A comparative study of the psychological problems of HIV-infected and HIV-uninfected children in a South African sample.

According to research children living with HIV experience elevated levels of depression, anxiety, ADHD and disruptive behavioural disorders. Although South Africa's paediatric population that is infected with the human immunodeficiency virus (HIV) is the largest worldwide, little research has been conducted on their mental health challenges. However, attributing high levels of mental health problems solely to their HIV status can be problematic as there may be other contributory factors. This research explored the mental health problems of HIV-infected children and compared these to the mental health problems of their HIV-unaffected peers from similar backgrounds. Data was gathered from two samples of child and caregiver pairs. HIV-infected children (aged 6-12 years) and their caregivers/mothers (n = 54) were recruited from the Kalafong paediatric clinic where they received medical treatment and routine ART. A comparison group of 113 HIV-uninfected children and their uninfected mothers were recruited from primary care clinics in the same community. Caregivers completed the Child Behaviour Checklist (CBCL) to assess children's mental health. Children completed the Self-Description Questionnaire (SDQ-I) and the Revised Children's Manifest Anxiety Scale (RCMAS). The scores of the psychometric sub-scales of the two groups were compared using parametric and non-parametric statistics. HIV-infected children experienced more somatic and affective problems, physiological anxiety, less ADHD and lower self-esteem than HIV-uninfected children in the comparison group, while controlling for age differences. The high levels of mental health problems of both groups of children may be attributed to similar difficult socio-economic circumstances. The fact that most infected children were not aware of their HIV-status could have influenced the results. Mental health services should not be limited to HIV-infected children but should form part of all health care services.

Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?!

One of the most disabling symptoms of hepatitis C virus (HCV) infection is chronic fatigue. While this is accepted for HCV polymerase chain reaction (PCR)-positive patients, a relationship between HCV infection and chronic fatigue is questioned after successful virus eradication. As fatigue is a subjective criterion, we aimed to evaluate in addition mood alterations and cognitive function in HCV-exposed patients with only mild liver disease and to assess a) possible interrelationships between these factors and health-related quality of life and b) the impact of viremia and former interferon treatment. One hundred and fifty-nine anti-HCV-positive individuals without advanced liver disease answered health-related quality of life (HRQoL), fatigue and depression questionnaires and underwent a battery of attention and memory tests. Accompanying diseases which could distort the results of the study such as HIV co-infection or drug addiction were exclusion criteria. The patients were subdivided into four groups according to their viremia status and interferon treatment history. Patients' data were evaluated with respect to norms given in the respective test manuals and in addition compared to those of 33 age-matched healthy controls. Eighty-five per cent of the patients had chronic fatigue, 50-60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. HRQoL correlated negatively with chronic fatigue (P<.001), while cognitive deficits-especially memory function-were independent from fatigue and depression. HCV infection may cause long-standing cerebral dysfunction that significantly impairs HRQoL and may even persist after clearance of the virus.

[Pleural empyema - treatment strategies in light of etiology]. / Pleuraempyem - Behandlungsstrategien unter Berücksichtigung der Ätiologie.

The variety of strategies in the treatment of parapneumonic pleural empyema demonstrates the ambiguity for the method of choice. Parapneumonic pleural empyema has been classified into different stages and classes. While the American Thoracic Society (ATS) classification is based on the natural course of the disease, or according to the radiological, physical and biochemical characteristics respectively, the American College of Chest Physicians (ACCP) has categorized the patients with pleural empyema according to the risk of a poor outcome. The British Thoracic Society (BTS) developed a treatment algorithm based on a systematic review of peer-reviewed literature. With regard to this classification the management of parapneumonic and postoperative pleural empyema is based on the stage of the disease. Therapeutic strategies include chest tube alone, chest tube with fibrinolysis, thoracoscopic debridement and decortication in open or minimally invasive techniques, closed empyemectomy, or treatment with thoracomyoplasty, open window treatment or vacuum clothing with negative pressure. The different conservative and operative therapeutic possibilities determinate the central treatment function of thoracic surgery.

Association of tobacco use and periapical pathosis - a systematic review.

