Polyneuropathy and Cerebral Infarction Complicating Scrub Typhus

We describe a 64-year-old man with scrub typhus who presented with both polyneuropathy and cerebral infarction. A eurological examination revealed a confused mental state, stiff neck, hearing impairment, symmetric weakness, sensory loss, and ataxia. Electrophysiologic studies showed demyelinating sensorimotor polyneuropathy and sensorineural hearing loss. Brain magnetic resonance imaging showed multiple infarctions. Brain involvement or polyneuropathy associated with scrub typhus has been rarely reported, and the pathogenic mechanism underlying the multiple neurological complications remains to be elucidated.     

The effect of gastroenterology training on the efficiency and cost of care provided to patients with diverticulitis

BACKGROUND & AIMS: National trends emphasize the need for cost- efficient medical care with no diminution in quality. The most appropriate role for various physician groups has yet to be determined. The aim of this study was to investigate the efficiency of medical care provided by family practitioners (FPs), internists (IMs), and gastroenterologists (GIs) for acute diverticulitis. METHODS: All medicare hospitalizations from 1990 to 1993 in Illinois caused by acute diverticulitis, with FPs, IMs, or GIs as the primary attending physician, were included in the study. RESULTS: The primary attending physician was an FP in 1019 cases, an IM in 2535 cases, and a GI in 163 cases. The age and sex distributions were similar. The length of stay was significantly shorter (P < 0.0001) for GIs (7.4 +/- 6 days) than for FPs (7.9 +/- 14 days) or IMs (8.6 +/- 7 days). Readmission rate was significantly less (P < 0.03) for GIs (4.5%) than for FPs (7.7%) or IMs (10.0%). No significant differences were noted in complication rates or mortality. CONCLUSIONS: Patients with diverticulitis treated by GIs have a shorter hospital stay and a lower risk for readmission than patients treated by FPs or IMs. This improved quality of care should be considered by managed care organizations because they decide the role of various physician groups. (Gastroenterology 1997 Jun;112(6):1859-62)     

High-dose intravenous gammaglobulin in alloimmunized platelet transfusion recipients

High-dose intravenous gammaglobulin (polyvalent immunoglobulin G) has been shown to be of benefit in some patients with immune thrombocytopenic purpura (ITP), possibly by producing reticuloendothelial system blockade. We studied this approach in patients refractory to random donor platelet transfusion using an IV IgG preparation manufactured by the Swiss Red Cross. Eleven adult patients with acute leukemia received either 0.4 g IgG/kg/d intravenously X five days (four patients) or 0.6 g/kg/d X five days (seven patients). All patients had high levels of lymphocytotoxic antibody and poor responses to random donor platelets. Except for mild headaches in two patients, there were no side effects related to the IgG infusions. All patients had significant elevations of serum IgG on the day after completion of treatment. Either random donor or partially HLA-matched platelet transfusions were administered the day after and, in some cases, during the IgG therapy. No patient had an improvement in one hour posttransfusion platelet count increments. Two additional patients received pooled platelet concentrates incubated for 30 minutes at 37 degrees C with IgG at a final concentration of 3 g% prior to transfusions. These results indicate that high-dose IgG, an extremely expensive treatment, cannot be recommended for alloimmunized adults with leukemia.     

Fludarabine: a new agent with major activity against chronic lymphocytic leukemia

Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.     

Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-kappaB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation

Roflumilast, a potent and selective phosphodiesterase 4 (PDE4) inhibitor, has been demonstrated to be an effective anti-inflammatory agent in airway inflammatory diseases. In the present study, we investigated the mechanism of anti-inflammatory effects of roflumilast in murine macrophage cell line RAW264.7 cells. Roflumilast inhibited NO, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta production via suppression of their gene expressions in lipopolysaccharide (LPS)-stimulated macrophages. To elucidate the mechanism by which roflumilast inhibits the production of inflammatory mediators, we examined the effect of roflumilast on the activation of nuclear factor-kappaB (NF-kappaB) in these cells. Roflumilast inhibited the DNA binding activity of NF-kappaB by preventing inhibitor kappaBalpha phosphorylation and degradation. The phosphorylation of mitogen-activated protein (MAP) kinases, including stress-activated protein kinase/c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase, was also markedly inhibited by roflumilast. Similar to the effects of roflumilast, treatment of either SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole] or SP600125 [anthra(1,9-cd)pyrazol-6(2H)-one 1,9-pyrazoloanthrone], specific inhibitors of p38 MAP kinase and JNK, respectively, suppressed NO, TNF-alpha, and IL-1beta production. Consistent with in vitro results, administration of roflumilast recovered the survival rate of LPS-treated mice, with concurrent suppression of plasma levels of nitrite/nitrate, TNF-alpha, and IL-1beta. These results suggest that the inhibitory activity of roflumilast on the production of inflammatory mediators seems to be mediated via inhibition of NF-kappaB, p38 MAP kinase, and JNK activation in macrophages.