Dimercaptosuccinic acid loading test for assessing mercury burden in healthy individuals.

BACKGROUND: Oral chelation tests have been used to try to define mercury toxicity in individuals with dental amalgams, who are suffering from a variety of non-specific symptoms. METHODS: Self-reported healthy individuals volunteered to undergo an oral chelation test using dimercaptosuccinic acid (DMSA) at a dose of 30 mg/kg body weight. Urinary mercury : creatinine ratios were measured pre-dose and 3 h post-dose. RESULTS: Urinary mercury : creatinine ratios were similar to levels previously reported in individuals with symptoms that could have been attributed to mercury toxicity. One volunteer suffered a serious reaction to DMSA. CONCLUSION: The oral chelation test using DMSA may lead to misleading diagnostic advice regarding potential mercury toxicity and can be associated with serious side effects.

A non-class I MHC intestinal epithelial surface glycoprotein, gp180, binds to CD8.

The activation of CD8(+) T cells by normal intestinal epithelial cells in antigen-specific or allogeneic mixed cell culture systems has significant implications for the modulation of mucosal immune responses due to the fact that these T cells appear to have regulatory rather than cytolytic activity. A 180-kDa glycoprotein (gp180) has been identified and shown to be important in CD8(+) T cell activation by intestinal epithelial cells. In this study, we examine, in further detail, the role that the CD8 molecule plays in this interaction. It has been previously shown that monoclonal antibodies against gp180 inhibited the activation of CD8-associated p56(lck) in T cells. Although indirectly suggested by these data, there was no evidence that the activation of this protein tyrosine kinase was a direct result of gp180 interacting with the CD8 molecule. In this study, we document that soluble gp180 is able to bind to CD8-Fc fusion proteins and is absorbed by human CD8 alpha but not CD4 transfected murine T cells and that this interaction is dependent upon carbohydrate on the gp180 molecule. Furthermore, the sites used for binding by gp180 are distinct from those used by the conventional CD8 ligand, class I MHC. Thus, gp180 appears to be a novel CD8 ligand that plays an important role in the activation of CD8-associated kinases and of CD8(+) T cells.

Goat-associated Q fever: a new disease in Newfoundland.

In the spring of 1999 in rural Newfoundland, abortions in goats were associated with illness in goat workers. An epidemiologic investigation and a serologic survey were conducted in April 1999 to determine the number of infections, nature of illness, and risk factors for infection. Thirty-seven percent of the outbreak cohort had antibody titers to phase II Coxiella burnetii antigen >1:64, suggesting recent infection. The predominant clinical manifestation of Q fever was an acute febrile illness. Independent risk factors for infection included contact with goat placenta, smoking tobacco, and eating cheese made from pasteurized goat milk. This outbreak raises questions about management of such outbreaks, interprovincial sale and movement of domestic ungulates, and the need for discussion between public health practitioners and the dairy industry on control of this highly infectious organism.

Expression of IL-10 receptors on epithelial cells from the murine small and large intestine.

The appearance of chronic intestinal inflammation in IL-10 knockout mice suggests IL-10 may inhibit adverse responses to luminal antigen. Moreover, this inflammation is associated with an increase in class II MHC molecule expression on intestinal epithelial cells. Thus, the role of IL-10 regulation in epithelial cell function was investigated. Using RT-PCR, it was shown that intestinal epithelial cells express mRNA for both subunits of the IL-10 receptor-signaling complex. In addition, biotinylated IL-10 was shown to bind to both cultured and freshly isolated intestinal epithelial cells prepared from the small or large intestine. This binding appeared specific as it was blocked by neutralizing antibodies to IL-10 but not the isotype control. Moreover, an excess of native IL-10 also inhibited the binding of radiolabeled IL-10. To evaluate whether IL-10 mediated any functions through this receptor, epithelial cells were cultured with IL-10 alone or with IFN-gamma plus IL-10. IL-10 alone had no detectable effects on epithelial cell growth or their expression of class II MHC molecules but it did antagonize the effect of IFN-gamma on the viability of cultured cells. In addition, IL-10 blocked the IFN-gamma-induced expression of class II MHC molecules on cultured epithelial cells. These results suggest that IL-10 binds to a specific receptor on intestinal epithelial cells and may regulate the contribution of epithelial cells to the inflammatory and immune response in the digestive tract.

