Comparing patient dissatisfaction and rational judgment in intentional medication non-adherence versus unintentional non-adherence.

WHAT IS KNOWN AND OBJECTIVE: Patients' poor adherence to medications is reported to be related to the individual patients' beliefs and cognitions and their trust of the medical staff. However, the causes of the two forms of non-adherence, intentional and unintentional behaviours, have yet to be clarified. This study compared psychological latent factors associated with intentional and unintentional non-adherence to chronic medication regimens, focusing on the potential effects of (i) patients' dissatisfaction with treatment and their relationships with the medical staff and (ii) patients' subliminal rational thinking processes, which weighed the positive values such as their expectations of benefits from treatment against negative values such as their dissatisfaction. METHODS: Two cross-sectional surveys were undertaken of patients given medications for chronic diseases, using a questionnaire developed and validated in this study. One survey was undertaken in three hospitals and the other survey, online throughout Japan. We scored the individual latent factors using the questionnaire and calculated the differential score between two negatively correlated latent factors to quantify patients' subliminal rational thinking process. We compared the adjusted odds ratio (OR) of latent factors between intentional and unintentional non-adherence to medication in both surveys. RESULTS AND DISCUSSION: Of the eligible subjects, 149 hospitalized patients and 524 survey participants completed the questionnaire. Intentional non-adherence was associated with patient dissatisfaction with treatment including interpersonal relationships with medical staff in both hospitalized patients and online survey participants (95% confidence interval of adjusted OR for Dissatisfaction, 1·20-16·26 in the hospital-based survey and 1·33-3·45 in the online survey). In both surveys, intentional non-adherence was significantly associated with the differential score between two negatively correlated latent factors, Willingness and Dissatisfaction (P = 0·02 in the hospital-based survey and P < 0·001 in the online survey). However, these associations were not evident in unintentionally non-adherent patients. WHAT IS NEW AND CONCLUSIONS: Patients' dissatisfaction and their resulting rational judgments are unique, consistent determinants of intentional non-adherence to medications, but not of unintentional non-adherence.

Are Self-Reported Masticatory Ability and Regular Dental Care Related to Mortality?

AIM: The aim of the study was to examine whether a combination of self-reported masticatory ability and regular dental care is linked to mortality and issuance of new long-term care insurance (LTCI) service certifications. METHODS: Older residents in institutions or in need of LTCI certification requirements were excluded, and self-administered questionnaires were sent to 5,400 older adults in 2013; these participants were followed for 5 years. The total response rate was 94.3%, and our final sample comprised 4,824 older adults (89.3%). We used 3 items to assess self-reported masticatory ability and regular dental care. These included (1) decline in chewing abilities of the posterior teeth on either side, (2) not brushing one's own teeth or dentures at least once a day, and (3) not visiting the dentist at least once a year. RESULTS: The mean age of the participants at baseline was 75.9 years, and 58.4% of them were women. Main outcomes included mortality (n = 562) or new LTCI certification requirements (n = 1187) during the 5-year period. Multivariate analyses revealed that a poor score on masticatory ability and on regular dental care produced significant adverse health outcomes leading to earlier negative outcomes. The score is considered poor as it increases relative to the 0-point reference. DISCUSSION: Regular dental care (both self-and professional care) and maintaining masticatory ability are both important. Hence, public activities focusing on preventive oral health from middle age onward is important.

Postoperative adjuvant therapy for patients with loco-regionally advanced oral squamous cell carcinoma who are at high risk of recurrence.

Extranodal extension (ENE) of lymph node metastasis and the presence of a positive or close margin (PCM) are major risk factors for head and neck squamous cell carcinoma recurrence. This retrospective multicentre cohort study compared the prognostic impact of postoperative radiotherapy (RT) and concurrent chemoradiotherapy (CCRT) in oral squamous cell carcinoma (OSCC) patients at high risk of recurrence. One hundred and eighteen patients with PCM and/or ENE who underwent definitive surgery plus either adjuvant RT or CCRT using cisplatin for OSCC were investigated. The cohort-wide 5-year loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates (the main outcome measures) were 54.3%, 35.8%, and 43.2%, respectively. Multivariate analysis showed that age ≥64 years (hazard ratio (HR) 0.584), cT3-4 stage (HR 1.927), ≥4 metastatic lymph nodes (HR 1.912), and PCM (HR 2.014) were significant independent predictors of OS. Moreover, postoperative CCRT with cisplatin was associated with a significantly improved LRC rate, but not with improved DFS or OS rates, compared to postoperative RT (HR 0.360). Given that CCRT with cisplatin does not significantly improve survival, additional clinical trials will be required to validate new regimens that further improve the outcomes of patients with loco-regionally advanced OSCC going forward.

