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Biomedical subjects

G Weaver

Publications and source records attributed to G Weaver.

At least 19 recordsLinked to original sources

Increased osmolality of breast milk with therapeutic additives.

AIM: To evaluate the changes in the osmolality of expressed breast milk (EBM) after the addition of seven additives and four proprietary fortifiers commonly used during neonatal intensive care. METHODS: The osmolality of 5 ml EBM was measured with increasing doses of 6% NaCl, caffeine, sodium ironedetate, folic acid, and multivitamin drops. Sodium acid phosphate and chloral hydrate were added to 8 ml EBM, and the fortifiers were added to standard volumes of EBM. Dose-effect curves were plotted, and the volume of milk that must be added to the above additives to maintain osmolality below 400 mOsm/kg was calculated. RESULTS: The osmolality of the pure additives ranged from 242 to 951 mOsm/kg. There was a significant increase in the osmolality of EBM with increasing doses of all additives except caffeine. The osmolality of EBM with many additives in clinically used dosages potentially exceeded 400 mOsm/kg. The greatest increase occurred with sodium ironedetate syrup, where the osmolality of EBM increased to 951.57 (25.36) mOsm/kg. Proprietary fortifiers increased the osmolality of EBM to a maximum of 395 mOsm/kg. CONCLUSION: Routine additives can significantly increase the osmolality of EBM to levels that exceed current guidelines for premature infant feeding. A simple guide for clinical use is presented, which indicates the amount of milk required as diluent if hyperosmolality is to be avoided.

Dose-Response Relationship, Drug↗

Morphological transformation of C3H/M2 mouse fibroblasts by, and genotoxicity of, extracts of human milk.

Breast cancer may be initiated by environmental/dietary agents and human milk may act as an ex vivo indicator of in vivo exposure of mammary epithelial cells to genotoxins. Extracts of human milk from UK-resident women (n=7) were tested for their abilities to morphologically transform C3H/M2 mouse fibroblasts. Genotoxicities were assessed in the Salmonella typhimurium reverse-mutation assay in the presence of S9 using strains TA1538 and YG1019, and in metabolically-competent human MCL-5 cells with the micronucleus and with the alkaline single cell gel electrophoresis (comet) assays. Two of the seven extracts were inactive in the transformation assay both in the presence or absence of S9, two appeared to be equally transforming either in the presence or absence of S9, and two other extracts induced increased transformation frequencies in the presence of S9. A seventh extract, tested only in the absence of S9, was inactive. Extracts were either active or inactive in at least three of the four tests applied. Four extracts were active or inactive in all four tests. The results suggest that human milk could be used as a resource for investigations of the as-yet-unidentified transforming agents previously detected in mammary lipid.

Animals↗

Genotoxicity of human breast milk from different countries.

Dietary and/or environmental factors appear to play a key role in the international variations that exist in breast cancer incidence. The genotoxicity of breast milk extracts is being examined as a possible indicator of in vivo exposure of mammary epithelial cells to DNA-damaging agents. Breast milk samples were obtained from the UK (n = 32), a high risk country, and from Hong Kong (n = 10), India (n = 20) and Singapore (n = 20), countries of lower breast cancer incidence. The abilities of breast milk extracts to induce DNA damage detected as single-strand breaks (SSBs) in the alkaline Comet assay and to induce micronuclei in MCL-5 cells and mutations in Salmonella typhimurium YG1019 were investigated. In the Comet assay 18 of 32 (56%) UK samples induced significant increases in DNA SSBs compared with 2 of 10 (20%), 5 of 20 (25%) and 8 of 20 (40%) of the samples from Hong Kong, India and Singapore, respectively. The proportion of positive samples was significantly higher in the UK group than in the combined low breast cancer incidence group and significantly higher than in the Indian group (P < 0.05, Fisher's exact test). In the micronucleus assay 9 of 32 (28%) UK samples showed significant activity compared with 0 of 10 (0%), 2 of 20 (10%) and 3 of 20 (15%) of the samples from Hong Kong, India and Singapore, respectively. Extracts of all the aforementioned milk samples were also tested for bacterial mutagenicity. Nine of 32 (28%) UK samples induced significant activity with a dose-response effect. Although activity was detected in samples from the other countries, comparable dose-response data could not be obtained because of a lack of material. This pilot study suggests that genotoxic components occur more frequently in UK breast milk than in milk from some other countries with a lower incidence of cancer. More work is required to confirm these initial findings and to examine their relevance to variations in breast cancer incidence.

