Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded by rapid clearance of HCV-RNA from serum

BACKGROUND/AIMS: Prediction of response to interferon therapy is important in the management of chronic hepatitis C. Pre-therapy data are valuable but they may be inaccurate in some cases. Our aim was to investigate whether the biochemical and virological events that occur early during interferon therapy in chronic hepatitis C may predict the final result of the treatment. METHODS: ALT and serum HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a standard 6-month course of interferon therapy. Eleven patients with a sustained response, 23 who responded but subsequently relapsed and 19 who did not respond were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV). RESULTS: After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained responders, in 26% of transient responders (p = 0.02) and in none of the non-responders. Corresponding figures after 8 weeks of therapy were 82% in sustained responders, 61% in transient responders and 9% in non-responders. The difference between sustained and transient responders at this time was not significant. After 4 weeks of therapy, 82% of sustained responders, 52% of transient responders and none of the non-responders presented normalization of alanine transferase. The difference between sustained and transient responders was not significant. Corresponding figures for normalization of alanine transferase at 8 weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained responders, 70% of transient responders and none of the non-responders had cleared HCV-RNA from serum. CONCLUSIONS: A rapid normalization of alanine transferase induced by interferon therapy is associated with response, but does not differentiate between transient and permanent response. In contrast, clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is significatively associated with sustained response. Testing for HCV-RNA early during interferon administration may be valuable for further decisions concerning therapy in patients with chronic hepatitis C.     

Are frequent short gastro-oesophageal reflux episodes the cause of symptoms in patients with non-ulcer dyspepsia responding to treatment with ranitidine?

BACKGROUND: Patients with non-ulcer dyspepsia (NUD) responding to treatment with H2-receptor antagonists have no clinically useful characteristics. This trial compares the gastro-oesophageal reflux pattern as measured by 24-h oesophageal pH monitoring in patients responding to ranitidine with that of non-responders. METHODS: Thirty-one patients with NUD were randomized to 6 weeks' double-blind alternating treatment with 150 mg ranitidine twice daily or placebo and classified as responders or non-responders. RESULTS: Pathologic gastro-oesophageal reflux was seen in 3 of the 13 responders and 4 of the 18 no-responders (NS). The responders had frequent short reflux episodes (< 1 min in duration). When 4 patients with > or = 5 reflux episodes longer than 5 min were excluded, the number of short reflux episodes (median) in responders and non-responders was 32 and 14, respectively. The difference is statistically significant (p = 0.025). There were no other differences between the groups. CONCLUSIONS: In this study patients with NUD responding to ranitidine were characterized by frequent short reflux episodes in the absence of numerous long reflux episodes.     

Prediction of short-term changes in symptom severity by baseline plasma homovanillic acid levels in schizophrenic patients receiving clozapine

The relationship between pretreatment levels of plasma homovanillic acid (pHVA) and the outcome of clozapine treatment was studied in 18 male patients with schizophrenia who were resistant to treatment with conventional neuroleptics. After 6 months of clozapine treatment, 7 patients demonstrated > or = 20% decrease in the Brief Psychiatric Rating Scale (BPRS) (responders), while 11 patients did not (non-responders). Responders and non-responders did not differ with respect to the baseline pHVA level. The BPRS Positive Symptom scores at 6 weeks and 3 months, but not those at baseline and 6 months, following initiation of clozapine treatment negatively correlated with pHVA levels for all patients. The correlations became stronger when only responders were included. No significant correlation between Positive Symptom scores and pHVA levels was observed for non-responders. The BPRS Total and Negative Symptom scores did not correlate with pHVA for all patients, responders or non-responders at any time. The percent decrease in the BPRS Positive Symptom scores from baseline at 6 weeks following clozapine treatment correlated significantly with pHVA levels in responders. These results suggest that pretreatment levels of pHVA can be used to predict relatively short-term changes in the positive symptoms of patients with schizophrenia receiving clozapine treatment, particularly for clozapine responders.     

Motor impersistence in patients with unilateral cerebral disease: A cross-validational study.

Evaluated 8 simple motor tasks comprising a motor impersistence test battery both individually and in combination as indicators of unilateral cerebral disease. Previously developed scoring criteria were applied to the performances of 32 right-handed brain-damaged and 32 control patients. Classificatory efficiency provided by overall performance on 6 of the tasks (70%) approached the level achieved by overall performance on the full battery of 8 tests. Side of lesion was found to be unrelated to performance within the brain-damaged group. Further study of an unselected patient sample is indicated in order to evaluate the incremental validity of the test battery in the neuropsychological examination. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?

