Previous miscarriages influence IVF and intracytoplasmatic sperm injection pregnancy outcome.

Previous conceptions are one predictor for the outcome of assisted reproductive technology procedures. Approximately 18-34% of clinical pregnancies following assisted reproduction procedures result in spontaneous abortion. The risk of such pregnancy loss is believed to increase with women's age, previous miscarriages and use of frozen-thawed embryos. This study analyses German IVF Registry data to examine the impact of previous miscarriages on the outcome of assisted reproduction procedures. The data set consists of a total of 174,909 assisted reproduction procedures performed between January 1998 and December 2000. Multiple logistic regression is used to assess the correlation between women's age, spousal/partner change, and infertility diagnosis. It is demonstrated that any previous miscarriage will increase the treatment-dependent miscarriage rate in assisted reproduction procedures. A significantly higher impact is shown for one previous miscarriage achieved by assisted reproduction procedures compared with spontaneous conception. Partner change is shown to have no specific impact on the treatment dependent miscarriage rate, whereas a statistically significant increase in miscarriages in all assisted reproduction procedures was found among women older than 34 years of age. Overall, the highest rate of treatment-dependent miscarriages was seen in assisted reproduction procedures with cryopreserved embryo transfer.

Scleromyxoedema: treatment of cutaneous and systemic manifestations with high-dose intravenous immunoglobulin.

Scleromyxoedema is a rare disease characterized by cutaneous sclerosis, mucin deposition and paraproteinaemia. Internal disease is common, particularly musculoskeletal, gastrointestinal and central nervous system involvement. We report a series of three consecutive patients with scleromyxoedema treated with high-dose intravenous immunoglobulin (hdIVIg). Each of the three patients had relatively low levels of a highly basic IgG-lambda paraprotein, and each has demonstrated a sustained response of both their cutaneous and extracutaneous disease to hdIVIg. As all patients had perioral skin involvement and microstomia, one measure of cutaneous improvement was the increase in intraincisor distance. Extracutaneous manifestations of scleromyxoedema that improved included ureteral stricture, vocal strength and dysphagia.

Colic in breast-milk-fed infants: treatment by temporary substitution of neocate infant formula.

Infant colic is a common problem characterized by excessive crying and fussing. We examined whether colic symptoms of exclusively breast-milk-fed infants would be improved by temporary substitution of Neocate, an amino acid-based infant formula, for breast milk. Six infants with colic were studied using Barr-type infant behavior diaries for a 3-5 d baseline period while they continued exclusive breast-milk-feeding, followed by a 4-8 d intervention period of exclusive Neocate feeding. All infants showed improvement in distressed behavior during intervention; five of the six improved within 1-2 d. For the period after 1 d of Neocate feeding, the total recorded crying and fussing time was reduced by an average of 42%, representing a decrease of 1.0 to 3.1 h daily. A significant difference was found between cry and fuss time at baseline versus during exclusive Neocate use. Concurrent with Neocate intervention, mothers strictly avoided all milk and dairy products. After colic symptoms improved, infants were reintroduced to breast milk, which was reasonably well tolerated in four of the six infants. Two infants had rapid recurrences of crying and fussing upon return to breastfeeding and required an additional period of Neocate feedings before subsequent reintroduction to breastfeeding. All infants exhibited colic symptoms when directly or indirectly challenged with bovine IgG (BGG), suggesting that BGG may play an etiologic role in colic. We propose that a brief intervention with Neocate, coupled with strict maternal avoidance of milk and dairy products under direct supervision of a lactation consultant, may be an effective treatment for colic in some breast-milk-fed infants.

Treatment of infant colic with amino acid-based infant formula: a preliminary study.

Infant colic, a common disorder of infancy, is characterized by excessive crying and fussing. In this preliminary study we examined whether Neocate, an amino acid-based formula, would be accepted by formula-fed infants with colic, 3-7 wk of age, and whether Neocate would improve their symptoms. Six infants with colic were studied using Barr-type infant behavior diaries for 3-6 d on their current formula and then for 5-17 d on Neocate exclusively. All infants tolerated Neocate well and all improved, usually within 1-2 d. The total time spent crying and fussing was reduced by an average of 45%, representing a decrease of 1.0 to 5.2 h daily. After colic symptoms improved, infants were challenged with oral doses of 75 mg of bovine IgG at a 1 mg/ml concentration in order to assess its potential role in colic. Bovine IgG challenges resulted in increased crying and fussing behavior, suggesting that this protein may be etiologically important.

