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The small colony variant (SCV) concept -- the role of staphylococcal SCVs in persistent infections.

The recovery of small colony variants (SCVs) from clinical specimens was first described at the beginning of the last century. However, not until the past decade was an association of these variants with chronic, recurrent, and persistent infections such as chronic osteomyelitis and persistent skin and softtissue infection described. Since then, a number of reports and prospective studies have supported a pathogenic role for SCVs in disease. Biochemical and other characteristics of SCVs have suggested a link between electron-transport defective SCV strains and persistent infections, however, the strains examined were genetically undefined SCVs. Therefore, a stable mutant in electron transport was generated by interrupting one of the hemin biosynthetic genes, hemB, in Staphylococcus aureus. This mutant showed characteristics typical of clinical SCVs such as slow growth, decreased pigment formation, low coagulase activity, reduced hemolytic activity, and resistance to aminoglycosides. Furthermore, the mutant was able to persist within cultured endothelial cells due to decreased a-toxin production. It was suggested that the intracellular location of this subpopulation might shield the variants from host defenses and antibiotics, thus providing one explanation for the difficulty in removing SCVs from host tissues. Therefore, a defect in the electron-transport system allows S. aureus SCVs to resist aminoglycosides and persist intracellularly. Because of their fastidious growth characteristics, they are easily missed or misidentified in the clinical laboratory. Therefore, when an infection persists for weeks or months or fails to respond to antimicrobial therapy, clinicians as well as laboratory personnel should consider further efforts to search for this staphylococcal subpopulation.

Animals↗

Persistent systemic inflammation in unstable angina is largely unrelated to the atherothrombotic burden.

OBJECTIVES: The aim of this study was to assess the relationship between systemic inflammation, atherosclerosis, and thrombosis in two distinct clinical models of atherothrombosis. BACKGROUND: Persistent unstable angina (UA) is commonly associated with coronary thrombosis and persistent systemic inflammation. METHODS: We assessed circulating markers of activation of the thrombotic and fibrinolytic cascades and systemic soluble and cellular markers of inflammation on admission in 40 patients with persisting UA (Braunwald class IIIB; group 1) and 30 patients with Leriche-Fontaine stage IIB-III peripheral artery disease awaiting revascularization (group 2). RESULTS: The extent of atherosclerosis (p < 0.01) and activation of the coagulation system were greater in group 2, which had higher thrombin-antithrombin III complexes and D-dimer levels (2.7 and 24.4 microg/l, respectively), than in group 1 (2.0 microg/l and 12.9 microg/l, p = 0.02 and p = 0.0001, respectively). In contrast, C-reactive protein and interleukin-6 levels were higher in group 1 (7.6 pg/ml and 7.8 pg/ml, respectively) than in group 2 (4.5 pg/ml and 3.0 pg/ml, p < 0.01 and p = 0.03, respectively). Moreover, neutrophil activation was only found in group 1 (neutrophil myeloperoxidase content -4.0 arbitrary units vs. +3.4 arbitrary units in group 2, p < 0.0001). These differences persisted during the initial three days of hospitalization. CONCLUSIONS: Such a large, consistent discrepancy between atherothrombotic burden and systemic inflammation suggests that atherothrombosis, by itself, is an unlikely cause of persisting, recurring UA. An understanding of the primary inflammatory mechanisms of persistent and recurrent coronary instability could open the way to novel therapeutic strategies.

Aged↗

The outcome of episodic versus persistent adolescent depression in young adulthood.

OBJECTIVE: Study of the impact of episodic and persistent depression on psychosocial and mental functioning of young adults. METHODS: In a longitudinal representative community sample, four groups of subjects were identified who were depressed either in pre-adolescence, late adolescence or young adulthood or persistently depressed across time, and compared among each other and with a young adult control group. The 90th percentile on one or two self-reported symptom scales (i.e., the Center for Epidemiological Depression Scale (CES-D) or the Anxious/Depressed subscale of either the Youth Self-Report (YSR) or the Young Adult Self-Report (YASR)) served as the cut-off for the depression groups. Outcome was studied with regard to various psychosocial variables including life events, coping, self-related cognitions, size and efficiency of the social network, perceived parental behaviour, family relations and mental functioning. RESULTS: For the large majority of psychosocial variables, the persistent depression group showed the most abnormal scores. The YASR profile of mental functioning at outcome of the persistent depression group was also clearly distinguishable by higher scores from all other groups on the majority of scales. On a few scales, the young adult episodic group was not significantly different from the persistent depression group. CONCLUSION: This study shows that persistent rather than episodic adolescent depression carries a risk for abnormal psychosocial and mental functioning in young adulthood. The study also reflects the burden of young adult depression.

