[A Case of Concomitant Administration of Anti-Cancer Drug and Anti-Tuberculosis Drug for Pulmonary Tuberculosis Developed during Postoperative Chemotherapy for Gastric Cancer].

An 86-year-old man was referred to our hospital with pulmonary tuberculosis developed during postoperative chemotherapy for gastric cancer. We initiated treatment with an anti-tuberculosis drug. Following confirmation of the effectiveness of this regimen, we combined the treatment with anti-cancer drugs. Tuberculosis treatment was completed without any drug interactions or serious side effects due to multidrug administration. For cancer patients who developed tuberculosis, combination treatment requires careful observation; however, it is a treatment option that can control both diseases.

The REICA method for quantification of cerebral blood flow is less affected by lung washout of [123I] IMP than the graph-plot method.

OBJECTIVE: The [Formula: see text]-Ray Evaluation with Iodoamphetamine for Cerebral blood flow Assessment (REICA) method is a new method for cerebral blood flow (CBF) quantification with SPECT and [123I] IMP, which does not require invasive arterial blood sampling, or the use of a regression formula. Moreover, it takes into consideration tracer retention, while the Graph-Plot (GP) method does not. This study aims to confirm the reliability of the REICA method in calculating CBF by accounting for pulmonary tracer retention artefact. METHODS: Data of 100 patients were retrospectively analyzed. Washout rate (WR) was defined as 1- (max count /min count) in the lungs. The bias due to WR was analyzed by dividing the data into high/low WR groups and a multiple regression analysis was also performed. RESULTS: The REICA method did not show significant bias according to the [Formula: see text] test ([Formula: see text]), while the GP method showed significant bias ([Formula: see text]). Both the REICA and GP methods showed significant correlation with autoradiography (ARG) method ([Formula: see text], [Formula: see text]) and WR ([Formula: see text], [Formula: see text]) when analyzed via multiple regression analysis with covariates of age and sex. CONCLUSIONS: The REICA method is a reliable method for CBF quantification, which is unaffected by tracer washout through the lungs unlike the GP method.

Phase II study of S-1-based sequential combination chemotherapy including oxaliplatin plus bevacizumab and irinotecan with or without cetuximab for metastatic colorectal cancer: the SOBIC trial.

BACKGROUND: Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. PATIENTS AND METHODS: From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. RESULTS: The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35-67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7-35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3-4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. CONCLUSION: Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.

Comparison of Long-Term Clinical Outcomes after Drug-Eluting Stent Implantation in Patients with Coronary Artery Disease with and without Prior Cerebral Infarction.

OBJECTIVE: To compare the clinical and angiographic outcomes after implantation of drug-eluting stents (DESs) in patients with coronary artery disease (CAD) with or without prior cerebral infarction. MATERIALS AND METHODS: Ninety-eight consecutive patients (130 lesions) who underwent successful coronary DES implantation were prospectively classified into two groups: those with a clinical history of symptomatic cerebral infarction (cerebral infarction group, 49 patients, 69 lesions) and those without a clinical history of symptomatic cerebral infarction (noncerebral infarction group, 49 patients, 61 lesions). The primary endpoint was defined as death, nonfatal myocardial infarction, and cerebrovascular events. RESULTS: The Kaplan-Meier method was used to create a primary endpoint curves to determine the time-dependent cumulative primary endpoint-free rate, which were compared using the log-rank test. The incidence of primary endpoints was higher in the cerebral infarction group than in the noncerebral infarction group (p = 0.0075). The Cox proportional hazards regression model for primary endpoint identified prior cerebral infarction (p = 0.0331, hazard ratio = 2.827) and patients with peripheral artery disease (p = 0.0271, hazard ratio = 2.757) as explanatory factors. CONCLUSION: The results showed that clinical outcomes were poorer in patients with CAD who had prior cerebral infarctions than in those who did not have infarction.

Nicotine facilitates reinnervation of phenol-injured perivascular adrenergic nerves in the rat mesenteric resistance artery.

Nicotine has been shown to have neuroprotective and neurotrophic actions in the central nervous system. To elucidate the peripheral neurotrophic effects of nicotine, we determined whether nicotine affected the reinnervation of mesenteric perivascular nerves following a topical phenol treatment. A topical phenol treatment was applied to the superior mesenteric artery proximal to the abdominal aorta in Wistar rats. We examined the immunohistochemistry of the distal small arteries 7 days after the treatment. The topical phenol treatment markedly reduced the density of tyrosine hydroxylase (TH)-LI and calcitonin gene-related peptide (CGRP)-LI fibers in these arteries. The administration of nicotine at a dose of 3 mg/kg/day (1.5 mg/kg/injection, twice a day), but not once a day or its continuous infusion using a mini-pump significantly increased the density of TH-LI nerves without affecting CGRP-LI nerves. A pretreatment with nicotinic acetylcholine receptor antagonists hexamethonium, mecamylamine, and methyllycaconitine, but not dextrometorphan, canceled the TH-LI nerve reinnervation induced by nicotine. Nicotine significantly increased NGF levels in the superior cervical ganglia (SCG) and mesenteric arteries, but not in the dorsal root ganglia, and also up-regulated the expression of NGF receptors (TrkA) in the SCG, which were canceled by hexamethonium. These results suggested that nicotine exhibited neurotrophic effects that facilitated the reinnervation of adrenergic TH-LI nerves by activating α7 nicotinic acetylcholine receptor and NGF in the SCG.

