Adrian K. Turner

Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States)

Objectives: Because several serum studies of vitamin D metabolites have produced equivocal results on their relation to prostate cancer risk, the purpose of this study is to evaluate this association further.Methods: A nested case-control study in a cohort of 3,737 Japanese-American men examined from 1967 to 1970 was conducted in Hawaii (United States). At the time of examination, a single blood specimen was obtained, and the serum was frozen. After a surveillance period of over 23 years, 136 tissue-confirmed incident cases of prostate cancer were identified. Their stored sera and those of 136 matched controls were measured for the following: 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, phosphorus, and parathyroid hormone.Results: There were no notable differences between cases and controls in their median serum levels of the five laboratory measurements. Odds ratios (OR) for prostate cancer, based on the quartiles of serum levels in controls, were also determined. The ORs for the highest quartiles relative to the lowest were 0.8 (95 percent confidence interval [CI] = 0.4-1.8) for 25-hydroxyvitamin D and 1.0 (CI = 0.5-2.1) for 1,25-dihydroxyvitamin D.Conclusion: It is possible that the lack of sufficient numbers of study subjects with low vitamin D levels affected the results. Nonetheless, the findings suggest that there is a lack of a strong association between vitamin D and prostate cancer.

Safety and efficacy of oral calcitriol (1,25-dihydroxyvitamin D3) for the treatment of psoriasis.

plaque‐type psoriasis has been successfully treated with oral calcitriol. but there has been no long‐term follow‐up on the safety and efficacy of this calciotropic hormone for psoriasis. In a single centre study, patients were enrolled in an open trial to evaluate the efficacy and safety of oral calcitriol for psoriasis. Of the 85 patients who received oral calcitriol, 88.0% had some improvement in their disease: 26.5, 36.2 and 25.3%. had complete, moderate and slight improvement in their disease. respectively. The mean baseline psoriasis area severity index score (PASI) of 18 4 ± 1.0 was reduced to 9.7 ±0.8 and 7.8±1.3 after 6 and 24 months on oral calcitriol therapy. Serum calcium concentrations and 24 h urinary calcium excretion increased by 3.9% and 148.2%, respectively. but were not outside the normal range. Bone mineral density remained unchanged. The clearance of creatinine decreased by 13 4% from baseline during the first 6 months of treatment, and thereafter. remained unchanged after 3 years of follow up. An evaluation of creatinine, inulin and para‐aminohypurate (PAH) clearance was performed in eight patients. After 6 months on oral calcitriol. there was a 22.5% decline in creatinine clearance but no significant changes were observed in either inulin or PAH clearance, suggesting that calcitriol alters creatinine metabolism or secretion hut does not affect renal function. Oral calcitriol is effective and safe for the treatment of psoriasis.

DIFFERENTIATING BETWEEN ORCHIECTOMIZED RATS AND CONTROLS USING MEASUREMENTS OF TRABECULAR BONE DENSITY : A COMPARISON AMONG DXA, HISTOMORPHOMETRY, AND PERIPHERAL QUANTITATIVE COMPUTERIZED TOMOGRAPHY

In studies of rat bone metabolism, trabecular bone density should be measured. Three established methods of measuring trabecular bone include trabecular bone volume by histomorphometry (BV/TV%), trabecular bone density by peripheral quantitative computerized tomography (pQCT), and areal bone density of trabecular-rich regions by dual x-ray absorptiometry (DXA). We compared the ability of these three methods to discriminate between orchiectomized (orchidectomized) rats and controls. Sixteen male Sprague-Dawley rats (400–425 g) were orchiectomized, and 16 others were controls. In vivo spine bone mineral density (BMD) was measured at the beginning of the study and again after 11 weeks. Rats were sacrificed, and ex vivo BMDs of the right femur and tibia were measured by DXA, followed by trabecular bone density of the right proximal tibia by pQCT. BV/TV% of the left proximal tibia was measured by histomorphometry. Differences between groups were detected by all three methods, but both the magnitude of the difference between groups and the variance of the measurements was much greater for histomorphometry and pQCT than for DXA. Consequently, the statistical significance for the difference between groups was comparable for all three methods. Of the sites measured with DXA, the proximal tibia had the greatest statistical significance for the difference between groups. In summary, all three methods can demonstrate the effect of orchiectomy on trabecular bone. The large differences between groups seen by histomorphometry are also seen by pQCT but not by DXA. We conclude that trabecular bone density by pQCT may be a reasonable surrogate for measurements by histomorphometry.

Efficacy and safety of topical calcitriol (1,25‐dihydroxyvitamin D3) for the treatment of psoriasis

Summary Plaque‐type psoriasis has been successfully treated with topical calcitriol. but there has been no term follow‐up study of the safety and efficacy of this calciotropic hormone.

Complement Processing and Immunoglobulin Binding to Neisseria gonorrhoeae Determined In Vitro Simulates In Vivo Effects

Local inflammation elicited by Neisseria gonorrhoeae correlates closely with sensitivity to killing by normal human serum. Serum-sensitive (SS) isolates are rendered resistant in vitro by lipooligosaccharide sialylation. Differences in C3b processing on N. gonorrhoeae in vitro were found to match findings at the cervical level in vivo. Nonsialylated SS gonococci bound 5-fold more C3b than did stably serum-resistant (SR) gonococci; most was processed to iC3b, yet significant C3b persisted. Sialylated SS gonococci bound 4-fold less total C3 antigen than did SR gonococci, which was promptly converted to iC3b. C3b bound later on stably SR gonococci but again was processed swiftly to iC3b. In vivo, the iC3b/C3 ratio of SS isolates more closely resembled nonsialylated SS isolates in vitro, implying heterogeneous sialylation or desialylation in vivo. In vitro, total IgM bound was unchanged by sialylation of SS isolates, but total C4 bound decreased by 75%, suggesting that sialylation may indirectly regulate the classical complement pathway.

