Culture of presenteeism: emergent perspectives from an NHS-workforce convenience sample.

BACKGROUND: The United Kingdom's National Health Service (NHS) has been under strain for more than a decade, which has been exacerbated by the 2019 coronavirus disease (COVID-19) pandemic. According to NHS staff, this is felt especially during the winter (also called 'winter pressure'), when both absenteeism and presenteeism rates are high in the healthcare workforce. AIMS: To understand the culture of presenteeism amongst NHS staff, focusing specifically on how presenteeism both persisted and changed during the COVID-19 pandemic and during periods of annual winter pressure. METHODS: Data for this study were derived from 20 in-depth interviews conducted with NHS staff, drawn from a convenience sample of primary- and secondary-care services. Interviews were guided by a semi-structured interview protocol. RESULTS: This study contributes to an understanding of presenteeism by describing the ways in which the practice both changed and, in some ways, stayed the same during COVID-19 self-isolation regulations, with remote work arrangements enabling some healthcare workers to continue working even when unwell. Despite this, isolation guidelines threw into stark relief NHS workers' deeply held beliefs about duty, service, and commitment to the wider healthcare system, while exposing their experiences and perceptions of profound systemic challenges and a lack of wider support to carry out their work. CONCLUSIONS: The emergent findings from this study suggest that the culture of presenteeism is linked to wider NHS staff's identification with the institutional goals of the NHS, resulting in their motivation to continue working, even if remotely; yet, the consequences are not fully understood.

High prevalence of asymptomatic Leishmania spp. infection among liver transplant recipients and donors from an endemic area of Brazil.

Visceral leishmaniasis is an uncommon disease in transplant recipients; however, if left untreated, the mortality can be high. If an organ donor or recipient is known to be an asymptomatic Leishmania spp. carrier,monitoring is advised. This study proposes to assess the prevalence of asymptomatic Leishmania spp.infection in liver transplant donors and recipients from an endemic area. A total of 50 liver recipients and 17 liver donors were evaluated by direct parasite search, indirect fluorescent antibody test (IFAT), anti-Leishmania rK39 rapid test and Leishmania spp.DNA detection by polymerase chain reaction (PCR).Leishmania spp. amastigotes were not observed in liver or spleen tissues. Of the 67 serum samples, IFAT was reactive in 1.5% and indeterminate for 17.9%, and the anti-Leishmania rK39 rapid test was negative for all samples. The PCR test was positive for 7.5%, 8.9%, and 5.9% of blood, liver and spleen samples, respectively(accounting for 23.5% of the donors and 8% of the recipients). Leishmania infantum-specific PCR confirmed all positive samples. In conclusion, a high prevalence of asymptomatic L. infantum was observed in donors and recipients from an endemic area, and PCR was the most sensitive method for screening these individuals.

Evaluation of antimicrobial consumption in the neonatal population undergoing antimicrobial stewardship programmes: a systematic review.

BACKGROUND: Indiscriminate use of antimicrobials in neonatal sepsis treatment contributes to consumption misuse, and the optimization of prescription programmes is encouraged as a way of reducing this inappropriate use. AIM: To evaluate the impact of intervention programmes for adequate antimicrobial use (antimicrobial stewardship programmes) in consumption measurements of such drugs in neonatology. METHODS: The search for articles was performed in electronic databases and by manual search for citations in publications initially identified. Electronic databases searched were BVS (Virtual Health Library), Cochrane Library, Embase, MEDLINE/PubMed, SciELO, Scopus, and Web of Science. There was no date or period limit for inclusion of articles. The PICO question was defined as populations of neonates admitted to neonatal intensive care units undergoing an intervention programme to optimize antimicrobial therapy in relation to neonates not exposed to the programme and the outcome obtained in antimicrobials consumption. FINDINGS: The initial search in databases resulted in 1223 articles. Articles were screened and 16 original studies related to subject were selected, which conducted a quantitative approach to antimicrobials consumption for the population of interest. Most articles used days of therapy (DOT) as the main measure of antimicrobial consumption and have had a high-quality rating by Newcastle-Ottawa Scale. All studies were carried out in local hospitals at a single centre and most were in high-income countries. CONCLUSION: Of all studies identified by the search, few evaluated antimicrobial consumption in neonatology. New studies are needed, and DOT was shown to be the most adequate metric to measure consumption.

