Levodopa/carbidopa intestinal gel infusion and weight loss in Parkinson's disease.

BACKGROUND AND PURPOSE: Weight loss (WL) is a frequent yet under-recognized complication of levodopa/carbidopa intestinal gel (LCIG) infusion, as well as a milestone of Parkinson's disease (PD) disability progression. The complex association between WL, poor nutritional status, motor complications and PD progression, however, remains unclear. METHODS: Consecutive consenting patients with PD treated with LCIG (n = 44; PD duration, 18.3 ± 6.5 years) were enrolled in an open-label observational study assessing the extent of WL occurring during LCIG treatment. As secondary aims, we correlated the nutritional status, as detected by the Mini Nutritional Assessment, with the severity of motor symptoms [Movement Disorder Society Unified Parkinson's Disease Rating Scale part III], motor complications (Unified Parkinson's Disease Rating Scale part IV), activities of daily living (Schwab and England scale), cognitive impairment (Mini Mental State Examination), depression (Beck Depression Inventory), difficulties in feeding (Edinburgh Feeding Evaluation in Dementia Questionnaire) and levodopa equivalent daily dose (LEDD). RESULTS: There was an average WL of 9.9 ± 10.5% (7.6 ± 7.1 kg) over an LCIG treatment period of 51.6 ± 28.5 months. The extent of WL correlated with the percentage of the waking day spent with dyskinesia (P < 0.05). The nutritional status correlated with motor symptom severity (P < 0.01), dysphagia (P < 0.01) and LEDD (P < 0.01). CONCLUSIONS: Weight loss may occur in patients with PD undergoing LCIG in correlation with the percentage of the waking day spent with dyskinesia. Regardless of the extent of WL, the nutritional status correlated with higher LEDD, as well as with indices of disease progression, such as motor symptom severity and dysphagia.

Unawareness of bipolar disorder: the role of the cingulate cortex.

Reduced awareness of illness is a well-known phenomenon that has been understudied in remitted patients with bipolar disorder. In particular, the relationship between reduced awareness and executive dysfunction is an intriguing question that has yet to be resolved. The aim of the current study is to analyze the link between reduced awareness, brain dysfunction, and concomitant cognitive-behavioral disturbances from a neurocognitive perspective. In previous studies, we demonstrated the role of the anterior cingulate cortex (ACC) in the unawareness of distinct pathologies that exhibit overlapping symptoms in the context of overlapping circuit-specific dysfunction. Given the clinical importance of the results obtained, the present study considers six aware and four unaware remitted bipolar disorder patients. Cingulate functionality was assessed with functional magnetic resonance imaging while patients performed a go/no-go task. Patients were also studied on an overall cognitive task battery and with behavioral assessment of mood changes in terms of apathy and disinhibited behavior. Unaware patients showed frontoparietal hypo-perfusion, with a significant reduction of task-sensitive activity in the bilateral superior and middle frontal gyrus, putamen, insular, and ACCs.

Unawareness of deficits in ischemic injury: role of the cingulate cortex.

Reduced awareness of illness is a well-known phenomenon that has been studied in patients with vascular disease, but the precise nature of their executive dysfunction is an intriguing question that still has to be resolved. It would be particularly interesting to study patients with reduced awareness of disease possibly related to vascular lesions of the prefrontal cortex. Due to the clinical importance of the case, here we present a patient with a selective right anterior cingulate ischemic injury and impaired awareness of deficits. We suggest that the cingulo-frontal area dysfunction may represent one of the corresponding neurobiological substrates of his persistent unawareness, which has not yet been evaluated in the literature on patients with acquired brain injury (ABI).

Validation of RiskCheck Bladder Cancer ©, version 5.0 for risk-adapted screening of bladder cancer.

INTRODUCTION: The aim of the study was to assess the strength of the online tool RiskCheck Bladder Cancer©, version 5.0 (RCBC) for early detection of bladder cancer (BC). MATERIALS AND METHODS: RCBC was evaluated retrospectively based on the data of 241 patients, of which 141 were suffering from BC. Statistical analysis was performed by descriptive statistics, nonparametric group comparison, classification tree analysis and ROC analysis. RESULTS: ROC analysis of the risk classification showed a sensitivity of 71.6%, a specificity of 56.5%, a positive predictive value of 67.8%, a negative predictive value of 52% and an accuracy of 63.5%. BC risk factors ranked by importance are time of smoking (p < 0.0001), gender (within the nonsmoking group: p < 0.009), occupational toxin exposure (within the group <35 years of smoking: p < 0.048) and amount of consumed cigarettes resulting in a 95% association with BC (within the group >35 years of smoking: p < 0.0001). CONCLUSIONS: The high predictive power of RCBC for the identification of asymptomatic patients living under risk could be demonstrated.

