Increase of antipsychotic medication in depressive inpatients from 2000 to 2007: results from the AMSP International Pharmacovigilance Program.

While international guidelines recommend monotherapy with antidepressants for depressed patients, recent investigation has demonstrated augmenting effects of antipsychotics (APs) in patients with major depression. We set out to investigate the use of APs in a European sample of depressed inpatients and the possible changes in their prescription over the period from 2000 to 2007. On two reference days in the years 2000 (32 psychiatric institutions, N=1078) and 2007 (54 psychiatric institutions, N=1826), the following data were recorded for all depressed inpatients (ICD-10: F32.00, F32.01, F32.1, F32.10, F32.11, F32.2, F33.0, F33.00, F33.01, F33.1, F33.10, F33.11, F33.2), monitored as part of the AMSP (Arzneimittelsicherheit in der Psychiatrie) surveillance programme: age, sex, ICD-10 diagnosis and all medication applied on that day. Depressed inpatients with psychotic symptoms were excluded. We found a significant increase in the number of AP-treated inpatients from 37.9% in 2000 to 45.8% in 2007 (χ²=17.257, p<0.001). The number of inpatients who received an atypical AP rose significantly between 2000 and 2007, from 12.8% to 28.3% (χ²=93.37, p<0.001). On the contrary, the percentage of inpatients receiving typical APs showed a significant decrease from 30.2% to 24.1% over the same period (χ²=13.179, p<0.001). Examining only the subgroup of severely depressed inpatients we found an increase in the number of AP-treated inpatients, but this was not statistically significant (χ²=2.047, p=0.15). Our study revealed a significant increase in the usage of atypical APs. However, this effect was not only due to augmentation strategies for severely depressed inpatients. Further studies are needed to examine possible putative effects of AP augmentation treatment in mild to moderate depression.

Early and late complications of stapled haemorrhoidopexy: a 6-year experience from a single surgical clinic.

PURPOSE: Introduction of stapled hemorrhoidopexy (SH) brought a radical change in the treatment of haemorrhoidal disease. The aim of this study is to evaluate the results and the complications (early and late) from the use of this technique. METHODS: During the last 6 years (2005-2011), 123 patients underwent a SH in our ward. Our sample consists of 79 male and 44 female patients with an average age of 48.2 years (range 22-83 years). Of them, 83 had third-degree haemorrhoidal disease, 34 had fourth-degree and 6 had second-degree bleeding haemorrhoids. The follow-up period was 6-72 months. RESULTS: Pain was minimal or even not existent. Additional sutures or use of adrenaline 1:200.000 for haemostasis were required in 6 patients (4.8%). The bleeding has been diminished with the use of this new haemorrhoidectomy stapler PPH03. Urinary retention, which was observed in 3 patients (2.4%), was temporary and the use of catheter was not needed. As a late complication, 'faecal urgency' occurred in 8 patients (6.5%), and disappeared after some months. No recurrent haemorrhoidal disease occurred. No cases of chronic pain were reported. Average hospital stay was 1 day, except for 2 patients who remained for 2 days for bleeding observation. CONCLUSIONS: The correct application of SH reduces the possible complications. The advantages of the stapled procedure are reduced postoperative pain, the minimal hospital stay and early return to work.

Light sensitivity and pain sensation during cataract surgery. A comparative study of two modes of anaesthesia.

The objective of this study was to compare the light sensitivity and pain experienced by patients undergoing cataract surgery under subtenon and topical with intracameral anaesthesia. Fifty-four patients were randomly assigned to receive either two drops of proxymethacaine 0.5% as topical anaesthesia with 0.5 ml preservative-free 1% intracameral lidocaine or 4 ml 2% lignocaine as subtenon anaesthesia. Light sensitivity and overall pain perception were recorded at the end of surgery. The mean pain score in the subtenon group (0.11; range 0-1) was lower than in the topical group (1.07; range: 0-3, P < 0.001). The mean light-sensitivity score was lower in the subtenon group (0.26; range: 0-4) than in the topical group (1.29; range: 0-4, P = 0.001). Subtenon anaesthesia was more effective in suppressing light sensitivity and pain during cataract surgery than topical with intracameral anaesthesia. This suggests that use of subtenon anaesthesia may lead to a more comfortable operative experience.

