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Immunoarchitecture of the regenerating rat spleen: effects of partial splenectomy and heterotopic autotransplantation.

To investigate the microstructure of in situ (eutopic) and autotransplanted (ectopic) splenic remnants, adult Sprague-Dawley rats were studied 60 days after subtotal (approximately 80%) splenectomy, total splenectomy followed by single or multiple remnant intraperitoneal autotransplantation, or sham operation. Total nucleated cell counts were determined in excised splenic remnants, and immunohistochemical staining using monoclonal antibodies to rat B- and T-cell antigens was performed in serial tissue sections. Immunoarchitecture of eutopic remnants was indistinguishable from that of intact spleens and total nucleated cell counts remained proportional to weight. In contrast, ectopic remnants showed sparsity and abnormal mixing of B and T lymphocyte subpopulations with widespread loss of follicles and periarteriolar lymphoid sheaths in addition to lower density and marked reduction of total nucleated cells. These findings provide immunohistologic evidence that preservation of intact vasculature is critical to splenic architecture, which may account in part for the demonstrable functional inferiority of ectopic remnants.

Animals↗

Urethral disease and interventional cystourethrography.

The innovation of balloon dilatation of urethral stricture and prostatic hypertrophy is a major contribution to interventional radiology. The procedure involves minimal trauma, produces immediate relief of symptoms, and probably results in less frequent and less difficult redilatations. The sparsity of reports in the literature on this subject reflects the reluctance of urologists to refer patients for balloon dilatation of urethral strictures. Every effort must be made by the radiologist to impress the urologist with the value of this procedure, which would eliminate the production of false passages and likely reduce the recurrence rate. Initial results with this procedure are encouraging, but larger series are required and long-term follow-up is necessary for evaluation of cure rate, rate of recurrence, and possible complications.

Dilatation↗

In situ monitoring.

In situ monitoring has been increasingly accepted during the past five years. This approach has been applied to measurement of gas tensions such as pO2 and pCO2, to pH and ions, to the assessment of jaundice by measurement of bilirubin, and to analysis for 14CO2 after administration of labeled antipyrine and aminopyrine, for evaluation of hepatic damage. Various techniques have been developed for in situ monitoring: transcutaneous measurements, implantable sensors, ingestible radio-sensitive pills, and breath analysis. Here I review some of these approaches and their limitations. These limitations include the sparsity of circumstances under which the technique can be applied and the probable increase in health-care costs.

Bilirubin↗

Electron microscopy of clear cell thyroid carcinoma.

Three thyroid carcinomas composed in part or entirely of clear cells were studied by light and electron microscopy, and thyroglobulin content was determined by biochemical methods. Clear cells have been found in follicular and papillary thyroid carcinomas and in undifferentiated carcinomas. The clear (wasserhelle) appearance of the cytoplasm was due to the accumulation of glycogen. The major ultramicroscopic features of the clear cells were the presence of glycogen granules, the decreased amounts of rough endoplasmic reticulum, the increased amounts of free ribosomes arranged in polysomes, a hypertrophic Golgi apparatus, and a sparsity of dense bodies of lysosomal character. It is hypothesized that the intracellular accumulation of glycogen may be a result of a selective loss of the peptide portion of thyroglobulin, and may influence the degree of biochemical differentiation and the natural course of the tumors.

Adenocarcinoma↗

Fragile-X syndrome ascertained by the presence of macro-orchidism in a 5-month-old infant.

The fragile-X syndrome, an X-linked form of mental retardation, is estimated to affect one in every 1,000 to 2,000 live-born male infants. Most commonly, fragile-X syndrome has been detected only after patients clearly demonstrate developmental delay, and frequently detection occurs only if the family history is consistent with X-linked mental retardation. Macro-orchidism is a finding commonly associated with the fragile-X syndrome. It has been suggested that the sparsity of reports of macro-orchidism among prepubertal boys with the fragile-X syndrome might be due to lack of careful measurement of the tests rather than to initiation of the enlargement at puberty. A 5-month-old infant with fragile-X syndrome, ascertained through testicular enlargement noted by actual measurement of testicular size as part of his physical examination, is reported.

