Purification of alpha-fetoprotein from human cord serum with demonstration of its antiestrogenic activity.

Alpha-fetoprotein (AFP) was purified from pooled human cord serum to determine whether it would be similar to purified mouse AFP in its ability to be transformed into an antiestrogen by incubation with estradiol (E2). Greater purity was attained with a three-step purification procedure of chromatofocusing, Blue-Sepharose chromatography and immunoaffinity chromatography than with a two-step procedure of polyacrylamide gel electrophoresis followed by Blue-Sepharose chromatography. Nevertheless, both procedures rendered AFP in a form that was transformable by E2 to an antiestrogen, although the product of the three-step procedure afforded more consistent biological activity. Removal of albumin from AFP was crucial for transformation of AFP to an antiestrogen. Thus, human AFP is similar to mouse AFP in being transformed to an antiestrogen upon incubation with E2, even though there is only 66% structural homology between the two proteins, and human AFP lacks the high-affinity binding site for E2 present in the mouse AFP molecule.

Prolactin and autoimmune disease.

A number of reports have shown that PRL is an immune-stimulating hormone that is capable of stimulating organ-specific inflammatory disease in humans. More recently, hyperprolactinemia has been associated with the active phase of the immune-complex-mediated autoimmune disease, systemic lupus erythematosus. The theory that PRL contributes substantially to disease activity was upheld in the NZB/W mouse model of spontaneous, hormone-sensitive lupus. Implanted pituitary glands resulted in hyperprolactinemia, accelerated proteinuria, high levels of circulating IgG, and premature death. Therapeutic studies with NZB/W mice, as well as anecdotal evidence from a small number of patients, have provided evidence that PRL suppressive therapy may be beneficial in selected cases of autoimmune disease.

Changes in bone mineral density and markers of bone remodeling during lactation and postweaning in women consuming high amounts of calcium.

A randomized clinical intervention trial to determine effects of lactation and 1 g of calcium (Ca) on bone remodeling was conducted in 15 women (calcium = 7, placebo [P] = 8) consuming 1.3-2.4 g of Ca/day from diet + prenatal supplement. Study periods were baseline, < or = 2 weeks postpartum; lactation, 3 months lactation; and postweaning, 3 months postweaning. Bone mineral density (BMD) corrected for body weight was determined by dual-energy X-ray absorptiometry (DXA). Indicators of calcium metabolism, bone turnover, and lactation were measured: calcium metabolism, parathyroid hormone (PTH), 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D); bone turnover, formation, procollagen I carboxypeptides (PICP), osteocalcin, and bone alkaline phosphatase (B-ALP), resorption, tartrate resistant acid phosphatase (TRAP); and lactation, prolactin (PRL). Mean BMD changes differed by site: baseline to lactation -4.3% (P) (p < 0.04) and -6.3% (Ca) (p < 0.01) at the lumbar spine (L2-L4) and 5.7% gains of the ultradistal (UD) radius (Ca) (p < 0.04); lactation to postweaning, -6% to -11% at all sites of the radius and ulna (Ca, P) (p < 0.04) +3% at L2-L4 (Ca) (p < 0.03); baseline to postweaning, (UD) radius -5.2% (P) (p < 0.03), UD radius + ulna -6% to -8% (Ca, P) (p < 0.04) but no significant loss of L2-L4 or total body. Bone turnover markers were higher at lactation than postweaning: PICP (+34%, p < 0.001), osteocalcin (+25%, p < 0.01), TRAP (+11%, p < 0.005) as well as PRL (+81%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Purification and characterization of human bone tartrate-resistant acid phosphatase.

Tartrate-resistant acid phosphatase (TRAP) is a histochemical marker for osteoclasts, the multinucleated bone resorbing cell. This type 5 acid phosphatase has been purified 500-fold from human bone by three chromatographic steps: cation exchange, gel filtration, and HPLC cation exchange. Like most other TRAPs isolated, it is a basic glycoprotein of a molecular weight about 33,000. Its pH optimum Km, and Vmax for p-nitrophenyl phosphate are 5.7, 0.8 mM, and 12 units/mg, respectively. Human bone TRAP hydrolyzes aryl phosphates, nucleoside di- and triphosphates, pyrophosphate, and phosphoproteins. It is activated by mild reducing agents but inhibited by molybdate, fluoride, arsenate, phosphate, and dithionite. Its activity is not inhibited by tartrate, a feature that distinguishes it from other acid phosphatases. Sodium etridonate, the bisphosphonate used clinically to reduce bone resorption, is a relatively poor inhibitor of bone TRAP. Human bone TRAP is immunologically related to the porcine uterine secretory TRAP, uteroferrin. Monospecific rabbit antibodies to the bone TRAP have been immunopurified by using affinity chromatography with uteroferrin immobilized on Sepharose and can be used to detect low amounts of the enzyme in a simple dot-blot assay.

Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study.

Ten women were followed serially to determine the effect of stages of reproduction on calcium and bone metabolism. The study periods were nonpregnant nonlactating, the end of each trimester of gestation, 3 mo lactation, and postweaning. Comparisons were with nonpregnant nonlactating status for each individual. Fractional calcium absorption (P < 0.0001) and concentrations of 1,25-dihydroxyvitamin D (P < 0.01) were higher in the second and third trimesters. Total urinary calcium was higher during pregnancy and lower postweaning. Parathyroid hormone (PTH) concentrations were higher only postweaning (P < 0.01). Markers of bone turnover increased at the third trimester and during lactation: serum tartrate resistant acid phosphatase and bone specific alkaline phosphatase, and urinary deoxypyridinoline (P < 0.01). Serum procollagen I carboxypeptides increased only in the third trimester (P < 0.01). Bone mineral density by single-photon absorptiometry did not differ by period. We conclude that absorption and urinary excretion of calcium increase during pregnancy whereas bone turnover increases during late pregnancy and lactation; only renal changes consistent with an increase in PTH were seen postweaning.

Effects of prolactin in stimulating disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a chronic autoimmune illness, is influenced by hormones. High prolactin concentrations were associated with early death from autoimmune renal disease in NZB/NZW mice, an animal model of severe SLE. NZB/NZW mice that delivered and nursed pups and those that underwent pseudopregnancy had changes in serum IgG and autoantibodies. NZB/NZW mice treated with the prolactin-suppressing drug bromocriptine had prolonged lives. Elevated serum prolactin concentrations are reported in SLE patients of both sexes. We found four women with long-standing hyper-prolactinemia who developed SLE. A survey of premenopausal women whose sera were submitted for autoantibody testing showed that 20% with anti-ds-DNA antibodies also had high prolactin levels. Many hyperprolactinemic patients whose sera were referred to an endocrinology laboratory had positive FANA tests (women 33%, men 53%) but did not have SLE. Disease activity was suppressed in six of seven SLE patients treated with bromocriptine. All had elevated disease activity and five became unexpectedly hyperprolactinemic after treatment stopped. Manipulating serum prolactin affords a means of treating clinical SLE activity.

Exercise considerations for postmenopausal women with osteoporosis.

Individuals with osteoporosis are at an increased risk of fracture due to a net loss of bone mass. The cellular mechanisms causing decreased bone mass are increased osteoclast-mediated bone resorption and/or decreased osteoblast-mediated bone formation. Clinical studies have shown that bone loss can be prevented by estrogen replacement therapy and calcium supplementation. Weight-bearing and strengthening exercise may also play a role in retarding bone loss in the postmenopausal woman, and it may even increase bone mass. The essential components of an exercise program include intensity, duration, frequency, and type of activity. Additional goals of a therapeutic exercise program are to improve flexibility and balance, and to prevent falls. Structure-function relationships in normal and osteoporotic bone and the effects of exercise on bone are reviewed. A rational approach for exercise strategies is discussed.

Acute demyelinating encephalomyelitis (ADEM) in a patient with HIV infection.

A case of acute demyelinating encephalomyelitis (ADEM) in a patient with HIV infection is reported. Although the diagnosis of ADEM is based on clinical and radiological findings, the potential for full recovery, with appropriate treatment, is highlighted by this case. A concise review of the subject is given in the discussion.

Osteonecrosis of the knee in a patient receiving antiretroviral therapy.

A case of avascular osteonecrosis of the right knee is described in a patient with HIV infection. The patient had been receiving highly active antiretroviral therapy for two years prior to presentation. Osteonecrosis is an uncommon albeit serious complication of HIV infection and is associated with use of antiretroviral agents.

