A case of elderly-onset herpes simplex encephalitis in an 89-year-old woman, who recovered with acyclovir therapy, showed relapse 2 months later, and died

The number of case reports on elderly-onset herpes simplex encephalitis (HSE) has been increasing. We encountered the case of an 89-year-old woman with HSE, who was probably one of the oldest-onset patients in Japan. She was a bed patient with underlying diseases of old cerebral infarction and cholangitis. These conditions might be risk factors for the onset of HSE. Concerning HSE among the elderly, it is important to pay attention to underlying diseases that weaken their immunity. Although we delayed in diagnosing her case and started treatment 1 month after convulsions appeared, she completely recovered with intravenous acyclovir (ACV) therapy. However, relapse occurred 2 months after the therapy ended. We treated her again with intravenous ACV but she died without improvement. ACV, which was initially effective, was ineffective at relapse. Cases of ACV-resistant herpes simplex virus (HSV) infection have been reported in immunodeficient patients. The immune system of elderly patients is sometimes too weak to suppress the mutation of the virus. In this case, the HSV may have become resistant to ACV. Therefore, the possibility of ACV resistance should be considerd in HSE relapse in the elderly population.     

Somatic symptoms in those hospitalized for dizziness or vertigo

Anxiety and depression greatly affect the prognosis of and burden on subjects seen for dizziness or vertigo, who usually report multiple somatic symptoms. We studied the prevalence of these symptoms in 145 subjects hospitalized for dizziness or vertigo and taking part in 4-day group vestibular rehabilitation. Questionnaires given to determine the prevalence of somatic symptoms assessed headache, insomnia, diarrhea, constipation, stomachache, chest pain, palpitations, dyspnea, general fatigue, and stress. Quantitation used aerical rating scale (NRS). Anxiety and depression were assessed using the hospital anxiety and depression scale (HADS). Disability due to dizziness was assessed using the dizziness handicap inventory (DHI). We conducted correlational analysis between dizziness and somatic symptoms. The top four average NRS scores for somatic symptoms were dizziness at 3.5 +/- 2.8, general fatigue at 2.8 +/- 2.6, insomnia at 2.4 +/- 2.6, and headache at 1.8 +/- 2.3. These symptoms resembled those reported for subjects with anxiety and depression. The correlation between headache and dizziness NRS scores was R = 0.48 (P < 0.0001). The total HADS score was 13.9 +/- 8.1 points (anxiety 7.2 +/- 4.3, depression 6.7 +/- 4.3). The average DHI score was 36.3 +/- 24.1 points. These results indicate that those with dizziness reported several somatic symptoms related to anxiety and depression attributable to dizziness. This underscores the need to treat these somatic symptoms when treating subjects seen chiefly dizziness or vertigo.     

MR imaging of clear cell carcinoma of the ovary

Magnetic resonance imaging findings are reported for 12 pathologically proven lesions of clear cell carcinoma (CCC) of the ovary in 11 women (mean age 50 years). T1- and T2-weighted MR images were obtained in all patients, and gadolinium-enhanced MR images were obtained in 9. The mean diameter of the tumors was 13 cm. Seven patients presented with stage-I tumors. All 12 lesions consisted of cystic masses with solid protrusions occurring in 10 and solid masses in 2. The cysts were unilocular in 9 lesions and multilocular in 1. In four lesions, the cysts displayed with high intensity on T1-weighted images. Round solid protrusions were identified in 8 lesions. In 5 lesions, the number of protrusions was only a few. The solid portions of 5 masses had slightly high-intensity regions on T1-weighted images. The number of patients with ascites was three. Magnetic resonance imaging of CCC usually shows a unilocular large cyst with solid protrusions, which are often round and few in number. Such MR imaging findings suggest malignant tumor but are not specific. Received: 26 July 1999 Revised: 11 February 2000 Accepted: 10 August 2000     

Analysis of Various Treatments for Pulmonary Aspergillomas

The objective of this study was to analyze the results of various treatments for pulmonary aspergilloma and to determine the surgical indications. A total of 41 patients with pulmonary aspergilloma hospitalized at the National Minamifukuoka Chest Hospital between 1973 and 1999 were analyzed with regard to their response to treatment and long-term prognosis. Five asymptomatic patients who were untreated demonstrated no change in the clinical status of aspergilloma. Analysis of the short-term response revealed surgery to be the most effective treatment. Systemic and intracavitary injections of antifungal drugs were not definitely effective, although they had a positive effect in some patients. A survival analysis revealed that all eight patients who underwent surgery are still alive. Using the Cox proportional hazard model, it was found that the favorable prognostic factors were the absence of symptoms, the absence of a superimposed bacterial infection, and surgery. There were ten deaths: three from lung cancer and seven related to uncontrollable superimposed bacterial infections, often resulting in hemoptysis. We conclude that patients with asymptomatic pulmonary aspergillomas should be clinically observed for signs of the development of lung cancer, but do not require active treatment. On the other hand, patients who are symptomatic and have uncontrollable superimposed bacterial infection will benefit from surgery. Received: August 24, 2000 / Accepted: March 6, 2001     

Role of Endothelium in the Action of Isoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries

Background: It is believed that isoflurane decreases blood pressure predominantly by decreasing systemic vascular resistance with modest myocardial depression. Nevertheless, little information is available regarding the direct action of isoflurane on systemic resistance arteries.

