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Background: All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. Methods. To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. Results: We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean ± SE: 1.61 ± 0.41) than in SCA2 (0.71 ± 0.31), SCA3 (0.65 ± 0.24) and SCA6 (0.87 ± 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). Conclusions: The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies. © 2013 Ashizawa et al.; licensee BioMed Central Ltd.

The different conclusions reached by studies investigating the utility of DSEPs prevent a confident conclusion regarding utility. Some investigators are strong believers in the diagnostic usefulness of this technique. Others are mere skeptical. One possible cause is variable study design. Most studies provide evidence no higher than level III (case reports, expert opinions). Controlled studies, especially with blinded interpreters of the tests, would provide needed evidence of efficacy in view of the existing confusion in the literature. It is our consensus that the current evidence supporting the diagnostic use of DSEPs is Type D and that DSEPs should be regarded as Investigational, meaning that current evidence is insufficient to determine appropriateness. This group does encourage further study.

Purpose: Uveal melanoma (UM) is the most prevalent and lethal intraocular malignancy in adults. Here, we examined the importance of hypoxia in UM growth and tested the antitumor effects of arylsulfonamide 64B, an inhibitor of the hypoxia-induced factor (HIF) pathway in animal models of UM and investigated the related mechanisms., Experimental Design: UM cells were implanted in the uvea of mice eyes and mice systemically treated with 64B. Drug effect on primary eye tumor growth, circulating tumor cells, metastasis formation in liver, and survival were examined. 64B effects on UM cell growth, invasion and hypoxia-induced expression of C-X-C chemokine receptor type 4 (CXCR4) and mesenchymal-epithelial transition factor (c-Met) were measured. Luciferase reporter assays, chromatin immunoprecipitation, co-immunoprecipitation, and cellular thermal shift assays were used to determine how 64B interferes with the HIF transcriptional complex., Results: Systemic administration of 64B had potent antitumor effects against UM in several orthotopic mouse models, suppressing UM growth in the eye (∼70% reduction) and spontaneous liver metastasis (∼50% reduction), and extending mice survival ( P < 0.001) while being well tolerated. 64B inhibited hypoxia-induced expression of CXCR4 and c-Met, 2 key drivers of tumor invasion and metastasis. 64B disrupted the HIF-1 complex by interfering with HIF-1α binding to p300/CBP co-factors, thus reducing p300 recruitment to the MET and CXCR4 gene promoters. 64B could thermostabilize p300, supporting direct 64B binding to p300., Conclusions: Our preclinical efficacy studies support the further optimization of the 64B chemical scaffold toward a clinical candidate for the treatment of UM., (©2018 American Association for Cancer Research.)

Background: The clinical effects of inhaled corticosteroids (ICS) on chronic beryllium disease (CBD) are unknown. Although frequently used for symptoms or disease not requiring systemic therapy, the clinical course of patients on ICS has not been evaluated., Methods: In a retrospective cohort study, forty-eight subjects with CBD, diagnosed by granulomas on lung biopsy and treated with inhaled corticosteroids, were matched to sixty-eight subjects with CBD who were not treated. Pulmonary function testing, exercise tolerance, blood BeLPT, BAL cell count, and symptoms were evaluated., Results: Treated patients showed no significant change over time in pulmonary function, when compared to controls, by forced vital capacity (FVC, p = 0.28) or diffusion capacity (DLCO, p = 0.45) or in exercise tolerance testing. However, symptoms of cough significantly improved in 58% (compared to 17% in controls) and dyspnea improved in 26% after ICS treatment (compared to 0 in controls). Symptoms of cough were improved in patients with a lower baseline FEV1 and FEV1/FVC ratio. Subgroup analysis showed significant lung function response in cases with lower baseline FEV1/FVC and higher residual volume (RV)., Conclusion: Although FVC and DLCO did not improve in the ICS treated group, we saw no difference in decline compared to matched controls. Symptoms of dyspnea and cough improved with ICS especially in those with obstruction and air trapping suggesting that these should be considered an indication of ICS use in CBD patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

While progress has been made in treating cancer, cytotoxic chemotherapeutic agents are still the most widely used drugs and are associated with severe side-effects. Drugs that target unique molecular signalling pathways are needed for treating cancer with low or no intrinsic toxicity to normal cells. Our goal is to target hypoxic tumours and specifically the hypoxia inducible factor (HIF) pathway for the development of new cancer therapies. To this end, we have previously developed benzopyran-based HIF-1 inhibitors such as arylsulfonamide KCN1. However, KCN1 and its earlier analogs have poor water solubility, which hamper their applications. Herein, we describe a series of KCN1 analogs that incorporate a morpholine moiety at various positions. We found that replacing the benzopyran group of KCN1 with a phenyl group with a morpholinomethyl moiety at the para positions had minimal effect on potency and improved the water solubility of two new compounds by more than 10-fold compared to KCN1, the lead compound.

