Racial differences in social network experience and perceptions of benefit of arthritis treatments among New York City Medicare beneficiaries with self‐reported hip and knee pain

Objective

To determine whether social network experience and perceptions of benefit of arthritis treatments influence the decision to seek diagnosis and treatment.

Methods

A population‐based telephone survey of 515 black and 455 white Medicare beneficiaries was conducted. Validated questionnaires adapted for use in a telephone interview were used to identify people with self‐reported symptoms of hip or knee pain. Treatment history for arthritis‐related pain and perceptions of benefit of treatment were also assessed.

Results

Forty‐two percent of blacks and 31% of whites reported hip or knee pain. Forty‐two percent of blacks and 65% of whites reported knowing someone who had surgery for hip or knee pain (P < 0.0001). Blacks were less likely than whites to report that surgery had helped someone they knew with hip or knee pain (not significant).

Conclusion

Blacks know fewer people who have had surgical treatment of hip and knee pain than whites and appear to be less likely to perceive that such treatment is beneficial.

     

Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects

The extension locus has been identified in many mammalian species as a gene that determines the relative amounts of eumelanin and phaeomelanin pigments in hair and skin. In at least three species, this locus has been demonstrated to encode the melanocyte-stimulating hormone receptor (MC1-R), and functionally variant alleles have been demonstrated to cause a broad range of pigmentation phenotypes. To test for MC1-R allelic variation in man, genomic DNA was extracted from skin samples collected from patients with different skin types (I–VI), and eye and hair color. A PCR-based approach was used to amplify the full-length coding sequence of the MC1-R and the resulting products were sequenced. Two polymorphic alleles were identified with single point mutations in the coding sequence: a valine-to-methionine substitution at position 92 (V92M), and an aspartic acid-to-glutamic acid substitution at position 84 (D84E). RFLP analysis demonstrated the presence of the V92M allele in 4 out of 60 (6.6%) of individuals examined, predominantly those with blue eyes and blond hair. This polymorphism was found in both heterozygous and homozygous states in individuals with type I skin. The D84E allele was found in one individual with skin type I; this person also has the V92 M allele and thus is a compound heterozygote. © 1997 Wiley-Liss, Inc.     

p53 accumulation and mutation are prognostic indicators of poor survival in human gastric carcinoma

The aim of our study was to examine the prognostic significance of p53 protein accumulation and gene mutation in a series of 116 gastric carcinomas from a low incidence population. Formalin-fixed, paraffin-embedded tumour sections were used to investigate p53 protein accumulation by immunostaining with monoclonal antibody (MAb) DO-7 and p53 gene mutation by single-strand conformation polymorphism analysis of exons 5-8. Nuclear p53 accumulation was detected in 23% of tumours and mutation in 28%. Concordance between the 2 alterations was observed in 73% of cases. p53 protein accumulation was more frequent in tumours with lymph node metastasis, while p53 mutations were more frequent in tumours from older patients. The histopathological parameters of depth of invasion, grade and histological type showed no significant associations with either p53 alteration. In univariate analysis, both alterations were associated with significantly shortened patient survival. The 5-year survival rate for patients with a p53 mutation was 9% compared to 42% for those without a mutation. In multivariate analysis adjusted for the other histopathological parameters, p53 gene mutation but not immunohistochemically-detected p53 protein accumulation was an independent prognostic indicator of poor survival in gastric carcinoma. © 1996 Wiley-Liss, Inc.     

Glutamate-dopamine interactions in the ventral striatum: role in locomotor activity and responding with conditioned reinforcement

Previous evidence suggests that glutamatergic limbic afferents participate in the potentiation of responding with conditioned reinforcement produced by intra-accumbens d-amphetamine. The present experiments were designed to investigate glutamate-dopamine interactions in the ventral striatum in both conditioned reinforcement and locomotor activity. Glutamate receptor agonists and antagonists were infused into the nucleus accumbens both alone and in combination with 3 µg d-amphetamine, and the effects of these interactions on responding with conditioned reinforcement and locomotor activity were measured. The glutamate receptor agonists NMDA, AMPA and quisqualate (agonists at the NMDA, AMPA and metabotropic glutamate receptor subtypes, respectively) and the antagonists AP5 and CNQX, (antagonists at the NMDA and AMPA receptor subtypes, respectively) were used in these investigations. These compounds were used in a dose range of 0.3 to 3 nmol, except CNQX, which was used in 0.2 to 2 nmol doses. While all agonists and antagonists increased locomotor activity when administered alone, the antagonists attenuated the locomotor response to d-amphetamine. In contrast, the agonists AMPA and quisqualate enhanced d-amphetamine-induced locomotor activity, although NMDA interfered with the effects of d-amphetamine. In the conditioned reinforcement paradigm, both the agonists and the antagonists abolished amphetamine's potentiation of responding with conditioned reinforcement, suggesting that the glutamatergic transmission of information about the conditioned reinforcer could be blocked by glutamate receptor antagonists and disrupted by administration of the agonists. The dissociation between the effects of these excitatory amino acids on amphetamine-induced locomotor activity versus their effects on amphetamine's potentiation of responding with conditioned reinforcement provides insight into the nature of the reward enhancement by accumbens dopamine versus its locomotor stimulant effects.     

