Detection of human papillomavirus in the oral cavities of persons with Fanconi anemia.

OBJECTIVE: We conducted a cross-sectional study to describe the prevalence and correlates of type-specific human papillomavirus (HPV) DNA in the oral cavities of persons with Fanconi anemia. MATERIALS AND METHODS: Oral swabs were collected from 67 participants with Fanconi anemia and tested for 27 HPV genotypes using polymerase chain reaction-based methods. RESULTS: Participants were a mean of 18.6 (standard deviation, 10.0) years of age (range 4-47 years). The prevalence of oral HPV infection was 7.5%, and the prevalence of high-risk HPV infection was 6.0%. HPV type 16 was not detected in any samples. Prevalence was higher in adults than in children (13.3% vs 2.7% in those ≥18 vs <18 years of age). Among adults, prevalence was higher in males than in females (25.0% vs 9.1%, respectively). CONCLUSIONS: Prevalence of oral HPV infection in persons with Fanconi anemia was comparable to estimates from other studies in the general population. However, in contrast to previous studies, we did not identify HPV type 16 (the type found in most HPV-related head and neck cancers) in any participants.

Improving the promise of embedded pragmatic trials: Surmountable barriers encountered in an evaluation of home-based HPV self-sampling to increase cervical cancer screening in overdue women.

Despite increased attention on how to conduct pragmatic trials and their importance, there remains an under-appreciation for the reality of what they take to design, compete and secure funding and execute. Many barriers are surmountable through increased exposure to experiences from completed trials. This report summarizes our experience in designing, securing funding and implementing the Home-Based Options to Make screening Easier (HOME) pragmatic trial, which was designed to evaluate home human papillomavirus testing for cervical cancer screening in underscreened women (women who had not received a cervical cancer screening test in ≥3.5 years). This report highlights factors at the level of research teams, organizations seeking to conduct embedded research, reviewers and funding agencies that challenge pragmatic trial design and execution. There is an urgent need to train on peer-reviewers how to evaluate embedded trial grant proposals, for agencies to pursue more rapid and innovative funding strategies, and to consider strategies for reviewers and funders to evaluate stakeholder buy-in (beyond letters of support). These factors together are needed to realize the promise of pragmatic trials to more efficiently and effectively generate critical data that inform changes in health care delivery and benefit patients.

Changing manifestations of brown tumors on bone scan in renal osteodystrophy.

In a patient with chronic renal failure and secondary hyperparathyroidism, brown tumors, visualized initially as photon-deficient areas on bone scintigraphy, reverted to areas of abnormally increased activity following parathyroidectomy. This dual appearance on bone scan paralleled the functional state of the parathyroid gland. The possible relationship of hyperhosphatemia to the increased bone-scan activity noted in the calvarium, mandible, and facial bones is discussed.

Ultrastructural examination of urinary sediment. Value in renal amyloidosis.

Examination of urinary sediment has been recommended as a useful diagnostic aid for renal amyloidosis. This procedure was evaluated in the cases of 57 patients, including 11 with proven renal amyloidosis and 13 considered very likely to have the disease. At least three types of urinary fibrillar material were observed: 10-12-nm-diameter fibrils similar to amyloid; 7-10-nm-diameter fibrils with characteristics of intracellular tonofibrils; and 15-30-nm-diameter fibrils suggestive of fibrin tendrils. Only four of 24 patients who had renal amyloidosis proven or suspected had amyloid-like fibrils in the urinary sediment, while four control patients, including three with diabetic nephropathy, had similar fibrils. Sixty-eight per cent of all urines contained material consistent with tonofibrils. Ultrastructural examination of urinary sediment as a diagnostic aid for renal amyloidosis lacks sensitivity and specificity and has very limited clinical value.

Preservation of normal adrenal androgen secretion in end stage renal disease.

A common endocrine defect in uremia is gonadal dysfunction with decreased testosterone production. Since gonadal and adrenal tissues share androgen biosynthetic pathways, we studied the stimulated adrenal androgen response in uremic patients. In contrast to the delayed or subnormal gonadal response to hCG reported by others, the adrenal response of androgens, as well as cortisol and aldosterone, to cosyntropin stimulation was unimpaired. In summary, the secretory reserve capacity of the adrenal gland for androgen, glucocorticoids and mineralocorticoids in uremia was studied with cosyntropin stimulation and found to be wall preserved.