Positive urine cytology and carcinoma in situ prior to second transurethral resection of the bladder correlate with positive second resection histology and the need for subsequent cystectomy.

OBJECTIVE: A second transurethral resection of the bladder (TURB) is recommended for high-grade bladder cancer (BC) yet yields negative results in over half of the cases. Aim of this study was to identify prognostic indicators of a positive second TURB or the need for a subsequent cystectomy. MATERIALS AND METHODS: The study cohort consisted of 101 patients with high-risk BC (T1G2-3, TaG3, Carcinoma in situ) who underwent second TURB after complete first resection. Age, gender, stage, grade, carcinoma in situ (Cis), tumour number, size, localization, surgeon experience and bladder wash cytology before the second TURB were considered as potential prognostic factors of positive histology at second TURB or the need for subsequent cystectomy. RESULTS: The mean follow-up period was 23.8 months. The study cohort was comprised of 82 males and 17 females. Cytology on bladder wash urine was performed in 85/101 patients and in 39 was negative; 55.5 % of second TURB specimens were negative. The rate of upstaging to ≥T2 was 4.9 %. Cis (OR 8.4; 95 % CI 1.3-54.2; p = 0.03) and positive cytology (OR 6.8; 95 % CI 2.3-19.9; p = <0.01) were independent prognostic factors of a residual tumour in the second TURB. Cytology also correlated with clinical need for cystectomy in the follow-up (HR 6.5; 95 % CI 1.3-30.5; p = 0.02). CONCLUSIONS: CIS and positive cytology prior to second TURB increased the risk of a positive second TURB specimen. A positive cytology also increases the risk of the subsequent need for cystectomy.

Subfascial endoscopic perforator surgery (SEPS) in chronic venous insufficiency. A 14 years experience.

INTRODUCTION: Subfascial Endoscopic Perforator Surgery (SEPS) enables the direct visualization and section of perforating veins. Morbidity and duration of hospitalization are both less than with conventional open surgery (Linton's or Felder's techniques). PATIENTS AND METHODS: A total of 322 legs from 285 patients with a mean age of 56 years (range 23-90) were treated at our Department from May 1996 to January 2010. In 309 cases, an endoscope (ETM Endoskopische Technik GmbH, Berlin, Germany) was introduced through a transverse incision approximately 1.5 cm in length and 10 cm from the tibial tuberosity, as with Linton's technique. A spacemaker balloon dissector for SEPS, involving a second incision 6 cm from the first, was used in only 13 cases. RESULTS: The procedure used in each case was decided on the basis of preoperative evaluation. SEPS and stripping were performed in 238 limbs (73.91%), SEPS and short stripping in 7 limbs (2.17%), SEPS and crossectomy in 51 limbs (15.84%), and SEPS alone in 26 limbs (8.07%). 103 patients presented a total of 158 trophic ulcers; the healing time was between 1 and 3 months, with a healing rate of 82.91% after 1 month and 98.73% after 3 months. CONCLUSION: Subfascial ligature of perforating veins is superior to sclerotherapy and minimally invasive suprafascial treatment for the treatment of CVI. It is easy to execute, minimally invasive and has few complications.

[Micromedullary thyroid carcinoma: school experience]. / Il microcarcinoma midollare della tiroide: esperienza di Scuola.

Medullary microcarcinomas occurrence are rare and fortuitous, it's usually related to the calcitonin measurement, that's the gold standard for the diagnosis. In other cases performing a thyroidectomy for a benign thyroid disease it's found a sub-centimeter tumor. Actually it's not clear the most appropriate surgical treatment for those kind of tumors because the number of cases in literature is limited and because there are different surgical approaches. In this study 17 patients were operated for medullary thyroid microcarcinoma and the Authors found central lymph node metastases in 33.3% of cases. The Authors, analyzing those results, think that total thyroidectomy with lymphadenectomy of the central compartement is the best choice in a sporadic microcarcinoma, while a total thyroidectomy without lymphadenectomy should be performed when the microcarcinomas are incidentals.

Toll-like receptor 4 genetic diversity among pig populations.

