Cross-tissue immune cell analysis reveals tissue-specific features in humans.

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

The impact of regional 99mTc-HMPAO single-photon-emission computed tomography (SPECT) imaging on clinician diagnostic confidence in a mixed cognitive impairment sample.

AIM: To assess the clinical impact of regional cerebral blood flow (rCBF) single-photon-emission computed tomography (SPECT) imaging on diagnosis and clinician diagnostic confidence in a cohort of individuals with cognitive impairment. MATERIALS AND METHODS: Forty-one clinicians who referred 79 patients for a [99mTc]-hexamethylpropyleneamine oxime (HMPAO) SPECT for cognitive complaints completed a two-part questionnaire to determine the diagnosis and diagnostic confidence (using a 0-100 visual analogue scale [VAS]) before and after imaging. SPECT images were analysed using statistical parametric mapping and interpreted semi-quantitatively. Clinicians were also asked directly for their opinion on whether the imaging contributed to their diagnostic process. RESULTS: Diagnosis changed after imaging in 44% of cases, and confidence was significantly improved (VAS score change= +26.3±22.2) after imaging in cases where the pre-imaging confidence was low (p<0.001). Clinician confidence was not significantly different (VAS score change=-6.6±25.5) after imaging when pre-imaging confidence was moderate to high. Interestingly, a proportion of clinicians with the highest confidence levels became less certain about their diagnosis following imaging results. When asked directly, 96% of clinicians stated that the imaging contributed to the diagnostic process. CONCLUSIONS: In a mixed clinical cognitive impairment cohort, perfusion SPECT is valued by referring clinicians and contributes to diagnostic decision making. Imaging is of particular value when diagnostic confidence is low prior to imaging.

Assessment of behavioral determinants influencing success of supervised exercise therapy in patients with intermittent claudication: A cross sectional survey.

BACKGROUND: Supervised exercise therapy is the first step in treatment of intermittent claudication. However, adherence to supervised exercise therapy is low. Limited access and reimbursement issues are known reasons, though lack of motivation is often leading. Behavioral determinants influencing motivation and thus adherence to supervised exercise therapy remain to be investigated. In this study we sought to determine which behavioral determinants would be of influence on the long-term adherence of supervised exercise therapy. METHODS: 200 patients, newly diagnosed with peripheral arterial disease Rutherford classification II-III, were sent a questionnaire to assess motivation and behavior with regard to supervised exercise therapy. The questionnaire was constructed using the I-CHANGE model for explaining motivational and behavioral change. Baseline characteristics were acquired from medical records. Alpha Cronbach's was calculated to test reliability of the questionnaire. RESULTS: 108 (54%) patients returned their questionnaire. A total of 79% patients followed supervised exercise therapy. Patients who increased their walking distance after supervised exercise therapy have significantly greater knowledge (p = 0.05), positive attitude (p = 0.03) and lower negative attitude (p = 0.01). Patients with a higher self-efficacy remained significantly more active after participating in supervised exercise therapy (p = 0.05). CONCLUSION: Increasing the determinants knowledge, attitude and self-efficacy will improve adherence to supervised exercise therapy and result in delayed claudication onset time.

Epidemiology, management and survival outcomes of primary cutaneous melanoma: a ten-year overview.

BACKGROUND: Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained. METHODS: Files of patients treated for primary cutaneous melanoma (n = 686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed. Relevant patient features, tumour characteristics, and (surgical) outcomes were evaluated. RESULTS: The majority of all the patients presented thin tumours (59.1% stage 1A/in situ melanoma). Men showed more ulceration (17.7% vs. 8.4%, p < .01) and a significantly higher Breslow thickness than women (1.2 mm vs. 0.9 mm, p < .01). 14.6% (40/273) underwent sentinel lymph node biopsy (SLNB); 10/40 (25%) showed nodal metastasis, 50 patients (7.3%) developed distant metastases (M: 10.6%, F: 5%, p < .01). One-, 5- and 10- year disease specific survival rates were 96%, 86% and 84%, respectively. Median survival for stage 4 MM was 3 months. Extensive surgery was uncommon (n = 3). CONCLUSIONS: Patients generally presented with thin melanomas. Lymph node disease and distant metastases remained infrequently observed during following years, and general 1- and 5-year overall disease-specific survival rates exceeded 85%. Small numbers of rescue surgery and palliative medical treatment warrant further centralisation and investigation.

The Actim Partus test to predict pre-term birth in asymptomatic high-risk women.

