A lack of ongoing diabetes is an important factor in preserving eyes from late or suboptimally treated endogenous endophthalmitis secondary to Klebsiella pneumoniae liver abscess

Purpose:

The purpose of this study is to identify the possible factors for preserving the eyes after late or suboptimally treated endogenous endophthalmitis secondary to Klebsiella pneumoniae (KP) liver abscess.

Methods:

A retrospective chart review was conducted for patients admitted with KP liver abscess from January 1991 to June 2012.

Results:

Six hundred and ninety-three patients with KP liver abscess were recorded, in which endophthalmitis was identified in 53 cases (65 eyes, 8.29%). Diabetes was significantly associated with the development of endophthalmitis (p = 0.014). Eleven eyes received their last ocular treatment ≥10 days and final vision ≥ counting fingers, and were defined as benign type KP endophthalmitis. The absence of diabetes was the only consistent candidate factor for benign type KP endophthalmitis.

Conclusion:

A lack of ongoing diabetes is an important factor in preserving eyes with late or suboptimally treated endogenous endophthalmitis second to KP liver abscess.     

The effect of fluvastatin on fibrinolytic factors in patients with hypercholesterolemia

Several studies have shown cardiovascular benefit in treating hypercholesterolemia with HMG-CoA reductase inhibitor. However, in addition to the lowering of cholesterol, the beneficial effects of this inhibitor reflect other pharmacological activities. Whether these beneficial effects are partly mediated by changes in fibrinolytic factors remains to be proven, since clinical studies on the effects of HMG-CoA reductase inhibitors on fibrinolytic factors have not yielded consistent results. The purpose of this study was to evaluate the effects of fluvastatin on fibrinolytic factors in hypercholesterolemic patients. After 6 weeks on a low-fat, low-cholesterol diet, 23 outpatients known to have primary hypercholesterolemia with low density lipoprotein cholesterol (LDL-C) > or = 130 mg/dl with at least 2 risk factors or fasting LDL-C > or = 160 mg/dl were selected for the study. Venous blood samples were collected at baseline and at 8 weeks after fluvastatin therapy (40 mg/day) to measure of tissue plasminogen activator (t-PA), plasminogen activators inhibitor-1 (PAI-1), fibrinogen, D-dimer and lipid profile. After 8 weeks of therapy, fluvastatin reduced serum cholesterol by 11% (261.9 mg/dl vs 233.2 mg/dl, P < 0.01) and LDL-C by 22% (191.9 mg/dl vs 149.3 mg/dl, P < 0.01). D-dimer was significantly decreased (0.38 ng/L vs 0.28 ng/L, P = 0.02) and tPA, PAI-1 and fibrinogen tended to decrease after therapy. Fluvastatin therapy improved fibrinolytic profile; the result of this study may in part explain the benefit of HMG-CoA reductase inhibitor on cardiovascular system other than lipid lowering.     

Intratumor injection of OK-432 for the treatment of small hepatocellular carcinoma

Intratumor injection of OK-432, a biological response modifier, in the treatment of small HCC was studied in 7 inoperable patients. After evaluation with ultrasound (US), computed tomography (CT), angiography and US-guided biopsy, implantation of a steel coil in the tumor, intratumor injection was performed under US guidance. After completion of the treatment, liver biopsy and image studies were again done to evaluate the extent of tumor necrosis. One patient was alive and well without recurrence 19 months after treatment. Four had recurrent tumors at different site of the liver 4 months, 9 months, 9 months and 8 months later. Two died of progressive malignancy 3 months and 8 months later. In the 6 patients with elevated serum alpha-fetoprotein (AFP) levels, 4 had decreased AFP after treatment, and the 2 mortalities had steadily increased AFP. The most common side effects are fever and chills. Transient abdominal pain with elevated transaminase activities, cough with hemoptysis, and vomiting were seen in 1 case each. After treatment, the biopsy specimens showed total necrosis of HCC. Although the T4/T8 ratio of peripheral blood was increased as compared with that before treatment in 4 cases, peritumoral cytotoxic T lymphocyte and monocyte infiltration were seen in one specimen only, and another 7 examined specimens showed negative staining with monoclonal antibodies of T cells. We conclude that intratumor injection of OK-432 is an alternative treatment for small HCC in inoperable cases. The effectiveness may be due to the direct tumoricidal mechanism of OK-432.     

