The Voronoi theory of the normal liver lobular architecture and its applicability in hepatic zonation.

The precise characterization of the lobular architecture of the liver has been subject of investigation since the earliest historical publications, but an accurate model to describe the hepatic lobular microanatomy is yet to be proposed. Our aim was to evaluate whether Voronoi diagrams can be used to describe the classic liver lobular architecture. We examined the histology of normal porcine and human livers and analyzed the geometric relationships of various microanatomic structures utilizing digital tools. The Voronoi diagram model described the organization of the hepatic classic lobules with overall accuracy nearly 90% based on known histologic landmarks. We have also designed a Voronoi-based algorithm of hepatic zonation, which also showed an overall zonal accuracy of nearly 90%. Therefore, we have presented evidence that Voronoi diagrams represent the basis of the two-dimensional organization of the normal liver and that this concept may have wide applicability in liver pathology and research.

Surface color spectrophotometry in a murine model of steatosis: an accurate technique with potential applicability in liver procurement.

Steatosis is the most important prognostic histologic feature in the setting of liver procurement. The currently utilized diagnostic methods, including gross evaluation and frozen section examination, have important shortcomings. Novel techniques that offer advantages over the current tools could be of significant practical utility. The aim of this study is to evaluate the accuracy of surface color spectrophotometry in the quantitative assessment of steatosis in a murine model of fatty liver. C57BL/6 mice were divided into a control group receiving normal chow (n = 19), and two steatosis groups receiving high-fat diets for up to 20 weeks-mild steatosis (n = 10) and moderate-to-severe steatosis (n = 19). Mouse liver surfaces were scanned with a hand-held spectrophotometer (CM-600D; Konica-Minolta, Osaka, Japan). Spectral reflectance data and color space values (L*a*b*, XYZ, L*c*h*, RBG, and CMYK) were correlated with histopathologic steatosis evaluation by visual estimate, digital image analysis (DIA), as well as biochemical tissue triglyceride measurement. Spectral reflectance and most color space values were very strongly correlated with histologic assessment of total steatosis, with the best predictor being % reflectance at 700 nm (r = 0.91 [0.88-0.94] for visual assessment, r = 0.92 [0.88-0.95] for DIA of H&E slides, r = 0.92 [0.87-0.95] for DIA of oil-red-O stains, and r = 0.78 [0.63-0.87] for biochemical tissue triglyceride measurement, p < 0.0001 for all). Several spectrophotometric parameters were also independently predictive of large droplet steatosis. In conclusion, hepatic steatosis can accurately be assessed using a portable, commercially available hand-held spectrophotometer device. If similarly accurate in human livers, this technique could be utilized as a point-of-care tool for the quantitation of steatosis, which may be especially valuable in assessing livers during deceased donor organ procurement.

Idiopathic myointimal hyperplasia is a distinct cause of chronic colon ischaemia.

AIM: Colon ischaemia (CI) is most commonly an acute and reversible manifestation of a transient, non-occlusive decrease of blood flow in the colonic microvasculature. Irreversible complications are uncommon and the progression to chronic CI remains controversial. Our objective was to identify cases of chronic CI and assess for distinct clinicopathological features. METHOD: A retrospective review was performed of CI patients having symptom chronicity of ≥ 1 month and ischaemic histology at our institution from 1994 to 2015. Demographic, clinical, endoscopic, radiological, pathological and outcome variables were abstracted. Histological evaluation was performed by two gastrointestinal pathologists. RESULTS: Fifteen patients (n = 9; 67% men) with a median age of 65 years (range 22-88) were identified. The most common presenting symptoms were diarrhoea and abdominal pain (n = 6, 86%; n = 5, 71%, respectively). The typical endoscopic appearance was segmental ulceration of the sigmoid colon (n = 6, 75%). Vascular imaging showed patent mesenteric vessels in all patients. Histopathological evaluation revealed venous intimal hyperplasia consistent with idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) in eight patients; the remainder showed non-specific ulceration and fibrosis. Surgical resection was performed in seven IMHMV patients, resulting in symptom resolution. On re-review of pre-resection biopsies, all IMHMV patients had characteristic changes of hyperplastic, thick-walled, hyalinized vessels in the lamina propria. CONCLUSIONS: IMHMV is a unique histopathological entity causing chronic CI. The small vessel histological changes in IMHMV are distinctive in colonic resections and undetectable by routine vascular imaging. Preoperative diagnosis of IMHMV is possible with endoscopic biopsy and segmental colon resection is curative.

Adequacy of lymph node harvesting in colorectal cancer management: improving standards, ensuring quality.

