Protective Effects of Melatonin against Cyclophosphamide-induced Oxidative Lung Toxicity in Mice.

This study was undertaken to evaluate the protective effects of melatonin against cyclophosphamide (CP)-induced oxidative lung toxicity in mice. Mice were pre-treated with various doses of melatonin for 7 consecutive days and were then injected with CP (200 mg/kg b. w.) 1 h after last melatonin injection. After 24 h, the mice were euthanized and their lungs were immediately harvested. Several biomarkers associated with oxidative stress in lung homogenates, such as thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH) levels and the activity of superoxide dismutase (SOD) and catalase (CAT) were measured spectrophotometrically. A single dose of CP markedly altered the levels of these oxidative stress biomarkers in lung homogenates. However, increased lipid peroxidation, measured as TBARs, was significantly inhibited in the lung tissues of the melatonin-pretreated mice compared to the CP alone-injected group. In addition, pretreatment with melatonin also significantly restored GSH levels and SOD and CAT activities. Melatonin also effectively protected animals from CP-induced histological abnormalities in lung tissue. In conclusion, the increase in oxidative stress markers and concomitant adaptations by the antioxidant defense system indicates that oxidative stress plays an important role in CP-induced damage to the lung. Moreover, melatonin is a potent natural antioxidant that helps prevent CP-induced oxidative toxicity in mouse lung tissues. Thus, because melatonin is regarded to be a safe pineal secretory product, it may be used concomitantly as a supplement to reduce lung damage in patients undergoing chemotherapy.

Hepatoprotective effects of zataria multiflora ethanolic extract on liver toxicity induced by cyclophosphamide in mice.

Although cyclophosphamide (CP), an alkylating agent, has been extensively used in chemotherapy, it possesses a wide spectrum of adverse effects including hepatotoxicity. This study was aimed to evaluate the protective effects of Zataria multiflora against hepatic damage induced by CP in mice.Mice were orally (gavages) pretreated with the ethanolic extract aerial parts of Zataria at doses of 50, 100, 200, or 400 mg/kg for 7 consecutive days before a single intraperitoneal injection of 200 mg/kg CP. After 24 h, animals were anesthetized, blood samples and hepatic tissues were collected and used for biochemical and histological examination.Serum levels of hepatic markers were significantly increased after only CP treated animals but restored in Zataria pretreated groups. A single dose of CP administration also markedly induced abnormality in the levels of several biomarkers associated with oxidative stress in liver tissues homogenates. However, pretreatment with Zataria significantly inhibited the abnormality of antioxidant enzymes defense system in the liver tissues. In addition, histopathological studies proved that CP causes damage to the liver, and this was evidenced by the induced dilated and congested sinusoidal space, lymphocytic infiltration between hepatocytes, portal space with moderate to severe inflammation and necrotic hepatocyte with absence of nuclei. Zataria effectively protected animals against CP-induced hepatic tissue damages.Our results reveal that Zataria produces a potent hepatoprotective role and could be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity of CP for the patients undergoing chemotherapy.

The potential ameliorative effects of melatonin against cyclophosphamide-induced DNA damage in murine bone marrow cells.

OBJECTIVES: The protection afforded by melatonin, a pineal secretory product, against cyclophosphamide (CP)-induced genotoxicity in murine bone marrow cells was tested using micronuclei as an index of induced chromosomal damage. MATERIALS AND METHODS: Mice were pretreated with four different doses of melatonin (2.5, 5, 10 and 20 mg/kg by weight, b.w.) via intraperitoneal injection for five consecutive days followed by injection with CP (60 mg/kg b.w.) 1 hr after the last injection of melatonin on the fifth day. After 24 hr, mice were euthanized by cervical dislocation to evaluate micronucleated polychromatic erythrocytes (MnPCEs) and the ratio of polychromatic erythrocyte/polychromatic erythrocyte+normochromatic erythrocyte [PCE/(PCE+NCE)]. Histological examination of the bone marrow was also performed. RESULTS: Treatment with melatonin significantly reduced the number of MnPCEs induced by CP at all doses (p < 0.0001). At 20 mg/kg, melatonin had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.93 fold and completely normalized the PCE/ (PCE+NCE) ratio. Administration of 20 mg/kg of melatonin led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP, as well as mitigated bone marrow suppression induced by CP. CONCLUSIONS: Our study revealed that melatonin has a potent antigenotoxic effect against CP-induced toxicity in mice, which may be due to the scavenging of free radicals and increased antioxidant status. Because melatonin is a safe, natural compound, it could be used concomitantly as a supplement to protect people undergoing chemotherapy.