In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.     

Occurrence and toxicity of Fusarium subglutinans from Peruvian maize

In a phase II clinical trial of 5-fluorouracil (5FU) plus N-(phosphonacetyl)-L-aspartate (PALA) therapy administration, a number of slowly developing clinical responses were observed. Because of this, a variety of immune parameters were sequentially studied in 21 patients on this trial. Of the 21 patients studied, 20 provided sufficient samples to compare baseline with subsequent values, 10 of the 20 patients responded to treatment. Responders and non-responders did not differ in any studied parameter at baseline. After 2 months of therapy, non-specific monocyte cytotoxicity (NSMC), antibody-dependent monocyte cytotoxicity (ADMC) and natural killer (NK) activity were higher in the entire study population, but these increases were not statistically significant. When responders and non-responders were evaluated separately, it was apparent that the trend was due solely to the changes observed in the responding patient population. When mean lysis values for each patient group were determined for each studied time point, it was possible to generate a mean area under the cytotoxicity/time curve (AUC) for each studied parameter. NSMC and ADMC did not differ in responders and non-responders. However, NK activity was significantly greater by mean AUC analysis (P = 0.006) in the responding group; NK activity was maintained in the responders, but decreased in non-responders. When lymphocyte and monocyte expression of the surface markers beta 2-microglobulin, HLA-DR, CD56, HNK-1, CD16 and interleukin-2 receptor were evaluated, there were no differences among responders and non-responders at baseline by mean AUC analysis or when comparing baseline with non-baseline values. It is concluded that although baseline immunological characteristics do not identify patients who are likely to respond to weekly 5FU and PALA, treatment is not associated with deleterious effects on the immune effector function parameters evaluated in this study, there being no effects on expression of a variety of associated cell-surface molecules.     

HMPAO SPECT in Parkinson's disease before and after levodopa: correlation with dopaminergic responsiveness

Regional cerebral perfusion was evaluated by SPECT with technetium 99m hexamethylpropyleneamine oxime (99mTc HMPAO) as a tracer in 21 patients presenting with Parkinson's disease and in 11 normal controls. In the parkinsonian patients, scans were performed both off treatment, and after levodopa, and clinical dopaminergic responsiveness was evaluated. Uptake of HMPAO by the basal ganglia was significantly decreased in the parkinsonian subjects, compared with normal controls. This reduction was seen in both responders (n = 14) and non-responders (n = 7) to dopaminergic treatment. Uptake of HMPAO by the basal ganglia rose after treatment with levodopa, but the change was similar in both responders and non-responders. By contrast a striking difference in cortical HMPAO uptake was found between responders and non-responders, with significantly lower uptake in the medial temporal and posterior parietal cortex in the non-responders. This reduction was symmetrical. Basal ganglia perfusion assessed by this technique is unlikely to be of use in the diagnosis of Parkinson's disease that is responsive to dopaminergic treatment. The presence of extensive cortical involvement on a baseline scan correlates with a lack of dopaminergic responsiveness, however, and this may be useful diagnostically.     

Immunomodulatory effect of pentoxifylline in Graves ophthalmopathy

In the pathomechanism of the thyroid associated ophthalmopathy (TAO) the inflammatory cytokines produced by infiltrating lymphocytes of the retroorbital tissues are involved. The activated lymphocytes have been shown to secrete a number of cytokines including tumour necrosis factor-alpha, interleukin-1 and interferon-gamma. The widely used immunosuppressive therapies have potential serious side effects. The pentoxifylline (Ptx) is known to have effect on production of cytokines. The aim of this study was to investigate the effect of Ptx on expression of HLA-DR molecules and production of glycosaminoglycan of human retroorbital tissue cultures and potential efficacy in patients with TAO. It was found that pentoxifylline (Ptx) was able to inhibit significantly the HLA-DR expression and glycosaminoglycan synthesis induced by inflammatory cytokines including TNF-alpha, IFN-gamma and IL-1. Ten patients with untreated moderate severe ophthalmopathy (8 female and 2 male) were excluded from steroid treatment due diabetes mellitus and psychiatric disease. Classification of eye changes was made by NOSPECS categories and total eye score. All patients were euthyroid during the study and was no remarkable difference in thyroid function and eye symptoms. Before and during Ptx therapy the laboratory parameters were also determined including glycosaminoglycan. TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies in the patients'sera. It was found a remarkable improvement in the eye symptoms in eight of ten patients. The levels of glycosaminoglycan (uronic acid) and TNF-alpha gradually decreased in eight patients who considered to be responders. The levels of uronic acid in plasma of the responders were found to be significantly lower after Ptx treatment. Before Ptx therapy the TNF-alpha in the sera was not different remarkably in non-responders and responders. After 4 weeks Ptx treatment the TNF-alpha decreased significantly in responders compared to non-responders (20.9 +/- 4.8 pg/ml v. s. 28.3 +/- 6.1 pg/ml) (p < 0.01). The titre of anti-eye muscle antibodies were found to be lower at the end of observation, however, the anti-thyroid antibodies were not changed remarkably. It was concluded that Ptx in the majority of patients (8/10) has a beneficial effect on inflammatory symptoms of TAO and laboratory parameters and suggested to use as an additive therapy, however, further comparative studies are required for final evaluation of Ptx in the treatment of TAO.     

