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At least 1,063 records · Page 59Linked to original sources
PubMed2006

Can thiazolidinediones delay disease progression in type 2 diabetes?

BACKGROUND: Type 2 diabetes results from increasing insulin resistance coupled with progressive loss of beta-cell function. Further deterioration of beta-cell function is associated with progression of diabetes and the potential development of microvascular and macrovascular complications. SCOPE: This review examines current knowledge of beta-cell function and uses this information to assess how the results of ongoing trials could increase our understanding of disease progression and potential interventions. Data were derived from a Medline search using the search terms 'beta-cell dysfunction', 'IGT', 'thiazolidinediones', 'metformin', and 'sulfonylurea'. RESULTS: The mechanisms that underlie beta-cell dysfunction are complex and most likely involve the interplay of a range of factors that reduce both beta-cell mass and secretory function. These include detrimental effects associated with hyperglycemia itself, elevated free fatty acids, and inflammatory responses linked to adipocyte-derived cytokines, with apoptosis a key underlying mechanism. Early intervention with treatments that address these defects, and preserve beta-cell function while improving insulin sensitivity, may delay disease progression in patients with type 2 diabetes and also prevent the development of diabetes in 'at-risk' individuals. Two of the studies examining the effects of interventions on development and progression of diabetes that are due to report shortly are ADOPT (A Diabetes Outcome Progression Trial), comparing a thiazolidinedione, metformin and a sulfonylurea in patients with type 2 diabetes not previously treated with oral hypoglycemic agents, and DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication), assessing the effects of a thiazolidinedione and an angiotensin-converting enzyme inhibitor in subjects with impaired glucose tolerance and/or impaired fasting glucose. CONCLUSIONS: Although we do not have a full understanding of the mechanisms driving progression of type 2 diabetes, there is growing evidence that we may be able to modulate them and thereby improve patient outcomes.

Diabetes Complications↗
PubMed2005

Progression of kidney disease in type 2 diabetes - beyond blood pressure control: an observational study.

BACKGROUND: The risk factors for progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (DM) have not been fully elucidated. Although uncontrolled blood pressure (BP) is known to be deleterious, other factors may become more important once BP is treated. METHODS: All patients seen in the outpatient clinics of our hospital between January 1993 and September 2002 with type 2 DM and clinical evidence of CKD were evaluated. Progression of kidney disease was evaluated by rate of decline of glomerular filtration rate (GFR) as estimated from the simplified MDRD formula. Variables associated with progression in univariate analyses were examined by multivariate analysis to determine the factors independently associated with kidney disease progression. RESULTS: 343 patients (mean age 69 years; all male; 77% Caucasian) were studied. Mean BP, glycated hemoglobin, and serum cholesterol during the study period were 138/72 mmHg, 8.1%, and 4.8 mmol/L, respectively. Mean decline of GFR was 4.5 ml min-1 1.73 m2-1 yr-1 (range -14 to +32). Low initial serum albumin (p < 0.001), black race (p < 0.001), and degree of proteinuria (p = 0.002), but not blood pressure, glycated hemoglobin, or serum cholesterol, were independently associated with progression. CONCLUSION: In a cohort of diabetic patients with CKD in whom mean BP was < 140/80 mmHg, the potentially remediable factors hypoalbuminemia and proteinuria but not blood pressure were independently associated with progression of kidney disease. Further understanding of the relationship between these factors and kidney disease progression may lead to beneficial therapies in such patients.

Adult↗
PubMed2003

Multicenter prevention trial of slowly progressive type 1 diabetes with small dose of insulin (the Tokyo study): preliminary report.

