Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit

Summary Malnutrition involving protein deficiency, which commonly occurs in cancer patients receiving anthracycline treatment, is considered to be a risk factor for the development of cardiotoxicity. Protein deficiency has been shown to impair the metabolism of drugs such as theophylline and acetaminophen. If protein deficiency also impairs anthracycline metabolism, it could explain at least in part the enchanced anthracycline toxicity associated with malnutrition. We tested this idea by determining the effect of a low- protein, isocaloric diet on doxorubicin pharmacokinetics in rabbits. The animals were randomized into two groups for 8–12 weeks. Rabbits in group 1 received a low-protein (5%), isocaloric diet, whereas those in group 2 received a normal-protein (15%) diet. Both groups (group 1,n=15; group 2,n=14) were given 5 mg/kg doxorubicin by i.v. bolus. After doxorubicin injection, blood samples were obtained over the next 52 h for the measurement of doxorubicin and doxorubicinol plasma concentrations by high-performance liquid chromatography (HPLC) with fluorometric detection. The low-protein diet significantly decreased doxorubicin clearance (48±3 vs 59±4 ml min^–1 kg^–1;P<0.05), prolonged the terminal climination half-life (28±2 vs 22±2 h;P<0.05), and increased the area under the plasma concentration/time curve extrapolated to infinity (1722±122 vs 1405±71 ng h ml^–1;P<0.05) as compared with the values determined for rabbits fed the standard rabbit chow (15% protein). The volume of distribution for doxorubicin was not altered by the low-protein diet. In addition, in rabbits fed the the low-portein diet, the terminal elimination half-life of the alcohol metabolite, doxorubicinol was prolonged (52±5 vs 40±2 h;P<0.05). Thus, a low-protein diet causes a reduction in the ability of rabbits to eliminate doxorubicin and possibly its alcohol metabolite doxorubicinol. If a similar alteration in anthracycline pharmacokinetics occurs in malnourished cancer patients, this phenomenon may contribute to their increased risk of developing cardiotoxicity associated with anthracycline therapy.Supported by the Department of Veterans Affairs and the American Heart Foundation     

Dermatophyte infection in ichthyosis vulgaris.

A 31-year-old male who had been suffering from ichthyosis vulgaris developed hyperkeratosic lesions on the palms and soles and ungual alterations of both hands and feet. These lesions were resistant to topical corticosteroid and emollient cream treatments and were found to be caused by Trichophyton rubrum. Association of ichthyosis vulgaris and dermatophytosis--both very common disorders--is to our knowledge a very rare event.     

Recent advances of laparoscopic approach in adnexal torsion of premenarcheal girls

The adnexal torsion is an uncommon gynaecological emergency; however, it must be excluded in young girls in order to conserve their future ovarian function and fertility. The diagnosis of adnexal torsion is particularly difficult in girls before the menarche during which time the clinical examination is very delicate. We review the recent literature and laparoscopic advances in this domain and propose a management algorithm.     

Predictors of Paternal Versus Maternal Stress in Families of Children With Neural Tube Defects

This study examined the types of stress experienced by maternal and paternal caretakers of children with Neural Tube Defects (NTD) and examined child and family characteristics that correlated with stress. Participants were 71 two-parent families of a child with spina bifida. Parents completed the Parenting Stress Index-Short Form to measure types of stress. Additional measures were completed to investigate variables potentially related to reported stress. Fathers reported significantly higher levels of stress from “dysfunctional parent-child interaction.” Mothers' personal stress correlated with disability and medical characteristics of the child. Fathers reported more stress when the child had maladaptive behaviors and when experiencing fewer social supports and resources. Mothers and fathers coparenting a child with NTD have both common and unique stresses. It is important that both be included in parent support and education initiatives.     

A Retrospective Review of the Use and Safety of Droperidol in a Large, High-risk, Inner-city Emergency Department Patient Population