The effect of dietary oregano essential oil on microbial growth of rabbit carcasses during refrigerated storage.

The effect of dietary supplementation with oregano essential oil on microbial growth of rabbit carcasses during refrigerated storage was investigated. A total of 45 weaned rabbits were separated into three equal groups with three subgroups each. One group was given the basal diet and served as control and the other two groups were administered diets supplemented with oregano essential oil at levels of 100 and 200mg/kg diet, respectively (OR100 and OR200 groups). Total viable counts, Pseudomonas spp., lactic acid bacteria, Brochothrix thermosphacta, Enterobacteriaceae and yeast and mould counts, as well as off-odours and appearance of slime were all assessed on rabbit carcasses stored at 3±1°C for 12 days. The results showed that performance parameters were not affected (p>0.05) whereas the dietary supplementation with oregano essential oil resulted in lower (p<0.05) average microbial counts on the carcasses, compared to controls, throughout storage. Dietary supplementation with oregano essential oil at 200mg/kg was more effective in inhibiting microbial growth compared with 100mg/kg. Sensory evaluation scores indicated that the carcasses obtained from OR100 and OR200 groups gave a noticeable putrid odour after days 8 and 10, respectively, whereas the control carcasses developed off-odours after the 6th day of storage. Slime formation in the controls was observed after day 6, while the OR100 and OR200 groups were just beginning to show slime after days 8 and 10, respectively.

Myelin Sheath Development in the Maxillary Nerve of the Newborn Pig.

Myelination, the ensheathing of neuronal axons by myelin, is important for the proper function of both central and peripheral nervous systems. Various studies have investigated the quantitative parameters of myelination in certain species. Pigs are among the species of which their use as laboratory animals in neuroscience research increased the past few decades. However, there is limited data regarding the myelination process in the pig. Moreover, the maxillary nerve is crucial for Pseudorabies Virus (PrV) neuropathogenesis. In this context, a quantitative analysis of various myelination parameters of the maxillary nerve was performed, during the first 5 weeks of porcine post-natal development, the time period, which exhibits the highest interest for PrV neuropathogenesis. The evaluation was conducted in four groups of uninfected pigs, at the time of birth (group 0w), at the age of 1 week (group 1w), 3 weeks (group 3w) and 5 weeks (group 5w), using toluidine blue staining, immunofluorescence and electron microscopy. Axon and fibre diameter, perimeter and surface, myelin sheath thickness and g-ratio were measured on histological sections transverse to the longitudinal axis of the maxillary nerve. The thickness of myelin sheath was 0.76 µm for group 0w, 0.94 µm for group 1w, 0.98 µm for group 3w and 1.03 µm for group 5w. The g-ratio was 0.529, 0.540, 0.542 and 0.531 for the respective animal groups. The results of this study contribute to the understanding of the myelination process in the pig will be used for the study of PrV effects on the myelination development of newborn piglets' maxillary nerve and may shed new light to their vulnerability to the virus.

Epidemiology and socioeconomic impact of seasonal affective disorder in Austria.