In 1996, we designed a randomized multicenter study to assess the effects of small doses of insulin on beta cell failure in slowly progressive type 1 diabetes (the Tokyo Study). We report here the preliminary results of this study. Glutamic acid decarboxylase 65 antibody (GADA)-positive patients were randomly divided into 2 groups: one group received insulin (Ins group), the other a sulfonylurea (SU group). Fifty-four patients (24 Ins group, 30 SU group) were analyzed at the end of a 4-year period. All patients underwent a 75 g oral-glucose test (O-GTT) every 6-12 months. The insulin-dependent stage was defined based on an integrated value of serum C-peptide levels on O-GTT ( summation operator CPR; sum of CPR at 0, 30, 60, 90, and 120 min) below 4.0 ng/mL. The summation operator CPR in the SU group decreased progressively from 22.0 +/- 10.6 to 11.3 +/- 7.5 ng/mL over the 48-month period (p < 0.001 vs. baseline). The summation operator CPR in the Ins group was unchanged. Among the SU group, 30% of subjects (9/30) progressed to IDDM, while 8.3% of Ins group subjects (2/24) progressed to IDDM (p = 0.087). With regard to the subjects who had a preserved C-peptide response ( summation operator CPR >/= 10 ng/mL), the proportion of SU group subjects who progressed to IDDM was significantly higher than that of the Ins group (7/28, 25% vs. 0/21, 0%, p = 0.015). Among subjects with a high GADA titer (>/=0 U/mL), 9/14 (64.3%) of the SU group, but only 2/16 (12.5%) of the Ins group, developed IDDM (p = 0.0068). As to those with a high GADA titer and a preserved C-peptide response, SU group subjects progressed to IDDM (7/12, 58.3%) more frequently than Ins group subjects (0/14, 0%) (p = 0.0012). In summary, our results suggest that small doses of insulin effectively prevent beta cell failure in slowly progressive type 1 diabetes. We recommend avoiding SU treatment and instead administering insulin to NIDDM patients with high GADA titer.

Autoantibodies↗
PubMed2004

Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia.

BACKGROUND: Mild cognitive impairment (MCI) is widely viewed as the transition phase between normal aging and Alzheimer disease (AD). Given that MCI can also result from cerebrovascular disease (CVD), the authors used clinical, MRI, and cognitive measures of AD and CVD to test the hypothesis that CVD increases the likelihood of progression from MCI to dementia within 3 years. OBJECTIVE: To examine the impact of CVD on progression of MCI to dementia. METHODS: Fifty-two consecutive patients with MCI (71% men) including many with symptomatic CVD were longitudinally evaluated for 3.1 +/- 1.3 years. MCI was defined as a Clinical Dementia Rating Scale (CDR) score of 0.5. Dementia was defined as progression to a CDR score of > or =1.0. RESULTS: Forty-four percent of the MCI patients had MRI infarcts, 50% of which were symptomatic. Thirty-three percent of patients progressed to dementia, and 37.8% of these had MRI infarcts. Clinically probable or possible AD was diagnosed in approximately 82% of converters. Of the clinical and MRI measures, only hippocampal volume was associated with increased risk to progression (hazard ratio [HR] = 0.31 [95% CI 0.1 to 0.92], p = 0.03). When neuropsychological measures were included in the analysis, memory (HR = 0.90 [95% CI 0.84 to 0.96], p = 0.002) and executive function (HR = 0.96 [95% CI 0.92 to 1.0], p = 0.045) were associated with increased risk of dementia progression, whereas APOE genotype, cerebrovascular risk factors, clinical stroke, presence or absence of lacunes, and extent of white matter hyperintensities did not predict progression. CONCLUSION: Within a heterogenous group of MCI patients, including many with clinically significant CVD, baseline memory and executive performance significantly predicted likelihood to develop dementia.

Aged↗
PubMed2002

Progression of gait disorder and rigidity and risk of death in older persons.

