Pancytopenia with hypercellular bone marrow—a possible paraneoplastic syndrome in carcinoma of the lung: A report of three cases

Three patients with idiopathic pancytopenia and hypercellular bone marrow who developed carcinoma of the lung within two years of diagnosis are reported. All three patients had macrocytic anemia associated with a megaloblastic marrow in the presence of normal serum vitamin B12 and folic acid levels. Neutropenia with monocytosis, elevated serum muramidase and LAP scores, and increased fetal hemoglobin levels were also found. In all cases Ham's tests were negative with a normal bone marrow karyotype. In all three patients, pancytopenia due to myelodysplasia, a probable preleukemic state, was diagnosed initially prior to the appearance of carcinoma of the lung. One of the patients showed improved leukocyte and platelet counts during chemotherapy, while the other two died before chemotherapy could be administered. In the light of the above findings we suggest that carcinoma of the lung may be the cause of a paraneoplastic syndrome with pancytopenia, particularly in patients with a hypercellular marrow with a normal karyotype.     

Role of the central amygdala in modulating the pituitary-adrenocortical and clinical responses in experimental herpes simplex virus-1 encephalitis

The amygdala is known to regulate neuroendocrine and behavioral responses to a variety of stimuli. Herpes simplex virus-1 (HSV-1) is the common cause of viral encephalitis, manifested by hypothalamic-pituitary-adrenal (HPA) axis activation, fever, hypermotor activity and aggression. We examined here the role of the central amygdala (cAMG) in regulating the HPA axis function, febrile and behavioral responses to HSV-1 infection in rats. Bilateral electrolytic lesions were performed in the cAMG. HSV-1 encephalitis was induced by intracerebroventricular (ICV) inoculation of purified virions. Motor activity and body temperature were examined by a biotelemetric system. ICV inoculation of HSV-1 caused a marked time-dependent increase in serum corticotropin (ACTH) and corticosterone at 4 and 24 h post-infection. These responses were attenuated in rats with bilateral lesions of the cAMG. HSV-1 infection induced fever, motor hyperactivity and aggressive behavior. These responses were also attenuated in rats with cAMG lesions. The cAMG plays an important role in mediating the neuroendocrine, febrile and behavioral responses to HSV-1 infection.     

Age, sex and regional brain volumes predict perceptual-motor skill acquisition

Neural mechanisms of skill acquisition across the lifespan are largely unknown. Neuroimaging in younger adults and research on neurodegenerative disorders suggests that perceptual-motor learning relies on the striatum, cerebellum, and prefrontal cortex. Our objective in this study was to explore whether individual differences in regional brain volumes modify the effects of age and sex on the acquisition of a perceptual-motor skill in healthy adults. The participants (N = 85, age 22-80) performed five 5-trial blocks of a mirror-drawing task on three separate days (for a total of 25 trials). Index of performance was time to completion and number of errors committed. All participants improved with practice, but younger adults performed better than their older counterparts, and women performed better than men. Four brain regions--lateral prefrontal cortex (LPFC), hippocampus (HC), cerebellar hemispheres (Cb) and the caudate nucleus (Cd)--were selected on the basis of the relevant literature and measured on MRI scans. All regional volumes were negatively associated with age, although the magnitude of association differed from LPFC (the strongest) to Cd (the weakest). Larger lateral PFC was associated with better performance on the mirror drawing task, and this link was stronger in the older participants and was strengthened at the later stages of learning. Larger caudate was related to better performance, especially at later learning, among men, but among women the link was evident only during early learning. Thus, mirror-drawing represents a task that, despite its visual-spatial nature, favors women, and may exhibit sexually dimorphic brain substrates.     

Social anxiety disorder in primary care

OBJECTIVE: To examine the prevalence, comorbidity, disability and mental health treatment associated with social anxiety disorder (SAD) in primary care, and to determine whether patients with SAD avoid seeking help from their primary care providers. DESIGN: We analyzed data from a health survey conducted on a systematic sample of patients. Data were then cross-linked to the practice's automated database in order to compare primary health care utilization by patients with SAD to that of patients with other psychiatric disorders and well controls. SETTING: Urban primary care practice at a teaching hospital. PATIENTS: A systematic sample (n=207) of primary care patients. MEASUREMENTS AND MAIN RESULTS: Patients were interviewed by mental health professionals using the Composite International Diagnostic Interview. Lifetime prevalence of SAD was 5.7%. Substance use disorders were far more common among patients with SAD than patients with other psychiatric disorders (33.3% vs. 3.3%, P=.01). Social anxiety disorder patients were functionally impaired and made fewer primary care visits per year (mean 4.1) compared to patients with other psychiatric disorders (mean 6.9; P=.016) or well controls (mean 6.4; P=.031); 41.7% reported receiving mental health treatment in the past year. CONCLUSION: Patients with SAD made fewer primary care visits compared to patients with other psychiatric disorders and well controls. These results, together with the high prevalence of substance use in SAD, and the finding that less than one half received past year mental health treatment, suggest substantial unmet need for care and are especially important in view of available effective treatments for SAD.     

