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Biomedical subjects

B Sachs

Publications and source records attributed to B Sachs.

At least 37 records · Page 2Linked to original sources
PubMed1999

Procainamide, a drug causing lupus, induces prostaglandin H synthase-2 and formation of T cell-sensitizing drug metabolites in mouse macrophages.

Procainamide (PA) may cause drug-induced lupus, and its reactive metabolites, hydroxylamine-PA (HAPA) and nitroso-PA, are held responsible for this. Here, we show that N-oxidation of PA to these metabolites can take place in macrophages and lead to formation of neoantigens that sensitize T cells. Murine peritoneal macrophages (PMvarphi), exposed to PA in vitro, generated neoantigens related to HAPA as indicated by (1) their capacity to elicit a specific recall response of HAPA-primed T cells in the adoptive transfer popliteal lymph node (PLN) assay and (2) the appearance of metabolite-bound protein in PA-pulsed PMvarphi, as determined by Western blot. Analysis of five phase I enzymes that might be responsible for HAPA formation by PMvarphi pointed to prostaglandin H synthase-2 (PGHS-2) as a likely candidate. Experimental evidence that PA can be oxidized to HAPA by PGHS was obtained by exposing PA to PGHS in vitro. The resulting metabolites were identified by mass spectral analysis and covalent protein binding in ELISA. In vitro, PA exposure of PMvarphi of slow acetylator A/J and fast acetylator C57BL/6 mice failed to show significant strain differences in enzyme mRNA expression, enzyme activities, or formation of HAPA-related neoantigens. By contrast, after long-term PA treatment in vivo only in slow acetylators the PMvarphi harbored HAPA-related neoantigens and T cells were sensitized to them. PMvarphi of fast acetylator C57BL/6 mice only contained HAPA-related neoantigens, and their T cells were only sensitized to them if, in addition to long-term PA treatment, their donors had received injections of phorbol myristate acetate (PMA), a known enhancer of oxidative enzymes in phagocytes. In conclusion, PA treatment leads to N-oxidation of PA by enzymes, in particular PGHS-2, present in antigen-presenting cells (APC) and, hence, to generation of neoantigens which sensitize T cells. The enhanced neoantigen formation and T cell sensitization seen in slow acetylators might be explained by their higher concentration of PA substrate that is available for extrahepatic N-oxidation in APC.

Animals↗
PubMed1999

Potential for abusive parenting by rural mothers with low-birth-weight children.

PURPOSE: To describe factors influencing the potential for abusive parenting by rural mothers of low-birth-weight children (< 2,500 gm). Low-birth-weight (LBW) children are at risk for child abuse. However, little is known about the added risks created for these children by rural residency. DESIGN: Data for this descriptive and exploratory study were collected using a cross-sectional design. A convenience sample of 48 rural mothers delivering LBW children participated in 1994. METHODS: In-home interviews were conducted using structured questionnaires to assess mothers' everyday stressors, depressive symptoms, social resources, and child abuse potential. FINDINGS: The prevalence of high depressive symptoms among the mothers was 54%. Higher everyday stressors and less functional social support predicted greater depressive symptoms. Everyday stressors had a direct effect on the mothers' potential for child abuse and an indirect effect via maternal depressive symptoms. CONCLUSIONS: Rural mothers of LBW children are at risk for abusive parenting. Health care providers should pay particular attention to the mental health of mothers living in rural, isolated areas. Assistance with mobilization of community resources, including social support and child care, may provide needed help for these mothers to improve parenting and thus child health outcomes.

Adolescent↗
PubMed1999

The physical health of rural mothers and their low birth weight children.

The purpose of this research was to examine the physical health of rural mothers and their low birth weight children (< 2,500 gm). The health of rural mothers is of concern because rural families have poorer health than urban ones, and as the primary caregiver for the low birth weight child, mother's health affects the child's care and potentially the child's health. In this cross-sectional, exploratory study, in-home interviews were conducted with 48 mothers between 2 weeks and 18 months after their children were discharged from their birth hospitalization. Mothers' physical health and their perceptions of their children's health were assessed. The mothers were more concerned about their children's health than their own (p = .0005). The concerns included uncertainty about the children's future health, growth, and development. Suggestions for community health care providers are addressed.

Adolescent↗
PubMed1998

Allergic and autoimmune reactions to xenobiotics: how do they arise?

Induction of allergic and autoimmune reactions by drugs and other chemicals constitutes a major public health problem. Elucidation of the underlying mechanisms might help improve diagnostic tools and therapeutic approaches. Here, Peter Griem and colleagues focus on several aspects of neoantigen formation by xenobiotics: metabolism of xenobiotics into reactive, haptenic metabolites; polymorphisms of metabolizing enzymes; induction of costimulatory signals; and sensitization of T cells.