Adult↗

Regulation of fibrin deposition by malignant mesothelioma.

Malignant mesothelioma (MM) is a locally aggressive tumor that spreads by poorly understood mechanisms. Because neoplastic spread has been linked to altered fibrin turnover, we used immunohistochemistry of nine MM and three fibrous tumors of the pleura to confirm in vivo fibrin deposition and expression of selected coagulation and fibrinolytic reactants in MM. Tumor-associated fibrin was readily detectable at site of tissue invasion. Little fibrin was distributed within the tumor, but tissue factor and tissue factor pathway inhibitor, urokinase, urokinase receptor, and plasminogen activator inhibitors 1 and 2 were all detected in either epithelioid or sarcomatous areas of MM. We used the MS-1 human pleural mesothelioma cell line to determine how expression of these reactants is regulated. Fibrinolytic activity of MS-1 is mainly due to urokinase and is responsive to cytokine stimulation. Functional extrinsic activation and prothrombinase complexes assemble at the cell surface. MM express procoagulants as well as fibrinolytic reactants in vivo and in vitro that promote local fibrin formation and remodeling. Fibrin deposition occurs primarily at areas of tissue invasion and could promote local extension of this neoplasm. Sparsity of fibrin within the central portions of the tumor stroma suggests that local resorption of transitional fibrin occurs at sites of established MM.

Blood Coagulation↗

Aspects of hernia surgery in Wales.

The management of elective inguinal herniorrhaphy in Wales was assessed by means of a postal survey of consultant general surgeons. This included technique of repair, length of inpatient stay, follow-up, use of heparin thromboprophylaxis and advice regarding driving, strenuous activities and work. In all, 54 replies (77%) were received. The views of patients on their surgery was assessed by a questionnaire sent to 80 patients treated on a single surgical unit; 60 replies (75%) were received. Waiting times were relatively short among this group, 67.5% of patients being treated within 6 months of seeking medical advice; 16.25% suffered a complication. All wound infections occurred after discharge and 15% of patients had some groin discomfort 6 months after operation. Accuracy of clinical examination of 50 inguinal hernias by different grades of surgeon was assessed. Consultants were significantly more accurate when compared with house officers (P < 0.001). There is a wide range of repair techniques and postoperative advice practised by consultant general surgeons in Wales. Patients' main complaint was that of a sparsity of postoperative advice, although there also appears to be an appreciable postoperative morbidity. Clinical experience plays a significant role in assessment of the suitability of hernias for surgery.

Elective Surgical Procedures↗

Standardizing performance-based criteria for support surfaces.

Due to the sparsity of prospective, controlled, clinical studies on the efficacy of and the lack of standardized information about support surfaces, current literature does not clearly define how these surfaces address patient needs. Standardization would help healthcare professionals make better informed decisions about the use of support surfaces. Standardization would also help researchers design and implement controlled, clinical studies by defining characteristics of surface evaluation, making it possible to replicate research activities. The first step toward standardization is to develop a performance-based set of criteria for classifying these surfaces. With respect to the three purposes identified: comfort, postural control and pressure management, only parameters that can be measured noninvasively, have been considered. The nine parameters are life expectancy of the surface, skin moisture control, skin temperature control, redistribution of pressure, product service requirements, fail safety, infection, flammability, and patient/product friction. Specific guidelines for each of these nine parameters are discussed in depth. With testing and evaluation of support surfaces standardized, clinicians will be able to choose a surface to meet the needs of patients the same way they make other treatment decisions: based on outcomes and the results of controlled, clinical studies.

Beds↗

Secretory and ultrastructural responses of hyperfunctioning human parathyroid tissues to varying calcium concentration and vinblastine.

