Changes in Marijuana Use Over the Transition Into Marriage

Reductions in substance use tend to coincide with marriage, as both may occur during emerging adulthood. During the transition to marriage, it is possible that one's spouse may be the influence that causes the reduction in substance use. Data on participants (N = 471 couples) for this report are taken from a longitudinal study of early marriage. The objective of the current analysis is to determine if having a spouse who uses marijuana is associated with a greater likelihood of one's own use. Additionally, we are interested in spousal influence and cessation. The findings support spousal influence. Husbands are more likely to start using marijuana if their wives use marijuana, but the reverse is not true. Husbands also are more likely to stop using if their spouses do not use. During the transition into marriage, the drug use of one spouse does affect the other. However, this influence appears to be unidirectional, with wives influencing their husbands more often.     

Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.      

Shwachman syndrome: Exocrine pancreatic dysfunction and variable phenotypic expression

BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602)     

Prostaglandin E2 potentiates platelet aggregation by priming protein kinase C

Prostaglandin E2 (PGE2) is produced by activated platelets and by several other cells, including capillary endothelial cells. PGE2 exerts a dual effect on platelet aggregation: inhibitory, at high, supraphysiologic concentrations, and potentiating, at low concentrations. No information exists on the biochemical mechanisms through which PGE2 exerts its proaggregatory effect on human platelets. We have evaluated the activity of PGE2 on human platelets and have analyzed the second messenger pathways involved. PGE2 (5 to 500 nmol/L) significantly enhanced aggregation induced by subthreshold concentrations of U46619, thrombin, adenosine diphosphate (ADP), and phorbol 12-myristate 13-acetate (PMA) without simultaneously increasing calcium transients. At a high concentration (50 mumol/L), PGE2 inhibited both aggregation and calcium movements. PGE2 (5 to 500 nmol/L) significantly enhanced secretion of beta-thromboglobulin (beta TG) and adenosine triphosphate from U46619- and ADP-stimulated platelets, but it did not affect platelet shape change. PGE2 also increased the binding of radiolabeled fibrinogen to the platelet surface and increased the phosphorylation of the 47-kD protein in 32P- labeled platelets stimulated with subthreshold doses of U46619. Finally, the amplification of U46619-induced aggregation by PGE2 (500 nmol/L) was abolished by four different protein kinase C (PKC) inhibitors (calphostin C, staurosporine, H7, and TMB8). Our results suggest that PGE2 exerts its facilitating activity on agonist-induced platelet activation by priming PKC to activation by other agonists. PGE2 potentiates platelet activation at concentrations produced by activated platelets and may thus be of pathophysiologic relevance.     

Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid cell-specific monoclonal antibodies

Second or third chemotherapy-induced remissions in acute myelogenous leukemia (AML) are limited by early relapse of the leukemia. We developed monoclonal antibodies (MoAbs) that are cytotoxic to myeloid leukemia cells to treat bone marrow from these patients ex vivo for autologous transplantation. In this pilot study, bone marrow was harvested from ten patients with AML in remission, treated with one or two complement-fixing MoAbs, PM-81 and AML-2-23, which react with myeloid differentiation antigens, incubated with rabbit complement, and cryopreserved. These MoAbs were chosen because they have broad reactivity with AML cells but not with pluripotent progenitor cells. At the time of transplant, 6 patients were in second complete remission, 1 each was in third complete or partial remission, and 2 were in early first relapse. The patients were treated with cyclophosphamide (60 mg/kg a day for 2 days) and total body irradiation (200 cGy twice a day for 3 days) and given infusions of MoAb-treated bone marrow. Full bone marrow reconstitution was observed in eight patients; two patients did not recover platelets. Seven of the ten patients are surviving and disease-free at 21.0, 15.0, 13.0, 10.0, 6.0, 3.0, and 2.0 months posttransplant. Treating bone marrow with MoAbs to myeloid differentiation antigens does not interfere with pluripotential stem cell engraftment. Longer follow-up and a controlled study are necessary to prove that the apparent efficacy of this therapeutic approach in some patients is attributable to MoAb-mediated killing of leukemia cells.     

Spirituality is associated with better prostate cancer treatment decision making experiences

This study examined whether spiritual beliefs are associated with greater decision-making satisfaction, lower decisional conflict and decision-making difficulty with the decision-making process in newly diagnosed men with prostate cancer. Participants were 1114 men diagnosed with localized prostate cancer who had recently made their treatment decision, but had not yet been treated. We used multivariable linear regression to analyze relationships between spirituality and decision-making satisfaction, decisional conflict, and decision-making difficulty, controlling for optimism and resilience, and clinical and sociodemographic factors. Results indicated that greater spirituality was associated with greater decision-making satisfaction (B = 0.02; p < 0.001), less decisional conflict (B = ?0.42; p < 0.001), and less decision-making difficulty (B = ?0.08; p < 0.001). These results confirm that spiritual beliefs may be a coping resource during the treatment decision-making process. Providing opportunities for patients to integrate their spiritual beliefs and their perceptions of their cancer diagnosis and trajectory could help reduce patient uncertainty and stress during this important phase of cancer care continuum.     

Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia

The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors.     

Cigarette Smoking and Mental Illness: A Study of Nicotine Withdrawal

Objectives. We compared prevalence, severity, and specific symptom profiles for nicotine withdrawal across categories of mental illness. We also examined the influence of nicotine withdrawal on efforts to quit smoking among those with mental illness.Methods. We analyzed data from 2 sources: wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions, limiting the sample to current smokers (2001–2002; n = 9913); and a 2-wave cohort telephone survey of a national sample of adult smokers (2004–2006; n = 751).Results. Mental illness was associated with a substantially greater likelihood of nicotine withdrawal syndrome; approximately 44% of nicotine withdrawal syndrome diagnoses were attributable to mental illness. Symptom profiles were highly comparable between mental illness categories, although anxiety-related symptoms were better markers of withdrawal for those with an internalizing disorder. Smokers with mental illness were motivated to quit but were less likely to be successful in their quit attempts, and both dependence and withdrawal independently accounted for this lower likelihood of success.Conclusions. Nicotine withdrawal may be a particularly important target for intervention among those with mental illness who smoke cigarettes.Individuals with mental illness are more likely to smoke cigarettes, are more dependent on nicotine, and have greater difficulty quitting smoking1,2 than are those without mental illness. The prevalence of mental illness in the United States is approximately 28%; yet, smokers with mental illness consume 40%–50% of cigarettes.1,2 A self-medication hypothesis has largely driven the conceptualization of this issue3–8: smoking is initiated and maintained to reduce psychiatric symptoms, and these symptoms are exacerbated during abstinence. This notion, that smoking can be important for symptom self-management, has likely contributed to smoking disparities between those with and those without mental illness.3 There are effective means of treating smoking for those with mental illness9; however, nontreatment remains the norm.10 A growing body of researchers, clinicians, and policymakers has called for a paradigm shift in how we approach this issue.3,11–13 Smoking is becoming increasingly viewed as a preventable and treatable cause of diminished life quality among those with mental illness,3,12 rather than a necessary form of self-medication.A 2008 National Institute of Mental Health report noted that the focus on a self-medication hypothesis has come at the expense of research on other important facets of smoking, particularly nicotine withdrawal.3 Studies have found that cigarette smokers with mental illness may experience more severe nicotine withdrawal symptoms14,15; however, these studies were conducted among small samples with a limited range of diagnoses. Weinberger et al. conducted an investigation using data from a US nationally representative sample of cigarette smokers and found that those with mental illness were more likely to report nicotine withdrawal symptoms and life problems associated with their withdrawal.16 Weinberger et al. focused on a few particular diagnoses; thus, they did not investigate the overall extent to which nicotine withdrawal is an issue among those with mental illness or comparisons of nicotine withdrawal between mental illness diagnoses. Previous research on this topic has also been limited in that specific nicotine withdrawal symptom profiles have not been compared across mental illness diagnoses. This type of analysis will potentially highlight specific nicotine withdrawal symptom targets for intervention. Finally, it remains unclear whether nicotine withdrawal in itself is associated with lower likelihood of quit success among those with mental illness or whether nicotine withdrawal is simply an extension of greater nicotine dependence among those with mental illness.We conducted 2 studies of nicotine withdrawal, mental illness, and tobacco cessation. In the first, we compared the likelihood of being diagnosed with a nicotine withdrawal syndrome and the severity of nicotine withdrawal symptoms between smokers with and those without mental illness and across mental illness diagnoses. We then estimated the proportions of nicotine withdrawal syndrome in the population of smokers attributable to each mental illness category. We compared nicotine withdrawal symptom profiles between mental illness categories to better understand consistencies and differences in specific nicotine withdrawal symptoms.In the second study, we examined whether smokers with mental illness were more or less motivated to quit smoking and more or less likely to make quit attempts. Among smokers who made a quit attempt, we examined whether those with mental illness were more or less likely to successfully stop using tobacco and how nicotine withdrawal and dependence influenced cessation efforts.     

Parathyroid adenomas evaluated by Tl-201/Tc-99m pertechnetate subtraction scintigraphy and high-resolution ultrasonography

Thallium-201/technetium-99m pertechnetate subtraction scintigraphy of the parathyroid glands was performed in a prospective study of 33 patients who had undergone bilateral neck exploration for elevated serum calcium and serum parathyroid hormone levels. In 31 cases, the Tl-201/Tc-99m subtraction technique yielded an overall sensitivity of 81%, specificity of 99%, and accuracy of 94% for identifying solitary parathyroid adenomas. Tl-201/Tc-99m subtraction scintigraphy correctly identified 73% of parathyroid adenomas weighing less than 499 mg, 79% of those weighing 500-1,499 mg, and 100% of adenomas weighing more than 1,500 mg. In a subgroup of 24 patients with solitary parathyroid adenomas who underwent both scintigraphy and high-resolution sonography, the sensitivity, specificity, and accuracy of both procedures were similar.