Low energy intake during the first week in an emergency intensive care unit is associated with reduced duration of mechanical ventilation in critically ill, underweight patients: a single-center retrospective chart review.

BACKGROUND: Although nutrition support is essential in intensive care units, optimal energy intake remains unclear. Here, we assessed the influence of energy intake on outcomes of critically ill, underweight patients. METHODS: A retrospective chart review was conducted in patients with body mass index (BMI) of <20.0 kg/m(2) in an emergency intensive care unit (EICU). Patients were categorized into 4 groups by initial Sequential Organ Failure Assessment score (I-SOFA) and average daily energy intake during the first week: group M-1, I-SOFA ≤8 and <16 kcal/kg/d; group M-2, I-SOFA ≤8 and ≥16 kcal/kg/d; group S-1, I-SOFA >8 and <16 kcal/kg/d; and group S-2, I-SOFA >8 and ≥16 kcal/kg/d. RESULTS: The study included 51 patients with a median age of 69 years. No significant differences were noted in all-cause mortality and length of stay in the EICU and hospital between groups M-1 and M-2 or groups S-1 and S-2. The mechanical ventilation duration (MVD) was significantly shorter in group M-1 than M-2 (2.7 [1.0-5.7] vs 9.2 [4.2-17.4] days; P = .040) and in group S-1 than S-2 (3.1 [0.7-6.0] vs 8.8 [6.1-23.1] days; P = .006). The number of patients who underwent tracheostomy in hospital was significantly lower in group S-1 than in S-2 (20% vs 32%; P = .002). Multivariable analyses to adjust for confounders revealed that average energy intake during the first week in EICU was a significant factor independently associated with MVD but not with the requirement of tracheostomy. CONCLUSION: Reduced energy intake during the first week in EICU was associated with a reduced MVD in clinically ill patients with BMI <20.0 kg/m(2).

Assessment of left ventricular systolic and diastolic function using ECG-gated technetium-99m tetrofosmin myocardial perfusion SPECT.

Because left ventricular (LV) diastolic dysfunction is frequently the earliest indicator of LV dysfunction in patients with heart failure, the estimation of LV diastolic function is very important. On the other hand, electrocardiography (ECG)-gated technetium (Tc) -99m tetrofosmin single-photon emission computed tomography (SPECT) has been reported to be a useful method for evaluation of LV function. The objective of this study was to examine the usefulness of ECG-gated Tc-99m tetrofosmin SPECT in terms of estimation of cardiac diastolic function. Consecutive 145 patients underwent an ECG-gated Tc-99m tetrofosmin SPECT to estimate systolic and diastolic LV function, and were compared with those evaluated by ultrasound echocardiography (UCG). LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction values obtained by quantitative gated SPECT (QGS) showed significant positive linear correlations with those obtained by UCG. All 145 patients were classified into 3 groups according to diastolic function estimated by UCG. The first-third mean filling rate (1/3 MFR) and peak filling rate (PFR) that revealed the LV diastolic function of the group B (normal systolic function and mild diastolic dysfunction) patients (1.01 ± 0.35, 1.85 ± 0.57) were both significantly lower than those of the group A (normal systolic and diastolic function) patients (1.43 ± 0.37, 2.43 ± 0.56). The 1/3 MFR and PFR of the group C (moderate ~ severe systolic and diastolic dysfunction) patients (0.47 ± 0.34, 0.92 ± 0.62) were also significantly lower than those of the group A and B patients. QGS may be a useful method for the evaluation of cardiac systolic and diastolic function, especially in patients with normal systolic function and diastolic dysfunction.

Does motor dysfunction after cerebral infarction impede the development of angina symptoms? A comparison of coronary angiographic findings in patients with and without prior cerebral infarction.