Adaptation, Psychological↗

Outcome of prenatal depression and risk factors associated with persistence in the first postnatal year: prospective study from Rawalpindi, Pakistan.

BACKGROUND: Rates of prenatal and postnatal depression in developing countries are high. Prolonged depression during the postnatal period is associated with impaired infant growth and development. Little is known about the factors predicting the persistence of prenatal depression beyond the first few postnatal months. METHODS: From a sample of 701 women in a rural sub-district of Pakistan, the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used to identify those with ICD-10 depressive disorder in the third trimester of pregnancy (n=160). Depressed women were re-assessed at 3, 6 and 12 months postnatal. Persistently depressed women (depressed at all time points) were compared with the remainder. Psychiatric symptoms, disability and life events were measured using the Self-Reporting Questionnaire (SRQ), Brief Disability Questionnaire (BDQ), and a modified Life Events Checklist. RESULTS: Of 129 mothers who completed follow-up, 73 (56%) were depressed at all points of assessment. These persistently depressed mothers had higher SRQ and BDQ scores prenatally and had experienced more life events in the year preceding the third pregnancy trimester than the mothers whose depressive disorder resolved (none received treatment). Persistent depression was significantly associated also with poverty, having 5 or more children, an uneducated husband and lack of a confidant or friend. On multivariate analysis, higher SRQ score and poverty during pregnancy predicted persistent depression. LIMITATIONS: The sample was from one rural sub-district only. We did not assess the women for physical conditions such as anaemia and thyroid-deficiency. CONCLUSION: Women who are poor and have more psychological symptoms during pregnancy are more likely to remain depressed one year after giving birth. This study highlights the need for developing mechanisms of early identification and suitable psychosocial interventions to minimise the damaging effects of persistent postnatal depression in poor communities.

Adult↗

Detection of persistent high risk human papillomavirus infections with hybrid capture II and SPF10/LiPA.

BACKGROUND: HPV infection in young women is common. However only a certain number of HPV genotypes are oncogenic. It is necessary for high risk HPV infection to persist at the cervix for a considerable time before oncogenesis occurs. OBJECTIVES: To look for persistence of high risk HPV in women attending a colposcopy clinic. Two DNA detection methods were used and the results compared to determine the rates of persistent, resolved and acquired infections over a 6-month period. HPV genotyping was used to determine type specific persistence. STUDY DESIGN: One hundred and thirty-eight women were tested for HPV infection when attending the colposcopy clinic at UCLH and then tested again at a subsequent visit approximately 6 months later. HPV DNA was detected by the Digene HC II assay using the high risk probes only and by PCR with the SPF10 primer set. All SPF10 PCR-positive samples were then specifically genotyped by a Line Probe Assay (LiPA) [Kleter et al. 1999. J. Clin. Microbiol. 1999;37:2508]. RESULTS: At entry of the study high risk HPV was detected in 43% of the samples by Digene HC II and in 60% of the samples by SPF10/LiPA. Thirty-eight (28%) of the women had a true persistent infection with the same high risk HPV genotype over a median period of 6.3 months. Nine (7%) women resolved one HR HPV infection after their first colposcopy visit, but obtained a different high risk HPV infection by the time they were tested at their second visit as identified by LiPA. Thirty-seven (27%) of the 138 women had mixed HPV infections, representing 45% of all those infected. CONCLUSIONS: The SPF10/LiPA assay detected more high risk infections than the Digene HC II assay. The Digene HC II assay was unable to distinguish between persistent infections with the same high risk genotype and those where the genotype had changed between visits.

Colposcopy↗

Fusiform aneurysm of a persistent trigeminal artery.

OBJECTIVE: Fusiform aneurysms of the persistent trigeminal artery are rare and endovascular treatment of these aneurysms has not been attempted previously. We describe a case of persistent trigeminal artery with a fusiform aneurysm in its middle third, managed using Guglielmi detachable coils (GDC). CLINICAL PRESENTATION: A 50-year-old, diabetic and hypertensive patient presented with sudden onset headache and neck stiffness. On examination, she was conscious but disoriented, without cranial nerve or sensorimotor deficits. Four-vessel cerebral digital subtraction angiography revealed a fusiform aneurysm of the middle third of a persistent trigeminal artery on the left side with adult type posterior cerebral arteries. INTERVENTION: Guglielmi detachable coils were used for occlusion of the persistent trigeminal artery. RESULTS: The procedure was well tolerated but delayed ischemic neurological deficits developed due to vasospasm. CONCLUSIONS: (1) In spite of angiographically documented independence of the anterior and posterior cerebral circulation, occlusion of a persistent trigeminal artery using endovascular techniques may result in posterior circulation stroke due to a number of factors, including occlusion of brainstem perforators taking origin from the persistent trigeminal artery or vasospasm. (2) The timing for endovascular intervention following aneurysmal rupture remains poorly defined.

