A systematic review assessing the effectiveness of interventions to improve persistence with anti-resorptive therapy in women at high risk of clinical fracture.

BACKGROUND: despite availability of effective treatments for osteoporosis, impact on fracture rates may be suboptimal because of failure to adhere to recommended anti-resorptive therapy. OBJECTIVE: to identify randomized controlled trials (RCTs) evaluating interventions intended to improve persistence with anti-resorptive therapy for treating women with osteoporosis or osteopenia. The design of the study is a systematic review and meta-analysis of RCTs. METHODS: included trials were those reporting interventions to improve persistence with or adherence to anti-resorptive treatment compared to a control medication or usual care. A search of MEDLINE, EMBASE, CINAHL and the Cochrane Library was supplemented by review of cited literature. Reports were reviewed and data pooled where appropriate. The primary outcome was duration of persistence with medication. RESULTS: six trials met inclusion criteria, including four reporting persistence as an outcome measure indicating a relative reduction in non-persistence of 22% (pooled relative risk: 0.78, 95% confidence interval 0.65-0.95) for active compared to control interventions. Heterogeneity between the trial effects was present but not significant (I(2) = 47%, P = 0.11). Interventions were varied in design, and some measurements of adherence were subject to self-report bias. Two trials included the majority of participants (3386/3497), accounting for >90% of the weight in the pooled estimate. CONCLUSIONS: trials to date suggest potential for improving persistence with medication taking thus improving treatment outcomes and reducing fracture risk. More precise measurement of medication taking and promoting fidelity to a precisely defined intervention protocol may lead to better assessment of impact on clinically important outcomes.

Comparison of slow oscillating versus fast balloon inflation strategies for coronary angioplasty.

Previous studies suggest that slow and/or oscillating balloon inflation during coronary angioplasty may decrease the incidence of coronary dissection and improve clinical outcomes. To compare the effect of slow oscillating versus conventional fast inflation techniques on the incidence of severe coronary dissection during angioplasty, 622 patients were randomized to slow oscillating inflation versus fast inflation. Angiographic outcomes of the procedures and in-hospital clinical events were recorded. The primary end point of severe (type C, D, E, F) dissection occurred in 7.7% of patients undergoing slow oscillation and 6.6% of patients undergoing fast inflation (p = 0.87). Major complications (death, urgent coronary artery bypass graft surgery, stroke, abrupt closure, or Q-wave myocardial infarction) occurred in 4.7% of patients undergoing slow oscillation and 3.5% of patients undergoing fast inflation (p = 0.45). The 2 inflation strategies did not differ in the pressure at which the balloon achieved full expansion, angiographic success rate, residual stenosis, and incidence of all minor and/or major complications. We conclude that there is no benefit of slow oscillating inflation over routine fast inflation in angioplasty. Slow oscillating inflation did not dilate lesions at lower pressures, decrease the incidence of dissection or severe dissection, or reduce the incidence of adverse clinical outcomes.

Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.

BACKGROUND: The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI. METHODS AND RESULTS: Patients with acute MI of <12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, P=0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, P=0.003, at 7 days; 11.2% versus 5.8%, P=0.03, at 30 days; and 17.8% versus 11.6%, P=0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, P=0.047, at 7 days; 5.8% versus 3.2%, P=0.20, at 30 days; and 12.0% versus 6.9%, P=0.07, at 6 months. The need for unplanned, "bail-out" stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, P=0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, P=0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group. CONCLUSIONS: Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected.

Contemporary percutaneous treatment of unprotected left main coronary stenoses: initial results from a multicenter registry analysis 1994-1996.

BACKGROUND: Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG. METHODS AND RESULTS: To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15+/-8 months. Results varied considerably, depending on presentation and treatment. For patients with acute myocardial infarction, technical success was achieved in 75%, and survival to hospital discharge was 31%. For elective patients, technical success was achieved in 98.9%, and in-hospital survival was strongly correlated with left ventricular ejection fraction (P=.003). Longer-term event (death, infarction, or bypass surgery) -free survival was correlated with ejection fraction (P<.001) and was inversely related to presentation with progressive or rest angina (P<.001). Surgical candidates with ejection fractions > or = 40% had an in-hospital survival of 98% and a 9-month event-free survival of 86+/-5%, whereas patients with ejection fractions < 40% had 67% and 22+/-12% in-hospital and 9-month event-free survivals, respectively. Nine hospital survivors (10.6%) experienced cardiac death within 6 months of hospital discharge. CONCLUSIONS: While results for selected patients appear promising, until early post-hospital discharge cardiac death can be better understood and minimized, percutaneous revascularization of ULMT stenosis should not be considered an alternative to bypass surgery for most patients. When percutaneous revascularization of ULMT is required, directional atherectomy and stenting appear to be the preferred techniques, and follow-up angiography 6 to 8 weeks after treatment is probably advisable.