Background: Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in cystic fibrosis., Objectives: To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the cystic fibrosis population., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 08 July 2013., Selection Criteria: Randomised and quasi-randomised controlled studies of vitamin D supplementation compared to placebo in the cystic fibrosis population regardless of exocrine pancreatic function., Data Collection and Analysis: Both authors independently assessed the risk of bias of each included study and extracted outcome data (from published study information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events., Main Results: Six studies (239 participants) are included, although only three studies provided data from 69 adults and children with cystic fibrosis for analysis. One study compared a single high dose of vitamin D (250,000 IU) to placebo at the time of hospital admission with a respiratory exacerbation in 30 pancreatic insufficient adults with cystic fibrosis. The second study compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The third study compared supplemental 1 g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1 g calcium and placebo in a double-blind randomised cross-over study; only nine children who completed both vitamin D and placebo groups after six-months supplementation and a three-month washout period are included; pancreatic sufficiency or disease status of participants are not defined. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (e.g. severity of lung disease, growth and nutrition, pancreatic sufficiency).The only outcome for which we could combine data from more than two studies was 25-hydroxyvitamin D levels; patients receiving vitamin D supplementation had significantly higher levels, mean difference 7.24 ng/ml (95% confidence interval 5.01 to 9.46). However, ironically one study reported 1,25(OH)2D with levels significantly favouring the placebo group, mean difference -30.30 pmol/ml (95% confidence interval -59.89 to -0.71). Bone mineral density was measured in two studies; both described no significant change between groups. There were no adverse events in any study.The remaining three studies are published as abstracts only and did not provide data for analysis. These abstracts include: a report of pre-intervention data in a study comparing daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults; an interim report of a double-blind randomised control study comparing 5000 IU vitamin D daily for 12 weeks during winter in 67 adult cystic fibrosis patients; and a comparison of the effect of three months of vitamin D supplementation (dose not specified) with placebo on bone mineral density in 42 children with cystic fibrosis and low bone mineral density.Risk of bias was highly variable between all studies. Only one study had a low risk of bias for the five main criteria (random sequence generation, allocation, blinding, attrition and reporting). The rest of the studies had unclear or high risks of bias. Two studies had a low risk of bias for blinding and another two studies for attrition bias. In the studies published as abstracts, assessment of the risks of bias was uncertain in many aspects., Authors' Conclusions: In patients receiving vitamin D supplementation, 25-hydroxyvitamin D levels are significantly higher. However, there is no evidence of clinical benefit or harm in the limited number of small-sized published studies. Adherence to relevant cystic fibrosis guidelines on vitamin D supplementation should be considered until further evidence is available.

Background: Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in CF., Objectives: To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the CF population., Search Methods: We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 15 February 2012., Selection Criteria: Randomised and quasi-randomised controlled trials of vitamin D supplementation compared to placebo in the CF population regardless of exocrine pancreatic function., Data Collection and Analysis: Both authors independently assessed the 'risk of bias' of each included trial and extracted outcome data (from published trial information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events., Main Results: Three studies are included, although only data from two were available (41 adults and children with CF). One of these studies compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The other (abstract only) compared supplemental 1g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1g calcium and placebo in a double-blind randomised cross-over trial; only 11 children (vitamin D and placebo groups) after six-months supplementation are included; inclusion criteria, pancreatic sufficiency or disease status of participants are not defined. There were no significant differences in primary or secondary outcomes in either study. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (eg severity of lung disease, growth and nutrition, pancreatic sufficiency). There were no adverse events in either study. The third study (abstract only) compared daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults, only pre-intervention data were available., Authors' Conclusions: There is no evidence of benefit or harm in the limited number of small-sized published trials. Adherence to relevant CF guidelines on vitamin D should be considered until further evidence is available.