Rapid response to psychosocial treatment for adolescent depression: a two-year follow-up

OBJECTIVE: To examine the differential course and treatment outcome of patients who participated in a randomized clinical trial, comparing cognitive, family, and supportive psychotherapies for adolescent major depressive disorder. METHOD: In a sample of 100 depressed adolescents, remission, clinical recovery, recurrence, and functional improvement were examined at the end of acute treatment and at 1- and 2-year follow-up, according to their type of response to treatment. Rapid response was defined as a decline of > or = 50% in the Beck Depression Inventory (BDI) score from pretreatment until the beginning of the second session of psychotherapy, intermediate as a decline of < 50% but > 0%, and initial nonresponse as a BDI score that stayed the same or increased. RESULTS: Rapid responders showed a better outcome at acute treatment, 1-year, and in some measures, 2-year follow-up. For those who had recurrences over time, rapid responders showed a longer period before recurrence. Subjects were most likely to respond rapidly, or not at all, in the supportive cell. CONCLUSIONS: These findings suggest that milder forms of depression may benefit from initial supportive therapy or short trials of more specialized types of psychotherapy. The use of a placebo run-in period might help to "wash out" nonspecific responders.     

Tear hyperosmolarity in renal dialysis patients asymptomatic for dry eye

Plasma levels of IGF-I, IGFBP-I and IGFBP-3 were measured before and during treatment with tamoxifen up to 19+ months in 34 post-menopausal patients with advanced breast cancer. In 28 patients, pro-IGF-IIE (IGF-IIE) levels were determined and IGFBP-3 was evaluated by immunoblot in 27 patients. Tamoxifen suppressed plasma levels of IGF-I by a mean value of 25.5%-37.7% at different times. This effect was fully developed after 1-2 months of treatment. IGF-IIE was decreased by a mean value of 7.7-23.2% at different time intervals during treatment with tamoxifen, but this effect was significant after long-term treatment (19 months +) only. Plasma IGFBP-I increased by a mean value varying between 48.6% and 190.1%. Tamoxifen had no significant effect on total IGFBP-3 levels. However, patients responding to treatment had a 28% reduction in fragmentation of IGFBP-3, while patients with progressive disease had a 36% increase in fragmentation. The difference between responders and non-responders was highly significant. These findings confirm and extend previous observations regarding the effects of treatment with tamoxifen on IGF-I and IGFBP-I. The finding that patients responding to tamoxifen achieve a reduction in the ratio of fragmented to intact IGFBP-3, while patients progressing on therapy experience an increase in the IGFBP-3 fragmentation ratio, suggest that the tumor burden influences IGFBP-3 protease activity in breast- cancer patients.     

Test length and cognitive fatigue: An empirical examination of effects on performance and test-taker reactions.

