Fibroma (myxoma) molle in a hamster (Mesocricetus auratus).

An adult female Syrian hamster (Mesocricetus auratus) presented with a large, ulcerated lesion in its right cheek pouch; this wound interfered with the animal's ability to masticate. As a result, the hamster became inappetant and lethargic and lost about 25% of its original body weight within 6 to 9 weeks of presentation. The mass was surgically excised and submitted for histopathological evaluation. Microscopically, the mass was characterized as a neoplastic process partially encapsulated with fibrous connective tissue in the submucosa. Loosely arranged bundles of spindle to stellate cells with round to oval hyperchromatic nuclei and amphophilic cytoplasm were abundant. Some cells had multiple nucleoli, and some mitotic figures were observed. Special stains were used to definitively diagnose fibroma (myxoma) molle, a rare spontaneous neoplastic lesion in the hamster.

Analgesic responses to intrathecal morphine in relation to CSF concentrations of morphine-3,beta-glucuronide and morphine-6,beta-glucuronide.

This study was performed to determine whether variations in analgesic responses to intrathecal morphine could be explained by cerebrospinal fluid (CSF) concentrations of morphine metabolites. Twenty-four CSF samples were collected at the beginning, middle and end of treatment periods in seven cancer patients with pain of malignant origin. CSF concentrations of morphine-3,beta-glucuronide (M3G) and morphine-6,beta-glucuronide (M6G) metabolites were measured by gas chromatography/mass spectrometry. Analgesic responses to morphine were estimated concurrent with CSF collection using a visual analog scale representing percentages of pain relief. Effective analgesia was defined as > or = 75% pain relief. CSF concentration of M3G and M6G in the 24 samples were 722 +/- 116 ng/ml and 699 +/- 158 ng/ml, respectively. CSF samples were categorized into two groups: (1) those collected during effective analgesia (N=14), and (2) those collected during ineffective analgesia (N=10). M6G levels detected in group 1 samples (effective analgesia) were significantly greater than those found in group 2 samples (ineffective analgesia) (978 +/- 243 ng/ml vs 309 +/- 68 ng/ml, P<0.05). Intergroup differences in CSF M3G concentrations and M3G/M6G ratios were not significant. It is concluded that CSF M6G may be indicative of effectiveness of analgesia in cancer patients subjected to intrathecal morphine.

Carotenoids and retinoids: a review of research, clinical, and public health applications.

Traditionally, the carotenoids and retinoids have been regarded as dietary sources of vitamin A and have been evaluated regarding their respective physiologic roles in vision, growth, immune system integrity, and prevention of vitamin A deficiency. In the 1990s, however, vitamin A deficiency is no longer widespread in Western countries. Therefore, the role of carotenoids and retinoids is evolving to encompass treatment and prevention of conditions such as cancer and cardiovascular disease, which are prevalent in Western societies. This review summarizes current research concerning the therapeutic utility of vitamin A and its analogues and their roles in the prevention of cancer and cardiovascular disease.

Interpatient variability: genetic predisposition and other genetic factors.

Polymorphisms and other genetic factors related to enzymes metabolizing drugs and xenobiotic chemicals are well known. This article focuses on selected molecular mechanisms and introduces some of the clinical implications arising from genetically determined interpatient variability or expression in some of these enzymes. Selected are the polymorphic enzymes of cytochromes P-450 (CYP) as examples of phase I enzymes and methyl transferases, n-acetyl transferases, and glutathione-s-transferases as examples of phase II enzymes. The polymorphism surrounding arylhydrocarbon hydroxylase induction is briefly described. Phase I enzymatic reactions are predominantly oxidative, whereas phase II reactions often couple with the byproducts of phase I. Overall, in poor metabolizers, whether phase I or phase II, there is limited metabolism in most patients unless another major metabolic pathway involving other enzymes exists. Drug metabolism also depends on whether the parent compound is a prodrug that forms an active metabolite, and poor metabolizers under this condition will form only trace amounts of an active compound. Therefore, the clinical significance of genetic polymorphisms and other genetic factors may be related to substrate, metabolite, or the major elimination pathway.

The effect of caffeine on pregnancy outcome variables.

