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.

Is penicillin the appropriate treatment for recurrent tonsillopharyngitis? Results from a comparative randomized blind study of cefuroxime axetil and phenoxymethylpenicillin in children. The Swedish Study Group.

The efficacy of cefuroxime axetil compared with phenoxymethylpenicillin (PcV) was studied in group A beta-haemolytic streptococci (GAS) culture-proven tonsillitis in children aged 3-12 years with a history of at least 1 episode of tonsillopharyngitis requiring antibiotic therapy during the previous 3 months. This was a comparative, randomized, investigator-blind, multicentre study. A total of 236 children received either cefuroxime axetil suspension or PcV syrup. Inclusion criteria were a positive, rapid, group A strep test verified by bacteriological culture and clinical signs and symptoms of tonsillopharyngitis. Cefuroxime axetil treatment gave a significantly higher bacteriological eradication rate and clinical cure rate than PcV. At day 2-5 post treatment the eradication rates were 99/114 (87%) for cefuroxime axetil vs 61/109 (56%) for PcV (p < 0.001). The clinical cure rates were 98/114 (86%) and 73/109 (67%) respectively (p < 0.01). Up to 21-28 days post-treatment, 9/114 (8%) cefuroxime axetil patients and 37/109 (34%) PcV patients were treatment failures or had recurrence/reinfection of GAS tonsillopharyngitis (p < 0.001). More than 90% of the patients who experienced bacteriological treatment failure at either the first or second follow-up had the same serotype isolated pre- and post-treatment. During the study period, 21/114 (18%) patients in the cefuroxime axetil group and 50/109 (46%) patients in the PcV group received additional antibiotics (p < 0.001). No serious adverse events were noted and the mild adverse events were equally distributed among the patients in the 2 study groups: 15% for cefuroxime axetil and 14% for PcV.

Involvement of maternity and health care staff in breast-feeding.

The prerequisites of the staff for their interest and concern in working with questions related to breast-feeding have been studied by questionnaires which were answered by 133 nurses at pregnancy care centres, child health centres and maternity wards. The intention was to identify possible obstacles for the staff in supporting the mother's breast-feeding. In spite of extensive experience and positive attitudes to breast-feeding, about half of the staff found it difficult to work with these questions and to give enough support. The most common reasons for this fact were insufficient knowledge about breast-feeding, few possibilities for further training and a heavy workload. It was also evident that some routines need to be corrected. For instance, information about breast-feeding was provided late during pregnancy, the fathers were infrequently engaged and the communication between the departments was limited. A reorganization of the staff's working routines and their continuous further training in issues related to breast-feeding are recommended.

A survey of Swedish mothers' view on breastfeeding and experiences of social and professional support.

The purpose of this cross-sectional study was to investigate conditions for breastfeeding among 452 mothers. Three different groups of women, participating in the Swedish health care system, were asked to complete a questionnaire about breastfeeding and related issues: 1) pregnant women attending the pregnancy care centres (n = 186), 2) women staying at the maternity wards after delivery (n = 171) and 3) women with two-month-old child attending the child health stations (n = 95). We found that the majority of the mothers were in favour of breastfeeding and intended to or had begun to breastfeed their infants. The main problems were "sore nipples", "children who cannot take the breast" and "insufficient milk production". Negative experiences of previous breastfeeding and overwhelming demands were motives for weaning. The personnel within the health care system were shown to be important for the mothers as regards advice and support. However, we found that certain routines could be revised to strengthen the mothers' attitude towards breastfeeding: 1) information on and discussions about breastfeeding occurred infrequently at the pregnancy care centres. 2) Water or formulated milk was often given to the newborn baby at the maternity wards and 3) the participation of the fathers was limited. Continuous surveillance of the routines and education of the health care staff would be desirable to enable them to give the mothers the right breastfeeding support and advice at the right time.

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.

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.

Escherichia coli in patients with renal scarring: genotype and phenotype of Gal alpha 1-4Gal beta-, Forssman- and mannose-specific adhesins.