Comet Assay↗

Activation of genotoxins to DNA-damaging species in exfoliated breast milk cells.

Exfoliated cells, isolated from breast milk samples donated by UK-resident women (n=15), were incubated, either immediately or after culture for 7 days, with one of a series of genotoxins, either in the presence or absence of the DNA-repair inhibitors, hydroxyurea (HU), and cytosine arabinoside (ara-C). The numbers of DNA single-strand breaks induced were then assessed as comet tail length (CTL) (microm) using the alkaline single cell-gel electrophoresis ('Comet') assay; cell viability was measured by trypan blue exclusion. The heterocyclic aromatic amines (HAAs) (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (0.4 mM), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) (1.67 mM), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) (1.77 mM)), a polycyclic aromatic hydrocarbon (benzo[a]pyrene (B[a]P) (0.36 mM)), a nitro-polycyclic aromatic hydrocarbon (1-nitropyrene (1-NP) (1.84 mM)) and aromatic amines (o-toluidine (0.85 mM), p-chloroaniline (0. 71 mM)) each induced statistically significant (P<0.0001, Mann-Whitney test) increases in median CTLs in breast milk cells from all the donors examined when incubated (30 min, 37 degrees C) in the presence of HU/ara-C. In some cases, these compounds were also active in the absence of the repair inhibitors. There were marked variations in comet formation between donors and between genotoxins. Cell culture appeared to increase the epithelial cell proportion and cultured cells retained their ability to activate genotoxins. The results suggest that breast milk is a valuable source of human mammary cells for the study of the metabolic activation of possible carcinogens.

Biotransformation↗

Variables associated with adolescent alcohol use: a multiethnic comparison.

The authors examined the influence of sociodemographic variables on the frequency and intensity of alcohol use among a nationally representative sample of Black, Hispanic, and White adolescents who had participated in the 1991 National Household Survey on Drug Abuse (U.S. Department of Health and Human Services, 1993). The sample consisted of 8,756 U.S. adolescents aged 12 to 18 years. The authors found that (a) approximately 19% of the respondents had used alcohol in the last 30 days: (b) among the respondents who had used alcohol, 21% had consumed 1 or more drinks per drinking episode; and (c) there were important similarities as well as important differences in variables that promoted alcohol use among Black. Hispanic, and White adolescents.

Adolescent↗

DNA damage in human breast milk cells and its induction by 'early' and 'late' milk extracts.

Environmental and dietary factors are thought to be significant in breast cancer aetiology. The alkaline single-cell gel electrophoresis ('Comet') assay was used to examine breast milk cells for DNA damage and to measure the activity of extracts of the milk in causing such damage. UK-resident women were recruited as donors (n = 16) and provided 'early' ( approximately 4 weeks post-partum) and/or 'late' ( approximately 4 months post-partum) milk samples. Cells (79-94% viable, trypan blue exclusion) were either examined immediately for DNA damage or were cultured for 1 week prior to treatment with a breast milk extract. DNA damage in the form of single-strand breaks was quantified as comet tail length (CTL). Cell preparations examined immediately exhibited interindividual variation in median CTL (range 2.0-40.0 microm) with or without the DNA repair inhibitors hydroxyurea (HU) and cytosine arabinoside (ara-C). DNA damage decreased following culture, suggesting either DNA repair or death of DNA-damaged cells. Some donors' breast milk extracts induced DNA damage in their cultured cells and increases in median CTL were significantly greater with HU/ara-C (range 4.0-72.5 microm) than without (range 2.5-27.5 microm). Genotoxicity occurred without cytotoxicity (81-97% viability after treatment). Comparisons between cells and extracts from 'early' and 'late' milk samples did not support the idea of a progressive clearance of genotoxins from mammary lipid during lactation. Donors whose untreated cells contained the most DNA damage tended to yield genotoxic breast milk extracts. Cells isolated from milk activated the rodent mammary carcinogens o-toluidine and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The relevance of genotoxic exposures to breast cancer initiation requires further investigation.

