Measures of low food variety and poor dietary quality in a cross-sectional study of London school children.

BACKGROUND/OBJECTIVES: The use of simple screening tools to measure nutritional adequacy in a public health context in developed countries are currently lacking. We explore the relationship between food variety and nutrient intake of London school children using a simple tool with potential use for screening for inadequate diets. SUBJECTS/METHODS: A cross-sectional survey was carried out in 2010. The survey included 2579 children aged 7-10 years in 52 primary schools in East London in the United Kingdom. The analysis included 2392 children (93% of the original sample). Food variety was assessed as the total number of listed foods recorded over 24 h using the validated Child and Diet Assessment Tool (CADET) comprising 115 listed foods divided into 16 food categories. Dietary quality was determined by the proportion of children meeting recommended intakes of individual micronutrients, namely, calcium, iron, zinc, folate, vitamin A and vitamin C. RESULTS: The mean number of CADET-listed foods consumed daily by children was 17.1 (95% CI: 16.8, 17.5). Children who consumed fewer than 11 foods on the collection day had particularly low nutrient intakes. Children consuming three different vegetables and two different fruits on average consumed 19-20 listed foods. It was estimated between 4 and 20% of children did not meet the recommended levels for individual micronutrients during the period of data collection. CONCLUSIONS: A simple method using food counts to assess daily food variety may help public health nutritionists identify groups of children at risk of inadequate diets.

Impact of the International Nosocomial Infection Control Consortium (INICC)'s multidimensional approach on rates of ventilator-associated pneumonia in intensive care units in 22 hospitals of 14 cities of the Kingdom of Saudi Arabia.

BACKGROUND: To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and use of INICC Surveillance Online System (ISOS) on ventilator-associated pneumonia (VAP) rates in Saudi Arabia from September 2013 to February 2017. METHODS: A multicenter, prospective, before-after surveillance study on 14,961 patients in 37 intensive care units (ICUs) of 22 hospitals. During baseline, we performed outcome surveillance of VAP applying the definitions of the CDC/NHSN. During intervention, we implemented the IMA and the ISOS, which included: (1) a bundle of infection prevention practice interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback on VAP rates and consequences and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using generalized linear mixed models to estimate the effect of intervention. RESULTS: The baseline rate of 7.84 VAPs per 1000 mechanical-ventilator (MV)-days-with 20,927 MV-days and 164 VAPs-, was reduced to 4.74 VAPs per 1000 MV-days-with 118,929 MV-days and 771 VAPs-, accounting for a 39% rate reduction (IDR 0.61; 95% CI 0.5-0.7; P 0.001). CONCLUSIONS: Implementing the IMA was associated with significant reductions in VAP rates in ICUs of Saudi Arabia.

Embryo-fetal toxicity signals for 17alpha-hydroxyprogesterone caproate in high-risk pregnancies: a review of the non-clinical literature for embryo-fetal toxicity with progestins.

OBJECTIVE: A large National Institutes of Health (NIH) study showed that pharmacy-compounded 17alpha-hydroxyprogesterone caproate (17-OHP-C) reduced the incidence of preterm birth. The study results included a signal that 17-OHP-C may be associated with an increase in the rate of miscarriages and stillbirths. The most probable cause of an increased incidence of miscarriage/stillbirths may be the use of 17-OHP-C in high-risk patients. The current search of the non-clinical literature was performed to identify whether there were any signals from studies in animals that might suggest concerns for the safe use of progestins generally, and 17-OHP-C specifically, in the prevention of preterm birth in humans. METHODS: An extensive literature search was performed for progesterone, 17-hydroxyprogesterone, and 17-OHP-C, using Medline and Toxline databases, textbooks, and then the obtained publications. Because 17-OHP-C does not have a standardized clinical formulation or optimal route of administration identified, all formulations, vehicles, routes and doses were included in the search, as well as treatment during any stage of pregnancy. All publications obtained were reviewed for relevancy; those in German, French, Italian or Russian were translated. RESULTS: None of the relevant non-clinical studies conducted in mice, rats, rabbits, guinea pigs, horses or non-human primates met current standards for determining reproductive and developmental effects as part of the process of drug development. Most studies focused on the potential of 17-OHP-C for teratogenicity. Many studies used supra-pharmacologic and/or high multiples of human exposure in their study design. Overall, 17-OHP-C was consistently shown to be less potent than progesterone, and neither progesterone nor 17-OHP-C consistently adversely affected maternal weight, embryo-fetal viability or caused malformations. One study in rhesus monkeys raises concerns because resorption/abortion occurred at the human equivalent dose of 17-OHP-C, 10 mg/kg; this finding did not occur in cynomolgus monkeys. The absence of information regarding the serum levels of both progesterone and 17-OHP-C in the animal studies and in humans, as well as presumed inter-species metabolic differences, make it difficult to conclude that the findings with 17-OHP-C in rhesus monkeys and the signal in the NIH trial are related. A few studies in rats raised questions regarding potential effects on postnatal development, but in the absence of better study designs, the relevancy of these findings to human risk are also questionable at best. CONCLUSION: There is a signal for embryo-fetal toxicity associated with 17-OHP-C in the two largest clinical trials conducted to date; there is also a signal for embryo-fetal toxicity with 17-OHP-C in rhesus monkeys and possibly one in rodent species. The relationship between these signals is unclear given the absence of state-of-the-art reproductive toxicology studies and human pharmacokinetic studies.