Methods: With use of the isometric force recording method, the action of isoflurane on contractile response to norepinephrine, a neurotransmitter that plays a central role in sympathetic maintenance of vascular tone in vivo, was investigated in isolated rat small mesenteric arteries.

Results: In the endothelium-intact strips, the norepinephrine response was initially enhanced after application of isoflurane (2-5%), but it was subsequently almost normalized to the control level during exposure to isoflurane. However, the norepinephrine response was notably inhibited after washout of isoflurane. In the endothelium-denuded strips, the norepinephrine response was gradually inhibited during exposure to isoflurane (>= 3%), and the inhibition was prolonged after washout of isoflurane. The isoflurane-induced enhancement of norepinephrine response was still observed after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of endothelin-1, angiotensin-II, and serotonin receptors; however, it was prevented by superoxide dismutase.     

Epidermal growth factor receptor lacking C-terminal autophosphorylation sites retains signal transduction and high sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor

Constitutively active mutations of epidermal growth factor receptor (EGFR) (delE746_A750) activate downstream signals, such as ERK and Akt, through the phosphorylation of tyrosine residues in the C-terminal region of EGFR. These pathways are thought to be important for cellular sensitivity to EGFR tyrosine kinase inhibitors (TKI). To examine the correlation between phosphorylation of the tyrosine residues in the C-terminal region of EGFR and cellular sensitivity to EGFR TKI, we used wild-type (wt) EGFR, as well as the following constructs: delE746_A750 EGFR; delE746_A750 EGFR with substitution of seven tyrosine residues to phenylalanine in the C-terminal region; and delE746_A750 EGFR with a C-terminal truncation at amino acid 980. These constructs were transfected stably into HEK293 cells and designated HEK293/Wt, HEK293/D, HEK293/D7F, and HEK293/D-Tr, respectively. The HEK293/D cells were found to be 100-fold more sensitive to EGFR TKI (AG1478) than HEK293/Wt. Surprisingly, the HEK293/D7F and HEK293/D-Tr cells, transfected with EGFR lacking the C-terminal autophosphorylation sites, retained high sensitivity to EGFR TKI. In these three high-sensitivity cells, the ERK pathway was activated without ligand stimulation, which was inhibited by EGFR TKI. In addition, although EGFR in the HEK293/D7F and HEK293/D-Tr cells lacked significant tyrosine residues for EGFR signal transduction, phosphorylation of Src homology and collagen homology (Shc) was spontaneously activated in these cells. Our results indicate that tyrosine residues in the C-terminal region of EGFR are not required for cellular sensitivity to EGFR TKI, and that an as-yet-unknown signaling pathway of EGFR may exist that is independent of the C-terminal region of EGFR. ( Cancer Sci 2009; 100: 552–557)     

Second myeloablative allogeneic stem cell transplantation (SCT) using cord blood for leukemia relapsed after initial allogeneic SCT

There are many reports of second allogeneic stem cell transplantation (allo-SCT) using cord blood (CB) for graft failure after initial allo-SCT. However, the efficacy of second allo-SCT using CB for patients with leukemia relapsed after initial allo-SCT is unknown. We report the results of second allo-SCT using CB in seven adult patients with leukemia relapsed after initial allo-SCT. All patients received a myeloablative conditioning regimen including oral busulfan 16 mg/kg, intravenously fludarabine 100mg/m(2) and cyclophosphamide 120 mg/kg. All but one patient had myeloid reconstitution and four patients remain alive at between 4 and 40 months after second SCT. We conclude that second myeloablative allo-SCT using CB may be feasible in selected patients with the relatively younger age, less organ damage and longer time interval between first and second allo-SCT.     

Soy consumption reduces the risk of non-small-cell lung cancers with epidermal growth factor receptor mutations among Japanese

Epidermal growth factor receptor (EGFR) mutations play substantial roles in genesis and proliferation of non-small-cell lung cancers (NSCLCs). We recently found that reproductive factors have a substantial impact on risk of development of NSCLCs featuring such EGFR mutations. Therefore, we explored the influence of dietary habits on NSCLC risk with reference to the EGFR mutational status. We conducted a case-control study using 353 patients with NSCLCs (122 EGFR mutated and 231 EGFR wild-type) and 1765 age-sex matched non-cancer control subjects. Dietary exposure was based on a semiquantitative food frequency questionnaire and impact of major food items, like meats, seafoods, vegetables and soybean products was assessed by multivariate logistic regression. Soybean products demonstrated a protective association with EGFR mutated, but not EGFR wild-type NSCLCs, with multivariate-adjusted odds ratios and 95% confidence intervals for the 2nd and 3rd tertile of soybean product consumption of 0.79 (0.50–1.27) and 0.56 (0.34–0.93) relative to those in the lowest tertile (trend P  = 0.023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis. ( Cancer Sci 2008; 99: 1202–1208)