Coagulation cascade, fibrinolytic system, antithrombin III, protein C and protein S in patients maintained on continuous ambulatory peritoneal dialysis.

We studied the coagulation cascade, fibrinolytic system and naturally occurring anticoagulants in a group of 14 patients with end-stage renal disease maintained on continuous ambulatory peritoneal dialysis (CAPD). The results were compared with those obtained in a group of ten normal volunteers. Plasma procoagulant activities of factors XII, XI, IX, VIII, VII, X and II were significantly greater in the CAPD group as compared to the normal control group. Likewise plasma concentrations of total and free protein S were increased in the CAPD group. Although the mean value for plasma factor V activity in the CAPD group was higher than that found in the control group the difference did not attain statistical significance. In addition plasma fibrinogen concentration and factor VIII-related antigen level were significantly increased in CAPD patients. No significant difference was found between the CAPD patients and the control group with respect to plasma levels of protein C, antithrombin III, plasminogen or alpha 2-antiplasmin. In summary, the results demonstrate a tendency for increased levels of various coagulation factors and protein S in CAPD patients with no significant alterations in the levels of various fibrinolytic and endogenous anticoagulant agents, i.e. antithrombin III and protein C. The clinical significance and the mechanism responsible for the observed changes require further investigation.

The relationship of arterial compliance with endothelial-derived proteins of the hemostatic system.

Cardiovascular risk factors associated with hypertension include alterations in arterial compliance and an increased tendency to thrombosis. In this study we examined the relationship between arterial compliance and endothelial derived components of the hemostatic system: von Willebrand factor (vWF) and tissue plasminogen activator (t-PA). Ten males (4 normal and 6 untreated hypertensives, 41 +/- 12 years) were studied. Compliance of proximal (large vessel) and distal (small vessel) arteries was measured by intraarterial pulse wave analysis; left ventricular wall thickness by echocardiography; and vWF and t-PA by immunoassay of plasma obtained before and immediately after maximum treadmill exercise. Baseline t-PA and vWF correlated inversely with distal compliance (r = -0.74, p = 0.01; r = -0.56, p = 0.09). Exercise strengthened the relationship between vWF and both distal compliance (r = -0.56 to r = -0.86) and proximal compliance (r = -0.44 to r = -0.70). Moreover, post-exercise levels of vWF and t-PA were each significantly related to left ventricular posterior wall and septal thickness. Of note, these protein concentrations correlated more strongly with arterial compliance and left ventricular wall thickness than with blood pressure. Thus, arterial compliance and left ventricular wall thickness appear to be more powerful than blood pressure as predictors of the endothelial release of vWF and t-PA in response to exercise. These findings indicate that some of the key cardiac and arterial characteristics of hypertension might be linked to increased endothelial reactivity to hemodynamic stress.

Peritoneal leucocyte response to bacterial peritonitis in patients receiving peritoneal dialysis.

We evaluated the quantitative peritoneal leucocyte response to antibiotic therapy in 25 CAPD patients with 57 episodes of bacterial peritonitis. Eighty-eight percent of the peritonitis episodes were initially treated with a first generation cephalosporin, but results of microbial sensitivity studies led to a change in the initial antibiotic regimen in 23 episodes. Overall, 47/57 (82%) episodes were cured by antibiotic therapy alone (responders), while 10/57 (18%) required removal of the peritoneal catheter as a curative procedure (nonresponder). Neither the duration of symptoms on initial presentation nor the status of being a nonresponder could be related to the baseline peritoneal leucocyte values, either the total (PLC) or polymorphonuclear counts (PMN). Since the baseline PLC and PMN showed a 500-fold variation, subsequent changes were expressed as a percent [PLC (%) and PMN-PLC (%)] of the baseline value. On day 3 of peritonitis, PLC (%) and PMN-PLC (%) were less in responders (26% and 10%) than nonresponders (251% and 254%) (p less than 0.001). Differentiation between responders and nonresponders based on PLC (%) and PMN-PLC (%) was associated with a high degree of sensitivity (90%) and specificity (90%). Similar results were obtained for day 4. These data suggest that the temporal pattern of PLC and PMN, when expressed as a percentage of the baseline value, may be useful in predicting those episodes of peritonitis which require removal of the peritoneal catheter.

