Actin-free Gc globulin: a rapidly assessed biomarker of organ dysfunction in acute liver failure and cirrhosis.

Reductions in serum levels of Gc globulin, a hepatically synthesized component of the extracellular actin scavenger system responsible for complexing circulating actin and attenuating intravascular microthrombus formation, are associated with poor outcome in acute liver failure. Clinically applicable assays of the important actin-free fraction (Af-Gc) have not been available until now. We measured actin-free Gc globulin levels with a novel, rapid assay in 61 cases of acute liver failure (ALF) and in 91 patients with cirrhosis (40 of whom were clinically unstable with extrahepatic organ dysfunction), and studied associations with liver dysfunction, extrahepatic organ dysfunction, indices of disseminated coagulation, and outcome. Reductions in Af-Gc levels mirrored hepatic dysfunction and organ dysfunction in both groups, and discriminated patients with poor prognosis from those with good prognosis in the ALF cohort. Levels were lowest in patients with ALF (10% of control values), but levels were also markedly reduced in both unstable (28%) and stable (44%) patients with cirrhosis. Associations with markers of disseminated intravascular coagulation were seen in both groups, most notably in the cirrhosis cohort, supporting a pathophysiological role for reduced Af-Gc in the evolution of organ dysfunction. In acetaminophen-induced ALF, Af-Gc identified patients with poor prognosis as well as did the Acute Physiology and Chronic Health Evaluation (APACHE II) score (area under the receiver operating characteristic curve, 0.7), and in cirrhosis, Af-Gc was an independent predictor of mortality by multifactorial analysis. In conclusion, the importance of Af-Gc reductions in the development of multiple organ dysfunction in ALF and cirrhosis is highlighted, probably resulting from reduced hepatic production and peripheral exhaustion of this arm of the extracellular actin scavenger system.     

Mycobacterium tuberculosis and Mycobacterium avium inhibit IFN- gamma -induced gene expression by TLR2-dependent and independent pathways.

Mycobacteria-infected macrophages are poor responders to interferon-gamma (IFN-gamma), resulting in decreased expression of IFN-gamma-induced genes. In the present study, we examined the inhibition of IFN-gamma-induced gene expression by Mycobacterium tuberculosis and four different Mycobacterium avium strains in mouse RAW264.7 macrophages. Gamma-irradiated M. tuberculosis inhibited mRNA expression of a panel of six different IFN- gamma-induced genes. All four of the M. avium strains completely inhibited IFN-gamma-induced expression of MHC class II Aalpha and Ebeta mRNA. However, the Mac101 strain, which is serovar 1, inhibited IFN-gamma induction of IFN regulatory factor-1 (IRF-1) and guanylate-binding protein-1 (GBP-1) mRNA to a greater extent than the other M. avium strains, which are serovar 2. In this study, we also show that mycobacteria inhibit gene expression by both toll-like receptor 2 (TLR2)-dependent and independent pathways. The inhibition of IFN-gamma-induced gene expression by M. avium was reduced but not completely blocked in macrophages from TLR2(/) mice. IFN-gamma-induced gene expression was also inhibited by mycobacteria in RAW264.7 cells expressing dominantnegative TLR2 or myeloid differentiation factor 88 (MyD88), further indicating the existence of a pathway independent of TLR2 and MyD88. These data suggest that mycobacteria inhibit IFN-gamma-induced gene expression by multiple pathways involving both TLR2 and non-TLR receptors.     