The population, environment, and health nexus: an Arab world perspective.

PIP: This report describes models of the links between population growth, environmental degradation, and health in Arab countries and in the world; management of the commons; urbanization and water as critical issues; and challenges in Lebanon. It is concluded that the complexity of interrelationships is difficult to untangle. Researchers frequently neglect health issues in modeling the relationships. The lack of attention to the health, development, and environment nexus has serious implications in the Middle East and North Africa. In Lebanon, national strategies do not include a national waste management strategy based on reduction, reuse, and recycling. Most Arab countries face the major issue of the lack of adequate planning in many economic sectors, which results in imbalances in supply and demand. Most Arab countries do not have adequate statistical databases upon which to base development, planning, and policy-making. The last census in Lebanon was in 1932. Information is missing on health. Health economics are ignored. It is not possible to estimate the health costs due to deficiencies in sanitation, hygiene, water, and air quality. Capacity building for environmental management and intersectoral collaboration is hampered. Arab countries with large oil reserves have ignored the population and environment links. Poorer countries will suffer the most from limited renewable water resources and their decline due to population growth. The political agenda in Arab countries should give priority to health, environment, development, and population issues.^ieng

Cow's milk-free diet does not prevent diabetes in NOD mice.

Early dietary exposure to cow's milk proteins has been proposed as an important environmental factor in the development of IDDM both in humans and in diabetes-prone rodents. To examine the significance of cow's milk protein in IDDM, 120 NOD mice were maintained, starting from conception until sacrifice, on one of four diets: standard PMI Picolab Rodent Diet 20, a milk-free modification of the standard Picolab diet, a milk-free diet incorporating 0.036% bovine serum albumin (BSA), and a milk-free diet including 0.036% bovine IgG (BGG). The cumulative IDDM incidence at 7 months for these mice in a specific pathogen-free environment on the respective diets was 78, 93, 93, and 67% for females, and 17, 54, 17, and 0% for males. The ages of diabetes onset and insulitis scores were similar for mice on each diet. The unexpectedly lower incidence of IDDM in mice on the milk-free diet that included BGG raises the possibility this cow's milk protein might possibly have some protective effect against the development of IDDM in NOD mice. Our main finding was that the standard, milk-free, and BSA-containing diets resulted in comparable incidences of IDDM in NOD mice, demonstrating that neither cow's milk whey proteins in general nor BSA in particular are significantly important as etiologic dietary agents in IDDM in NOD mice.

Abortion and fertility regulation.

To achieve their desired fertility, women use a combination of contraception and abortion, and some societies also place constraints on marriage and sexual activity. The degree to which these means are adopted varies considerably, but for the foreseeable future abortion will remain an important element of fertility regulation. Globally, complications of unsafe abortion affect hundreds of thousands of women each year, and account for as many as 100,000 deaths annually (about two in ten maternal deaths), mainly in poor countries, where abortion typically remains illegal. Access to safe abortion is both essential and technically feasible and should be provided in combination with good quality family planning services.

PIP: This article presents a review of abortion-related issues that suggests that worldwide abortion will remain a form of fertility regulation. It is estimated that about 2 in 10 maternal deaths occur worldwide due to unsafe abortion practices, which are mostly in developing countries and in countries where abortion is illegal. The 1994 International Conference on Population and Development was the first forum to focus in a global way on the serious health threat to women from unsafe abortion. In the US, about 60% of all pregnancies are unwanted or mistimed and about 50% are aborted. In most European countries, about 66% of women had at least one unintended pregnancy. The annual worldwide abortion rate is estimated to range from 32 abortions/1000 women to 46/1000 women aged 15-44 years. In most developed countries the abortion rate varies from 1 to 30/1000. The Netherlands has the lowest rate (5/1000) and the most liberal abortion laws. The former USSR has the highest rate (112/1000), although some central regions of European Russia have a higher rate of 186/1000. Variation in abortion rates by country can be accounted for by contraceptive prevalence and use-effectiveness, prevailing fertility preferences, laws and policies relating to abortion and contraception, and the relationship between abortion and contraception. Contraceptive usage is a key factor. For example, in the US, 7% of sexually active women aged 15-44 years, who were not using contraception nor seeking to become pregnant, accounted for 53% of unintended pregnancies. Developing countries shifting from high to low fertility may experience a rise in abortions. Where contraceptives are unavailable to adolescents, abortion rates are high and increasing. Women seek abortion for many reasons. Abortion laws vary widely by country. Vacuum aspiration is considered the safest, simplest, and most medically and economically effective way of inducing first-trimester abortions or treating incomplete abortions. The issue of abortion is complicated by political, religious, and moral concerns.

