The efficacy and safety of bucillamine as a second-line DMARD in the treatment of rheumatoid arthritis: a retrospective cohort study

We investigated the efficacy and safety of bucillamine administered as a second-line DMARD compared to administration as a first-line DMARD in the treatment of rheumatoid arthritis (RA). We conducted a retrospective cohort study and reviewed medical records of 86 patients with active RA who began to receive bucillamine at Yokohama Minami Kyosai Hospital between January 1998 and July 2004. The efficacy of treatments was compared based on rates of achievement of 20, 50, and 70% improvement in ACR core set 6 months after initiation of the therapy. In the group administered bucillamine as a first-line DMARD (18 patients), 44.4, 22.2, and 11.1% of patients achieved ACR 20, 50, 70, respectively, while 56.5, 34.1, and 19.5% achieved ACR 20, 50, 70, respectively, in the group administered bucillamine following switching from MTX (46 patients), and 53.3, 33.3, and 13.3% achieved ACR 20, 50, and 70, respectively, in the group administered bucillamine following switching from Sulfasalazine (SSZ) (15 patients). The rates of achievements of ACR 20, 50, 70 did not differ statistically between the three groups and there was no increase in risk of serious adverse effects related to previous DMARDs. The usefulness of bucillamine as a second-line DMARD was demonstrated.     

Effects of gastric inhibitory polypeptide and glucagon on portal venous and hepatic arterial flow in conscious dogs

Gastric inhibitory polypeptide (GIP) has considerable structural homology with glucagon, which is known to increase liver blood flow. We compared the effects of GIP on portal venous and hepatic arterial flow with those of glucagon in conscious dogs. Injection of GIP significantly increased portal venous flow in a dose-related manner (by 7%, 15%, and 46% at doses of 1, 100, and 500 pmol/kg, respectively). The increase in portal venous flow induced by GIP and glucagon was comparable; however, the increase in portal venous flow after GIP injection reached its peak significantly earlier than that after glucagon injection. Hepatic arterial flow decreased after GIP injection (by 17%, 21%, and 35% at doses of 1, 100, and 500 pmol/kg, respectively), whereas it was not altered by glucagon. Thus, GIP causes significant changes in both portal venous and hepatic arterial flow in conscious dogs. Although structurally related, GIP and glucagon may influence liver blood flow through different mechanisms.Supported by a grant from the Ministry of Education, Japan (No. A-02404052)     

Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys

Contrast‐induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty‐six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m² (CKD and non‐CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = ?0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non‐CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non‐CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media.     

Relationships between the autonomic nervous system and the pancreas including regulation of regeneration and apoptosis: recent developments

Substantial new information has accumulated on the mechanisms of secretion, the development, and regulation of the gene expression, and the role of growth factors in the differentiation, growth, and regeneration of the pancreas. Many genes that are required for pancreas formation are active after birth and participate in endocrine and exocrine cell functions. Although the factors that normally regulate the proliferation of the pancreas largely remain elusive, several factors to influence the growth have been identified. It was also reported that the pancreas was sensitive to a number of apoptotic stimuli. The autonomic nervous system influences many of the functions of the body, including the pancreas. In fact, the parasympathetic nervous system and the sympathetic nervous system have opposing effects on insulin secretion from islet beta cells; feeding-induced parasympathetic neural activity to the pancreas stimulates insulin secretion, whereas stress-induced sympathetic neural activity to the pancreas inhibits insulin secretion. Moreover, it has been reported that the autonomic nervous system is one of the important factors that regulate pancreatic regeneration and stimulate the carcinogenesis. The present review focuses on the relationships between the autonomic nervous system and the pancreas, and furthermore, presents evidence of the autonomic nervous system-related pancreatic regeneration and carcinogenesis.     