The aim was to review the current evidence regarding an association between tobacco use, that is, cigarette smoking, and periapical pathosis. A systematic MEDLINE search of articles published prior to October 2011 (4th) was conducted using the keywords 'smoking and endodontics OR smoking and periapical index'. The study selection, data preparation and validity assessment were conducted by two reviewers. Nine studies fulfilled the inclusion criteria and represented data from 3008 individuals. The studies differed with respect to (i) study design, (ii) radiographic techniques, (iii) assessment of periapical pathosis, (iv) classification of smoking characteristics and/or (v) potential confounders accounted for in the analyses. Five of six cross-sectional studies revealed a significant positive association (OR 1.35-16.8) between periapical pathosis and current cigarette smoking. One of three longitudinal studies indicated an increased risk (OR 1.7) of root treated teeth for current smokers. The substantial heterogeneity of the included studies limited their interpretation. Further, well-designed studies are required to investigate the association between tobacco use and periapical pathosis.

Computer-aided classification of colorectal polyps based on vascular patterns: a pilot study.

BACKGROUND AND STUDY AIMS: Recent studies have shown that narrow-band imaging (NBI) is a powerful diagnostic tool for differentiating between neoplastic and nonneoplastic colorectal polyps. The aim of the present study was to develop and evaluate a computer-based method for automated classification of colorectal polyps on the basis of vascularization features. PATIENTS AND METHODS: In a prospective pilot study with 128 patients who were undergoing zoom NBI colonoscopy, 209 detected polyps were visualized and subsequently removed for histological analysis. The proposed computer-based method consists of image preprocessing, vessel segmentation, feature extraction, and classification. The results of the automated classification were compared to those of human observers blinded to the histological gold standard. RESULTS: Consensus decision between the human observers resulted in a sensitivity of 93.8 % and a specificity of 85.7 %. A "safe" decision, i. e., classifying polyps as neoplastic in cases when there was interobserver discrepancy, yielded a sensitivity of 96.9 % and a specificity of 71.4 %. The overall correct classification rates were 91.9 % for the consensus decision and 90.9 % for the safe decision. With ideal settings the computer-based approach achieved a sensitivity of approximately 90 % and a specificity of approximately 70 %, while the overall correct classification rate was 85.3 %. The computer-based classification showed a specificity of 61.2 % when a sensitivity of 93.8 % was selected, and a 53.1 % specificity with a sensitivity of 96.9 %. CONCLUSIONS: Automated classification of colonic polyps on the basis of NBI vascularization features is feasible, but classification by observers is still superior. Further research is needed to clarify whether the performance of the automated classification system can be improved.

Value of magnifying endoscopy in classifying colorectal polyps based on vascular pattern.

BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) has been developed as a new technique to differentiate tissue patterns in vivo. The aim of this study was to evaluate the diagnostic accuracy of NBI endoscopy with and without high magnification for the differentiation of neoplastic from non-neoplastic colorectal polyps. PATIENTS AND METHODS: Among 200 colorectal polyps from 131 patients, 100 lesions were classified according to vascular patterns by NBI endoscopy with high optical magnification and 100 lesions by high-definition endoscopy without high magnification. Additionally, the clarity of the vessel network was assessed. Histologic analysis was performed on all lesions. RESULTS: NBI endoscopy with high magnification resulted in a sensitivity of 92.1 % and a specificity of 89.2 % for the differentiation of neoplastic versus non-neoplastic lesions. This performance was statistically comparable to high-definition NBI endoscopy without high magnification, which showed a sensitivity of 87.9 % and specificity of 90.5 %. However, vessel network was significantly better visualized by NBI endoscopy with optical magnification compared with high-definition NBI endoscopy without high magnification. In comparison with NBI endoscopy, white-light endoscopy, with or without magnification, resulted in inferior discrimination between neoplastic and non-neoplastic polyps. CONCLUSION: The results demonstrate that the superior visibility of capillary vessels by the NBI technique allows the evaluation of colorectal lesions - based on the vascular patterns - with high diagnostic accuracy. In clinical routine, high-definition NBI endoscopy without high magnification may be used to sufficiently predict colorectal polyp histology, and high magnification can additionally facilitate visualization of vascular networks.

A combination of cetirizine and pseudoephedrine has therapeutic benefits when compared to single drug treatment in allergic rhinitis.