Recurrent hepatocellular carcinoma presenting with superior vena cava syndrome

A 45-year-old male received wedge resection for his small hepatocellular carcinoma in April 1989 and extended right lobectomy for tumor recurrence 8 months later. Unfortunately, recurrent hepatic tumor with lung metastases were found 18 months after the second operation. Both the hepatic and pulmonary recurrent tumors were resected and transcatheter arterial embolization was added for the residual hepatic tumors. He remained symptom free for another 18 months. However, mediastinal lymphadenopathy, superior vena cava thrombus with superior vena cava syndrome, cardiac and brain metastases developed subsequently. He died of increased intracranial pressure. It is rare for hepatocellular carcinoma to have mediastinal metastases, superior vena cava thrombus and superior vena cava syndrome.     

Simvastatin reduces plasma concentration of high-sensitivity C-reactive protein in type 2 diabetic patients with hyperlipidemia

High-sensitivity C-reactive protein (hs-CRP) is positively associated with the prevalence of coronary artery disease by epidemiologic data. Prospective studies indicate that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduced the plasma hs-CRP concentration and the risk of recurrent coronary events after myocardial infarction. Type 2 diabetes is associated with high mortality risk of coronary heart disease and this high risk may be involved in the inflammatory factors. We have therefore conducted a prospective study to assess whether simvastatin can rapidly reduce the plasma hs-CRP concentration in type 2 diabetic patients with hyperlipidemia. Seventeen type 2 diabetic patients with hyperlipidemia were enrolled in the study after 6 weeks on a lipid-lowering diet. Fourteen patients completed the study, taking simvastatin 20 mg daily for 8 weeks. Fasting blood samples were collected from each patient before and after 8-week administration of simvastatin. In response to 8-week administration of simvastatin, hs-CRP levels significantly decreased from 0.312±0.057 to 0.193±0.045 mg/dl (P<.01). Plasma LDL cholesterol also decreased significantly from 130±9 to 74±3 mg/dl (P=.001). This study shows that plasma hs-CRP concentration can be reduced by 8-week administration of simvastatin in type 2 diabetic patients with hyperlipidemia.     

DNA clonal heterogeneity of hepatocellular carcinoma demonstrated by Feulgen-DNA analysis

To demonstrate DNA clonal heterogeneity of hepatocellular carcinomas (HCC), the DNA histographic pattern of both primary HCCs and their recurrent or metastatic lesions were studied among 36 patients (33 men and 3 women). Thirty-six paired aspirations or imprints taken from primary, recurrent or metastatic lesions were stained, using the modified Feulgen method, and the DNA content was measured with a scanning microdensitometer at a wavelength of 550 nm. Paired aspirations or imprints taken from different parts of the same HCC were examined in 17 cases; the DNA distribution patterns were similar in 15 (88%) and differed in only two (12%). A similar DNA histogram was also shown among different tumors in 10 (71%) of 14 patients with multiple HCCs, with a DNA ploidy discrepancy in only four (29%). Two of two subcutaneous metastases and two of three recurrent tumors showed DNA distribution patterns similar to those in their primary HCCs. In summary, a DNA clonal heterogeneity of HCC was found in 19% (7/36). In contrast, the similar DNA histographic patterns found in most instances among different parts of the HCC and between the primary and recurrent or metastatic lesions suggest that HCC may derive from a single cell clone in the majority of cases.     

Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications

The growth rate of 31 asymptomatic hepatocellular carcinomas (diameter less than or equal to 5 cm) discovered in 28 patients by a prospective screening program was determined by real-time ultrasonography over 36-860 days. Except for one tumor that shrank on follow-up, the doubling time ranged from 29 to 398 days, with a median of 117 days, an arithmetic mean of 136 days, and a geometric mean of 110 days. In 17 tumors with more than two measurements, the growth rate remained exponential in nine, declined in growth in seven, and showed an initial lag period in one. Doubling time correlated with initial tumor diameter but was independent of the patient's age, sex, hepatitis B surface antigen status, tumor location, liver function tests, stage of liver cirrhosis, histologic type, or grade of malignancy. Although initial alpha-fetoprotein levels did not correlate well with growth rate, in 14 patients with an exponential increase of serum alpha-fetoprotein, the alpha-fetoprotein doubling time was closely related to the tumor doubling time. Based on the above data, the median detectable subclinical period of hepatocellular carcinoma was deduced to be 3.2 yr, and the suitable screening interval for its early detection in our area was 4-5 mo.     