Liver failure complicating segmental hepatic ischaemia induced by a PTFE-coated TIPS stent.

The use of polytetrafluoroethylene (PTFE)-covered prostheses improves trans-jugular intrahepatic porto-systemic shunt (TIPS) patency and decreases the incidence of clinical relapses and re-interventions. Therefore, the improvement provided by covered stents might expand the currently accepted recommendations for TIPS use. Stent-related occlusion of the hepatic vein with consequent ischaemia of the corresponding liver parenchyma emerges as a novel complication reported in at least 5% of patients implanted with coated stents. However, this complication was reported to be mild, without signs or symptoms of liver failure, and self-limiting. We report a case of segmental liver ischaemia following PTFE-covered stent placement resulting in a marked impairment in liver function in a patient with hepatitis C virus cirrhosis implanted because of refractory oesophageal bleeding, thus expanding the severity range of this new procedural complication. Moreover, we discuss the possible involvement of additional pathogenetic mechanisms other than out-flow obstruction in the onset of coated-stent induced congestive liver ischaemia.

Reliability of transient elastography for the diagnosis of advanced fibrosis in chronic hepatitis C.

BACKGROUND: Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in patients with chronic liver disease. AIM: To assess the value of TE for predicting the stage of fibrosis. METHODS: Liver biopsy and TE were performed in 150 consecutive patients with chronic hepatitis C-related hepatitis (92 men and 58 women, age 50.6 (SD 12.5) years on the same day. Necro-inflammatory activity and the degree of steatosis at biopsy were also evaluated. RESULTS: The areas under the curve for the prediction of significant fibrosis (> or = F2), advanced fibrosis (> or = F3) or cirrhosis were 0.91, 0.99 and 0.98, respectively. Calculation of multilevel likelihood ratios showed that values of TE < 6 or > or = 12, < 9 or > or = 12, and < 12 or > or = 18, clearly indicated the absence or presence of significant fibrosis, advanced fibrosis, and cirrhosis, respectively. Intermediate values could not be reliably associated with the absence or presence of the target condition. The presence of inflammation significantly affected TE measurements in patients who did not have cirrhosis (p<0.0001), even after adjusting for the stage of fibrosis. Importantly, TE measurements were not influenced by the degree of steatosis. CONCLUSIONS: TE is more suitable for the identification of patients with advanced fibrosis than of those with cirrhosis or significant fibrosis. In patients in whom likelihood ratios are not optimal and do not provide a reliable indication of the disease stage, liver biopsy should be considered when clinically indicated. Necro-inflammatory activity, but not steatosis, strongly and independently influences TE measurement in patients who do not have cirrhosis.

Prophylactic regimens with fluconazole for candidiasis in neonates under 1.500g: A retrospective chart review of two cohorts.

BACKGROUND: The incidence rate of invasive candidiasis in newborns with birth weight below 1,500 g ranges from 2% to 8%, and fluconazole prophylaxis in neonatal units is recommended when the incidence of invasive candidiasis is higher than 5%. This study aimed to compare the effectiveness of targeted prophylaxis and universal prophylaxis with fluconazole in the prevention of invasive candidiasis. METHODS: This was a historical cohort comparing the targeted prophylaxis for newborns weighing less than 1,500 g and the universal prophylaxis for newborns weighing less than 1,000 g. RESULTS: The overall incidence rate of invasive candidiasis was 5.25% and was reduced from 7.1% to 3.72% with universal prophylaxis (p = 0.04). In a multivariate analysis, the significant factors associated with the development of candidiasis were birth weight less than 1,000 g, prolonged hospitalization, previous surgery, prolonged use of mechanical ventilation, prior exposure to antimicrobial treatments, and use of targeted prophylaxis. CONCLUSIONS: Universal prophylaxis had lower incidence of invasive candidiasis, and preventive measures considering the risk factors are mandatory to reduce the incidence of invasive candidiasis.