Safety assessment of aqueous olive pulp extract as an antioxidant or antimicrobial agent in foods.

The olive fruit, its oil and the leaves of the olive tree have a rich history of nutritional, medicinal and ceremonial uses. Olive oil, table olives and olive products are an important part of the Mediterranean diet, the greatest value of which may be due to olive polyphenols that contribute to the modulation of the oxidative balance in vivo. The objective of this review is to examine the available safety/toxicity literature on olive polyphenols, particularly hydroxytyrosol, to determine the safety-in-use of a standardized aqueous olive pulp extract (HIDROX). Among the polyphenols found in the extract, the major constituent of biological significance is hydroxytyrosol (50-70%). In oral bioavailability studies, urinary excretion of hydroxytyrosol and its glucuronide was found to be associated with the intake of hydroxytyrosol. Oral bioavailability of hydroxytyrosol in olive oil and in an aqueous solution was reported as 99% and 75%, respectively. In comparative studies, urinary excretion of hydroxytyrosol was greater in humans than in rats. The LD(50) of the extract and hydroxytyrosol was reported to be greater than 2000 mg/kg. In a subchronic study, the no observed adverse effect level (NOAEL) of the extract in rats was found to be 2000 mg/kg/day. In developmental and reproductive toxicity studies, HIDROX did not cause toxicity at levels up to 2000 mg/kg/day. In an in vivo micronucleus assay, oral exposure of rats to HIDROX at dose levels up to 5000 mg/kg/day for 29 days did not induce increases in polychromatic erythrocytes in bone marrow. Based on the available studies of the extract and polyphenols, and a history of exposure and use of components of the extract through table olives, olive products and olive oil, the consumption of HIDROX is considered safe at levels up to 20 mg/kg/day.

Measuring diet in primary school children aged 8-11 years: validation of the Child and Diet Evaluation Tool (CADET) with an emphasis on fruit and vegetable intake.

BACKGROUND/OBJECTIVES: The Child And Diet Evaluation Tool (CADET) is a 24-h food diary that measures the nutrition intake of children aged 3-7 years, with a focus on fruit and vegetable consumption. Until now CADET has not been used to measure nutrient intake of children aged 8-11 years. To ensure that newly assigned portion sizes for this older age group were valid, participants were asked to complete the CADET diary (the school and home food diary) concurrently with a 1-day weighed record. SUBJECTS/METHODS: A total of 67 children with a mean age of 9.3 years (s.d.: ± 1.4, 51% girls) participated in the study. Total fruit and vegetable intake in grams and other nutrients were extracted to compare the mean intakes from the CADET diary and Weighed record using t-tests and Pearson's r correlations. Bland-Altman analysis was also conducted to assess the agreement between the two methods. RESULTS: Correlations comparing the CADET diary to the weighed record were high for fruit, vegetables and combined fruit and vegetables (r=0.7). The results from the Bland-Altman plots revealed a mean difference of 54 g (95% confidence interval: -88, 152) for combined fruit and vegetables intake. CADET is the only tool recommended by the National Obesity Observatory that has been validated in a U.K. population and provides nutrient level data on children's diets. CONCLUSIONS: The results from this study conclude that CADET can provide high-quality nutrient data suitable for evaluating intervention studies now for children aged 3-11 years with a focus on fruit and vegetable intake.