Parathyroid hormone (PTH) secretion from abnormal hyperfunctioning human parathyroid tissues was studied in vitro to determine whether abnormal tissues were responsive to changes in calcium concentration and what role their subcellular organelles played in secretion. Hyperfunctioning tissues from one patient with secondary parathyroid hyperplasia, four patients with parathyroid adenomas, and one patient with parathyroid carcinoma were incubated in media containing low calcium (0.75 mM), normal calcium (1.5 mM), high calcium (3.0 mM), or vinblastine (0.01 mM), a microtubular disrupter. Also, in order to correlate ultrastructural responses with PTH secretion, after incubation tissues of one adenoma were objectively quantitated by stereologic techniques. Low calcium consistently stimulated mean PTH secretion from hyperplastic and adenomatous tissue, but only during the 1st hour of secretion. Low calcium inconsistently stimulated carcinomatous tissue. High calcium suppressed mean PTH release from all tissues. Vinblastine did not consistently inhibit secretion from adenomatous or hyperplastic tissue. Ultrastructural analysis of adenomatous tissue showed a sparsity of granules (0.87 per cent of cellular volume) compared to previously studied bovine tissues. Low calcium significantly increased the volume fraction of pinocytotic vesicles to 300 per cent (p less than 0.01) and reduced the surface area of straight (inactive) membrane to 60 per cent (p less than 0.01) of the normal calcium control. Secretion granules, when present, were adjacent to submembrane vesicles. The number and structure of microtubules were not changed by low or high calcium or vinblastine. Our findings indicate that parathyroid adenomas and hyperplastic tissues can respond acutely to low calcium stimulation and high calcium suppression. However, the acute response to low calcium stimulation may not be sustained in some cases because of limited storage of hormone. The increase in pinocytosis in low calcium-stimulated tissue suggests a coupling of exocytosis with membrane endocytosis, possibly related to membrane recycling. Our findings with vinblastine suggest that microtubular integrity is not a prerequisite for basal PTH secretion in adenomatous tissue.

Adenoma↗

Orthodontic care provided by general practitioners and specialists in three Swedish counties with different orthodontic specialist resources.

Three counties in Sweden (A, G, and W) with free orthodontic care and different orthodontic resources and geographic structures were studied in 1987. Samples of totally 942 young adults (mean age 18.8 years, SD 0.44) were examined concerning malocclusions and all orthodontic treatment provided by general practitioners or by orthodontic specialists. The care in a rural area (county G) with abundant specialist resources was based on specialist treatments easy assessable to the patients and supplemented by treatments, mainly without appliances and provided by general practitioners. There was a generous attitude of consultation with specialists and of providing treatment. The sparsity of specialist resources had in an urban area (county A) resulted in a greater restriction on providing treatments. The treatments were performed in a higher age and were, to a greater extent, not completed by the age of 19, and a smaller percentage of individuals were treated than in the other two counties. The care in a large rural area (county W) with long distances to the only specialist clinic was based on treatments provided by general practitioners. In spite of the few specialist resources there was a generous attitude of providing treatments. Interceptive methods were used to a great extent, and later completed with appliance therapy. According to a treatment priority index 44% of the untreated individuals in the three counties had malocclusions and an objective treatment need, and there were no significant differences between the counties. Regardless of differences in specialist resources and structure of the free public orthodontic care, a substantial and equal proportion of the untreated individuals in the counties had malocclusions with treatment need, but they had no treatment desire.

Adolescent↗

Orthodontic treatment outcome in three Swedish counties with different orthodontic resources.

The orthodontic treatment outcomes of 350 19-year-old individuals in three Swedish counties (A, G, and W) with different orthodontic resources and geographic structures were analyzed. The aim was to evaluate the qualitative outcome of orthodontic treatment provided by general practitioners or specialists. In a small rural area (county G), with most specialist resources, the standard of the treatments was high in both specialist treated as well as in nonspecialist treated individuals. The possibilities for the specialists to supervise the nonspecialist care and to treat individuals in need of specialist treatment were good. In an urban area (county A), with less specialist resources (than county G), the standard of the treatments provided by the specialists was high, and higher than the untreated individuals in the same county. The standard of the treatments provided by general practitioners was, however, low. The lack of specialist resources had implied a greater restriction on starting treatments, and the treatments were performed in a higher age than in the other two counties. In a large rural area (county W), with the fewest specialist resources, the standard of the treatments was in general lower than in the other two counties and did not attain the standard of the untreated individuals in county W. Attempts to compensate for a sparsity of orthodontic specialists by an extended engagement of general practitioners resulted in a generous attitude of providing orthodontic treatments, and a lower standard of the treatments in general. The orthodontic treatments substantially improved the malocclusions, especially treatments provided by specialist. The standard of the treatments in the counties showed a good correlation with the available resources in terms of orthodontic specialists and the ability to supervise the treatments of general practitioners. The lack of sufficient supervision of non-specialist orthodontic treatment had negative influence on the quality.