BACKGROUND: Bradykinesia, gait disturbance, rigidity, and tremor are common motor signs in old age. All of these signs are associated with increased morbidity and mortality, but the extent to which they are progressive is unknown. METHODS: Study participants were 787 older Catholic clergy members without clinically diagnosed PD, related conditions, or dementia at baseline. They were evaluated annually for up to 7 years, with >95% follow-up participation by survivors. Evaluations included administration of a modified version of the motor portion of the Unified PD Rating Scale (UPDRS), from which previously established measures of the global UPDRS and four specific motor signs were derived. Scores represent the percent of the total possible UPDRS score obtained. RESULTS: At baseline, the global UPDRS score ranged from 0 to 36.3 (mean +/- SD, 7.3 +/- 6.4). It increased by an average of 0.69 unit per year during follow-up, with more rapid progression in older persons, but there was wide variability with no progression in 21% of subjects and annual increases of up to 8.23 units in the remaining 79%. Of 129 persons who died, 106 had follow-up UPDRS data. In a proportional hazards model, risk of death was associated with both the level of the global UPDRS score at baseline and the annual rate of progression (both p < 0.001). Overall, risk of death in subjects who had some worsening of the global UPDRS score was 2.93 times the rate among those without progression (95% CI, 1.32-6.50). Gait disorder/postural reflex impairment and rigidity worsened, but bradykinesia and tremor did not. Risk of death was associated with worsening of gait/posture but not with the other signs. CONCLUSION: Gait disorder and rigidity, as assessed with the modified UPDRS, are usually progressive in old age. Both the severity of the gait disorder and its rate of progression are strongly associated with risk of death.

Aged↗
PubMedDate not supplied

Effect of tuberculosis preventive therapy on HIV disease progression and survival in HIV-infected adults.

PURPOSE: To determine whether tuberculosis (TB) preventive therapies alter the rate of disease progression to AIDS or death and to identify significant prognostic factors for HIV disease progression to AIDS. METHOD: In a randomized placebo-controlled trial in Kampala, Uganda, 2,736 purified protein derivative (PPD)-positive and anergic HIV-infected adults were randomly assigned to four and two regimens, respectively. PPD-positive patients were treated with isoniazid (INH) for 6 months (6H; n = 536), INH plus rifampicin for 3 months (3HR; n = 556), INH plus rifampicin plus pyrazinamide for 3 months (3HRZ; n = 462), or placebo for 6 months (n = 464). Anergic participants were treated with 6H (n = 395) or placebo (n = 323). RESULTS: During follow-up, 404 cases progressed to AIDS and 577 deaths occurred. The cumulative incidence of the AIDS progression was greater in the anergic cohort compared to the PPD-positive cohort (p < .0001). Among PPD-positive patients, the relative risk of the AIDS progression with INH alone was 0.95 (95% CI 0.68-1.32); with 3HR it was 0.83 (95% CI 0.59-1.17); and with 3HRZ it was 0.76 (95% CI 0.52-1.08), controlling for significant baseline predictors. Among anergic patients, the relative risk of the AIDS progression was 0.81 (95% CI 0.56-1.15). Survival was greater in the PPD-positive cohort compared to the anergic cohort (p = .0001). CONCLUSION: The number of signs or symptoms at baseline and anergic status are associated with increasing morbidity and mortality. Even though the tuberculosis preventive therapies were effective in reducing the incidence of TB for HIV-infected adults, their benefit of delaying HIV disease progression to AIDS was not observed.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Factors influencing progression of renal failure in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end-stage renal failure (ESRF) in the sixth decade of life, but considerable heterogeneity exists in the rate of progression of renal failure. The respective contribution of genetic factors and of potentially amendable factors, such as blood pressure control or protein intake limitation, on the rate of progression in ADPKD patients is still debated. To evaluate the role of factors influencing the rate of progression of renal failure in ADPKD, we retrospectively analyzed the annual rate of decline of creatinine clearance (Ccr) in 109 ADPKD patients followed from the time a Ccr value of 30 to 50 mL per min/1.73 m2 was measured until ESRD and need for hemodialysis (Study A), and in 48 undialyzed ADPKD patients followed for at least 4 yr from the time a Ccr value of 50 to 60 mL per min/1.73 m2 was measured (Study B). In Study A, the decline in Ccr (delta Ccr) (mean +/- SE) was 5.8 +/- 0.2 mL per min/1.73 m2 per year in the whole series, and was lower in females than in males (5.0 +/- 0.2 versus 6.4 +/- 0.2, P < 0.001). Accordingly, ESRF was reached at a later age in female patients (55.1 +/- 1.2 versus 50.6 +/- 1.2 yr, P < 0.01). The age at ESRF in male patients was lower when the disease was transmitted by mother than by father (46.3 +/- 1.9 versus 54.1 +/- 1.8 yr, P < 0.01), whereas no significant effect of the gender of the affected parent was apparent in female patients. By regression analysis, there was a positive but weak relationship between delta Ccr and mean arterial pressure (average value during follow-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not with dietary protein intake (mean value in follow-up, 0.87 +/- 0.03 g/kg per day, r = 0.10, P = 0.33) nor with proteinuria at baseline, which was lower than 0.3 g/day in 104 cases (r = 0.10, P = 0.28). There was a negative relationship between age at ESRF and delta Ccr (r = 0.245, P < 0.05), with a later and slower progression in older subjects. In Study B, the mean decline in renal function during follow-up was 5.3 +/- 0.4 mL/min/1.73 m2 per year, a value close to that observed in Study A. By multiple regression analysis of the overall population (studies A and B combined), only MAP, age and gender were independent predictive factors of delta Ccr but all studied parameters taken together accounted for at best 20% of delta Ccr variation. We conclude that the rate of progression of renal failure in ADPKD patients is mainly determined by gene expression, with female gender and older age associated with a slower progression, whereas blood pressure control, but not protein intake, exerts a limited beneficial influence on the rate of progression in patients with advanced polycystic kidney disease who already have significant renal insufficiency.