Droperidol (DROP) is used in the emergency department (ED) for sedation, analgesia, and its antiemetic effect. Its ED safety profile has not yet been reported in patients (pts). OBJECTIVES: To document the use of DROP in high-risk pts (those with head injury, alcohol or cocaine intoxication, and/or remote or recent seizures), and to determine the number of serious and minor adverse events (AEs)-seizures, hypotension, extrapyramidal side effects (EPSEs)-after DROP. METHODS: The ED database (EmSTAT) was queried to determine who received intramuscular or intravenous DROP in the ED in 1998; further chart review was done if the patient was considered high risk for or had experienced an AE. Multiple regression analysis using a random-effects model determined the significance of each variable in the occurrence of AEs. RESULTS: 2,468 patients (aged 20 months to 98 years; 112 < or =17 years; 141 > or =66 years) received DROP for agitation (n = 1,357), pain (1,135), anxiety (99), vomiting (173), or other reasons (50). There were 945 pts considered high risk; 933 charts were reviewed (DROP mean dose 4.1 +/- 2.0 mg); of these, 50 patient visits did not meet the criteria for high risk. There were 622 pts with head trauma (401 with alcohol use), including 47 with computed tomography (CT) scans positive for brain injury, 64 with cocaine use, and 197 with recent or remote seizures (137 with alcohol use). Minor AEs such as transient hypotension occurred in 96 pts after DROP (73 with alcohol use); 20 received intravenous fluids, while an additional 28 pts (8 with alcohol use) received rescue medications for EPSEs. Six possible serious AEs occurred in pts with serious comorbidities; 2 cases of respiratory depression, 3 post-DROP seizures, and 1 cardiac arrest (resuscitated) 11 hours after DROP in a cocaine-intoxicated pt (normal QT interval). There was no significant difference among high-risk groups in the occurrence of AEs. CONCLUSIONS: The vast majority of pts who received DROP in the ED did not experience an AE. A few serious AEs were noted following DROP in patients with serious comorbidities; it is not clear that DROP was causative.     

Alpha-interferon activated cytotoxic lymphocytes in hairy cell leukemia patients: evaluation of cytotoxic events

To further define the mechanisms responsible for the alpha-interferon (alpha-IFN) efficacy in the treatment of hairy cell leukemia (HCL), experiments were carried out to specify the cytotoxic events taking place following this type of therapy. Although an increased natural killer (NK) activity was demonstrable after alpha-IFN treatment, evidence has been provided that hairy cells were not specifically lysed either by fresh autologous/allogenic NK lymphocytes or by lymphokine activated killer (LAK) cells. This property could not be induced in vitro by alpha-IFN or by interleukin-2 (IL-2). Our data favour the hypothesis that the increase of NK cell activity observed following alpha-IFN therapy has not a direct antineoplastic effect but is likely to be of relevance for a non-specific enhancement of the host immune system. In alpha-IFN treated HCL this latter property may account for the better resistance to infections which usually represents the major cause of mortality in these patients.     

Infants thinner at birth exhibit smaller kidneys for their size in late gestation in a sample of fetuses with appropriate growth

Fetal ultrasound measurements were employed to investigate the relationship between weight and ponderal index at birth and kidney size during the second (23 weeks) and third (32 weeks) trimesters of pregnancy in a sample of 25 normally growing fetuses. Kidney volume and kidney volume / fetal weight ratio at 32 weeks are significantly and positively related to both weight and ponderal index at birth, controlling for sex, gestational age at birth, and day of ultrasound measurement. A second‐degree polynomial relationship approximates the predictability of kidney volume fetal weight ratio at 23 weeks to that at 32 weeks, demonstrating shifting growth rates in fetal organ and body growth relationships during midgestation. Sex and parental size are suggested as contributing to these patterns. Females have a surge in renal growth between 23 and 32 weeks to catch up to earlier growing males, and maternal weight significantly predicts incremental growth in kidney volume and the kidney volume / fetal weight ratio at 32 weeks of gestation. The observation that fetuses relatively thin at birth have relatively smaller kidneys for their size in late gestation suggests that the influence of maternal weight on birth outcome may act through organ growth. Am. J. Hum. Biol. 14:398–406, 2002. © 2002 Wiley‐Liss, Inc.     

Pituitary volume in pediatric obsessive-compulsive disorder.

BACKGROUND: Abnormalities in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). To our knowledge, however, no prior study has measured pituitary gland volume in OCD. METHODS: Volumetric magnetic resonance imaging studies were conducted in 31 psychotropic drug-na?ve children (10 boys, 21 girls) aged 8-17 years and 31 case-matched healthy comparison subjects. RESULTS: Pituitary volume was significantly smaller in patients with OCD as compared with healthy control subjects (11% smaller). Smaller pituitary volume in patients with OCD was associated with increased compulsive but not obsessive symptom severity. Boys with OCD had smaller pituitary gland volumes compared with control boys (20% smaller). No significant differences in pituitary volume were observed between girls with OCD and control girls. Boys with OCD had significantly smaller pituitary volumes than girls with OCD (31% smaller), whereas control boys also had smaller pituitary gland volumes compared with control girls (21% smaller). CONCLUSIONS: These findings provide new evidence of reduced pituitary volume in pediatric OCD that seems to be more prominent in male patients. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the LHPA axis in OCD.