Calcaneal osteotomy for the treatment of posterior tibial tendon dysfunction.

The surgical treatment of PTTD has been well-discussed in the literature. The calcaneal displacement osteotomy is a powerful, yet relatively easy, procedure that accomplishes a significant amount of frontal plane correction in the surgical treatment of PTTD. It can be performed as a straight medialization osteotomy for moderate hindfoot valgus, and must be performed with a resectional wedge in the treatment of large valgus angles. To achieve optimal correction, it must be coupled with procedures that address the triplanar nature of the deformity. When used in combination with other reconstructive procedures, it provides a valuable alternative to other more joint-destructive procedures.

The nonclassical class I molecule CD1d associates with the novel CD8 ligand gp180 on intestinal epithelial cells.

Previous studies have shown that normal intestinal epithelial cells (IECs) are able to selectively activate CD8(+) T cells with suppressor activity, inducing proliferation associated with the activation of both the CD8-associated kinase p56(lck) and the T cell receptor (TCR)-associated kinase p59(fyn). This process appears to relate in part to a 180-kDa IEC surface glycoprotein, gp180, which binds to CD8 and activates CD8-associated p56(lck). However, purified gp180 alone is unable to induce T cell proliferation and does not activate p59(fyn). Because the class Ib molecule CD1d is expressed by IECs and monoclonal antibodies (mAbs) against CD1d inhibit IEC-induced proliferation of CD8(+) T cells, co-immunoprecipitation and enzyme-linked immunosorbent assay studies were performed, which demonstrated an association of gp180 and CD1d on the IEC surface. Interestingly, the activation of p59(fyn) in IEC-T cell co-cultures was blocked by the anti-CD1d mAb D5 but not by the anti-gp180 mAb B9. Conversely, treatment of IECs with mAb B9 inhibited IEC-induced activation of p56(lck) but not p59(fyn). More directly, a human CD1d cDNA (FO-1 D5) transfectant was able to activate p59(fyn) but not p56(lck). These data suggest that the CD1d-gp180 complex on the surface of IECs can be recognized by the TCR-CD8 co-receptor, resulting in the activation of CD8(+) T cells.

On the calculation of a robust S-estimator of a covariance matrix.

An S-estimator of multivariate location and scale minimizes the determinant of the covariance matrix, subject to a constraint on the magnitudes of the corresponding Mahalanobis distances. The relationship between S-estimators and w-estimators of multivariate location and scale can be used to calculate robust estimates of covariance matrices. Elemental subsets of observations are generated to derive initial estimates of means and covariances, and the w-estimator equations are then iterated until convergence to obtain the S-estimates. An example shows that converging to a (local) minimum from the initial estimates from the elemental subsets is an effective way of determining the overall minimum. None of the estimates gained from the elemental samples is close to the final solution.

Physicians' liability for adverse drug reactions.

Although the Food and Drug Administration's spontaneous reporting system for adverse drug reactions has been collecting reports since 1960, the number of adverse drug reactions reported is low. One of the perceived deterrents to reporting adverse drug reactions is physicians' fear of involvement in litigation. We discuss the basis for physicians' liability and review the standard of care concept regarding physicians' liability associated with adverse drug reactions. Examination of the elements of a professional negligence case and "informed consent" shows what physicians can do to avoid malpractice related to adverse drug reactions.

Ethical issues in a drug information center.

The frequency and nature of ethical issues faced by pharmacists have not been well documented. To address these issues a retrospective study of the potential ethical problems encountered by pharmacists in a drug information center was conducted. Of the 744 calls received over a 13-month period, 50 raised ethical issues. Consumer calls were more likely to raise ethical issues than were health-provider calls. The calls mainly fell into five categories: drug identification, assessment of a physician's recommendations for consumers, conflict between callers' needs and legal or public-health considerations, therapeutic issues in the pharmacist-patient relationship, and paternalistic treatment of "difficult" callers. These questions raised ethical issues related to confidentiality, truth telling, and pharmacists' societal obligations. Pharmacists may confront an increased number of ethical issues as more drug information centers provide consumer services. Although there is no empirical evidence regarding pharmacists' ability to deal with ethical issues, there are reasons to believe that training in medical ethics will better equip pharmacists to recognize, analyze, and resolve ethical dilemmas.