Adult↗
PubMed1998

Chronic obstructive uropathy in severe combined immunodeficient (SCID) mice: lymphocyte infiltration is not required for progressive tubulointerstitial injury.

Progressive renal injury in humans and experimental animal models is characterized by tubular atrophy, infiltration of mononuclear inflammatory cells, and interstitial fibrosis. Permanent unilateral ureter ligation represents a reproducible model for investigating mechanisms of progressive kidney injury, and in the rat is characterized by tubular epithelial cell proliferation followed by apoptosis and progressive infiltration of monocytes and lymphocytes. Nevertheless, whether monocytes or lymphocytes play a dominant role in causing tubulointerstitial damage remains to be elucidated. In the current study, a model of chronic obstructive uropathy in the mouse is established and the role of lymphocyte infiltration in the evolution of the tubule and interstitial alterations is investigated. Permanent ligation of the left ureter in wild-type (C3H/HeJ) mice resulted in progressive atrophy of tubules and interstitial fibrosis compared with the contralateral kidney over a 30-d period. Immunoperoxidase studies on frozen sections taken from kidneys at 0, 3, 10, 20, and 30 d after ureter ligation showed that the tubulointerstitial injury was accompanied by a marked and progressive increase in interstitial macrophages and T lymphocytes, with no appreciable increase in B lymphocytes. No increase in inflammatory cells was detected in contralateral kidneys over the same time frame. The significance of T lymphocyte infiltration was examined by comparing the degree of tubular atrophy and interstitial fibrosis and the nature and quantity of the inflammatory infiltrate in wild-type mice and C3HSMn.C-Scid/J (SCID) mice subjected to permanent left ureter ligation. SCID mice have genetic defects in immunoglobulin and T cell receptor gene rearrangements and are devoid of circulating mature B and T lymphocytes. Wild-type and SCID mice developed tubular atrophy and interstitial volume expansion in the ligated kidney to the same degree and at the same rate. SCID mice developed a prominent and marked monocyte/macrophage infiltrate in the ligated kidney, which was essentially equal to that in wild-type mice. In contrast, consistent with the known absence of mature lymphocytes in SCID mice, there was essentially no T lymphocyte infiltration into the ligated kidney of SCID mice. These results demonstrate the effective establishment of the model of maintained unilateral ureter ligation in mice, which is readily applicable to genetic mutant strains thus allowing for specific investigation of the role of individual components of the inflammatory response in progressive tubulointerstitial injury. These studies further demonstrate that lymphocyte infiltration is not required for progressive tubular atrophy and increased interstitial fibrosis after maintained unilateral ureter ligation.

Animals↗
PubMed2000

Periodontal disease progression.