OBJECTIVE: The aim of this study was to determine the adequacy of nodal sampling in resection specimens for colorectal carcinoma in a Jamaican population. METHODS: The pathology records of all patients who underwent operation for colorectal carcinoma at the University Hospital of the West Indies (UHWI) during the five-year period, 2003-2007, were reviewed. Pertinent clinical and pathologic data were obtained and analysed. RESULTS: One hundred and ninety-one patients were identified with M:F ratio of 1.1:1 and a mean age of 66 years. There were 119 (63%) left-sided lesions and 70 (37%) right-sided lesions. Stage T3N0 lesions were the most common and accounted for 41.1% of cases. The predominant histologic type was adenocarcinoma (99.5%) with the majority being moderately differentiated. The mean number of nodes sampled in node-negative cases was 13.8 +/- 9.75 nodes for right-sided lesions and 10.64 +/- 7.25 nodes for left-sided lesions (p = 0.05, CI 95%). The adequacy of nodal sampling was acceptable in cases of N0 right-sided carcinomas but was unsatisfactory in cases of N0 left-sided carcinomas. More importantly, however in two cases from the right and 10 cases from the left, two or fewer nodes were harvested. CONCLUSION: This review suggests the need for re-examination of the adequacy of surgical resection and/or nodal sampling technique for colorectal cancer resection specimens, given the importance of nodal status in determining the need for adjuvant therapy. Less than adequate node sampling should not be accepted by the reporting pathologist or attending surgeon as this has important prognostic implications.

Penile cancer in Jamaicans managed at the University Hospital of the West Indies.

OBJECTIVES: The aim of this study is to determine the prevalence and clinicopathological correlates of penile cancer as well as the clinical outcomes in a sample of Jamaicans managed at the University Hospital of the West Indies (UHWI). METHODS: All available records of patients diagnosed with penile cancer from 1998-2008 at the UHWI were obtained. Patient demographics, circumcision status, sexually transmitted infection status, lesion duration, location and size, and lymph node status were obtained. Histology, differentiation and stage were recorded. Information was obtained regarding treatment and outcome. The current data were compared with a previous report from UHWI in 1959. RESULTS: The records of 22 of 26 patients with penile cancer were available for review. Mean (SD) age of patients was 68 (13) years. Eighteen (86%) patients were uncircumcised Mean tumour size was 5.7 (2.6) cm; 8 (36%) lesions involved the entire penis. Sixteen (73%) lesions had clinically regional disease and 11 (52%) patients had advanced pathological stage. Surgical treatment was performed in 15 (68%) patients. Case fatality was 38%, with median survival following surgical intervention of 38 person-months. The major predictor of death in this series was increasing age (HR = 1.06, 95% CI 0.99, 1.1, p = 0.079). There was an increase in age and clinical stage of the cancer at presentation in the current series; however there was no difference in survival. CONCLUSION: Penile cancer is an uncommon cancer, seen at an advanced stage in Jamaicans. Overall survival is poor and advanced age is a major predictor of death.

Angiomyolipoma of the kidney: the experience at the University Hospital of the West Indies.

OBJECTIVE: Angiomyolipoma (AML) of the kidney is an uncommon tumour that, until recently, was often misdiagnosed preoperatively as renal cell carcinoma (RCC). Newer radiological techniques have allowed more accurate preoperative diagnosis which can facilitate preoperative counselling and planning for conservative therapy. This study reviews the experience with these uncommon tumours at the University Hospital of the West Indies. METHODS: All cases of AML diagnosed during the period 1980 to 2007 were retrospectively identified from the files of the Department of Pathology. From these records, selected data were retrieved and analysed. These included patient demographics, clinical history, clinical diagnosis and pathologic characteristics of the specimen submitted. The total number of primary renal tumours diagnosed in adults during the same period was also determined for comparison. RESULTS: Eleven cases of AML were identified among 149 primary renal tumours in adults. Ten of these cases occurred in women. Amongst these, a single case of tuberous sclerosis was confirmed in a patient with bilateral lesions. Excluding this patient, who was 24-years-old, ages ranged from 24 to 86 years with a mean of 44 years (median 40.5 years) and an equal number of lesions was present on each side. Abdominal or flank pain were the most common clinical symptoms, present in six cases but in three cases, the tumours were discovered incidentally. The correct clinical diagnosis was made pre-operatively in a single case. By contrast, a diagnosis of RCC or other malignant tumour was proffered in eight cases. Pathologically, the maximum dimension of the seven excised tumours, in whom such information was recorded, ranged from 3.5 cm to 12 cm with a median of 7 cm. Spontaneous haemorrhage in the tumour was noted in three cases, all greater than 4.5 cm in maximum dimension. CONCLUSIONS: These data confirm that AML is uncommon at the University Hospital of the West Indies. There was an overwhelming female preponderance and patients presented, most commonly, in the 3rd to 4th decades. Tuberous sclerosis was identified in a solitary case. In this series, symptomatic lesions were > 4.5 cm in maximum dimension and haemorrhage complicated three cases. Most cases were incorrectly diagnosed preoperatively.