Hormone replacement therapy and age-related brain shrinkage: regional effects

Neuroprotective properties of estrogen have been established in animal models, but clinical trials of hormone replacement therapy (HRT) produced contradictory results. We examined the impact of HRT on age-related regional changes in human brain volume. Six brain regions were measured twice, five years apart, in 12 healthy women who took HRT and in matched controls who did not. The controls showed a typical pattern of differential brain shrinkage in the association cortices and the hippocampus with no change in the primary visual cortex. In contrast, women who took HRT showed comparable shrinkage of the hippocampus but no significant shrinkage of the neocortex. Future large scale studies may benefit from applying regional rather than global measures in assessment of brain integrity.     

Interstitial cystitis and panic disorder: a potential genetic syndrome

BACKGROUND: Evidence from a genetic linkage study had suggested a possible syndrome in some families with panic disorder (PD). This syndrome includes bladder problems (possibly urinary interstitial cystitis [IC]), thyroid disorders, chronic headaches/migraine, and/or mitral valve prolapse. In 19 multiplex families with PD, one marker (D13S779) on chromosome 13 gave a logarithm of odds score of more than 4 when individuals with any of the syndrome conditions were analyzed as affected. Families with the bladder problems yielded the highest logarithm of odds scores. These findings were replicated in an extended sample of 60 families. Whereas PD had been well characterized by direct interview, the urologic problems had been found only via medical history checklists and records. A case review by a board-certified urologist suggested they could be IC. OBJECTIVE: To determine whether patients diagnosed as having IC by urodynamics and/or cystoscopy and their first-degree relatives (FDRs) have increased rates of the syndrome conditions, thus validating that the bladder problems observed in the linkage study could be IC and providing further support for the panic syndrome. DESIGN: Case-control and family history study. SETTING: Two metropolitan urology clinics. PARTICIPANTS: One hundred forty-six probands (67 with IC and 79 with other urologic disorders) and 815 FDRs. MAIN OUTCOME MEASURES: Lifetime rates of syndrome conditions in probands and FDRs who were blind to urologic or psychiatric diagnoses in the proband. RESULTS: Compared with patients without IC, patients with IC had a significantly higher lifetime prevalence of PD (controlling for age and sex) (odds ratio, 4.05; 95% confidence interval, 1.22-13.40; P =.02) and a higher lifetime prevalence of any of the syndrome disorders (controlling for age and sex) (odds ratio, 2.22; 95% confidence interval, 0.89-5.54; P =.09). First-degree relatives of probands with (vs without) IC were significantly more likely to have PD, thyroid disorder, urologic problems, and any of the syndrome disorders (controlling for age and sex of the relative and sex of the proband) (adjusted odds ratio, 1.95; 95% confidence interval, 1.13-3.38; P =.02). These results in relatives were not influenced by PD in probands, and did not change substantially when controlling for the proband-relative relationship, modeling age as a categorical (vs continuous) variable, or excluding FDRs with PD. There were no interactions between proband IC status and sex of the relative. CONCLUSIONS: The increased frequency of seemingly disparate disorders in patients with IC and their FDRs is consistent with the genetic linkage findings in families with PD. These findings suggest that the bladder problems observed in the linkage study may be IC. The hypothesis that there is a familial, possibly pleiotropic, syndrome that may include IC, PD, thyroid disorders, and other disorders of possible autonomic or neuromuscular control deserves further investigation.     

Treatment of severe cholestasis in neonatal Dubin-Johnson syndrome with ursodeoxycholic acid

We report a case of Dubin-Johnson Syndrome in a neonate presenting with severe direct hyperbilirubinemia, which failed to respond to phenobarbital treatment. Ursodeoxycholic Acid added to therapy was well tolerated, and resulted in declining bilirubin concentration. We suggest ursodeoxycholic acid in treatment for Dubin-Johnson Syndrome with severe direct hyperbilirubinemia presenting in the neonatal age.