Improving diet, activity and wellness in adults at risk of diabetes: randomized controlled trial.

OBJECTIVE: The purpose of this analysis is to examine the effect of an algorithm-driven online diabetes prevention program on changes in eating habits, physical activity and wellness/productivity factors. METHODS: The intervention, Alive-PD, used small-step individually tailored goal setting and other features to promote changes in diet and physical activity. A 6-month randomized controlled trial was conducted among patients from a healthcare delivery system who had confirmed prediabetes (n =339). Change in weight and glycemic markers were measured in the clinic. Changes in physical activity, diet and wellness/productivity factors were self-reported. Mean age was 55 (s.d. 8.9) years, mean body mass index was 31 (s.d. 4.4) kg m(-2), 68% were white and 69% were male. RESULTS: The intervention group increased fruit/vegetable consumption by 3.71 (95% confidence interval (CI) 2.73, 4.70) times per week (effect size 0.62), and decreased refined carbohydrates by 3.77 (95% CI 3.10, 4.44) times per week both significantly (P<0.001) greater changes than in the control group. The intervention group also reported a significantly greater increase in physical activity than in the control group, effect size 0.49, P<0.001. In addition, the intervention group reported a significant increase in self-rated health, in confidence in ability to make dietary changes and in ability to accomplish tasks, and a decrease in fatigue, compared with the control group. These changes paralleled the significant treatment effects on glycemic markers and weight. CONCLUSIONS: In addition to promoting improvements in weight and glycemic markers, the Alive-PD program appears to improve eating habits and physical activity, behaviors important not just for diabetes prevention but for those with diagnosed diabetes or obesity. The improvements in wellness/productivity may derive from the diet and activity improvements, and from the satisfaction and self-efficacy of achieving goals.

Integrin-mediated stimulation of monocyte chemotactic protein-1 expression.

We investigated whether activation of integrin receptors could modulate the expression of monocyte chemotactic protein-1 (MCP-1) in human hepatic stellate cells (HSC), mesenchymal cells responsible for extracellular matrix synthesis within the liver. When compared to non-adherent cells, HSC plated on collagen types I or IV, or fibronectin, showed increased MCP-1 gene expression and protein secretion in the conditioned medium. Increased MCP-1 secretion was also observed when cells were plated on dishes coated with a monoclonal antibody directed against the beta1-integrin subunit, demonstrating that ligation of beta1-integrins is sufficient to stimulate MCP-1 expression. Conversely, integrin-independent cell adhesion on poly-L-lysine did not modify MCP-1 secretion. Disruption of the actin cytoskeleton by cytochalasin D blocked the collagen-dependent increase in MCP-1 secretion. Chemotactic assay of HSC-conditioned medium showed that HSC plated on collagen secrete higher amounts of chemotactic factors for lymphomonocytes, and that MCP-1 accounts for the great majority of this effect. These findings indicate a novel mechanism of MCP-1 regulation possibly relevant in those conditions where HSC interact with an altered extracellular matrix.

Synthesis and biological profile of the enantiomers of [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-cis-octahydroquinoxalin- 1-yl]furan-2-ylmethanone (cyclazosin), a potent competitive alpha 1B- adrenoceptor antagonist.

