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Medical examination of Israeli 17-year-olds before military service as a national resource for health information.

At age 17 years Israelis undergo medical examination for the purpose of health classification for military service. The potential use of this extensive data collection system for epidemiologic studies is illustrated for selected conditions. Trends in diagnosed disorders over a 25-year period are exemplified in the changing prevalence of tuberculosis, bronchial asthma, diabetes, epilepsy and heart defects. Within birth cohorts, cross-sectional analyses of height, body mass, blood pressure and disorders--such as bronchial asthma, allergic rhinitis, diabetes, psychiatric diagnoses and such genetic conditions as familial Mediterranean fever--point to clear ethnic differences. Educational level is strongly associated with measures of health status. Potential uses of this resource include: detecting groups in need of preventive, curative and rehabilitative care, assessing changing needs and priorities of health care, evaluation of intervention programs and health services provided in childhood, a wide spectrum of etiologic studies including assessment of health effects of social change, follow-up studies including the natural history of disorders, and developing data systems such as national registries of rare or important conditions. Issues relating to data reliability and validity, changing disease classification and nonexamination of groups exempted from military service limit interpretation of findings and restrict uses of this resource. Emphasis on standardization of data collection and diagnostic criteria, quality assurance and improved data management will be necessary.

Adolescent↗

hypeR-GEM: connecting metabolite signatures to enzyme-coding genes via genome-scale metabolic models.

MOTIVATION: Enrichment analysis is a cornerstone of "omics" data interpretation, enabling researchers to connect analysis results to biological processes and generate testable hypotheses. Enrichment analysis in metabolomics poses distinct challenges for interpretation and multi-omics integration due to the lack of well-defined and consistent connections to well-curated gene-centered biological knowledge repositories. To address these challenges, we developed hypeR-GEM, a methodology and associated R package that adapts gene set enrichment analysis to metabolomics. hypeR-GEM leverages genome-scale metabolic models (GEMs) to infer reaction-based links between metabolites and enzyme-coding genes, enabling the mapping of metabolite signatures to gene signatures and their subsequent annotation via gene set enrichment analysis. RESULTS: We validated hypeR-GEM using paired metabolomics-proteomics and metabolomics-transcriptomics datasets by assessing whether genes mapped from metabolites significantly overlapped with differentially expressed proteins or transcripts. We further evaluated whether pathways enriched via hypeR-GEM-mapped genes corresponded to those derived from paired proteomic or transcriptomic data. In most datasets analyzed, both the predicted enzyme-coding genes and the associated enriched pathways showed significant concordance with independently derived omics signatures, supporting the utility and robustness of hypeR-GEM. Finally, we applied hypeR-GEM to the analysis of age-associated metabolic signatures from the New England Centenarian Study. The results revealed consistent enrichment of lipid-related pathways, aligning with the well-established role of lipid metabolism in aging, and highlighted additional pathways not captured in the metabolites' annotation, demonstrating hypeR-GEM's practical utility in a real-world use case. AVAILABILITY AND IMPLEMENTATION: The hypeR-GEM R package, documentation, and workflow examples are freely available at https://github.com/montilab/hypeR-GEM and archived at https://doi.org/10.5281/zenodo.20586748.

Metabolomics↗

A clinicopathologic and prognostic study of epithelial tumors of the renal pelvis.

The aim of the present investigation was to assess the prognosis of epithelial pelvic tumors and evaluate from multivariate analysis the influence of different morphologic and clinical factors on the prognosis. The basic data are derived from the Swedish national series of patients with epithelial renal pelvic tumors diagnosed by histologic examination during 1962-63. Ninety-four of the 102 patients studied had a urothelial pelvic tumor and eight had an epidermoid carcinoma. The corrected 5-year survival rate was 51% in the curatively operated series, 60% among the males and 33% among the females. Infiltration depth was found to be of significant importance for the 5-year survival and thus a strong predictor for prognosis. Furthermore, each tumor grade and tumor structure exerts some influence on the prognosis independent of the infiltration depth. Nine patients had verified, and 16 patients had suspected phenacetin abuse and/or renal papillary necrosis. The survival rate was low and the relative frequency of females was high in this group of patients. These data may indicate a poorer prognosis in patients with phenacetin abuse, and may explain the sex difference in 5-year survival. Thirty-eight per cent of the patients with urothelial tumors of the renal pelvis had a synchronous or asynchronous tumor elsewhere in the urinary tract. The high frequency of local recurrence as well as the high frequency of infiltrating tumors and multiple tumors indicate the necessity for a more extensive operation such as perifascial nephrectomy with total ureterectomy including a cuff of the bladder.

