Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.

Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius. INTRODUCTION: The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age. MATERIALS AND METHODS: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables. RESULTS: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049). CONCLUSIONS: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.     

Auditory steady-state evoked potentials (ASSEPs): a study of optimal stimulation parameters for frequency-specific threshold measurement in dogs.

OBJECTIVE: To define the optimal stimulation parameters (AM/FM vs AM alone and modulation rate) for frequency-specific threshold measurements using ASSEPs in dogs. Dependent variables were thresholds and recording times needed to obtain a response at threshold. To compare the ASSEP threshold results obtained with the optimal stimulation parameters to those obtained with the Tone-Burst/Auditory Brainstem Response (TB/ABR) combination. METHODS: Thirty-two sedated Beagle puppies were tested at 5 audiometric frequencies (0.5-8 kHz) and 6 ASSEP modulation rates (21-199 Hz). RESULTS: The ASSEP threshold-modulation rate functions had a high-pass profile with corner frequencies of 101 Hz for 0.5, 1 and 2 kHz carriers and of 151 Hz for 4 and 8 kHz carriers. AM stimuli did not yield higher thresholds than the AM/FM ones except at 1 kHz. Modulation type had no effect on testing duration. Audiometric profiles were obtained much more rapidly with ASSEPs than with TB/ABRs (mean: 50 vs 135 min). Both ASSEP and TB/ABR provided thresholds estimates characterized by low intersubject variability. CONCLUSIONS: ASSEPs are a valid and rapid method for audiometric assessment in sedated dogs. SIGNIFICANCE: ASSEPs offer a new, competitive tool for frequency-specific assessment of hearing in the canine species.     

Pulmonary resection for metastases from colorectal cancer

Aim: The prognosis of patients with disseminated colorectal carcinoma is poor except for those with single organ pulmonary or hepatic metastases. The objective of the present study was to evaluate the result of pulmonary metastasectomy for colorectal secondary and to identify the prognostic factors. Methods: This was a retrospective study of 80 patients who had pulmonary metastasectomy for pulmonary secondary from colorectal carcinoma in Queen Elizabeth Hospital, Hong Kong. Results: The overall 5‐year and 10‐year survival rates of the entire cohort were 42.5% and 35.5%, respectively. High premetastasectomy carcinoembryonic antigen (> 20 μg/dL), short disease‐free interval (< 12 months) and incomplete resection were the independent prognostic factors. Neither the characteristics of the primary colorectal tumour nor the number of metastatic nodules had a significant contribution to the long‐term survival. Six patients underwent second pulmonary metastasectomy and three were still free from tumour recurrence after the second operation. Conclusion: Patients with pulmonary metastases from colorectal carcinoma would benefit from pulmonary metastasectomy. High premetastasectomy carcinoembryonic antigen and short disease‐free interval were negative predictive factors for survival. Long‐term follow‐up study is required, as recurrence can occur more than 5 years after pulmonary metastasectomy. Also, whether the survival benefit is due to surgical treatment effect or lead‐time bias remains undecided.     

Correlation of growth factor receptor expression with clinical growth in vestibular schwannomas.

OBJECTIVE: To examine the relationship between growth rate of vestibular schwannomas and the expression of various growth factor receptors. STUDY DESIGN: Retrospective case review of clinical growth rate in conjunction with a histopathologic and immunohistochemical reexamination of archival specimens. SETTING: A tertiary referral neurotologic center. PATIENTS: Three groups: a historical group to act as controls, consisting of 30 patients with sporadic vestibular schwannomas removed before the unit adopted an initial interval scan policy; a group of 14 patients with sporadic vestibular schwannomas who had undergone an initial interval scan policy, showed radiologic evidence of growth, and therefore had their schwannoma removed; and a group of 16 schwannomas removed from 11 neurofibromatosis Type 2 patients. MAIN OUTCOME MEASURES: A comparison between the three clinical groups using immunohistochemical studies to determine the level of expression of the proliferation factor Ki-67, c-erbB-2, and c-erbB-3 receptors and fibroblastic growth factor receptors 1 and 4. RESULTS: The level of expression of the proliferation factor Ki-67 was very low and similar in all three groups. C-erbB-2 and c-erbB-3 receptors were not expressed in any of the groups. fibroblastic growth factor receptor 4 expression was not significantly different, but there was a variation in the expression of fibroblastic growth factor receptor 1 between the three groups that correlated well with the differing incidence of growth in the groups. The increase in expression of fibroblastic growth factor receptor 1 in the neurofibromatosis Type 2 group was not statistically significant, but the increase in expression of fibroblastic growth factor receptor 1 in the growing sporadic group was statistically significant when compared with the historical controls. The level of fibroblastic growth factor receptor 1 expression correlates significantly with the rate of growth as measured on interval magnetic resonance imaging. CONCLUSIONS: Overexpression of fibroblastic growth factor receptor 1 has a positive correlation with the incidence and the rate of growth of sporadic vestibular schwannomas.     