Reciprocal modulation of C/EBP‐α and C/EBP‐β by IL‐13 in activated microglia prevents neuronal death

In response to aggravation by activated microglia, IL‐13 can significantly enhance ER stress induction, apoptosis, and death via reciprocal signaling through CCAAT/enhancer‐binding protein alpha (C/EBP‐α) and C/EBP‐beta (C/EBP‐β). This reciprocal signaling promotes neuronal survival. Since the induction of cyclooxygenase‐2 (COX‐2) and peroxisome proliferator‐activated receptor gamma/heme oxygenase 1 (PPAR‐γ/HO‐1) by IL‐13 plays a crucial role in the promotion of and protection from activated microglia, respectively; here, we investigated the role of IL‐13 in regulating C/EBPs in activated microglia and determined its correlation with neuronal function. The results revealed that IL‐13 significantly enhanced C/EBP‐α/COX‐2 expression and PGE₂ production in LPS‐treated microglial cells. Paradoxically, IL‐13 abolished C/EBP‐β/PPAR‐γ/HO‐1 expression. IL‐13 also enhanced ER stress‐evoked calpain activation by promoting the association of C/EBP‐β and PPAR‐γ. SiRNA‐C/EBP‐α effectively reversed the combined LPS‐activated caspase‐12 activation and IL‐13‐induced apoptosis. In contrast, siRNA‐C/EBP‐β partially increased microglial cell apoptosis. By NeuN immunochemistry and CD11b staining, there was improvement in the loss of CA3 neuronal cells after intrahippocampal injection of IL‐13. This suggests that IL‐13‐enhanced PLA2 activity regulates COX‐2/PGE₂ expression through C/EBP‐α activation. In parallel, ER stress‐related calpain downregulates the PPAR‐γ/HO‐1 pathway via C/EBP‐β and leads to aggravated death of activated microglia via IL‐13, thereby preventing cerebral inflammation and neuronal injury.     

Is peptic ulcer disease a risk factor of postherpetic neuralgia in patients with herpes zoster?

Postherpetic neuralgia is the most common complication of herpes zoster which is caused by a reactivation of latent varicella zoster virus. The pathogenesis of postherpetic neuralgia may involve peripheral and central mechanisms. Reported risk factors for postherpetic neuralgia include female gender, old age, diminished cell-mediated immunity and nutritional deficiencies. Based on our clinical observation which revealed that peptic ulcer disease (PUD) is one of the common comorbidities in patients with postherpetic neuralgia, we hypothesize that herpes zoster patients with PUD may be at a greater risk for the development of postherpetic neuralgia due to their impaired cellular immunity and depressed nutritional status. Major causes of PUD include Helicobacter pylori infection and usage of ulcerogenic medications. Patients with H. pylori infection may develop T cell dysfunctions and nutritional deficiencies including vitamin C, iron, cobalamin, carotenes and alpha-tocopherol. Ulcerogenic medications such as nonsteroidal anti-inflammatory drugs and steroids have been found not only to be ulcerogenic but also immunosuppressive to T cells. In addition, usage of steroids and nonsteroidal anti-inflammatory drugs may cause deficiencies of alpha-tocopherol, carotenes, cobalamin, iron, zinc and vitamin C. Vitamin C, carotenes and alpha-tocopherol are anti-inflammatory and the major oxidant scavengers in the aqua phase and biomembranes. Deficiencies of these nutrients may induce dysregulated inflammation and oxidative damage leading to neuropathic pain in patients with herpes zoster. Furthermore, nutrient deficiencies including zinc, iron, cobalamin and vitamin C are associated with dysregulation of Ca(v)3.2 T-channels and N-methyl-d-aspartate receptors, upregulation of nitric oxide synthase, the increase of nitric oxide formation and dysfunction of central norepinephrine inhibitory pain pathway. Prospective cohort studies are suggested to test the hypothesis. We further propose that a follow-up study that contains two groups of herpes zoster patients, i.e., with or without gastroendoscopy-proven PUD, be conducted to determine their incidence of postherpetic neuralgia. In addition, despite of the high proportion of zoster patients having been treated with antiviral therapies, prevention and treatment of postherpetic neuralgia remain challenging in clinical practice. The potential risk of postherpetic neuralgia in zoster patients with PUD could mean that physicians need to pay more attention to the comorbidity - PUD in patients with herpes zoster and treat PUD earlier in order to prevent the development of postherpetic neuralgia.