Endogenous endophthalmitis and disseminated intravascular coagulation complicating a Klebsiella pneumoniae perirenal abscess in a patient with type 2 diabetes

We describe a 56-year-old woman with type 2 diabetes complicated by a Klebsiella pneumoniae perirenal abscess. The patient further developed incipient diabetic ketoacidosis, disseminated intravascular coagulation, and endogenous endophthalmitis. Occurrence of the latter as a metastatic infection from perirenal abscess caused by this organism is very rare, and we know of no previously reported patient with the additional occurrence of disseminated intravascular coagulation. Since prompt intravitreal antibiotic administration is needed, physicians should be aware of these rare but severe complications of K pneumoniae infection, especially in patients with poorly controlled diabetes.     

Relation between serum high molecular weight adiponectin and serum ferritin or prohepcidin in patients with type 2 diabetes

An increase of serum ferritin, an indicator of body iron store, is associated with insulin resistance and with an increased risk of type 2 diabetes in the general population. A low serum adiponectin is also associated with insulin resistance. Recently, hepcidin was identified as a regulator of iron metabolism. We investigated whether serum adiponectin was associated with serum ferritin or prohepcidin, a precursor of hepcidin, in healthy subjects and patients with type 2 diabetes. We studied 65 healthy subjects and 104 patients with type 2 diabetes. A serum ferritin concentration ≥ 300 ng/ml for men or ≥ 150 ng/ml for women was defined as hyperferritinemia. Serum ferritin was significantly higher and serum prohepcidin was significantly lower in diabetic patients than in control subjects. Serum total and high molecular weight (HMW) adiponectin correlated negatively with serum ferritin in control subjects or diabetic patients, while serum total and HMW adiponectin correlated positively with serum prohepcidin in diabetic patients, but not in control subjects. Serum total and HMW adiponectin were lower in patients with hyperferritinemia than in those without it. In conclusion, serum ferritin was increased in type 2 diabetic patients, while serum prohepcidin was decreased. A high serum ferritin was associated with insulin resistance, and with low serum total and HMW adiponectin in patients with type 2 diabetes.     

Hydration of surfactant-modified and PEGylated cationic cholesterol-based liposomes and corresponding lipoplexes by monitoring a fluorescent probe and the dielectric relaxation time

For the optimization of plasmid DNA (pDNA)-cationic lipid complexes and lipoplex delivery, proper indexes of the physicochemical properties of lipoplexes are required. In general, the characteristics of lipoplexes are defined by particle size and zeta-potential at various mixing ratios of cationic liposomes and pDNA. In this study, we characterized the hydration level of surfactant-modified and PEGylated cationic cholesterol-based (OH-Chol) liposomes and their lipoplexes by monitoring both the fluorescent probe laurdan and the dielectric relaxation time. Fluorescence measurement using laurdan detected hydration of the headgroup of lipids in surfactant-modified liposomes and PEGylated DOTAP-liposomes, but hardly any fluorescence was detected in PEGylated OH-Chol-liposomes because the PEG layers may extend and cover the fluorescent maker. On the other hand, the measurement of dielectric relaxation time of water molecules revealed total hydration, including hydration of the PEG layer and the headgroup of cationic lipids. Furthermore, we found an inverse correlation between hydration level and cellular uptake of PEGylated lipoplexes (R=0.946). This finding indicated that the dielectric relaxation time of water molecules provides an important indicator of hydration of liposome and lipoplexes along with the fluorescence intensity of laurdan.     

Orally Administered Prion Protein Is Incorporated by M Cells and Spreads into Lymphoid Tissues with Macrophages in Prion Protein Knockout Mice