The Water Cycle, a Potential Source of the Bacterial Pathogen Bacillus cereus.

The behaviour of the sporulating soil-dwelling Bacillus cereus sensu lato (B. cereus sl) which includes foodborne pathogenic strains has been extensively studied in relation to its various animal hosts. The aim of this environmental study was to investigate the water compartments (rain and soil water, as well as groundwater) closely linked to the primary B. cereus sl reservoir, for which available data are limited. B. cereus sl was present, primarily as spores, in all of the tested compartments of an agricultural site, including water from rain to groundwater through soil. During rain events, leachates collected after transfer through the soil eventually reached the groundwater and were loaded with B. cereus sl. In groundwater samples, newly introduced spores of a B. cereus model strain were able to germinate, and vegetative cells arising from this event were detected for up to 50 days. This first B. cereus sl investigation in the various types of interrelated environments suggests that the consideration of the aquatic compartment linked to soil and to climatic events should provide a better understanding of B. cereus sl ecology and thus be relevant for a more accurate risk assessment of food poisoning caused by B. cereus sl pathogenic strains.

Reproductive toxicity and teratology evaluations of naltrexone.

Reproductive toxicology and teratology studies of naltrexone are reviewed. Naltrexone produced behavioral changes in rats at doses below those which affected body weight. Excitatory signs and increased production of seminal plugs occurred in male rats. Prolonged administration to female rats resulted in excitatory signs and impaired maternal activity. Estrus cycling and fertility were decreased in female rats at doses that depressed body weight gain. Higher doses given to pregnant rats for shorter periods of time did not impair fertility or produce embryo or fetal toxicity. In rabbits, there was no evidence of behavioral changes. The highest dosage administered produced transient weight depression and possibly increased resorption. These data are consistent with a report of transient changes in some normal men given single doses of naltrexone. These effects may be mediated via hypothalamic and pituitary mechanisms involved in the control of luteinizing hormone levels.

Lack of developmental neurotoxicity of MN rgp 120/HIV-1 administered subcutaneously to neonatal rats.

The potential for neurotoxic effects was evaluated in rat off-spring after exposure in utero and/or during the neonatal period to a recombinant subunit vaccine of gp120 prepared from the MN strain of HIV-1 (MN rgp 120/HIV-1). Thirty pregnant female rats were given MN rgp120/HIV-1 with alum adjuvant, and 30 rats were given vehicle, once every 3 days from Day 1 of presumed gestation until parturition. One pup/sex/litter from treated and control group dams were given a daily subcutaneous injection, from Day 1 through Day 22 postpartum (PP) of vehicle, MN rgp120/HIV-1, MN rgp120/HIV-1 with alum, or MN rgp120/HIV-1 with QS-21 adjuvant. Neurobehavioral and physical development were evaluated (preweaning reflex and development, sexual maturation, motor activity, acoustic startle, passive avoidance, functional observational battery, and water M-maze testing), and tissues were processed for anatomical examination (whole and regional brain weights, and neuropathology). Administration of MN rgp120/HIV-1, with or without adjuvant, to pups did not cause any persistent effect on any parameter evaluated. Neurohistological examination did not reveal any pathological effects related to treatment. Thus, MN rgp120/HIV-1 alone or formulated as a vaccine does not cause neurotoxicity or developmental toxicity in neonatal rats after exposure in utero and/or during the neonatal period.

Lack of effects of nose-only inhalation exposure on testicular toxicity in male rats.