BACKGROUND: The objective of this investigation is to use noninvasive, state-of-the-art, diagnostic techniques to measure periodontal disease progression and model periodontal disease activity over time. In this investigation, digital subtraction radiography and an electronic controlled force periodontal probe capable of attachment level measurement were used to measure bone loss and attachment loss, respectively. The use of these nearly continuous measures of attachment and bone loss allowed detection of small amounts of disease activity and provided data to be used in modeling of the disease process over time. METHODS: Forty-four patients were studied for 18 months. Examinations used clinical attachment level measures at 1-month intervals and quantitative radiology at 6-month intervals. The sites were analyzed by regression for statistically significant changes. These data were used to determine sites of periodontal disease activity for testing various models of periodontal disease progression. RESULTS: Overall 22.8% of sites lost attachment, 5.4% gained, and 71.7% demonstrated no statistically significant change. The mean time to lose 1 mm of attachment was 8.4 +/- 0.6 months. In the first model tested a step-wise discriminant analysis was used to determine whether or not baseline measurements of plaque (PI), gingival inflammation (GI), attachment loss, and probing depth (PD) could be used to derive a satisfactory model for disease progression. Although the overall model was statistically significant with PI, PD, and GI contributing to the model (Wilks' lambda = 0.859, F = 5.71, P <0.0012), its predictive power was relatively weak. A considerably stronger significant model resulted when the rate of attachment loss over the first 6 months, baseline PI, and baseline GI were included (Wilks' lambda = 0.712, F = 14.17, P<0.00001). A significant model also resulted when bone loss during the first 6 months and baseline probing depth were included (Wilks' lambda = 0.438, F = 61.48, P<0.00001). When the last model was applied to each site, the sensitivity in predicting disease progression was 80.0% and the specificity in ruling out progressive disease was 93.9%. CONCLUSIONS: This study indicates that clinically significant progression of attachment loss in posterior tooth sites occurs as a frequent event in adult periodontitis. The modeling data also suggest that short-term (6 month) measures of periodontal disease progression greatly improve the ability to model attachment loss over a longer period in untreated periodontitis patients.

Calibration↗
PubMed1996

Use of the Milwaukee brace for progressive idiopathic scoliosis.

One hundred and two (92 per cent) of 111 immature patients in whom idiopathic scoliosis had been treated with a Milwaukee brace were followed to determine the effectiveness of the brace in preventing progression of the scoliosis. The average time from cessation of bracing until the latest radiographs were made for the patients who were managed non-operatively was six years and four months. The average progression of the curve, from the time of initial bracing until use of the brace was stopped, in the eighty-eight patients who were included in the statistical analysis was 4 degrees. The curve continued to progress an average of 5 degrees after use of the brace was stopped in the patients who did not have an arthrodesis. Forty-two patients (48 percent) had more than 5 degrees of progression at the time that use of the brace was stopped. Thirty-seven patients (42 per cent) had an operation or a curve of sufficient magnitude to warrant operative intervention. The maximum correction of the Cobb angle in the brace had prognostic importance for progression of the curve. The patients in whom the curve did not progress or who did not need operative intervention had had an average correction of 20 per cent, while the patients who had a failure had had an average correction of 8 per cent. The patients who eventually had the indications for an arthrodesis were on the average, one year younger (eleven years and none months) and had a curve of a larger magnitude at the time of bracing than the patients who did not need an arthrodesis. The findings of this study do not agree with previously reported favorable results with bracing and raise questions about whether the natural history of progressive idiopathic scoliosis is truly altered by use of the Milwaukee brace.

Adolescent↗
PubMed2004

Does hypervascularity of liver metastases as detected on MRI predict disease progression in breast cancer patients?

OBJECTIVE: The aim of our study was to evaluate the association of the vascularity of liver metastases, as characterized by MRI, and disease progression in breast cancer patients. MATERIALS AND METHODS: Sixteen breast cancer patients with liver metastases who underwent MRI before and after systemic therapy were retrospectively identified. On the basis of comparison of each MRI examination with the previous examination, disease status of the patients was classified as complete response, partial response, stable disease, or progressive disease. Liver metastases were characterized as hyper- or hypovascular on the basis of the degree of enhancement in the arterial, portal, and interstitial phases of imaging after administration of a contrast agent. Fisher's exact test and ordinal logistic regression models, including the type of systemic therapy, presence of multiple metastases, and hormone receptor status, were used to estimate the unadjusted and risk-adjusted association between the presence of hypervascular liver metastases and disease progression. RESULTS: All patients in our sample (n = 16) were women and most (12/16, 75%) were white. Their median age was 51.5 years. In unadjusted analyses, the association between the presence of hypervascular liver metastases and disease progression was statistically significant (p < 0.0001). In multiple logistic regression analyses, hypervascular liver metastases were found to be an independent predictor of disease progression. Patients with hypervascular liver lesions were 20.5 times more likely to experience disease progression than patients without hypervascular metastases (odds ratio, 20.5; 95% confidence interval, 5.1-83.5; p < 0.0001). CONCLUSION: Our analysis provides suggestive evidence that disease progression can be predicted through MRI assessment of the vascularity of liver metastases in patients with breast cancer.

