A), metamizole (group B) or buprenorphine (group C), the patients had undergone low abdominal surgery with the same anesthetic protocol. Pain was recorded during the first 48 h after surgery on an orally-communicated scale of none or slight = 0, moderate = 1 and severe = 2. Upon the first report of moderate pain, patients were administered an intravenous bolus containing 5 mg morphine, 1 g metamizole or 0.15 mg buprenorphine. A perfusion pump was then connected and set with one bolus of 1.2 mg morphine, one of 333 mg metamizole or one of 0.04 buprenorphine. The maximum dose allowed in 24 h was 40 mg morphine, 8 g metamizole or 1.2 mg buprenorphine. The minimum interval between doses was 30 min for all three groups. Side effects reported were respiratory depression, sedation, nausea, vomiting, pruritus, perspiration and pain upon administration. Patients and nurses were asked to evaluate the system when the pump was disconnected and the results were then analyzed statistically. RESULTS: The analgesic effect was satisfactory in all three groups, with no significant differences among them. The percentages of patients reaching the maximum allowed dose on the first day were 2% with morphine, 18% (p < 0.05) with metamizole and 8% with buprenorphine. No respiratory depression was observed. Sedation was greater with morphine and buprenorphine than with metamizole (p = 0.0001). Pruritus was also greater with morphine and buprenorphine than with metamizole (p = 0.02) and pain upon infusion was greater with metamizole (p = 0.0002). CONCLUSIONS: Intravenous postoperative PCA was effective with all three drugs studied. Patient and nurse acceptance was good and side effects were few in the three groups. The lower rate of side effects for metamizole makes it the drug of choice.