Murine strain differences in response to mercuric chloride: antinucleolar antibodies production does not correlate with renal immune complex deposition.

Mercuric chloride (HgCl2) induces the production of antinucleolar antibodies (ANucA) in susceptible strains of mice. Responder strains bearing the H-2(5) haplotype as well as several ANucA resistant strains have been shown to develop renal immune complex deposits after HgCl2 treatment. Sera obtained throughout 12 to 16 weeks of HgCl2 treatment from mice of four ANucA responder strains (A.SW/SnJ, A.CA/SnJ, DBA/1J, and P/J) and one ANucA-resistant strain (C57BL/10SnJ) were examined for ANucA production. Terminal sera were also tested for the presence of anti-glomerular basement membrane antibodies, and the kidneys were examined for the deposition of IgG and C3. Only one strain, A.SW, developed significant deposits of IgG in the renal glomeruli, although all four responder strains exhibited similar ANucA induction/production profiles. The differences seen by direct immunofluorescence assay (IFA) in renal immune complex deposition between the A.SW and histocompatibility congenic A.CA mice were corroborated by individually eluting and then quantitating the deposited IgG from renal tissues of Hg-treated A.SW and A.CA mice as well as control A.SW mice. The average amount of IgG eluted from A.SW renal tissue was significantly greater than that eluted from either A.CA or control A.SW renal tissues. All eluates from Hg-treated animals gave only a nucleolar fluorescence pattern when assayed by indirect IFA against a panel of rat organ tissues. In summary, no correlation was found between ANucA production and renal IgG deposition in response to treatment with HgCl2.

Parathyroidectomy for hyperparathyroidism associated with renal disease.

Between 1969 and 1993, 123 patients were accepted in this unit for surgery for refractory hyperparathyroidism associated with chronic renal failure. Subtotal parathyroidectomy was the procedure of choice. At operation, four or more parathyroids were identified in 75% of patients. Methylene blue localised additional parathyroids in 32% of initial explorations in which it was used. Coincidental thyroid pathology was found in 8.3%, including papillary carcinoma in 2.4%. No further parathyroid surgery was required in 90% of patients at a mean of 6.6 years after operation. Reoperation (10%) was more likely to be required (14.3%) when less than four glands were found than when four or more were found (8.5%). Patients continuing on dialysis were more likely to need reoperation than those with functioning renal transplants.

Measurements on ferroelectric liquid-crystal spatial light modulators: contrast ratio and speed.

The contrast ratio and the speed of a 16 × 16 electrically addressed spatial light modulator, composed of a ferroelectric liquid-crystal layer on top of a VLSI silicon backplane, are measured with different methods but consistent results. The results are presented and compared with recently reported results on a similar spatial light modulator [Appl. Opt. 33, 2775 (1994)].

Prolactin-secreting pituitary adenomas with mammary dysplasia in New Zealand white rabbits.

Nine aged (mean age = 3.2 years) nulliparous New Zealand white rabbit does were found to have markedly enlarged teats. The teats were frequently engorged with fluid but were not hot and did not cause signs of pain. The number of affected teats per animal ranged from 1 to 8 (mean = 4). The teats and associated glandular tissue were typically discolored grey, blue, or greenish black (n = 6). Prolactin concentrations were evaluated by radioimmunoassay. Serum prolactin concentrations ranged from 22.4 ng/ml to 2.21 micrograms/ml (mean = 397.3 ng/ml), which was 10- to 1000-fold greater than normal values in nonpregnant rabbits. Conventional radiography of the skull of six rabbits did not reveal pituitary enlargement. Necropsy revealed an enlarged pituitary gland and sella turcica in six of nine does. The diaphragma sellae had ruptured in two rabbits. All nine rabbits had pituitary acidophil adenomas. The neoplastic portions of the pituitaries were diffusely immunoreactive when stained immunohistochemically for prolactin. In contrast, only small clusters of five to seven cells stained positively in normal pituitaries selected as controls. Histologic examination of the mammary glands revealed numerous large dilated cystic spaces containing proteinaceous fluid. Many cysts had numerous papillary epithelial infoldings. The cystic dilations extended into and included the teat canal producing the gross appearance. Prolactin-secreting acidophil adenomas have not been previously reported in the rabbit, and the association with mammary dysplasia is unique.

Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. RAAMI Study Investigators.

