Maximizing the power of comparing single cases against a control sample: An argument,a program for making comparisons,and a worked example from the Pyramids and Palm Trees Test

Optic ataxia, a disorder of visually guided reaching, has been attributed to a failure in the transmission of visuospatial information to motor systems. This account fails to explain why many patients w ith optic ataxia misreach only when targets are presented in non-foveal vision, but not w hen targets are view ed directly. We present data from two patients with unusually severe optic ataxia that suggest an alternative account of this relatively com mon pattern of misreaching. DP is utterly unable to reach to targets unless he gazes directly at them. We provide evidence that he is unable to program reaches in appropriate shoulder and hand-centred spatio-motor coordinates, but instead reaches using oculocentric coding. The gaze (and visual attention) of AM is frequently “captured” by his own hand, and his attentional allocation is influenced by the location at which he performs a hand movement. This suggests that he programs eye movements within hand-centred spatial coordinate frames. Taken together, these data suggest that residual reaching in optic ataxia may be enabled by linkage of the systems coding the spatio-m otor actions of the eye and hand.     

Reemergence of yellow fever in West Africa: lessons from the past, advocacy for a control program

In French speaking West Africa, yellow fever vaccine became compulsory in 1941 for the entire African and European population. From 1941 to 1960, 146 million doses were distributed and the number of yellow fever cases declined sharply. No case was reported from 1954 to 1960. As a result of an interruption in systematic immunization after 1960, ten major epidemics broke out in West Africa between 1965 and 1995 (over 200,000 cases and 40,000 deaths). In 1967, the WHO programme for eradication of smallpox was initiated and it mobilized WHO's energy and finances. The expanded programme of immunization (EPI) was initiated in 1977 but it did not include the yellow fever vaccine. In 1978, Primary Health Care advocated an immunization strategy through fixed health facilities. In 1986, to amend this strategy, WHO recommended accelerating EPI progress and instituting National Immunization Days (NIDs). In 1990, a recommendation was made to include the yellow fever vaccine in the EPI. In 1997, the target of global poliomyelitis eradication by the year 2000 reinforced the NID programme and led to the use of mobile teams. At a time when a measles eradication programme is going to take over from the poliomyelitis programme, we must firmly advocate not omitting the yellow fever vaccine as was the case in 1977. Indeed, in yellow fever endemic areas, WHO recommends a simultaneous association of yellow fever and measles vaccines for nine month-old infants. This opportunity must be seized to initiate a yellow fever control programme.     

Development and performance of a sleep estimation algorithm using a single accelerometer placed on the thigh: an evaluation against polysomnography

Accelerometers placed on the thigh provide accurate measures of daily physical activity types, postures and sedentary behaviours, over 24 h and across consecutive days. However, the ability to estimate sleep duration or quality from thigh-worn accelerometers is uncertain and has not been evaluated in comparison with the ‘gold-standard’ measurement of sleep polysomnography. This study aimed to develop an algorithm for sleep estimation using the raw data from a thigh-worn accelerometer and to evaluate it in comparison with polysomnography. The algorithm was developed and optimised on a dataset consisting of 23 single-night polysomnography recordings, collected in a laboratory, from 15 asymptomatic adults. This optimised algorithm was then applied to a separate evaluation dataset, in which, 71 adult males (mean [SD] age 57 [11] years, height 181 [6] cm, weight 82 [13] kg) wore ambulatory polysomnography equipment and a thigh-worn accelerometer, simultaneously, whilst sleeping at home. Compared with polysomnography, the algorithm had a sensitivity of 0.84 and a specificity of 0.55 when estimating sleep periods. Sleep intervals were underestimated by 21 min (130 min, Limits of Agreement Range [LoAR]). Total sleep time was underestimated by 32 min (233 min LoAR). Our results evaluate the performance of a new algorithm for estimating sleep and outline the limitations. Based on these results, we conclude that a single device can provide estimates of the sleep interval and total sleep time with sufficient accuracy for the measurement of daily physical activity, sedentary behaviour, and sleep, on a group level in free-living settings.     

The perceived personal control (PPC) questionnaire: reliability and validity in a sample from the United Kingdom

Outcome measures are important assessment tools to evaluate clinical genetics services. Research suggests that perceived personal control (PPC) is an outcome valued by clinical genetics patients and clinicians. The PPC scale was developed in Hebrew to capture three dimensions of PPC: Cognitive, decisional, and behavioral control. This article reports on the first psychometric validation of the English translation of the PPC scale. Previous research has shown that the Hebrew and Dutch translations have good psychometric properties. However, the psychometric properties of the English translation have not been tested, and there is disagreement about the factor structure, with implications for how to score the measure. A total of 395 patients attending a clinical genetics appointment in the United Kingdom completed several measures at baseline, and a further 241 also completed measures at 2-4 weeks follow-up. The English language PPC has (a) a one-factor structure, (b) convergent validity with internal health locus of control (IHLC), satisfaction with life (SWL), depression, and authenticity, (c) high internal consistency (α?=?0.83), and (d) sensitivity to change, being able to identify moderate changes in PPC following clinic attendance (Cohen's d?=?0.40). These properties suggest the English language PPC measure is a useful tool for both clinical genetics research and for use as a Patient Reported Outcome Measure (PROM) in service evaluation.     