The American public consumes a wide array of caffeinated products as coffee, tea, chocolate, cola beverages, and caffeine-containing medication. Therefore, it seems of value to inform both the scientific community and the consumer about the potential effects of excessive caffeine consumption, particularly by pregnant women. The results of this literature review suggest that heavy caffeine use (> or = 300 mg per day) during pregnancy is associated with small reductions in infant birth weight that may be especially detrimental to premature or low-birth-weight infants. Some researchers also document an increased risk of spontaneous abortion associated with caffeine consumption prior to and during pregnancy. However, overwhelming evidence indicates that caffeine is not a human teratogen, and that caffeine appears to have no effect on preterm labor and delivery. More research is needed before unambiguous statements about the effects of caffeine on pregnancy outcome variables can be made.

Demographic profile, methodology, and biochemical correlates during the course of pregnancy.

This five-year prospective, observational study of urban women during their pregnancies was initiated in 1985 with the recruitment of women between the ages of 18 and 35 years in the prenatal clinics of Howard University Hospital and the District of Columbia Department of Human Services. The objective of the investigation was to characterize African American women by nutritional, biochemical, medical, sociocultural, psychological, lifestyle, and environmental parameters which could be used to formulate interventions to improve pregnancy outcomes. The women were all nulliparous, free of diabetes and abnormal hemoglobins, such as sickle cell disease, and no more than 28 weeks pregnant. During the early course of the study, it was apparent that 96% of the low income clinic patients had delivered infants of normal birth weight (> or = 2500 g), P = 0.001. Recruitment was then initiated at the District of Columbia General Hospital; women 16 and 17 years of age and at any gestational stage were included. This paper is the first in the series on African American women and their pregnancies. It will present the demographic characteristics of this regular cohort of 443 women who delivered live infants, the methodology used for biochemical, dietary, and psychosocial data sets, the mean values for infant gestational age, head circumference, body length, and birth weight from singleton births, and correlates of the mean values of biochemical variables for three trimesters of pregnancy with other biochemical parameters and those pregnancy outcomes.

Biochemical profile of African American women during three trimesters of pregnancy and at delivery.

The data presented are the results from a prospective observational study which was conducted to investigate the effects of nutrition and other related factors on the outcome of pregnancy in nulliparous African American women 16-35 years old. Fasting blood samples were collected from the women during the first, second and third trimesters of pregnancy. At delivery, both maternal and cord samples were collected. Biochemical variables such as, serum folate, vitamin B12, ascorbic acid, vitamin E, ferritin, selected minerals as well as complete blood count (CBC) and red cell folate were analyzed in the blood samples. The concentrations of hematocrit, hemoglobin, white blood cells, red blood cells and vitamin B12 were below the reference non-pregnant ranges throughout gestation. Maternal concentrations of folate and vitamin E increased sequentially with increased gestational age. Serum ferritin, during the third trimester, declined to 58% of the first trimester concentration. Maternal levels of ferritin at delivery were one third of the values found in the infant (cord) sample. Cord levels of folate, ascorbic acid and vitamin B12 were higher than the concentrations in the maternal delivery samples. The data suggest that among this group of pregnant women, major physiological changes, such as plasma volume expansion which alters blood chemistry and maternal to fetal transfer of nutrients, were similar to the findings of other investigators. In this population however, the findings for serum and whole blood folate are contrary to those reported by other researchers, and the sequential increase in the maternal concentration of the vitamin during pregnancy could be attributed to the use of vitamin supplements.

Relationships of serum illicit drug concentrations during pregnancy to maternal nutritional status.

Findings reported are for a subset of African American subjects, residing in the urban area of Washington, D. C., who participated in a Program Project designed to study nutrition, other factors, and the outcome of pregnancy. Fasting blood samples, drawn during each trimester of pregnancy and at delivery, were screened for concentrations of cocaine, phencyclidine (PCP) and marijuana. Since substance abusers are expected to consume inadequate diets, these samples were also analyzed for serum folate, vitamin B12, ferritin and ascorbic acid. Data for these biochemical variables were compared for subjects whose serum values for drugs were either above or below the drug screening threshold concentrations established by ADAMHA/NIDA. Pearson's correlations were used to determine relationships between pregnancy outcome variables and maternal serum drug concentrations. Blood samples drawn at delivery showed higher maternal: cord ratios (mean +/- SEM) for marijuana (3.3 +/- 2.2) and PCP (2.9 +/- 1.0) than for cocaine (1.0 +/- 0.2). The subjects whose serum values were above the ADAMHA/NIDA ranges for marijuana, PCP and cocaine had concentrations of folate and ferritin that were significantly less than those of subjects with lower serum drug levels (P < or = 0.05). High maternal serum concentrations of illicit drugs were accompanied by a significant increase in leukocyte count (P < or = 0.05). The level of maternal cocaine during the third trimester was inversely correlated with birthweight (r = -0.29; n = 52; P = 0.038) and head circumference (r = -0.28; n = 52; P = 0.047).(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal low level lead and pregnancy outcomes.