Reductions in testicular mass, sperm motility, and mating frequency have been attributed to the stresses caused by confinement of Sprague-Dawley male rats in nose-only inhalation exposure tubes. Testicular changes, including an increase in testicular atrophy, have been detected at an increased incidence in male rats used in inhalation studies as compared with rats of the same age and strain used in oral toxicity studies. This study was designed to determine whether nose-only exposure of male rats caused testicular toxicity under conditions of cooling of the exposure room and appropriate acclimation to the exposure tubes. In order to acclimate the rats to the nose-only inhalation exposure apparatus, all male rats were placed in the exposure tubes for at least four successively increasing time intervals (15, 30, 45, and 60 min) on 4 separate days, with a rest period of approximately 48 h between the first and second acclimation. Twenty male rats were exposed nose-only to filtered air for approximately 2 h per day for 28 days before cohabitation and continuing throughout a 14-day cohabitation period. To reduce thermal stress, the exposure room temperature was maintained at 64 to 70 degrees F. Twenty control rats were housed in the same room as the exposed rats but were not placed in exposure tubes. End points monitored were body weight, testicular weight, sperm count, sperm motility, and histopathology of the testes, epididymides, prostate, and seminal vesicles. The control rats gained weight more rapidly than the exposed rats. All the rats in both groups mated successfully, and testicular weights, normalized to body weight, were similar for both groups. More importantly, there were no microscopic changes that could be considered an adverse effect on the reproductive tissues in the male rats placed in exposure tubes. Thus, nose-only exposure for up to 2 h per day for a total of 42 days did not cause adverse effects on the reproductive organs, fertility, or reproductive performance of male rats under the conditions of this study.

Review of reproductive and developmental toxicity of 1,3-butadiene.

Toxic doses of 1,3-butadiene (BD) have been reported to cause reproductive and/or developmental toxicity. Regardless of the strain used, mice were always affected by BD at lower doses than rats, an expected observation, based on well recognized differences in pharmacokinetic (PK) parameters in these two species. Because the mouse is particularly sensitive to BD in comparison with other laboratory species, and there are important functional and anatomical differences between humans and mice, the NOELs and LOELs identified for BD for various reproductive endpoints in mice may not be relevant to human reproductive risk. In mice, the LOELs for reproductive endpoints include developmental toxicity at 200 ppm, genotoxic effects at 500 ppm (mouse spot test), ovarian atrophy in females at 6.25 ppm (carcinogenicity study), reduced testicular weights at 200 ppm and testicular atrophy at 625 ppm BD in males (carcinogenicity studies), low incidences of abnormal sperm heads at 1000 and 5000 ppm BD (sperm head morphology study), small reversible increases in resorption at 1250/1300 ppm or 5000 ppm (dominant lethal studies), and other possible sequelae of genotoxicity resulting from exposure of male mice at 12.5 ppm BD and higher (dominant lethal study). When available, the much higher NOELs and LOELs of other species tested for the same endpoints should be considered. For example, maternal and developmental NOELs for BD in the rat were 200 and 1000 ppm, respectively, and 40 ppm in the mouse. Likewise, exposure of cohabited pairs of rats, guinea pigs and rabbits or of female dogs to BD concentrations as high as 6700 ppm for 8 months did not impair fertility or cause testicular or ovarian atrophy in these species. Thus, consideration of these remarkable species-dependent differences in toxicity is necessary. In addition, there are alternative scientific interpretations for some of the mouse studies and this review attempts to address these areas. For example, it may be incorrect to categorize results indicating weak in vivo genotoxic effects in male mice (sperm head morphology and dominant lethal studies) at 12.5 ppm BD and higher as reproductive effects because concentrations of BD as high as 5000 ppm did not affect mating, fertility or live litter sizes, even in this sensitive species. Similarly, it may be inappropriate to identify the ovary as a target organ for reproductive risk since the ovarian atrophy in mice was identified after completion of the normal reproductive life and after more than 15 months of exposure. Neither ovarian nor testicular atrophy occurred in Sprague-Dawley rats after exposure to BD concentrations as high as 8000 ppm for 105 (females) or 111 (males) weeks.

Developmental toxicity studies of four fragrances in rats.