Melatonin ameliorates oxidative stress and reproductive toxicity induced by cyclophosphamide in male mice.

The present study evaluated the efficacy of melatonin in cyclophosphamide (CP)-induced testicular injury, lipid peroxidative damage, and antioxidant enzymes status of the mice testis on the basis of biochemical and histological studies. Mice were pretreated with four different doses of melatonin (2.5, 5, 10, and, 20 mg/kg by body weight (b.w.)) via intraperitoneal injection for five consecutive days followed by injection with CP (200 mg/kg b.w.) 1 h after the last injection of melatonin on the 5th day. After 24 h, mice were euthanized, testes were immediately removed, and biochemical and histological studies were conducted. Treatment with melatonin significantly mitigates lipid peroxidation, superoxide dismutase, and catalase activity and the level of reduced glutathione content abnormality induced by CP in mice testis. Histological examination clearly demonstrates that pretreatment of melatonin prevented CP-induced spermatogenesis toxicity and spermatogenic cells reduction in mice testis. The protective effect of melatonin is likely due to the antioxidative properties of the indolamine existed in the chemical structure. Because melatonin is a safe, natural compound, it could be used concomitantly as a supplement to protect people undergoing chemotherapy against reproductive toxicity.

Evidence-based management of Mastalgia: a meta-analysis of randomised trials.

Several agents have been utilised for therapy of mastalgia based on data from small trials. No meta-analysis of trials on mastalgia exists. We have conducted a meta-analysis on trials on mastalgia published in the English language. Study was restricted to randomised controlled trials comparing Bromocriptine, Danazol, Evening primrose oil (EPO) and Tamoxifen with placebo. The analysis was carried out on the REVMAN statistical package. Weighted mean difference in the pain score in favour of Bromocriptine was -16.31(95% CI -26.35 to -6.27). Danazol produced a significant benefit with a mean pain score difference -20.23(95% CI -28.12 to -12.34). EPO did not offer any advantage over placebo in pain relief, mean pain score difference being -2.78 (95% CI -7.97 to 2.40). Tamoxifen achieved a relative risk (RR) of pain relief of 1.92 (95% CI 1.42-2.58). Tamoxifen is associated with least side effects and should be the drug of first choice.

Cladosporium bantianum meningitis in a neonate.

Cladosporium bantianum meningitis has been reported mostly in adult farmers between 20 and 30 years of age. We report a 6-day-old male neonate who was admitted with fever, focal seizures and not accepting feeds. Initial investigations suggested a diagnosis of pyogenic meningitis but antibiotic therapy for 14 days did not result in any significant clinical improvement. Repeat CSF examination after 14 days suggested a diagnosis of C. bantianum meningitis which was supported by presence of multiple abscesses in the cerebral cortex on CT scan of the head and confirmed by CSF culture. Clinical response to antifungal therapy remained unsatisfactory.

Detector sensitivity influences blood flow sampling in scanning laser Doppler flowmetry.