Cerebral Angiography↗

Autologous blood patch in persistent air leaks after pulmonary resection.

OBJECTIVE: Persistent air leak is among the most common complications after pulmonary resection, leading to prolonged hospitalization and increased costs. At present there is not yet a consensus on their treatment. METHODS: During a 7-year experience, 21 patients submitted to pulmonary resection were postoperatively treated with an autologous blood patch for persistent air leaks. Persistent air leaks were catalogued twice daily according to the classification previously reported by Cerfolio and associates. Chest radiographs showed a fixed pleural space deficit in 18 (86%) patients. A total of 50 to 150 mL of autologous blood was drawn from the patient and injected into the chest tube, which was removed 48 hours after cessation of the air leak. RESULTS: We observed a 4% incidence of persistent air leaks after pulmonary resection in our series. Persistent air leaks were categorized as follows: 14% forced expiratory, 57% expiratory, 29% continuous, and 0% inspiratory. The mean duration of prolonged air leaks was 11 days after surgery. In 81% of the cases examined, a blood patch was only carried out once and gave successful results within 24 hours. In the remaining 19% of cases, the air leak ceased within 12 hours after the second procedure. Mean hospital stay was 15 days. In our experience this procedure had a 100% success rate. CONCLUSIONS: Pleurodesis with an autologous blood patch is well tolerated, safe, and inexpensive. This procedure is an effective technique for treatment of postoperative persistent air leaks, even in the presence of an associated fixed pleural space deficit.

Adult↗

Prolonged relaxation consistent with persistent soluble guanylyl cyclase activation in canine pulmonary artery following brief treatment with nitric oxide donors.

Recent work has indicated that prolonged treatment with nitric oxide (NO) donors results in tissue storage of NO as S-nitrosothiols and N-nitrosamines. The possibility thus exists that NO treatment may result in the development of tissue stores of NO with functionally significant effects following removal of the original NO source. In these studies, the effects of 10 min treatment with two chemically distinct NO sources, S-nitrosoglutathione (GSNO) and (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NO) were determined in canine pulmonary artery using a superfusion system that permitted continuous isometric force recording during addition and removal of the NO donors. Relaxation that persisted for up to 1 h after removal of the NO source, was demonstrated for both NO sources, but at lower concentrations relative to the relaxant EC(50) for GSNO versus DEA-NO. Persistent relaxation with both NO sources was fully reversed by both the sGC inhibitor, ODQ, and an inhibitor of cGMP-dependent protein kinase, Rp-8-Br-PET-cGMPS, indicating that persistent relaxation was consistent with persistent activation of the sGC-cGMP signaling pathway. In separate measurements, a GSNO-induced persistent increase in both tissue cGMP ([cGMP](i)) and relaxation were fully reversed by both ODQ and the thiol reducing agent dithiothreitol (DTT). The results indicate that vascular smooth muscle is capable of converting short-lived NO responses following short term exposure to NO donors by a mechanism consistent with prolonged sGC activation, resulting in persistent relaxation. Reversal of this cGMP-dependent process with DTT suggests that it occurs via mechanisms that are thiol redox sensitive.

Animals↗

Differential expression of three Chlamydia trachomatis hsp60-encoding genes in active vs. persistent infections.