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases. Infection by the oral route is assumed to be important, although its pathogenesis is not understood. Using prion protein (PrP) knockout mice, we investigated the sequence of events during the invasion of orally administered PrPs through the intestinal mucosa and the spread into lymphoid tissues and the peripheral nervous system. Orally administered PrPs were incorporated by intestinal epitheliocytes in the follicle-associated epithelium and villi within 1 hour. PrP-positive cells accumulated in the subfollicle region of Peyer''s patches a few hours thereafter. PrP-positive cells spread toward the mesenteric lymph nodes and spleen after the accumulation of PrPs in the Peyer''s patches. The number of PrP molecules in the mesenteric lymph nodes and spleen peaked at 2 days and 6 days after inoculation, respectively. The epitheliocytes in the follicle-associated epithelium incorporating PrPs were annexin V-positive microfold cells and PrP-positive cells in Peyer''s patches and spleen were CD11b-positive and CD14-positive macrophages. Additionally, PrP-positive cells in Peyer''s patches and spleen were detected in the vicinity of peripheral nerve fibers in the early stages of infection. These results indicate that orally delivered PrPs were incorporated by microfold cells promptly after challenge and that macrophages might act as a transporter of incorporated PrPs from the Peyer''s patches to other lymphoid tissues and the peripheral nervous system.Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative diseases that infect humans and both wild and domestic animals. They include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, and bovine spongiform encephalopathy (BSE) in cattle.¹ The common neuropathological features within the central nervous system (CNS) of TSEs are seen as a spongiform pathology, neuronal loss,² glial activation,³ and the accumulation of an abnormal and protease-resistant conformer of the scrapie-associated prion proteins (PrP-res or PrP^Sc),⁴ which are closely associated with the infection.⁵It has been reported that variant CJD in humans is most likely to have occurred because of the transmission of BSE after the consumption of beef contaminated with the BSE agent.⁶ Therefore, the oral route of TSE infection is widely assumed to be important under natural conditions. Many of the infectious agents accumulate in the gut-associated lymphoid tissues (GALT) after oral infection, such as the Peyer''s patches and mesenteric lymph nodes (MLN) before spreading to the CNS.⁷ It is necessary for the infectious agents to cross the intestinal epithelium before they can accumulate in the GALT. In addition, there are microfold cells (M cells) within the follicle-associated epithelium (FAE) that are specialized for the transepithelial transport of macromolecules and particles.⁸ One in vitro study has demonstrated that M cells actively transcytose the scrapie agents into the basolateral side of the epithelium.⁹ However, it is still a matter of controversy as to whether M cells may be involved in the in vivo transport of the infectious agents across the intestinal epithelium. After alimentary uptake of the infectious agents, they accumulate in the GALT and the lymphoreticular systems (eg, the spleen and other peripheral lymph nodes) long before they are detected in the CNS.¹⁰ As the GALT and the lymphoreticular systems are highly innervated, they are believed to be important sites for the infectious agents to gain contact with the nervous system (ie, neuroinvasion).¹¹ Once neuroinvasion occurs, the infectious agents reach their initial CNS target sites by spreading in a retrograde direction along efferent nerve fibers.¹²In the lymphoid tissues, it is believed that the macrophages, dendritic cells (DCs), and follicular dendritic cells (FDCs) are involved in the transportation and replication of the infectious agents. Macrophages are prevalent candidates for both spread¹³ and clearance¹⁴ of the infectious agents. DCs can capture and retain protein antigens in a nondegraded state.^15,16 These characteristics suggest that the macrophages and DCs may act as a transporter of the infectious agents from the gut to lymphoid tissues. FDCs express high levels of cellular PrPs (PrP^c), and therefore an early accumulation of PrP^Sc is seen in them.^17,18 Many studies of the alimentary pathogenesis of TSEs have been conducted to elucidate how infectious agents spread from the GALT to the CNS, although this has not been clearly determined yet. Therefore, the aim of the present study was to reveal the cells involved in the early stages of the pathogenesis of oral TSE infection, such as the sites of entry, spread, and neuroinvasion.     

Primary pulmonary cryptococcosis: a case series of 9 patients

We retrospectively reviewed 9 consecutive cases of primary pulmonary cryptococcosis having no comorbidity. At diagnosis, seven had no subjective symptoms and two had subtle symptom. Chest CT scan showed nodular shadows in 8, while 3 cases had infiltrative shadows. Eight of the nine were diagnosed with histopathology obtained by transbronchial lung biopsy or CT-guided needle aspiration biopsy. We also assessed PHA and Con A lymphocyte stimulation tests to measure cellular immune function in 6, four of whom showed decreased reaction of lymphocytes. We successfully treated seven of the nine with fluconazole alone and used fluconazole as a maintenance regimen in two. No relapse or treatment failure was seen after completion of antifungal treatment. Six cases were seropositive for serum cryptococcus antigen titer at diagnosis and only one showed seroconversion. We concluded that the duration of therapy for primary pulmonary cryptococcosis should not be necessarily determined by serum cryptococcus antigen seroconversion.     