Retroviruses and schizophrenia in Jamaica

Reports of an 18-fold higher incidence of schizophrenia among second-generation Afro-Caribbeans, and especially Jamaican migrants in the United Kingdom were soon called “an epidemic of schizophrenia,” with the inference that a novel virus, likely to be perinatally transmitted, was a possible etiological agent. This intriguing observation led us to explore a possible link with human T-cell lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in the Caribbean Islands, is perinatally transmitted, known to be neuropathogenic, and the cause of a chronic myelopathy (tropical spastic paraparesis/ HTLV-I associated myelopathy). We therefore examined inpatients at the Bellevue Mental Hospital, Kingston, Jamaica and did standard serological tests for retroviruses HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and DSM III-R criteria for schizophrenia. Our results produced important negative data, since the seropositivity rates for HTLV-I, the most likely pathogen, were no greater than the seropositivity range for HTLV-I carriers in this island population, indicating that HTLV-I and the other retroviruses tested do not play a primary etiological role in Jamaican schizophrenics.     

Associated occurrence of persistent truncus arteriosus and asplenia

Summary An infant with persistent truncus arteriosus associated with splenic agenesis and the asplenia syndrome is reported, including clinical, echocardiographic and autopsy findings. To the authors' knowledge this association has not been previously reported.     

Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and Sézary syndrome: a critical reappraisal

It is often difficult to make a clinical or histologic diagnosis of erythrodermic mycosis fungoides (MF) and Sézary syndrome (SS). Whereas the histologic parameters for making a diagnosis of MF with well-developed patch and plaque stage lesions are clearly defined, the same criteria appear to be less relevant for diagnosing MF in patients with erythroderma secondary to the disease. In order to better define the histologic features of erythrodermic MF and SS, we studied 28 routine histologic sections of 17 patients with known erythrodermic MF or SS. Sections were reviewed independently by 2 dermatopathologists. Each of 24 parameters was scored semi-quantitatively and the data were compared to data previously reported from a group of 64 patients with limited patch and plaque stage lesions of MF. When compared to biopsies from patients with limited patch/plaque lesions, biopsies taken from erythrodermic patients displayed more parakeratosis (p=0.0492) and acanthosis (p=0.0046), less disproportionate epidermotropism, fewer lymphocytes aligned within the basal layer (p=0.0045), fewer hyper-convoluted cells in the epidermis, more dermal hyperconvoluted cells (p=0.0191), more papillary dermal fibrosis (p=0.0002), more prominent teleangiectasias (p=0.0028) and more mitotic figures.
The histologic features of erythrodermic MF and Sézary syndrome are even more subtle than the features of patch and plaque stage MF, thus rendering the histologic diagnosis more difficult.     

Neuroblastoma of the Anterior Mediastinum in an 80-Year-Old Woman

A 7-cm anterior mediastinal tumor in an 80-year-old woman was found by light and electron microscopy to be a neuroblastoma. Immunoreactivity for neuron-specific enolase, synaptophysin, and chromogranin supported the diagnosis. Neuroblastoma is an uncommon tumor in adults and we are not aware of a previous report of such a tumor in a patient of this age.     

Corneal pathophysiology with contact lens wear

Contact lens wear induces a wide spectrum of changes in the appearance and function of the cornea. The most salient effect of lens wear is the hypoxically induced reduction in the rate of metabolic activity of the corneal epithelium and its sequellae. Other important alterations to corneal health associated with contact lens wear may be caused by antigenic and toxic stimuli, mechanical forces, osmotic effects and carbon dioxide retention. Perhaps the most important task facing the contact lens clinician is to distinguish between an acceptable state of physiological modification and an anomalous or pathological state of hypofunction. In this article, we review the assortment of corneal changes primarily on the basis of the causative agents and time scale with reference to the physical and chemical processes leading to the observed signs or symptoms. This procedure allows a strong foundation for understanding the etiology and management principles for the variety of effects that contact lenses may have on the cornea.     

Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.     

A case of Datisca glomerata poisoning in beef cattle

Six of 175 Angus heifers died after ingesting excessive amounts of Durango root (Datisca glomerata). Animals had rumens full of Durango root, were extremely lethargic, and had diarrhea prior to death. The animals had nonspecific postmortem lesions. This case is discussed in light of previous findings from trials in which Durango root was experimentally fed to cattle.