Adult↗

Treatment of stage I carcinoma of the anterior floor of the mouth.

A retrospective study of 27 patients treated for stage I squamous cell carcinoma of the floor of the mouth was performed to assess the effectiveness of therapy. Of these patients, 23 (85%) underwent surgical therapy. Four patients (15%) were treated with radiation therapy alone, and three (11%) underwent combined surgery and radiation treatment. Initial treatment failed in seven patients (26%), and further therapy was curative in only four of seven. This small study suggests that stage I floor-of-the-mouth squamous cell carcinoma is not an easy lesion to cure. Other studies support these data. A three-dimensional monobloc resection with a 2-cm margin, including resection of the submandibular glands, is advocated. Toluidine blue O mucosal staining and Mohs' chemosurgery are helpful adjuncts in determining the tumor margins.

Adult↗

[Does selective intervention affect other areas of primary health care? Evaluation of a vaccination program in Somali refugee camps].

The discussion, whether poor countries of the third world should work towards comprehensive or selective primary health care has been based on political and economical arguments. The present study examines how far a selective strategy with one target problem influences other areas of primary health care. The study is based on the experiences with a vaccination program in the Somalia refugee camps. The program produced for the first time a reliable census of the refugee population which produced much smaller figures than had been reported previously. Data on the nutritional status of all children under 5 was collected at the vaccination places. These data provided a new basis for the general food distribution. At the same time the data served to evaluate the supplementary feeding program for vulnerable groups. The study also showed that general food distribution was more important for the reduction of malnutrition than other interventions, such as curative health care, community water supplies, sanitation, supplementary feeding program and vaccination program. Furthermore it illustrates the conditions in which sectorial actions can become a useful asset to community oriented health programmes.

Child, Preschool↗

Laparoscopic-assisted resection of colorectal carcinoma: five-year audit.

INTRODUCTION: The place of laparoscopic-assisted colectomy for colorectal carcinoma is controversial. This study reviewed a consecutive series of patients who underwent laparoscopic-assisted resection of colorectal carcinoma in the past five years. METHODS: Two hundred seventeen laparoscopic-assisted resections of colorectal carcinoma were attempted starting in April 1992. Initially, we only selected patients with metastatic disease or patients who were older than 65 years. Subsequently, both palliative and curative resections were attempted in patients with a suitable tumor, with no age limitation. Thus, all suitable patients were randomly assigned to received either laparoscopic-assisted or conventional open surgery. RESULTS: Data collection was completed in 201 patients. In 22 patients open surgery was performed after a diagnostic laparoscopy. In the remaining 179 patients (90 males) in whom laparoscopic dissection was actually performed, the mean follow-up was 19.8 months, and the mean age was 66.3 years. The procedures performed included right hemicolectomy or extended right hemicolectomy (30 patients), transverse colectomy (2 patients), left hemicolectomy (3 patients), sigmoidectomy (48 patients), anterior resection (59 patients), and abdominoperineal resection (37 patients). Thirty-two (17.7 percent) procedures were converted to open surgery. The mean operation time was 203 minutes. The median blood loss was negligible, and the median requirement of transfusion was zero. The median number of postoperative parenteral analgesic injections was three. The median time to resume diet and hospital discharge were four and six days, respectively. The operative mortality was 1.7 percent. The survival rates at four years were 100, 88.3, and 64.5 percent for patients with Dukes A, B, and C disease, respectively. There was only one (0.65 percent) port-site recurrence. CONCLUSION: Laparoscopic-assisted resection of colorectal carcinoma was technically feasible and safe. It allowed early postoperative recovery with satisfactory long-term survival. This is at the expense of a long operation. Its benefits over the conventional open technique await the results of the randomized trials.

