Trauma as an etiologic factor of primary bone lymphoma: a report of 4 cases.

Primary bone lymphoma (PBL) is a rare entity. Nevertheless, very high long-term complete remission and survival rates following adriamycin-based chemotherapy alone or combined with involved-field radiation therapy have been reported. While the etiology is unknown, factors comprising local or general immunocompromised states have been suggested. Sporadic cases of local trauma followed by the emergence of primary bone lymphoma have been described. We describe 4 patients who developed primary bone lymphoma following direct trauma to a specific bone area. All 4 are alive with no evidence of disease after being treated with a combined chemo-radiotherapy regimen.

Urging college alcohol and drug policies that target adverse behavior, not use.

Although "zero tolerance" policies are being enacted on campuses nationwide, these policies may not be the most effective means of creating safer and healthier environments for students. Many historical precedents illustrate the value of moderation over prohibition. College drug and alcohol policies should focus primarily on dysfunctional and disruptive student behaviors, not on student drug and alcohol use only.

Changes in conceptions of learning for indigenous Australian university students.

BACKGROUND: Conceptions of learning have been investigated for students in higher education in different countries. Some studies found that students' conceptions change and develop over time while others have found no changes. Investigating conceptions of learning for Australian Aboriginal and Torres Strait Islander university students is a relatively new area of research. AIMS: This study set out to investigate conceptions of learning for Aboriginal and Torres Strait Islander university students during the first two years of their undergraduate degree courses in three Australian universities. Conceptions for each year were compared. Knowing more about learning as conceived by this cultural group may facilitate more productive higher educational experiences. SAMPLE: The sample comprised 17 students studying various degrees; 11 were male and 6 were female. Ages ranged from 18 to 48 years; mean age was 26 years. METHOD: This was a phenomenographic, longitudinal study. Individual semistructured interviews were conducted each year to ascertain students' conceptions of learning. Conceptions for second year were derived independently of those from first year. A comparative analysis then took place to determine any changes. RESULTS: These students held conceptions of learning that were similar to those of other university students; however there were some intrinsic differences. On a group level, conceptions changed somewhat over the two years as did core conceptions reported by some individual students. Some students also exhibited a greater awareness of learning during their second year that resulted in three dimensions of changed awareness. CONCLUSIONS: We believe the changed conceptions and awareness resulted from learning at university where there is some need to understand and explain phenomena in relation to theory. This brought about new understandings which allowed students to see their own learning in a relational sense.

A health risk benchmark for the neurologic effects of styrene: comparison with NOAEL/LOAEL approach.

Benchmark dose (BMD) analysis was used to estimate an inhalation benchmark concentration for styrene neurotoxicity. Quantal data on neuropsychologic test results from styrene-exposed workers [Mutti et al. (1984). American Journal of Industrial Medicine, 5, 275-286] were used to quantify neurotoxicity, defined as the percent of tested workers who responded abnormally to > or = 1, > or = 2, or > or = 3 out of a battery of eight tests. Exposure was based on previously published results on mean urinary mandelic- and phenylglyoxylic acid levels in the workers, converted to air styrene levels (15, 44, 74, or 115 ppm). Nonstyrene-exposed workers from the same region served as a control group. Maximum-likelihood estimates (MLEs) and BMDs at 5 and 10% response levels of the exposed population were obtained from log-normal analysis of the quantal data. The highest MLE was 9 ppm (BMD = 4 ppm) styrene and represents abnormal responses to > or = 3 tests by 10% of the exposed population. The most health-protective MLE was 2 ppm styrene (BMD = 0.3 ppm) and represents abnormal responses to > or = 1 test by 5% of the exposed population. A no observed adverse effect level/lowest observed adverse effect level (NOAEL/LOAEL) analysis of the same quantal data showed workers in all styrene exposure groups responded abnormally to > or = 1, > or = 2, or > or = 3 tests, compared to controls, and the LOAEL was 15 ppm. A comparison of the BMD and NOAEL/LOAEL analyses suggests that at air styrene levels below the LOAEL, a segment of the worker population may be adversely affected. The benchmark approach will be useful for styrene noncancer risk assessment purposes by providing a more accurate estimate of potential risk that should, in turn, help to reduce the uncertainty that is a common problem in setting exposure levels.

Medical student attitudes toward drug addiction policy.