Self-Reported Cognitive Frailty Predicts Adverse Health Outcomes for Community-Dwelling Older Adults Based on an Analysis of Sex and Age.

OBJECTIVES: The present study examined whether the combination of self-reported mobility decline (SR-MD) and cognitive decline (SR-CD) was associated with mortality and new long-term care insurance (LTCI) service certifications based on sex and age. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: We analyzed cohort data from a sample of older adult residents in Kami Town, Japan. The response rate was 94.3%, and we followed 5,094 older adults for 3 years. Full analyses were conducted on 5,076 participants. MEASURES: A total of four groups were determined through self-reported responses on the Kihon Checklist for SR-MD (a score of 3 or more on 5 items) and SR-CD (a score of 1 or more on 3 items): non-SR-cognitive frailty, non-SR-MD and SR-CD, SR-MD and non-SR-CD, and SR-cognitive frailty. RESULTS: Main outcomes included mortality (n = 262) or new certifications for LTCI services (n = 708) during the 3-year period. Excluding overlapping, this included 845 older adults (16.6%). Among men, prevalence of non-SR-cognitive frailty, non-SR-MD and SR-CD, SR-MD and non-SR-CD, and SR-cognitive frailty (SR-MD and SR-CD) was 48.2%, 26.4%, 11.5%, and 13.8%, respectively. Respective rates for women were 45.7%, 15.5%, 23.1%, and 15.7%. Multivariate analyses revealed that for men, SR-MD and non-SR-CD significantly affected adverse health outcomes, leading to earlier negative outcomes relative to the non-SR-MD and SR-CD group. For women, non-SR-MD and SR-CD and SR-MD and non-SR-CD had similar slopes. CONCLUSIONS: The impact of SR-MD or SR-CD on adverse health outcomes differed as a function of age and sex. Thus, we need to consider preventive approaches according to these specific target group features.

Effectiveness of a comprehensive oral management protocol for the prevention of severe oral mucositis in patients receiving radiotherapy with or without chemotherapy for oral cancer: a multicentre, phase II, randomized controlled trial.

The aim of this phase II, multicentre, randomized controlled trial was to evaluate the effectiveness of a comprehensive oral management protocol for the prevention of severe oral mucositis in patients with oral cancer receiving radiotherapy alone or chemoradiotherapy. In total, 124 patients with oral cancer were enrolled from five institutions. Of these, 37 patients undergoing radiotherapy were randomly divided into an intervention group (n=18) and a control group (n=19). The remaining 87 patients, who were undergoing chemoradiotherapy, were also randomized into an intervention group (n=42) and a control group (n=45). During radiotherapy, patients in the control group received only oral care, while those in the intervention group additionally received spacers to cover the entire dentition, pilocarpine hydrochloride, and topical dexamethasone ointment for oral mucositis. The primary endpoint was the incidence of severe oral mucositis. The intervention was significantly associated with a decreased incidence of severe oral mucositis in patients receiving radiotherapy alone (P=0.046), but not in those receiving chemoradiotherapy (P=0.815). These findings suggest that an oral management protocol can prevent severe oral mucositis in patients with oral cancer undergoing radiotherapy without concurrent chemotherapy.

[Dissection of descending aorta with spinal paralysis].

A 56-year-old man had undergone ascending aorta and total arch replacement because of aortic dissection (Stanford type A) in 1997. He had onset of diplegia of the lower limb and vesicorectal disability. Computed tomography (CT) showed serpentine aneurysm in the descending aorta, it was seen between the left subclavian artery and diaphragm level. It was 80 mm of maximum diameter. Magnetic resonance imaging (MRI) was performed for identified Adamkiewicz artery, but we could not identify it. We performed a graft replacement. The 8th intercostal artery was reconstructed with a branch graft. The postoperative course was uneventful. We conclude that graft replacement for spinal ischemia can be effective.

Spheric mass beneath the alar base: MR images of nasolabial cyst and schwannoma.

We report 2 cases of nasolabial cyst and a case of schwannoma beneath the alar base that required a differential diagnosis because of clinical features and MR images that resembled the nasolabial cyst. The morphologic analysis on MR images revealed the characteristic appearance of the nasolabial cyst, and the sagittal MR image may be most helpful for diagnosing this rare disease.

Growth inhibition and differentiation of human salivary adenocarcinoma cells by medium conditioned with normal human fibroblasts.

