Medication as a potential cause of depression

Many different drugs have been reported to cause depression. The substantive literature is reviewed, with particular attention to antihypertensive and cardiac drugs, oral contraceptives, levodopa and major tranquilizers. The nature of the relationship between physical illness, therapeutic drug use and the potentiation or precipitation of depression is explored.     

Monosomal karyotype in primary myelofibrosis is detrimental to both overall and leukemia-free survival

Survival in cytogenetically high-risk patients with acute myeloid leukemia or myelodysplastic syndromes is significantly worse in the presence of a monosomal karyotype (MK). The objective of the present study was to determine whether the same held true for primary myelofibrosis. Among 793 primary myelofibrosis patients seen at our institution, 62 displayed an unfavorable karyotype by way of complex karyotype (n = 41) or sole trisomy 8 (n = 21). Seventeen (41%) of the 41 patients with complex karyotype were classified as having an MK. Median survival was 6, 24, and 20 months in patients with MK, complex karyotype without monosomies, and sole trisomy 8, respectively (P < .0001). The corresponding 2-year leukemic transformation rates were 29.4%, 8.3%, and 0 (P < .0001); hazard ratios (95% confidence intervals) were 6.9 (1.3-37.3) and 14.8 (1.7-130.8). The prognostic relevance of MK was not accounted for by the Dynamic International Prognostic Scoring System. We conclude that MK in primary myelofibrosis is associated with extremely poor overall and leukemia-free survival.     

Abdominal vein thrombosis in essential thrombocythemia: prevalence, clinical correlates, and prognostic implications

Among 460 consecutive patients with essential thrombocythemia (ET) seen at our institution, 19 cases (4%) of abdominal vein thrombosis (AVT) were documented either at (n = 9) or after (n = 10) diagnosis. Women (P = 0.03) and the young (P = 0.002) were preferentially affected. Accordingly, clinical comparisons were performed among three groups of female patients: those with AVT (group A; n = 17), a control group without AVT but closely matched to group A in terms of age and year of diagnosis (group B; n = 34), and all female patients without AVT (group C; n = 288). As expected from the consequences of AVT-associated portal hypertension and anticoagulant therapy, patients in group A experienced significantly higher rates of hemorrhage, palpable splenomegaly, and anemia. Unexpectedly, however, compared with group B, group A displayed both a higher conversion rate into myelofibrosis/acute leukemia (P = 0.0008) and a shorter median survival (116 vs. 156 months; P = 0.0012). Multivariable analysis including all female patients with ET identified AVT, along with advanced age, leukocytosis, and tobacco use, as an independent risk factor for inferior survival. Groups A, B, and C did not differ in either JAK2(V617F) mutational frequency or incidence of non-abdominal thrombosis. We conclude that AVT in ET is a marker of aggressive disease biology.     

Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response

At mammalian body temperature, the plague bacillus Yersinia pestis synthesizes lipopolysaccharide (LPS)-lipid A with poor Toll-like receptor 4 (TLR4)-stimulating activity. To address the effect of weak TLR4 stimulation on virulence, we modified Y. pestis to produce a potent TLR4-stimulating LPS. Modified Y. pestis was completely avirulent after subcutaneous infection even at high challenge doses. Resistance to disease required TLR4, the adaptor protein MyD88 and coreceptor MD-2 and was considerably enhanced by CD14 and the adaptor Mal. Both innate and adaptive responses were required for sterilizing immunity against the modified strain, and convalescent mice were protected from both subcutaneous and respiratory challenge with wild-type Y. pestis. Despite the presence of other established immune evasion mechanisms, the modified Y. pestis was unable to cause systemic disease, demonstrating that the ability to evade the LPS-induced inflammatory response is critical for Y. pestis virulence. Evading TLR4 activation by lipid A alteration may contribute to the virulence of various Gram-negative bacteria.     

Cytogenetic studies at diagnosis in polycythemia vera: clinical and JAK2V617F allele burden correlates

The prognostic significance of cytogenetic findings at diagnosis in polycythemia vera (PV) was investigated in a retrospective series of 137 patients. Cytogenetics were normal in 117 patients (85%) and displayed a -Y abnormality in five patients (7% of male patients), and other chromosomal abnormalities in 15 patients (11%). The most frequent cytogenetic anomalies were trisomy 8 (n = 4), trisomy 9 (n = 2), deletion 20q (n = 2) and chromosomal 1 abnormalities (n = 2). Parameters that were significantly associated with abnormal cytogenetics included age > or = 60 yr (P = 0.02), but not JAK2V617F allele burden, thrombosis, hemorrhage, leukemic/fibrotic transformation, or survival. We conclude that cytogenetic anomalies occur infrequently at PV diagnosis and do not confer an adverse outcome.