Testosterone increases bone mineral density in female-to-male transsexuals: a case series of 15 subjects

objective  Testosterone therapy for osteoporosis has not been studied extensively in women because of its potential to cause virilization. Female‐to‐male transsexuals are genetic females who suffer from gender dysphoria and thus take supra‐physiologic doses of testosterone to change from the female to male phenotype. The aim of this study is to examine the effects of testosterone treatment on the genetic female skeleton.

Severe Generalized Bone Pain and Osteoporosis in a Premenopausal Black Female: Effect of Vitamin D Replacement

Abstract A 39-yr-old black female, with a history of partial gastrectomy, presented with worsening low back and left hip pain. Initial evaluation revealed an elevated sedimentation rate, the presence of antinuclear antibodies, and the absence of rheumatoid factor. Prednisone therapy, for early seronegative rheumatoid arthritis, was of minimal benefit. A bone scan showed radionuclide uptake in the left sacrum. Subsequent biopsy revealed a healing fracture. The pain later involved both hips, knees, feet, hands, spine, shoulders, and ribs. Laboratory evaluation revealed hypocalcemia, hypophosphatemia, a 25-hydroxyvitamin D level of 12 ng/mL (normal, 9–52 ng/mL), and an intact parathyroid hormone level of 304 pg/mL (normal, 10–65 pg/mL). The initial bone density by dual energy X-ray absorptiometry of the lumbar spine was 0.871 g/cm 2 (T-score –1.81) and of the femoral neck, 0.553 g/cm 2 (T score –3.84). Vitamin D and calcium therapy corrected the vitamin D deficiency and secondary hyperparathyroidism, with resolution of pain over the ensuing 4 mo. A repeat bone density 2 yr later revealed a 23.7% increase in the lumbar spine and a 36.2% increase in the femoral neck. Clinical osteomalacia results from long-standing vitamin D deficiency. Treatment can result in resolution of bone pain, while producing marked increases in bone density.

A method for the determination of the circulating concentration of vitamin D.

Determination des concentrations des vitamines D 2 et D 3 dans le serum et le plasma par extraction lipidique. Separation des lipides et des vitamines par chromatographie. Quantification des vitamines en injectant la fraction contenant les vitamines dans une colonne HPLC puis par absorption aux ultraviolets

Bone Mineral Density Assessment: Comparison of Dual-Energy X-ray Absorptiometry Measurements at the Calcaneus, Spine, and Hip

It is widely accepted that bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA) at the spine, hip, and calcaneus predict fracture risk. Few published studies to date have examined the relationship between pDXA measurements at the calcaneus to those at the hip and spine. It has been demonstrated that T-score-based criteria cannot be universally applied to all skeletal sites and measurement technologies. Our goal was to define the calcaneal T-score threshold equivalent to low bone mass at the hip or spine. A total of 119 female patients between the ages of 33 and 76 yr of age were recruited at Boston University Medical Center for bone densitometry screening. Bone density measurements were obtained at the calcaneus using the portable Norland Apollo Densitometer (Norland Medical Systems, Fort Atkinson, WI) and at the hip and spine using the Norland Eclipse densitometer. By defining a pDXA T-score < or =-1 as a positive test and DXA scores < or =-1 as the presence of low bone mass, we obtained a specificity of 100% and a sensitivity of 73% (positive predictive value 100% and negative predictive value 80%) in detecting low bone mass at the femoral neck in women over age 65 yr. In women between 40 and 65 yr of age, we obtained a sensitivity of 50% and a specificity of 93% (positive predictive value 93% and negative predictive value 50%) in detecting low bone mass at the femoral neck. In women less than 40 yr of age, we obtained a sensitivity of 13% and a specificity of 100% (positive predictive value 100% and negative predictive value 75%) in detecting low bone mass at the femoral neck. From receiver operating characteristic curves, a calcaneal T-score < or =0.0 detects those with a T-score < or =-1 at the femoral neck and lumbar spine with 100% and 85% sensitivity, respectively. Peripheral DXA of the calcaneus is a sensitive and specific test to diagnose low bone mass in women over 65 yr of age. In women under 65 yr of age, this modality, though not as sensitive, is specific in detecting low bone mass. We conclude that a pDXA calcaneal T-score < or =0 is highly sensitive in predicting osteopenia and osteoporosis at the femoral neck and lumbar spine.

The significance of urinary free cortisol and progesterone in normal and anencephalic pregnancy.

Urinary free cortisol and progesterone were determined by radioimmunoassay in 18 normal and 16 anencephalic pregnancies and urinary free cortisol levels in 9 nonpregnant women. In normal pregnancy the urinary free cortisol (46.89 +/- 34.02 mug per 24 hours) was significantly higher (P less than 0.001) than that found with anencephaly (17.19 +/- 13.20 mug per 24 hours) and 2 1/2 times (P less than 0.001) the nonpregnant value (18.47 +/- 5.44 mug per 24 hours). In 12 of the anencephalic pregnancies, urinary free cortisol levels (11.05 +/- 5.56 mug per 24 hours) were significantly lower than in nonpregnant women (P less than 0.001). Urinary progesterone levels in normal pregnancy (15.57 +/- 9.66 mug per 24 hours) and anencephaly (18.54 +/- 12.69 mug per 24 hours) were comparable. The cortisol excretion values associated with anencephaly indicate that the normal fetus contributes substantially to the maternal plasma cortisol pool. Urinary free cortisol determinations may be a useful index of fetal adrenal dysfunction.