The present study demonstrates that normal human fibroblasts (WI-38) exert a profound influence on the growth and differentiation of HSGc-C5, a clonal neoplastic epithelial cell line of human salivary gland origin. Coculture of HSGc-C5 with WI-38 resulted in a slowing of growth and an increase in glycosaminoglycan synthesis by an indirect effect involving a diffusible factor(s). Conditioned medium (CM) from WI-38 grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum affected HSGc-C5 as follows. The CM suppressed growth of monolayer cells; inhibited DNA synthesis; suppressed growth (decrease in size of colonies) in semisolid agar; stimulated glycosaminoglycan synthesis, induced expression of functional markers of the salivary gland, such as the secretory component, lactoferrin, and lysozyme; inhibited expression of alkaline phosphatase; and induced morphological alteration into elongated cells. These findings strongly suggest that WI-38 CM contains a factor(s) which inhibits growth and induces differentiation of HSGc-C5. The CM was also active on other human cancer cells as a growth inhibitor, but not on normal human fibroblasts. Partial purification and characterization of the factor(s) suggests that it may be a novel protein carrying both tumor inhibiting and differentiation inducing activities.

[Successful removal of T4 lung cancer with left atrial invasion after induction chemotherapy].

A 53-year-old man presented with cough, sputa and chest pain. The chest X-ray revealed a large mass shadow in the right lower lobe. Massive tumor extending into the left atrium was diagnosed by computed tomography (CT). The brushing cytology by broncoscopy was squamous cell carcinoma and its stage was IIIB. Chemothrapy using cisplatin, paclitaxel and gemcitabine hydrochloride was performed 8 courses during 6 months. The effect of the chemotherapy was complete response, enabling the surgical treatment. The right pneumonectomy with partial resection of the left atrium was performed by using vascular clamp. The defect of the left atrium could be sutured directly. Wide-spread necrotic change with very small amount of cancer cells in the atrial wall was confirmed by pathology. The patient has been well for 3 years and 6 months after surgery.

Establishment of bone morphogenetic protein 2 responsive chondrogenic cell line.

A clonal cell line named RMD-1 was established from the skeletal muscle of a 20-day fetal rat. RMD-1 represents a morphologically homogeneous population of undifferentiated mesenchymal cells, expressing alpha-smooth muscle actin and type I collagen, but no cartilage-associated genes. When cultured in agarose gel containing 100 ng/ml of recombinant human bone morphogenetic protein 2 (rhBMP-2; BMP-2), RMD-1 cells formed colonies and showed chondrocyte-like features as assessed by their ultrastructure, metachromatic staining with toluidine blue, and the production of large hydrodynamic-size proteoglycans. RMD-1 cells also differentiated into chondrocytes when the cells were plated at high density (over 2.5 x 10(5) cells/cm2) on type I collagen and incubated in medium containing 0.5% fetal bovine serum and 100 ng/ml of BMP-2. This chondrogenic differentiation was evidenced by a distinct morphological change into spherical cells, an increase in the levels of sulfated glycosaminoglycans, a decrease in type I collagen mRNA and the expression of cartilage-associated genes, including type II collagen, type IX collagen, aggrecan and alkaline phosphatase. In the presence of ascorbic acid and 10% serum, RMD-1 cells increased in size and expressed type X collagen as well as high alkaline phosphatase activity, then induced matrix mineralization. Thus, RMD-1 is a unique cell line that can differentiate from undifferentiated mesenchymal cells into hypertrophic chondrocytes.

Effects of monoclonal anti-c-kit antibody (ACK2) on melanocytes in newborn mice.

Previous studies indicate that c-Kit is required for postnatal melanocyte development. To understand the precise mechanisms of c-Kit dependence, we studied melanocyte development in newborn C57BL/6 mice by means of peritoneal injection of a monoclonal anti-c-Kit antibody (ACK2), which blocks c-Kit functions. The mice were injected once or more with ACK2 at various intervals after birth. In experiment 1, skin samples were examined on day 10 post-partum and in experiment 2 they were examined daily until day 10 post-partum. We studied melanocytes in the hair follicles, epidermis, and dermis by light and electron microscopy with dopa reactions and immunohistochemistry. Epidermal melanocytes in untreated mice were dopa negative and c-Kit positive on day 0 post-partum but became dopa positive soon thereafter. In ACK2-treated mice, the earlier the mice received ACK2 injections after birth, the fewer melanocytes they had, not only in the epidermis, but also in follicles. In these mice, melanocytes that had undergone apoptosis in the dermis and the follicles were detected ultrastructurally. Some appeared to have produced tyrosinase, because they had dopa-positive melanosomes. These results suggest that melanocytes in newborn mice are c-Kit dependent and undergo apoptosis when c-Kit receptors are blocked by ACK2 in the early days after birth. During this c-Kit-dependent period, melanocytes differentiate from dopa negative to positive and migrate from the epidermis to hair follicles.