MLPA screening in the BRCA1 gene from 1,506 German hereditary breast cancer cases: novel deletions, frequent involvement of exon 17, and occurrence in single early-onset cases

We present a comprehensive analysis of 1,506 German families for large genomic rearrangements (LGRs) in the BRCA1 gene and of 450 families in the BRCA2 gene by the multiplex ligation-dependent probe amplification (MLPA) technique. A total of 32 pathogenic rearrangements in the BRCA1 gene were found, accounting for 1.6% of all mutations, but for 9.6% of all BRCA1 mutations identified in a total of 1,996 families, including 490 with small pathogenic BRCA1/2 mutations. Considering only high risk groups for hereditary breast/ovarian cancer, the prevalence of rearrangements is 2.1%. Interestingly, deletions involving exon 17 of the BRCA1 gene seem to be most frequent in Germany. Apart from recurrent aberrations like del ex17, dupl ex13, and del ex22, accounting for more than 50% of all BRCA1 LGRs, we could fully characterize 11 novel deletions. Moreover, one novel deletion involving exons 1-7 and one deletion affecting the entire BRCA1 gene were identified. All rearrangements were detected in families with: 1) at least two breast cancer cases prior to the age of 51 years; 2) breast and ovarian cancer cases; 3) ovarian cancer only families with at least two ovarian cancer cases; or 4) a single breast cancer case prior to the age of 36 years, while no mutations were detected in breast cancer only families with no or only one breast cancer case prior to the age of 51 years. Analysis for gross rearrangements in 412 high-risk individuals, revealed no event in the BRCA2 gene and only two known CHEK2 mutations. However, in an additional 38 high-risk families with cooccurrence of female breast/ovarian and male breast cancer, one rearrangement in the BRCA2 gene was found. In summary, we advise restricting BRCA1 MLPA screening to those subgroups that revealed LGRs and recommend BRCA2 MLPA screening only for families presenting with cooccurrence of female and male breast cancer.     

Light microscopic examination of scalp hair samples as an aid in the diagnosis of paediatric disorders: retrospective review of more than 300 cases from a single centre

BACKGROUND: Microscopic examination of scalp hair can provide important diagnostic information in a range of paediatric conditions. It is a non-invasive and cost effective investigation, which is not widely performed.AIMS: To examine retrospectively the value of hair examination by light microscopy, including polarising microscopy, in a specialist paediatric pathology department during a 15 year period (1989-2004) and to describe the morphological abnormalities indicative of specific paediatric conditions.METHODS: Three hundred and twenty two hair samples were submitted. Microscopic changes were analysed in the light of clinical information categorised as: (1) erythroderma, (2) neurological impairment, (3) immunological/haematological defect, (4) ectodermal dysplasia, (5) abnormal hair only, and (6) non-specific/absent clinical details.RESULTS: Abnormalities were evident in 49% of the samples. In 25%, the changes were compatible with specific diagnoses including Menkes disease, Netherton's syndrome, trichothiodystrophy, Griscelli and Chediak-Higashi syndromes, monilethrix, uncombable hair, and loose anagen syndromes. In respect of the clinical presentation groups noted above, diagnostic changes were seen in 41%, 32%, 33%, 0%, 29%, and 0%, respectively.CONCLUSIONS: Morphological light microscopic examination of scalp hair is an inexpensive, rapid, and non-invasive investigation, which can provide valuable diagnostic information in a range of paediatric conditions.     

Spectrum of neuroendocrine carcinomas of the uterine cervix,including histopathologic features,terminology, immunohistochemical profile,and clinical outcomes in a series of 50 cases from a single institution in India