Person and situational determinants of cognitive ability test performance and subjective reactions were examined in the context of tests with different time-on-task requirements. Two hundred thirty-nine first-year university students participated in a within-participant experiment, with completely counterbalanced treatment conditions and test forms. Participants completed three test sessions of different length: (a) a standard-length SAT test battery (total time 4? hr), (b) a shorter SAT test battery (total time 3? hr), and (c) a longer SAT test battery (total time 5? hr). Consistent with expectations, subjective fatigue increased with increasing time-on-task. However, mean performance increased in the longer test length conditions, compared with the shorter test length condition. Individual differences in personality/interest/motivation trait complexes were found to have greater power than the test-length situations for predicting subjective cognitive fatigue before, during, and at the end of each test session. The relative contributions of traits and time-on-task for cognitive fatigue are discussed, along with implications for research and practice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preseasonal intranasal immunotherapy in birch-alder allergic rhinitis. A double-blind study

A double-blind, placebo-controlled study was carried out to test the clinical efficacy and safety of local nasal immunotherapy (LNIT) in powder form. Twenty-two patients suffering from allergic rhinitis strictly associated with early spring symptoms, with positive skin prick tests and RAST for birch-alder, all responders to a specific nasal provocation test (NPT), received randomly active or placebo treatment for 4 months. Immunotherapy consisted of administration of a set of capsules containing progressively increasing amounts of birch (Betula pendula) and speckled alder (Alnus incana) allergens in powder form with controlled granulometry. The active (birch-alder) and placebo (lactose) group completed the treatment according to a similar schedule. During the pollen season (March-April), the patients who took the active treatment reported less sneezing and rhinorrhea than the placebo group, on the basis of a symptoms score, and the differences were statistically significant; the need for drugs (terfenadine) was also significantly reduced. These findings agreed well with the results of specific NPT after the treatment; only patients in the active group had a higher threshold dose of nasal specific reactivity to birch-alder allergens than in tests before the LNIT.     

Bispectral analysis of the electroencephalogram during induction of anesthesia may predict hemodynamic responses to laryngoscopy and intubation

The use of electroencephalography as a measure of adequacy of anesthesia has achieved limited success. Our purpose was to determine whether the non-linear properties of the electroencephalogram (EEG) as defined by the bispectral index was a better predictor of autonomic responses to endotracheal intubation during opioid-based anesthesia than the linear statistical properties of the EEG formulated by power spectral analysis. Thirty-nine adults scheduled for elective non-cranial surgery had a continuous EEG recorded during induction of anesthesia and endotracheal intubation. Anesthesia consisted of thiopental and nitrous oxide in oxygen, followed by 1 of 5 randomized opioid dose regimens. The EEG was continuously recorded and blood pressure was measured every minute. All electroencephalographic parameters were derived for the 3 min before and after intubation and were compared to the blood pressure and heart rate responses. Responders were defined by 2 analyses: patients who had a 20% or greater increase (1) in blood pressure or (2) in heart rate to laryngoscopy. Responders and non-responders were compared using Student's unpaired t test, and differences due to dose regimens were examined with logistic regression. Based on the criterion for blood pressure change, there were 27 responders and 12 non-responders. Heart rate changes did not differentiate between the two groups. There was a significant difference between response groups as measured by the bispectral index which distinguished responders from non-responders independently of the amount of drug given. None of the variables of power spectral analysis accurately distinguished responder from non-responder.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidemiology of gonococcal and chlamydial infections in Harrow and Brent

We evaluated 355 subjects who entered one of six double-blind placebo-controlled antidepressant drug trials with respect to the occurrence of antecedent adverse life events and their meaning to the patient. Patients were also assessed with regard to the degree of social support they received for the negative life event. The groups differed as to whether they did or did not meet the criteria for melancholic depression; 43 one-week placebo responders were statistically significantly more likely to believe that adverse life events predisposed them to depressive illness and that such life events precipitated their current depression, compared to 312 one-week placebo non-responders. Of the 312 patients who went on to the double-blind phase in which they were treated with either drug (n = 204) or placebo (n = 108), it was noted that, for both melancholic and non-melancholic patients, responders to drug treatment (but not placebo) had a more favourable ratio of social support received/social support desired than non-responders. Non-melancholic responders to both drug and placebo were statistically significantly more likely to report fewer adverse life events and have a less strong belief that adverse life events predispose one to depressive illness than non-responders. Melancholic patients did not show this trend.     

Olfactory functioning before and after temporal lobe resection for intractable seizures.