Clot dissolution with restoration of infarct-related artery blood flow is the likely mechanism for the improved prognosis and mortality reduction seen after thrombolytic therapy of acute myocardial infarction. A pilot study has suggested that 100 mg of recombinant tissue-type plasminogen activator (rt-PA) infused over 90 min may lead to higher patency rates than the current standard of 100 mg over 3 h. In this multicenter, randomized, open label trial, 281 patients with acute myocardial infarction receive 100 mg of rt-PA according to either the standard 3-h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h) or an accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min). All patients also received intravenous heparin and oral aspirin during and after rt-PA infusion. At 60 min after initiation of the rt-PA infusion, the observed angiographic patency rates were 76% (95% confidence intervals 65% to 84%) in the accelerated regimen group and 63% in the control group (52% to 73%, p = 0.03). At 90 min these rates were 81% (73% to 87%) and 77% (68% to 84%), respectively (p = 0.21). Both randomized groups experienced similar rates of recurrent ischemia, reinfarction, angiographic reocclusion, other complications of myocardial infarction (including stroke and death) and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of ozone inhalation on metabolic functioning of vascular endothelium and on ventilatory function.

The primary purpose of this research was to determine the effect of ozone inhalation on pulmonary vascular endothelium. Male Fischer-344 rats were exposed to 0.5 or 0.7 ppm ozone, 20 hr/day for 7 days. Lungs were excised and perfused with Krebs medium containing [14C]serotonin or [14C]hippurylhistidylleucine (HHL). When compared to controls, the animals exposed to the lower ozone concentration showed no statistically significant changes in serotonin removal. In contrast, the higher ozone concentration resulted in a 32% decrease (p less than 0.0001) in serotonin removal, but had no effect on HHL. Rats similarly exposed to 0.7 ppm ozone but allowed to recover for 14 days in clean air showed no decrease in serotonin removal compared to their controls. Animals exposed sequentially to 0.5 ppm ozone for 7 days and then to 0.7 ppm for 7 days showed no alteration in serotonin metabolism, suggesting the development of tolerance initiated by the lower dose. After 7 days exposure to 0.7 ppm ozone, lung ventilatory function measurements revealed small though significant decreases in several parameters. Electron microscopic evaluation of lung capillary endothelium from animals exposed to the 0.7 ppm ozone showed no changes. Positive control animals exposed to greater than 95% oxygen, 20 hr/day for 2 days showed a 23% decrease in serotonin removal (p less than 0.03) and a 12% decrease in HHL removal (p less than 0.017). These studies indicate that inhalation of ozone can induce functional alterations in the lung endothelium, and that this effect occurs at a dosage of ozone that produces minimal ventilatory changes and no observable endothelial ultrastructural changes.

Response of guinea pigs to intravaginal inoculation with guinea pig cytomegalovirus.

Female guinea pigs were inoculated intravaginally with guinea pig cytomegalovirus (GPCMV) propagated either in guinea pig embryo fibroblast cultures (GPEF) or salivary glands. The incidence of infection was higher with GPEF virus. Rare instances of isolation of GPCMV from cervical swabs 9-48 hr after inoculation was attributed to survival of inoculum in the genital tract. Neither immunofluorescence microscopy nor histopathologic examination showed evidence for active infection of genital tract tissue examined up to day 5 after inoculation. At necropsy on days 30-49, GPCMV was isolated from salivary glands and occasionally from pancreas and lymph nodes. Seroconversion following intravaginal inoculation was demonstrated by an enzyme-linked immunosorbent assay (ELISA) test, and titers were comparable to those after intraperitoneal or subcutaneous inoculation. However, titers of neutralizing antibody, determined by plaque-reduction assay, were significantly lower in the group inoculated intravaginally. These findings are relevant to consideration of cytomegalovirus as a sexually transmitted agent in humans.

Chlamydial salpingitis in female guinea pigs receiving oral contraceptives.

Female guinea pigs were given daily doses of a combination of oral contraceptive (OC) agents, consisting of mestranol and norethynodrel suspended in sesame oil or distilled H2O, and were infected in the genital tract with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). Counts of chlamydial inclusions in cells of vaginal smears collected during infection, showed prolongation and enhancement of infection in OC-treated animals as compared with controls. Appearance of IgG and IgA antibodies to GPIC in genital secretions, as determined by enzyme-linked immunosorbent assay (ELISA), was also delayed in OC-treated animals as compared with controls. OC-treated infected animals were killed on days 15 and 43, and gross pathological evidence for ascending infection culminating in salpingitis was found in all of five and four of five animals, respectively. On the other hand, among untreated infected controls on each sacrifice day, only one of five animals had any evidence for ascending infection. Chlamydiae were detected by light and electron microscopy in fallopian tube tissue collected on day 15 following OC-treatment but not in tissue from control animals.

