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Maternal and child health in China.

China has made great progress in improving the health of women and children over the past two generations. The success has been attributed to improved living standards, public health measures, and good access to health services. Although overall infant and maternal mortality rates are relatively low there are large differences in patterns of mortality between urban and rural areas. The Chinese have developed a hierarchical network of maternal and child health services, with each level taking a supervisory and teaching role for the level below it. Maternal and child health in China came to international attention in 1995 with the promulgation of the maternal and child health law. In China this was seen as a means of prioritising resources and improving the quality of services, but in the West it was widely described as a law on eugenics.

Child↗

A case for justified non-voluntary active euthanasia: exploring the ethics of the Groningen Protocol.

One of the most recent controversies to arise in the field of bioethics concerns the ethics for the Groningen Protocol: the guidelines proposed by the Groningen Academic Hospital in The Netherlands, which would permit doctors to actively euthanise terminally ill infants who are suffering. The Groningen Protocol has been met with an intense amount of criticism, some even calling it a relapse into a Hitleresque style of eugenics, where people with disabilities are killed solely because of their handicaps. The purpose of this paper is threefold. First, the paper will attempt to disabuse readers of this erroneous understanding of the Groningen Protocol by showing how such a policy does not aim at making quality-of-life judgements, given that it restricts euthanasia to suffering and terminally ill infants. Second, the paper illustrates that what the Groningen Protocol proposes to do is both ethical and also the most humane alternative for these suffering and dying infants. Lastly, responses are given to some of the worries expressed by ethicists on the practice of any type of non-voluntary active euthanasia.

Attitude to Health↗

The repertoire of human efforts to avoid sexually transmissible diseases: past and present. Part 1: Strategies used before or instead of sex.

BACKGROUND/OBJECTIVE: Despite the focus by public health programmes on condoms, chastity, or monogamy, people use a much wider variety of strategies to minimise their personal risk of sexually transmissible disease (STD). The objective of this study was to compile a comprehensive list of personal and societal STD avoidance strategies. METHODS: Data from clinical and research observations, computer searches, and historical texts were pooled. RESULTS: In addition to discriminating between potential sexual partners, a variety of behaviours before or instead of sex were identified that have been perceived to alter STD risk. Traditional STD avoidance strategies were often poorly documented and difficult to disentangle from other drives such as the maintenance of social order, paternity guarantee, and eugenics. They also varied in popularity in time and place. Some examples were displacement activities such as masturbation or exercise, circumcision, infibulation, shaving, vaccination, or requiring partners to be tested for infection. Social and moral forces typically discourage non-marital sex, and this affects most people most of the time but few people all of the time. CONCLUSION: The full spectrum of STD avoidance strategies warrants further study because some are ubiquitous across cultures and because they have the potential to complement or undermine safer sex programmes. Because of their greater acceptability, some less efficacious strategies may have greater public health importance than less popular but more efficacious strategies such as condoms.

Female↗

Imaging transgenic animals.

Transgenic and eugenic animals as small as 30 g can be studied non-invasively by radionuclides with resolutions of 1-2 mm, by MRI with resolution of 100 microns and by light fluorescence and bioluminescence with high sensitivities. The technologies of radionuclide emission, magnetic resonance imaging, magnetic resonance spectroscopy, optical tomography, optical fluorescence and optical bioluminescence are currently being applied to small-animal studies. These technologies and examples of their applications are reviewed in this chapter.

Animals↗

Moral and policy issues in long-acting contraception.

The advent of reversible long-acting contraceptives-IUDs, injectables and implants-has provided women throughout the world with valuable new fertility regulation options. These highly effective methods, together with male and female sterilization, have proven to be enormously popular and are now used by the majority of women and men who are currently contracepting worldwide. Despite their remarkable popularity, long-acting contraceptives have engendered considerable controversy. Political, ethical, and safety questions have emerged, stemming from the ways in which these contraceptives have been developed and used over the course of this century. At the heart of the concern is the issue of reproductive rights and freedom. This paper reviews the history of the development of long-acting contraceptives, including the prospect of new methods that will likely emerge from ongoing research and development. It also examines the history, in the United States and in developing countries, of the use and abuse of long-acting methods, including sterilization, in the context of eugenics and population control policies. It then describes a new paradigm of reproductive health and rights that has emerged from the International Conference on Population Development in Cairo, and which offers an enlightened approach to future policies and programs. In light of the wide variety of ways in which long-acting contraceptives have been provided, the paper examines the rights and responsibilities of governments, family planning providers, and individuals. An ethical framework for the use of long-acting methods is discussed, and public policies for the future are proposed.