PURPOSE: To establish the effect of photodiode sensitivity on the DC (brightness) value and the resultant blood flow measurements of retina and rim tissue using a scanning laser Doppler flowmeter (SLDF). METHODS: The sample consisted of one eye of each of 15 healthy subjects (mean age 27.8 +/- 6.1 years). Using the Heidelberg Retina Flowmeter (HRF), three 10-deg images of the superior temporal retina and three further images of the superior temporal rim were acquired for each of five DC bands: band 1: 30-70; band 2: 70-110; band 3: 110-150; band 4 150-190; band 5: 190-230. Retinal blood volume, flow and velocity were determined for each image using a 10 x 10 pixel square grid located at a predetermined location on the retina and rim for each subject. Following image acquisition, the DC values corresponding to each pre-assigned retinal or rim location were determined. The mean and standard deviation were determined for the blood flow parameters within each DC band for each subject in both locations. Analysis of variance was used to identify significant change in the data as a function of the DC value (P<0.05). RESULTS: Analysis of variance revealed that retinal blood flow measures acquired within DC band 5 resulted in significantly lower measures of blood flow and velocity (P=0.035 and P=0.049 respectively) than at lower DC values. Band 5 values of flow, volume and velocity in the neuroretinal rim were also significantly low (P=0.016, P= 0.003 and P=0.026 respectively). Peak neuroretinal rim blood flow was recorded when the DC value was between 70 and 110. For blood flow measurement at the retina and neuroretinal rim the DC value should not exceed 190. CONCLUSION: Photodiode sensitivity as indicated by the DC value affects measurements of ocular blood flow using the HRF.

A comparison of long pediatric hospitalizations in 1985 and 1994.

The objective of this study was to identify pediatric conditions commonly resulting in long hospitalizations, to evaluate changes in hospital use for these conditions over a 9-year period, and to describe the characteristics of children hospitalized for long periods (longer than 7 days). To accomplish this purpose we conducted a population-based, descriptive analysis of pediatric hospitalizations for children aged 1 to 12 years in California in 1985 and 1994 using hospital discharge data. We found that hospitalizations of longer than 7 days accounted for 10.8% of pediatric hospitalizations in 1985 (58.4% of pediatric hospital days) and 11.8% of hospitalizations in 1994 (50.4% of hospital days). Rates of long pediatric hospitalization decreased from 312.1/100,000 children in 1985 to 236.4/100,000 children in 1994. Rates fell for both sexes, in all racial/ ethnic groups, and among both preschool-age and school-age children. Common reasons for long hospitalizations in both 1985 and 1994 included lower-limb fractures, pneumonia, appendicitis, and malignancies. The rate of long hospitalization for mental disorders increased by 57% between 1985 and 1994, while the rate for injuries and poisoning decreased by 38%. In summary, long pediatric hospitalizations in 1985 and 1994 accounted for under 12% of all hospitalizations of children but for more than 50% of all hospital days. Although the overall rate of long pediatric hospitalizations decreased, rates for certain conditions, notably mental disorders, increased. As states continue to implement major health care changes, further study of conditions among children that account for a large proportion of hospital days is warranted.

Hospitalization for mental illness in adolescents: risk groups and impact on the health care system.

PURPOSE: To determine the extent and cost of hospitalizations for mental illness among adolescents and to identify differences in acute care hospital use by gender and between racial/ethnic groups. METHODS: Analysis of discharge data for adolescents, 10 to 19 years of age (n = 27,595), with a principal diagnosis of mental illness from acute care hospitals in California in 1994. Relative risks (RRs) were calculated by race/ethnicity and gender and stratified by race/ethnicity and payment source. RESULTS: Mental illness accounted for 14.8% of hospitalizations in this age group; the mean length of stay was 10.9 days. Total charges exceeded $300 million. Overall, adolescent boys had a slightly lower risk of hospitalization for mental illness than did adolescent girls (RR = 0.90, 95% confidence interval [CI] = 0.87, 0.92) but a higher risk for certain diagnoses. Overall, nonwhite adolescents had a lower risk of hospitalization for mental illness than did white adolescents: African-Americans (RR = 0.77, 95% CI = 0.74, 0.81), Latinos (RR = 0.32, 95% CI = 0.31, 0.33), and Asians/others (RR = 0.27, 95% CI = 0.26, 0.29). These differences remained significant after stratification by payment source. CONCLUSIONS: The risk of hospitalization for mental illness among adolescents varies by specific mental illness and by race/ethnicity. In light of the significant human and financial costs associated with hospitalization for mental illness, further research into the determinants of illness and the options for care is warranted.

Demographic characteristics in adult paternity for first births to adolescents under 15 years of age.