The enantiomers of [4-(4-amino-6, 7-dimethoxyquinazolin-2-yl)-cis-octahydroquinoxalin-1-yl]-fu ran- 2-ylmethanone (cyclazosin, 1) were synthesized from the chiral furan-2-yl(cis-octahydroquinoxalin-1-yl)methanone [(+)-2 and (-)-2], which were obtained by resolution of the racemic amine with (S)-(+)- and (R)-(-)-mandelic acid. The binding profile of the enantiomers of 1 was assessed at alpha 1-, alpha 2-, D2, and 5-HT1A receptors as well as at native alpha 1A- and alpha 1B- and cloned alpha 1a-, alpha 1b-, and alpha 1d-adrenoceptor subtypes in comparison with prazosin, spiperone, and AH11110A. (+)-1 displayed a 40-90-fold selectivity for the alpha 1B(alpha 1b)-adrenoceptor relative to alpha 1A(alpha 1a) and alpha 1d subtypes. A significant enantioselectivity was observed at the alpha 1A(alpha 1a)-adrenoceptor and particularly at alpha 1d-adrenoceptors since (-)-1 was 11-14- and 47-fold, respectively, more potent than (+)-1. Furthermore the enantiomer (+)-1 displayed selectivities of 1100-, 19000-, and 12000-fold in binding to alpha 1b-adrenoceptors relative to alpha 2-adrenoceptors and 5-HT1A and D2 receptors. These results indicate that (+)-1, [(+)-cyclazosin] is the most potent and selective ligand for the alpha 1B-adrenoceptor subtype so far described and may be a valuable tool in the characterization of alpha 1-adrenoceptor subtypes.

Effect of pentoxifylline on the degradation of procollagen type I produced by human hepatic stellate cells in response to transforming growth factor-beta 1.

1. Pentoxifylline (PTF) may act as a potential antifibrogenic agent by inhibiting cell proliferation and/or collagen deposition in cell type(s) responsible for the accumulation of extracellular matrix. The aim of the present study was to investigate at which level PTF may affect synthesis and degradation of type I collagen in human hepatic stellate cells (HSCs), a key source of connective tissue in fibrotic liver. 2. Procollagen type I synthesis and release were evaluated in cells maintained in serum free/insulin free medium for 48 h and then stimulated with transforming growth factor-beta 1 (TGF-beta 1) for different time periods in the presence or absence of PTF. TGF-beta 1 caused an upregulation of procollagen I mRNA levels with a peak increase after 3-6 h of stimulation. This effect was followed by an increase in both the cell associated and the extracellular levels of the corresponding protein, with a peak effect at 9-12 h after the addition of TGF-beta 1. Co-incubation with PTF slightly but consistently reduced basal as well as stimulated procollagen I mRNA levels, with negligible effects on the cell-associated expression of the corresponding protein. Conversely, PTF dose-dependently reduced procollagen type I levels detected in supernatants from unstimulated and stimulated cells. 3. Pulse-chase experiments employing L-[3H]-proline revealed that PTF was able to induce significantly the degradation of procollagen, mainly in the extracellular compartment. We next analysed the effect of PTF on the major pathway involved in type I collagen degradation. PTF did not affect the expression of metalloproteinase 1 (MMP-1) mRNA both in basal and stimulated conditions, whereas it markedly reduced the expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA. Accordingly incubation with PTF increased the levels of 'activated MMP-1' in cell supernatants in both basal and stimulated conditions. 4. These results suggest that the antifibrogenic action of PTF on human HSCs is mainly mediated by extracellular collagen degradation rather than by a reduction of collagen synthesis.

Intramural left anterior descending coronary artery: significance of the depth of the muscular tunnel.