Influence of HIV-1 and/or HIV-2 infection and CD4 count on cervical HPV DNA detection in women from Senegal, West Africa.

BACKGROUND: HIV infection is associated with greater risk of precancerous lesions and cervical cancer in women. However, several factors remain unclarified regarding the association between HIV infection and HPV detection, especially among those with HIV type 2 versus type 1 infection and severely immunocompromised persons. OBJECTIVES: To evaluate HPV overall and type-specific detection among HIV-infected and uninfected women in Senegal. STUDY DESIGN: Detection of HPV DNA for 38 genotypes in cervical swabs using PCR-based methods was evaluated in HIV-positive (n=467) and HIV-negative (n=2139) women participating in studies in Senegal. Among HIV-1 and/or HIV-2 positive women, CD4 counts were assessed. Adjusted multivariable prevalence ratios (PR) were calculated. RESULTS: The prevalence of any HPV DNA and multiple HPV types was greater among HIV-infected individuals (78.2% and 62.3%, respectively) compared with HIV-negative women (27.1% and 11.6%). This trend was also seen for HPV types 16 and 18 (13.1% and 10.9%) compared to HIV-negative women (2.2% and 1.7%). HIV-infected women with CD4 cell counts less than 200 cells/µl had a higher likelihood of any HPV detection (PRa 1.30; 95% CI 1.07-1.59), multiple HPV types (PRa 1.52; 95% CI 1.14-2.01), and HPV-16 (PRa 9.00; 95% CI 1.66-48.67), but not HPV-18 (PRa 1.20, 95% CI 0.45-3.24) compared to those with CD4 counts 500 cells/µl or above. CONCLUSION: HIV-infected women, especially those most severely immunocompromised, are more likely to harbor HPV. Measures to prevent initial HPV infection and subsequent development of cervical cancer through focused screening efforts should be implemented in these high risk populations.

Renal cortical necrosis in systemic lupus erythematosus.

A patient with active systemic lupus erythematosus had acute and irreversible renal failure after an uncomplicated cholecystectomy, and renal biopsy established the diagnosis of acute cortical necrosis. Patients with lupus have a diathesis for intravascular coagulation, and the interactive effects of immune complex or endotoxin-induced vascular injury, change in platelet dynamics, impairment of fibrinolysis, alterations in the mononuclear phagocytic system, and/or concomitant use of corticosteroids may have singularly or in combination been important in generating this rare renal complication of systemic lupus erythematosus in our patient.

Verapamil kinetics during maintenance hemodialysis.

The kinetics of verapamil during chronic oral therapy were evaluated in a maintenance hemodialysis patient. The elimination half-lives of verapamil and its major metabolite norverapamil were 3.8 and 15.2 h. The former is shorter, while the latter is similar to that in patients with normal renal function. Hemodialysis did not affect drug half-life, and neither drug could be detected in the dialysate. Our studies suggest that verapamil kinetics are altered in end-stage renal disease and that hemodialysis does not remove significant amounts of the drug or its metabolite.

Acyclovir pharmacokinetics in a patient on continuous ambulatory peritoneal dialysis.

Acyclovir is an effective agent for the treatment of herpes virus infections, however, the pharmacokinetics of the drug are altered in renal failure. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) patient who was immunocompromised and had cutaneous herpes infection. The elimination half-life (17.1 hours) was similar to that reported for end-stage renal disease (ESRD) patients, while the volume of the central compartment (29.6 L/1.73 m2), the steady state volume of distribution (68.1 L/1.73 m2), and the total body clearance (48.3 mL/min/1.73 m2) were greater. The mean CAPD clearance was only 4.4 mL/min, with less than 10% of an administered dose being recovered in the 24-hour dialysate. Further studies are needed to establish a dosing regimen for CAPD patients.

Ketoconazole treatment of fungal infection in acute renal failure.

A patient with diabetes mellitus and acute renal failure requiring hemodialysis developed Candida sepsis which was effectively treated with the oral antifungal drug, ketoconazole. Plasma drug levels during hemodialysis suggested that ketoconazole was not dialyzed, but that its pharmacokinetics, specifically gastrointestinal absorption, may be altered in renal failure.

Diabetes mellitus with immune complex glomerulonephritis.