Bone mineral metabolism in children with juvenile rheumatoid arthritis.

Osteopenia has emerged as a major determinant of the outcome of children with juvenile rheumatoid arthritis. Although vertebral compression fractures and fractures of long bones were recognized historically as important clinical developments in the course of disease, a decrease in skeletal mass could only be quantitated and documented early in disease by the recent introduction of bone absorptiometry. This article is limited to recent data from studies on osteopenia in juvenile rheumatoid arthritis and suggests directions of future research that have relevance to current unanswered questions in prevention or management.

Alcohol availability and homicide in New Orleans: conceptual considerations for small area analysis of the effect of alcohol outlet density.

OBJECTIVE: To determine the geographic relation between homicide rate and two competing measures of exposure to alcohol outlets, alcohol outlets per square mile and alcohol outlets per person. METHOD: Homicides occurring in 1994 and 1995 and on-sale and off-sale alcohol outlets with active 1995 licenses were geocoded by address for aggregation at the census tract level. Ecologic analysis of the 155 urban residential census tracts in New Orleans was conducted with controls for potential sociodemographic confounders (% black, % adults unemployed, % unmarried households, and ratio males 15-24/males 35-44). RESULTS: After logarithmic transformation of all study variables, sociodemographic confounders alone accounted for 58% (R2 = .58) of the variance of homicide rates. Adding off-sale alcohol outlet density to the models, measured (beta +/- SE) either as outlets per square mile (beta = .211 +/- .062) or outlets per person (beta = .244 +/- .063), yielded strong geographic relations with homicide and increased the amount of variance explained (R2 = .62). A 10% higher off-sale outlet density accounted for a 2.4% higher homicide rate. CONCLUSIONS: Both off-sale alcohol outlets per square mile and off-sale outlets per person demonstrate strong geographic associations with homicide rates among urban residential census tracts in New Orleans. These findings suggest that communities faced with high rates of assaultive violence might consider policy interventions that address alcohol outlet related factors.

Antepartum reversal of hematologic abnormalities associated with the HELLP syndrome. A report of three cases.

The "HELLP syndrome" refers to the occurrence of thrombocytopenia, elevated liver enzymes and, at times, hemolysis in patients with preeclampsia. Although uncontrolled series have reported a reversal of thrombocytopenia and elevated liver enzymes with aspirin and colloid infusion, most authors recommend that delivery be done soon after the diagnosis is made. The abnormal laboratory parameters of the HELLP syndrome may be reversed completely with bed rest alone, and with preterm gestations, conservative management may be possible.

Primary osteoporosis. Methods to combat bone loss that accompanies aging.

Osteoporosis is a major public health problem in the United States. The key to its management is prevention by ensuring adequate amounts of calcium, vitamin D, and protein and exercise throughout life. When a significant amount of bone mass has been lost, therapeutic interventions are aimed at preventing further loss with use of antiresorptive agents (ie, estrogen, progestin, calcitonin, and bisphosphonates). Use of pharmacologic agents that stimulate bone formation is still in experimental stages. Research efforts focusing on prevention, diagnosis, and treatment of osteoporosis are in progress and should provide improved strategies in the future.

Estrogen replacement therapy at menopause. How benefits outweigh risks.

Bone loss and cardiovascular disease are the most important complications of menopause. Because estrogen has been shown to prevent bone loss and also reduce fracture rates in menopausal women, the authors recommend early replacement therapy. They also examine evidence that estrogen replacement may offer these women protection from cardiovascular disease and discuss the risks of estrogen-related endometrial and breast cancer.

The successful use of extra-corporeal membrane oxygenation in the management of a pregnant woman with severe H1N1 2009 influenza complicated by pneumonitis and adult respiratory distress syndrome.

We report a case of H1N1 2009 influenza A, in a previously fit woman at 24 weeks of gestation, who presented atypically with abdominal pain. The infection was complicated by severe respiratory failure and acute respiratory distress syndrome, requiring ventilatory support, including extra-corporeal membrane oxygenation (ECMO). This was one of the first cases of severe H1N1 disease presenting in the UK. Use of extra-corporeal membrane oxygenation for the complications of H1N1 resulted in full maternal recovery and subsequent delivery of a healthy infant.