Aged↗

Selection and delineation of lymph node target volume for lung cancer conformal radiotherapy. Proposal for standardizing terminology based on surgical experience.

PURPOSE: To select and delineate the target volumes for definitive or postoperative radiotherapy for lung cancer. METHODS AND MATERIALS: The lymphatics of the lung and the dissemination of tumor cells to the intra- and extrathoracic lymph nodes are described. The incidence of involvement of the different lymph node sites in the chest is analyzed. The involvement of the contralateral hilar and/or supraclavicular lymph nodes and the consequences for target volume selection for curative radiotherapy are discussed. CT-based nodal classification and distribution of lymph nodes in the chest in CT-axial slices are presented. The sentinel node concept (SNC) and the preliminary data available for lung cancer are described. RESULTS: A critical review of the current TNM classification for lung cancer and the implications for target volume selection is given. The individual target volume selection and delineation have to be based on clinical and pathological data from large surgical. studies and upon the individual pathological and diagnostic patient data. The selection and delineation of the clinical target volumes for definitive and for postoperative radiotherapy, dependent on the lymph node involvement, are presented. CONCLUSIONS: Criteria for the selection and delineation of the clinical target volumes for definitive and for postoperative conformal radiotherapy in axial CT slices under consideration of site, size and stage of the lung cancer are described. Recommendations for target volume selection for definitive or postoperative radiotherapy are presented.

Humans↗

[Submucosal infiltration and local recurrence in pT1 low-risk rectal cancer treated by transanal endoscopic microsurgery].

BACKGROUND: The association between submucosal infiltration and tumor recurrence was analyzed by long-term follow-up of patients with pT1 "low risk" rectal carcinoma. PATIENTS AND METHODS: Forty patients with pT1 rectal cancer of the upper and middle rectum were treated by transanal endoscopic microsurgery. All carcinomas fulfilled the low-risk criteria, and were completely resected. No further treatment was carried out. Follow-up data were available for all 40 patients, with a median follow-up of 5.4 years. RESULTS: Two patients (5.0%) developed local tumor recurrence after 14 and 18 months, respectively, and had curative rectal resection after neoadjuvant radiochemotherapy. In the histology of the initial specimens, both patients had deep submucosal infiltration (sm3). Another patient, primarily sm2 without local recurrence, developed a metachronous singular liver metastasis which was curatively resected. The risk of developing a recurrent tumor was significant for sm3 carcinomas (sm1+sm2 vs sm3, P=0.046). CONCLUSION: Transanal endoscopic microsurgery is an excellent method of treating low-risk pT1 carcinomas of the rectum. Deep submucosal infiltration (sm3) seems to be an additional high-risk factor for developing local recurrence.

Adult↗

Conventional megavoltage radiotherapy in the management of malignant epithelial tumours of the parotid gland.

This is an evaluation of definitive conventional megavoltage radiotherapy in a consecutive series of 35 patients presenting malignant epithelial tumours of the parotid gland. In this series, the 5-year actuarial locoregional control rate was 41% with a 5-year crude survival rate of 36%. The results are analyzed according to tumour presentation and tumour doses. Six of 15 patients with tumours larger than 6 cm have had a lasting locoregional control. During the same period 43 other patients received radiotherapy as a post-operative modality. Results obtained in this group confirm the previously published data. While recent studies tend to demonstrate the specific efficacy of high LET radiation in the management of locally advanced salivary gland tumours, radical conventional radiotherapy can still be employed with a curative intent when neutron facilities are not available.

Adult↗

Radical prostatectomy as primary treatment modality for locally advanced prostate cancer: a prospective analysis.