The present study describes 3 patients with the simultaneous occurrence of diabetic nephropathy and immune-complex mediated glomerulonephritis. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal histology showed the characteristic change of diabetic nephropathy along with those of immune complex glomerulonephritis. Immunofluorescence studies showed a linear pattern with a superimposed granular pattern of IgG and C3 deposits. Renal function and urinary findings improved in the 2 patients who were followed up.

Biochemical cardiac risk factors during diuretic therapy.

The effects of six weeks of treatment with fixed doses of the diuretics chlorthalidone and ticrynafen on serum total cholesterol, low density lipoproteins, high density lipoproteins, triglycerides and other biochemical parameters were studied in 24 hypertensive patients. Chlorthalidone increased total serum cholesterol by 40 +/- 11 (SEM) mg/dl (P less than 0.01) and triglycerides by 80 +/- 30 mg/dl (P less than 0.05). The increase of 16 +/- 12 mg/dl in low density lipoproteins and the decrease of 5 +/- 6 mg/dl in high density lipoproteins induced by this drug were not significant. An investigational uricosuric diuretic, ticrynafen, caused no significant changes in any of the serum lipid concentrations measured. Fasting blood glucose levels were elevated, but not significantly, by both diuretics. Serum uric acid concentrations tended to increase in patients given chlorthalidone while ticrynafen treatment decreased uric acid levels by 2.9 +/- 1.4 mg/dl (P less than 0.01). The elevations induced by chlorthalidone in serum lipid levels may partially counteract the potential benefits of its antihypertensive effects.

Fibrinolytic and protease inhibitory systems in spinal cord injured patients with end-stage renal disease.

Earlier studies have revealed a variety of coagulation abnormalities in patients with long-standing spinal cord injury (SCI) and end-stage renal disease (ESRD). The present study was undertaken to examine the fibrinolytic and protease inhibitory systems in this population. Twelve spinal cord injured men with ESRD were studied. All patients had chronic active urinary tract infections, pressure ulcers and were practically bed-bound. The results were compared with those obtained in a group of 32 normal volunteers. Plasma plasminogen and unstimulated tissue-type plasminogen activator (t-PA) concentrations in the SCI-ESRD group were comparable with those found in the control group. No significant difference was found in plasma plasminogen activator inhibitor (PAI) activity in the two groups. In contrast, plasma alpha 2-antiplasmin antigen concentration and antiplasmin activity were significantly reduced in the study population. In addition, plasma alpha 1-antitrypsin activity and antigen concentration were significantly increased while the alpha 2-macroglobulin activity-to-antigen concentration ratio was significantly reduced in the SCI-ESRD group. Although the mechanism of the observed reduction in alpha 2-antiplasmin and total antiplasmin activity is uncertain, its presence could enhance fibrinolysis in this otherwise thrombosis-prone population. Likewise, elevated alpha 1-antitrypsin could attenuate tissue damage by leukocyte-derived proteases in the face of persistent suppurative infections. The reduced alpha 2-macroglobulin activity-to-antigen concentration ratio was thought to reflect the presence of alpha 2-macroglobulin complexes with various proteases generated by the activation of leukocytes, coagulation, fibrinolytic and other proteolytic systems.

Protein C abnormalities in spinal cord injured patients with end-stage renal disease.

Patients with chronic spinal cord injury (SCI) and end-stage renal disease (ESRD) exhibit antithrombin III deficiency and several other coagulation abnormalities. In view of increasing recognition of protein C (PC) as an important, naturally occurring anticoagulant and fibrinolytic factor, we studied plasma PC in this population. PC antigen concentration and its anticoagulant activity were measured in nine SCI men with ESRD maintained on hemodialysis and in a control group of ten normal able-bodied men. The results showed a significant increase in PC anticoagulant activity in the SCI group. Consequently, the ratio of the PC activity to its concentration, which is a measure of the functional integrity of PC molecule, was markedly depressed. These findings are indicative of the presence of inactive or abnormal PC in SCI-ESRD patients and may suggest its in vivo activation. The combination of impaired PC activity shown in this study, with previously demonstrated antithrombin III deficiency and other coagulation abnormalities, is suggestive of a hypercoagulable state.

Intrinsic coagulation pathway in end-stage renal disease associated with spinal cord injury treated with hemodialysis.