BACKGROUND: Seasonal affective disorder (SAD) is a subtype of recurrent depressive or bipolar disorder that is characterized by regular onset and remission of affective episodes at the same time of the year. The aim of the present study was to provide epidemiological data and data on the socioeconomic impact of SAD in the general population of Austria. METHODS: We conducted a computer-assisted telephone interview in 910 randomly selected subjects (577 females and 333 males) using the Seasonal Health Questionnaire (SHQ), the Seasonal Pattern Assessment Questionnaire (SPAQ), and the Sheehan Disability Scale (SDS). Telephone numbers were randomly drawn from all Austrian telephone books and transformed using the random last digits method. The last birthday method was employed to choose the target person for the interviews. RESULTS: Out of our subjects, 2.5% fulfilled criteria for the seasonal pattern specifier according to DSM-5 and 2.4% (95% CI=1.4-3.5%) were diagnosed with SAD. When applying the ICD-10 criteria 1.9% (95% CI=0.9-2.8%) fulfilled SAD diagnostic criteria. The prevalence of fall-winter depression according to the Kasper-Rosenthal criteria was determined to be 3.5%. The criteria was fulfilled by 15.1% for subsyndromal SAD (s-SAD). We did not find any statistically significant gender differences in prevalence rates. When using the DSM-5 as a gold standard for the diagnosis of SAD, diagnosis derived from the SPAQ yielded a sensitivity of 31.8% and a specificity of 97.2%. Subjects with SAD had significantly higher scores on the SDS and higher rates of sick leave and days with reduced productivity than healthy subjects. CONCLUSIONS: Prevalence estimates for SAD with the SHQ are lower than with the SPAQ. Our data are indicative of the substantial burden of disease and the socioeconomic impact of SAD. This epidemiological data shows a lack of gender differences in SAD prevalence. The higher rates of females in clinical SAD samples might, at least in part, be explained by lower help seeking behaviour in males.

A case report of Merkel cell carcinoma on chronic lymphocytic leukemia: differential diagnosis of coexisting lymphadenopathy and indications for early aggressive treatment.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a monoclonal disorder, characterized by a progressive proliferation of functionally incompetent B lymphocytes. There is increased evidence of association between CLL and skin cancers, including the uncommon Merkel cell carcinoma (MCC). CASE PRESENTATION: A case report of an 84-year old male, who presented with an aggressively recurrent form of MCC on the lower lip, on the background of an 8-year history of untreated CLL. During the recurrences of MCC, coexisting regional lymphadenopathy, posed a problem in the differential diagnosis and treatment of lymph node involvement. Histopathology and immunoistochemistry showed that submandibular lymphadenopathy coexisting with the second recurrence of MCC, was due to B-cell small lymphocytic lymphoma. The subsequent and more aggressive recurrence of the skin tumor had involved the superficial and deep cervical lymph nodes. Surgical excision followed by involved field radiation therapy has been proven effective for both malignancies. CONCLUSION: MCC has a high incidence of regional lymphadenopathy at presentation (12-45%) and even when it arises on the background of chronic leukemia, lymphadenopathy at presentation should be managed agressively with elective lymph node dissection. We overview the postulated correlation between Merkel tumor and CCL, the differential diagnosis of regional lymphadenopathy during the recurrences of the skin tumor and the strategies of treatment.

Impact of body mass on autonomic function in persons with type 2 diabetes.

The aim of this study was to investigate the influence of body mass on autonomic nerve function in persons with type 2 diabetes. Towards this aim we studied two groups of diabetic persons. Group 1: n = 30 lean (mean age 57.2+/-12.5 years, body mass index (BMI) 22.5+/-1.8 kg/m2]. Group 2: n = 35 overweight and obese (age 52.3+/-10.3 years, BMI 28.8 + 3.2 kg/m2). Autonomic neuropathy (DAN) was assessed using the battery of the five classical tests. DAN was diagnosed when at least two of the five tests were abnormal. Abnormalities of the heart rate based tests were considered as indication of parasympathetic and of blood pressure changes as indication of sympathetic dysfunction. The prevalence rates of DAN were not different between group 2 and group 1 (54.2 and 53.3%, respectively, P = 0.54). The same was valid for the rates of parasympathetic and sympathetic dysfunction in the studied groups (51.4 and 53.3% (P = 0.87) in group 2 and 34.2 and 33.3% (P = 0.93) in group 1, respectively). When the values of the arithmetic expression of each single autonomic function test were compared, no significant difference could be shown between the studied groups. In addition, no significant correlation was found between BMI and indices of DAN. These data indicate that moderate increase of body mass does not affect autonomic function in persons with type 2 diabetes.