Adult↗
PubMed1998

Progression to type 2 diabetes among high-risk groups in Kin-Chen, Kinmen. Exploring the natural history of type 2 diabetes.

OBJECTIVE: To examine the natural history of 654 high-risk subjects (340 men and 314 women) with fasting hyperglycemia (first fasting plasma glucose [FPG] level 5.6-7.8 mmol/l) who also exhibited 2-h postload glucose concentrations < 11.1 mmol/l and an FPG level < 7.8 mmol/l in a 75-g oral glucose tolerance test (OGTT). We were particularly interested in comparing the likelihood of developing type 2 diabetes for those with persistent fasting hyperglycemia (PFH), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). PFH is a relatively new definition, and those with PFH used to be defined as NGT according to WHO criteria. RESEARCH DESIGN AND METHODS: Subjects were located in a 1992-1994 community-based population survey and followed up and reexamined during 1995-1996. An OGTT was used to determine who had progressed to type 2 diabetes. Risk factors predictive of subsequent progression to type 2 diabetes were determined by comparing baseline variables from the 1992-1994 survey with data of those who had or had not progressed to type 2 diabetes in 1995-1996. RESULTS: Of 654 high-risk subjects screened in the baseline survey, 481 (73.5%, 255 men and 226 women) were followed up. Of these, 8.1% had progressed to diabetes (4.1% progression/year, 95% CI 2.3-5.9). Of 131 baseline IGT subjects, 17.6% progressed to diabetes (8.8% progression/year, 6.3-11.3), but only 7.4% of 95 PFH subjects (3.7% progression/year, 2.0-5.4) and 3.5% of 255 NGT subjects (1.8% progression/year, 0.1-3.0) progressed to diabetes. CONCLUSIONS: The rates of progression to type 2 diabetes were lowest from the NGT subgroup, highest from the IGT group, with the PFH group in the middle, suggesting that PFH might be a transitional condition that precedes IGT and diabetes. Other significant predictors of subsequent diabetes were baseline BMI, baseline hyperuricemia, baseline FPG, and 2-h plasma glucose concentration.

Adult↗
PubMed1995

Progressive multifocal leukoencephalopathy: the evolution of a disease once considered rare.

Progressive multifocal leukoencephalopathy, a formerly rare disease that chiefly occurred in persons with underlying lymphoma and chronic lymphocytic leukemia, is now seen with increasing frequency in the era of acquired immunodeficiency syndrome. Progressive multifocal leukoencephalopathy is currently estimated to arise in 5% of all human immunodeficiency virus-infected individuals. The clinical features of the disorder in patients with acquired immunodeficiency syndrome do not appear to be significantly different from progressive multifocal leukoencephalopathy occurring in association with other immunosuppressive disorders. Radiographically, the appearance of HIV dementia on magnetic resonance imaging is sometimes confused with that of progressive multifocal leukoencephalopathy. Among the characteristics that are helpful in distinguishing between the two disorders are the presence of focal findings, the rate of disease progression, the specific magnetic resonance imaging attributes, including the location of the lesions, and certain cerebrospinal fluid parameters, including surrogate markers for human immunodeficiency virus dementia and the presence of myelin basic protein. The remarkable increase in the burden of progressive multifocal leukoencephalopathy has provided a vital impetus for its study, particularly with respect to diagnosis and therapy. Establishing an unequivocal diagnosis of progressive multifocal leukoencephalopathy currently requires brain biopsy. The application of polymerase chain reaction for JC virus amplification to cerebrospinal fluid samples suggests that it may provide an alternative means of diagnosis. Recent in vitro studies of cytosine arabinoside and camptothecin suggest that they, or similar agents, may prove useful in the treatment of this illness and well-designed clinical trials are underway.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[Slowly progressive dressing and constructional apraxia: symptomatological study, especially for dressing apraxia].