Previous studies based on coronary angiography or computed tomography coronary angiography have demonstrated a high prevalence of coronary stenosis in patients with cerebral infarction and no prior history of coronary artery disease (CAD). The purpose of the present study was to compare the coronary angiographic findings of patients with prior cerebral infarction with those of patients with no prior cerebral infarction. Consecutive patients (n = 126) who underwent a first coronary angiography for suspected CAD but had no prior history of CAD were classified into 2 groups, those with a clinical history of cerebral infarction (cerebral infarction group) and those without a clinical history of cerebral infarction (noncerebral infarction group). The incidences of diabetes mellitus, peripheral artery disease, coronary stenosis, and multivessel disease were significantly higher in the cerebral infarction group than in the noncerebral infarction group. Multiple logistic regression analysis relating to coronary stenosis identifi ed prior cerebral infarction (P = 0.0027, odds ratio = 4.414) and diabetes mellitus (P = 0.0446, odds ratio = 2.619) as explanatory factors. Thirty-four of 78 patients (44%) with coronary stenosis did not have angina symptoms. Multiple logistic regression analysis regarding the lack of angina symptoms identified motor dysfunction (modified Rankin scale ≥ 2) (P = 0.0028, odds ratio = 8.323) as an explanatory factor. The results of the present study suggest that compared with patients without cerebral infarction those with the disorder have a high prevalence of coronary stenosis, and indicate that the development of angina symptoms is influenced by the severity of motor dysfunction.

Altered function of nitrergic nerves inhibiting sympathetic neurotransmission in mesenteric vascular beds of renovascular hypertensive rats.

Neuronal nitric oxide (NO) has been shown to modulate perivascular adrenergic neurotransmission by inhibiting noradrenaline release from terminals in rat mesenteric arteries. This study was conducted to investigate changes in the inhibitory function of NO-containing nerves (nitrergic nerves) in mesenteric vascular beds of 2-kidney, 1-clip renovascular hypertensive rats (2K1C-RHR). Rat mesenteric vascular beds without endothelium were perfused with Krebs solution and the perfusion pressure was measured. In preparations from sham-operated rats (control) and 2K1C-RHRs, vasoconstriction induced by periarterial nerve stimulation (PNS; 2-8 Hz), but not vasoconstriction induced by exogenously injected noradrenaline (0.5, 1.0 nmol), was markedly facilitated in the presence of a nonselective NO synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME) (100 microM). The facilitatory effect of L-NAME in preparations from 2K1C-RHR was smaller than that in control preparations. L-NAME augmented PNS-evoked noradrenaline release, which was smaller in 2K1C-RHRs than in controls. The expression of neuronal NO synthase (nNOS) measured by western blotting in mesenteric arteries from 2K1C-RHRs was significantly decreased compared with control arteries. Immunohistochemical staining of mesenteric arteries showed dense innervation of nNOS-immunopositive nerves that was significantly smaller in arteries from 2K1C-RHR than that in control arteries. Mesenteric arteries were densely innervated by tyrosine hydroxylase-immunopositive nerves, which coalesced with nNOS-immunopositive nerves. These results suggest that the inhibitory function of nitrergic nerves in adrenergic neurotransmission is significantly decreased in 2K1C-RHRs. This functional alteration based on the decrease in nNOS expression and nitrergic innervation leads to enhanced adrenergic neurotransmission and contributes to the initiation and development of renovascular hypertension.

Proton acts as a neurotransmitter for nicotine-induced adrenergic and calcitonin gene-related peptide-containing nerve-mediated vasodilation in the rat mesenteric artery.

Nicotine stimulates presynaptic nicotinic acetylcholine receptors in perivascular adrenergic nerves and releases unknown transmitter(s) that activate transient receptor potential vanilloid-1 (TRPV1) located on calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerves, resulting in vasodilation. The present study investigated a potential transmitter transmitting between perivascular adrenergic nerves and CGRPergic nerves. Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs' solution containing methoxamine, and the perfusion pressure and pH levels of the perfusate were measured. Nicotine perfusion for 1 min induced concentration-dependent vasodilation and lowered pH levels, which were abolished by cold-storage denervation of preparations, guanethidine (adrenergic neuron blocker), and mecamylamine (nicotinic alpha(3)beta(4)-acetylcholine receptor antagonist). Capsazepine (TRPV1 antagonist) blunted nicotine-induced vasodilation, but had no effect on the reduction of pH. Injection of hydrochloric acid (HCl) and perfusion of Krebs' solution at low pH (6.0-7.2) induced vasodilation. HCl-induced vasodilation was inhibited by cold-storage denervation, capsazepine, capsaicin (CGRP depletor), and CGRP(8-37) (CGRP receptor antagonist). Perfusion of adrenergic transmitter metabolites (normetanephrine and 3-methoxydopamine), but not of other metabolites, induced vasodilation, which was not inhibited by capsaicin treatment. Immunohistochemical staining of mesenteric arteries showed dense innervation of CGRP- and TRPV1-immunopositive nerves, with both immunostainings appearing in the same neuron. Mesenteric arteries were densely innervated by neuropeptide Y-immunopositive nerves, which coalesced with CGRP-immunopositive nerves. Scanning and immunoscanning electron microscopic images showed coalescence sites of different perivascular fibers before they intruded into smooth muscles. These results indicate that nicotine initially stimulates adrenergic nerves via nicotinic alpha(3)beta(4)-receptors to release protons and thereby induces CGRPergic nerve-mediated vasodilation via TRPV1.