Maternal grieving response after perinatal death.

The nature and incidence of psychological and related physical disturbances were investigated in 110 mothers who had lost a child in the perinatal period. The mothers were interviewed six to 36 months after their loss. The demographic characteristics, hospital experiences, effects of bereavement and perceived social support system of the women were assessed. A pathological bereavement outcome, which was defined as a marked deterioration in health and evidence of increased social adjustment problems, was identified in 21% of the women. A pathological bereavement outcome was found to be related to two main factors--a reported crisis during pregnancy and the perceived support of the husband and/or family. Whether the mother saw but did not hold her baby was also a factor. These results suggest that the loss of a baby may have at least as severe an effect on a woman as the death of her husband. The implication of these findings is that women who are at risk of a pathological outcome of bereavement may be identified soon after their loss.

Water sodium and blood pressure in rural school children.

Blood pressures were measured in 326 boys and 309 girls, 12 to 14 yr of age, who attended schools in six rural towns with water sodium levels ranging from 1.46 to 9.69 mmol/L. Although there were significant differences between mean blood pressure levels in children living in the six towns, they did not appear to result from differences in water sodium levels. Children who lived on farms and who drank low-sodium rain water did not have lower blood pressures than children who lived in the towns. The estimated intake of sodium from drinking water in the towns varied between 1.5 and 11.6 mmol/day and represented between 1.2% and 10.4% of the estimated daily sodium intake. No effect of water sodium level on urinary sodium excretion was found. Blood pressure levels showed significant positive relationships with pulse rate, body height and weight, Quetelet's index, mid-upperarm circumference, and triceps skinfold thickness. Diastolic blood pressures in girls were inversely related to the measure of physical activity. Control of these variables, where relevant, by covariance analysis did not uncover any relationship between water sodium level and blood pressure.

Summarizing dietary patterns using multivariate analysis.

Data on the frequency of consumption of 76 foods were collected from 142 native-born Australians of Australian or British parentage, 26 of Italian parentage and 140 Italian migrants to Australia. Clear separation of the three groups was achieved, using a few as 27 food items in a discriminant function analysis. Potatoes, cauliflower, pumpkin and salt were consumed more by Australians, while salad dressings and grapes were eaten more by Italians. Australian-Italians fell between the two groups, although they tended to be more like Italians. The discriminant score derived for each person was used as an overall food score and this was then related to the serum cholesterol level. There was no consistent relationship between food score and serum cholesterol level.

Apoplastic transport of ions in the motor organ of Samanea.

Turgor-mediated leaf movements of the legume Samanea saman are associated with the migration of K(+) and Cl(-) between opposing sides of the motor organs (pulvini). We have investigated the pathway of this ion migration by localizing K(+) and Cl(-) within the secondary pulvinus at various times during leaf movements. Ion distributions in freeze-dried cryosections of pulvini were determined by scanning electron microscopy/x-ray microanalysis. The results indicate that the apoplast is a major pathway for the migration of K(+) and Cl(-) within the pulvinus.

Vacuolar reorganization in the motor cells of Albizzia during leaf movement.

During the leaf movements of Albizzia julibrissin Durazzini, volume changes in the motor cells of the pulvinule (tertiary pulvinus) are closely correlated with a reversible reorganization of the vacuolar compartment. Motor cells have central vacuoles when expanded, but become multivacuolate during the time the cell volume decreases. The central vacuole reforms - apparently by fusion of small vacuoles - during motor-cell expansion. The volume changes of the vacuolar compartment account for all of the change in the size of the protoplast, while the cytoplasmic volume remains constant during the leaf movements.

Calcium and potassium in the motor organ of the sensitive plant: localization by ion microscopy.

The ion microscope was used to study potassium and calcium distributions in the main motor organ of Mimosa pudica L. The cortex of the motor organ has two cell types differing in location, structure, and ion distribution. Histochemical features portrayed in ion micrographs were plainly correlated with structures seen in the light and electron microscopes.