A study of apoptosis in brain tumors by in situ end-labeling method.

Recognition of apoptotic cells has recently been facilitated by in situ end-labeling (ISEL) techniques which identify DNA strand breaks. The ISEL assay has been applied in 26 brain tumors, meningiomas, and gliomas of different grade of malignancy in order to determine the apoptotic index (AI). Apoptotic cells were readily found in all the examined tumors; in most cases the AI values were below 1%. Any significant relationship between AI and grade of malignancy could not be determined. However, the AI mean value of the meningiomas was higher than that of gliomas WHO II and III, respectively. Furthermore, it seemed that in the examined gliomas, with the exception of the glioblastoma group, low grade malignancy was related with higher AI values. The latter decreased gradually in the WHO II and III group of tumors, respectively. Our preliminary results indicate that an apoptotic process may play a significant role in brain tumor kinetics and will probably contribute to our understanding of the biologic behavior of those tumors.

Distribution of muscle fibre types in human skeletal muscle fascicles: an autopsy study of three human muscles.

The predominance of type 2 fibres in the periphery of the muscle fascicle is a phenomenon attributed to local factors or to the adaptation of the muscle to functional needs. As the majority of relevant studies has been performed on quadriceps muscle of males, the purpose of this study was to examine other muscles along with quadriceps, in females as well as in males, with parallel morphometric analysis of fibres, in order to determine whether differences in size exist in addition to differences in proportion. Cryostat sections (ATPase, pH 9.4) were studied from 13 quadriceps femoris, 13 biceps brachii and 11 deltoid muscles taken at autopsy from 11 males and 8 females. The number and smallest diameter of type 1 and 2 fibres were counted and the percentage and mean diameter of the two types of fibres were calculated in the interior and the periphery of randomly selected fascicles. We found that: the predominance of type 2 fibres in the periphery is constant in all muscles studied, regardless of sex and age; there is a progressive age-related reduction in the diameter of type 2 fibres.

Tuberculous choroidal granuloma in an HIV-positive patient.

We report a case of a 34-year-old HIV-positive patient undergoing treatment for pulmonary and lymph node Mycobacterium tuberculosis infection, who developed loss of vision secondary to a tuberculous choroidal granuloma.

The impact of COMT gene polymorphisms on suicidality in treatment resistant major depressive disorder--a European multicenter study.

Many association studies have reported associations between the catechol-O-methyltransferase (COMT) gene and psychiatric disorders including major depression (MDD). The COMT gene has further been associated with suicidal behaviour, as well as with treatment response, although with conflicting results. In the present study, we further elucidate the impact of COMT in treatment response in MDD patients with suicide risk and/or a personal history of suicide attempts. Two hundred fifty MDD patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for seven SNPs (rs4680, rs2075507, rs737865, rs6269, rs4633, rs4818 and rs165599) within the COMT gene. With regard to suicide risk and personal history of suicide attempts, neither single marker nor haplotypic association was found with any SNP after multiple testing correction. In non-responders, we found significant single marker and haplotypic association with suicide risk, but not in responders. The same holds true for both remitters and non-remitters, and when testing for association with a personal history of suicide attempts and treatment response phenotypes. In conclusion, we found significant association of COMT SNPs with suicide risk in MDD patients not responding to antidepressant treatment. Larger well-defined cohorts will be required to dissect this further.

Predicting local control of choroidal melanomas following ¹°6Ru plaque brachytherapy.