The transmembrane glycoprotein encoded by the Toll-like receptor 4 gene (TLR4) acts as the transducing subunit of the lipopolysaccharide receptor complex of mammals, which is a major sensor of infections by Gram-negative bacteria. As variation in TLR4 may alter host immune response to lipopolysaccharide, the association between TLR4 polymorphisms and immune traits of the respiratory and gut systems has important implications for livestock. Here, a sequence dataset from 259 animals belonging to commercial and traditional European pig populations, consisting of 4305 bp of TLR4, including the full transcribed region, a portion of intron 2 and the putative promoter region, was used to explore genetic variation segregating at the TLR4 locus. We identified 34 single nucleotide polymorphisms, 17 in the coding sequence and 17 in the non-coding region. Five non-synonymous mutations clustered within, or in close proximity to, the hypervariable domain of exon 3. In agreement with studies in other mammals, a major exon 3 haplotype segregated at high frequency in the whole sample of 259 pigs, while variants carrying non-synonymous substitutions showed frequencies ranging between 0.6% and 8.7%. Although results on exon 3 provided suggestive evidence for purifying selection occurring at the porcine TLR4 gene, the analysis of both coding and non-coding regions highlighted the fact that demographic factors strongly influence the tests of departure from neutrality. The phylogenetic analysis of TLR4 identified three clusters of variation (ancestral, Asian, European), supporting the evidence of Asian introgression in European main breeds and the well documented history of pig breed domestication previously identified by mtDNA analysis.

Thyroid tissue remnants after "total thyroidectomy".

Total Thyroidectomy (TT) is a gold standard for benign bilateral pathologies and malignant pathologies of the thyroid. TT has numerous advantages over less radical approaches, such as the resolution of the thyroid pathology, avoidance of recurrences, and improved response to life-long substitutive organotherapy. TT has a negligible rate of recurrence. Near Total Thyroidectomy (NTT) is associated with a low rate of recurrence. Subtotal Thyroidectomy (ST), in which a portion of the thyroid gland is deliberately left in the thyroid lodge, has a considerably higher rate of recurrence. The incidence of complications with TT is similar to that with other techniques of thyroid exeresis. However, despite the radical intent of surgeons, a real TT is not always carried out. The complete removal of all the thyroid tissue employing TT is not the norm and micro/macroscopic remnants almost always remain. The literature on these tissue remnants is often based on techniques that are not very accurate in terms of determining the diameters of the tissue remaining. In our study, conducted by colour echo-doppler of the thyroid lodge in 102 patients who had undergone TT for benign thyroid pathologies, we demonstrated significant thyroid tissue remnants after TT in 34 cases of 102 (33,3%). Therefore, out of a total of 102 so-called "total thyroidectomies", only 68 (66,7%) were really total, whereas 12 patients (11,76%) had near total thyroidectomy, leaving tissue remnants < 1 cm, and 22 patients (21,57%) had subtotal thyroidectomy, with tissue remnants > or = 1 cm.

A novel neurocognitive approach for placebo analgesia in neurocognitive disorders.

Neural correlates of placebo analgesia (PA) in patients with neurocognitive disorders have not yet been elucidated. The present study aimed to evaluate how and to what extent executive (dys)functions of the medial prefrontal cortex (MPFC) may be related to PA. To this end, twenty-three subjects complaining of different cognitive deficits (from mild cognitive impairment likely due to Alzheimer's disease to mild AD) were recruited. PA was investigated by a well-known experimental venipuncture pain paradigm (open versus hidden [O-H] application of lidocaine). Patients also underwent a comprehensive neuropsychological evaluation and a functional magnetic resonance imaging (fMRI) GO/No-GO task for eliciting selective activation of the MPFC. Selected neuropsychological variables were correlated to the OH-PA paradigm. The association between the fMRI response on the "No-GO" versus "GO" contrast and PA was investigated over the whole-brain by regression analysis. We showed the existence of a relationship between a lower PA and MPFC dysfunctions through the neuropsychological and fMRI assessment. A separate voxel-based morphometry (VBM) analysis controlled for possible influence of grey matter (GM) volume reduction on both fMRI results and PA. fMRI results were not directly affected by, and therefore independent of, disease-specific GM atrophy, which was indeed located more anteriorly within the rostral anterior cingulate and inversely correlated with PA. Our findings shed new light on the underestimated contribution of executive (dys)functions mediated by the MPFC (response-inhibition, self-monitoring and set-shifting abilities) in PA pathogenesis, with a special purely (i.e. independently from brain structural alterations) functional role played by the MCC. Results are discussed in terms of possible clinical relevance in the management of patients with neurocognitive disorders.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

[Two cases of synchronous papillary and medullary thyroid carcinoma]. / Due casi di carcinomi tiroidei sincroni di tipo midollare e papillifero.

The Authors describe two cases of simultaneous association of papillary and medullary thyroid carcinoma. They emphasize the treatment of these cases stressing the correlation between the therapeutic criteria and the malignancy of medullary carcinoma.