Retinol binding protein-4 levels and clinical features of type 2 diabetes patients

CONTEXT: Retinol binding protein (RBP)-4 is a recently identified adipocytokine that is associated with insulin resistance. OBJECTIVES: The aim was to investigate the association between RBP4 and various markers related to insulin resistance and diabetic complications in type 2 diabetic patients. The effect on RBP4 of the addition of pioglitazone to other diabetic medications was also examined. DESIGN, SETTING, PATIENTS, INTERVENTION, AND MAIN OUTCOME MEASURES: RBP4 levels were measured in 101 hospitalized patients with type 2 diabetes and in 22 nonhospitalized control subjects. Endothelial function was evaluated using flow-mediated vasodilatation. In a further 22 nonhospitalized type 2 diabetic patients, pioglitazone (30 mg/d) was administered for 12 wk while other medications for diabetes were continued. RESULTS: There was a significant elevation of RBP4 levels in diabetic patients compared with healthy subjects. RBP4 showed significant positive correlations with triglyceride, systolic blood pressure, and log urinary albumin excretion, and significant negative correlations with high-density lipoprotein cholesterol and flow-mediated vasodilatation. In stepwise regression analysis, log urinary albumin excretion, triglyceride, and gender showed a significant association with RBP4. RBP4 was significantly elevated in patients with proliferative-diabetic retinopathy compared with nondiabetic retinopathy and simple-diabetic retinopathy patients. The addition of pioglitazone for 12 wk to other diabetic medications the patients were already taking did not affect the serum RBP4 concentration. CONCLUSIONS: The current study shows that RBP4 is associated with variables related to insulin resistance and diabetic complications. The addition of pioglitazone for 12 wk to other diabetic medications the patients were already taking did not affect serum RBP4 levels.     

Emotional state and coping style among gynecologic patients undergoing surgery

The aim of the present study was to investigate changes in emotional state and the relationship between emotional state and demographic/clinical factors and coping style among gynecologic patients undergoing surgery. Using the Japanese version of the Profile of Mood States (POMS), 90 patients (benign disease: 32, malignancy: 58) were examined on three occasions: before surgery, before discharge, and 3 months after discharge. They were also examined using the Coping Inventory for Stressful Situations (CISS) on one occasion before discharge. The scores for the subscales depression, anger, and confusion were the highest after discharge while those for anxiety were the highest before surgery. The average scores of the POMS subscales for all subjects were within the normal range. With regard to the relationship between these emotional states and other factors, multiple regressions showed that the principal determinants of anxiety before surgery were religious belief, psychological symptoms during hospitalization and emotion-oriented (E) coping style; further, it was found that depression after discharge could be explained by chemotherapy, duration of hospitalization, and E coping style. The principal determinants of anger after discharge and vigor before surgery were length of education and E coping style, and severity of disease, chemotherapy, E coping style and task-oriented coping style, respectively. Those of post-discharge fatigue and confusion were length of education, psychological symptoms, and E coping style. In summary it is suggested that the following should be taken into account in patients undergoing gynecologic surgery: anxiety before surgery, depression, anger, and confusion after surgery, including coping styles.     

Diagnosis of incomplete Kawasaki disease

We defined incomplete Kawasaki disease (KD) as those having less than 5 principal symptoms of KD in this article. Japanese Nationwide KD surveys revealed that the prevalence of coronary artery lesion in incomplete KD is almost the same as that of complete KD. Thus, incomplete KD should not be equated with mild KD. However, there is no royal way to make the correct diagnosis of incomplete KD. We have to remind that incomplete KD is not uncommon (around 15%) and is not mild KD when we work-up patients with few principal symptoms of KD. We have to pay attention also to other significant symptoms or findings of the guideline, especially to the skin changes at the site of BCG inoculation.     

The role of prostaglandin E, cyclic AMP, and cyclic GMP in the proliferation of guinea-pig ear skin stimulated by topical application of vitamin A acid.

Daily treatment of guinea-pig ear skin with topical 0.5% retinoic acid in acetone produced erythematous scaly dermatitis. Histologic sections revealed bandlike thickening of the epidermis on days 2 to 4, psoriasiform acanthosis, papillomatosis and increased mitotic activity on days 5 to 6. Also seen were dilatation of the upper dermal blood vessels and a fibroblastic, histiocytic reaction in the dermis. Prostaglandin E, cyclic AMP, and cyclic GMP levels were increased in the treated skin and thymidine incorporation was enhanced. Cyclic AMP and GMP levels peaked on day 5 simultaneous with maximal epidermal hyperplasia, increased mitotic activity and dermal reaction. Tritiated thymidine uptake peaked on days 4 and 5, and prostaglandin E levels continued to increase up to day 6. Cyclic AMP phosphodiesterase activity of treated skin on day 5 did not appear to be significantly different from control.