To establish whether an intramural left anterior descending coronary artery (LADA) is a simple anatomic or a singularly pathologic variant we studied 39 hearts, each with an intramural course of the LADA and no coronary artery disease, valvular derangement, cardiomyopathy, or congenital anomaly. Seventeen of the 39 hearts had no myocardial lesions, while 22 had gross and/or microscopic alterations in the myocardial territory supplied by the intramural LADA. The myocardial lesions consisted of one or more of the following: interstitial fibrosis, replacement fibrosis, contraction band necrosis, and/or increased vascular density in areas of focal fibrosis. The coronary anatomy of the 22 hearts with myocardial lesions (group 1) was compared with that of the 17 hearts without myocardial changes (group 2). Each of the group 1 hearts had an intramural LADA deeply placed within the ventricular wall and attenuation of potential collateral blood flow because of a co-existing intramural course of the posterior descending artery, other epicardial coronary arteries, and/or a diminutive right coronary artery. The myocardial changes in group 1 hearts and their absence in group 2 hearts suggest that the deep, intramural LADA of the group 1 hearts is abnormal rather than a simple anatomic variant of normal. Furthermore, the deep intramural LADA may be associated with sudden death since 13 of the 22 group 1 hearts were from sudden death victims. Six of these 13 persons died suddenly during vigorous exercise.

Myxoid heart disease: an assessment of extravalvular cardiac pathology in severe mitral valve prolapse.

Because of the microscopic features of the affected leaflets in mitral valve prolapse (MVP), myxoid degeneration of the valve is a common pathologic designation applied to this condition. We undertook this study as a means of gaining an insight into the occurrence and prevalence of extravalvular cardiac alterations in hearts with severe MVP. Tissues of 24 hearts with severe myxomatous transformation of the mitral valve as the sole cardiac abnormality were examined. Eighteen of the 24 subjects with severe MVP died suddenly. Only two of these had pathologic evidence of severe mitral insufficiency. Twenty-four normal hearts served as controls. The two groups of hearts came from victims of homicide, suicide, accident, or natural death. Sections of the mitral valve, working myocardium, conduction system, and cardiac nerves and ganglia were studied by routine and special connective tissue and proteoglycan stains. Similar to the findings in severely affected mitral valves, prominent deposits of proteoglycans in neural and conduction tissue readily distinguished hearts with myxomatous valve changes from the control hearts. We conclude that the commonly recognized local derangement of valvular tissue in MVP is but one specific reflection of a more general myxomatous alteration in cardiac connective tissue.

Left anterior descending coronary artery bridge. A cause of early death after cardiac transplantation.

Immediately following orthotopic transplantation, a patient suffered left pump failure, which resulted in death. Autopsy of the donor heart revealed a proximal left anterior descending artery bridge with a thrombus causing segmental distal anteroseptal infarction. In this case report, myocardial coronary bridges and their clinical implications are reviewed. Myocardial bridging and acute coronary obstruction should be considered in the differential diagnosis of patients with acute pump dysfunction following orthotopic cardiac transplantation.

Hepatorenal syndrome and its treatment today.

The pathogenesis of ascites, a severe and the most frequent complication during cirrhosis, is still not completely understood, but present evidence indicates that portal hypertension principally triggers renal sodium and water retention. Ascites is associated with profound disturbances of splanchnic and systemic haemodynamics, which in turn may influence renal function. Within the kidney the balance between vasoconstricting and vasodilating factors is critical for the maintenance of renal function. As the disease progresses, vasoconstricting factors (mainly angiotensin II, catecholamines, thromboxane, leucotrienes and endothelins) prevail, probably due to the exhaustion of the vasodilating renal autacoid system (mainly prostaglandins). In this setting, vasoconstriction of the intrarenal vascular system induces marked and often irreversible sodium and water retention, leading to refractory ascites, a progressive rise in plasma creatinine levels and reduction of renal clearances (hepatorenal syndrome, HRS). This persistent renal hypoxia may also favour the occurrence of tubular damage due to several causes. A careful therapeutic approach is first based on sequential diuretic treatment (and the addition of adequate plasma expansion with human albumin for patients with diuretic resistant ascites), which may lead to control of ascites for years. However, when HRS occurs, all the proposed treatments (such as paracentesis, administration of renal vasodilators, systemic vasoconstrictors, calcium channel antagonists, TIPS, surgical portosystemic shunts) have been shown to moderately or temporarily improve renal function only, leaving liver transplantation as the only choice of treatment for patients.