BACKGROUND: We evaluated the control rate of choroidal melanomas treated with ¹°6Ru plaque brachytherapy to identify the risk factors associated with local recurrence and lack of response. METHODS: A retrospective review of ¹°6Ru plaque brachytherapy for patients with choroidal melanoma treated at St Bartholomew's Hospital, London. Survival analysis was used to assess associations between evaluated age, sex, location, foveal proximity, tumour base and height, presence of lipofuscin and subretinal fluid, apex dose, radiation rate and type of plaque with time to local recurrence. Logistic regression analysis was used to assess to evaluate the association between the same set of variables and lack of tumour response. RESULTS: From January 2002 to December 2006 189 patients were treated. The follow-up ranged from 12 to 78 (median 33) months. None of the patients received adjuvant diode laser thermotherapy. The control rate was 85.7% (14 recurred while 13 did not respond). Of the patients who had local recurrence, univariate survival analysis demonstrated an association with younger patients, foveal proximity, preoperative subfoveal fluid and tumour base >11 mm. Age and foveal proximity remained significant in a Cox multiple variable model (p=0.03). Of the patients who did not respond, logistic regression analysis showed that lack of response was associated with a tumour height >5 mm, confirmed through multiple variable analysis (p=0.027). CONCLUSIONS: Tumours that are close to the fovea in young patients appear more likely to show local recurrence. Tumour height >5 mm was the only prognostic factor that determined lack of response. These results may be used to select which tumours require adjuvant therapy.

A survey of investigations used for the management of glaucoma in hospital service in the United Kingdom.

AIMS: This study surveys the current use of investigations for the management of glaucoma in hospital practice by UK ophthalmologists. METHODS: A total of 1007 questionnaires were posted to all active NHS consultant ophthalmologists. They were asked to indicate the type of hospital (whether university (UTH) or general (DGH) hospital), glaucoma specialist status, and availability and use of automated perimetry, disc photography, HRT, GDx, OCT, and pachymetry. RESULTS: A total of 493 completed questionnaires were received and 469 were analysed: 284 (60.6%) DGH, 185 (39.4%) UTH, 144 (30.7%) glaucoma specialists. There was good availability of automated perimetry (467, 99.6%), disc photography (420, 89.6%), pachymetry (374, 79.7%), OCT (212, 45.2%), HRT (206, 43.9%), and GDx (59, 12.6%). A total of 308 (65.7%) consultants had at least one digital imaging instrument available. The majority of consultants used SAP (347, 74.0%) and SITA-fast (282, 60.1%) for glaucoma suspects, and for monitoring glaucoma (283, 60.3% and 197, 42.0%, respectively). Some used Esterman (155, 33.0%) and Goldmann fields (90, 19.2%) in addition to SAP and SITA-fast for glaucoma suspects. Few consultants used short-wavelength automated perimetry and frequency-doubled perimetry. Of the three imaging tests, HRT was the most commonly used investigation for disc asymmetry, early glaucoma, glaucomatous progression, ocular hypertension, normal tension glaucoma, and unreliable visual fields (P<0.0001). Where pachymeters were available, 333 (89.0%) consultants and 117 (98.3%) glaucoma specialists used pachymetry in glaucoma management. CONCLUSIONS: There was some variation in the use of investigations for the diagnosis and management of glaucoma, reflecting the range of techniques available. SAP, SITA-fast, and pachymetry were the most commonly utilised investigations followed by HRT. Glaucoma specialist status, type of hospital, and presence of research influenced the availability and use of all investigations, except visual fields.

Optochiasmal avulsion secondary to minor occipital trauma.

BACKGROUND: Optic nerve avulsion is an extremely rare occurrence and usually arises in the setting of severe fronto-orbital fractures or penetrating orbital injuries. However, a few cases have been associated with minor injury. OBJECTIVE: To overview the pathophysiology of delayed optochiasmal avulsion following minor ocipital trauma and discuss management options. METHODS: Report of a unique case of a 79-year-old woman who presented with delayed partial expulsion of the right globe and complete optic nerve avulsion following closed head injury to the occiput. CONCLUSION: Antero-posterior distortion of the skull following such a deceleration injury can cause laceration and thrombosis of the pre-chiasmal and pial arteries supplying the optic chiasm. The ensuing ischaemic changes subsequently caused delayed softening of the chiasm and its avulsion. The concomitant retrobulbar haemorrhage and mass effect within the orbit consequently led to the partial expulsion of the globe.