The relationship between hypertrophy and dilatation in the postmortem heart.

Confusion may exist at the time of postmortem examination as to whether the diseased heart is dilated, hypertrophied, or both. Ventricular dilatation and ventricular hypertrophy were therefore evaluated by cardiac partition techniques in 441 subjects at autopsy to determine their relationship. Specific weight and surface area of each ventricle were obtained and patients were divided into categories of disease. Wall thickness measurements, a parameter routinely used in the ordinary autopsy, were found to be unreliable in defining hypertrophy. Ventricular surface area (an index of dilatation) was highly correlated with ventricular weight in most disease categories. Exceptions were cardiomyopathy and aortic stenosis, in which hypertrophy predominated. We conclude from these data that dilatation and hypertrophy occur proportionately in the postmortem heart in most disease categories except in cardiomyopathy and aortic stenosis. These findings clarify the relationship of dilatation and hypertrophy at the time of autopsy in most cases. Therefore, uncertainty as to whether cardiac dilatation or hypertrophy is present or which predominates is usually related to the inability to assess these states critically at the time of autopsy when the ordinary pathological methods are used.

Holographic implementation of a Hopfield model with discrete weightings.

This paper investigates the feasibility of constructing a Hopfield neural network using optical techniques. The particular implementation utilizes parallel holographic interconnections and could have a processing speed vastly greater than the serial electronic computers we use today. This improvement in speed is of great importance, particularly in the field of computer vision. It is found that present day technology would seriously limit the size of the network that could be implemented. Our analysis suggests, however, that the construction of an optical machine is now possible with a connectivity exceeding any electronic machine available.

Quantitation of ozone-induced lung lesion density after treatment with an interferon inducer or an anti-interferon antibody.

Inhalation of ozone by experimental animals produces activation of lymphocytes in the mediastinal lymph node complex. Both the number and functional reactivity are affected, with evidence of blastic transformation in T cell but not B cell areas of the nodes. In the present work we determine the extent that modulation of a possible product of immune system activation, interferon, is capable of influencing the way that experimental animals respond to zone. Outbred CD-1 mice were treated with an interferon inducer, poly I:C, or with an anti-interferon antibody while being exposed to ozone at a concentration of 0.7 or 0.9 ppm for 20 h per day for 4 days. Interferon induction produced a significant reduction in lesion volumes in both exposure groups, while anti-interferon produced the opposite effect. Less alveolar damage was observed in interferon-induced, ozone-exposed animals than in animals exposed to ozone alone. In contrast, anti-interferon-treated, ozone-exposed animals showed larger lesions which extended to more peripheral structures and were more extensively infiltrated with neutrophilic leukocytes. These results show that interferon induction protects against zone-mediated lung damage. They also suggest that cells are activated during ozone inhalation which mitigate the effects of ozone on the lung by secretion of interferon.

Response of T-cell-deficient mice to ozone exposure.

The number, appearance, and functional reactivity of T-lymphocytes of mediastinal lymph nodes are altered during experimental ozone inhalation. The purpose of the present work is to determine how the lymph nodes and lungs of a mutant strain of animal, which lacks this type of cell, differ in their response to ozone exposure when compared with animals that possess a normal complement of lymphocytes. We exposed athymic nude (nu/nu) mice or heterozygous (nu/+) euthymic mice to 0.7 ppm ozone for 20 h/d for 7 or 14 d while maintaining control groups in clean air. At 7 d the lymph-node hyperplastic response normally seen in euthymic, ozone-exposed animals was greatly reduced in exposed athymic animals. By both 7 and 14 d, greater damage had occurred in the lungs of ozone-exposed, athymic animals than in similarly exposed euthymic animals. Lung wet weight divided by body weight, which was used as a general indicator of lung damage, increased by substantially more in athymic animals than in conventional animals. In a parallel manner, quantitative microscopic analysis, a more sensitive indicator, revealed a marked increase in the lung lesion volumes. Qualitative histologic analysis showed that the change in the response in the athymic animal was most prominent in the peripheral region of the lung extending from the alveolar duct to the alveoli, and was characterized by a greater acute inflammatory cell reaction. Possible mechanisms by which the T-cell could produce the observed effect include secretion of factors that enhance inherent resistance of the lung's target cells, or alterations in the way the inflammatory response to ozone-mediated damage occurs. The results support the idea that the mediastinal lymph node lymphocyte response is adaptive in nature and aids in protecting the lung from ozone-mediated effects.