PURPOSE: To examine parental demographic characteristics by adult (> or = 20 years at baby's conception) and teenage (< 20 years at baby's conception) paternity in births to very young adolescents (< 15 years at baby's conception). METHODS: This was a population-based, retrospective cohort analysis of all 12,317 very young adolescent mothers residing in California with a first singleton live birth during 1993-1995. Risks for adult, compared to teenage, paternity were evaluated using multivariate logistic regression. RESULTS: Adult fathers, responsible for 26.7% of births to very young adolescents, were a mean of 8.8 years older than the mother. The risk factors for adult compared to adolescent paternity were as follows: father's educational attainment of at least 3 years below that considered adequate for his age [adjusted odds ratio (AOR) = 8.34], father's (AOR = 2.46) or mother's (AOR = 1.36) educational attainment 1-2 years below that considered adequate for their age, mother's birthplace outside the United States (AOR = 3.12), and father's Hispanic ethnicity (AOR = 1.60) or African-American race (AOR = 1.50). CONCLUSIONS: Adult fathers were responsible for over one quarter of the births in our study. Adolescent pregnancy prevention focusing on younger adolescents must programmatically address adult paternity. Variations in adult paternity patterns across cultural groups suggest that we need further study of the role that cultural beliefs and practices play in very young adolescent pregnancy.

PIP: This study examined parental demographic characteristics among persons aged over 20 years, under 20 years, and under 15 years at conception of the first birth in California. Data were obtained from California birth certificates in 1993, 1994, and 1995 and from the 1990 Census. The sample included 12,317 very young mothers of a total of 657,122 single first live births to California residents. The mean age of very young mothers was 13.7 years. Very young mothers tended to be in high school, Hispanic, and born in the US. The birth rate for mothers aged 10-14 years was 1.4/1000; 2.6/1000 for Hispanics, 3.0/1000 for African-Americans, and 0.3/1000 for Whites. Adult males were fathers of 24.3% of babies born to mothers aged 11-12 years. The mean age of fathers was 22.7 years. Adult males were fathers of 26.8% of babies born to mothers aged 13-14 years. Final multivariate models reveal that inadequate educational attainment was a risk factor for adult paternity in births to very young mothers. The risk for adult paternity increased as the father's education adequacy decreased. Race or ethnicity were lower risk factors than father's educational attainment. Very young adolescent mothers who were foreign born were very likely to be involved with an adult male. Adult fathers were an average of 8.8 years older than very young mothers. Adolescent pregnancy prevention programs need to target adult men.

Mental illness in elementary-school-aged children.

We conducted a retrospective analysis of 1992 hospital discharge data to determine the incidence of mental illness hospitalizations among elementary-school-aged children and to analyze differences in hospital use by selected population characteristics. We analyzed population-based records of hospitalizations of 6- to 12-year-olds (n = 4,460) with a principal diagnosis of mental illness and calculated relative risks (RRs) for hospitalization by sex, race/ethnicity, and payment source. Mental illnesses accounted for 8.1% of hospitalizations and 28.9% of hospital days for 6- to 12-year-olds. Hospital charges totaled $85 million. Boys had a higher risk of mental illness hospitalization than girls (RR 1.96; 95% confidence interval [CI] 1.84-2.08). Latino children had a lower risk than whites (RR 0.22; 95% CI 0.20-0.24), as did children in the "Asian/other" group (RR 0.12, 95% CI 0.10-0.15). Inpatient hospitalizations for mental illness have a major impact on hospital morbidity for elementary-school-age children. Boys are overrepresented and Latinos and Asians/others are underrepresented among mental illness hospitalizations. Clinical implications for these findings and barriers to the delivery of inpatient mental health care are discussed.

Characteristics of children having multiple Medicaid-paid asthma hospitalizations.