A movement to create a global patient registry for as many as 7,000 rare diseases was launched at a workshop, "Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories, and Clinical Data." http://rarediseases.info.nih.gov/PATIENT&#95;REGISTRIES&#95;WORKSHOP/. The workshop was sponsored by the Office of Rare Diseases Research (ORDR). The focus was the building of an infrastructure for an internet-based global registry linking to biorepositories. Such a registry would serve the patients, investigators, and drug companies. To aid researchers the participants suggested the creation of a centralized database of biorepositories for rare biospecimens (RD-HUB)http://biospecimens.ordr.info.nih.gov/ that could be linked to the registry. Over two days of presentations and breakout sessions, several hundred attendees discussed government rules and regulations concerning privacy and patients' rights and the nature and scope of data to be entered into a central registry as well as concerns about how to validate patient and clinician-entered data to ensure data accuracy. Mechanisms for aggregating data from existing registries were also discussed. The attendees identified registry best practices, model coding systems, international systems for recruiting patients into clinical trials and novel ways of using the internet directly to invite participation in research. They also speculated about who would bear ultimate responsibility for the informatics in the registry and who would have access to the information. Hurdles associated with biospecimen collection and how to overcome them were detailed. The development of the recommendations was, in itself, an indication of the commitment of the rare disease community as never before., (Published by Elsevier Inc.)

Background: Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in CF., Objectives: To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the CF population., Search Strategy: We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 09 June 2009., Selection Criteria: Randomised and quasi-randomised controlled trials of vitamin D supplementation compared to placebo in the CF population regardless of exocrine pancreatic function., Data Collection and Analysis: Both authors independently assessed the 'risk of bias' of each included trial and extracted outcome data (from published trial information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events., Main Results: Three studies are included, although only data from two were available (41 adults and children with CF). One of these studies compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The other (abstract only) compared supplemental 1g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1g calcium and placebo in a double-blind randomised cross-over trial; only 11 children (vitamin D and placebo groups) after six-months supplementation are included; inclusion criteria, pancreatic sufficiency or disease status of participants are not defined. There were no significant differences in primary or secondary outcomes in either study. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (eg severity of lung disease, growth and nutrition, pancreatic sufficiency). There were no adverse events in either study. The third study (abstract only) compared daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults, only pre-intervention data were available., Authors' Conclusions: There is no evidence of benefit or harm in the limited number of small-sized published trials. Adherence to relevant CF guidelines on vitamin D should be considered until further evidence is available.

This study examined the impact of age on contractile function, Ca(2+) homeostasis, and cell viability in isolated myocytes exposed to simulated ischemia and reperfusion. Ventricular myocytes were isolated from anesthetized young adult (3 mo) and aged (24 mo) male Fischer 344 rats. Cells were field-stimulated at 4 Hz (37 degrees C), exposed to simulated ischemia, and reperfused with Tyrode solution. Cell shortening and intracellular Ca(2+) were measured simultaneously with an edge detector and fura-2. Cell viability was assessed by Trypan blue exclusion. Ischemia (20-45 min) depressed amplitudes of contraction equally in isolated myocytes from young adult and aged animals. The degree of postischemic contractile depression (stunning) was comparable in both groups. Ca(2+) transient amplitudes were depressed in early reperfusion in young adult and aged cells and then recovered to preischemic levels in both groups. Cell viability also declined equally in reperfusion in both groups. In short, some cellular responses to simulated ischemia and reperfusion were similar in both groups. Even so, aged myocytes exhibited a much greater and more prolonged accumulation of diastolic Ca(2+) in ischemia and in early reperfusion compared with myocytes from younger animals. In addition, the degree of mechanical alternans in ischemia increased significantly with age. The observation that there is an age-related increase in accumulation of diastolic Ca(2+) in ischemia and early reperfusion may account for the increased sensitivity to ischemia and reperfusion injury in the aging heart. The occurrence of mechanical alternans in ischemia may contribute to contractile dysfunction in ischemia in the aging heart.

Objectives: To analyze the response patterns and trends of 68 surveys of successive NIH consensus panels' views on the NIH consensus process., Methods: Each panel's responses were compared to an "average" panel's responses calculated by determining the mean response for each survey question across panels., Results: The results show a stable pattern of panelists' generally positive views. However, several conferences were judged very positively and some very negatively compared to the norm. Most negatively viewed conferences occurred early in the consensus program's history., Conclusions: The disparate perceptions are discussed and interpreted as reflecting favorable panels' views of recent changes in the NIH Consensus Development Program.

