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Biomedical subjects

D Freedman

Publications and source records attributed to D Freedman.

At least 19 recordsLinked to original sources

Methodology for constructing guidance.

Although guidance exists for the use of many laboratory tests in a wide range of clinical situations, this guidance is spread among a range of literature sources, and is often directed at laboratory specialists rather than test users. Individual general practices display large variations in standardised test requesting, yet much of their testing activity involves a relatively small range of tests. This paper describes a methodological approach to review the available evidence and guidance and to extract relevant primary research work to examine a range of testing scenarios in general practice, with the aim of formulating guidance based on the best available evidence or consensus opinions.

Clinical Laboratory Techniques↗

Vulvar squamous cell carcinoma in young women: a clinicopathologic study of 21 cases.

OBJECTIVES: Invasive squamous cell carcinoma (ISCC) of the vulva occurs most often in older women and the clinical, pathological, and immunohistochemical features of vulvar ISCC in young women are poorly characterized. The aim of this study was to examine clinical and pathological features of ISCC presenting in women younger than 40 years of age. METHODS: Patients younger than 40 years of age who presented with vulvar ISCC were identified in the population-based tumor registry of the British Columbia Cancer Agency (BCCA) for the period 1970-1998. Clinical data and follow-up were obtained. The pathologic material was reviewed and morphologic features assessed. Immunohistochemical staining for MIB-1 and p53 proteins was done and the presence of human papillomavirus (HPV) DNA was assessed by microdissection/PCR. RESULTS: Twenty-one cases, accounting for 5% of all cases of vulvar ISCC encountered at BCCA during this period, were identified, with patient's ages ranging from 17 to 39 years (mean 33). The number of cases of vulvar ISCC in young women, as a percentage of all cases of vulvar ISCC, increased significantly over the study period. Lichen sclerosus was seen in 3 cases. Vulvar intraepithelial neoplasia (VIN) was present in 20 of 21 cases and was multifocal in 4 of them. VIN was subclassified as warty in 7 cases, mixed warty and basaloid in 6, basaloid in 4, and differentiated in 3. There was MIB-1 immunostaining throughout the full thickness of warty and basaloid VIN. Only basal cells stained for MIB-1 in differentiated VIN. Increased p53 expression was present in only 2 cases; both were differentiated-type VIN. HPV DNA was detected in 17 of 20 cases. The tumors were staged as follows: stage IA, 3 cases; stage IB, 13 cases; stage II, 3 cases; stage III, 2 cases. Depth of invasion ranged from <1 to 8.5 mm. The definitive surgical procedure was vulvectomy with lymph node dissection in 14 cases, wide local excision in 6, and excisional biopsy in 1. Clinical follow-up of 1 to 28 years (median, 5 years) showed that 5 patients had local recurrence and 2 died of disease. Of the 21 patients in this study, 1 had concurrent HIV infection and 1 patient with Crohn's disease was treated with corticosteroids; the remaining patients had no clinical evidence of depressed immune function. CONCLUSIONS: The incidence of vulvar ISCC in young women has increased over time; this increase cannot be accounted for by ISCC in immunocompromised patients. The overall disease outcome was excellent, with 2 of 21 patients dead of disease. Most tumors were associated with HPV, but cases of ISCC in the absence of HPV, and associated with differentiated VIN, were encountered. p53 staining of the basal layer can aid in recognition of differentiated VIN while MIB-1 staining within the upper layers of the squamous epithelium is consistently present in warty and basaloid VIN, but not in differentiated VIN.

Adolescent↗

Heteroleptic lanthanide compounds with chalcogenolate ligands: reduction of PhNNPh/PhEEPh (E = Se or Te) mixtures with Ln (Ln = Ho, Er, Tm, Yb). Thermolysis can give LnN or LnE.

Lanthanide metals reduce mixtures of azobenzene and PhEEPh (E = Se or Te) in pyridine to give the bimetallic compounds [(py)2Ln(EPh)(PhNNPh)]2 (E = Se, Ln = Ho (1), Er (2), Tm (3), Yb (4); E = Te, Ln = Ho (5), Er (6), Tm (7), Yb (8)). The structures of [(py)2Er(mu-eta 2-eta 2-PhNNPh)(SePh)](2).2py (2) and [(py)2Ho(mu-eta 2-eta 2-PhNNPh)(TePh)](2).2py (5) have been determined by low-temperature single-crystal X-ray diffraction, and the nearly identical unit cell volumes of the remaining compounds indicate they are most likely isomorphous to 2 or 5. In all compounds, the Ln(III) ions are bridged by a pair of mu-eta 2-eta 2-PhNNPh ligands that, from the N-N bond length, have clearly been reduced to dianions. Charge is balanced by the single terminal EPh ligand on each Ln, and the coordination sphere is saturated by two pyridine donors to give seven coordinate metal centers. Thermal decomposition of 5 gives HoTe, 8 gives a mixture of YbN and YbTe, and 1 does not give a crystalline solid-state product. Crystal data (Mo K alpha, 153(2) K) are as follows: 2, monoclinic group P2(1)/n, a = 11.864(3) A, b = 14.188(2) A, c = 17.624(2) A, beta = 91.62(2) degrees, V = 2965(1) A3, Z = 4; 5, triclinic space group P1, a = 10.349(2) A, b = 17.662(4) A, c = 17.730(8) A, alpha = 75.82(3) degrees, beta = 74.11(3) degrees, gamma = 89.45(2) degrees, V = 3016(2) A3, Z = 2.