Utilizing an Ingestible Biosensor to Assess Real-Time Medication Adherence

Medication adherence monitoring has relied largely on indirect measures of pill ingestion including patient self-report, pharmacy refills, electronically triggered pill bottles, and pill counts. Our objective is to describe an ingestible biosensor system comprising a radio-frequency identification (RFID)-tagged gelatin capsule. Once the capsule dissolves in the stomach, the RFID tag activates to transmit a unique signal to a relay device which transmits a time-stamped message to a cloud-based server that functions as a direct measure of medication adherence. We describe a constellation of mobile technologies that provide real-time direct measures of medication adherence. Optimizing connectivity, relay design, and interactivity with users are important in obtaining maximal acceptability. Potential concerns including gut retention of metallic components of the ingestible biosensor and drug dissolution within a gelatin capsule should be considered. An ingestible biosensor incorporated into a medication management system has the potential to improve medication compliance with real-time monitoring of ingestion and prompt early behavioral intervention. Integration of ingestible biosensors for multiple disease states may provide toxicologists with salient data early in the care of poisoned patients in the future. Further research on device design and interventions to improve adherence is needed and will shape the evolving world of medication adherence.     

High anxiety is a predisposing endophenotype for loss of control over cocaine, but not heroin, self-administration in rats

Rationale

Although high anxiety is commonly associated with drug addiction, its causal role in this disorder is unclear.

Objectives

In light of strong evidence for dissociable neural mechanisms underlying heroin and cocaine addiction, the present study investigated whether high anxiety predicts the propensity of rats to lose control over intravenous cocaine or heroin self-administration.

Methods

Sixty-four rats were assessed for anxiety in the elevated plus-maze, prior to extended access to intravenous cocaine or heroin self-administration.

Results

High-anxious rats, identified in the lower quartile of the population, showed a greater escalation of cocaine, but not heroin, self-administration compared with low-anxious rats selected in the upper quartile of the population. Anxiety scores were also positively correlated with the extent of escalation of cocaine self-administration.

Conclusions

The present data suggest that high anxiety predisposes rats to lose control over cocaine??but not heroin??intake. High anxiety may therefore be a vulnerability trait for the escalation of stimulant but not opiate self-administration.     

Amifostine (WR-2721) shortens the engraftment period of 4- hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty- three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high- dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T

Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes.     

Ectopic ureter and ureterocele: their varied sonographic manifestations

The sonographic examinations of four patients with simple ectopic ureters and 11 with ectopic ureteroceles were reviewed to determine distinguishing characteristics. Ectopic ureters, in cases of extreme dilatation and tortuosity, sometimes mimic multiseptated, cystic abdominal masses. However, the proximal portions of some severely dilated ureters are surprisingly small. Ectopic ureters sometimes indent the lower vesical wall, simulating a ureterocele. Ectopic ureteroceles are dynamic structures, changing in shape and size according to intravesical pressure. The lower pole of a duplex kidney may be difficult to detect because of displacement by the dilated upper renal pelvis and ureter. The renal parenchyma associated with an ectopic ureter may be equally difficult or impossible to find because of diminutive dysplasia or, less commonly, acquired atrophy. Dysplasia is characterized sonographically by highly echogenic parenchyma, lack of corticomedullary differentiation, and occasionally massive enlargement by cysts. Ectopic ureters and ureteroceles can be identified by fetal sonography.     

Acute experimental cerebral ischemia: MR enhancement using Gd-DTPA

The effects of a paramagnetic contrast agent, gadolinium-DTPA (Gd-DTPA), on magnetic resonance (MR) imaging of acute cerebral ischemia was investigated in a feline model of middle cerebral artery occlusion. Imaging was performed both before and after administration of an intravenous dose of 0.2 mmol/kg of Gd-DTPA. The animals were then sacrificed for pathologic correlation. No changes in intensity or relaxation times were noted before or after Gd-DTPA administration in two animals with 2 hours of occlusion. Infarcts were noted before and after contrast enhancement in all six cats with ischemia of greater than 16-hours duration. Gd-DTPA caused significant increase in intensity of infarct but not in that of normal cerebral tissue. Rapid enhancement was visible in infarcts of 16-24 hours, but such enhancement was slower in infarcts of 72-168 hours, presumably owing to slowed inflow caused by increased vasogenic edema in the latter group. Contrast enhancement of acute cerebral ischemic lesions with Gd-DTPA offers no improvement in sensitivity of MR imaging, although the conspicuity of the lesion may be improved. Additionally, contrast media may provide potential temporal and pathophysiological data for better characterization of cerebral ischemia.