There are gaps in understanding between practicing physicians (curative medicine) and those trained in public health and epidemiology (population medicine). In the last century, these groups were closer, as physicians played a role in public health, sanitation and in the prevention of the spreading of infection. However, with the recent extraordinary successes of the biomedical model in explaining disease, and the ensuing explosion of remarkable - and expensive - medical procedures and treatments, public health, preventive medicine and the population approach in general have been overshadowed. In this essay, I try to explain how the training of physicians and the daily care of patients may hinder their appreciation of the population model. For instance, for many of the myriad decisions involved in patient care in daily practice, there is little evidence, population derived or otherwise. What little evidence there is may be dominated by personal experiences, opinions and values. Additionally, the statistical and epidemiologic approach necessary for the maintenance of health and prevention of illness may not be valued by practitioners whose training and focus is on treating sick people one by one. To illustrate these disparities in understanding, examples are given from the NIH Consensus Conference on mammography screening for women aged 40-49, and from the use of science in the courtroom in adjudicating toxic tort cases. Understanding population medicine requires an appreciation of the concepts of chance, probability and statistics and of epidemiologic principles, difficult areas for many - including the general public. These topics play a small to nonexistent role in the formal training of most physicians. Some closing of the gap in understanding may be occurring. It is hoped this essay will help.

Objectives: In February 1994, an National Institutes of Health (NIH) Consensus Development Conference panel unequivocally recommended antimicrobial therapy to eradicate Helicobacter pylori in the treatment of peptic ulcer disease. The goal of this study was to determine if these recommendations resulted in a change in physician prescribing among an underserved population., Methods: Computerized Pennsylvania Medicaid data from January 1993 through February 1996 were used to evaluate prescribing patterns in the year before and 2 years after the NIH conference. An interrupted time series model, based on 12,737 outpatient peptic ulcer disease encounters, assessed the impact of the conference in influencing physician prescribing., Results: The prescription of antimicrobial agents for the treatment of peptic ulcer disease significantly increased across the study period, from 6.5% in January 1993 to 10.2% in February 1996. Similarly, the prescription rate for the proton pump inhibitor, omeprazole, significantly increased from 9.4% in January 1993 to 25.6% in February 1996. Neither trend, however, could be attributed to the NIH Consensus Development Conference. Stratification by physician specialty, ulcer type, nonsteroidal anti-inflammatory drug use, and patient demographics did not affect these results. The traditional treatment approach, using H2-receptor antagonists, remained the preferred pharmacotherapy (72% of all prescriptions)., Conclusions: Two years after the highly publicized NIH conference on the eradication of Helicobacter pylori, antimicrobial agents were not widely prescribed among the Pennsylvania Medicaid population. In treating this underserved population, physicians do not appear to be using recommendations developed by an NIH expert panel based on recent scientific advances.

The U.S. National Institutes of Health (NIH) Consensus Development Program (CDP) Guidelines have undergone some modifications over the program's 18-year history. They have never been published in archival form. This article reviews the evolution of the NIH CDP Guidelines and then presents the complete 1995 version.

The NIH CDCs are a highly visible, public forum to evaluate controversial medical technologies by synthesizing current medical science data. The consensus statements, although not intended as medical practice guidelines, may form part of the database preceding guideline formulation. It is difficult to assess the effect of the conferences on physician practice, in part reflecting the interference of the many other influences, medical and nonmedical, on physician behavior. Yet the program has had some success in influencing reimbursement policy for some technologies here and abroad and in influencing specialty organization policy, thereby indirectly affecting physician behavior. On the other hand, OMAR's dissemination activities have apparently been so successful that demand for CDC statements has more than doubled over the past five years, prompting OMAR to establish an information service (including fax and the Internet). And finally, the program has spawned consensus conferences throughout the world, including Canada, Western Europe, and Israel (Goodman & Baratz 1990).

Ambulatory blood pressure monitoring (ABPM) was used as an effective methodology by a primary care physician to assess normalcy of blood pressure (BP) and heart rate during pregnancy. One hundred fifty pregnant women in one of three periods (18 to 22, 30 to 32, and 36 to 38 weeks) of gestation and 30 age-matched nonpregnant women participated in this study. The study was designed to establish ABPM standards of normalcy during critical times of gestation. Twenty-four-hour BP (systolic and diastolic BP) values monitored during gestational weeks 18 to 22 and 30 to 32 were similar to each other and lower than the same values recorded in nonpregnant women. Blood pressures monitored during gestational weeks 36 to 38 were significantly higher than similar values observed during the two earlier gestational periods but not significantly higher than nonpregnancy BP values. Heart rates were significantly elevated during all gestational periods when compared with nonpregnancy heart rates. The results of this study established normalcy BP curves during three different gestational periods. Mean 24-h, daytime, and nighttime BPs were significantly elevated during weeks 36 to 38 when compared with BPs recorded during gestational weeks 18 to 22 and 30 to 32. Ambulatory blood pressure monitoring is a useful tool for the measurement and treatment of BP abnormalities during pregnancy.