OBJECTIVES: Locally advanced prostate cancer is frequently treated with radiotherapy and androgen deprivation because of the greater rate of extracapsular disease and the concern that radical prostatectomy (RP) may not be curative in most cases. A case for surgery for locally advanced disease may be made on the basis of a lower rate of local recurrence compared with radiotherapy in our comparative database, data suggesting a survival advantage with pelvic lymph node dissection in those with positive nodes, and the observation of improved survival in those with metastatic disease treated by RP compared with radiotherapy. We report on the feasibility of RP as a primary treatment modality for locally advanced disease. METHODS: A total of 281 consecutive patients treated by RP between January 1998 and June 2004 were reviewed. Locally advanced disease was defined as clinical Stage T2b or worse, prostate-specific antigen level greater than 15 ng/mL, and/or a Gleason score of 8 or greater. Data on the pathologic characteristics, operative complications, and follow-up were obtained from a prospectively maintained institutional review board-approved database. RESULTS: Pathologic examination demonstrated organ-confined disease in 11.7%, extracapsular extension in 56.9%, seminal vesicle involvement in 23.1%, and positive lymph nodes in 8.9%. The overall complication rate was 9.7% compared with 6.9% for all patients undergoing RP. At a mean follow-up of 34 months (range 1 to 78), 198 (70.4%) of 281 patients had an undetectable prostate-specific antigen level at the last follow-up examination. CONCLUSIONS: RP for locally advanced prostate cancer is feasible, with acute morbidity similar to RP for more localized disease. Furthermore, RP results in short-term biochemical recurrence-free survival similar to that of combined radiotherapy and androgen ablation.

Feasibility Studies↗

[From familial Mediterranean fever to amyloidosis].

The progression of familial Mediterranean fever is marked by the recurrence, at varying intervals, of acute flares that regress spontaneously. Prognosis, which depends on the occurrence of amyloidosis, has been transformed by colchicine treatment. Incidence of amyloidosis is higher in certain ethnic groups (Jews from North Africa, Turks) and depends on by the specific MEFV mutation. Amyloid is composed of clusters of protein strands identical to the AA protein of secondary amyloidosis and infiltrates the walls of all arterioles except those of the central nervous system. The earliest and most consistent localization is in the kidney, where it develops over several years and in 4 stages--preclinical (latency), proteinuric, nephrotic and uremic--before concluding in end-state renal failure. Before the advent of colchicine, dialysis and transplantation, only renal amyloidosis caused clinical manifestations and lethal complications; any amyloidosis at any other sites remained latent. Prolonged survival with hemodialysis and kidney transplantation now leaves time for manifestation of these other localizations, such as infiltration into the intestines causing malabsorption, or potentially lethal cardiac lesions. Treatment of familial Mediterranean fever is based on the continuous administration of colchicine, which at the average dose of 1 to 2 mg per day can prevent flares or at least reduce their frequency or intensity. Systematic use of colchicine also prevents the onset of amyloidosis, even in the rare cases where it cannot prevent flares. These data fully justify the systematic use of colchicine for continuous prophylactic treatment from diagnosis and even after kidney transplantation, to prevent recurrence of the grafted kidney or extension to other organs. The curative efficacy of colchicine on flares is debatable, although several studies report positive results against progression of early amyloidosis.

Acute Disease↗

The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia.

Unrelated donor (UD) transplantation is the only potentially curative therapy for many leukaemia patients but is associated with a high mortality and morbidity. We sought to identify factors that could be optimised to improve outcome following UD transplantation in adults. Data was retrospectively analysed on 55 patients sequentially receiving UD transplants for CML or acute leukaemia (AL), all of whom received serotherapy for the prevention of GVHD and rejection. All patients received standard conditioning regimens. The first 28 patients transplanted also received combined pre- and post-transplant serotherapy with Campath 1G (days -5 to +5) and standard dose CsA plus MTX as GVHD prophylaxis (protocol 1). The subsequent 27 patients received a 5-day course of pre-transplant serotherapy alone either with ATG (CML patients) or Campath 1G (AL patients) on days -5 to -1 inclusive, with high-dose CSA plus MTX (protocol 2). The incidence of acute GVHD was low with no patient receiving either protocol developing > grade 2 disease. The use of protocol 2 and the administration of a bone marrow cell dose above the median (2.17 x 10(8)/kg) were the most important factors predicting engraftment (P = 0.03 and P = 0.001, respectively) but this only remained significant for cell dose in multivariate analysis (P = 0.03). Overall survival for the group was 45% at 3 years and was influenced by both age (P = 0.02) and disease status at transplantation (P = 0.001). Receiving a cell dose above the median was also associated with a trend towards better survival (P = 0.08), due primarily to a reduction in the TRM to 8.2% compared with 54.5% in those receiving a lower cell dose (P = 0.002). We conclude that pre-transplant serotherapy alone is highly effective at preventing acute GVHD following UD BMT and that additional post-transplant serotherapy does not confer any benefit. Furthermore, a high marrow cell dose infused has a major effect in reducing transplant related mortality following UD BMT.