Plasma procoagulant activities of factors XII, XI, IX, and VIII and plasma concentrations of factor XII antigen and high molecular weight kininogen (HMK) were determined in nine men with chronic renal failure (CRF) associated with long-standing spinal cord injury (SCI) treated with hemodialysis. The results were compared with those obtained in a group of 10 ambulatory CRF patients and 8 normal volunteers (control group). Congenitally deficient plasmas were used as the substrate for the measurement of procoagulant activities in a one-stage clotting assay. Monospecific antibodies were employed in the measurement of factor XII antigen and HMK using gradient plate immunodiffusion and rocket immunoelectrophoresis. Factor XII coagulant activity and antigen concentration were significantly increased in the SCI group. The mean values for plasma factor XI and IX activities in the SCI group were comparable with those observed in the ambulatory patients and normal control group. However, marked variations in factor XI and IX levels were noted among the SCI patients with a few instances of mild to moderate factor deficiencies and several cases of markedly elevated levels. Factor VIII activity was markedly increased, with only two of the nine patients exhibiting normal values. HMK concentration in the SCI group was comparable with values obtained for the other groups. Following dialysis, factor XII antigen concentration rose and factor XI activity fell slightly but significantly. The results indicate that the combination of CRF and long-standing SCI is associated with marked aberrations of intrinsic coagulation pathway. The underlying mechanisms and the clinical consequences of these abnormalities are not known and require further investigation.

Pressure ulcer, fibronectin, and related proteins in spinal cord injured patients.

Pressure ulcer is a common occurrence in spinal cord injured (SCI) patients and can lead to serious complications. With proper management, some patients exhibit satisfactory healing whereas others show slow or nonhealing ulcers. Fibronectin has been shown to accumulate in wound, opsonize macroaggregate debris for phagocytosis, promote revascularization, and facilitate fibroblast migration and proliferation. We explored the relationship of plasma fibronectin with healing potential in 21 SCI men with pressure ulcer. They received standard wound care and were observed for eight weeks. Ten otherwise healthy SCI men without pressure ulcer (SCI-controls) and 32 able-bodied normal individuals (normal controls) were also studied. Plasma fibronectin and related proteins, ie, fibrinogen, plasminogen, alpha 2-antiplasmin and Factor XIII, were measured. Ten of 21 SCI patients with pressure ulcer showed rapid healing within four weeks and had significantly higher fibronectin levels as compared with the 11 patients with poor healing ulcers, SCI controls, and normal controls. Factor XIII and alpha 2-antiplasmin were mildly reduced and fibrinogen values were significantly increased in all SCI groups. Plasminogen concentrations were comparable in all groups studied. It thus appears that plasma fibronectin rises in patients with fast healing ulcers but fails to do so in those with poor healing ulcers and as such may be predictive of the course of pressure ulcers.

Vitamin D, parathormone, and calcitonin profiles in persons with long-standing spinal cord injury.

Rapid immobilization after acute spinal cord injury (SCI) leads to increased bone resorption, net calcium efflux from the bone, hypercalciuria, depressed parathormone (PTH) and increased calcitonin release. However, the effects, if any, of long-standing SCI on calcium regulatory system is not well understood. We measured plasma concentrations of 25 hydroxy (OH) vitamin D, 1,25(OH)2 vitamin D (calcitriol), intact PTH molecule, calcitonin, ionized calcium [Ca++] and phosphorus in 40 clinically stable men with long-standing SCI of 3-year to 50-year duration (22 persons with paraplegia and 18 persons with quadriplegia). The results were compared with those obtained in 14 able-bodied control men. Plasma PTH concentration in the SCI group was significantly lower than that found in the able-bodied controls despite virtually identical concentrations of ionized calcium. Likewise, plasma calcitriol concentration in the SCI group was significantly lower than the value found in the able-bodied control group and lower in persons with quadriplegia than in those with paraplegia. In contrast, plasma calcitonin concentration in the quadriplegic group was significantly higher than that in persons with paraplegia and insignificantly higher than that in the control group. No significant difference was noted in serum ionized calcium between the study groups. PTH and calcitriol levels were positively related to one another (r = 0.35, p < .01) and negatively related to the level of injury (r = -0.43, p < .002 and r = -0.54, p < .001, respectively). In conclusion, long-standing SCI is associated with significant depression of calcitriol and PTH concentrations despite normal ionized calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)