Analgesic effects of ketamine ointment in patients with complex regional pain syndrome type 1

OBJECTIVE: Ketamine hydrochloride (KET), an agent used for general anesthesia, has local anesthetic effects and N-methyl-D-aspartate (NMDA) receptor antagonist action. Because recent studies emphasized the role of peripherally distributed NMDA receptors in processing the nociceptive information, we investigated whether peripheral application of the ointment containing KET is able to attenuate the symptoms of local neuropathic pain. CASE REPORTS: We applied ointment containing KET (0.25%-1.5%) to the affected area on limbs in 5 patients with complex regional pain syndrome type I (CRPS I) and in 2 patients with type II (CRPS II). One to 2 weeks later, we observed improvement of the report of pain intensity, measured by the visual analog scale, in 4 patients with acute early dystrophic stage of CRPS I. Swelling of the affected limbs subsided as well. No apparent changes were noticed in 1 patient with chronic atrophic stage of CRPS I and in both patients with CRPS II. CONCLUSION: Topical application of KET appears to be beneficial for the patients with acute early dystrophic stage of CRPS I because of either its local anesthetic effect or NMDA receptor antagonist action. Patients with chronic atrophic stage of CRPS I and CRPS II patients do not appear to respond to this treatment.     

Impact of pneumonia on hyperactive delirium in end-stage lung cancer patients

Purpose

Patients with incurable lung cancer often receive palliative care. Hyperactive delirium is a burden not only for the patient??s family but also for caregivers. There are no reports describing the risk factors for delirium among lung cancer patients. The present study investigated the frequency of incidence and risk factors for hyperactive delirium among end-stage lung cancer patients.

Methods

Patients who died of lung cancer in our institute from January 2010 to December 2010 were retrospectively investigated. Information was obtained from medical records, and patients who developed hyperactive delirium (delirium group, group D) were compared with patients who did not (control group, group C) based on clinical and laboratory data.

Results

A total of 146 patients (median age, 70?years; 80?% male) died of lung cancer. Thirty-one (21.2?%) patients developed hyperactive delirium. Sex (P?=?0.0093) and pneumonia (P?=?0.023) were statistically significant variables in univariate analysis. Pneumonia occurred in 27.4?% of all patients. The incidence of pneumonia was 45.2?% in group D and 22?% in group C. Only pneumonia (odds ratio, 2.89; 95?% confidence interval, 1.22?C6.85; P?=?0.016) was identified as a significant factor for predicting hyperactive delirium in multivariate analysis.

Conclusions

Pneumonia was identified as a significant risk factor for the development of hyperactive delirium among end-stage lung cancer patients.     

Adenosine A1 and benzodiazepine receptors and glucose metabolism in the visual structures of rats monocularly deprived by enucleation or eyelid suture at a sensitive period

PURPOSE: To determine the changes in the adenosine A(1) and benzodiazepine receptor density and in glucose metabolism in the visual centers of the rat brain following monocular enucleation or eyelid suture on postnatal day 10 (PN10). METHODS: Following monocular enucleation or eyelid suture on PN10 rats, the alterations in adenosine A(1) and benzodiazepine receptor density, and in glucose metabolism were evaluated in the superior colliculus (SC), the dorsal lateral geniculate body (DLG), and the visual cortex (VC) by ex vivo autoradiography with [11C]MPDX, [11C]flumazenil and [14C]2-deoxyglucose, respectively. RESULTS: Enucleation reduced the [11C]MPDX binding in the SC and DLG, and enhanced the [11C]flumazenil binding in the SC. Eyelid suture reduced the [11C]flumazenil binding in the VC at day 20. [14C]2-deoxyglucose uptake was not decreased by enucleation in any region except in the SC and DLG at day 1, but was decreased by eyelid suture in the SC at days 20 and 55 and in the VC at day 55. CONCLUSIONS: The decrease in the presynaptic adenosine A(1) receptors in the SC following enucleation is coupled with an upregulation of postsynaptic benzodiazepine receptors. These neural reactions are completely different from those following eyelid suture. The development of neural architecture for visual functions is not completed at PN10 in rats.     