Neuroendocrine carcinomas of the cervix are uncommon, characterized by a histomorphological spectrum and, mostly, an aggressive clinical course. There are only few substantial studies on such cases documented from our country, where cervical cancer is the second most common cancer affecting women. Herein, we present a spectrum of 50 cervical neuroendocrine carcinomas, including histopathologic features, terminology, immunohistochemical (IHC) profile, and clinical outcomes, wherever available. Fifty tumors occurred in women, with their age ranging from 23 to 69 years (mean, 48.6 years; median, 46.5 years). Stagewise, among 25 cases, most cases (6, or 24%) presented with stage IB. Average tumor size was 4.7 cm. On histopathologic review, 26 tumors (52%) were classified as small cell carcinoma (SMCA); 14 (28%), as large cell neuroendocrine carcinomas (LCNECs); 4 (8%), as SMCA + LCNECs; and 6, as mixed carcinomas, including 3 tumors (6%) with SMCA and squamous cell carcinoma (SCC), 2 tumors (4%) with LCNEC and adenocarcinoma, and a single tumor (2%) with LCNEC and squamous cell carcinoma. On IHC performed in 41 tumors (82%), 36 tumors (87.8%) were positive for at least a single neuroendocrine marker, and 22 (53.6%) expressed 2 neuroendocrine markers. Synaptophysin was positive in 22 (59.4%) of 37 tumors; chromogranin, in 27 (72.9%) of 37; CD56, in 8 (100%) of 8; and neuron-specific enolase in 7 (87.5%) of 8 tumors. Treatment wise, among 30 patients (60%), 6 (20%) underwent surgery, including Wertheim hysterectomy (5) and simple hysterectomy (1); 8 (26.6%) underwent surgery with adjuvant treatment, and 10 patients (33.3%) were offered chemotherapy and/or radiotherapy. On follow-up (27 patients, or 54%) over 1 to 144 months, 16 patients (59.2%) were alive with disease over median duration of 9 months, and 7 (25.9%) were free of disease over median duration of 26.5 months. There were 5 recorded deaths. Thirteen tumors (48.1%) metastasized, most commonly to liver. In cases with early stage disease and adjuvant treatment, including radiotherapy, LCNEC histology fared well. This study forms the largest documented series on cervical neuroendocrine carcinomas from our country, testifying the current histopathologic classification system. Although SMCAs can be recognized on morphology, LCNECs need to be correctly identified because these can be misdiagnosed in the absence of neuroendocrine markers. Synaptophysin, chromogranin, and CD56 are optimal IHC markers. Small cell carcinomas, pure or mixed, are relatively more aggressive. All these tumors are best treated with multimodal therapy. Early stage disease treated with radical surgery and adjuvant treatment seems to increase survival. Despite aggressive treatment, prognosis is dismal.     

Candida rugosa, an emerging fungal pathogen with resistance to azoles: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program

Candida rugosa is a fungus that appears to be emerging as a cause of infection in some geographic regions. We utilized the extensive database of the ARTEMIS DISK Antifungal Surveillance Program to describe the geographic and temporal trends in the isolation of C. rugosa from clinical specimens and the in vitro susceptibilities of 452 isolates to fluconazole and voriconazole. C. rugosa accounted for 0.4% of 134,715 isolates of Candida, and the frequency of isolation increased from 0.03% to 0.4% over the 6.5-year study period (1997 to 2003). C. rugosa was most common in the Latin American region (2.7% versus 0.1 to 0.4%). Decreased susceptibility to fluconazole (40.5% susceptible) was observed in all geographic regions; however, isolates from Europe and North America were much more susceptible (97 to 100%) to voriconazole than those from other geographic regions (55.8 to 58.8%). C. rugosa was most often isolated from blood and urine in patients hospitalized at the Medical and Surgical inpatient services. Notably, bloodstream isolates were the least susceptible to both fluconazole and voriconazole. C. rugosa should be considered, along with the established pathogens Candida krusei and Candida glabrata, as a species of Candida with reduced susceptibility to the azole antifungal agents.     

Paranasal sinus fungus ball: epidemiology, clinical features and diagnosis. A retrospective analysis of 173 cases from a single medical center in France, 1989-2002.

Over the last decade, we have observed a high frequency of Aspergillus rhinosinusitis in french medical centers. The epidemiological data, clinical presentations, radiology, mycology and histology results of 173 consecutive patients with paranasal sinus fungus balls who were admitted from 1989 to 2002 have been reviewed. The most common symptoms included purulent nasal discharges and nasal obstructions, with the maxillary sinus being the most common site of infection (152 cases, 87.8%). Computed tomography scans (CT scan) were performed in 92% (159/173) of the cases and heterogeneous opacities were observed in 132 patients (83%). Histology examinations were performed in all cases and proved positive in 162 patients. Fungi were recovered, mainly Aspergillus fumigatus, from samples of 50 patients, while specimens from the remaining 123 patients were negative. Since no specific clinical sign could be found, a diagnosis of fungus ball is frequently made after a long term symptomatic period. CT scan findings of metallic or calcified densities within an opacified sinus cavity are highly suggestive of a fungus ball, but mycological and histological studies are essential to confirm the diagnosis. Treatment consisted of functional endonasal sinus surgery and was successful in 172 out of 173 cases.     

Clinical,cytological, and pathological characteristics of metastatic renal cell carcinoma to the thyroid: A study of 14 cases at a Japanese single institution

A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.     