This study explores the attitudes and perceptions of medical students concerning patients with addictions and policy issues related to drugs. Over 1,250 students from 15 medical schools responded to an anonymous survey concerning their experience and training regarding addictions, and their level of support or opposition for various drug policy approaches. Medical students expressed general support for treatment funding and related demand reduction strategies, but the strength of their support was influenced more by their political orientation than their perception of the effectiveness of the strategy. Students who identified themselves as liberals more strongly favored demand reduction and alternatives strategies such as needle exchange programs and drug courts. Conservatives more strongly favored supply reduction strategies including harsher sanctions for users. Need for additional training in medical school was indicated by the fact that 20% reported no training in addictions.

Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation.

The effects of drug dependence on social systems has helped shape the generally held view that drug dependence is primarily a social problem, not a health problem. In turn, medical approaches to prevention and treatment are lacking. We examined evidence that drug (including alcohol) dependence is a chronic medical illness. A literature review compared the diagnoses, heritability, etiology (genetic and environmental factors), pathophysiology, and response to treatments (adherence and relapse) of drug dependence vs type 2 diabetes mellitus, hypertension, and asthma. Genetic heritability, personal choice, and environmental factors are comparably involved in the etiology and course of all of these disorders. Drug dependence produces significant and lasting changes in brain chemistry and function. Effective medications are available for treating nicotine, alcohol, and opiate dependence but not stimulant or marijuana dependence. Medication adherence and relapse rates are similar across these illnesses. Drug dependence generally has been treated as if it were an acute illness. Review results suggest that long-term care strategies of medication management and continued monitoring produce lasting benefits. Drug dependence should be insured, treated, and evaluated like other chronic illnesses. JAMA. 2000;284:1689-1695.

Plasma pharmacokinetics of warfarin enantiomers in cats.

The purpose of this study was to determine the dispositions of S-warfarin and R-warfarin in normal cats following intravenous and oral administrations of racemic warfarin. Citrated blood samples were collected from 10 cats prior to and at times 5, 15, and 30 min, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 72, 96, and 120 h following a single intravenous bolus of 0.5 mg/kg of racemic warfarin. After a 21-day washout period, samples were then similarly collected in three groups of four cats for 120 h following oral administration of 0.1, 0.25, and 0.5 mg/kg racemic warfarin. S-warfarin and R-warfarin were detected using a high-performance liquid chromatography assay validated for cat plasma. Drug concentration-time curves were subjected to non-compartmental analysis. Median pharmacokinetic parameters associated with the intravenous administration of 0.5 mg/kg racemic warfarin were as follows: t1/2 (S:28.2, R:18.3 h), area under the plasma concentration-time curve (AUC; S:33.0, R:24.6 h*microg/mL), area under the moment curve (AUMC; S:1889, R:527.8 h*h*microg/mL), and mean residence time (MRT; S:38.7, R:20.9 h). For each parameter, S-warfarin was significantly different from R-warfarin (P<0.05). Warfarin was absorbed rapidly after oral administration, and the dosage did not affect the time to maximum concentration (S:0.87, R:0.75 h). Oral dosage significantly influenced maximum plasma concentration (ng/mL, S:1267, R:1355 at 0.5 mg/kg; S:614.9, R:679.4 at 0.25 mg/kg; S:250.5, R:367.6 at 0.1 mg/kg), AUC (h*microg/mL, S:45.12, R:30.91 at 0.5 mg/kg; S:22.98:, R:18.99 at 0.25 mg/kg; S:3.922, R:3.570 at 0.1 mg/kg) and AUMC (h*h*microg/mL, S:2135, R:1062 at 0.5 mg/kg; S:943.1, R:599.9 at 0.25 mg/kg; S:132.2, R:59.03 at 0.1 mg/kg), but not t1/2 (S:23.5, R:11.6 h) nor MRT (S:26.3, R:13.5 h). Both warfarin enantiomers were highly (>96.5%) protein-bound. Quantitation of the warfarin content in commercially available tablets indicated an unequal distribution of the drug throughout the tablet.

Pharmacodynamics of warfarin in cats.

The overall purpose of this study was to evaluate the pharmacodynamic response to warfarin in cats. The specific aim was to determine if a log-linear indirect response model (Nagashima et al., 1969) used to describe the in vivo effect of warfarin in humans could be applied to cats. The pharmacokinetics of racemic warfarin were described using a non-compartmental approach. The relationship between prothrombin complex activity (PCA) and normalized prothrombin time (PTR) was defined for feline plasma under our experimental conditions, and determined to be: %PCA=12.38+648 e-PTR/0.492. These data were then integrated and used to predict the warfarin dose associated with therapeutic anti-coagulation defined as an International Normalized Ratio (INR) of 2.0-3.0. The maximum prothrombinopenic response to warfarin in cats after a single intravenous dose of 0.5 mg/kg occurred at 24-48 h. Pharmacodynamic modeling suggested that each cat had a narrow therapeutic range of the steady-state concentration of total warfarin required to appropriately block prothrombin complex synthesis (median: 265.2-358.7 ng/mL). The median daily dose range predicted to yield therapeutic concentrations of warfarin was 0.061-0.088 mg/kg per day. Wide inter-individual variations in both pharmacokinetics and pharmacodynamic response suggest that a more optimal dosing of warfarin may be possible with the development of individual pharmacokinetic/pharmacodynamic algorithms, analogous to those currently employed in human patients.