Human breast milk contains bovine IgG. Relationship to infant colic?

Previous studies have suggested that an unidentified cow's milk protein, other than beta-lactoglobulin and casein, might play a pathogenetic role in infant colic. Therefore, a radioimmunoassay was used to analyze human breast milk and infant formula samples for the presence of bovine IgG. Milk samples from 88 of the 97 mothers tested contained greater than 0.1 micrograms/mL of bovine IgG. In a study group of 59 mothers with infants in the colic-prone 2- to 17-week age group, the 29 mothers of colicky infants had higher levels of bovine IgG in their breast milk (median 0.42 micrograms/mL) than the 30 mothers of noncolicky infants (median 0.32 micrograms/mL) (P less than .02). The highest concentrations of bovine IgG observed in human milk were 8.5 and 8.2 micrograms/mL. Most cow's milk-based infant formulas contained 0.6 to 6.4 micrograms/mL of bovine IgG, a concentration comparable with levels found in many human milk samples. The results suggest that appreciable quantities of bovine IgG are commonly present in human milk, that significantly higher levels are present in milk from mothers of colicky infants, and that bovine IgG may possibly be involved in the pathogenesis of infant colic.

Genomic organization of mouse Fc gamma receptor genes.

We have isolated and characterized the gene coding for the mouse Fc receptor that is termed Fc gamma RIIa. The gene contains five exons and spans approximately 9 kilobases. Unlike most members of the immunoglobulin gene superfamily, this gene utilizes multiple exons to encode its leader peptide. The first exon encodes the hydrophobic region of the signal sequence; the second exon, which contains only 21 base pairs, encodes a segment of the signal peptidase recognition site; and the beginning of the third exon encodes the predicted site of peptidase cleavage. The third and fourth exons each code for immunoglobulin-like extracellular domains. The fifth exon encodes the hydrophobic transmembrane domain and the cytoplasmic tail. Partial characterization of the Fc gamma RIIb gene indicates that it also contains multiple leader exons, including a 21-base-pair exon and two exons coding for homologous immunoglobulin-like extracellular domains. However, the Fc gamma RIIb gene uses four exons to encode its intracytoplasmic region. Analysis using contour-clamped homogeneous electric field (CHEF) gels indicates that the Fc gamma RIIa and Fc gamma RIIb genes are linked within 160 kilobases on mouse chromosome 1.

Bovine IgG1, but not IgG2, binds to human B cells and inhibits antibody secretion.

We previously observed that milk-derived bovine IgG, but not serum-derived bovine IgG, strongly inhibits antibody secretion by pokeweed mitogen (PWM)-stimulated human peripheral blood mononuclear cells (PBMC). Bovine milk contains a greater percentage of IgG1 (90%) than does bovine serum (53%). To determine whether bovine IgG subclasses have different functional capabilities, we have examined the effects of bovine IgG1 and IgG2 subclasses upon not only antibody secretion but also mitogenesis by human PBMC. Both bovine IgG subclasses markedly inhibited PWM-stimulated mitogenesis. However, only bovine IgG1, and not IgG2, inhibited antibody secretion during a 14-day in vitro culture period. Also, antibody secretion was inhibited following a 24-hr preincubation of human PBMC with bovine IgG1, but not with IgG2. To determine whether these differences corresponded to specificities of human Fc gamma receptors on subsets of mononuclear cells, fluorescence-activated cell sorter (FACS) analyses were performed. Both bovine IgG subclasses bound to human monocytes. However, only bovine IgG1 bound to human B cells, and bovine IgG1 bound more avidly to human B cells than did human IgG. One model to explain these findings is that inhibition of mitogenesis may be due to the binding of both bovine IgG1 and IgG2 subclasses to monocytes; whereas subclass-specific inhibition of antibody secretion may result from the selective binding of bovine IgG1, but not bovine IgG2, to B cells. The observation that bovine IgG1 has a greater avidity for human B lymphocyte Fc receptors than human IgG may have important implications for future studies of Fc gamma receptors on human leucocytes.