Candida guilliermondii, an opportunistic fungal pathogen with decreased susceptibility to fluconazole: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program

Although a rare cause of invasive candidiasis, Candida guilliermondii has been reported to exhibit decreased susceptibility to antifungal agents. Aside from case reports and small surveys, there is little information regarding the epidemiology and antifungal susceptibility profile of C. guilliermondii. We report geographic and temporal trends in the isolation and antifungal susceptibilities of 1,029 C. guilliermondii clinical isolates collected from 127 medical centers as part of the ARTEMIS DISK Antifungal Surveillance Program. In addition, we report the in vitro susceptibility of 132 bloodstream isolates of C. guilliermondii to caspofungin. C. guilliermondii represented 1.4% of the 75,761 isolates collected from 2001 to 2003 and was most common among isolates from Latin America (3.7% versus 0.6 to 1.1%). Decreased susceptibility to fluconazole was noted (75% susceptible; range, 68 to 77% across regions), and voriconazole was more active in vitro against C. guilliermondii than fluconazole (91% susceptible; range, 88 to 93% across regions). Fluconazole was least active against isolates from dermatology (58%) and surgical (69%) services and against isolates associated with skin and soft tissue infection (68%, compared to 85% susceptible for bloodstream isolates). There was no evidence of increasing azole resistance over time among C. guilliermondii isolates tested from 2001 to 2003. Of 132 bloodstream isolates of C. guilliermondii tested against caspofungin, most were inhibited by < or =2 microg/ml (96%; MIC50/MIC90, 0.5/1.0 microg/ml). C. guilliermondii, a species that exhibits reduced susceptibility to fluconazole, is the sixth most frequently isolated Candida species from this large survey and may be an emerging pathogen in Latin America.     

Angiofibroblastoma of the skin: a histological, immunohistochemical and ultrastructural report of two cases of an undescribed fibrous tumour

AIMS: The aim of this report is to present two cases of a distinct mesenchymal tumour of the skin that does not fit into one of the established entities. METHODS AND RESULTS: All cases of fibromyxoid tumours from the files of two dermatopathology centres, together with clinical data and histopathological records, were reviewed. Two cases of a lesion composed of stellate and spindle-shaped cells with the phenotype of fibroblasts embedded in a fibromyxoid to dense fibrous stroma were identified. Because of the large number of capillary-sized blood vessels and their peculiar distribution within the stroma, the name angiofibroblastoma of the skin is proposed for this peculiar neoplasm. In both cases, the tumour appeared as an indolent and slowly growing nodule on the extremities of adults. Immunohistochemical and, in one case, ultrastructural studies were performed. CONCLUSIONS: The lack of recurrences during a follow-up period of 9 and 3 years, respectively, after complete excision together with the bland histopathological appearance supports the benign character of the tumour.     

Serous papillary carcinoma of the endometrium arising from endometrial polyps: a clinical, histological, and immunohistochemical study of 13 cases

Serous papillary carcinoma is an aggressive tumor. Point mutations in the p53 suppressor gene might explain in part the rapid growth of this malignant tumor and its unfavorable outcome. The aims of this study were to evaluate the behavior of serous papillary carcinoma developing in endometrial polyps and to assess the p53 protein overexpression. Patients included in this study were treated in our institution between 1982 and 2003. All clinical and pathological materials were examined. A p53 protein immunohistochemical analysis was performed on paraffin-embedded tissues. Thirteen serous papillary carcinomas arising from benign polyps of the endometrium were identified. The patients' age averaged 73 years. All patients were treated surgically. After an average follow-up of 22 months, 54% of the patients were dead or alive with disease. Of 10 serous papillary carcinomas, 8 (80%) for which paraffin blocks were available overexpressed the p53 protein. A serous papillary carcinoma arising from benign polyps of the endometrium remains a malignant neoplasia with an unfavorable outcome even if the primary tumor is limited to the polyp. The high rate of protein p53 overexpression suggests that a p53 gene mutation occurs early in the disease and might explain the rapid growth of the tumor.     

The concept of bronchioloalveolar cell adenocarcinoma: redefinition,a critique of the 1999 WHO classification,and an ultrastructural analysis of 155 cases

Bronchioloalveolar cell adenocarcinoma (BACA) is bronchioloalveolar because (1) it arises in bronchioles and alveoli and (2) differentiates into bronchiolar and alveolar cells. Every entity possesses unique characteristics that separate it from other entities. The unique characteristic of BACA is its cell type. Lepidic growth is a clue to the cell type and, even though present in the vast majority, is not unique or absolutely essential. Because of the algebraic nature of concepts, the degree of differentiation, the extent of lepidic growth, and the degree of stromal desmoplasia cannot be used as definitional requirements. Likewise, in malignant tumors, absence of stromal invasion cannot be required. An epistemologically valid definition of BACA is proposed and a study of 155 cases defined this way and examined ultrastructurally is presented.