Are clinical practice guidelines valid for primary care?

Development of evidence-based clinical practice guidelines has emphasized treatment efficacy under methodologically rigorous conditions; internal validity (i.e., efficacy) has been assessed well. Despite their experimental foundations, guidelines originally were considered physician education tools relevant to singular, idealized encounters. Now, in rushing to generalize, quantify, and regulate quality, guidelines are being applied to whole populations as quality review criteria. Clinical guidelines do not make operational how, or even make clear whether they should be so used. We studied the external validity, the generalizability and measurability for primary care, of a guideline for treatment of systolic heart failure. Patient and clinical factors reducing generalizability were examined. Imprecise definition and reliance on single measures of recommendations were studied as limits to measurability. Patient, physician, organizational, and system factors influenced guideline validity. Attention to myriad invalidity sources undermining implementation and evaluation of efforts to improve quality and outcomes of primary care is critical.

Exploring instructional quality indicators in ambulatory medical settings: an ethnographic approach.

BACKGROUND AND OBJECTIVES: As medical education moves to community settings, the quality of learning is influenced by differences in the practice environment, organization, resources, patient case mix, and demographics. This ethnographic study identified experiences and processes that influence student learning in community-based practice settings. METHODS: Trained field researchers conducted participant observation in eight community teaching sites. Data were analyzed using a qualitative, grounded theory approach. RESULTS: Three dominant themes emerged: 1) the preceptor's role in situating learning opportunities, 2) the learner's role in transforming experience into learning, and 3) the practice organization as a classroom setting. The findings highlight the importance of exploiting learning opportunities and the contributions of other medical staff and patients in facilitating unique learning experiences. CONCLUSIONS: This research suggests the need to move beyond the typical student ratings of teacher effectiveness to consider and assess additional important factors and processes that affect instructional quality.

Managed care in rural markets: availability and enrollment.

The objective of this research was to test the hypothesis that urban-rural differences in managed care availability and enrollment are primarily due to differences in population socioeconomic and health system characteristics rather than geographic location, population size, or density. These two groups of variables were entered into a regression equation to determine which group could best account for the variance in managed care availability and enrollment. In general, the results of these analyses indicated that socioeconomic and health system characteristics did a much better job of explaining differences in managed care availability and enrollment. Therefore, focusing on factors such as adjacency to metropolitan areas or population size or density in making managed care policy decisions may be less productive than focusing on the socioeconomic and health system characteristics of an area.

Readiness for Medicaid managed care reform initiatives: a profile of rural family physicians.

Medicaid managed care is now an important factor in the financing of rural health care delivery. The participation of rural family physicians in Medicaid managed care is vital for the rural poor to access health services. This study examined 855 family physicians practicing in nonmetropolitan counties across the United States to determine their readiness to participate in Medicaid managed care. Physicians were asked about their experience with prepaid programs and the factors that would influence their participation in such a program. A shortage of health care providers and low reimbursement rates were most frequently cited as barriers to successful implementation. Physicians who had participated in prepaid programs in the past but were no longer participating had the most negative opinions about the potential for Medicaid managed care programs to enhance care for the poor in their communities. Overall, physicians reported potential for the program to improve access and quality of care, but they also expressed reservations about the financial and administrative effects on their practices. These results reveal that negative attitudes were associated with prepaid programs that failed to meet expectations, but physicians also expressed an optimism about the potential to serve the poor within a managed care model.

Heart failure in primary care: measuring the quality of care.

BACKGROUND: Concerns exist about the quality of care provided to heart failure patients by primary care physicians. Using an evidence-based clinical guideline, we evaluated the care given to patients with systolic heart failure. METHODS: We retrospectively reviewed the medical records of 420 patients from 25 primary care practices in upstate New York who had received a diagnosis of heart failure. Chart documentation confirmed the diagnosis (n = 395). We excluded patients with noncardiogenic volume overload or correctable valvular disease (n = 338). Performance profiles measured use of diagnostic tests, left ventricular ejection fraction (LVEF) measurement, patient education, and prescription of angiotensin-converting enzyme (ACE) inhibitors. For treatment recommendations, patients were classified according to LVEF status. RESULTS: Only 82% of the patients studied had an LVEF test result documented in their charts. Of these, 49% had an LVEF < or = 40%. ACE inhibitor use was greater among patients with low LVEF (91%) than among those with a normal LVEF (62%). Among patients with systolic heart failure taking ACE inhibitors, 87% were at target doses. Adherence measures were low for laboratory evaluation and patient-education criteria. CONCLUSIONS: Heart failure with normal LVEF was as prevalent as systolic heart failure in these primary care practices. Performance profiles for the physicians' prescriptions of ACE inhibitors exceeded those published in the literature. Patients who did not have a documented measure of LVEF, however, received lower quality of care as measured by this disease-specific guideline. This underscores the importance of measuring LVEF.

