Soluble HLA-G blood levels are not increased during ongoing pregnancy in women with a history of recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) affects 1-2 % of couples who are trying to conceive. At some point, some couples do maintain a healthy pregnancy to term, but the underlying mechanism of RPL remains elusive. Human leukocyte antigen (HLA)-G is an immune modulatory molecule. Our group previously showed increased HLA-G levels in the decidua of term pregnancies after RPL, while other studies showed reduced soluble HLA-G (sHLA-G) blood levels in women with RPL. This led us to investigate sHLA-G levels in blood of women with RPL who had either a subsequent pregnancy loss (RPL-pregnancy loss) or a healthy term pregnancy (RPL-live birth), and compare these to healthy control pregnancies and non-pregnant controls. Soluble HLA-G concentrations were quantified by ELISA. Women with healthy term pregnancy had increased sHLA-G levels compared to non-pregnant controls. In contrast, RPL-live birth women at term did not have increased blood sHLA-G levels. Soluble HLA-G levels remained stable between first and third trimester. Interestingly, when comparing first trimester samples of RPL-live birth to RPL-pregnancy loss, sHLA-G levels also did not significantly differ. High sHLA-G levels in blood seem not to be crucial for an ongoing healthy pregnancy after RPL. However, since it was previously shown that women with RPL-live birth have increased HLA-G levels in term decidua compared to control pregnancies, the current data suggest that local and systemic immune regulation are not necessarily in concert. Further study of the contribution of fetus-derived HLA-G and HLA-G of maternal origin may provide more insight in the pathophysiology of RPL.

A Memory B Cell Crossmatch Assay for Quantification of Donor-Specific Memory B Cells in the Peripheral Blood of HLA-Immunized Individuals.

Humoral responses against mismatched donor HLA are routinely measured as serum HLA antibodies, which are mainly produced by bone marrow-residing plasma cells. Individuals with a history of alloimmunization but lacking serum antibodies may harbor circulating dormant memory B cells, which may rapidly become plasma cells on antigen reencounter. Currently available methods to detect HLA-specific memory B cells are scarce and insufficient in quantifying the complete donor-specific memory B cell response due to their dependence on synthetic HLA molecules. We present a highly sensitive and specific tool for quantifying donor-specific memory B cells in peripheral blood of individuals using cell lysates covering the complete HLA class I and class II repertoire of an individual. Using this enzyme-linked immunospot (ELISpot) assay, we found a median frequency of 31 HLA class I and 89 HLA class II-specific memory B cells per million IgG-producing cells directed at paternal HLA in peripheral blood samples from women (n = 22) with a history of pregnancy, using cell lysates from spouses. The donor-specific memory B cell ELISpot can be used in HLA diagnostic laboratories as a cross-match assay to quantify donor-specific memory B cells in patients with a history of sensitizing events.

Predicting expenditures for Medicare beneficiaries with diabetes. A prospective cohort study from 1994 to 1996.

OBJECTIVE: To describe health care expenditures and utilization patterns among older adults with diabetes and to examine factors associated with expenditures over a 3-year period. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of health care expenditures and utilization by diabetic patients from a random nationwide sample of aged Medicare beneficiaries from 1994 to 1996. All services covered by the Medicare program were examined. Multivariate regression was used to assess the contribution of patient characteristics in 1994 on Part B, inpatient, and total expenditures in 1995 and 1996. RESULTS: Per capita expenditures for beneficiaries with diabetes (n = 169,613) were 1.7 times greater than those for those beneficiaries without diabetes (n = 968,832) in 1994. This ratio remained fairly constant over the 2 years of follow-up. Expenditures for beneficiaries with diabetes were highly skewed. However, few of these individuals remained in the highest expenditure quintile over the 2 years of follow-up. Using multiple regression analysis to adjust for demographic and clinical characteristics, we were able to explain 7% of the variation in total expenditures in 1995 and 6% of the variation in 1996. Using the same model, we were able to explain 10.7% of the variation in Part B expenditures in 1995 and 8% in 1996. CONCLUSIONS: Beneficiaries with diabetes are consistently more expensive than beneficiaries without diabetes. Demographic and clinical factors at baseline are able to predict only a small portion of future expenditures among this population, and the most expensive patients in one year were often not the most expensive in subsequent years. More work is necessary to assure equitable risk adjustment in the calculation of capitation rates for health plans and practitioners who specialize in the care of individuals with diabetes.

A community-based study of explanatory factors for the excess risk for early renal function decline in blacks vs whites with diabetes: the Atherosclerosis Risk in Communities study.