Four fragrances, 6-acetyl-1,1,2,4,4,7-hexamethyltetraline (AHTN), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-ben zopyran (HHCB), musk ketone and musk xylene were tested for developmental toxicity in Sprague-Dawley rats (25/group, 3 groups/fragrance, 2 fragrances/corn oil control). Dosages tested were HHCB: 50, 150, 500 mg/kg per day; AHTN: 5, 15, 50 mg/kg per day; musk ketone: 15, 45, 150 mg/kg per day; musk xylene: 20, 60, 200 mg/kg per day. All dosages tested exceeded multiples of the estimated maximal daily human dermal exposure. Treatment (gavage, 5 ml/kg) occurred on GDs 7-17 and Caesarean-sectioning on GD 20. Based on the results of these studies, none of the four fragrances tested were more toxic in the conceptuses than in the dams. Maternal NOAELs were 50, 5, 15 and 20 mg/kg per day for HHCB, AHTN, musk ketone and musk xylene, respectively (150, 50, 45 and 60 mg/kg per day caused clinical signs and reduced weight gain and feed consumption). Developmental NOAELs were 150, 50, 45 and 200 mg/kg per day for HHCB, AHTN, musk ketone and musk xylene, respectively. No adverse effects on embryo-fetal viability, growth or morphology occurred at the highest dosages of AHTN (50 mg/kg per day) or musk xylene (200 mg/kg per day). Developmental toxicity occurred at the high-dosages of HHCB (axial skeletal malformations at 500 mg/kg per day) and musk ketone (increased postimplantation loss and reduced fetal body weight at 150 mg/kg per day). The results of this study indicate that under conditions of normal use, the tested fragrances do not pose a risk to human conceptuses.

Is there any place for nonmammalian in vitro tests?

In vitro developmental toxicity testing procedures have two potential uses: 1) prediction of Adult/Developmental Ratios (A/D Ratios); and 2) study of the mechanisms of embryo development. Historically there has been an incorrect emphasis on malformation as the most relevant endpoint of developmental toxicity, as well as an incorrect assumption that this endpoint alone could be identified by an in vitro procedure. The literature is filled with tests that have later been shown to be inaccurate predictors of mammalian developmental toxicity. In addition, industrial experience with in vitro tests used to predict bimodal responses (e.g., potential carcinogenicity) has produced a basic mistrust of the results of these tests and an unwillingness to perform a test because of fear of inappropriate delays in the regulatory process. Because no single test has been identified as one that can replace mammalian testing procedures, there is also little need seen for these procedures, although some tests are used, not necessarily correctly, to prioritize testing. Better understanding of the utility of these tests would increase their use in the prioritizing process, possibly allow their use when remarkable acute environmental hazards occur, and assist in identifying the mechanism underlying the observed effect.

Reproductive effects of chronic administration of murine interferon-gamma.

Daily subcutaneous doses of 0.02, 0.2, or 2 mg/kg/d of recombinant murine interferon-gamma (rmuIFN-gamma) were given to mice on postnatal days 8 through 60 to determine effects on maturation, behavioral/ functional development, and reproductive capacity. Male mice receiving 2 mg/kg/d rmuIFN-gamma had delayed sexual maturation, reduced epididymal and testes weights, reduced sperm count and concentration, and sperm abnormalities (crimped flagellum). Mating performance and fertility were also reduced in the absence of altered histopathology of the testes. Males given 0.2 and 2 mg/kg/d had swelling and ulcerative dermatitis around the urogenital area, which were observed after sexual contact and attributed to a bacterial infection. Motor activity (time spent in movement) was decreased in all mice receiving 2 mg/kg/d. No microscopic changes observed in any organs were attributed to rmuIFN-gamma administration.

Developmental (embryo-fetal toxicity/teratogenicity) toxicity studies of synthetic crystalline lycopene in rats and rabbits.

Synthetic crystalline lycopene is a nutritional supplement to increase dietary intake of lycopene, an antioxidant carotenoid. Its potential oral developmental toxicity was studied in rats and rabbits. Each study included 3 control groups (water and matrix for Lycopene 10 CWD or LycoVit 10%), 3 Lycopene 10 CWD groups [500, 1500 and 3000 (rats)/2000 (rabbits) mg/kg/day] and 1 LycoVit 10% group [3000 mg/kg/day (rats)/2000 (rabbits)]. The high dosages were at maximum achievable concentrations and dosage volumes (15 and 10 ml/kg for rats and rabbits, respectively) of the highly viscous test material suspensions. Dosages were administered on gestation days (GDs) 6 through 19 (rats) or GDs 6 through 28 (rabbits). Endpoints evaluated included viability, body weight, feed consumption, necropsy observations [GD 20 (rats)/GD 29 (rabbits)], uterine contents and fetal viability, gender, body weight and morphology (skeletons double-stained). Feed consumption and weight gain were essentially unaffected in rats and rabbits, despite intubation problems in both species and reduced gastrointestinal motility and mortality in rabbits attributable to the physical properties of the gels. Neither Lycopene 10 CWD nor LycoVit 10% caused direct maternal or developmental toxicity in rats or rabbits at dosages as high as 3000 or 2000 mg/kg/day, respectively.