UNLABELLED: Antihistamines and nasal decongestants are well-established therapeutics in allergic rhinitis. However, no data are available which directly compare the effect size of the single substances with their combination in a single study including placebo (PLA) treatment. OBJECTIVE: The aim of this study was to evaluate the effect of a combination of cetirizine (CET) and pseudoephedrine (PSE) and to compare it to treatment with CET or PSE alone and to PLA during grass pollen allergen challenge in an environmental challenge chamber (ECC). MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled, four-way crossover study the effect of a combination of 10 mg CET with 120 mg PSE (CET + PSE) versus CET or PSE alone or PLA on symptoms, nasal flow, and nasal secretions was investigated in 49 patients with intermittent allergic rhinitis. Subjects underwent four 6-h pollen exposures in an ECC with administration of the drugs after 2 h. RESULTS: The induction of nasal symptoms, nasal secretion and nasal obstruction (measured as nasal flow) during the first 2 h of pollen exposure was highly reproducible at the 4 consecutive exposures. The symptom of nasal obstruction was significantly reduced after treatment with CET + PSE compared to the treatment with CET or PSE alone or PLA (p < 0.0001). Furthermore, the combination treatment significantly reduced the total nasal symptom score (TNSS) and visual analogue scale score (VAS) compared to the single treatments or PLA. Nasal flow was significantly increased after treatment with CET + PSE and PSE and nasal secretions were significantly reduced by CET + PSE and CET without significant additional improvement of the combination therapy. CONCLUSION: The combination treatment with CET and PSE is more effective than treatment with single substances in subjects with allergic rhinitis.

Bovine jugular veins in the pulmonary position in adults -- 5 years' experience with 64 implantations.

OBJECTIVE: The midterm durability of bovine jugular veins (BJV) in children is comparable to that of homografts. We present the results of 64 bovine jugular vein implantations in adults in a pulmonary position. METHODS: Between August 2003 and July 2008, 60 patients (aged 18 to 65 years) received 64 BJVs. 97 % of them had had previous reconstructions of the right ventricular outflow tract. Diagnoses for treatment included tetralogy of Fallot (n = 49 patients), other congenital malformations (n = 14), and Ross operation (n = 1). Four bovine jugular veins had a diameter of 20 mm, the others had a diameter of 22 mm. RESULTS: Survival after 5 years was 98.4 +/- 1.6 %. Freedom from endocarditis: 84.8 +/- 8.0 % (4 patients required explantation for endocarditis); freedom from explantation for structural valve degeneration: 96.2 +/- 2.6 % (2 patients required explantation); freedom from intervention: 93.2 +/- 2.8 % (3 patients required intervention); moderate insufficiency: 62.9 +/- 15.1 % (8 patients); gradient > or = 50 mmHg: 79.6 +/- 7.4 % (7 patients); degeneration: 56.4 +/- 12.9 % (11); any adverse event: 43.1 +/- 12.8 % (15 patients); calcification or aneurysmal dilatation: 100 %. At any postoperative interval, more than 75 % of the BJVs had neither been explanted nor were they degenerated. CONCLUSION: The BJV might be a promising alternative to homografts, also in adults. Strict antibiotic prophylaxis is mandatory. A prospective randomized multicenter comparison of homografts and BJVs would help to identify the preferable conduit.

Endodontics or implants? A review of decisive criteria and guidelines for single tooth restorations and full arch reconstructions.

This review describes practical criteria and a systematic process to aid the treatment planning decision of whether to preserve teeth by root canal treatment (RCT) or extract and provide an implant. Recommendations presented are based on best available evidence from the literature and the expert views of specialists in endodontics and restorative dentistry, including dental implantology. A MEDLINE search was conducted using the terms 'root canal therapy', 'dental implants', 'decision making', 'treatment planning', 'outcome' and 'human', and supplemented by hand-searching. When evaluating the outcome of root canal treatment, an observation period of 4-5 years is required for complete healing of periapical lesions. Dental implants, however, present a de novo situation and a functional period of at least 5 years is often required before peri-implant diseases are established and detected. Good long-term success rates and greater flexibility in clinical management indicate that RCT or retreatment should be performed first in most instances unless the tooth is judged to be unrestorable. When deciding if a compromised tooth of questionable prognosis should be maintained or replaced by an implant, both local, site-specific and more general patient-related factors should be considered. Following systematic evaluation and consideration of the best treatment option in a particular case, a treatment recommendation may then be given in favour or against tooth retention. Whilst single risks are possibly accepted for single tooth restorations, teeth with questionable prognosis and multiple pre-treatment requirements are better not included as abutments in fixed dental prostheses to reduce the risk to survival of the entire restoration.