Adult↗

Genotoxicity of human milk extracts and detection of DNA damage in exfoliated cells recovered from breast milk.

Genotoxic agents of environmental or dietary origin may play a role in breast cancer initiation. The ability of extracts of human milk to cause mutations in S. typhimurium TA1538 and YG1019 and to induce micronuclei and DNA strand breaks in MCL-5 cells was investigated. Twenty samples from different donors were analysed and of these, 6 were adjudged to produce positive mutagenic response in one or both bacterial strains. The same samples also induced significant micronucleus formation in MCL-5 cells. In the comet assay, 13/20 samples caused DNA strand breaks in MCL-5 cells. Viable exfoliated breast cells were recovered from fresh milk samples and the ability of milk extracts to cause DNA damage in these cells was demonstrated. The results show that human milk can contain components capable of causing genotoxic damage in test systems and in human breast cells, events that may be significant in the initiation of breast cancer

Breast↗

Genotoxicity of human milk extracts and detection of DNA damage in exfoliated cells recovered from breast milk.

Genotoxic agents of environmental or dietary origin may play a role in breast cancer initiation. The ability of extracts of human milk to cause mutations in S. typhimurium TA1538 and YG1019 and to induce micronuclei and DNA strand breaks in MCL-5 cells was investigated. Twenty samples from different donors were analysed and of these, 6 were adjudged to produce a positive mutagenic response in one or both bacterial strains. The same samples also induced significant micronucleus formation in MCL-5 cells. In the comet assay, 13/20 samples caused DNA strand breaks in MCL-5 cells. Viable exfoliated breast cells were recovered from fresh milk samples and the ability of milk extracts to cause DNA damage in these cells was demonstrated. The results show that human milk can contain components capable of causing genotoxic damage in test systems and in human breast cells, events that may be significant in the initiation of breast cancer.

Breast↗

Tough choices: women, abusive partners, and the ecology of decision-making.

In a qualitative study, 35 women who had lived with violent partners were interviewed regarding their experience making decisions about their relationships to their abusers. This paper explores their stories, integrating the common themes with reports from other studies. The insights of the women participating in this and other research support an ecological understanding of the tough choices they face--a framework which respects the role of environmental factors (demands and resources) in helping or constraining choices at the same time as it recognizes the importance of powerful mediating factors (beliefs, values, and a sense of personal efficacy).

Adult↗

Inoculation herpes simplex virus infections in patients with AIDS: unusual appearance and location of lesions.

Two patients with AIDS developed protracted infection due to autoinoculation of herpes simplex virus in the great toe and the external ear, respectively, both unusual areas for inoculation. The appearances of the lesions were also unusual; severe hyperkeratosis was noted in both cases and a mass lesion in the external ear in one case. Both patients' conditions responded to acyclovir, although one patient required amputation of a digit due to intractable pain. In each case, the diagnosis was delayed despite the presence of mucocutaneous lesions, resulting in inappropriate treatment and prolonged discomfort. Inoculation disease due to herpes simplex virus should be suspected in patients with AIDS who have unusual skin lesions, particularly if oral and/or perianal lesions are also present.

AIDS-Related Opportunistic Infections↗

Furazolidone in turkey tissues following a 14-day feeding trial.