[Reproductive and developmental toxicity studies of tazobactam/piperacillin or tazobactam (3)--Perinatal and postnatal study in rats with intraperitoneal administration].

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor and piperacillin (PIPC) is an antibiotics which is used in clinical field widely. The combination of TAZ and PIPC (TAZ/PIPC), which is combined with TAZ and PIPC at rate of 1:4, has been developed because of PIPC is unstable to various beta-lactamases. Perinatal and postnatal toxicity were studied in rats given daily intraperitoneal doses of TAZ/PIPC (200, 800 or 1600 mg/kg/day) or TAZ (40, 320 or 1280 mg/kg/day). TAZ/PIPC or TAZ were given from day 17 of pregnancy through day 21 of lactation. Total daily doses were administered in two equally divided doses. In this study, evaluation of the late stage of gestation, parturition, lactation and maternal behavior in adult rats and postnatal evaluation of the growth and development, and reproductive performance of the F1 generation occurred. In the TAZ/PIPC, maternal toxicity (decreased food consumption) was observed at 800 and 1600 mg/kg groups during perinatal period. A slight decrease in body weight gain during perinatal period and increased pup mortality and decreased pup weight in lactation period were observed at 1600 mg/kg group. An increase in stillbirths also was observed at 1600 mg/kg group. In the TAZ, maternal toxicity (decreased food consumption) was observed at all dosage groups during perinatal period. A decrease in body weight gain also were observed during perinatal period at 1280 mg/kg group. At maternotoxic doses of 320 and 1280 mg/kg groups, decreased pup weight were observed during lactation period. An increase in stillbirths also was observed at 1280 mg/kg group. Transient, significant decrease in pup body weights at 1280 mg/kg group in early postweaning period. No other effects occurred for the F1 generation rats. In conclusion, perinatal development and postnatal growth and development of offspring were affected only at the intermediate and high doses that caused maternal toxicity in this study. Therefore it is seemed that non-observed effect dose levels (NOELs) of TAZ/PIPC for dams is less than 200 mg/kg/day and that of TAZ is less than 40 mg/mg/day, and NOELs of TAZ/PIPC is 200 mg/kg/day and that of TAZ is 40 mg/kg/day for offspring under the condition of this study.

[Reproductive and developmental toxicity studies of tazobactam/piperacillin or tazobactam (2)--Teratological study in rats with intravenously administration].

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor and piperacillin (PIPC) is an antibiotics which is used in clinical field widely. The combination of TAZ and PIPC (TAZ/PIPC), which is combined with TAZ and PIPC at rate of 1:4, has been developed because of PIPC is unstable to various beta-lactamases. Teratogenic potential were studied in rats given daily intravenous doses of TAZ/PIPC (625, 1250, 2500 or 3750 mg/kg/day) or TAZ (125, 500 or 3000 mg/kg/day). TAZ/PIPC or TAZ were given from day 7 to day 17 of pregnancy. Total daily doses were administered in two equally divided doses. The study includes postnatal evaluation of the growth and development and reproductive performance of the F1 generation. Maternal deaths occurred in all groups given TAZ/PIPC. The incidence (range of 3 to 6 animals/group) was not dose dependent. Maternal body weight was decreased in rats receiving 3000 mg/kg of TAZ and food consumption was reduced in all drug-treated groups. Slight decreases in fetal body weights were observed at some doses that caused maternal body-weight or food-consumption decreases (2500 or 3750 mg/kg of TAZ/PIPC, 3000 mg/kg of TAZ). But these depressions of fetal body weights were not significant from control data. There were no fetal malformations or variations attributable to the test articles. Postnatal growth and development, behavior and reproductive performance of the F1 generation were not affected by the administration of TAZ/PIPC or TAZ. In conclusion, TAZ/PIPC or TAZ was not teratogenic in the rats. It is seemed that non-observed effect dose levels (NOELs) of TAZ/PIPC and TAZ for dams is less than 625 and 125 mg/kg/day in general toxicity respectively, however, NOELs of TAZ/PIPC is 3750 mg/kg/day or more and that of TAZ is 300 mg/kg/day or more for their offspring under the condition of this study.