We examined the relationship between the concentrations of blood lead and pregnancy outcomes in a subset of 349 African American women who enrolled in the program project, "Nutrition, Other Factors, and the Outcome of Pregnancy." Vitamin-mineral supplement users had significantly higher serum levels of ascorbic acid and vitamin E. Also, in supplement users, there were significantly lower mean concentrations of maternal blood lead. Inverse correlations were found between maternal levels of lead and the antioxidant vitamins, vitamin E and ascorbic acid. In addition, significant Pearson's correlations were observed between maternal blood lead levels and the following variables: positive correlations with calcium, phosphorus, mean corpuscular volume; inverse correlations with gestational age, Ponderal Index, infant orientation, and hematologic values. In the total subset, the three trimester sample means for maternal blood lead concentrations were not significantly different for mothers of infants who weighed less than 2500 g (low birth weight) and those who were delivered infants who weighed 2500 g or more. Clinically, nutrition may play a role in the reduction of potentially adverse effects from lead during pregnancy, i.e. protection of the fetus against lead toxicity and/or free radical damage through the antioxidant actions of vitamin E and ascorbic acid. Even when maternal blood lead levels are within the so-called "safe" range, maternal/use of a vitamin supplement supplying vitamin E and ascorbic acid during pregnancy may offer protection.

Biological response modifiers and chemotherapeutic agents that alter interleukin 2 activities.

IL2 immunotherapy alone or with LAK cells represents a novel approach to the treatment of metastatic cancers. Similarly, other BRMs and classical chemotherapeutic drugs through their molecular effects on the components of the immune system reveal new and exciting prospects for the better use of these agents. Both approaches converge in that they restore balance among numerous components of the immune surveillance system. This review raises the possibility of improved protocols through the judicious use of these agents and stresses the need for further investigation of combined use of chemotherapy and immunotherapy.

The function of noradrenergic neurons in mediating antinociception induced by electrical stimulation of the locus coeruleus in two different sources of Sprague-Dawley rats.

Although noradrenergic neurons in the nucleus locus coeruleus are known to project to the spinal cord, these neurons appear to innervate different regions of the spinal cord in Sprague-Dawley rats obtained from two different vendors. Recent anatomical studies demonstrated that the noradrenergic neurons in the locus coeruleus in Sasco Sprague-Dawley rats primarily innervate the ventral horn, whereas Harlan Sprague-Dawley rats have coeruleospinal projections that terminate in the dorsal horn of the spinal cord. This report describes the results of behavioral experiments that were designed to determine the functional significance of these anatomical differences. Electrical stimulation of neurons in the locus coeruleus produced antinociception in both Harlan and Sasco rats. The antinociception in Harlan rats was readily reversed by intrathecal injection of yohimbine, a selective alpha 2-adrenoceptor antagonist, or by phentolamine, a non-selective alpha 2-adrenoceptor antagonist. In contrast, these antagonists did not alter the antinociception produced by locus coeruleus stimulation in Sasco rats. Finally, the alpha 2-antagonist, idazoxan, did not alter the antinociceptive effect of locus coeruleus stimulation in either group of rats. These observations indicate that coeruleospinal noradrenergic neurons in Harlan and Sasco Sprague-Dawley rats have different physiological functions. Thus, electrical stimulation of noradrenergic neurons in the locus coeruleus that innervate the spinal cord dorsal horn (Harlan rats) produces antinociception, but stimulation of coeruleospinal noradrenergic neurons that project to the ventral horn (Sasco rats) does not produce antinociception. It is likely that genetic differences between these outbred stocks of rats account for the fundamental differences in the projections of coeruleospinal neurons and their function in controlling nociception.

Ten milestone issues in AOTA history.