Contraception↗

The life and death of laboratory teaching of medical physiology: a personal narrative. Part II.

Part II of this essay describes the author's participation in the laboratory course instituted by Eugene Landis at Harvard in 1943, a course that drew heavily on Thomas Lewis's example. He describes in detail his own methods of laboratory teaching at Utah and Michigan when, as department chair, he had the responsibility for organizing courses in physiology for medical students. In conclusion, the author laments the curtailment and eventual abolition of laboratory teaching in the 1970s that resulted from curriculum reform, student revolt, and faculty indifference.

Animals↗

OMP gene deletion results in an alteration in odorant-induced mucosal activity patterns.

Previous behavioral work, using a complex five-odorant identification task, demonstrated that olfactory marker protein (OMP) is critically involved in odor processing to the extent that its loss results in an alteration in odorant quality perception. Exactly how the lack of OMP exerts its influence on the perception of odorant quality is unknown. However, there is considerable neurophysiological evidence that different odorants produce different spatiotemporal patterns of neural activity at the level of the mucosa and that these patterns predict the psychophysically determined perceptual relationship among odorants. In this respect, OMP gene deletion is known to result in a constellation of physiologic defects (i.e., marked reduction in the electroolfactogram (EOG) and altered response and recovery kinetics) that would be expected to alter the odorant-induced spatiotemporal activity patterns that are characteristic of different odorants. This, in turn, would be expected to alter the spatiotemporal patterning of information that results from the mucosal projection onto the bulb, thereby changing odorant quality perception. To test the hypothesis that odorant-induced mucosal activity patterns are altered in mice lacking the gene for OMP, we optically recorded the fluorescent changes in response to odorant stimulation from both the septum and turbinates of both OMP-null and control mice using a voltage-sensitive dye (di-4-ANEPPS Molecular Probes, Eugene, OR) and a Dalsa 120 x 120, 12-bit CCD camera. To maintain continuity with the previous behavioral work, the odorants 2-propanol, citral, carvone, ethylacetoacetate, and propyl acetate were again used. Each odorant was randomly presented to each mucosal surface in a Latin-Square design. The results of this study demonstrated that, for both mouse strains, there do indeed exist different spatiotemporal activity patterns for different odorants. More importantly, however, these patterns significantly differed between OMP-null and control mice. That is, although the general regions of characteristic activity for different odorants were the same in both mouse strains, the patterns in the null animals were degraded relative to controls. These data suggest therefore that the alterations in mucosal activity may serve as the substrate for the behaviorally observed changes in odorant quality perception in the null mutant.

Animals↗

Genetic predictive testing for bowel cancer predisposition: the impact on the individual.

When considering the impact of a genetic diagnosis of hereditary predisposition to colon cancer, there are many similarities to other predictive genetic tests, but also many differences. The development and availability of such genetic diagnoses, and the concept of testing being linked to effective prevention, have advanced rapidly, opening up not only unique opportunities but also unique psychosocial situations for the affected families-and unusual ethical issues for the professional. Compared to a diagnosis of sporadic colorectal cancer for a patient, hereditary colorectal cancer requires an understanding of genetics, heredity, and the attendant mathematics of risk calculation, but, most importantly, there must be a belief that it is possible to remain healthy whilst having an increased risk. This paper outlines the possible impact of a genetic diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP) on both the individual and the family and concludes that genetic testing should be accompanied by genetic counseling. Relevant ethical issues are also introduced, with the opinion presented suggesting that if primary considerations are always for the individual rather than the family or society, then unethical or eugenic decisions are likely to be avoided.

Adenomatous Polyposis Coli↗

Gene therapy.

Severe genetic disorders are potentially correctable by the addition of a normal gene into tissues. Although the technical problems involving integration, stable expression, and insertional damage to the treated cell are not yet fully solved, enough scientific progress has already been made to consider somatic cell gene therapy acceptable from both the ethical and scientific viewpoints. The resolutions to problems evolving from somatic cell gene therapy will help to overcome the technical difficulties encountered presently with germ line gene manipulation. This procedure would then become morally permissible as it will cause, in time, a reduction in the pool of abnormal genes in the population. Enhancement genetic engineering is technically feasible but morally unacceptable. Eugenic genetic engineering is not technically possible or ethically permissible in the foreseeable future.

Ethics, Medical↗

[Room with a view for the "daughters of pain": 1828 was the beginning of new obstetrics in Erlangen].