[Reproductive and developmental toxicity studies of tazobactam/piperacillin or tazobactam(1)--Fertility and general reproduction study in rats with intraperitoneal administration].

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor and piperacillin (PIPC) is an antibiotics which is used in clinical field widely. The combination of TAZ and PIPC (TAZ/PIPC), which is combined with TAZ and PIPC at rate of 1:4, has been developed because of PIPC is unstable to various beta-lactamases. Fertility and general reproductive performance were studied in rats given daily intraperitoneal doses of TAZ/PIPC (200, 800 or 1600 mg/kg/day) or TAZ (40, 160 or 640 mg/kg/day). TAZ/PIPC or TAZ were given during premating period (70 days in males and 15 days in females), the pairing period (in males and females) and the gestation and lactation periods (in females). Total daily doses were administered in two equally divided doses. The study includes evaluation of the F1 generation and the F2 generation through weaning. In the TAZ/PIPC, maternal toxicity (decreased food consumption) was observed at 200 mg/kg and above dosage groups. At maternotoxic doses of 800 and 1600 mg/kg groups, increased resorptions, decreased live litter size, and increased fetal variations (reversible changes in ribs) were observed. Reversible delays in ossification of caudal vertebrae were also observed at 1600 mg/kg group. In the TAZ, maternal toxicities were observed at 160 mg/kg group (decreased food consumption) and 640 mg/kg group (decreased body weight gain and food consumption). Furthermore, necropsy (raised and/or colored areas present in the cecum) revealed slight increases at 40 mg/kg and above dosage groups. Slight decreases in implantations and resultant slight decreases in live litter size, reversible delays in renal development, and increased stillbirths were observed at 640 mg/kg group. Postnatal growth and development, behavior and reproductive performance of the F1 generation were not affected by the administration of TAZ/PIPC or TAZ. There were no effects on any of the fetal or pup parameters evaluated in the F2 generation. In conclusion, mating behavior and fertility were not affected by TAZ/PIPC or TAZ in this study. TAZ/PIPC or TAZ caused adverse change in reproductive performance of the F0 generation only at doses that caused maternal toxicity. The F1 and F2 generation were not affected.(ABSTRACT TRUNCATED AT 400 WORDS)

Traumatic rupture of the spleen.

Sixty-three cases of traumatic rupture of the spleen were analyzed. The patients were admitted to our hospitals during the last 24 years and there has been a steady increase in the numbers seen. The great majority of these cases resulted from road traffic accidents, and 33% of the patients had multiple injuries. Most were in the second and fourth decades; males outnumbered females by nearly four to one. Associated injuries, which occurred in 33% of cases, significantly raised the mortality. The mortality was also higher in the older age group and in those patients who had multiple injuries and were severely shocked on admission. Difficulty and delay in diagnosis occurred particularly in the unconscious patients and also in those in whom shock was not apparent, particularly when abdominal signs were late in developing. Treatment by resuscitation and splenectomy was used routinely and our overall mortality was 17.5%. Complications were frequent, the most serious being gastrointestinal and respiratory. A long-term follow-up showed that the great majority of patients have done well. There has been no evidence of an increased infection risk following splenectomy, and all but a few patients were able to return to their former sporting activities.

Incidence and implications of natural deaths of road users.

A prospective study was carried out over the 10 years 1978-87 to determine the incidence and implications of sudden death in road users--that is, drivers, pedestrians, cyclists, and motorcyclists. During the study period 30,000 patients were seen in the same accident and emergency departments of East Berkshire after road traffic incidents or accidents, of whom 267 either were brought in dead or died within two hours after arrival. Of these patients, 64 (24%) were found to have died of natural causes due to pre-existing disease or to have been killed in an incident that occurred as a result of a medical or psychiatric condition. Twelve of the patients sustained physical injury; all 64 came to necropsy. Only one incident resulted in the death of another person in addition to the natural death of a patient. It is concluded that sudden natural death occurring in road users does not present an appreciable hazard to other road users.