Real time RT-PCR was used to assess expression of the three Chlamydia trachomatis hsp60-encoding genes (Ct110, Ct604, Ct755) over time in in vitro systems of active vs. persistent infection, and in synovial samples from patients with Chlamydia-induced arthritis. In HEp-2 cells actively infected with C. trachomatis (serovar K), mRNA from Ct110 (groEL) was apparent by 8 h post-infection (p.i.) and increased more than 10-fold through 48 h p.i.; mRNA from Ct604 followed a similar pattern. Transcripts from Ct755 were abundant at 8 h p.i. and remained 2-3-fold higher than those from Ct110 at all times. In persistently infected human monocytes in culture, expression of Ct110 and Ct755 was low from 1 to 7d p.i., while mRNA from Ct604 was abundant at 1d p.i. and increased more than 3-fold from 1 to 3d p.i., as the organism transited to the persistent state. Those mRNA levels remained high through 7d p.i. Real time analyses of RNA/cDNA from synovial tissue of patients with Chlamydia-associated arthritis showed high Ct604 mRNA levels, consistent with results from the in vitro monocyte system of persistence. These data demonstrate that each chlamydial hsp60-encoding gene is expressed independently, and that the three genes are expressed differentially in active vs. persistent infection. The results further suggest that the Ct604 gene product may function importantly during chlamydial persistence.

Adult↗

Clinically masked increases in bronchial inflammation in guideline-treated persistent asthma.

BACKGROUND: Current guidelines generally recommend a combination of inhaled corticosteroids and a Beta2-agonist for persistent asthma. The adjustment of anti-inflammatory therapy in persistent asthma is advised to be guided mainly by the presence of symptoms. OBJECTIVE: To investigate whether clinically masked increases in bronchial inflammation occur in guideline-treated, persistent asthma following allergen exposure. METHODS: After a 4-week steroid-run-in period (fluticasone 250 microg twice daily) 48 allergic patients with persistent asthma underwent a bronchial challenge with a single dose of allergen, after inhalation of salbutamol (400 microg, nebulized dose). FEV1 and sputum markers of bronchial inflammation were measured before and after allergen challenge. Furthermore, additional rescue-salbutamol usage was recorded following allergen challenge. RESULTS: After allergen challenge there was a significant increase in sputum eosinophil numbers (geometric mean number x 10(4)/g [95% CI]: 0.5 [0.3; 1.0] before, and 2.4 [1.3; 4.2] after challenge, p=0.01). The mean change in FEV1 between 4 and 8h after challenge relative to baseline was -0.04% [95% CI-2.3; 2.2], p>0.9. None of the patients took additional rescue salbutamol over 8 h after allergen challenge. CONCLUSIONS: Clinically masked increases in bronchial inflammation occur in guideline-treated, persistent asthma following allergen exposure. This finding underscores the need for additional guides for the adjustment of anti-inflammatory therapy in persistent asthma.

Adolescent↗

Deficient alpha-1-antitrypsin phenotypes and persistent airflow limitation in severe asthma.

BACKGROUND: Persistent airflow limitation is common among patients with severe asthma, but its pathogenesis has not been fully clarified. Severe alpha-1-antitrypsin (AAT) deficiency is a risk factor of chronic airflow limitation and emphysema, and partially deficient phenotypes have been associated with an accelerated decline in lung function. We hypothesized that partial deficiency of AAT (non-PiM AAT phenotype) is a risk factor of persistent airflow limitation in asthma. METHODS: In 122 patients with severe asthma (86 females; age (median (range)): 44.0 yr (18-75)) postbronchodilator FEV1 and FEV1/VC were measured and the AAT phenotype was determined. Persistent airflow limitation was defined as postbronchodilator FEV1 or FEV1/VC < 75% pred. with TLC > 75% pred. RESULTS: Six patients (4.9%) had a non-PiM phenotype (1 MF, 3 MS, 1 MZ and 1 SZ). Of the 58 patients with persistent airflow limitation only 1 patient (1.7%) had a non-PiM phenotype vs. 7.8% among the patients without persistent airflow limitation (P = 0.21). Postbronchodilator FEV1/VC (% pred.) was higher in the non-PiM patients than in the PiM patients (P = 0.02), the other lung function parameters were not different. Linear regression analysis showed no association between AAT phenotype and FEV1% predicted (P = 0.26). CONCLUSIONS: AAT heterozygoty does not seem to be an important risk factor of persistent airflow limitation in patients with asthma. Although confirmation by longitudinal follow-up studies with larger sample sizes is needed, these results suggest that routine assessment of the AAT phenotype is not indicated in asthmatic patients even if they exhibit fixed airflow limitation.

Adolescent↗

Preventable reoperations for persistent and recurrent papillary thyroid carcinoma.

