Single high-dose dexamethasone improves the effect of ondansetron on acute chemotherapy-induced nausea and vomiting but impairs the control of delayed symptoms.

The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.

A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy.

BACKGROUND: There are few randomised studies comparing anti-emetic drugs for the prevention of nausea and vomiting in patients treated with fractionated radiotherapy. The aim of the study was to compare the anti-emetic efficacy of 8 mg dose ondansetron twice a day with placebo. MATERIALS AND METHODS: One hundred eleven patients who were to commence a course of 10 or more daily fractionated radiotherapy including the abdomen were included in the study. The patients recorded daily emesis, nausea and bowel habit and graded weekly symptoms of nausea, vomiting, diarrhoea and lack of appetite. The EORTC C30 questionnaire was completed. RESULTS: 67% of patients given ondansetron had complete control of emesis compared with 45% of patients with placebo (P < 0.05). The number of emetic episodes recorded on the worst day was 1.4 for the ondansetron group and 3.1 for the placebo group (P < 0.01). Patients given ondansetron had fewer days with emesis and nausea compared with placebo (P < 0.05). The mean sum score of patients weekly grading of symptoms showed that the ondansetron group had less inconvenience than the placebo group (P < 0.05). This difference persisted during the first three weeks, but not thereafter. Similarly, some quality of life measures showed significant differences in favour of the ondansetron group. More patients (n = 13) withdrew due to lack of efficacy in the placebo group compared with patients (n = 8) in the ondansetron group. CONCLUSIONS: The present study illustrates that prophylactic anti-emetic administration of ondansetron is effective in preventing nausea and vomiting in patients undergoing fractionated radiotherapy of the abdomen.

Blood group non-secretors have an increased inflammatory response to urinary tract infection.

The aim of this study was to assess the possible relationship between secretor state and the inflammatory response to urinary tract infection (UTI). Girls with recurrent UTI were prospectively studied. They included 61 secretor and 23 non-secretor individuals with 604 episodes of recurrent UTI. The response to each UTI episode was measured as the levels of C-reactive protein, erythrocyte sedimentation rate and the body temperature as well as renal concentrating capacity and pyuria. The levels of C-reactive protein, erythrocyte sedimentation rate and the body temperature were significantly higher in non-secretors than in secretors (p less than 0.04). As a consequence, non-secretors had an increased probability of being assigned a diagnosis of acute pyelonephritis rather than asymptomatic bacteriuria (p less than 0.05). The higher inflammatory response in non-secretors was independent of the Gal alpha 1-4Gal beta adhesin expression of the infecting Escherichia coli strains. The increased inflammatory response to UTI in non-secretors might explain the accumulation of these individuals among patients with renal scarring.

The effect of ondansetron on radiation-induced emesis and diarrhoea.

Fractionated radiotherapy of malignancies in the abdomen induces nausea and vomiting in approximately 50% of the patients. During abdominal irradiation the damaged gastrointestinal mucosa releases 5-HT with ensuing activation of 5-HT3 receptors which may explain the nausea and vomiting. Ondansetron is a new 5-HT3-antagonist with antiemetic properties. In this consecutive study, 33 patients receiving fractionated upper abdominal irradiation (> or = 100 cm2, 1,8-4 Gy daily dose for a mean of 13 days) were treated with ondansetron (8 mg t.d.s. p.o.). Emesis was completely controlled in 26/33 (79%) patients throughout their radiation course, which embraced 628 (94%) treatment days. Ondansetron was well tolerated. Eleven patients developed mild constipation. No patients experienced diarrhoea (a common distressing side-effect of abdominal irradiation). It is suggested that ondansetron can be of value in preventing emesis in patients receiving fractionated radiotherapy. The possible beneficial effect in preventing diarrhoea must be further evaluated.

Virulence-associated traits in Escherichia coli causing first and recurrent episodes of urinary tract infection in children with or without vesicoureteral reflux.

Virulence-associated properties of 606 urinary isolates from 174 children with urinary tract infections were related to severity of infection and factors increasing host susceptibility, e.g., vesicoureteral reflux (grade II or higher) and P1 blood group phenotype. A high proportion of strains of Escherichia coli causing first or recurrent episodes of acute pyelonephritis in children without reflux expressed the previously noted high frequency of certain O antigens, resistance to serum killing, hemolysin production, and adhesive capacity. A significantly lower frequency of these traits and a higher frequency of non-E. coli were seen among isolates from children with pyelonephritis and reflux, cystitis, and asymptomatic bacteriuria. Reflux was thus found to be a determinant of the level of infection and of the bacterial properties required to produce pyelonephritis. Efforts aimed at preventing or treating urinary tract infection by interfering with "virulent" bacteria may be of less value in patients with recurrent pyelonephritis and reflux, who are most likely to develop renal scars.

Chemical and clinical studies on the interaction of Escherichia coli with host glycolipid receptors in urinary tract infection.

The role of glycosphingolipids as host receptors, and fimbriae as bacterial ligands, for the adhesive and hemagglutinating reactions of uropathogenic E. coli was assessed. Glycolipids including globotetraosylceramide and globotriaosylceramide, which contain the disaccharide Gal alpha 1 leads to 4Gal were bound by many strains isolated from patients with pyelonephritis and cystitis. The fimbriae of one strain were shown to serve as ligands for these receptors. Although most pyelonephritic E. coli recognized globotetraosylceramide, as measured by the agglutination of glycolipid coated erythrocytes, some also recognized D-mannose residues (i.e. mannose-sensitive hemagglutination). Several strains were exclusively mannose-sensitive or bound neither globotetraosylceramide nor mannose. A genetic basis for susceptibility to infection was indicated. The erythrocytes of blood group P2 have lower amounts of Gal alpha 1 leads to 4Gal containing glycolipids than individuals of blood group P1. Blood group P2 was significantly less frequent (1/28) among patients with recurrent urinary tract infection compared to the normal population (10/40, p less than 0.02). Therefore, globoseries glycolipids may be determinants of susceptibility to urinary tract infection.

Attachment of Proteus mirabilis to human urinary sediment epithelial cells in vitro is different from that of Escherichia coli.

The in vitro attachment of 335 Proteus mirabilis strains from various human sources to human urinary tract epithelial cells was measured. No significant difference in adhesive capacity was found between P. mirabilis strains isolated from the blood of 89 patients with bacteremia, the stools of 36 healthy subjects and 56 patients with diarrhea, and the urine of 62 adults and 92 children with bacteriuria. High mean adhesion values were observed in all groups. The P. mirabilis strains attached only to squamous cells and not to transitional epithelial cells, whereas most of the Escherichia coli strains tested attached to both cell types; strains from patients with acute pyelonephritis attached more often than those from patients with acute cystitis or asymptomatic bacteriuria. The attachment of P. mirabilis to squamous epithelial cells was high about day 15 of the menstrual cycle of the epithelial cell donor, but low at the beginning and the end of the cycle. In contrast, the attachment of E. coli to squamous and transitional epithelial cells did not vary significantly with the menstrual cycle of the cell donor. Differences in adhesion characteristics of E. coli and P. mirabilis may relate to the differences in clinical appearance of urinary tract infections produced by the two organisms.