Longitudinal study of relapse from AIDS-preventive behavior among homosexual men.

There is no viable alternative to the control of AIDS besides prevention; factors contributing to relapse from behaviors presumed to reduce risk of that disease were investigated. The authors studied 524 homosexual men who had refrained from or used condoms during receptive or insertive anal sex (RAS and IAS, respectively) for at least 12 months, contacting them at 6-month intervals thereafter to ascertain current practices. They determined, via interviews, personal traits, appraised stress of maintaining safer sex, mental health, life events, and efforts to cope with potential infection. Negative life events, personal control beliefs, problem-solving abilities, and coping via problem-focused (e.g., seeking a monogamous union) rather than emotion-focused (e.g., "when I need a cure, they will have one") behaviors were associated with RAS, but less so with IAS safer sex behaviors. These findings provide a basis for individual and community-level interventions to change behavior and reduce AIDS risk.

Patient-centered clinical decisions and their impact on physician adherence to clinical guidelines.

BACKGROUND: This study was undertaken to assess the impact of traditionally unmeasured patient-centered factors on primary care physicians' decisions to adhere to an evidence-based clinical practice guideline for heart failure. METHODS: Experimental and control scenarios were developed to test three patient-centered factors hypothesized to influence physician nonadherence to a heart failure guideline: patient concerns about finances, quality of life, and location of care. Each factor represented an implicit patient goal potentially in conflict with a goal of the guideline recommendations. A control scenario for one factor and an experimental scenario for a second were placed within a cross-sectional survey and questionnaires were mailed by random assignment to 978 Upstate New York family physicians. Experimental and control responses were compared by chi square. RESULTS: The response rate was 47% (n = 456). Each hypothetical patient-centered factor resulted in significant reductions in physicians' predicted adherence. Reductions in reported pharmaceutical usage and testing of left ventricular (LV) function were associated with patient financial difficulties (P < .01). The poor quality-of-life scenario was associated with reduced testing for LV function but increased discussion of advance directives (P < .01). The clinical scenario limiting access to services for a rural patient was associated with decreases in physician choice of LV function tests and cardiology referrals (P < .05). CONCLUSIONS: Patient-specific factors are associated with physician decisions to comply with guideline recommendations. These findings suggest that performance profiles measuring physician adherence to guidelines should be interpreted with caution, and that current case-mix methodologies may not adequately control for patient-centered factors that may influence health care quality.

Family physicians' attitudes about and use of clinical practice guidelines.

BACKGROUND: The use of clinical guidelines is one strategy intended to improve health care quality, rein in costs, and standardize medical practice. Clinical guideline development has been prodigious, while less effort has been expended on the guidelines' dissemination and implementation. This study examines family physician attitudes toward and perceived uses of clinical guidelines in practice. METHODS: A survey questionnaire was sent to 978 family physicians in Upstate New York to assess their confidence in clinical guidelines developed or endorsed by organizations and the perceived usefulness of such guidelines in practice. Descriptive analyses, chi-square tests, and comparison of means (one-way ANOVA) were conducted. RESULTS: After two mailings, the response rate was 43%. Most respondents perceived clinical guidelines as effective educational tools that should improve the quality of patient care, but were concerned about their potential regulatory intrusion into practice. Solo practitioners expressed more negative attitudes regarding clinical guidelines than physicians in non-solo practices. Respondents had greater confidence in clinical guidelines developed or endorsed by their professional society, the Centers for Disease Control and Prevention, the United States Preventive Services Task Force, and the National Institutes of Health, but less in those by insurance companies or state health departments. The reported adoption rate of clinical guidelines was low. The most preferred methods for adoption were continuing medical education and practice interventions. CONCLUSIONS: Family physicians found clinical guidelines to be valuable educational tools but were divided on their potential regulatory role. If clinical guidelines are to improve quality in practice, they must be more effectively disseminated and implemented. To broaden physicians' adoption of clinical guidelines, further research into dissemination and implementation methods is warranted, along with wider endorsement of guidelines by those whom family physicians trust.