Journal Article↗

Mortality among radiologic technologists in the united states (1926-1997). 2(nd) Follow up.

PURPOSE: To evaluate risk for all-cause and cause-specific mortality in a large, primarily female (73%) cohort of radiologic technologists.METHODS: The study consists of 145,915 radiation technologists, certified in the American Registry of Radiologic Technologists (1926-1982) and followed through 1997. Causes of death were obtained from death certificates or, more recently, through NDI Plus. Standardized Mortality Ratios (SMR) were computed and tests of homogeneity were performed to detect differences in mortality among causes. Poisson models were used to estimate risks using an internal comparison group.RESULTS: Significantly low SMRs were observed for all causes (0.76), all cancers (0.82), and diseases of circulatory system (0.69). Compared to U.S. women, the risk for breast cancer mortality bordered around unity (SMR 1.01, 95% CI 0.94-1.09). However, relative to all other cancers, breast cancer mortality was significantly increased (RSMR 1.24, p < 0.01). Elevated risk for breast cancer was associated with certification before 1940 (SMR 1.55, 95% CI 1.24-1.91), and duration of certification of 20-29 (SMR 1.21, 95% CI 1.06-1.37) and 30+ years (SMR 1.77, 95% CI 1.54-2.02). A 35% increase in leukemia risk was evident for women certified for a duration of 20-29 years and a 36% increase among women certified for 30+ years. Poisson analysis revealed a significant increase in breast cancer risk with increasing number of years certified among women first certified before 1940 (p < 0.001) and during 1940-49 (p = 0.05) compared to women first certified in 1950 or later.CONCLUSIONS: Preliminary findings of this study suggest increased breast cancer risk associated with occupational radiation exposures prior to 1950 and with long-term cumulative exposures. However, potential confounding by reproductive and other risk factors needs to be evaluated.

Journal Article↗

Trends in reproductive, smoking, and other chronic disease risk factors by birth cohort in a large occupational study.

PURPOSE: To illustrate the value of using large cohort studies to identify birth cohort trends in several chronic disease risk factors.METHODS: In collaboration with the American Registry of Radiologic Technologists (ARRT) and the University of Minnesota, the National Cancer Institute (NCI) initiated a cohort study of radiologic technologists who were certified by ARRT for at least two years between 1926 and 1982. Over 90,000 technologists (nearly four-fifths female) from all 50 states responded to a mailed questionnaire on reproductive, medical, work, and lifestyle factors. Ten, mostly five-year, birth cohorts, from before 1920 through 1960 and later, were evaluated.RESULTS: In this population, the mean height of both men and women generally rose in each subsequent birth cohort. The proportion of men who smoked before age 18 fell among those born since the late 1920s. In contrast, the proportion of women smoking before age 18 rose among those born since the early 1950s, reaching 14.2% among those born in 1960 and later. The mean age at menarche fell, until leveling off at 12.5, among those born after 1940. Recent birth cohorts (since 1950) show among the highest mean ages at birth of first child (>26 yeras), highest rates of nulliparity at age 25 (>/=63%), and lowest mean parity levels (</=1.7), compared with earlier birth cohorts. The proportion of women ever using oral contraceptives rose steadily by birth cohort, reaching 86 percent in the most recent birth cohort.CONCLUSIONS: Some of the trends observed may help explain historic chronic disease incidence patterns and predict future disease burdens.

Journal Article↗

Divalent samarium compounds with heavier chalcogenolate (EPh; E = Se, Te) ligands.