Evaluation of methods for predicting drug-drug interactions by Monte Carlo simulation

The ratio of the inhibitor concentration to the inhibition constant (K(i)) is used as the index for predicting drug-drug interactions involving metabolic inhibition. The maximum unbound concentration in the circulation (I(p, max, u)) and the maximum unbound concentration at the inlet to the liver (I(u, max)) have been used for the inhibitor concentration. In the present study, the methods for predicting drug-drug interactions using these concentrations were evaluated by Monte Carlo simulation. Information on the pharmacokinetic parameters of drugs and the K(i) values for cytochrome P450(CYP) were obtained from the literature. It was assumed that the pharmacokinetic parameters (intrinsic metabolic clearance, renal clearance and distribution volume for unbound fraction), serum protein binding and K(i) value for substrate and inhibitor are all log-normally distributed. Correlations among the parameters were assessed and were used for further simulations. A change in AUC of the substrate following co-administration of the inhibitor was simulated 1000 times using the physiologically based pharmacokinetic (PBPK) model. The percent of the drug combinations which exhibited a significant increase in the AUC (>125%) was 16.2% of the total combinations. The cases where the I/K(i) using I(u, max) and I(p, max, u) overestimated compared with the actual increased ratio of AUC (false positive prediction) were 41.2% and 16.7%, respectively. The cases where the predicted ratios of AUC from I/K(i) using I(u, max) and I(p, max, u) were comparable with the actual ratio were 3.2% and 8.7%, respectively. The prediction using I(p, max, u) was, thus, more reliable than that using I(u, max). However, in the case of I(u, max), there was no case where the actual increased ratio of AUC was greater than that predicted from I/K(i) (false negative prediction). On the other hand, for I(p, max, u), the rate of false negative prediction was 1.4%. The present study indicates that I(u, max) is better than I(p, max, u) for avoiding false negative predictions and I(p, max, u) is better than I(u, max) for increasing the probability of true positive and true negative predictions and avoiding false positive predictions.In conclusion, it is necessary to use both predictions involving I(u, max) and I(p, max, u) and to use them early on during the development stage of drug candidates. In order to finally choose which compound(s) to take forward to clinical trials, when predicting an interaction, the more quantitative and reliable method based on the PBPK model needs to be used.     

Nationwide registry for patients with neuroendocrine neoplasm of pancreas,gastrointestinal tract,lungs, bronchi,or thymus in Japan

International Journal of Clinical Oncology - Neuroendocrine neoplasm (NEN) is a comparatively rare tumor that has been considered indolent. Due to these characteristics, detailed epidemiological...     

Lower Body Mass Index is a Risk Factor for In-Hospital Mortality of Elderly Japanese Patients Treated with Ampicillin/sulbactam

Objectives: A retrospective examination was conducted to identify risk factors for in-hospital mortality of elderly patients (65 years or older) treated with the beta-lactam/beta-lactamase inhibitor combination antibiotic, ampicillin/sulbactam (ABPC/SBT).Methods: Clinical data from 96 patients who were hospitalized with infectious diseases and treated with ABPC/SBT (9 g/day or 12 g/day) were analyzed. Risk factors examined included demographic and clinical laboratory parameters. Parameter values prior to treatment and changes after treatment were compared between survivors and non-survivors.Results: The study patients had an average age of 81.9±8.4 years (±SD) and body mass index (BMI) of 19.9±4.2 kg/m². They were characterized by anemia (low hemoglobin and hematocrit levels), inflammation (high leukocyte count, neutrophil count, C-reactive protein level, and body temperature), and hepatic and renal dysfunction (high aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen levels). The BMI of non-survivors, 16.2±2.9 kg/m², was lower than that of survivors, 20.4±4.1 kg/m². In addition, the hematological parameters deteriorated more remarkably, inflammation markers were not altered (or the decrease was marginal), and hepatic function was not improved, in non-survivors.Conclusions: A lower BMI value is a risk factor for in-hospital mortality of elderly patients treated with ABPC/SBT.     

Development of POEMS syndrome after an initial manifestation of solitary plasmacytoma

A 44-year-old male was admitted for numbness in the left arm. CT showed a tumor impacting on the spinal cord with an adjacent thoracic vertebral osteosclerotic lesion. The histopathology of the tumor showed diffuse proliferation of atypical plasma cells with expressed vascular endothelial growth factor (VEGF), which is a known etiological factor in POEMS syndrome. Though serum VEGF (sVEGF) level was elevated, a diagnosis of solitary plasmacytoma with an osteosclerotic lesion was made as the patient presented no polyneuropathy, organomegaly, endocrinopathy, or skin changes. The patient experienced muscle weakness of the lower limbs and skin pigmentation/hemangioma one year after irradiation of the osteosclerotic lesion. Laboratory tests revealed hypothyroidism, hyperglycemia, serum monoclonal gammopathy, further elevation of sVEGF, and increased atypical bone marrow plasma cells. CT imaging showed splenomegaly, and a nerve conduction test revealed demyelinating motor peripheral neuropathy. The patient was therefore diagnosed with POEMS syndrome. Plasmacytoma is very rare as an initial manifestation of POEMS syndrome. Patients presenting with plasmacytoma with an osteosclerotic lesion should be carefully observed and evaluated for the expression of sVEGF and development of POEMS syndrome, as most bone plasmacytomas in POEMS syndrome patients are reported to be osteosclerotic. This is to our knowledge the first case of osteosclerotic plasmacytoma that progressed to POEMS syndrome, with an increase of sVEGF.