Genetic polymorphism across regions of the three open reading frames of "Norwalk-like viruses".

Genomic characterization of Norwalk-like human caliciviruses (NLVs) originating from outbreaks and sporadic cases of acute gastroenteritis has revealed surprisingly high levels of diversity, even in the RNA polymerase gene, which is anticipated to be highly conserved. Since information on antigenic relationship is limited, due to the lack of a tissue culture system for these viruses, strains mostly are described on the basis of their genetic relatedness. However, the lack of uniformly applied criteria has led to a confusing array of strains with different groups employing different names for similar genetic lineages. Our goal was to conduct a structured analysis of genomic relationships among NLV strains in an attempt to provide an interim framework for genotyping. We assembled a panel of 31 potentially distinct genogroup I (GGI) and genogroup II (GGII) NLVs that reflected the diversity seen in strains detected by our laboratories and in published sequences. Phylogenetic analysis of sequences from regions of the open reading frames (ORF) 1, 2 and 3 was performed in order to investigate genomic relationships. The strains sequenced fell into seven phylogenetic groups in GGI and at least five phylogenetic groups in GGII, based on greater than 80% nucleotide identity in the region of ORF2 encoding the N-terminus of the capsid protein, and consistent clustering with high bootstrap values irrespective of the method used. Analysis of the ORF1 and ORF3 regions supported for most strains the clustering as established for those derived from ORF2. In the ORF1 region, used by most laboratories for diagnostic RT-PCR, clustering was consistent when a putative genotype border was set at 15% nucleotide mismatches for viruses in GGI and at 10% for viruses in GGII. Two strains grouped within different clusters based on ORF1 and ORF2 indicating that recombination may have occurred. We discuss the implications of these observations for the classification and typing of NLVs.

Access to narcotic addiction treatment and medical care: prospects for the expansion of methadone maintenance treatment.

Methadone maintenance treatment (MMT) for opioid addiction is safe and effective but underutilized because of inaccessibility, under-financing and the stigma generally attached to maintenance therapies. In addition, cumbersome regulation of methadone prescription and treatment impedes the delivery of care and retards expansion of methadone maintenance into office practice settings. Exaggeration of the problem of methadone diversion further hinders development of MMT. Despite obstacles, methadone maintenance has been successfully expanded and extended into primary care settings abroad. Initial trials in the U.S. have shown that methadone maintenance in physician office-based settings yields positive results with some advantages over care in large methadone clinics. Alternatives to methadone, such as buprenorphine, are also being explored in primary care settings. With implementation of the NIH Consensus Statement on Effective Medical Treatment of Heroin Addiction, including training of primary care physicians, methadone maintenance treatment could reach many more patients, achieve higher success rates, and substantially reduce the deleterious effects of opioid addiction in the U.S.

Physician Leadership on National Drug Policy: advocacy for an effective drug policy.

The founders of the PLNDP envisioned an active and committed group willing to tackle the potentially controversial area of national drug policy. The group already initiated a serious national debate about drug policy, inside and outside of the medical profession. Several national professional societies moved beyond their existing policies to embrace components of the PLNDP initiative. The group meets again in the summer of 1999 to share goals and articulate the next steps in research and advocacy. This meeting invites leaders in law, the enforcement community, legislators, community coalition leaders, and experts in addiction medicine and addiction psychiatry. PLNDP leaders expect that the subsequent coalitions will affect the course of discussion about the nation's drug policy far into the future.

Clinical and morphologic features of mucopolysaccharidosis type II in a dog: naturally occurring model of Hunter syndrome.