The roots of clinical obstetrics at the University of Erlangen go back as far as the end of the 18th century. In 1796, Christian Friedrich Deutsch (1768-1843) was appointed as the first university teacher solely responsible for obstetrics. At the same time, he was also vehemently committed to the creation of a clinical institution for the purpose of training in obstetrics. For several reasons, the opening of a maternity home in a converted private house on the outskirts of town did not take place until 1828 under the leadership of Anton Bayer (1791-1832). In 1854/55, it was possible to move into a new building situated directly next to the university hospital; this new building was planned by Eugen Rosshirt (1798-1872). The increasing number of births and students as well as the introduction of gynecology finally led to the establishment, in 1878, of the first gynecological hospital in the sense understood by us today. The hospital was designed by Karl Schröder (1838-1887) who was the first Erlangen teacher of obstetrics to complete his habilitation in this field and probably has to be considered as the founder of the science of obstetrics at the University of Erlangen.

Female↗

Circulation Research: origin and early years.

Circulation Research, first published in 1953, was created by the American Heart Association as "the authoritative new journal for investigators of the basic sciences as they apply to the heart and circulation." This review of the early years of the journal highlights the contributions of the first four Editors: Carl J. Wiggers, Carl F. Schmidt, Eugene M. Landis, and Julius H. Comroe, Jr. The success of Circulation Research is seen not only in the high quality of the articles published in its pages but also in the remarkable improvements in prevention and treatment of cardiovascular disease that have occurred over the past half century.

American Heart Association↗

Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca.

PURPOSE: Neurturin has been identified as a neurotrophic factor for parasympathetic neurons. Neurturin-deficient (NRTN(-/-)) mice have defective parasympathetic innervation of their lacrimal glands. This study was conducted to evaluate tear function and ocular surface phenotype in NRTN(-/-) mice. METHODS: Determined by tail genomic DNA PCR, 25 NRTN(-/-) mice and 17 neurturin-normal (NRTN(+/+)) mice aged 6 weeks to 4 months were evaluated. Aqueous tear production, tear fluorescein clearance and corneal sensation were serially measured. Corneal permeability to AlexaFluor dextran (AFD; Molecular Probes, Eugene, OR) was measured by a fluorometric assay at 485 nm excitation and 530 nm emission. Histology was evaluated in PAS-stained sections. Mucin and HLA class II (IA) antigen were assessed by immunofluorescent staining. Tear IL-1beta was measured by ELISA, and tear matrix metalloproteinase (MMP)-9 by zymography. Gene expression in the corneal epithelia was analyzed by semiquantitative RT-PCR. RESULTS: In comparison to that in age-matched NRTN(+/+) mice, aqueous tear production, tear fluorescein clearance, and corneal sensation were significantly reduced in NRTN(-/-) mice, whereas corneal permeability to AFD was significantly increased. Immunoreactive MUC-4 and -5AC mucin and goblet cell density (P < 0.001) in the conjunctiva of NRTN(-/-) mice were lower than in NRTN(+/+) mice. The expression of MUC-1 and -4 mRNA by the corneal epithelium was reduced in NRTN(-/-) mice. There were a significantly greater number of IA antigen-positive conjunctival epithelial cells in NRTN(-/-) mice than NRTN(+/+) mice. Tear fluid IL-1beta and MMP-9 concentrations and the expression of IL-1beta, TNF-alpha, macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), and MMP-9 mRNA by the corneal epithelia were significantly increased in NRTN(-/-) mice, compared with NRTN(+/+) mice. CONCLUSIONS: Neurturin-deficient mice show phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca. This model supports the importance of a functional ocular surface-central nervous system-lacrimal gland sensory-autonomic neural network in maintaining ocular surface health and homeostasis.

Animals↗

Modulation of corneal epithelial cell functions by the neutrophil-derived inflammatory mediator CAP37.

PURPOSE: To investigate the effect of CAP37, an inflammatory mediator in neutrophils, on three important events in corneal wound healing: proliferation, migration, and adhesion. METHODS: Immortalized human corneal epithelial cells (HCEC) were treated with CAP37, and its effects on migration and proliferation were measured using the modified Boyden chemotaxis chamber and the proliferation assays (CyQUANT; Molecular Probes, Eugene, OR), respectively. Effects on adhesion were determined by measuring upregulation of adhesion molecules belonging to the selectin, integrin, and immunoglobulin superfamily using RT-PCR and flow cytometry. RESULTS: CAP37 promoted proliferation of HCEC in a time- and dose-dependent fashion. CAP37 was maximally chemotactic for HCEC over a range of 1.3 x 10(-8) to 5.2 x 10(-8) M. CAP37 upregulated intercellular adhesion molecule (ICAM)-1, platelet endothelial cell adhesion molecule (PECAM)-1, and integrin molecules alpha3 (CD49c) and beta1 (CD29). Data on migration and ICAM-1 and PECAM-1 upregulation were corroborated using primary human corneal epithelial cells. CONCLUSIONS: CAP37 modulated corneal epithelial cell proliferation and migration and upregulated adhesion molecules involved in leukocyte-epithelial and epithelial-extracellular matrix interactions.