Adult↗

Orthodontic care in Sweden. Outcome in three counties.

The purpose of this series of studies was to evaluate the outcome of orthodontic care in Sweden from the professional's and the patient's perspective. In addition, a model was devised for the priority-planning of orthodontic care and for evaluating the different factors influencing the decision for orthodontic treatment. The results may be summarized as follows: Treatment Decision. Treatment desire, followed by treatment need and treatment benefit were the most important factors to consider when deciding whether or not treatment should be carried out. Regardless of the differences in resources and the structure of the free public care, a substantial proportion of the untreated 19-year-olds had malocclusions with treatment need, but they had no desire for treatment. Most of the 27-year-old individuals were satisfied with their earlier treatment decision, regardless of whether they had undergone orthodontic treatment. Dental professionals were considered to have had the greatest influence on this decision, which means that desire for treatment may be guided by the orthodontist. Individuals with malocclusions and treatment need--but who had refused proposed orthodontic treatment--were in general more discontented with their dental arrangement than other respondents, and a majority of them regretted their decision. Greater information to these individuals would have been desirable. Resources and Treatments Provided by General Practitioners or by Specialists. The sparsity of specialist resources resulted in either a greater restriction on the number necessary treatments being initiated or a greater proportion of the treatment being provided by general practitioners. In the 3 counties analysed, the treatment standard correlated well with the available resources: the greater the number of orthodontic specialists and ability to supervise the work of general practitioners and taking care of patients in need of specialist treatment, the higher the standard of treatment. Individuals treated by specialists were more contented than individuals treated by general practitioners. The measures of treatment outcome in general yielded more favourable scores for specialist treatments than for treatments provided by general practitioners, despite the specialist treatments on the average being classified as more difficult than those provided by general practitioners. Perceived treatment difficulty. About one-fourth of all treatments were classified as easy, one-fourth as moderately difficult, and one-half as difficult. The perceived treatment difficulty was associated on a group basis with the pretreatment need. The treatment investment increased and the treatment outcome became less favourable with increasing perceived difficulty. The treatment outcome was least favourable in the group where no treatment was suggested. Almost every fourth treatment was successfully carried out by mere extraction therapy. Attitudes in 27-year-olds. Orthodontic treatment was considered important by three out of four individuals, even in cases where irregularities of the teeth were small. A majority of the individuals thought that they would have been able to wear visible braces if needed, even in adult age. Methodological aspects. Studies that have used different indices to evaluate treatment outcome can only be compared with great caution. Measures with wide bases for evaluation may be more valid than measures with narrow bases. To estimate treatment outcome in terms of decrease of treatment need, the Indication Index may be recommended.

Adolescent↗

Quantitative three-dimensional analysis of the catecholaminergic innervation of identified neurons in the macaque prefrontal cortex.

The present study provides a complete quantitative three-dimensional analysis of neurons in primate prefrontal cortex targeted by catecholaminergic axons. Individual pyramidal and nonpyramidal cells in fixed slices were filled with Lucifer yellow (LY) and recovered with anti-LY antibody combined with anti-tyrosine hydroxylase (TH) antisera to reveal catecholaminergic axons. The total number of TH contacts and TH apposition density (THAD) was obtained for pyramidal and nonpyramidal cells in different layers. Four TH contacts (two on spines and two on shafts) were selected for correlated electron microscopic examination and serially sectioned; all four were confirmed as membrane appositions. Quantitative analysis revealed 90 TH contacts per pyramidal neuron in layer III, with a density of 0.8 per 100 microm of dendritic length (i.e., averaging one contact per basal dendrite). Remarkably, pyramids of layers III, V, and VI had the same THAD values, with a highly regular distribution of TH terminals on their spiny dendritic trees. In contrast, TH contacts on nonpyramidal neurons in layer III were half as dense and, moreover, were distributed irregularly and showed large variation from cell to cell. Neurons in layers II and superficial III had the highest THAD, as compared with deeper layers (1.4 vs 0.7 per 100 micron of dendritic length for pyramids; 0.53 vs 0.4 for interneurons). The highly organized TH innervation of pyramidal neurons, with at least one contact on virtually every dendrite, indicates that catecholaminergic, presumably dopaminergic, terminals are placed strategically along the entire dendritic tree to modulate most, if not all, of the excitatory input of a neuron. At the same time, the sparsity of contacts per dendrite may explain cortical vulnerability in diseases involving dopamine.