A 5-year-old male Labrador Retriever had progressive incoordination, visual impairment, and exercise intolerance. Coarse facial features, macrodactylia, unilateral corneal dystrophy, generalized osteopenia, progressive neurologic deterioration, and a positive urine spot test for acid mucopolysaccharides suggested mucopolysaccharidosis. Intracytoplasmic vacuoles were most prevalent in epithelial cells, endothelial cells, and histiocytes of liver, kidney, thyroid gland, and spleen. Ultrastructural examination disclosed electron-lucent floccular to lamellar membrane-bound storage material characteristic of mucopolysaccharides. Periodic acid-Schiff-positive intracytoplasmic material was identified in multiple neurons in the medulla, pontine nucleus, cerebellum, and spinal gray matter horns. Biochemical assays identified a deficiency in iduronate-2-sulfatase (IDS) activity in cultured dermal fibroblasts compared with normal dogs. Hair root analysis for IDS showed that the dam was a carrier of X-linked Hunter syndrome and that a phenotypically normal male littermate of the affected dog was normal. This is the first report of Hunter syndrome or mucopolysaccharidosis type II in a dog.

Homotypic and heterotypic IgG and IgM antibody responses in adults infected with small round structured viruses.

Antibody responses to recombinant Norwalk (rNV) and Mexico (rMXV) viral capsid proteins were studied in 39 adults involved in outbreaks of gastroenteritis associated with genogroup 2 small round structured viruses (SRSVs). Nineteen individuals were involved in outbreaks associated with MXV-like strains and 20 in outbreaks associated with four other genogroup 2 SRSVs. IgG antibodies were measured in acute and convalescent sera using indirect enzyme-linked immunosorbent assay (ELISA), and IgM was measured by indirect and capture ELISAs. Nineteen (49%) patients demonstrated a significant rise in IgG to rMXV with four (10%) patients also showing anamnestic responses to rNV. Fourteen patients were positive in the rMXV IgM-capture ELISA, representing 74% of patients demonstrating IgG rises. IgG and IgM responses to rMXV were observed in both groups, although higher levels of responses were seen in adults infected with MXV-like strains than those infected with non-MXV genogroup 2 viruses. No significant IgM responses were observed to rNV. These results indicate that, following SRSV infection, adults show a rise in antibody which is broadly reactive to viruses within but not between genogroups, although greater homotypic than heterotypic responses are produced. These findings have implications for interpretation of seroepidemiological studies and serodiagnosis of SRSV infections using recombinant capsids.

Thrombocytopenia in dogs with anticoagulant rodenticide-induced hemorrhage: eight cases (1990-1995).

Thrombocytopenia was documented in eight of 11 dogs with anticoagulant rodenticide-induced hemorrhage. Thrombocytopenia was transient and generally mild-to-moderate, but it became marked (i.e., less than 30,000 platelets/microl) in two cases. Petechial hemorrhages were not noted in any case. There was no relationship between hematocrit and platelet count. Platelet count changes in response to treatment with fresh-frozen plasma and isotonic electrolyte solutions were variable. Anticoagulant rodenticide toxicity should be included as a differential diagnosis for dogs with hemorrhage accompanied by mild-to-moderate thrombocytopenia.

The role of the generalist in the care of the substance-abusing patient.

It will be some time before known effective practices on behalf of patients with ATOD problems are integrated into the mainstream of medical care. Ironically, much of the medical literature centers on the medical and psychiatric complications of substance abuse and on physician attitudes regarding treatment of these patients. Rather the focus should be on the ways in which physicians can intervene early and effectively to treat the substance abuse problem itself. Much of this issue serves to correct the imbalance.

Epidemiology of Mexico virus, a small round-structured virus in Yorkshire, United Kingdom, between January 1992 and March 1995.

The epidemiology of the small round-structured virus, Mexico virus (MxV), was investigated in North and West Yorkshire, United Kingdom, between January 1992 and March 1995 using a type-specific antigen ELISA. The results indicate that an epidemic of MxV occurred during the winter of 1993-1994, when this strain was associated with 45 of 99 outbreaks and sporadic childhood cases of gastroenteritis. Only 4 MxV-like isolates were found during the 1992-1993 winter season and none in the 1994-1995 season. This descriptive epidemiologic study suggests that MxV has an epidemic pattern of infection.

Alcoholism in the elderly: physicians can make a difference.

The prevalence of alcoholism among the elderly is significant. Drinking problems in the aged may be masked by a physical or psychological conditioning. Diagnosis can thus be difficult but once it is made, treatment is fairly standard.

Canine idiopathic thrombocytopenic purpura.

Canine idiopathic thrombocytopenic purpura (ITP) is a disease in which antibodies bound to the surface of platelets mediate premature platelet destruction by macrophages. ITP in dogs and chronic ITP in humans are analogous diseases. This article draws on information from the literature on ITP in dogs and in humans, and reviews the pathogenesis, diagnosis, and treatment of ITP in dogs.