In 1982, Mesulam drew attention to a clinical picture characterized by slowly progressive aphasia without dementia, and since then, there have been many such reports. Recently, there have been 30 reports of slowly progressive apraxia. However, the nature of this apraxia is not uniform. We now report a patient with slowly progressive dressing and constructional apraxia. The patient is a 60-year-old right-handed woman with a 2-year history of a slowly progressive praxic disturbance. On admission, she was alert and aware of this difficulty. A neurological examination disclosed mild rigidity and myoclonus in her left hand. A neuropsychological assessment disclosed severe dressing apraxia, which was unlikely to be caused by dementia and moderate constructional apraxia. Her dressing apraxia was manifested in upper limbs, neck, trunk and lower limbs. However, she could express verbally the action of dressing. She also showed mild limb-kinetic apraxia, but neither ideational apraxia nor ideomotor apraxia was present. Aphasia and agnosia were also absent. On an MRI, the bilateral cerebral hemispheres were atrophic (right > left). A 99m-Tc ECD SPECT revealed decreased uptake in the right cerebral hemisphere and left frontal lobe, and an EEG showed slow waves over the right cerebral hemisphere. There have been 30 reports of slowly progressive apraxia. Most of these cases presented with slowly progressive clumsiness in one or both hands as an initial symptom, followed by constructional, ideomotor or dressing apraxia. Our patient differed from these cases in that dressing and constructional apraxia progressed slowly without any other apraxia except only mild limb-kinetic apraxia. There was a similarity between dressing apraxia of our patient and that of Marie's and Brain's original cases.

Activities of Daily Living↗
PubMed1999

Dedifferentiation in the metastatic progression of prostate carcinoma.

BACKGROUND: Dedifferentiation is a distinctive feature of cancer progression. Detailed histologic analysis of primary prostate carcinoma and synchronous lymph node metastases may improve our understanding of the complex process of cancer progression and metastasis. METHODS: The authors studied 242 regional lymph node positive prostate carcinoma patients who underwent radical prostatectomy and bilateral lymphadenectomy between 1987 and 1992 at the Mayo Clinic. Patients ranged in age from 47-79 years (median, 66 years). The median follow-up was 6.1 years. Gleason scores of lymph node metastases and primary tumors were compared and correlated with systemic disease progression. Histologic dedifferentiation was defined as a higher Gleason grade in the lymph node metastases than in the primary tumor. Systemic disease progression was defined as the presence of distant metastases documented by biopsies, abdominal computed tomography, plain radiograph, or bone scan. RESULTS: The 5-year systemic progression free survival (PFS) rate was 90%. The Gleason score in the lymph node metastases was higher than in the primary tumor in 45% of patients, lower in 12% of patients, and matched exactly in 43% of patients. The 5-year PFS was significantly different between patients with histologic dedifferentiation (88% +/- 3) and those without dedifferentiation (94% +/- 2) (P = 0.04). Adjusting for the Gleason grade of the primary tumor and total lymph node tumor volume, the relative risk for disease progression associated with dedifferentiation was 1.8 (95% confidence interval, 0.7-4.7; P = 0.25). CONCLUSIONS: The findings of the current study demonstrate the morphologic heterogeneity of metastases from prostate carcinoma. There is a trend toward histologic dedifferentiation when prostate carcinoma metastasizes to regional lymph nodes. This dedifferentiation, although univariately significant, was not associated with disease progression when adjusted for lymph node tumor volume.

Aged↗
PubMed1999

[The prognostic markers of HIV infection progression. A study of the p24 antigen in a cohort of 251 patients].