Is the use of albumin of value in the treatment of ascites in cirrhosis? The case in favour.

In patients with cirrhosis, ascites accumulates because of sodium retention, triggered by a reduction of the effective arterial blood volume, and imbalanced Starling forces in the splanchnic area due to portal hypertension and hypoalbuminemia. Albumin is the ideal plasma expander in this setting, since it ameliorates systemic and reneal haemodynamics, so reducing sodium retention, and increases oncotic pressure in the splanchnic compartment. In particular, albumin proved useful in patients treated with diuretics, as demonstrated by a randomised study performed at our Instituition in which 126 ascitic inpatients were treated according to a stepped-care diuretic regimen. In fact, patients receiving diuretics plus albumin (n = 63) had a higher cummulative rate of response (p < 0.05) and a shorter hospital stay (20 +/- 1 versus 24 +/- 2 days, p < 0.05) than those given diuretics alone. Treatment with albumin on an outpatient basis (25 g/week) resulted in a lower probability of developing ascites (p < 0.02 vs. patients not given albumin) and a lower probability of readmission (p < 0.02). Patients given albumin also had a better quality of life. As discussed in another article, evidence also supports the use of albumin in patients treated for paracentesis, as well as in patients with spontaneous peritonitis or hepatorenal syndrome.

Update on ascites and hepatorenal syndrome.

Ascites is the most common complication occurring during liver cirrhosis. Even if a significant decrease in renal clearance may be observed in the first step of chronic active liver disease, renal impairment, at times complicated by the typical signs of hepatorenal syndrome, occurs only in patients with ascites, especially when tense and refractory. Experimental and clinical data seem to suggest a primary sodium and water retention in the pathogenesis of ascites, in the presence of an intrahepatic increase of hydrostatic pressure, which, by itself, physiologically occurs during digestion. Abnormal sodium and water handling leads to plasma volume expansion, followed by decreased peripheral vascular resistance and increased cardiac output. This second step is in agreement with the peripheral arterial vasodilation hypothesis, depicted by an increase in total blood volume, but with a decreased effective arterial blood volume. This discrepancy leads to the activation of the sympathetic nervous and renin-angiotensin-aldosterone systems associated with the progressive activation of the renal autacoid systems, especially, that of the arachidonic acid. During advanced cirrhosis, renal impairment becomes more sustained and renal autacoid vasodilating substances are less available, possibly due to a progressive exhaustion of these systems. At the same time ascites becomes refractory inasmuch as it is no longer responsive to diuretic treatment. Various pathogenetic mechanisms leading to refractory ascites are mentioned. Finally, several treatment approaches to overcome the reduced effectiveness of diuretic therapy are cited. Paracentesis, together with simultaneous administration of human albumin or other plasma expanders is the main common approach to treat refractory ascites and to avoid a further decrease in renal failure. Other effective tools are: administration of terlipressin together with albumin, implantation of the Le Veen shunt, surgical porto-systemic shunting or transjugular intrahepatic portosystemic stent-shunt, or orthotopic liver transplantation, according to the conditions of the individual patient.

The rational use of albumin in patients with cirrhosis and ascites. A Delphi study for the attainment of a consensus on prescribing standards.

BACKGROUND: Ascites is one of the most frequent severe complications in patients with liver cirrhosis. The treatment of this chronic disease usually requires the prolonged use of albumin, frequently continued even after patients' discharge from the hospital. AIMS: Aim of the study was to define a consensus among Italian physicians with regard to the use of albumin in patients with decompensated cirrhosis and ascites. METHODS: The study adopted the Delphi technique to conduct the consensus activities. All controversial issues related to the use of albumin were identified by the experts' board and proposed to the 68 participating hepatology centres through two subsequent questionnaires. The questionnaires, returned by the specialists involved, were collected and the answers classified to verify the elements on which a consensus was reached. RESULTS: The home use of albumin can help to improve the patient's general conditions and well-being. About 77% of the experts involved considered likely that albumin administration could shorten hospital stays or could reduce the number of hospital admissions. The results of the study, along with a socioeconomic analysis, were presented to the Italian Drug Commission, which subsequently removed the specific hypoalbuminemia level as a prerequisite for having the drug reimbursed by the National Health Service. CONCLUSIONS: For an outpatient prescription, the hypoalbuminemia limit of 2.5 g/dl or less is not sufficient, while the decision whether to administer the drug requires the evaluation of patient's overall clinical conditions as an essential criterion for the prescription of a home treatment with albumin.