Adenomas prolactínicos en mujeres menores de 20 años: a proposito de once casos / Prolactin adenomas on women under 20: report of 11 cases

Son analizados los aspectos clínicos, neuroendocrinos, terapéuticos y evolutivos de 11 pacientes del sexo femenino, portadoras de síndrome de amenorrea galactorrea, con inicio de síntomas en edad puberal y diagnóstico etiológico de adenoma prolactínico, cuya terapéutica neuroquirúrgica fue realizada en edades comprendidas entre 16 y 20 años. Es importantes su presentación pues: 10 la mayoria de estas pacientes fueron consideradas y tratadas inicialmente como portadora de trastornos "fisiológicos" del ciclo sexual compatibles con la edad, y 2) por la alta frecuencia de macroadenomas prolactínicos con expansión extraselar encontrados (3/11 casos, 27%), lo que trae como consecuencia, resección quirúrgica incompleta y pronóstico reservado. Las características principales de este grupo, fueron: 1) rítmo circadiano de PRL patológico, pruebas de TRH y MCP patológicas (100, 80 y 100%, respectivamente); 2) radiografías simples, politomografía lineal y tomografía axial computada de silla turca patológicas (73%, y 100% respectivamente); 3) terapéutica neuroquirúrgica por vía transepto esfenoidal en 10 casos y por vía subfrontal en un caso, y 4) evolución espontánea hacia la recuperación de ciclos sexuales en lapsos de 1 a 4 meses en aquellas pacientes operadas de adenomas intraselares, y persistencia del síndrome de amenorrea galactorrea en las pacietnes operadas de macroadenomas expansivos. El diagnóstico precoz (basado en los datos clínicos, bioquímicos y neurorradiólógicos) que orienta hacia la terapéutica neuroquirúrgica cuando el adnoma hipofisario es aúm intraselar, se acompaña de los mejores resultados evoluticos post-quirúrgicos

Adenomas prolactínicos en mujeres menores de 20 años: a proposito de once casos / Prolactin adenomas on women under 20: report of 11 cases

Son analizados los aspectos clínicos, neuroendocrinos, terapéuticos y evolutivos de 11 pacientes del sexo femenino, portadoras de síndrome de amenorrea galactorrea, con inicio de síntomas en edad puberal y diagnóstico etiológico de adenoma prolactínico, cuya terapéutica neuroquirúrgica fue realizada en edades comprendidas entre 16 y 20 años. Es importantes su presentación pues: 10 la mayoria de estas pacientes fueron consideradas y tratadas inicialmente como portadora de trastornos "fisiológicos" del ciclo sexual compatibles con la edad, y 2) por la alta frecuencia de macroadenomas prolactínicos con expansión extraselar encontrados (3/11 casos, 27%), lo que trae como consecuencia, resección quirúrgica incompleta y pronóstico reservado. Las características principales de este grupo, fueron: 1) rítmo circadiano de PRL patológico, pruebas de TRH y MCP patológicas (100, 80 y 100%, respectivamente); 2) radiografías simples, politomografía lineal y tomografía axial computada de silla turca patológicas (73%, y 100% respectivamente); 3) terapéutica neuroquirúrgica por vía transepto esfenoidal en 10 casos y por vía subfrontal en un caso, y 4) evolución espontánea hacia la recuperación de ciclos sexuales en lapsos de 1 a 4 meses en aquellas pacientes operadas de adenomas intraselares, y persistencia del síndrome de amenorrea galactorrea en las pacietnes operadas de macroadenomas expansivos. El diagnóstico precoz (basado en los datos clínicos, bioquímicos y neurorradiólógicos) que orienta hacia la terapéutica neuroquirúrgica cuando el adnoma hipofisario es aúm intraselar, se acompaña de los mejores resultados evoluticos post-quirúrgicos (AU)

Bovine IgG can aggregate at conditions simulating pasteurization and binds to some human Fc gamma receptors.