Using a clinical practice guideline to measure physician practice: translating a guideline for the management of heart failure.

BACKGROUND: Effective clinical practice guidelines should improve clinical outcomes, and measures of physician use of clinical practice guidelines should correlate with improved outcomes. This study translates a clinical practice guideline on heart failure into review criteria to measure physician performance and the effectiveness of the clinical practice guideline. METHODS: A panel of 11 family physicians and 1 cardiologist systematically reviewed the clinical practice guideline for its clinical importance, educational relevance, and evaluative appropriateness. Then a subset of 4 family physicians rigorously applied each recommendation to established criteria for measurability and developed an evaluation tool useful in medical record review. RESULTS: The heart failure clinical practice guideline was found to be an excellent educational tool. Using it to measure physician performance, however, was limited to diagnostic tests and drug prescribing. Of 45 recommendations, 5 fulfilled criteria for measurability; 1 recommendation had A-level evidence, whereas 2 recommendations had B-level and 2 had C-level evidence. CONCLUSION: This study illustrates the logistic issues and challenges in developing a measure of physician adherence to clinical practice guidelines. Medical record review is inadequate to measure many recommendations. Physicians use of this clinical practice guideline must be evaluated as an intermediate step to measuring the effectiveness of clinical practice guidelines based on patient outcomes.

Missed appointments and Medicaid managed care.

OBJECTIVES: To compare the demographic characteristics of patients who miss appointments with those who do not and to identify subgroups who would benefit from specific interventions for improving attendance. DESIGN: Retrospective cohort study of an 18-month period. SETTING: An urban primary care practice. PATIENTS: A random sample (N = 477) of patients who were seen at least twice during the study period. MAIN OUTCOME MEASURES: Number of missed visits and kept visits, insurer, age, sex, race, ZIP code, and diagnoses. RESULTS: Of the established patients, 48% missed 1 or more visits. Patients in managed care programs, private and Medicaid, were likely to have missed more visits during the study period than those not in managed care programs (P < .001). Medicaid managed care patients had also scheduled more visits. Significantly higher rates of missed appointments were found in patients aged 19 to 35 years (P = .02), blacks (P < .001), patients in Medicaid managed care programs (P < .001), and patients who scheduled more visits (P < .001). After adjusting for age, race, and sex, Medicaid managed care insurance remained a significant (P < .01) predictor of rate of missed appointments. CONCLUSIONS: Patients in managed care programs missed more appointments. Patients in Medicaid managed care programs scheduled more appointments and had higher rates of missed appointments than their counterparts in other insurance groups.

HIV/AIDS in the rural United States: epidemiology and health services delivery.

This integrated research review addresses the epidemiology of rural human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and the organization, financing, and delivery of health services for rural persons living with HIV or AIDS (PLWHIVs, PLWAs). Several abstracting services, indexing services, and bibliographies were searched. An annotation form served as the guideline for data extraction. Several conclusions emerged from this review. Epidemiological evidence indicates that there has been a dramatic increase in the relative proportion of rural HIV/AIDS incident cases over the past 5 years. Explanations for the rural increase focus on injection drug use, heterosexual behavior, and sexually transmitted disease levels. Dramatically elevated rates of infection in rural Black women are indicated. Rural areas experience important levels of in-migration of HIV/AIDS-infected individuals. The health services literature suggests that rural providers and institutions have limited resources and little experience with PLWHIVs or PLWAs.

SR 4233 cytotoxicity and metabolism in DNA repair-competent and repair-deficient cell cultures.

In order to understand in more detail the mechanism underlying the preferential hypoxic cytotoxicity of the benzotriazine N-oxide SR 4233, we have compared the hypoxic cytotoxicity of this drug to the rates of hypoxic metabolism in both DNA double strand break repair-competent and repair-deficient cell cultures. Rodent SCCVII cells and repair deficient, radiation sensitive cells (rodent XR-1, V-3, and human AT5BI) were most sensitive to SR 4233 under hypoxia with a lethal dose needed to kill 50% of cells (LD50) of less than 5 microM. SR 4233 was less cytotoxic to human AG 1522 (LD50 = 18 microM), CHO 4364 (LD50 = 25 microM) and human HT 1080 cells (LD50 = 33 microM). The sensitivities to SR 4233 were found to be inversely proportional to the rates of SR 4233 metabolism in repair-competent cells (R2 = 0.9). However, XR-1 and V-3 cells were more sensitive to SR 4233 than predicted by the metabolism rate. Thus, the toxicity by SR 4233 towards hypoxic cells appears to result from two mechanisms; the rate of drug metabolism and the ability to repair DNA double strand breaks.