The frequency of Escherichia coli with Gal alpha 1-4Gal beta-specific adhesins is reduced among children who develop renal scars. The adhesion-negative phenotype may be due to the absence of the pap DNA sequences which encode these adhesins or to a phase variation event induced by in vitro culture. In the present study the frequency of pap and pil homologous DNA was determined by dot blot analysis with probes specific for the respective sequence using E. coli strains from children with recurrent pyelonephritis with and without renal scarring. The frequency of pap was 79% in the strains isolated from the nonscarring group compared with 39% in the strains from the scarring group (P less than 0.001). The Gal alpha 1-4Gal beta phenotype was expressed by 89% of the pap-positive strains from the nonscarring group compared with 71% in the scarring group (P less than 0.05). In addition 13 of 77 of the pap-positive E. coli strains agglutinated sheep erythrocytes but not the Gal alpha 1-4Gal beta latex beads; a reaction attributed to reactivity with the Forssman glycolipid. DNA sequences homologous with pil were found in 95% of all strains and there was no significant difference between the nonscarring and the scarring groups. The low frequency of Gal alpha 1-4Gal beta specific strains in the scarring group was therefore due to the absence of pap-homologous DNA sequences and to a reduced rate of phenotypic expression among pap-positive scarring strains. There was no support for a relationship between type 1 fimbriae and renal scarring.

Overrepresentation of blood group non-secretors in adults with renal scarring.

Host factors are important in the pathogenesis of pyelonephritic renal scarring. The present study used blood group secretor state as a population marker to determine if patients developing renal scarring are a selected subgroup of individuals with urinary tract infections (UTI). Non-secretors represented 15/43 (35%) of the patients with renal scarring but only 7/41 (17%) of the patients without renal scarring (p = 0.059 and NS respectively vs. healthy controls 22%). The frequency of non-secretors among P1 phenotype patients with renal scarring was 38% (p = 0.05 vs. healthy controls). Among the patients born after the introduction of regular use of antibiotic treatment for UTI the frequency of non-secretors was 55% in the scarred group compared to 13% in the unscarred group (p = 0.011). Thus, in this younger group of patients with renal scarring 6/10 (60%) of the non-secretors developed renal scars compared to 5/32 (16%) of the secretors (p less than 0.05). Our data confirm that blood group non-secretors are overrepresented in patients with non obstructive renal scarring suggesting that blood group non-secretor state might be a host marker to consider for the subgroup of individuals with recurrent UTI at risk to develop renal scars. Renal function was not influenced by blood group secretor state. The mean glomerular filtration rate within the scarred group was similar for secretors and non-secretors (80 ml/min X 1.73 m2 and 79 ml/min X 1.73 m2, respectively). Whether blood group secretor state also is involved in the scarring process remains to be investigated.

Influence of P blood group phenotype on susceptibility to urinary tract infection.

Bacterial attachment is an important event in the pathogenesis of urinary tract infection (UTI). Increased receptivity on the host cells has been suggested influence proneness to infection. The dual function of the globoseries of glycolipids both as receptors for attaching E. coli and as P blood group antigens lead us to examine the P blood group phenotype distribution in UTI prone patient populations. A correlation between the P1 blood group phenotype and susceptibility to UTI was found. Patients with recurrent pyelonephritis had 74/79 (94%), P1 compared to 75% in healthy controls. In contrast patients with asymptomatic bacteriuria (ABU) had a reduced frequency of P1, 43/74 (58%). P1 and P2 individuals differ in amount and composition of the globoseries of glycolipids on their erythrocytes. A similar difference in other tissues, e.g. uroepithelial cells might explain the association of P1 with UTI. There was, however, no significant difference in bacterial adherence to uroepithelial cells from P1 and P2 individuals. Other mechanisms explaining the increase in P1 individuals in recurrent pyelonephritis are discussed.

Secretor state and renal scarring in girls with recurrent pyelonephritis.