Animals↗
PubMed1997

Parenting attitudes and behaviors of low-income single mothers with young children.

The purpose of this study was to explore parenting attitudes and behaviors of low-income single mothers with preschool-aged children. As part of a longitudinal study of the health of single-mother families, 44 unstructured and semistructured interviews were conducted over a 1-year period with a subsample of nine mothers. The mothers modelled desired behaviors and values, but held unrealistic expectations for child behaviors. They viewed their parenting responsibilities as overwhelming. The mothers perceived their children as unappreciative of the efforts required to maintain the family unit. Discipline was often punitive and directed toward aversive behaviors with a single child as the scapegoat for parenting frustrations. Implications for interventions are addressed.

Adult↗
PubMed1997

Lamotrigine-induced Stevens-Johnson syndrome: demonstration of specific lymphocyte reactivity in vitro.

The novel antiepileptic drug lamotrigine (LTG) is effective as an adjunctive medication in partial seizures. The main adverse effects of LTG are skin eruptions, occurring in 3-10% of the treated patients, but these are rarely severe. The risk of cutaneous side effects is increased in patients receiving sodium valproate comedication, probably by doubling the plasma half-life of LTG due to competition with hepatic glucuronidation. Conversely, the risk can be reduced by adding LTG in a lower dose. Here, we report a patient who developed Stevens-Johnson syndrome (SJS) 5 weeks after adding low-dose LTG comedication to sodium valproate. An LTG-induced pathogenesis of the SJS was considered likely by a positive lymphocyte transformation test to the drug. The patient showed maximal peripheral blood lymphocyte reactivity to 50 micrograms LTG/ml with a stimulation index of 4.7 but not to nontoxic concentrations of sodium valproate. Lymphocytes from untreated controls neither reacted to LTG nor to sodium valproate.

Adult↗
PubMed1997

Cutaneous adverse reaction to ciprofloxacin: demonstration of specific lymphocyte proliferation and cross-reactivity to ofloxacin in vitro.

Ciprofloxacin (CPFX) is a widely used fluoroquinolone antibiotic, inducing cutaneous adverse drug reactions in about 1 to 2% of the treated patients. Conclusive diagnosis of drug allergy, however, still remains a major problem in daily clinical practice. Here, we present 2 patients with drug allergy to CPFX. In both cases the clinical suspicion for CPFX as the causative agent was confirmed in vitro by means of the lymphocyte transformation test, whereas epicutaneous patch tests remained negative. In vivo, a small percentage of the drug is biotransformed to the three major metabolites desethylene-, sulfo- and oxociprofloxacin. Though structurally closely related to their mother compound, these metabolites failed to induce in vitro lymphocyte proliferation in both patients. On the other hand, in vitro crossreactivity to ofloxacin, another fluorinated quinolone, could be demonstrated, which to our knowledge has not previously been reported.

Aged↗
PubMed1996

The popliteal lymph node assay in mice: screening of drugs and other chemicals for immunotoxic hazard.

The popliteal lymph node assay (PLNA) in mice represents a predictive test for assessing the sensitizing (allergenic and autoimmunogenic) potential of drugs and low molecular weight chemicals. Measuring activation of the draining lymph node of the hind paw, the PLNA facilitates the detection and analysis of immunotoxic effects in a rapid and reproducible manner. An attractive feature of the PLNA is that it can be performed in combination with the routine toxicity testing required for new drugs. Thus, it is possible to investigate whether animals exposed by the oral, intravenous, or inhalative route have been sensitized to the test compound or a reactive metabolite of the test compound generated in vivo. PLNAs may be appropriate supplements to routine toxicity screening of chemicals, thereby enhancing chemical safety.

Administration, Inhalation↗
PubMed1995

Moving beyond survival: coping behaviours of low-income single mothers.

The purposes of this study were to describe the psychosocial and environmental contexts affecting the lives of low-income, single mothers and to explore their everyday coping strategies. Nine mothers of preschool children participated in multiple, unstructured and semi-structured in-home interviews. Traumatic childhood experiences including death of a parent and abuse contributed to the mothers' depression and to their coping strategies for survival. The women used creative economic survival strategies such as bartering to meet their families' basic needs. Social isolation, downward social comparison, conflict avoidance, and self-reliance were the emotional self-protective survival strategies used. Strategies to move up economically and emotionally related to the women's desire for a better life for themselves and their families.