Removal of stem cell factor or addition of monoclonal anti-c-KIT antibody induces apoptosis in murine melanocyte precursors.

Previous findings indicate that the protein c-KIT and its ligand, stem cell factor (SCF) play a crucial role in the development of melanocytes from their precursors in the embryonic neural crest cells. Using a monoclonal anti-c-KIT antibody, ACK2, which is an antagonistic blocker of c-KIT function, we and colleagues demonstrated that mouse melanocytes disappeared with the injection of ACK2 during certain periods of embryonic and postnatal life. The precise mechanisms of this disappearance, however, remain unclear. Because melanocytes disappeared without any inflammation in these in vivo studies, we suspect that apoptosis was a main cause of their disappearance. In this study, to clarify the underlying mechanism, we studied whether ACK2 induces apoptosis in c-KIT-positive melanoblasts, which appear in mouse neural crest cells cultured with SCF from 9.5 d old mouse embryos. With an in situ apoptosis detection kit, a significant increase in apoptosis was detected after the removal of SCF, which further increased with the addition of ACK2 during SCF-dependent periods. The occurrence of apoptosis in the cultured cells was also demonstrated by a DNA analysis and electron microscopy. Immunohistochemical double staining confirmed that the apoptotic cells were c-KIT positive, and the electron microscopy showed that these apoptotic cells were melanocyte precursors. It was therefore demonstrated that apoptosis was induced in the SCF-dependent c-KIT-positive melanocytes in vitro when the SCF/c-KIT interaction was obstructed. These findings elucidate the mechanism of the regulation of melanocyte development, and the survival and proliferation of these precursor cells, by SCF/c-KIT interaction.

Sulpiride, a D2/D3 blocker, reduces cataplexy but not REM sleep in canine narcolepsy.

Cataplexy, an abnormal manifestation of REM sleep atonia, is currently treated with antidepressants. These medications also reduce physiological REM sleep and induce nocturnal sleep disturbances. Because a recent work on canine narcolepsy suggests that the mechanisms for triggering cataplexy are different from those for REM sleep, we hypothesized that compounds which act specifically on cataplexy, but not on REM sleep, could be developed. Canine studies also suggest that the dopamine D2/D3 receptor mechanism is specifically involved in the regulation of cataplexy, but little evidence suggests that this mechanism is important for REM sleep regulation. We therefore assessed the effects of sulpiride, a commonly used D2/D3 antagonist, on cataplexy and sleep in narcoleptic canines to explore the possible clinical application of D2/D3 antagonists for the treatment of human narcolepsy. Both acute and chronic oral administration of sulpiride (300 mg/dog, 600 mg/dog) significantly reduced cataplexy without noticeable side effects. Interestingly, the anticataplectic dose of sulpiride did not significantly reduce the amount of REM sleep. Sulpiride (and other D2/D3 antagonists) may therefore be an attractive new therapeutic indication in human narcolepsy.

Neuronal activity in the cholinoceptive basal forebrain of freely moving narcoleptic dobermans.

Cholinergic stimulation in the basal forebrain (BF) triggers cataplexy in canine narcolepsy. Extracellular single unit recordings in the BF were carried out in freely moving narcoleptic dogs to study the neuronal mechanisms mediating cataplexy induction in the BF. Among the 64 recorded neurons, 12 were wake-active, three were slow wave sleep (SWS)-active, 17 were wake-/REM-active, 11 were REM sleep-active, three were cataplexy-active, and the other 18 were state-independent. Systemic administration of physostigmine, a cholinesterase inhibitor, induces status cataplecticus, decreases SWS and increases acetylcholine levels in the BF. Firing of most of the state-dependent neurons in the BF was significantly modified by physostigmine. Some of these neurons may thus mediate sleep stage changes or the effect on cataplexy observed after cholinergic stimulation in the BF.

Regional activation of human cerebral cortex upon an adaptation in mirror drawing.

To elucidate cerebral regions involved in adaptation to mirror drawing, changes in regional cerebral blood flow were measured using positron emission tomography at different levels of adaptation. A significant signal in subtraction images was localized in left Brodmann's area 45 (ventral sub-region of Broca's area) in the initial phase of the mirror drawing. This activity decreased as adaptation proceeded, and a small cluster in area 19 of the medial extrastriate cortex became significantly active. An after-effect of ca. 30 min of mirror-drawing was also detected in the right area 21 of the temporal association cortex. The results first demonstrated visuo-cortical regions where neurons might change their activity to evoke plastic response to the inverted vision.