Adolescent↗

Long-term results of wide surgical excision in 106 patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (acne inversa) is a chronic recurrent disorder characterized by abscessing inflammation, fistulating sinus tracts, and scarring. Predilection sites are the intertriginal regions. The severe course of the disease demands an early and curative treatment. OBJECTIVE: The aim of this study was to review the effect of radical surgical excision concerning cure rate and potential complications within a large group of patients. METHODS: We analyzed data for 106 patients suffering from hidradenitis suppurativa treated during the period 1980-1998. The mean duration of the disease was 7 years. In about 90% of the cases, two or more sites were affected. Inguinal (70.8%) and axillary regions (61.3%) were most commonly involved. All patients were treated by radical wide excision using intraoperative marking of sinus tracts with methylviolet solution. The method of reconstruction depended on the size and location of the defect. Median postoperative follow-up time was 36 months. RESULTS: The overall complication rate was 17.8%. Most of these were minor complications such as suture dehiscence, postoperative bleeding, and hematoma. Wound infection occurred in only 3.7% of patients. The rate of recurrence within the operated fields was 2.5%. There was no relation between the surgical method of reconstruction and the rate of recurrence. Recurrence was related to the severity of the disorder. CONCLUSION: Our results confirm early radical excision as the treatment of choice for hidradenitis suppurativa. Using intraoperative color-marking of sinus tracts, the recurrence rate is minimal. The method of reconstruction has no influence on recurrence and should be chosen with respect to the size and location of the excised area.

Adult↗

[New methods in the radiotherapy of bronchial carcinoma. Endobronchial small-field irradiation using the iridium-129 high-dose afterloading technic in combination with the neodymium-YAG laser].

106 patients with inoperable malignant tumours constricting the central bronchial tree underwent endobronchial small-field radiotherapy with iridium-192 at high dose between June 1983 and September 1985. Treatment was performed using the computer-guided after-loading technique and a flexible bronchoscope under local anaesthesia. In complete occlusion of a bronchus by the tumour, a neodymium YAG-laser was applied (57 patients) to allow insertion of the after-loading probe. Endoscopy showed tumour regression in 75% of the patients, accompanied by clinical improvement. Pulmonary function tests, arterial blood gas analyses and pulmonary perfusion scans yielded a highly significant improvement of data after treatment. The procedure also proved effective upon exhaustion of external radiation. Apart from its positive palliation, endobronchial small-field radiotherapy using high doses of iridium-192 also has a curative effect, thus opening up a new approach to the therapy of advanced bronchial carcinoma.

Aged↗

Literature mining and database annotation of protein phosphorylation using a rule-based system.

MOTIVATION: A large volume of experimental data on protein phosphorylation is buried in the fast-growing PubMed literature. While of great value, such information is limited in databases owing to the laborious process of literature-based curation. Computational literature mining holds promise to facilitate database curation. RESULTS: A rule-based system, RLIMS-P (Rule-based LIterature Mining System for Protein Phosphorylation), was used to extract protein phosphorylation information from MEDLINE abstracts. An annotation-tagged literature corpus developed at PIR was used to evaluate the system for finding phosphorylation papers and extracting phosphorylation objects (kinases, substrates and sites) from abstracts. RLIMS-P achieved a precision and recall of 91.4 and 96.4% for paper retrieval, and of 97.9 and 88.0% for extraction of substrates and sites. Coupling the high recall for paper retrieval and high precision for information extraction, RLIMS-P facilitates literature mining and database annotation of protein phosphorylation.

Abstracting and Indexing↗

Spinal abscess of Haemophilus paraphrophilus. A case report.