High-affinity blockade of voltage-operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues.

BACKGROUND AND PURPOSE: Voltage-operated sodium channels constitute major target sites for local anaesthetic-like action. The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions. These side effects render the search for new local anaesthetics a matter of high interest. EXPERIMENTAL APPROACH: We have investigated the effects of three halogenated structural analogues of propofol on voltage-operated human skeletal muscle sodium channels (Na(V)1.4) and the effect of one compound (4-chloropropofol) on neuronal sodium channels (Na(V)1.2) heterologously expressed in human embryonic kidney cell line 293. KEY RESULTS: 4-Iodo-, 4-bromo- and 4-chloropropofol reversibly suppressed depolarization-induced whole-cell sodium inward currents with high potency. The IC(50) for block of resting channels at -150 mV was 2.3, 3.9 and 11.3 microM in Na(V)1.4, respectively, and 29.2 microM for 4-chloropropofol in Na(V)1.2. Membrane depolarization inducing inactivation strongly increased the blocking potency of all compounds. Estimated affinities for the fast-inactivated channel state were 81 nM, 312 nM and 227 nM for 4-iodopropofol, 4-bromopropofol and 4-chloropropofol in Na(V)1.4, and 450 nM for 4-chloropropofol in Na(V)1.2. Recovery from fast inactivation was prolonged in the presence of drug leading to an accumulation of block during repetitive stimulation at high frequencies (100 Hz). CONCLUSIONS AND IMPLICATIONS: Halogenated propofol analogues constitute a novel class of sodium channel-blocking drugs possessing almost 100-fold higher potency compared with the local anaesthetic and anti-arrhythmic drug lidocaine. Preferential drug binding to inactivated channel states suggests that halogenated propofol analogues might be especially effective in suppressing ectopic discharges in a variety of pathological conditions.

Role of endotoxin in the pathogenesis of critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) occurs in association with sepsis and multiple organ failure; however, little is known about the pathomechanisms of CIP and its therapy. In order to determine the parameters which interfere with development of CIP, electrophysiological investigations of peripheral nerves and biochemical measures were correlated to each other. The present study includes 20 consecutive patients in an intensive care unit developing severe sepsis or septic shock. Nerve conduction studies and electromyography were performed with occurring sepsis (day 1, 7, 14) and neurophysiological parameters were correlated with biochemical measures, especially indicators of infection and inflammation. It was found that all patients developed neurophysiological signs of axonal motor polyneuropathy. There was a significant correlation between serum concentrations of endotoxin and interleukin-2 receptors (IL2-R) and reduction of the amplitude of the compound motor action potentials. Other clinical and biochemical parameters showed no significant correlations with neurophysiological data. This finding apparently indicates that endotoxin damages nerve axons directly or indirectly, e.g. by activation of inflammatory cascades (IL2-R). Endotoxin appears to be an essential factor in the pathogenesis of CIP in sepsis, and therapeutic options neutralizing endotoxin may prevent development of CIP.

Replantation of three avulsed permanent incisors with complicated crown fractures.

AIM: To report a rare case of multiple avulsions of permanent teeth associated with complicated crown fractures. SUMMARY: The case describes a 3-year follow-up of the treatment of three avulsed maxillary incisors with complicated crown fractures. The teeth were replanted after an extra-oral time of 90 min (extra-oral dry time 6 min). After root canal treatment, the fractured maxillary incisors were restored with a layered hybrid composite material to re-establish aesthetics and function. Follow-up visits showed signs of replacement resorption affecting the maxillary central incisors but only minor signs of root resorption on the maxillary right lateral incisor. These findings were supported by digital volume tomography, which was performed 18 and 36 months post-trauma in order to assess extent, severity and progression of root resorption more accurately. *Healing of avulsed teeth depends on the degree of periodontal ligament (PDL) damage. *Digital volume tomography might improve diagnostics of root resorption.

