Clinical characteristics and therapeutic outcome of patients with febrile neutropenia who present in shock: need for better strategies

OBJECTIVE: To study the frequency of neutropenic febrile patients who present in shock, to evaluate the influence of this presenting feature on response to antibiotic therapy, morbidity, and mortality and to identify discriminating demographic features and clinical characteristics of these individuals. METHODS: Prospectively collected data on all episodes of fever and neutropenia observed in cancer patients who were hospitalized for parenteral antibiotic therapy. RESULTS: Five hundred and seventy-six patients were evaluated; 22 (3.8%) presented in shock. This group of individuals was compared with the remainder. Patients presenting in shock were more likely to be older (P< 0.01) and have progressive unresponsive cancer (P< 0.01). They were also more likely to present with septic appearance (P< 0.01), dehydration (P< 0.01), diarrhoea (P< 0.01), altered mental status (P< 0.01) clinical bleeding (P= 0.02) and dyspnoea (P< 0.01). They more often had anaemia (P< 0.01), thrombocytopenia (P= 0.02) and abnormal liver function tests (P< 0.01). Eight of the 22 patients presenting in shock had documented bacteraemia. Non-bacteraemic microbiological infections were observed in three patients. Five patients had clinical evidence of infection and another five were severely dehydrated and volume depleted. One patient had cardiogenic shock. Three patients were managed with monotherapy, 19 received combination antibiotics as initial empirical therapy. Overall outcome of these patients was extremely poor, particularly those with infectious aetiology. Eighteen (82%) patients expired. CONCLUSION: Neutropenic febrile patients who present in shock have extremely poor outcomes irrespective of type of initial antibiotic therapy. Intense efforts are required to improve their outcome.     

Induction of Th1 cytokine responses by mycobacterial antigens in leprosy.

Twelve mycobacterial antigens were compared for induction of gamma interferon (IFN-gamma) secretion by human blood mononuclear cells of patients with leprosy. Fractionated Mycobacterium leprae antigens containing cell wall proteins or cytosolic and membrane proteins induced good IFN-gamma responses in tuberculoid leprosy patients. Lipoarabinomannan from M. tuberculosis Erdman and M. leprae mycolylarabinogalactan peptidoglycan were the poorest IFN-gamma inducers.     

Correlation of electrocorticographic to clinical seizure onset and interhemispheric propagation times in temporal lobe epilepsy

This study was performed to test the hypothesis that, in human temporal lobe epilepsy, electrocorticographic time factors involved in the ictal EEG to clinical ictal transition (electrocorticographic to clinical seizure onset time, ECOT) and the interhemispheric propagation of epileptic activity (interhemispheric propagation time, IHPT), which are independently correlated with temporal lobe epileptogenicity and predictive of seizure-free outcome following temporal lobectomy, are correlated with one another in a quantitative fashion. A series of 37 patients with medically intractable temporal lobe seizures was studied with long-term subdural videoelectroencephalographic monitoring. Temporal lobe seizure interhemispheric propagation time (IHPT) was found to be a negative, exponential function of electrocorticographic to clinical seizure onset time (ECOT) (f(x) = 8.201 × 10^−0.016x, r = 0.347, d.f. = 35, t = 2.19, p < 0.05, where f(x) = IHPT and x = ECOT). A small increase in ECOT was associated with a substantial decrease in IHPT and vice versa. The results suggest the electrophysiological time factor, ECOT, involved in the transition from ictal EEG seizure onset to clinical seizure onset, may determine the speed of interhemispheric propagation of established epileptic activity. The results suggest the interesting hypothesis that, in human temporal lobe epilepsy and, perhaps, under non-pathological circumstances, the human temporal lobe might possess a “time-labeling” function amenable to quantitative analysis.     

S-phase kinase protein 2 is an attractive therapeutic target in a subset of diffuse large B-cell lymphoma

S-phase kinase protein 2 (SKP2), an F-box protein, targets cell-cycle regulators including cycle-dependent kinase inhibitor p27KiP1 via ubiquitin-mediated degradation. SKP2 is frequently overexpressed in a variety of cancer cells and has been implicated in oncogenesis; however, its role in diffuse large B-cell lymphoma (DLBCL) has not been elucidated. Therefore, we investigated the role of SKP2 and its ubiquitin-proteasome pathway in a large series (301) of DLBCL patient samples and a panel of DLBCL cell lines. Using immunohistochemistry, SKP2 was detected in 41.6% of DLBCL tumours and was inversely associated with p27Kip1 protein level. The DLBCL subset with high SKP2 and low p27Kip1 showed a strong correlation with the proliferating index marker Ki-67 (p < 0.0001) and also with the germinal centre phenotype (p = 0.0147). Treatment of DLBCL cell lines with bortezomib or expression of SKP2-specific siRNA causes down-regulation of SKP2 and accumulation of p27Kip1, leading to suppression of growth by inducing apoptosis. Furthermore, treatment of DLBCL cells with bortezomib causes apoptosis via involving the mitochondrial pathway and activation of caspases. Finally, treatment of DLBCL cells with bortezomib down-regulated the expression of XIAP, cIAP1, and survivin. Altogether, these results suggest that SKP2 and the ubiquitin-proteasome pathway may be a potential target for therapeutic intervention in DLBCL.     

A case of acute infectious mononucleosis presenting with very high ferritin

Hepatitis is an important but uncommon manifestation of acute Epstein Barr infection. Infectious mononucleosis is usually a disease of young adults. We report a case of infectious mononucleosis in a 72-year old jaundiced gentleman with ferritin level of 2438 that normalised on clinical improvement.     

Cytochemical localization of 5'-nucleotidase activity in retinal photoreceptor cells

Further cytochemical studies on the ultrastructural localization of 5'-nucleotidase in the rat retina have revealed activity to be associated with the complex synapses formed by the rod spherules of the receptors and the bipolar and horizontal cell processes. Activity was also seen on the axolemma of receptor fibers. In the rod inner segment strong reaction product is located intracellularly. In the rod outer segment the enzyme appears to be located only on the cytoplasmic side of the disc membrane and not intradiscally . Retinal pigment cells are rich in 5'-nucleotidase. Their microvilli accompany the tips of the receptor cells and show enzyme activity in an ecto position. A role for 5'-nucleotidase is possible in the metabolism of guanylate and adenylate nucleotides both of which are important for visual transduction processes.     

Evaluation of Screening and Commercial Methods for Detection of Methicillin Resistance in Coagulase-Negative Staphylococci

The National Committee for Clinical Laboratory Standards recommends 48 h of incubation by the oxacillin salt agar screen (OSAS) method for the detection of methicillin-resistant coagulase-negative staphylococci (CoNS). An earlier identification of methicillin resistance is desirable. The time to detection of the mecA gene by PCR was compared with the times to detection by OSAS, by the oxacillin disk diffusion (ODD) method, and with MicroScan Gram Positive Combo type 6 panels (MicroScan Inc. Sacramento, Calif.) and Vitek GPS-SA cards (bioMérieux Vitek Inc., Hazelwood, Mo.). The combination of the Vitek card and the ODD method detected 92 of 99 methicillin-resistant strains of CoNS at 24 h; however, 6 mecA-positive strains were phenotypically methicillin susceptible. We conclude that most methicillin-resistant CoNS can be detected and the results can be reported after overnight incubation by a combination of methods.