Animals↗

[Treatment strategies in bite injuries].

Animal and human bites are a extremely common problem. Despite the prevalence of this problem, few systematic studies have been done. There is astounding sparsity of factual information in the literature to aid the therapeutic decision. Crucial questions regarding suturing, antibiotics, and other matters have been left unanswered. Therefore the literature was reviewed and therapeutic guidelines extracted.

Animals↗

Audit of populations in general practice: the creation of a national resource for the study of morbidity in Scottish general practice.

STUDY OBJECTIVE: To create a national data resource for studying morbidity in Scottish general practice, complementary to existing information systems and available for management and research purposes at national and local levels. DESIGN: The Department of General Practice, University of Aberdeen has worked since 1988 to collect and analyse computerised information at practice, regional, and national levels by distribution of a floppy disk-based software program, which extracts a predetermined dataset from each general practice computer system. SETTING: Almost 100% of patients in Scotland are registered with a general practitioner. Scotland has a national computer system, General Practice Administration System for Scotland (GPASS), used by over 75% of all Scottish practices. Escalating costs of health care and demographic changes in the national population emphasise the monetary value of the gatekeeper role of general medical practice. General practitioners' increasing involvement in the provision and purchasing of care has raised the importance of the management of populations as well as the care of individual patients. PATIENTS: Collection of major morbidity and prescribing data from up to 2.4 million patients, approximately half the population of Scotland, takes place biannually. A subset of practices (population 282,700 patients; 52 practices) are continuously collecting doctor/patient contact information (symptoms or diagnoses). MAIN RESULTS: The data collected provide information at the level of the individual patient. Morbidity, prescribing, screening, and administrative data can be linked by patient, date or postcode. The sample population studied is representative by age, sex, deprivation, and sparsity (using the postcode) of the national population. Large sub-populations of patients satisfying a selected criteria can be extracted for further study of needs assessment or of epidemiological research. CONCLUSIONS: The gatekeeping role of Scottish general practice and the predominance of GPASS favours standardisation of methods of data capture and the construction of large regional, national, and Continuous Morbidity databases. Analysis by geographical, demographic, and temporal distributions allows the changing patterns of illness and provision of health care to be studied in substantial detail to the benefit of patients, doctors, and the national health service.

Adolescent↗

Meta-analysis models with group structure for pleiotropy detection at gene and variant level using summary statistics from multiple datasets.

Genome-wide association studies (GWASs) have highlighted the importance of pleiotropy in human diseases, where one gene can impact 2 or more unrelated traits. Examining shared genetic risk factors across multiple diseases can enhance our understanding of these conditions by pinpointing new genes and biological pathways involved. Furthermore, with an increasing wealth of GWAS summary statistics available to the scientific community, leveraging these findings across multiple phenotypes could unveil novel pleiotropic associations. Existing selection methods examine pleiotropic associations one by one at a scale of either the genetic variant or the gene, and thus cannot consider all the genetic information at the same time. To address this limitation, we propose a new approach called MPSG (Meta-analysis model adapted for Pleiotropy Selection with Group structure). This method performs a penalized multivariate meta-analysis method adapted for pleiotropy and takes into account the group structure information nested in the data to select relevant variants and genes (or pathways) from all the genetic information. To do so, we implemented an alternating direction method of multipliers algorithm. We compared the performance of the method with other benchmark meta-analysis approaches such as GCPBayes, PLACO, and ASSET by considering as inputs different kinds of summary statistics. We provide an application of our method to the identification of potential pleiotropic genes between breast and thyroid cancers.

Humans↗