Endocrine stress response and inflammatory activation during CABG surgery. A randomized trial comparing remifentanil infusion to intermittent fentanyl.

BACKGROUND AND OBJECTIVE: Our aim was to compare a continuous infusion of remifentanil with intermittent boluses of fentanyl as regards the perioperative hormonal stress response and inflammatory activation in coronary artery bypass graft patients under sevoflurane-based anaesthesia. METHODS: In all, 42 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were prospectively randomized to a fentanyl group (n = 21, total fentanyl dose 2.6 +/- 0.3 mg), or a remifentanil group (n = 21, infusion rate 0.25 microg kg(-1) min(-1)). Haemodynamics, plasma levels of epinephrine, norepinephrine, antidiuretic hormone, adrenocorticotropic hormone, cortisol, complement activation (C3a, C5b-9), interleukin (IL)-6, IL-8 and tumour necrosis factor-alpha were measured at T1: baseline, T2: intubation, T3: sternotomy, T4: 30 min on cardiopulmonary bypass, T5: end of surgery and T6: 8 h postoperatively. Troponin T and creatine kinase-MB were measured postoperatively. RESULTS: Patients in the remifentanil group were extubated significantly earlier than fentanyl patients (240 +/- 182 min vs. 418 +/- 212 min, P = 0.006). Stress hormones 30 min after start of cardiopulmonary bypass showed higher values in the fentanyl group compared to the remifentanil group (antidiuretic hormone (ADH): 39.94 +/- 30.98 vs. 11.7 +/- 22.8 pg mL(-1), P = 0.002; adrenocorticotropic hormone: 111.5 +/- 116.8 vs. 21.81 +/- 24.71 pg mL(-1), P = 0.01; cortisol 185 +/- 86 vs. 131 +/- 82 ng mL(-1), P = 0.04). The interleukins were significantly higher at some perioperative time points in the fentanyl group compared to the remifentanil group (tumour necrosis factor: T5: 3.57 vs. 2.37; IL-6: T5: 4.62 vs. 3.73; and IL-8: T5: 4.43 vs. 2.65 and T6: 2.61 vs. 1.13). However, cardiopulmonary bypass times and aortic cross-clamp times were longer in the fentanyl group, which may to some extent account for the differences. CONCLUSIONS: The perioperative endocrine stress response was attenuated in patients supplemented with continuous remifentanil infusion as compared to intermittent fentanyl.

Value of magnifying chromoendoscopy and narrow band imaging (NBI) in classifying colorectal polyps: a prospective controlled study.

BACKGROUND AND STUDY AIMS: Chromoendoscopy in combination with magnifying endoscopy is useful in distinguishing neoplastic from non-neoplastic colorectal polyps. Narrow band imaging (NBI) has been developed as a new technique to differentiate tissue patterns in vivo. The aim of the present study was to directly compare the diagnostic values of chromoendoscopy and NBI for the differentiation of neoplastic from non-neoplastic colorectal polyps. PATIENTS AND METHODS: In total, 200 colorectal polyps from 99 patients were distributed in a 1 : 1 ratio in order to analyze the surface according to the pit pattern classification and vascular patterns by either magnifying chromoendoscopy or NBI magnification. Histologic analysis was performed on all lesions. RESULTS: Using the Kudo classification of mucosal patterns, NBI with magnification resulted in a sensitivity of 90.5 % and a specificity of 89.2 % for the differentiation of neoplastic vs. non-neoplastic lesions. This performance was comparable to magnifying chromoendoscopy with a sensitivity of 91.7 % and a specificity of 90 %, respectively. Using vascular patterns for differentiation, NBI with magnification correctly identified 93.7 % of neoplastic polyps and 89.2 % of non-neoplastic colorectal lesions, whereas magnifying chromoendoscopy had a specificity of 95 % but a sensitivity of only 66.7 %. CONCLUSION: NBI in combination with magnifying endoscopy is a promising tool for the differentiation of neoplastic from non-neoplastic colorectal polyps in vivo without the necessity of using dye. The detection of capillary vessels with NBI allows the evaluation of colorectal lesions based on the vascular patterns with high diagnostic accuracy.

Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors.

BACKGROUND: The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers. METHODS: A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided. RESULTS: Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%). CONCLUSIONS: Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.

Effective biomodulation by leucovorin of high-dose infusion fluorouracil given as a weekly 24-hour infusion: results of a randomized trial in patients with advanced colorectal cancer.

PURPOSE: To determine whether high-dose infusional fluorouracil (FU) is effectively modulated by leucovorin (LV), interferon (IFN) alpha-2b, or both when given to patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients (n = 236) with progressive, measurable disease were randomized to three groups and received FU 2,600 mg/m2 as a 24-hour continuous infusion (CI) weekly for 6 weeks with 2 weeks rest (FU24h) and LV 500 mg/m2 as a 2-hour infusion before FU or IFN 3 x 10(6) U subcutaneously 3 times weekly or both. Treatment continued until progressive disease or unacceptable toxicity was observed. Pairs of treatment arms were analyzed sequentially to detect equivalence or a 25% difference in response rates. RESULTS: The rate of objective remission in patients who received FU24h/LV (44%; 40 of 91) was significantly higher than in patients who received FU24h/IFN (18%; 16 of 90; P < .05). The response rates of patients who received FU24h/LV versus FU24h/LV/IFN (27%; 13 of 49) were statistically equivalent. Significant differences were observed for time to tumor progression (TTP) (FU24h/LV, 7.1 months; FU24h/IFN, 3.9 months; FU24h/LV/IFN, 6.3 months; global P value < .009) and survival (16.6 months, 12.7 months, 19.6 months, respectively; global P value < .04). Unpredictable and life-threatening toxicity in the FU24h/LV/IFN arm required dose reduction of FU to 2,000 mg/m2/day and early stoppage of this arm. Toxicity was manageable in patients who received both FU24h/LV (grade 3 to 4 diarrhea, 21%) and FU24h/IFN (grade 3 to 4 diarrhea, 15%). CONCLUSION: Response rate, TTP, and overall survival were superior for LV-containing regimens compared with IFN modulation alone. The addition of IFN to high-dose infusional FU plus LV offers no advantage and may increase toxicity. The regimen of high-dose infusional FU24h/LV warrants further evaluation in patients with metastatic colorectal cancer.

Progression of coronary artery disease is dependent on anatomic location and diameter. The INTACT investigators.

OBJECTIVES: This study represents the first prospective, quantitative analysis of the association of progression of coronary atherosclerosis with anatomic site and diameter. BACKGROUND: The progressive course of coronary artery disease has been documented in many angiographic follow-up trials. METHODS: The data of 348 patients with coronary artery disease from the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT) were reviewed. Standardized coronary angiograms were taken 3 years apart and were analyzed quantitatively. The coronary tree was subdivided into 25 segments. The progression of 1,063 preexisting coronary stenoses and the appearance of 247 newly formed stenoses was assessed in relation to the mean diameter of segments (< 2 mm, 2 to 3 mm, > 3 mm) and to their position in the coronary tree (proximal, mid, distal) and in the three major coronary arteries. RESULTS: Decreases in the minimal diameter of preexisting stenoses were largest in segments that were > 3 mm in diameter (mean +/- SD 0.23 +/- 0.5 mm vs. 0.10 +/- 0.4 mm and 0.02 +/- 0.3 mm, p < 0.001), in a proximal position (0.14 +/- 0.5 mm vs. 0.09 +/- 0.4 mm and 0.06 +/- 0.3 mm, p = 0.081) and in the right coronary artery (0.14 +/- 0.4 mm vs. 0.07 +/- 0.4 mm and 0.07 +/- 0.3 mm, p < 0.01). Changes in percent diameter stenosis of preexisting stenoses were lowest in segments that were < 2 mm in diameter and in a distal position (p = NS). The number of new stenoses/segment was lowest in segments that were < 2 mm in diameter (44 of 1,756 vs. 139 of 1,967 and 64 of 1,125, p < 0.001) and in a distal position (77 of 2,370 vs. 84 of 1,193 and 86 of 1,285, p < 0.001) and was highest in segments of the right coronary artery (100 of 1,546 vs. 66 of 1,496 and 72 of 1,492, p = 0.044). CONCLUSIONS: Progression of coronary artery disease occurs most frequently in coronary segments that are > 2 mm in diameter, in a proximal or midartery position and in the right coronary artery.