The Actim Partus test has been shown to be a useful predictor of pre-term birth in symptomatic women, but limited research has been carried out in high-risk asymptomatic women. This is a pilot study to evaluate the use of this test as a direct comparator with the fetal fibronectin test. All asymptomatic high-risk women attending a pre-term surveillance clinic over a 9-month period, took an Actim Partus and fetal fibronectin test, between 23(+0)-24(+6) weeks' gestation. A total of 45 women were eligible. The positive and negative predictive values of the Actim Partus test for delivery at ≤ 37 weeks' gestation were 0% and 70%, respectively, compared with the fetal fibronectin test, with values of 67% and 79%, respectively. It was concluded that the Actim Partus test did not perform well as a predictor of pre-term birth in high-risk asymptomatic women.

A review of the obstetric management of patients with epidermolysis bullosa.

Epidermolysis bullosa (EB) is a rare inherited skin condition characterized by the development of blisters after minor mechanical friction or trauma. There are few reported pregnancies in the literature in these women. We describe a pregnancy we recently managed. The collated series of pregnancies show that there are no additional antenatal or postnatal problems and that the skin itself does not worsen during pregnancy. Vaginal delivery is most favourable, but if a caesarean section is required, regional anaesthesia should be attempted. A multidisciplinary team should be active throughout the pregnancy of these women and a well-documented labour plan should be made in advance.

True to oneself? Broad and narrow ideas on authenticity in the enhancement debate.

Our knowledge of the human brain and the influence of pharmacological substances on human mental functioning is expanding. This creates new possibilities to enhance personality and character traits. Psychopharmacological enhancers, as well as other enhancement technologies, raise moral questions concerning the boundary between clinical therapy and enhancement, risks and safety, coercion and justice. Other moral questions include the meaning and value of identity and authenticity, the role of happiness for a good life, or the perceived threats to humanity. Identity and authenticity are central in the debate on psychopharmacological enhancers. In this paper, I first describe the concerns at issue here as extensively propounded by Carl Elliott. Next, I address David DeGrazia's theory, which holds that there are no fundamental identity-related and authenticity-related arguments against enhancement technologies. I argue, however, that DeGrazia's line of reasoning does not succeed in settling these concerns. His conception of identity does not seem able to account for the importance we attach to personal identity in cases where personal identity is changed through enhancement technology. Moreover, his conception of authenticity does not explain the reason why we find inauthentic values objectionable. A broader approach to authenticity can make sense of concerns about changes in personal identity by means of enhancement technologies.

A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer's disease.

OBJECTIVE: To determine the effects of cholinergic treatment on the muscarinic receptor in patients with Alzheimer's disease. METHODS: 12 patients with mild to moderate Alzheimer's disease and six controls were studied. The patients underwent ADAS-COG psychometric assessment and SPECT brain imaging with (123)I quinuclidinyl benzilate (QNB), to demonstrate the postsynaptic muscarinic M1 receptor, before being randomised in a double blind study to receive either an acetylcholinesterase inhibitor (donepezil) or placebo for four months. Following this, the ADAS-COG and the (123)I-QNB receptor scan were repeated. The controls were imaged on one occasion only. All image analyses were undertaken using SPM99. RESULTS: (123)I-QNB imaging showed a significant relation between baseline psychometric impairment and deficits on scanning. Both placebo and actively treated groups had reductions in (123)I-QNB uptake. Greater reductions in receptor binding were demonstrated in the placebo group than in those receiving active treatment. Intraindividual reproducibility of the (123)I-QNB imaging technique appeared highly robust. CONCLUSIONS: The results suggest that (123)I-QNB uptake is better preserved in Alzheimer's disease patients on cholinergic treatment than on placebo. Cholinergic treatment may play a neuroprotective role. Sequential (123)I-QNB imaging seems to be a powerful tool in monitoring the response of these receptors to disease modifying treatments.

A comparison of planar scintigraphy and SPECT measurement of total lung deposition of inhaled aerosol.