[Retroperitoneal giant mixed sarcoma. Case report]. / Un caso di sarcoma misto retroperitoneale gigante.

The Authors present a rare case of voluminous retroperitoneal tumor in a 41 years old woman. CT scan showed a solid abdominal expansive mass, with compression and displacement of the left lobe of the liver, spleen, stomach, pancreas, and left kidney. The patient underwent surgery for excision of a giant retroperitoneal mass. Surgery was uneventful. The patients recovered well. Histology showed a mixed liposarcoma and angiosarcoma with high grade of malignancy and positivity for vimentin, factor VIII, CD34, CD31 and negativity for S-100, CD68, AMS, AML. The prognosis of these tumours is closely related to local recurrence, histological type, size and radical surgery. A low-grade malignancy tumor, small sized and completely resected leads to a good prognosis. Radiation therapy and chemotherapy do not seem to have a strong influence on the prognosis. An aggressive surgical approach is the first choice for the treatment of such tumors. The resection of adjacent organs may be required for radical surgery.

[Medullary thyroid carcinoma: a study about 28 operated patients]. / Carcinoma midollare della tiroide: studio su 28 casi operati.

In this study on 28 operated patients, the Authors show that total thyroidectomy with elective central neck dissection and ipsilateral neck dissection is the most appropriate surgical treatment for medullary thyroid carcinoma. Pathologic study on lymph nodes removed in central and in latero-cervical compartments showed malignancy respectively in 75% and in 70% of the cases. However the role of elective ipsilateral lateral neck dissection remains controversial.

[Urological sequelae of female genital mutilation]. / Urologische Folgen der weiblichen Beschneidung.

Female genital mutilation (FGM) is the ritualistic removal of parts of the external female genitalia. The extent of mutilation as well as the age at which it is performed vary depending on ethnicity. We recognise four forms of mutilation based on the extent of tissue resection, ranging from clitridectomy to resection of the entire soft tissue of the external genitalia. The vast majority of the estimated 200 million mutilated women live in Africa and the Middle and Far East. Due to migration an estimated 150,000 mutilated women live in Germany to date. In approximately 30% of cases FGM leads to urologic complications and the chances of urologists facing these complications is rapidly increasing. The focus lies on chronic infections, pain syndromes and obstructed micturition with all associated late complications. This situation is made more complex if any neighbouring organs were damaged during the mutilation.

Multiprobe fluorescence in situ hybridisation: prognostic perspectives in superficial bladder cancer.

AIM: To establish independent prognostic factors on a chromosomal basis in superficial bladder cancer, using a multicolour fluorescence in situ hybridisation (FISH) probe mix. PATIENTS AND METHODS: In 2002, voided urine from 75 consecutive patients (mean age 71.7, range 52-93) years under follow-up for superficial urothelial cancer was studied prospectively. The patients were observed for a mean (standard deviation (SD)) period of 39.3 (6.8) months (range 27-58) until July 2005. A multicolour FISH on liquid-based voided urinary cytology was carried out on all patients. Univariate analysis, using a log rank test, was used to determine the prognostic relevance of a low-risk pattern and a high-risk pattern. Progression-free survival time was calculated from the date of first diagnosis to first recurrence or progression according to the Kaplan-Meier product-limit method. RESULTS: One patient was lost to follow-up. 27 of the 74 remaining (36.8%) patients showed recurrent disease. In 9 (33.3%) patients with a low-risk pattern disease recurred after a mean (SD) observation time of 29.7 (1.9) months (range 8.3-52.3, median 30.8 (12.4)). 18 (66.7%) patients with a high-risk pattern developed recurrence within a mean (SD) of 17.6 (2.0) months (range 4-38.8, median 16.7 (11.6)). The Kaplan-Meier curve for progression-free survival showed marked differences between the low-risk and the high-risk groups. CONCLUSION: Patients with a high-risk chromosomal pattern have a markedly shorter disease-free survival time and higher progression rate than patients with a low-risk pattern. High-risk patients can therefore be treated more aggressively to prevent tumour spreading.

What to Do, and What Not to Do, When Diagnosing and Treating Breakthrough Cancer Pain (BTcP): Expert Opinion.