Marrow fibrosis, indicator of therapy failure in chronic myeloid leukemia - prospective long-term results from a randomized-controlled trial.

Marrow fibrosis (MF) has rarely been considered in therapy studies on chronic myeloid leukemia (CML), and there is a lack of long-term observations on the basis of sequential bone marrow biopsies (BMBs) taken prospectively during the course of disease. A total of 848 BMBs from 400 patients with Ph(+) CML recruited in the German randomized CML study I were examined for MF before and during therapy. In total, 110 patients had been randomized to receive interferon (IFN)-alpha, and 290 to receive chemotherapy (hydroxyurea (HU): 154, busulfan: 136). During IFN-alpha and HU medication, MF was reduced or did not increase for about 2 years. Evolving or progressive MF was an independent and early predictor of therapy failure about 2 years earlier than indicated by changes in the peripheral blood, spleen size, marrow blast count and cytogenetics (P<0.00005), resulting in a significant shortening of the survival times of patients independent of the type of therapy applied including allografting (multivariate analyses; P<0.00005). The analyzed long-term observations strongly indicate that MF is an independent poor prognostic complication of CML, allowing an early prediction of therapy failure. Consideration of the fiber content in marrow may therefore significantly improve the prediction of therapy efficacy and outcome of disease.

Treatment intensity significantly influencing fibrosis in bone marrow independently of the cytogenetic response: meta-analysis of the long-term results from two prospective controlled trials on chronic myeloid leukemia.

Bone marrow fibrosis (MF) has been shown to indicate therapy failure in Ph(+) chronic myeloid leukemia (CML). However, the results on the development of MF during interferon-alpha therapy of CML are controversial. The significance of the interferon dose has not been considered as yet. In total, 627 bone marrow biopsies taken prospectively from 200 patients with CML recruited in two studies using different doses of interferon-alpha +/- low-dose cytosine arabinoside were examined for MF before and during therapy. The results showed that the risk of MF depended significantly on the interferon-alpha dose applied (P<0.000005). MF progressed during low-dose therapy (3 x 5 x 10(6) IU/week), but was prevented from progression when applying high dose (5 x 10(6) IU/m(2)/per day). MF disappeared when high-dose interferon-alpha was combined with low-dose cytosine arabinoside (P<0.000005). The risk of death markedly increased when MF occurred or progressed (P<0.0009), independent of all other prognostic factors evaluated including the cytogenetic response. In conclusion, the effectiveness of interferon-alpha on MF depends on the treatment intensity. MF reverses when combining high-dose interferon-alpha with low-dose cytosine arabinoside, but progresses when applying low-dose interferon-alpha. MF appears to be a significant early indicator of ineffective therapy in CML.

[Transpupillary thermotherapy for occult choroidal neovascularizations]. / Transpupillare Thermotherapie bei okkulten subretinalen Neovaskularisationen.

PURPOSE: This contribution describes the results of transpupillary thermotherapy (TTT) for age-related exudative macular degeneration (AMD) with regression. PATIENTS AND METHODS: In exudative AMD with occult choroidal neovascularization (CNV), transpupillary thermotherapy (TTT) was performed using a diode laser (Iridex) in unselected patients. Before therapy and 1, 3, and 6 months after the initial treatment the patients were examined clinically. Additionally threshold testing in the 10 degrees field (Humphrey) and fluorescein angiographies were documented at all check-ups. RESULTS: With respect to vision, differences in the slope of the regression lines between small, medium, and large CNV were significant (p<0.001). The slope of the regressions lines was significant except for small CNV. Regarding the 10 degrees field (Humphrey), there were no statistical differences in the slope of the regression lines (p=0.867). CONCLUSIONS: Transpupillary thermotherapy with small CNV did not show a statistically significant decrease of VA. Thus, in clinical terms early treatment of occult CNV with TTT seems to be able to prevent a further loss of visual acuity.