Modulation of in vivo cardiac function by myocyte-specific nitric oxide synthase-3

Nitric oxide (NO) functions principally as a diffusible paracrine effector. The exception is in cardiomyocytes where both NO synthases (NOS) and target proteins coexist, allowing NO to work in an autocrine/intracrine fashion. However, the most abundant myocyte isoform (NOS3) is far more expressed in vascular endothelium; thus, the in vivo contribution of myocyte-NOS3 remains less clear. The present study tested this role by transfecting whole hearts of NOS3-null (NOS3(-/-)) mice with adenovirus-expressing NOS3 coupled to a alpha-MHC promoter (AdV(NOS3)), comparing results to hearts transfected with marker-gene beta-galactosidase (AdVbeta(gal)). Total myocardial NOS3 protein and activity were restored to near wild-type (WT) levels in NOS3(-/-)+AdV(NOS3) hearts, and NOS3 relocalized normally with caveolin-3. Ejection function by pressure-volume analysis was enhanced in NOS3(-/-)+AdVbeta(gal) over WT or NOS3(-/-)+AdV(NOS3). More prominently, isoproterenol (ISO)-stimulated systolic and diastolic function in WT was amplified in NOS3(-/-)+AdVbeta(gal), whereas NOS3(-/-)+AdV(NOS3) returned the response to control. ISO-activated systolic function was inhibited 85% by concomitant muscarinic stimulation (carbachol) in NOS3(-/-)+AdV(NOS3) but not NOS3(-/-)+AdVbeta(gal) hearts. Lastly, NOS3(-/-)+AdVbeta(gal) mice displayed enhanced inotropy and lusitropy over WT at slower heart rates but a blunted rate augmentation versus controls. A more positive rate response was restored in NOS3(-/-)+AdV(NOS3) (P<0.001). Thus, myocyte autocrine/intracrine NOS3 regulation in vivo can underlie key roles in beta-adrenergic, muscarinic, and frequency-dependent cardiac regulation.     

Detection of circulating tumor cells in patients with pancreatic cancer: a preliminary result

Background/Purpose

It has been reported that circulating tumor cells (CTCs) can be used to predict survival in metastatic breast cancer. In this preliminary study, we examined the level of CTCs in pancreatic cancer (PC) patients to elucidate whether we could predict survival in PC.

Methods

The eligible subjects, at Tokyo Medical University Hospital, were 26 patients with PC, 11 with chronic pancreatitis, and 10 healthy volunteers. Three PC patients underwent surgery, 18 patients (who were stage IV) were treated with gemcitabine (GEM), and 5 patients received best supportive care (BSC).

Results

The CTC count was 1/7.5 ml blood or higher (defined as positive) in 11 of the 26 patients (42%; mean, 16.9/7.5 ml blood; range, 1-105/7.5 ml blood). Gemcitabine was administered to 6 of the 11 CTC-positive patients (3.8 courses on average). The treatment was continued for more than three courses in 2 patients, in both of whom the CTC count was only 1/7.5 ml blood. Operation was performed in 1 of the 11 CTC-positive patients. The remaining 4 patients of the 11 CTC-positive patients received only BSC. CTC was negative in 15 patients with PC (stage II, 1; stage III, 1; stage IVa, 7; and stage IVb, 6) and in the subjects with benign conditions. The median survival times (MSTs) of the CTC-positive and-negative patients were 110.5 and 375.8 days (P < 0.001). When the analysis was limited to the 14 stage-IVb patients, the MSTs of the CTC-positive and-negative patients were 52.5 and 308.3 days (P < 0.01).

Conclusions

The present study demonstrated that the detection of CTCs in peripheral blood may be useful to predict prognosis in patients with PC.     

An application of a patient-specific cardiac simulator for the prediction of outcomes after mitral valve replacement: a pilot study

Journal of Artificial Organs - Despite advancements in preoperative prediction of patient outcomes, determination of the most appropriate surgical treatments for patients with severely impaired...     

External compression due to seroma of ventricular assist device outflow graft

Journal of Artificial Organs - A 45-year-old woman with repaired complex congenital heart disease, who underwent placement of Jarvik 2000, a ventricular assist device (VAD) for 4&nbsp;years,...