Clinical management of breakthrough cancer pain (BTcP) is still not satisfactory despite the availability of effective pharmacological agents. This is in part linked to the lack of clarity regarding certain essential aspects of BTcP, including terminology, definition, epidemiology and assessment. Other barriers to effective management include a widespread prejudice among doctors and patients concerning the use of opioids, and inadequate assessment of pain severity, resulting in the prescription of ineffective drugs or doses. This review presents an overview of the appropriate and inappropriate actions to take in the diagnosis and treatment of BTcP, as determined by a panel of experts in the field. The ultimate aim is to provide a practical contribution to the unresolved issues in the management of BTcP. Five 'things to do' and five 'things not to do' in the diagnosis and treatment of BTcP are proposed, and evidence supporting said recommendations are described. It is the duty of all healthcare workers involved in managing cancer patients to be mindful of the possibility of BTcP occurrence and not to underestimate its severity. It is vital that all the necessary steps are carried out to establish an accurate and timely diagnosis, principally by establishing effective communication with the patient, the main information source. It is crucial that BTcP is treated with an effective pharmacological regimen and drug(s), dose and administration route prescribed are designed to suit the particular type of pain and importantly the individual needs of the patient.

Identification, cloning and characterisation of a novel copper-metallothionein in tetrahymena pigmentosa. Sequencing of cDNA and expression.

The protist Tetrahymena pigmentosa accumulates large amounts of metal ions, particularly cadmium and copper. This capability is linked to the induction of metallothioneins (MTs), cysteine-rich metal-binding proteins found in protists, plants and animals. The present study focuses on a novel inducible MT-isoform isolated from Tetrahymena after exposure to a non-toxic dose of copper. The cDNA sequence was determined utilising the partial peptide sequence of purified protein. The Cu-MT cDNA encodes 96 amino acids containing 28 cysteine residues (29%) arranged in motifs characteristic of the metal-binding regions of vertebrate and invertebrate MTs. Both the amino acid and nucleotide sequences differ, not only from other animal MTs, but also from the previously characterised Tetrahymena Cd-MT. Both MTs contain the structural pattern GTXXXCKCXXCKC, which may be proposed as a conservative sequence of Tetrahymena MTs. Cu-dependent regulation of MT expression was also investigated by measuring MT-mRNA and MT levels. MT synthesis occurs very quickly and MT contents increase with Cu accumulation. The induction of Cu-MT mRNA is very rapid, with no observable lag period, and is characterised by transient fluctuation, similar to that described for Cd-MT mRNA. The data reported here indicate that, also in the unicellular organism Tetrahymena, two very different MT isoforms, which perform different biological functions, are expressed according to the inducing metal, Cu or Cd.

A large Calabrian kindred segregating frontotemporal dementia.

Frontotemporal dementia (FTD) displays significant neuropathological and genetic heterogeneity among and within affected families. An early diagnosis is often difficult because cognitive symptoms are manifest only at a late stage of the disease. We have been studying a large pedigree segregating frontotemporal dementia (FTD) to which belong 34 identified affected persons, 11 of whom were personally examined. The kindred has been genealogically reconstructed; all FTD patients have been linked to the same ancestors who lived in the early 18(th) century (11 generations before the present one). Autosomal dominant transmission was evident. Clinical features were uniform within the kindred and met the Lund-Manchester criteria. Personality changes with absence of insight, lack of empathy and of social awareness manifested up to 5 years before medical advice was sought. Loss of fluency was the earliest neuropsychological sign, in the absence of memory, orientation and praxis deficits, which evolved late, together with hyperorality. Akinesia was observed early, rigidity appeared late, tremor was absent. Two patients showed myoclonus late in their evolution. No ALS signs were observed in this kindred. Mutations of the MAPt gene, coding for the Tau protein, were not detected in affected family members. Linkage studies excluded chromosomes 3 and 9 and gave indeterminate results that were model dependent for chromosome 17.

Multicenter trial comparing tramadol and morphine for pain after abdominal surgery.

Seventy patients (40 male, 30 female), mean (SD) age 60.8 +/- 13.7 years were treated with parenteral morphine (10 mg/1 ml ampul) or tramadol (100 mg/2 ml ampul) to verify their analgesic effects in pain following abdominal surgery. The multicenter trial followed an open, controlled experimental design between patients, randomized within the centers. The drugs were given by intramuscular injection, as requested by patients, starting in the postoperative period when pain was more than 70 mm, assessed on a visual analog scale. Patients were allowed up to six ampuls of tramadol or morphine in the 24-h trial but in the first 4 h, if they asked for supplementary analgesic, only diclofenac (75 mg in a 3-ml ampul) was allowed. Both test drugs gave rapid and constant pain relief. After the first dose, pain intensity was reduced 36.2% with tramadol, and 51% with morphine; the pain-free interval was similar for both treatments. The quality of sleep and the number of hours of sleep the night after surgery were similar for both groups. Tramadol was tolerated better, giving rise to no untoward reactions; with morphine there was one case of mild respiratory depression. In abdominal surgery, therefore, tramadol given by intramuscular injection has postoperative analgesic activity similar to morphine, but is better tolerated.