This paper identifies 10 professional questions that the author has labeled milestone issues in the history of the American Occupational Therapy Association. Subjects encompassed by these issues are medical control, certified occupational therapy assistants, licensure, proficiency testing, entry-level degrees, treatment media, maintenance of competency, whether occupational therapists serve patients or clients, professional autonomy, and the status of occupational therapy as a profession. Although this paper is primarily a factual record of events and discussions referenced in official publications, the reader will recognize the insertion of author commentary and opinion in several of the issues discussed.

Foward.

No abstract available for this article.

Inhibition of alpha-tocopherol and calcium calmodulin-stimulated phosphodiesterase activity in vitro by anthracyclines.

1. The inhibition of alpha-tocopherol and calmodulin-stimulated phosphodiesterase activities was investigated in vitro. 2. Anthracyclines--doxorubicin, daunorubicin and aclacinomycin--inhibited calcium calmodulin-stimulated cyclic 3',5'-AMP (cAMP) nucleotide phosphodiesterase (EC. 3.1.4-17) activity (IC50 = 33.00 +/- 3.50-36.50 +/- 2.75 mumol/l). The stimulation of this enzyme by alpha-tocopherol was also inhibited by doxorubicin (IC50 = 18.50 +/- 4.00 mumol/l). 3. The anthracycline-induced inhibition of the calcium calmodulin and alpha-tocopherol-stimulated phosphodiesterase activity was competitive with calmodulin and alpha-tocopherol respectively. Increasing the concentration of the substrate, cAMP or calcium ions did not attenuate the drug-induced inhibition. The basal activity of the enzyme was not inhibited by concentration of doxorubicin up to 50 mumol/l. 4. In vivo, single dose drug distribution studies of the fluorescence of doxorubicin indicate that in the heart after a cardiotoxic dose (20 mg/kg), myocardial concentrations were achieved which could cause 70-80% inhibition of this phosphodiesterase enzyme. 5. Inhibition of calmodulin function by anthracyclines via direct interaction with calmodulin may contribute significantly to the effects of anthracyclines, such as disturbance in calcium homeostasis as well as acute and chronic deleterious effects on the myocardium. The action of alpha-tocopherol to bind or complex anthracycline may in part contribute to its protection against anthracycline-induced membrane damage and cardiotoxicity.

Interaction of calmodulin with the particulate fraction of cardiac muscle.

Tritiated calmodulin (T-CM) was bound to the EGTA-treated particulate fraction of cardiac muscle in a calcium-dependent manner with half-maximal binding occurring between 0.8 to 1.2 microM calcium. Binding exhibited high specificity at an optimum pH of 7.4-7.6. An excess of parvalbumin and other globular proteins did not displace T-CM. The Kd for the interaction was 2.5 +/- 0.83 microM. Binding was trypsin-sensitive, inhibited by high ionic strength and was heat inactivated at a midpoint of 48 - 50 degrees C. Competitive displacement of T-CM occurred with unlabeled troponin C and calmodulin over the same concentration range. The first-order rate constant of T-CM dissociation was 3.27 min-1. Calcium-dependent binding of T-CM was inhibited equally by both mepacrine and trifluoperazine with 50 percent inhibition occurring at 70 microM.

A comparative study of the reproductive effects of methadone and benzo[a]pyrene in the pregnant and pseudopregnant rat.

Benzo[a]pyrene (BP; 50 mg/kg) or methadone (5 mg/kg) was given subcutaneously to pregnant rats at different stages of gestation. Both BP and methadone affected the reproductive performance of pregnant rats by significantly increasing the number of resorptions and fetal wastage, and by decreasing the fetal weight. The same dosage levels of BP and methadone were also given to pseudopregnant rats (PSP) with an induced decidual cell reaction (DCR) in an attempt to distinguish whether adverse effects occur in the maternal or fetal compartment or both. Since the hormonal requirements for DCR and implantation are similar and the anatomical, histological, cytological, time sequential changes as well as appearance of the vasculature system for DCR and decidua are indistinguishable, PSP with DCR is similar to pregnancy except for the lack of a fetal compartment. BP, in this PSP model, significantly reduced the uterine wet weight and cyclic nucleotide (cAMP) and cGMP) levels whereas methadone was without a detectable effect. Our findings then suggest that BP may exert its effects adversely on both the maternal and fetal compartments, whereas methadone may act primarily in the fetal compartment.