Crystalline coordination complexes of Sm(EPh)2 (E = Se, Te) are described. The selenolate compound Sm(SePh)2 is unstable in solution, but a divalent selenolate can be prepared and isolated when precisely 1 equiv of Zn(SePh)2 is present to form heterometallic [(THF)3Sm(mu 2-SePh)3Zn(mu 2-SePh)]n (1). This compound is a 1D coordination polymer with alternating Sm(II) and Zn(II) ions connected by an alternating (1,3) number of bridging selenolate ligands and three THF ligands bound to each Sm(II) ion. The tellurolate Sm(TePh)2 forms a stable pyridine coordination compound (py)5Sm(TePh)2 (2) that is isostructural with known Eu and Yb benzenetellurolates. Both compounds were characterized by conventional spectroscopic methods. Polymer 1 was characterized by low-temperature single-crystal X-ray diffraction, and the unit cell of the tellurolate was determined. Crystal data (Mo K alpha, 153(5) (K) are as follows. 1: monoclinic space group P21, a = 10.666(2) A, b = 16.270(3) A, c = 12.002(3) A, beta = 114.81(2) degrees, Z = 2.2: orthorhombic space group Pbca, with a = 13.865(3) A, b = 16.453(5) A, c = 31.952(7) A, Z = 8.

Journal Article↗

Precursors of lethal violence: a death row sample.

A qualitative methodology based on the standards of criminal defense investigation was used to analyze the social and family histories of 16 men sentenced to death in California. Using a multisource cross-validation methodology, we assessed patterns of impairment, injury and deficit at each of four ecological levels: family, individual, community and social institutions. Investigation documented consistent and pervasive patterns of serious impairment, injury and deficit across the cases and levels. The men share numerous risk factors and few resiliency factors associated with violence. We found family violence in all 16 cases, including severe physical and/or sexual abuse in 14 cases; individual impairments in 16, including 14 with post-traumatic stress disorder, 13 with severe depression and 12 with histories of traumatic brain injury; community isolation and violence in 12; and institutional failure in 15, including 13 cases of severe physical and/or sexual abuse while in foster care or under state youth authority jurisdiction. Appropriate interventions might have made a difference in reducing lethal violence and its precursor conditions.

Adolescent↗

Lack of prophylactic efficacy of an enteric-coated bovine hyperimmune milk product against enterotoxigenic Escherichia coli challenge administered during a standard meal.

Orally administered bovine immunoglobulins with specific activity against colonization factors of enterotoxigenic Escherichia coli (ETEC) could provide passive protection against ETEC challenge in volunteers. Twenty healthy adult volunteers ingested either a placebo or a partially enteric-coated preparation of bovine immunoglobulins with activity against the colonization factor antigens CFA/I, CS3, and CS6 and then were challenged with ETEC strain E24377A (CS1+, CS3+) administered with a standard meal. There was no difference in the incidence or severity of diarrhea among the 10 volunteers who received the bovine immunoglobulins and the 10 who received placebo. Either the specificity or titer of anti-colonization factor antibodies or the formulation of antibodies in this product was not adequate to provide passive protection against ETEC challenge.

Adult↗

Sexually transmitted diseases. Present problems-future prospects.

The tools of molecular biology have brought us to a new level of understanding of the epidemiology and pathophysiology of sexually transmitted diseases, which has been augmented and concentrated by the challenge of HIV/AIDS. We enter the next millennium with an unprecedented knowledge of these infections, but lacking the resources and drive to apply this broadly, especially where most needed in the areas of socioeconomic deprivation. We may develop cures or vaccines for complex viral infections, but for whom? Eventually, the knowledge will flow and disseminate, but will practice change?

Acquired Immunodeficiency Syndrome↗

Role of impression cytology during hypovitaminosis A.

AIMS: Evaluation of the morphological damage to the ocular surface of patients operated for biliopancreatic diversion for pathological obesity and the correlation of impression cytology with vitamin A plasma levels, adaptometry, and other general variables. METHODS: 48 patients (15 males, 33 females, age range 21-73) and 34 normal subjects were examined with fluorescein and rose bengal, a plasma dose of vitamin A, and adaptometry. The results of the various tests were subdivided into three levels (0 = normal, 1 = moderately altered, 2 = seriously altered). The impression cytology and adaptometry results were correlated with vitamin A levels and other patient data (age, nutritional condition, time since operation, percentage weight loss). All the examinations were repeated after intramuscular therapy with vitamin A. RESULTS: Corneoconjunctival alterations visible with fluorescein and rose bengal staining were present in 67.7% of cases, impression cytology alterations in 93.7%, adaptometric alterations in 82.2%; vitamin A plasma levels were below normal in 95.8% of cases. After the therapy with vitamin A a significant reduction was found for every examination. The correlation between impression cytology and adaptometry and vitamin A plasma levels and between corneoconjunctival alterations and vitamin A plasma levels was significant. There was no significant correlation between impression cytology and nutritional condition, age time since operation, and percentage weight loss. CONCLUSION: These results show impression cytology is a specific indicator for hypovitaminosis A because it is not influenced by other factors related to the general condition of the patient. Many patients with hypovitaminosis A not demonstrating ocular symptoms of changes visible with fluorescein and rose bengal showed alterations with impression cytology.

Adaptation, Ocular↗