An olfactory test battery was administered monorhinically to 21 epilepsy patients prior to and 6 mo after unilateral medial temporal lobe resection for treatment of intractable seizures. 33 matched control Ss were also tested. Presurgically, controls and patients exhibited normal sensitivity for 1-butanol. Patients performed at levels significantly below controls on tests for odor discrimination, odor memory, and odor naming. Left-resected patients did not show significant changes following surgery. Right-resected patients demonstrated significant right nostril decline. Postsurgical changes demonstrated by the right-resected group were not attributable to deficits in primary sensory function or to deficits in cognition brought on by surgery. These findings imply that right medial temporal lobe structures play a greater role in olfactory processing than do corresponding structures in the left hemisphere. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

European multicentre experience with modular device (Medtronic Aneurx) for the endoluminal repair of infrarenal abdominal aortic aneurysms

A double-blind study of the tryptophan depletion (TD) challenge was performed on a sample consisting of 20 patients with a major depressive disorder in clinical remission after citalopram treatment. TD was induced by the intake of 43 g of an amino acid mixture containing the five large neutral amino acids. The control group received the same mixture, to which 2.3 g tryptophan had been added. Five of the 12 challenged patients showed a worsening of depressive symptoms during the day of the test. In contrast, there was no mood alteration in the eight control patients. Baseline cortisol levels were significantly higher in responders to TD compared to those in non-responders and controls. Platelet serotonin-receptor function and plasma prolactin levels were correlated. There was a significant positive correlation in the baseline data between rated mood state and plasma cortisol and a significant inverse correlation between related mood state and plasma tryptophan concentration. Thus low mood appeared to be associated with low serotonin precursor availability as well as with high cortisol levels.     

Result of treatment of squamous cell carcinoma of the tongue and floor of the mouth

A statistical analysis was performed on 40 patients with squamous cell carcinoma of the tongue and mouth floor, which could be followed for 6 months or more after initial treatment in the Department of Otorhinolaryngology, School of Medicine, Keio University during the 14 years from 1983 to 1996. The 5-year survival rate determined by the Kaplan-Meier method for each stage was 100% for Stage I, 77.8% for Stage II, 60.0% for Stage III and 44.4% for Stage IV. Thirteen suffered a relapse after initial treatment and patients with relapses among them have all survived after the subsequent salvage surgery. In contrast, in nine patients with cervical relapse, however, the 5-year survival rate was 11.1% with an unfavorable prognosis. This confirmed that suppressing cervical relapses is important for treating tongue and floor mouth cancers. The treatment strategy in our department is characteristic of positive enforcement of prophylactic neck dissection in the surgery and introduction of neoadjuvant chemotherapy (NAC) in the chemotherapy. Prophylactic neck dissection was performed in the 17 patients and no relapse was observed on the side of prophylactic neck dissection. NAC was performed on 26 patients in consideration of suppressed minute metastases and preserved function and 24 determinable cases were statistically analyzed. Among patients who had received NAC, the oral function was successfully preserved without surgical intervention in six patients both patients who showed complete response (CR) and four out of 14 patients who had a partial response (PR) following NAC. This may indicate that the oral function could be preserved in those patients who exhibited CR following NAC, but that preservation could be difficult in patients who exhibited PR. In addition, concerning the accumulated 5-year survival rate in relation to the effect of NAC, responders (CR + PR) accounted for 90.9% and non-responders (no change + progressive disease following NAC) for 15.0% with a very good outcome noted in the responder group. These figures suggest that responders may have a significantly good prognosis in the multivariant analysis including additional background factors before treatment as well. Accordingly, the present therapeutic measures for non-responders must be reexamined and performed more carefully and accurately as compared with those for responders.     

CA 19-9 in evaluating the response to chemotherapy in advanced pancreatic cancer

BACKGROUND/AIMS: The determination of serum carbohydrate antigen 19-9 (CA 19-9) level is useful in managing pancreatic cancer. However, the usefulness of this marker in evaluating the response to chemotherapy has not been fully established. MATERIALS AND METHODS: Serial changes of serum CA 19-9 levels were studied during chemotherapy in 66 pancreatic cancer patients who showed CA 19-9 level of 100 U/ml or greater before treatment. We investigated the relationship between patient survival and reduction in serum CA 19-9 level after treatment. RESULTS: When a responder was defined as a patient whose serum CA 19-9 level was reduced by more than 50% of the pre-treatment level within 2 months after treatment, CA 19-9 response was observed in 9 (13%) of the 66 patients. Median survival times of CA 19-9 responders and non-responders were 141 and 88 days, respectively. Based on Cox regression analysis, the relative risk of cancer death in CA 19-9 responders for non-responders was 0.47 (95% confidence interval, 0.21 to 1.05). CONCLUSIONS: CA 19-9 reduction may be useful for assessing the efficacy of chemotherapy for advanced pancreatic cancer.