CONTEXT: The explanation for the excess risk for diabetic renal disease in blacks is uncertain. OBJECTIVES: To compare the incidence of early renal function decline in black and white adults with diabetes and to examine possible explanatory factors for racial differences. DESIGN: Prospective cohort study. SETTING: Four US communities participating in the Atherosclerosis Risk in Communities study. PARTICIPANTS: Community-based sample of 1434 diabetic adults aged 45 to 64 years. MEASUREMENTS: Detailed baseline assessment using structured interview, results of physical examination, and laboratory measurements. MAIN OUTCOME: Development of early renal function decline defined by an increase in serum creatinine of at least 35.4 micromol/L (0.4 mg/dL) during 3 years of follow-up. RESULTS: During 3 years of follow-up, early renal function decline developed in 45 blacks (28.4 per 1000 person-years [PY]) and 25 whites (9.6 per 1000 PY). After adjustment for age, sex, and baseline serum creatinine level, early renal function decline was more than 3 times as likely to develop in blacks than whites (odds ratio, 3.15; 95% confidence interval, 1.86-5.33). Additional adjustment for education, household income, health insurance, fasting glucose level, mean systolic blood pressure, smoking history, and physical activity level reduced the relative odds in blacks to 1.38 (95% confidence interval, 0.71-2.69), corresponding to a 82% reduction in excess risk. CONCLUSIONS: These data suggest that early renal function decline is 3 times more likely to develop in blacks than whites and that potentially modifiable factors, including lower socioeconomic status, suboptimal health behaviors, and suboptimal control of glucose level and blood pressure, account for more than 80% of this disparity.

Patterns of expenditures and use of services among older adults with diabetes. Implications for the transition to capitated managed care.

OBJECTIVE: To examine health care use and expenditures among older adults with diabetes, investigate factors that are associated with higher expenditures, and describe the policy implications of caring for this population under managed care. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of expenditures for individuals with diabetes over age 65 years from a nationwide 5% random sample of Medicare beneficiaries was conducted during 1992. All components of medical care covered under Medicare were examined. Multivariate analysis was used to assess the contribution of age, race, sex, number of diabetic complications, and comorbidity (Charlson Index) on total expenditures. RESULTS: On average, individuals with diabetes (n = 188,470) were 1.5 times (P < 0.0001) as expensive as all Medicare beneficiaries (n = 1,371,960). However, there were wide variations, with the most expensive 10% of beneficiaries with diabetes accounting for 56% of expenditures for individuals with diabetes and the least expensive 50% accounting for 4%. Acute care hospitalizations accounted for the majority (60%) of total expenditures, whereas outpatient and physician services accounted for 7 and 33%, respectively. There were no differences in the number of complications for all older adults with diabetes compared with those with the highest expenditures. However, the average number of hospitalizations was 1.6 times (0.53 vs. 0.34; P < 0.0001) higher, and the average length of stay was 2 days longer, among older adults with diabetes (P < 0.0001). In the regression model, age and male sex (factors currently used to set payment rates for Medicare managed care enrollees), and number of diabetic complications, but not race, were positively related to expenditures, yet had minimal predictive power (R2 = 0.0006). The addition of the Charlson Index, also positively related to expenditures, was able to explain up to 20% of the variation in total expenditures (R2 = 0.196). CONCLUSIONS: There are large variations in expenditures among older adults with diabetes. Because elderly beneficiaries with diabetes are more expensive than the average older adult, current Medicare capitation rates may be inadequate. To avoid selection bias and under-treatment of this vulnerable population under managed care, methods to construct fair payment rates and safeguard quality of care are desirable.

Chemical sensitivity after intoxication at work with solvents: response to sauna therapy.

OBJECTIVES: The purpose of this case study is twofold. One, to illustrate a simple method of detoxification using heat chamber depuration (sauna). Second, to raise awareness in the practice of medicine of the importance of taking an environmentally oriented history. SUBJECT: A patient with a chronic, debilitating multisystem disorder of 20-years' duration related to a chemical sensitivity resulting from low-level exposure to toxic chemicals (solvents) at work. INTERVENTIONS: Detoxification treatment consisted of heat chamber depuration (sauna) together with a specific protocol of oral and intravenous therapy. Appropriate advice was offered related to choosing a safe and suitable workplace. OUTCOME MEASURES: Observation of the dynamic interaction and elimination of chlorinated and aromatic hydrocarbons (solvents) from the patient's bloodstream and related clinical improvement during the course of treatment. RESULTS: The patient was able to discontinue, without ill effect, all medications previously prescribed to treat her symptoms. Heat chamber depuration (sauna) detoxification treatment brought substantial release of symptoms and returned the individual to gainful employment. CONCLUSION: The connection between symptoms of chronic degenerative diseases and environmental and/or nutritional factors is missed in many cases due to lack of obtaining an environmentally oriented medical history. Taking such a history and dealing with the cause of illness using avoidance and/or appropriate therapy is preventive and cost-effective for both the patient and society.