BACKGROUND: Cervical recurrence occurs in up to 25% of patients with papillary thyroid carcinoma (PTC) due either to the aggressive biology of PTC or to inadequate treatment. This retrospective study was designed to determine the frequency of inadequate surgical or medical therapy as a cause of persistent or recurrent PTC. METHODS: We identified all patients who underwent reoperation for persistent (within 6 months of initial or pre-referral operation) or recurrent (greater than 6 months after initial or pre-referral operation) PTC from 1992 to 2003. Medical records including initial preoperative imaging, operative, and histopathology reports were reviewed. The initial surgical procedure was considered incomplete if all gross neoplasm was not removed or if "node plucking" was performed, and a subsequent recurrence occurred in the same cervical compartment. RESULTS: Seventy-two consecutive patients underwent reoperation for persistent (17) or recurrent (55) PTC. Of the 17 patients with persistent PTC, reoperation was judged to have been possibly preventable in 14 (82%) due to inadequate preoperative imaging or incomplete initial surgery. Of the 55 patients with recurrent PTC, reoperation was judged to have been possibly preventable due to incomplete initial surgery in 14 (25%). Based on the National Comprehensive Cancer Network guidelines, 33 (46%) of 72 patients with persistent or recurrent PTC received inadequate initial local treatment. CONCLUSIONS: Reoperation in 28 (39%) of 72 patients with persistent or recurrent PTC was potentially preventable. Accurate preoperative staging and adherence to the suggested National Comprehensive Cancer Network treatment guidelines may minimize the need for cervical reoperation.

Adenocarcinoma, Papillary↗

Persistent thrombocytopenia in liver transplant patients.

INTRODUCTION: The occurrence of thrombocytopenia in the perioperative period after a liver transplant is not uncommon. However, there are few studies on persistent thrombocytopenia during the longer follow up period of patients after liver transplantation. We examined the prevalence of and contributing factors to persistent thrombocytopenia beyond 1 year post-liver transplantation. METHODS: We analyzed adult patients followed for at least 1 year posttransplant with full blood counts and abdominal scans, as well as clinical notes. RESULTS: The 35 patients of mean age at transplant of 50 years and showed a mean follow-up of about 4 years showed a prevalence of persistent thrombocytopenia at 12 months of 54% and at 3 years of 25%. Factors that were associated with persistent thrombocytopenia were pretransplant variceal bleeding, splenomegaly, and thrombocytopenia at 3 and 6 months posttransplant. After multivariate analysis only the latter represented independent factors for persistent thrombocytopenia at 1 and 3 years posttransplant, respectively. CONCLUSION: Persistent thrombocytopenia improved over time posttransplant; no bleeding problem was observed among the affected cases.

Adolescent↗

Persistent hypercalcemia is a significant risk factor for graft dysfunction in renal transplantation recipients.

Hypercalcemia is a common problem in renal transplant recipients, although in most cases, spontaneous resolution occurs within 1 year after renal transplantation. This condition may persist in some patients producing effects on renal function which are not well understood. In this study, we sought to analyze the effect of persistent hypercalcemia in the posttransplantation period on the function of renal transplants. A total of 121 recipients (31 women, 90 men; mean age, 34.1 +/- 9.9 years) underwent renal transplantation between 1999 and 2002. All patients underwent prospective evaluation of their serum calcium levels at 6-month intervals. A sustained corrected mean serum calcium level higher than 10.2 mg/dL was defined as "persistent hypercalcemia." Patients who had a gradual increase in their serum creatinine levels to >2 mg/dL or a 50% rise above the baseline were considered to display chronic allograft dysfunction (CAD). Among 121 recipients, 52 patients (43%) developed CAD and 37 patients (30.6%) had persistent hypercalcemia. Among the CAD patients, 22 suffered persistent hypercalcemia, while the other 15 patients were without CAD, a difference that was statistically significant (42.3% vs 21.7%, P = .01). The mean calcium levels were lower among patients without than with CAD, a difference that did not reach statistical significance (9.9 +/- 0.4 mg/dL vs 10.1 +/- 0.6 mg/dL, P = .1). In conclusion, persistent hypercalcemia in the posttransplantation period may significantly contribute to the development of chronic allograft nephropathy.

Adult↗

Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells.

Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface.

Agammaglobulinemia↗

Markedly reduced severity of Dengue virus infection in mosquito cell cultures persistently infected with Aedes albopictus densovirus (AalDNV).