OBJECTIVE--Because we found examples where courts of law ruled against insurance carriers that had been sued for reimbursement for unproven medical procedures, we conducted a case study to determine the reasoning behind these decisions that run counter to accepted medical science. Such actions circumvent health technology assessment and could contribute to escalating health care costs and poorer quality health care. DATA SOURCES--A literature search identified 17 cases between 1980 and 1989 in which an insurance company was sued to reimburse a patient who had received an unproven or questionable health technology; 14 of these suits were decided in favor of the plaintiff, and the insurance company was ordered to pay. Discussed in this article are six of these cases, two involving Laetrile (amygdalin), two involving immunoaugmentative therapy, and two involving thermography, technologies that had previously been assessed as not safe, not effective, or inadequately evaluated. DATA SYNTHESIS AND CONCLUSIONS--The circumstances determining how the courts arrive at these "unscientific" decisions fall into three general categories: (1) for legal reasons, the insurance contract is interpreted in favor of the insured; (2) the reluctance and/or inability, legal or otherwise, of the courts to use published scientific literature; and (3) the use of adversarial "expert" witnesses with potential conflicts of interest. To address this situation, we first urge the legal and insurance industries to cooperate in improving the contract language and process in a way that would be both legally and scientifically appropriate. Second, we encourage the courts to use and foster the use of published peer-reviewed scientific material as evidence whenever possible. Third, we recommend that the courts choose their own unbiased expert witnesses to interpret scientific material.

The treatment of prostate cancer was reviewed at a U.S. National Institutes of Health Consensus Development Conference in June 1987. Data from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results tumor registries were analyzed and showed that the proportion of eligible prostate cancer patients receiving the recommended therapies did not increase at a faster rate after the conference than before.

Background: Ambulatory blood pressure monitoring (ABPM) has been described as an effective method for the diagnosis and formulation of the treatment of hypertension by the primary care physician., Methods: Sixty patients selected from a suburban private primary care practice participated in a study that compared measurements of office blood pressures using a mercury sphygmomanometer with the same pressures recorded by ABPM., Results: Blood pressures and blood pressure loads measured by ABPM were significantly lower than blood pressures and pressure loads recorded in the office setting., Conclusions: Blood pressure recorded by ABPM differed from the same measurements made by office or casual sphygmomanometry. Use of ABPM changed diagnosis or treatment of hypertension in borderline and antihypertensive drug-treated patients. Ambulatory blood pressure monitoring is a useful tool for the diagnosis and treatment of hypertension by the primary care physician. It can be used to identify white-coat hypertension in various patient populations.

The National Institutes of Health (NIH) is periodically asked to conduct assessments of new medical technologies to assist in coverage decisions made at the Office of Health Technology Assessment (OHTA) for the Health Care Financing Administration coverage policy. Analysis of NIH assessments indicates that even though most NIH assessments rely only on expert opinion, OHTA agreed with NIH recommendations in over 90%.

Passive joint position sense was tested in 10 subjects after unilateral total hip replacement surgery (which included capsulectomy). Varied initial limb position, amplitude, and velocity of movement were used. The unoperated side was used as a control. Statistically barely significant errors (p less than 0.025) on the operated side were detected at 0.6 degrees per second but not at 2 degrees per second. No significant differences were noted among the different hip positions. The results indicate that the ability to detect passive hip joint position sense remains largely, but not completely, intact after hip joint replacement. The joint capsule, ligaments, and joint surfaces, although not essential for kinesthesia, may provide some limb movement and position information, the absence of which is not now clinically apparent.

1. Animals were acclimated at 3 +/- 1 degrees C and at room temperature (22 degrees C) for 3 weeks. 2. At each acclimation temperature animals were maintained under either an 8:16 L:D cycle or a 16:8 L:D cycle. 3. Blood samples were taken before and after exposure to -38 degrees C for 30 min. 4. Free fatty acid levels were greatest in cold acclimated animals which were maintained on a short light cycle. 5. Interaction between acclimation and photoperiod was apparent.