Antimicrobial Cationic Peptides↗

Kainic acid-mediated upregulation of matrix metalloproteinase-9 promotes retinal degeneration.

PURPOSE: Excitotoxicity has been proposed to play a pivotal role in retinal damage, but the mechanisms that underlie retinal damage are not clearly understood. In this study, the role of matrix metalloproteinases in excitotoxin-mediated retinal damage was investigated. METHODS: KA, CNQX (6-cyano-7-nitroquinoxaline-2,3,-dione), NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline), MK801, or PBS was injected into the vitreous of CD-1 mice. MMP expression in the retina was analyzed by zymography, Western blot, and immunohistochemistry. Retinal ganglion cells (RGCs) were retrogradely labeled with aminostilbamidine methanesulfonate (Molecular Probes, Eugene, OR), and loss of fluorescently labeled RGCs in retinal flatmounts was quantified. Apoptotic cell death was assessed by TUNEL staining. Astrocyte activation was determined by immunohistochemistry, and laminin decrease was determined by immunohistochemistry and Western blot analysis. RESULTS: Intravitreal injection of KA caused time- and dose-related MMP-9 upregulation in the retina. Increased MMP-9 activity and protein levels were associated with activation of astrocytes. Astrocyte-associated MMP-9 correlated with a decrease in laminin immunoreactivity in the ganglion cell layer and significant loss of retinal ganglion cells. KA-mediated upregulation of MMP-9 activity was associated with apoptosis of cells in the ganglion cell layer as early as 6 hours after injection, followed by apoptosis in cells in the inner nuclear layer by day 1. Intravitreal injection of the non-NMDA receptor antagonists, CNQX and NBQX decreased KA-induced MMP-9 activity and protein levels in the retina and attenuated retinal degeneration, whereas the NMDA receptor antagonist MK801 failed to offer protection. Further, a synthetic MMP inhibitor GM6001 decreased KA-mediated MMP-9 activity and offered significant protection against ganglion cell loss in the retina. CONCLUSIONS: These results indicate that KA-mediated upregulation of MMP-9 activity promotes retinal degeneration and suggest that inhibition of KA-mediated MMP activity may offer protection against excitotoxin-induced retinal damage.

Animals↗

(R)-alpha-lipoic acid protects retinal pigment epithelial cells from oxidative damage.

PURPOSE: To determine whether (R)-alpha-lipoic acid (LA) protects cultured human fetal retinal pigment epithelial (hfRPE) cells against oxidative injury and identify the pathways that may mediate protection. METHODS: Cultured hfRPE cells were pretreated with various concentrations of LA for 14 to 16 hours followed by treatment with a chemical oxidant, tert-butylhydroperoxide (t-BuOOH; 0.8 mM, 3 hours). Reactive oxygen species (ROS) production and cell viability were measured using H(2)DCF and MTT assays, respectively. RPE cells were evaluated with fluorescent dyes (SYTOX Orange and SYTO Green; Molecular Probes, Eugene, OR), which differentiate between live and dead cells. Apoptosis was visualized by using the TUNEL assay. Changes in mitochondrial membrane potential were detected by JC-1 dye. Intracellular levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were measured by HPLC. Regulation of gamma-glutamylcysteine ligase (GCL), the rate-controlling enzyme of GSH production, was assayed by RT-PCR. RESULTS: Pretreatment of hfRPE cells with LA, 0.2 mM and 0.5 mM, significantly reduced the levels of t-BuOOH-induced intracellular ROS, by 23% and 49%, respectively. LA (0.5 mM) prevented oxidant-induced cell death and apoptosis and also increased the viability of oxidant-treated hfRPE cells from 38% to 90% of control. LA upregulated the mRNA expression of GCL, and was protective against t-BuOOH-induced decreases in both mitochondrial membrane potential and intracellular levels of GSH and GSH/GSSG. CONCLUSIONS: The present study suggests that the protective effect of LA involves multiple pathways and that LA could be effective against age-associated increase in oxidative stress and mitochondrial dysfunction in RPE cells.

Antioxidants↗

Minocycline protects photoreceptors from light and oxidative stress in primary bovine retinal cell culture.