The non-secretor phenotype was significantly associated with the occurrence of renal scarring among patients with recurrent pyelonephritis. Girls (n = 77) with recurrent pyelonephritis were followed from the first known episode of infection for up to twelve years with repeated radiological investigations. They were divided into two categories: those with renal scars (n = 35) and those who did not develop scars (n = 42). There was a significant over-representation of non-secretors among the patients with scarring, (14/35, 40%) compared to the healthy controls (21.8%, P less than 0.05). The frequency of non-secretors among the girls who did not develop scars in spite of repeated episodes of acute pyelonephritis was not significantly different from the healthy controls (9/42, 21% n.s.). This study provides a basis for analysis of the influence of secretor state on host-parasite interaction in the urinary tract.

Bacterial and host determinants of renal scarring.

This review summarizes recent work examining the interaction between host and parasite in recurrent urinary tract infection (UTI) and renal scarring. Virulence in uropathogenic E. coli has been defined by the severity of acute disease. Isolates from patients with acute pyelonephritic strains differ from those causing asymptomatic bacteriuria by multiple traits which contribute to virulence, and which are coexpressed in a non-random manner. The single marker most characteristic for the pyelonephritogenic clones is bacterial adherence to uroepithelial cells binding specifically to the disaccaride Gal alpha 1-4 Gal beta within the globoseries of glycolipids. The notion that the most severe consequence of acute pyelonephritis, i.e. renal scarring, was caused by the most virulent clones, was contradicted by comparison of pyelonephritic strains isolated from children with and without scarring. The virulent clones were significantly less frequent in patients with renal scarring (22%) than in patients with recurrent pyelonephritis not developing renal scars (62%). In view of the unexpected inverse association of bacterial virulence with renal scarring lack of Gal alpha 1-4 Gal beta binding capacity of E. coli strains was found to predict the risk for renal scarring among boys with first-time acute pyelonephritis. Vesicoureteric reflux (VUR) is widely accepted as a host determinant of susceptibility to pyelonephritis and renal scarring. In our study the frequency of renal scarring was 57% among girls with VUR as compared to 8% of those without. The reflux alone did however, not explain the selection of bacteria of low virulence. Individuals prone to UTI and renal scarring were found to be a genetically selected subgroup of the general population. A correlation between P1 blood group phenotype and susceptibility to UTI and between blood group non-secretor state and renal scarring was found. The mechanisms behind these relationships need to be defined. The bacterial and host parameters combined indicate that host parameters are essential for the tendency to develop renal scarring after acute pyelonephritis.

P blood group and proneness to urinary tract infection in Japanese children.

The globoseries of glycolipids are antigens in the P blood group system as well as epithelial cell receptors for uropathogenic Escherichia coli. The P1 blood group is overrepresented in Swedish girls with recurrent pyelonephritis. In this study, Japanese children with urinary tract infection (UTI) were analyzed for P blood group phenotype. Out of 26 children with recurrent UTI, 50% were of the P1 blood group compared to the 31% of P1 individuals in the Japanese population at large (p less than 0.05). Of children defined as having febrile UTI 62% were P1. The P1 blood group was thus significantly enriched (3.5 times) in the children with febrile UTI. These results support the hypothesis that individuals of blood group P1 run an increased risk for recurrent pyelonephritis.

Host parasite interaction in urinary tract infection.

The last decade has provided new insight into the mechanisms of host-parasite interactions in the urinary tract. Reduction of host resistance appears to reduce the requirement for bacterial virulence, whereas the resistant host becomes infected with bacteria of high virulence. In the resistant host, bacterial virulence can be defined as the sum of properties required to colonize the urinary tract and induce tissue reactions. The ability to attach to uroepithelial cells is the single property most frequently associated with pyelonephritogenic clones. Attachment to the Gal alpha 1-4Gal beta-containing receptors promotes localization of bacteria to the kidney and the induction of lipopolysaccharide-mediated inflammation. Other virulence factors, defined by increased frequency in acute pyelonephritis compared with asymptomatic bacteriuria, include haemolysin and aerobactin production. Among the factors which influence the natural resistance to urinary tract infection are urinary flow and reactivity to endotoxin. The resistance induced by natural exposure to infection or immunization may be protective in experimental models, but the importance of this is not yet defined. The localization, severity and sequelae of urinary tract infection are determined by the balance between bacterial virulence and host resistance. Although disease is a result of the interaction between bacterial virulence and host resistance, these components are discussed separately for clarity.