A combined park management framework based on regulatory and behavioral strategies: use of visitors' knowledge to assess effectiveness.

In light of the increasing mandate for greater efficiency in conservation of natural reserves such as national parks, the present study suggests educational approaches as a tool to achieve conservation purposes. Currently, the management of human-wildlife interactions is dominated by regulatory strategies, but considerable potential exists for environmental education to enhance knowledge in the short run and to prompt attitude change in the long run. A framework for conservation based on both traditional regulatory- and behavior-oriented strategies was proposed whereby the level of knowledge that park visitors have acquired comprises an obvious outcome and establishes a basis upon which the effectiveness of regulatory- and behavior-based regimes could be assessed. The perceptions regarding park-related issues of two distinct visitor groups (locals and nonlocals) are summarized from a survey undertaken in Vikos-Aoos national park. The findings suggest a superficial knowledge for certain concepts but little profound understanding of the content of such concepts, indicating that knowledge-raising efforts should go a long way towards establishing a positive attitude for the resource. Visitors' poor knowledge of the park's operation regulation contest the efficiency of the presently dominant regulatory management regime. While geographical distances did not appear to significantly differentiate knowledge between the two groups, wilderness experience (as certified by visits to other parks) was proved to be an impetus for generating substantial learner interest in critical park issues among nonlocal visitors. School education and media were found to be significant knowledge providers.

[Effect of phenytoin on Purkinje cells in the cerebellum]. / Die Wirkung von Phenytoin auf die Purkinjezellen des Kleinhirns.

We have examined the effect of chronic administration of phenytoin on Purkinje cells of cerebellum in adult mice. After daily intramuscular administration of phenytoin for a period of six months no difference in the number of Purkinje cells could be found between the treated and control animals.

Corrected QT interval in relation to the severity of diabetic autonomic neuropathy.

The aim of this study was to investigate to what extent the existence of objective signs of diabetic autonomic neuropathy affects the corrected QT interval (QTc) in diabetic subjects. A total of 105 diabetic subjects (type 1, n = 53; type 2, n = 52) as well as 40 matched (by age and sex) control subjects were studied. All subjects underwent the battery of five Ewing tests. Autonomic neuropathy was diagnosed if two of the five tests were abnormal. In addition, the result of each test was considered as normal (grade = 0), borderline (grade = 1) or abnormal (grade = 2), and on the basis of the sum of the scores we calculated a total score for autonomic neuropathy. The QTc interval was measured at rest, and a value > 440 ms was considered abnormal. The QTc interval was significantly more prolonged in diabetic persons with autonomic neuropathy than in those without neutopathy and in control subjects: 408.4 +/- 24.2 ms vs. 394.6 +/- 27.9 ms and 393.6 +/- 25.5 ms respectively (P = 0.001). Furthermore, multivariate analysis controlling for age, sex, systolic and diastolic blood pressure, body mass index (BMI), waist-hip ratio (WHR), smoking, type and duration of diabetes, type of treatment, HBA1c and total score of autonomic neuropathy eliminated the role of all these factors as potential confounders except for the total score of autonomic neuropathy, which was found to affect QTc interval independently and significantly (P = 0.012). In summary, the present study confirmed the well-known relation between autonomic neuropathy and QTc interval; in addition, it showed that QTc prolongation is associated with major degrees of autonomic neuropathy.

Beck Depression Inventory in the detection of depression among neurological inpatients.

The validity of the Beck Depression Inventory (BDI) was assessed in a group of 150 neurological inpatients using Receiver Operating Characteristic analysis and DSM-III-R as external criterion. As regards depressive disorders as a whole, it was found that the best trade-off between sensitivity and specificity was the cutoff score of 20. The discriminating ability of the BDI for major depressive disorder was quite satisfactory at the cutoff score of 29 contrary to the dysthymic disorder in which the discriminating power of the BDI was not acceptable. In conclusion, the use of the BDI in neurological settings is useful with cutoff scores depending on the research purposes.