PURPOSE: To determine whether minocycline, a compound known to protect the retina against light-induced damage in rodent models, and its structurally related analogues would protect photoreceptor cells in primary bovine retinal cell culture against light and oxidative stress. METHODS: Minocycline and its analogues were tested in primary retinal cell culture to see whether they would inhibit light or oxidative stress-induced cell death. Primary cell cultures composed of photoreceptors, bipolar cells, and glial cells were prepared from bovine retinas. The extent of cell death induced by light or oxidative stress was assessed by using Sytox Green (Invitrogen-Molecular Probes, Eugene, OR) a nucleic acid dye uptake assay. Differential protection of photoreceptor cells from stress were examined using immunocytochemistry. RESULTS: Minocycline and methacycline were cytoprotective against light- or oxidative stress-induced damage of bovine primary photoreceptors in culture with an EC(50) < 10 microM. In contrast, structurally related analogues such as demeclocycline, meclocycline, and doxycycline were phototoxic at >3 to >10 microM. Though demeclocycline was found to be phototoxic, it was cytoprotective (EC(50) = 5 microM) against oxidative stress in the absence of exposure to light. CONCLUSIONS: The protective action of minocycline against light-induced damage in the cell-based assays agrees with earlier reports in animal models and suggests that the in vitro assay using bovine primary retinal cell culture is a suitable model for evaluating compounds for retinal protection. Cellular protection or toxicity produced by structurally related compounds show that minor structural modifications can alter the function of minocycline and lead to potent retinal protective compounds.

Animals↗

Long-term course of schizophrenic illness: Bleuler's study reconsidered.

OBJECTIVE: The influential 1972 study by Manfred Bleuler on the long-term course of schizophrenic illness has been reconsidered. The authors tested the diagnosis of schizophrenia in all patients and investigated how the distribution of the types of illness course and outcome would change after exclusion of patients whose diagnosis of schizophrenia could not be confirmed by modern diagnostic standards. METHOD: Clinical charts and Bleuler's research notes on the original sample were assessed, and all patients were rediagnosed with the help of DSM-IV, DSM-III-R, ICD-10, the Research Diagnostic Criteria (RDC), Schneider's criteria, and an operationalized version of the criteria of Eugen Bleuler. RESULTS: The diagnosis of schizophrenia was not confirmed in about 30% of the sample; the majority of these patients were rediagnosed with schizoaffective disorder. High diagnostic agreement was found between DSM-IV, DSM-III-R, ICD-10, and RDC; there was much less agreement with Bleuler's and Schneider's criteria. After exclusion of patients whose schizophrenia diagnosis was not confirmed, the proportion of patients with undulating course and recovery slightly decreased, and the proportion of patients with severe end state slightly increased. Nevertheless, the distribution of the types of long-term course did not significantly change, and even among patients with strictly defined schizophrenia, half had an undulating course with remissions and 12%-15% recovered. CONCLUSIONS: Schizophrenic illness remains heterogeneous with regard to illness course and outcome even when narrowly diagnosed with the help of modern operationalized diagnostic criteria. Contemporary differentiation between schizophrenic and schizoaffective disorders is prognostically valid.

Adolescent↗

Emotional responses evoked by dental odors: an evaluation from autonomic parameters.

Among the factors which could explain avoidance behavior toward dental care, the typical clinging odor of the dental office, due to eugenol, is investigated in this study. The hypothesis is supported by the well-known effects of odorants which may influence cognition, emotion, and behavior. The association between the odor of eugenol and dental fear and anxiety could be explained by the fact that eugenates (eugenol-containing cements) are often used in potentially painful restorative dentistry on vital teeth. The emotional impact of the odors of eugenol and two other dental products (menthol and methyl methacrylate) was evaluated on volunteer subjects through autonomic nervous system (ANS) analysis by recording the variations of six ANS parameters (two electrodermal, two thermovascular, and two cardiorespiratory) induced by the inhalation of the odorants. After the experiment, subjects were asked to fill out an 11-point hedonic scale to rate the pleasantness vs. unpleasantness for each odorant. Results were compared between two groups of subjects divided according to their own dental experience (fearful and non-fearful dental-care subjects). These showed that, in both groups, menthol was rated as pleasant and methyl methacrylate as very unpleasant, whereas eugenol was judged pleasant by non-fearful subjects but unpleasant by fearful subjects. Concerning autonomic analysis, only eugenol induced significantly different patterns of ANS responses between the two groups, with stronger variations for dentally fearful subjects, mainly observed through the electrodermal channel. These results suggest that eugenol can be responsible for different emotional states, depending on the unpleasantness of the subjects' dental experience. This seems to confirm the role of odors as elicitors of emotional memories and to support the possible influence of eugenol odor on the avoidance behavior of some subjects toward dental care.

Adult↗