OBJECTIVES: We undertook this population-based study to describe the characteristics of poor children with multiple asthma hospitalizations and to discern if poor minority children have a greater risk for these events than poor white children. METHODS: We conducted a retrospective analysis of 1994 California hospital discharge data for asthma hospitalizations among 1 to 12-year-old Medicaid patients (N = 6844 discharges). Risk factors for multiple Medicaid asthma hospitalizations were calculated by using logistic regression procedures. RESULTS: In 1994, asthma hospitalizations accounted for 11.6% of Medicaid-funded hospitalizations for 1 to 12-year-olds in California. These hospitalizations had a mean length of 2.7 days and a mean hospital charge of $6532. After we controlled for source of admission and length of stay, African American children (OR, 1.93; 95% CI 1.49-2.49) and Latino children (OR, 1.34; 95% CI 1.04-1.72) had a higher risk of multiple Medicaid-paid hospitalizations for asthma than did white children. Adjusted odds ratios for multiple asthma hospitalizations were 1.35 (CI, 1.05-1.74) for children with emergency room admissions, and 1.16 (CI, 0.97-1.39) for children having hospital stays of at least 5 days duration. CONCLUSIONS: Among children with Medicaid-paid hospitalizations for asthma, the risk for multiple asthma hospitalizations within a year was greater among African Americans and Latinos than among whites. Programs attempting to decrease repeat hospitalizations for asthma may benefit by focusing on these populations.

Risk factors for adult paternity in births to adolescents.

OBJECTIVE: To examine the risk factors for adult (aged 20 years and older) paternity in births to teenagers (14-17 years of age). METHODS: This was a population-based, retrospective cohort analysis of 27,215 adolescent mothers residing in California who had a live singleton birth during 1993. Adjusted risks for adult paternity by paternal and maternal characteristics were derived from comparisons of adult-teen and teen-teen couples. RESULTS: Adult fathers, who were responsible for 49.2% of births to teenage mothers, were a mean of 6.4 years older than the mother. The most important risk factors for adult paternity were as follows: father's (odds ratio [OR] 5.19; 95% confidence interval [CI] 4.43, 6.08) or mother's (OR 1.33; 95% CI 1.14, 1.55) educational attainment of at least 3 years lower than expected for their age, two or more previous live births (OR 3.34; 95% CI 2.48, 4.53), mother's birthplace outside the United States (OR 2.33; 95% CI 2.11, 2.58), father's (OR 2.16; 95% CI 1.98, 2.36) or mother's (OR 1.28; 95% CI 1.15, 1.42) educational attainment 1-2 years lower than expected for their age, one previous live birth (OR 1.92; 95% CI 1.75, 2.12), and Asian (OR 1.29; 95% CI 1.04, 1.62) or African American race (OR 1.25; 95% CI 1.06, 1.46) of the father. CONCLUSIONS: Teenage pregnancy prevention programs must address adult paternity, which contributed to almost half of the births in our study. These programs should consider education adequacy, cultural beliefs and practices, previous live births, and race and ethnicity when designing programs to decrease the number of adults involved in teenage births.

Hospital use by pediatric patients: implications for change.

INTRODUCTION: We conducted an analysis of population-based records of hospitalizations for all children 1-12 years old in California in order to provide detailed descriptive diagnostic information on pediatric hospitalizations and to analyze differences in hospital use by population group. METHODS: We analyzed 1992 computerized hospital discharge data for all children ages 1-5 years (n = 76,611) and 6-12 years (n = 54,827) in California acute care hospitals. We looked at the major diagnoses resulting in hospitalization and the total cost and total length of hospital stay by diagnosis. Relative risks for hospitalization by race and gender were calculated with 95% confidence intervals. RESULTS: Discharges among children ages 1-5 years accounted for $746 million in hospital charges and 319,059 days of hospitalization while discharges among children ages 6-12 years accounted for $580 million and 310,912 hospital days. Asthma, injuries, pneumonia, gastroenteritis, and congenital disease accounted for 46% of hospitalizations in children between 1 and 5 years old. Injury, appendicitis, asthma, mental illness, and pneumonia accounted for 45% of hospitalizations in those between 6 and 12. The risk of hospitalization varied significantly by gender and race. CONCLUSIONS: Many pediatric hospitalizations are preventable, and further efforts are needed to address this problem through improved access to primary care and education. Of particular significance are the racial variations in risk of hospitalization due to asthma and mental illness.

Squamous cell carcinoma arising in lesions of discoid lupus erythematosus in black persons.

Squamous cell carcinoma developing in lesions of discoid lupus erythematosus is rare. This article describes two patients, one with a carcinoma of the scalp and one with carcinoma of the upper lip. A review of the literature on squamous cell carcionoma in black persons as well as squamous cell carcinoma of the upper lip is presented.