Feed supplemented with furazolidone was fed to turkeys on a research farm near Modesto, CA. The birds fed furazolidone-medicated feed were housed in isolated pens in a manner to prevent any cross contamination from an adjoining treatment. Furazolidone-medicated feed was supplied to the ration for 14 days prior to withdrawal with two exceptions; the controls were not fed medicated feed, and a 400 g/ton treatment was fed for 24 hr prior to processing. Treatments, representing different withdrawal periods, ranged from 0 to 21 days. Two 400 g/ton treatments with 0-day withdrawal periods were included in the study. One of these treatments involved a 14-day medicated feeding period while the other was for 24 hr. All other treatments were fed medicated feed at the rate of 200 g/ton. Tissue samples from the processed birds included skin, fat, liver, kidney, as well as breast and thigh muscle. No detectable residues were found in any of the liver, kidney, fat, or muscle tissues at any of the withdrawal periods including the 0-day withdrawal groups. Skin tissues contained detectable furazolidone residues only in the 0-day withdrawal treatments, and even these levels were below the 2 ppb level.

Administration, Oral↗

Electroconvulsive treatment of depression associated with neurosyphilis.

The authors describe a 67-year-old woman with nontabetic parenchymatous neurosyphilis associated with an affective disorder. It was not possible clinically to distinguish the relative contributions of psychiatric and neurologic etiologies to the patient's depressive and delusional symptoms. ECT proved effective for this patient, who might have otherwise been considered a treatment failure. The authors argue that the signs and symptoms of severe affective disorder should be treated if the presumed physical illness does not respond to therapy.

Aged↗

Effects of dietary zearalenone on finishing broiler chickens and young turkey poults.

A total of 168 broiler chickens (6 to 9 weeks of age) and 192 turkey poults (3-1/2 to 6-1/2 weeks of age) were fed purified zearalenone at levels of 0 (control), 10, 25 (turkeys only), 50, 100, 200, 400, and 800 mg/kg diet for a 3 week period to evaluate its toxicity. Dietary zearalenone had no effect on body weight gain, feed consumption, weights of liver, heart, spleen, and bursa of Fabricius, serum calcium, phosphorus, alkaline phosphatase, total protein and cholesterol, hematocrit, hemoglobin, red blood cell count, white blood cell count, and differential leukocyte count in both chickens and turkeys. Male broiler comb and testes weights were reduced by high levels of zearalenone. Female comb weight, broiler oviduct weight, and turkey testes and ovaries were unaffected by zearalenone. Histopathological examination of tissues revealed no change due to zearalenone. Male turkeys fed 400 and 800 mg/kg zearalenone had increased development of dewlaps and caruncles and exhibited considerable strutting behavior. Muscle and fat tissue from broilers fed 800 mg/kg zearalenone had no detectable estrogenic activity as measured by mouse uterine bioassay. These studies indicate that the effects of dietary zearalenone on finishing broilers and young growing turkey poults are minimal.

Animals↗

Effect of dietary zearalenone on reproduction of chickens.

Variable quantities of zearalenone (0, 10, 25, 50, 100, 200, 400, or 800 mg/kg diet) were incorporated into a practical laying hen diet and fed to 30-week-old White Leghorn females in egg production. During the 3 week pretest and 8 week experimental periods hens were inseminated weekly with .05 ml of pooled semen from males fed normal diets. Zearalenone was without effect on egg production, egg size, feed consumption, change in body weight, fertility, hatchability of fertile eggs, growth of progeny to 3 weeks of age, comb, weight, oviduct weight, heart weight, liver weight, spleen weight, egg shell thickness, Haugh units, blood hematology, serum calcium, serum inorganic phosphorus, and serum alkaline phosphatase. Zearalenone above 50 mg/kg of diet caused reduced serum cholesterol. In a reciprocal study, adult male New Hampshire chickens were fed diets containing 0, 100, or 800 mg/kg zearalenone for an 8 week period. Semen was collected and inseminated into White Leghorn females fed normal diets. Zearalenone was without effect on fertility or hatch of fertile eggs resulting from matings of these males. Zearalenone resulted in reduced serum inorganic phosphorus, serum cholesterol, and serum alkaline phosphatase in males. Histological examination of a number of tissues in both males and females revealed no changes due to zearalenone feeding. It is concluded that zearalenone up to 800 mg/kg of diet is without effect on reproductive performance of mature chickens.

Animal Feed↗