Planar gamma camera imaging of inhaled aerosol deposition is extensively used to assess the total deposition in the lung. However, validation of the measurements is not straightforward, as gold standard measurements of lung activity against which to compare are not readily available. Quantitative SPECT imaging provides an alternative method for comparison. Four different methods for planar image quantification are compared. Two attenuation correction techniques, thickness measurement and transmission measurement, have been combined with two scatter correction techniques, reduced attenuation coefficient and line-source scatter function convolution subtraction. Each technique has been applied to 10 studies of aerosol deposition of a fine aerosol (mass median aerodynamic diameter 1.8 microm) and 10 studies using a coarse aerosol (mass median aerodynamic diameter 6.5 microm). The total activity in the right lung for each measurement has been compared to the value determined from SPECT imaging on the same subjects. When the thickness measurement and transmission techniques were applied with scatter compensation using a reduced attenuation coefficient, activity was systematically overestimated by 5% in both cases. The corresponding random errors (coefficient of variation) were 8.6% and 6.6%. Separate scatter correction reduced these systemic errors significantly to -1.5% and 2.7%, respectively. The random errors were not affected. All techniques provided assessment of total lung activity with an accuracy and precision that differed by less than 10% compared to the SPECT values. Planar gamma camera imaging provides a good method of assessing total lung deposition of inhaled aerosol.

Alzheimer's disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia.

OBJECTIVE: To compare the HMPAO SPECT cerebral perfusion patterns in early and late onset Alzheimer's disease. METHODS: Twenty patients with early onset disease (<65 years) and 44 patients with late onset disease (>65 years) were studied. All patients fulfilled NINCDS-ADRDA clinical criteria and had details of disease severity and length of history at the time of imaging. Technetium-99m HMPAO SPECT brain scans were acquired on a multi-detector gammacamera and analysed visually and with statistical parametric mapping (SPM99). RESULTS: Patients with early onset disease had significantly greater posterior cortical association area involvement whereas those with late onset disease had significantly greater medial temporal hypoperfusion. These findings were unchanged after controlling for disease severity and length of illness. DISCUSSION: These functional imaging findings of the differences between early and late onset Alzheimer's disease are supported by published findings that include histopathological and clinical evidence; namely late onset patients tend to present with the characteristic involvement of the medial temporal lobes producing marked memory loss whereas early onset patients present with predominant posterior cortical association area involvement. These age related findings should be borne in mind when clinically diagnosing, and interpreting functional brain imaging studies in, patients with suspected Alzheimer's disease.

Measurement of cerebral perfusion volume and 99mTc-HMPAO uptake using SPECT in controls and patients with Alzheimer's disease.

Methods for quantifying the changes in brain function observed in single photon emission computed tomography (SPECT) using hexamethylenepropylene amine oxime (HMPAO) for patients with Alzheimer's disease have the potential of improving the diagnostic accuracy of the procedure and its ability to monitor response to treatment. The absolute percentage uptake of HMPAO and the cerebral perfusion volume (CPV) of the brain were assessed using SPECT in 26 patients with mild to moderate Alzheimer's disease (AD) and 24 control subjects. A subset of 15 control subjects, which was age-matched to the AD patients, was selected to allow fair statistical comparison of parameters between groups. The percentage of brain volume with reduced perfusion (R) and a volume loss index (VLI), given by /CPV, were also calculated. Eight of the control subjects were studied on a second occasion after a mean period of 6 months. There was no significant difference in percentage uptake between controls and AD patients, the mean value being 5.8%. Cerebral perfusion volume in controls was found to depend on sex (mean value in males and females being 1327 ml and 1222 ml, respectively) and on age. The volume loss index corrected for age and sex provided good discrimination between controls and AD subjects giving a sensitivity and specificity of 81% and 96%, respectively. The repeatability coefficient, the 95% confidence limit for the difference between repeat measurements, on controls was 67 ml (5%). The measurement of cerebral perfusion volume and related indices may be of value in identifying patients with early Alzheimer's disease and in following their response to treatment.

Use of polypropylene prostheses for strangulated inguinal and incisional hernias.

We used monofilament polypropylene prostheses in 20 emergency operations for strangulated hernias. Sixteen of the operated patients had groin hernias (five of them recurrent), two had incisional and one had a Spigel's type hernia. Intestinal resection was performed because of bowel wall necrosis in one of the patients. During the postoperative period, we observed only one minor complication (a seroma formation). During the follow-up, no recurrence was observed. In our opinion, the use of monofilament polypropylene mesh in emergency hernia operations is safe, simple and effective.

Growth hormone in short children: beyond medicine?