STUDY DESIGN: A case of paraspinal abscess formation from Haemophilus paraphrophilus is presented. OBJECTIVES: To describe a case of paraspinal abscess formation from H. paraphrophilus, a fastidious commensal organism of the mouth and pharynx. A precise bacteriologic identification can be difficult; techniques for such identification are discussed. SUMMARY OF BACKGROUND DATA: Spinal abscess caused by H. paraphrophilus is unusual and can be very difficult to diagnose. METHODS: The etiology, clinical presentation, technical examinations, and treatment are reviewed. RESULTS: Prolonged antibiotic treatment was curative, although surgery was considered. CONCLUSIONS: Bacteriologic diagnoses in these rare infections are difficult. Antibiotic therapy was curative in the patient described.

Abscess↗

Glioma therapy in adults.

BACKGROUND: Gliomas are the most common type of primary brain tumor. Nearly two-thirds of gliomas are highly malignant lesions that account for a disproportionate share of brain tumor-related morbidity and mortality. Despite recent advances, two-year survival for glioblastoma with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. REVIEW SUMMARY: Surgery and radiation have been the mainstays of therapy for most glioma patients, but temozolomide chemotherapy has recently been proven to prolong overall survival in patients with glioblastoma. Intriguing data suggests that activity of O6-methylguanine-DNA methyltransferase (MGMT), in tumor cells may predict responsiveness to temozolomide and other alkylating agents. Novel treatment approaches, especially targeted molecular therapies against critical components of glioma signaling pathways, appear promising in preliminary studies. Optimal treatment for patients with low-grade gliomas has yet to be determined. Advances in oligodendroglioma biology have identified loss of chromosomes 1p and 19q as powerful indicators of a favorable prognosis. These same changes may predict response to chemotherapy. CONCLUSIONS: Though the prognosis for many patients with gliomas is poor, the last decade produced a number of important advances, some of which have translated directly into survival benefits. Rapid progress in the field of glioma molecular biology continues to identify therapeutic targets and provide hope for the future of this challenging disease.

Adult↗

Prostate-specific antigen decline: a major prognostic factor for prostate cancer treated with radiation therapy.

PURPOSE: To assess the prognostic significance of serum prostate-specific antigen (PSA) in the monitoring of patients with localized prostate cancer treated with primary radiation therapy, we analyzed the data from 179 patients treated at our institution between 1987 and 1990. PATIENTS AND METHODS: One hundred seventy-nine previously untreated patients received radiation at 69 Gy to the prostate with curative intent for prostate adenocarcinoma. The median follow-up duration is now 41 months. PSA levels were measured before radiotherapy and then evaluated periodically. RESULTS: Baseline levels were greater than 4 ng/mL in 83% of cases and were significantly correlated with clinical tumor stage (P = .002). Six months after completion of therapy, PSA values had returned to normal in 53% of the patients with initially elevated values. At the time of analysis, 32 patients have relapsed, including three of 30 patients (10%) with normal initial and 6-month values, five of 79 patients (6%) with initially elevated but normal 6-month values, and 24 of 69 patients (35%) with persistently elevated PSA levels at 6 months. Actuarial 4-year relapse-free survival was significantly correlated with initial and 6-month PSA values (84% in patients with normal 6-month values v 60% in patients with persistently elevated levels). Furthermore, when the relative decline between initial and 6-month PSA values exceeded 50%, the crude rate of recurrence was 14% as opposed to 34% when it failed to exceed 50%. The 4-year relapse-free survival rates were 77% and 59%, respectively (P = .008). By multivariate analysis restricted to the patients with elevated baseline PSA levels, the rate of decline of PSA values reached the highest prognostic significance (P < .0001). Age at diagnosis, clinical tumor stage, and Gleason score only reached statistical significance in univariate analysis. CONCLUSION: PSA values are of major prognostic significance in assessing the 4-year results of radical radiation therapy for localized prostate cancer. The rate of decline of PSA values is the strongest predictor of outcome and might help to identify a subset of patients with poorer prognosis who may benefit from early hormonal therapy.

Actuarial Analysis↗