The ability of bovine IgG preparations to bind to the various distinct human leukocyte Fc gamma receptors was studied. In experiments using intact cells and isolated Fc gamma receptors, it was demonstrated that bovine IgG can bind to Fc gamma receptors of four human cell types but not to Fc gamma receptors of human neutrophils. 125I-labeled Fc gamma receptors purified on human IgG-Sepharose columns from human B and T lymphocytes, monocytes and eosinophils were able to rebind specifically to insolubilized bovine IgG. In contrast, radioiodinated human neutrophil Fc gamma receptors did not rebind to bovine IgG-Sepharose. A similar pattern of specificity was demonstrated in studies of the binding of 125I-labeled heat-aggregated bovine IgG to various human leukocyte populations. The labeled aggregated bovine IgG bound to peripheral blood mononuclear cells, to B cells from chronic lymphocytic leukemia patients and to macrophage-like U-937 cells, but bound poorly to normal human granulocytes. Labeled non-aggregated bovine IgG was not appreciably bound to any of the cell populations. Since bovine IgG in dietary sources is frequently exposed to heat, the effect of heating on the physical state and Fc-binding properties of bovine IgG was examined. The data show that heating bovine IgG at concns of 0.9-3.6 mg/ml at 63 degrees C for 30 min in neutral buffer causes aggregation of bovine immunoglobulin (10-16% aggregation) and increases the ability of bovine IgG preparations to bind to human Fc gamma receptors of intact cells. Gel filtration studies suggest the possibility that bovine IgG may also be aggregated during the pasteurization of raw milk.

Bovine milk IgG, but not serum IgG, inhibits pokeweed mitogen-induced antibody secretion by human peripheral blood mononuclear cells.

Bovine milk IgG markedly inhibits the pokeweed mitogen (PWM)-induced secretion of immunoglobulins from human peripheral blood mononuclear cells. Heat-aggregated bovine milk IgG is even more inhibitory, demonstrating significant inhibition when levels as low as 5-9 micrograms/ml are continuously present in the in vitro 14-day culture system. However, bovine serum IgG, regardless of its state of aggregation, and control proteins have little effect on PWM-induced secretion of human IgG, IgA, and IgM. In a similar fashion, goat milk IgG, especially when aggregated, inhibits human antibody secretion whereas goat serum IgG does not. Inhibition appears to be mediated by Fc gamma receptors since F(ab')2 fragments of milk-derived bovine IgG do not inhibit PWM-induced antibody secretion. The continuous presence of bovine milk IgG is not essential since preincubation of milk IgG with PWM and human mononuclear cells for 24 hr also results in inhibition of human immunoglobulin secretion. In examining potential mechanisms of inhibition, it was found that bovine milk IgG, bovine serum IgG, and another chitin-containing protein, bovine thyroglobulin, each caused a small and equal inhibition of the binding of 125I-labeled PWM to human mononuclear cells, yet only the milk IgG inhibited antibody production. These studies raise the question of whether bovine milk IgG might modulate the human immune system in vivo.

Structure and expression of Fc gamma receptors on mouse suppressor T cell hybridomas.

Antigen-specific and idiotype-specific mouse suppressor T cell hybridomas were analyzed for the presence and specificity of Fc gamma receptors (Fc gamma R) by EA rosetting and by flow microfluorometry with the use of monoclonal antibodies. We found that four hybridomas expressed Fc gamma R specific for IgG1 and IgG2b, one of which became Fc gamma R- during prolonged culture. Four other hybridomas and the fusion parent, BW5147, consistently lacked Fc gamma R. The 125I-labeled Fc gamma R were isolated from surface radioiodinated hybridoma cells solubilized with 1% Nonidet P-40, were purified by using single or repetitive chromatography on mouse IgG-Sepharose columns, and were analyzed by SDS-PAGE. An 125I-labeled 56,000 to 61,000 Mr macromolecule was isolated from each of the Fc gamma R+ hybridomas, but from none of the Fc gamma R- hybridomas nor from BW5147 cells. This macromolecule rebound to insolubilized mouse IgG1, IgG2b, and human Fc fragments, but not to insolubilized mouse IgG2a, IgG3, or IgA or human F(ab')2 fragments, consistent with the specificity observed for Fc gamma R on intact hybridoma cells. The mouse suppressor T cell Fc gamma R differs in size and specificity from mouse B cell Fc gamma R. A 70,000 Mr protein expressed on all hybridomas and on BW5147 cells was radiolabeled and, despite preclearing with ovalbumin-Sepharose, bound to the mouse IgG-Sepharose columns, presumably due to mouse antibodies to gp-70. This macromolecule was completely and specifically removed by using goat antiserum to gp-70.