UNLABELLED: The indications for growth hormone (GH) treatment in non-GH-deficient short children are in debate, with some arguing that this treatment does not belong solely in the medical domain. We describe three different approaches to the issue, and argue that neither a disease-oriented nor client-oriented approach is sufficient. Both lead to withdrawal of medical interventions or to an undesirable application. CONCLUSION: An approach focusing on suffering as an indication for treatment of short stature is the most appropriate. The challenge is to develop proper tools by which to evaluate suffering and the efficacy of GH treatment in these children in order to relieve or prevent suffering.

[Changing views in the 20-th century regarding acute appendicitis]. / Jak w XX wieku zmienialy sie poglady na ostre zapalenie wyrostka robaczkowego.

In 1886 Reginald H. Fitz described the pathology of acute appendicitis suggested surgical treatment. 10 years later, during VII-th the Congress of Polish Surgeons in Cracow, Maksymilian Rutkowski was the first in Poland to present the results of that kind of treatment. Operations performed for that frequently, not seldom fatal disease-were not accepted from the beginning through the world. In Poland as well at the beginning of the 20-th century, indications for appendectomy were discussed. In 1920 previous views regarding the necessity for surgical treatment in acute and chronic cases changed. These changes were supported by the observation that in some cases involving pain in the right, pain remains even after appendectomy were the vermiform appendix was found to be unaffected and it was also found that adhesion of ileus can be a dangerous late complications. It might appear that today's knowledge relating to this disease is fully established. Close observation found successful results as shown by in decreasing mortality. Within 100 years in the Massachusetts General Hospital mortality feel from 40% to 0.8% to Fitzs between patients who had undergone appendectomy accompany high percentage failed preoperative diagnosis. Today at the beginning of the 21-st century with the availability of MRI, CT, videosurgery and organs transplant it is difficult to imagine that the cause of such a common disease is still unknown and that in almost 1/4 of the operations performed on patients do not confirm the preoperative diagnosis.

A technique for manual definition of an irregular volume of interest in single photon emission computed tomography.

A technique is described for manually outlining a volume of interest (VOI) in a three-dimensional SPECT dataset. Regions of interest (ROIs) are drawn on three orthogonal maximum intensity projections. Image masks based on these ROIs are backprojected through the image volume and the resultant 3D dataset is segmented to produce the VOI. The technique has been successfully applied in the exclusion of unwanted areas of activity adjacent to the brain when segmenting the organ in SPECT imaging using 99mTc HMPAO. An example of its use for segmentation in tumour imaging is also presented. The technique is of value for applications involving semi-automatic VOI definition in SPECT.

[Colonization with group B streptococcus in pregnant women taken into the care of unit K and hospitalized in the department of obstetric pathology]. / Kolonizacja paciorkowcami grupy B u ciezarnych, objetych opieka poradni K i hospitalizowanych w oddziale patologii ciazy.

Colonization with group B streptococci (GBS) in 714 pregnant women was investigated. Among 232 were hospitalised in department of pathological pregnancy and 512 were under ambulatory control. In 13.4% of hospitalised patients and 2.8% healthy pregnant women the colonization of vagina or throat with GBS was stated. The greatest percentage of vagina colonization was found in patients hospitalised in connection with gestosis or because of abortions, premature delivery and inanimate fetus. No correlation was found between range of GBS colonization and trimester of pregnancy. Almost all GBS strains proved to be susceptible for commonly used antibiotics but resistant to biseptol (88.2%). Patients of hospitalised group were more often colonized not only GBS but also other potentially pathogenic microorganisms.

Home detoxification from alcohol: its safety and efficacy in comparison with inpatient care.

The safety and short-term effectiveness of home detoxification (HD) was investigated by contrasting rates of treatment completion and of complications of 41 service users with those of a retrospectively matched inpatient comparison group. The latter comprised patients of a detoxification unit matched for age, sex and degree of alcohol dependence with HD subjects. HD subjects had severe problems with alcohol--they averaged 28.7 on the SADQ, 4.6 serious alcohol-related problems in the previous 2 months, a GGT of 123.8 and 174.6 reported units of alcohol consumed in the week before treatment. A high follow-up rate was achieved for both HD subjects and their relatives; there was close agreement between clients' reports, carers' reports and breathalyser readings with regard to further alcohol consumption. The HD subjects were visited at home an average of 6.9 times over 6.15 days. Chlormethiazole was prescribed in 36 cases at an average maximum daily dose of 6.3 capsules--significantly fewer than for the inpatient group. Both rates of completion and complication were virtually identical in the 2 groups. It is concluded that these data suggest HD is equivalent in both its safety and immediate efficacy to more expensive inpatient care.