125iodine reimplantation for locally progressive prostatic carcinoma

We treated 13 patients with a second 125iodine implant for local recurrence of prostatic carcinoma. All patients had biopsy proved palpable recurrence without evidence of distant metastases. Full doses of irradiation were used (median matched peripheral dose 170 Gy.). Six patients had complete regression of palpable recurrence, 2 had partial regression, 2 had no apparent response and 3 were unevaluable for local response. Actuarial freedom from local disease progression at 5 years was 51%. Despite a relatively high rate of local disease control the actuarial rate of distant metastases reached 100% at 6 years after reimplantation. There were 2 severe rectal complications and 4 instances of mild to moderate urinary incontinence among the 13 patients. Local regression of recurrent prostatic carcinoma may be achieved with 125iodine reimplantation but most patients still had distant metastases.     

Evidence of alkaline phosphatase interference in a zidovudine radioimmunoassay.

Phosphorylated zidovudine (ZDV) concentrations may provide a link between drug exposure and clinical efficacy since these would include the active, intracellular form of the drug, ZDV triphosphate. Many groups are investigating the optimal methodology that can be used to accomplish this goal. The initial purpose of the present studies was to examine the effect of the inclusion of cell wash steps on the quantitation of intracellular ZDV. Ten milliliters of whole blood collected from healthy volunteers was spiked with increasing ZDV concentrations (0.187, 0.375, 1.87, and 3.75 microM), allowed to equilibrate at room temperature for 1 h, and separated into whole-blood components by a density gradient procedure. A mononuclear cell pellet was obtained, reconstituted with 2 ml of phosphate-buffered saline (PBS), and split into two aliquots, one of which was not washed at all and the other of which was washed four times with 1 ml of PBS. All samples were analyzed by ZDV radioimmunoassay (RIA) after a 1:1 dilution with either 1 mg of alkaline phosphatase (type 1-S; Sigma) per ml or PBS. Parent ZDV was measured in those samples which were not treated with the enzyme, while total ZDV was measured in those samples which were exposed to alkaline phosphatase (21 degrees C for 1 h). The result of the difference between the two samples is total phosphorylated ZDV. During the experiment, evidence of alkaline phosphatase interference with the RIA became apparent, confusing interpretation of intracellular ZDV concentrations. This evidence was based on three sets of data. First, wash samples showed increases in ZDV concentrations of as great as 0.127 microgramM after exposure to alkaline phosphatase, even though on microscopic inspection the wash samples were acellular. Second, the sum of total ZDV recovered from the four wash samples plus the washed cell pellet was as much as 14-fold greater than the total ZDV measured in the unwashed cell pellet. Theoretically, at least, these two entities should be equal. Finally, control samples of alkaline phosphatase in PBS (0.5 mg/ml) run directly through the assay measured false ZDV levels ranging from 0.002 to 0.075 microgramM (0.6 to 20 ng/ml). Alkaline phosphatase is frequently used to measure phosphorylated anabolites of ZDV in peripheral blood mononuclear cells. These data show that the particular form of alkaline phosphatase used may interfere with the ZDV RIA and may confuse the interpretation of phosphorylated anabolite concentrations of ZDV.