AalDNV-infected C6/36 cells serially passaged for over 10 weeks showed a decline in percentage of anti-AalDNV-positive cells (APC) from an initial 92% to approximately 20%. Cultures of persistent APC were indistinguishable from uninfected cultures by direct microscopy but most stained cells from early APC passages had enlarged nuclei with eosinophilic inclusions, while late APC passages had few and naive cells none. Super challenge of persistent APC cultures did not increase percentage APC and supernatants from persistent APC cultures gave low APC (40%) in naive C6/36 cell cultures. When challenged with dengue virus serotype 2 (DEN-2), naive C6/36 cells showed severe cytopathic effects (CPE) and high mortality within 4 days, as did early passage APC cultures. Remarkably, DEN-2 infections in persistent APC cultures were much less severe, being characterized by reduced DEN-2 infection percentage, retarded DEN-2 virion production, no CPE and no significant mortality. Reasons for rapid reduction in APC and resistance to superinfection upon serial passage remain unproven but may relate to production of AalDNV-defective interfering particles (DIP) by molecular mechanisms still open to speculation. More difficult to explain is cross-protection against DEN-2-induced mortality seen in persistent APC cultures. However, by comparison to work on shrimp viruses, we speculate that this may involve blockage of viral-triggered apoptosis. The phenomena described raise questions regarding the potential for persistent infections by unknown viruses to confound experimental results with insect cell lines.

Aedes↗

Human papillomavirus-type persistence patterns predict the clinical outcome of cervical intraepithelial neoplasia.

BACKGROUND: Persistent infection with high-risk (HR) human papillomavirus (HPV) genotypes is required for the development of cervical carcinoma, and integration of HPV testing into cervical screening programs is under investigation. For the clinical value of HPV testing to be fully established, genotyping studies are needed to identify HR HPV persistence in samples of known cytology and histology, and to determine the relationship with clinical outcome. To date, methods for genotyping have been research-based, and subject to variation. The availability of the Roche prototype line blot assay (LBA) offers a PCR-based, reproducible genotyping method, with a 37-type target spectrum and many potential applications. METHODS: We applied the LBA to determine persistence of HR HPV in 54 women with low-grade histology. Median interval between genotyping was 12.5 months (range 5-48). RESULTS: All 15 lesions that progressed to CIN3 (PD) were associated with HR HPV persistence. Regression of lesions (REM) was observed in 31 HPV+ women, of whom nine had clearance of existing HPV infections, with one patient then acquiring additional types. Eight HPV+ patients had no change in lesions observed (NC). Persistence of HPV type 16 was more common in the PD group (60%), compared with the REM group (27%) and the NC group (38%). CONCLUSION: Our results show that the LBA is a useful tool to identify HPV persistence patterns under anonymized conditions, with potential for research and clinical studies.

Alphapapillomavirus↗

Chronic fatigue: risk factors for symptom persistence in a 2 1/2-year follow-up study.

BACKGROUND: The prolonged disability of patients suffering from chronic fatigue may be due to sustaining factors that are independent of the cause and subject to intervention. This study reexamined a cohort of patients with chronic fatigue to define medical and psychiatric predictors of persistent symptoms. METHODS: Seventy-eight patients with chronic fatigue present for 6 months or more (not required to meet the Centers for Disease Control case definition for chronic fatigue syndrome [CFS]) completed a self-report, follow-up questionnaire to measure the overall improvement or worsening of their condition at a mean of 2.5 years after their initial examination. At the time of initial evaluation, patients underwent a structured psychiatric examination, physical examination, laboratory studies, and self-report measures of psychological distress and functional disability. The psychiatric examination queried the patient about 28 somatic symptoms that are separate from those associated with CFS. Discriminant analysis was used to determine which variables present at the initial examination were significant predictors of persistent symptoms and disability at 2.5 years. RESULTS: The factors most important at the time of initial presentation in predicting persistent illness were: (1) more than eight medically unexplained physical symptoms separate from those associated with CFS case definition; (2) lifetime history of dysthymia; (3) duration of chronic fatigue symptoms greater than 1.5 years; (4) less than 16 years of formal education; and (5) age older than 38 years. None of the results of the initial physical examination, or immunologic, general laboratory, or viral antibody measurements were significant in predicting persistence of symptoms. Recovery rates for those who met the criteria for CFS by either of two case definitions were lower than the rate of noncases, but the differences were not statistically significant. The five aforementioned variables formed a significant discriminative function, correctly classifying 78% of those who recovered and 74% of those with persistent symptoms. CONCLUSIONS: At initial examination, patients with chronic fatigue, more than eight medically unexplained physical symptoms (excluding symptoms in the case criteria for CFS), a lifetime history of dysthymic disorder, longer than 1.5 years of chronic fatigue, less than 16 years of formal education, and who were older than 38 years were the most likely to have persistence of symptoms of chronic fatigue at the 2.5-year follow-up.

Adult↗