Adaptation, Psychological↗
PubMed1993

Burst fractures of the fifth lumbar vertebra.

Eleven patients with burst fractures of the fifth lumbar vertebra were reviewed. The results of nonoperative treatment were compared with that of immediate surgery and stabilization with pedicle screw fixation. Five patients were treated nonoperatively and six patients underwent pedicle screw instrumentation and spinal fusion. Five patients had neurologic injury associated with their L5 burst fracture. Nonoperative treatment yielded excellent results in young patients with minimal canal compromise. Neurologic deficits responded more predictably to surgical decompression than to conservative treatment and internal fixation with pedicle screws restores spinal stability and allows early mobilization.

Adult↗
PubMed1993

Childhood physical and sexual abuse: their relationship with depressive symptoms in adulthood.

The purposes of this study were to determine the prevalence of childhood physical and sexual abuse among 206 low-income single mothers and to examine the relationship of childhood abuse to current maternal depressive symptoms. Severe physical abuse was reported by 36 percent of the women. The prevalence of sexual abuse was 22 percent; more than one-half of these women were violently abused. High depressive symptoms were reported by 51 percent of the mothers. Both severe physical abuse and sexual abuse in childhood were associated with high depressive symptoms. Women who experienced violent sexual abuse were almost four and one-half times more likely to report high depressive symptoms, compared to the women who were not sexually abused. These findings provide further evidence that childhood abuse may have long-term consequences for women's mental health.

Adolescent↗
PubMed1992

Clinical determinants of the racial disparity in very low birth weight.

BACKGROUND: Although the risk of very low birth weight (less than 1500 g) is more than twice as high among blacks as among whites in the United States, the clinical conditions associated with this disparity remain poorly explored. METHODS AND RESULTS: We reviewed the medical records of over 98 percent of all infants weighing 500 to 1499 g who were born in Boston during the period 1980 through 1985 (687 infants), in St. Louis in 1985 and 1986 (397 infants), and in two health districts in Mississippi in 1984 and 1985 (215 infants). The medical records of the infants' mothers were also reviewed. These data were linked to birth-certificate files. During the study periods, there were 49,196 live births in Boston, 16,232 in St. Louis, and 16,332 in the Mississippi districts. The relative risk of very low birth weight among black infants as compared with white infants ranged from 2.3 to 3.2 in the three areas. The higher proportion of black infants with very low birth weights was related to an elevated risk in their mothers of major conditions associated with very low birth weight, primarily chorioamnionitis or premature rupture of the amniotic membrane (associated with 38.0 percent of the excess proportion of black infants with very low birth weights [95 percent confidence interval, 31.3 to 45.4 percent]); idiopathic preterm labor (20.9 percent of the excess [95 percent confidence interval, 16.0 to 26.4 percent]); hypertensive disorders (12.3 percent [95 percent confidence interval, 8.6 to 16.6]); and hemorrhage (9.8 percent [95 percent confidence interval, 5.5 to 13.5]). CONCLUSIONS: The higher proportion of black infants with very low birth weights is associated with a greater frequency of all major maternal conditions precipitating delivery among black women. Reductions in the disparity in birth weight between blacks and whites are not likely to result from any single clinical intervention but, rather, from comprehensive preventive strategies.

Black or African American↗
PubMed1992

Plasma endothelin levels in preeclampsia: elevation and correlation with uric acid levels and renal impairment.

OBJECTIVE: The purpose of this study was to determine if endothelin levels are elevated in women with preeclampsia and if these levels correlated with other laboratory features of disease severity. STUDY DESIGN: Parameters were compared in four groups of women volunteers by means of analysis of variance: (1) 16 women with preeclamptic pregnancies, (2) 11 pregnant women without preeclampsia, of similar lengths of gestation, (3) six otherwise normal women with pregnancies at term or beyond (greater than 38 weeks), and (4) 22 normotensive young women. RESULTS: Endothelin levels were elevated in women with preeclampsia as compared with those of gestation-matched pregnant and nonpregnant controls (22.6 +/- 2.0 vs 12.0 +/- 1.0 vs 10.4 +/- 1.3 pmol/L, p less than 0.005, preeclampsia vs controls) and also were increased in late gestation (17.7 +/- 2.0 pmol/L). Endothelin correlated positively with plasma levels of uric acid (r = 0.698, p less than 0.005) and inversely with creatinine clearance (r = -0.659, p less than 0.05). CONCLUSION: Circulating endothelin levels are elevated in women with preeclampsia and correlate closely with serum uric acid levels and measures of renal dysfunction. These observations suggest that endothelin may contribute to renal vasoconstriction in preeclampsia.

Adult↗