A double blind, randomized, controlled investigation of electrodermal testing in the diagnosis of allergies.

This investigation evaluates electrodermal (ED) testing in 41 polysymptomatic allergic patients. Electrodermal testing discriminated correctly 82% of the time between house dust mite and histamine (allergens) and saline or water (nonallergens) in our first study group involving 17 patients (p = 0.007). The second study involved 24 patients and used the same double-blind methodology discriminating 96% of the time between allergic and nonallergic substances (p = 0.000002). We conclude that ED testing is a reliable method of differentiating between allergic and nonallergic substances in the context of our study.

Clinical ecology and its role in diagnosis of chronic diseases caused by environmental pollution. Indoor air pollution as a major factor.

The author discusses the four basic principles of clinical ecology, which include total load, such as exposure to chemicals, effects of physical factors (cold, heat, positive ions, radiation), exposure to bacteria, viruses and fungi, effects of consumed foods and psychological stress. Adaptation is discussed in detail as it pertains to chronic degenerative disease and chemical sensitivity. Lack of understanding of adaptive phenomena leads contemporary physicians to prescribe drugs instead of finding and eliminating the cause of disease to alleviate suffering. Body response to environmental stimuli during adaptive processes is biphasic in nature and is characterized by stimulatory and withdrawal reactions. Symptoms developed during these phases are described in detail. Effects of foods and chemicals on patients' health should be examined and considered before excluding in favour of idiopathic, mental or psychosomatic disturbances. In order to understand the variety of symptoms and signs developed during the process of degenerative disease one has to accept and apply the concept of biological individuality. Each patient should be assessed and dealt with carefully since each represents a unique clinical picture. The author further on discusses indoor air pollution, its causes and effects on health. Particular emphasis is placed on the indoor use of pesticides in the Canadian setting. Four groups of population have been defined as the result of exposure to chemicals and are discussed in brief. The author concludes with a comparison of traditional and environmental medicine in respect to history taking, the stage at which disease is diagnosed, the patient's viewpoint, specialization and therapies.

Treatment and prophylaxis for patients suffering from environmental hypersensitivity disorder.

The author is discussing therapeutic modalities used by environmental physicians. Much emphasis is directed towards the need and methods to control the patient's environment in order to improve his/her health. Unique neutralization techniques to help patients cope with environmental exposures are presented. Importance of nutritional evaluation and correction as well as the 4-Day Rotation Diet are introduced. (The author realized that some of the foods mentioned are not on the market as yet in Poland but the idea can be adapted to available foods and a developing economy will increase diversity). The treatments should always be combined with psychological therapy and support. The paper ends with a discussion of global prophylaxis of environmental illness as it should be applied at home, school and work. All sectors of government and social institutions should be involved. Environmental medicine should be on the curriculum of medical schools.

The course of the assembly of ribosomal subunits in yeast.

The course of the assembly of the various ribosomal proteins of yeast into ribosomal particles has been studied by following the incorporation of radioactive individual protein species in cytoplasmic ribosomal particles after pulse-labelling of yeast protoplasts with tritiated amino acids. The pool of ribosomal proteins is small relative to the rate of ribosomal protein synthesis, and, therefore, does not affect essentially the appearance of labelled ribosomal proteins on the ribosomal particles. From the labelling kinetics of individual protein species it can be concluded that a number of ribosomal proteins of the 60 S subunit (L6, L7, L8, L9, L11, L15, L16, L23, L24, L30, L32, L36, L40, L41, L42, L44 and L45) associate with the ribonucleoprotein particles at a relatively late stage of the ribosomal maturation process. The same was found to be true for a number of proteins of the 40 S ribosomal subunit (S10, S27, S31, S32, S33 and S34). Several members (L7, L9, L24 and L30) of the late associating group of 60-S subunit proteins were found to be absent from a nuclear 66 S precursor ribosomal fraction. These results indicate that incorporation of these proteins into the ribosomal particles takes place in the cytoplasm at a late stage of the ribosomal maturation process.