The use of dynamic electromyography to evaluate motor control in the hands of adults who have spasticity caused by brain injury.

A dynamic electromyographic analysis of grasp and release, performed on forty-eight upper extremities of forty-two adults who had had injury to the brain causing spasticity, showed volitional motor control of the finger flexors in 80 per cent and active extension of the fingers in 60 per cent. The flexor pollicis longus showed volitional control in 75 per cent of the hands and the extensor pollicis longus showed active control in 50 per cent. The extensor carpi radialis longus acted as an appropriate stabilizer of the wrist in 85 per cent of the extremities. Fourteen muscles had out-of-phase activity that could not be detected on clinical examination. The position of the elbow did not appreciably influence the electromyographic pattern of motor control in the hand.

Assessment of a novel screening test for neutrophil collagenase activity in the diagnosis of periodontal diseases.

BACKGROUND: Increased levels of active neutrophil collagenase (MMP-8) in the gingival crevicular fluid (GCF) are associated with progressive periodontitis. The measurement of this enzyme in GCF could facilitate diagnosis. However, assays with sufficient sensitivity to detect collagenase in whole-mouth GCF currently use radiolabeled substrates and require several days to complete. To provide more rapid analyses of collagenase activity that are better adapted to clinical studies, we developed and validated a novel assay (soluble biotinylated-collagen assay: SBA) based on chemiluminescent detection of biotinylated collagen digestion products. METHODS: The concordance of the novel SBA assay with a radioactive collagen substrate assay was assessed by parallel analyses of enzyme from 35 neutrophil preparations and from 41 samples of GCF from periodontitis patients, followed by Pearson correlation analysis. To test whether the assay appropriately measured MMP-8 activity, enzyme activity was assessed after incubation with specific collagenase blockers. We examined the diagnostic utility of the SBA in cross-sectional and longitudinal analyses of 125 patients with adult periodontitis, 5 patients with early-onset periodontitis, 1 edentulous patient, and in 32 control patients without periodontitis. RESULTS: The assay detected <56 pg collagen degraded/hour/microl sample, which is comparable to the most sensitive radioactive assay. The total assay time was 22 hours and reproducibility on replicate measurements was high (r = 0.96). In direct comparisons of MMP-8 activity in GCF with enzyme from peripheral blood neutrophils using the SBA and radioactive assays, there was a high correlation (r = 0.97). As expected, EDTA and TIMP-1 and -2, known inhibitors of MMP-8, completely blocked enzyme activity with this assay. Cross-sectional and longitudinal analyses of GCF showed that MMP-8 activity was >18-fold higher in severe periodontitis than in stable periodontitis and decreased to <25% of pretreatment levels following therapy. Based on measurements of collagenase activity in different disease groups, we estimated a value of 80 nano units as a threshold for severe periodontitis. CONCLUSIONS: These results indicate that active MMP-8 is detected in GCF by a novel assay that is specific, simple, rapid, and reproducible and which may facilitate diagnostic discrimination between stable and progressive lesions.

Pigmented papillary carcinoma of the male breast.

A case of highly pigmented papillary carcinoma originating in the breast of a 70-year-old man is presented. The tumor was located in the subareolar region and did not affect the overlying skin, which was normally pigmented. The significance of the presence of melanocytes in the tumor and of melanin pigment in the cytoplasm of its cells is discussed.