Cognitive behavioral approaches to the patients suffering from depression due to maladjustment in the work place: two case reports.

The authors report two cases of depression in which Beck's cognitive therapy was effective. Case 1 was a 32-year-old man who had been troubled with the recurrent depression for about eight years in spite of regular medication. Case 2 was a 30-year-old man who had been chronically depressed for one year. Maladjustment in the work place was involved in the development of their depressive symptoms. Through the psychotherapeutic sessions, they were encouraged to identify their cognitive distortions such as emotional reasoning, all-or-nothing thinking and disqualifying the positive, and assisted to modify their cognitive distortions by means of cognitive behavioral techniques. Gradually gaining self-efficacy, they became able to cope well with their present problems. Both of them finally recovered from depression and, especially in case 1, he could overcome recurrence. The active ingredients in successful cognitive therapy were discussed. It was also stressed that the capacity to be sufficiently introspective to identify negative automatic thoughts and to be sufficiently logical to understand how the thoughts are distorted was requisite for this therapy.

The effects of qi-gong and acupuncture on human cerebral evoked potentials and electroencephalogram.

Although a number of studies on traditional Chinese medicine, such as qi-gong (QG), acupuncture (AC), moxibustion and Chinese herbal drugs, have been reported in recent years, there are few reports on human cerebral evoked potentials (EPs), especially relating only to QG and AC. In the present study, we examined the changes in EPs and electroencephalogram (EEG) by QG, and by AC stimulation to the point called "Zusanli" on the left lower leg, with one healthy male adult. 1. With regard to the effect of QG, significant changes in EP-components originated from the cortex suggest both facilitating and inhibitory effects of QG on the cortex. However, no significant changes in EP-components originated from the subcortex and no significant changes in EEG power% suggest that QG does not affect the subcortex. 2. With regard to the effects of AC, significant changes in EP-components originated from the cortex suggest facilitating and inhibitory effects of AC stimulation on the cortex. Furthermore, it is suggested that AC stimulation has few effects on the somatosensory and the visual pathways up to the cortex, while it has complicated effects on the auditory pathway up to the cortex.

Bilateral multiple pulmonary metastases in a patient with double advanced cancer of the head and neck.

A case of advanced gingival cancer is described. The cancer invaded into the mandible and skin of the cheek and was associated with cervical lymph node metastases, mediastinal lymph node metastases, and bilateral multiple pulmonary metastases. The patient received neoadjuvant chemoradiotherapy and local immunotherapy, followed by curative surgery for the primary and neck lesions. Histopathological examination of the primary cancer and the upper and middle cervical nodes (n = 7) indicated a diagnosis of squamous cell carcinoma. Sections of the lower cervical nodes (n = 5) revealed well-differentiated thyroid carcinoma, suggesting that the mediastinal and pulmonary lesions were of thyroid origin. After total thyroidectomy and mediastinal dissection followed by treatment with radioiodine, the multiple pulmonary nodules disappeared. There has been no evidence of recurrent tumour for 5 years.

Inheritance of von Willebrand's disease in a colony of Doberman Pinschers.

OBJECTIVE: To determine the mode of inheritance of von Willebrand's disease (vWD) and perform linkage analysis between vWD and coat color or narcolepsy in a colony of Doberman Pinschers. ANIMALS: 159 Doberman Pinschers. PROCEDURE: von Willebrand factor antigen (vWF:Ag) concentration was measured by use of ELISA, and results were used to classify dogs as having low (< 20%), intermediate (20 to 65%), or high (> 65%) vWF:Ag concentration, compared with results of analysis of standard pooled plasma. Buccal bleeding time was measured, and mode of inheritance of vWD was assessed by pedigree analysis. RESULTS: von Willebrand's disease was transmitted as a single autosomal gene defect. Results suggested that 27.04% of dogs were homozygous for vWD, 62.26% were heterozygous, and 10.69% did not have the defect. Most homozygous and some heterozygous dogs had prolonged bleeding times. Dogs with diluted coat colors (blue and fawn) were significantly overrepresented in the homozygous group, compared with black and red dogs, but a significant link between vWD and coat color was not detected. CONCLUSIONS AND CLINICAL RELEVANCE: von Willebrand's disease is transmitted as an autosomal dominant trait with variable penetrance; most dogs in this colony (89.3%) were carriers of vWD. Homozygosity for vWD is not likely to be lethal. Some heterozygous dogs have prolonged bleeding times. An association between diluted coat colors and vWD may exist.