BACKGROUND: Prospective study of AIDS or death progression in a cohort of 251 HIV infected patients whose time of seroconversion is unknown, with 2 main objectives: 1. To analyse plasma level p24 antigen as a marker of progression. 2. To evaluate stability of plasma levels of p24 antigen as a marker of progression. PATIENTS AND METHODS: 251 patients were studied, most on antiretroviral therapy, who were attended at HIV/AIDS Unit of Internal Medicine Service of the Hospital Universitario Arnau de Vilanova de Lleida. Mean initial CD4 cell count were 376 x 10(6)/L (range: 0.8-1350) 51 cases had been diagnosed previously with AIDS, their were therefore excluded. Analysis of survival, according to initial plasma p24 antigen and Cd4 cell count as well as the stability of plasma level p24 antigen was performed by Kaplan-Meier test. Relative risk were calculate by Cox's proportional hazard model. RESULTS: During a follow-up period of 24 months, 38 patients progressed to AIDS or died. Relative risk (RR) of progression to AIDS or death related to the group with p24 antigen < 40 pg/ml was 5.48 when p24 antigen => 40 pg/ml (p < 0.0005). Relative risk of progression to AIDS or death for the patients with unstable plasmatic level of p24 antigen related to the group with stable plasmatic level was 4.25 (p < 0.0005). CONCLUSIONS: Plasma level and stability of p24 antigen are useful as a markers of risk of AIDS progression or death and they behaves as an independent prognostic markers in our patients. p24 antigen < 40 pg/ml is associated with a better prognosis.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Progression curves for endometrial lesions.

OBJECTIVE: To derive a numeric measure for the progression of endometrial lesions as a baseline study for an eventual assessment of chemopreventive intervention efficacy. STUDY DESIGN: Tissue sections from normal endometrium at the proliferative and secretory phase, simple hyperplasia, atypical hyperplasia from cases free of concomitant adenocarcinoma and adenocarcinoma of the endometrium were recorded at high spatial resolution. Six cases from each diagnostic category were chosen as "typical," and 60 epithelial nuclei were randomly selected for measurement for each case. Discriminant analyses were carried out to derive a direction of progressive change in feature space and to correct the progression curve for the presence of cells not expressing progressive change among the random sample of nuclei. RESULTS: A well-conditioned progression curve was derived based on the mean discriminant function scores for each diagnostic category and the mean nuclear abnormality of the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei. The lesion signatures showed a clear trend toward extension into the range of higher nuclear abnormalities with increasing progression. There was an indication that abnormal endometrial lesions may comprise cases with distinctly different degrees of nuclear abnormality. CONCLUSION: A numeric assessment of lesion progression for endometrial lesions, based on karyometric measurements, is possible. The data suggest that additional analysis may provide further characterizing information for individual lesions.

Adenocarcinoma↗
PubMedDate not supplied

Relative tibial and femoral varus as a predictor of progression of varus deformities of the lower limbs in young children.

Many young children present to pediatric orthopaedic surgeons with genu varum and mild beaking of the medial metaphysis on x-ray. Predicting whether these deformities will progress is challenging. In addition, there is no consensus as to whether these children should all be classified as having Blount disease. To avoid this latter problem, the authors included in this study all children presenting with bowed legs, regardless of diagnosis. With the aim of improving the ability to predict progression, the authors tested the hypothesis that patients with progression have more tibial than femoral varus. The authors reviewed 173 varus limbs of 98 patients younger than 4 years old. The authors determined the angular deformity in both femur and tibia by measuring the angles between their mechanical axes and the transverse axis of the knee, and determined the contribution of tibial deformity as a percentage of the total (%DT). The metaphyseal-diaphyseal angles of the tibia (MDA) were also measured to compare the value of that test with the %DT. There were 22 limbs with progressive and 141 limbs with resolving varus. Both the MDA and %DT were significantly different between groups. Tibial varus was found to exceed femoral varus in all patients with progression and also in several patients whose deformity resolved spontaneously. Although more specific and more sensitive than the MDA, the %DT is a good, but not perfect, predictor of progression. However, all patients in this series with both a %DT >50% and an MDA of 16 degrees or greater went on to progress. Using both of these tests together may therefore provide the surgeon with a reliable indicator of the children who would benefit from surgical correction.

Bone Malalignment↗