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PubMed2000

Acute rejection-associated tubular basement membrane defects and chronic allograft nephropathy.

BACKGROUND: Acute rejection is a major risk factor for chronic allograft nephropathy, although the link(s) between these events is not understood. The hypothesis of this study is that alterations in tubular basement membranes (TBMs) that occur during acute rejection may be irreversible and thereby play a role in the development of chronic allograft nephropathy. METHODS: Fourteen renal transplant patients were selected, each having had two or more biopsies performed (42 total). All biopsies were scored for acute and chronic rejection using Banff 1997 criteria. The initial biopsy showed only acute interstitial rejection (type I rejection). No biopsies contained significant chronic arterial lesions of chronic vascular rejection. The entire cortex was examined on Jones methenamine silver-stained sections at x400 for interruption in TBM staining. The number of tubules with TBM abnormalities was counted, and the renal cortical area was measured by image analysis. Periodic acid-Schiff/immunoperoxidase stain was performed on 12 acute rejection biopsies stained for laminin, cytokeratin 7, CD3, CD20, and CD68. Controls consisted of 11 biopsies (8 negative for rejection and 3 acute tubular necrosis). RESULTS: Numerous TBM alterations in silver staining were identified as being associated with acute rejection and tubulitis, consisting of abrupt TBM discontinuities and/or extreme attenuation with segmental or complete absence of TBM. A loss of TBM matrix proteins was confirmed by absent laminin staining in areas of acute rejection and tubulitis. There was herniation of tubular cells into the interstitium through TBM defects confirmed by cytokeratin staining. The TBM defects were spatially associated with inflammatory cells, particularly macrophages. When the biopsies were divided into two groups, <10 and> 10 TBM breaks/mm2, there were statistically significant morphologic and clinical correlations. The number of TBM disruptions correlated with the serum creatinine at the time of biopsy, a combined Banff t + i score, the difference in tubular atrophy between the initial and most recent biopsy and the difference between the nadir creatinine and most recent creatinine. CONCLUSION: Damage to TBM develops in acute rejection as a consequence of interstitial inflammation and tubulitis. These lytic events correlate with the later development of clinical and morphologic evidence of chronic injury in the absence of arterial injury of chronic rejection. We suggest that chronic allograft nephropathy may have an inflammatory interstitial origin.

Acute Disease↗
PubMedDate not supplied

The effect of sodium valproate on sleep, reaction times, and visual evoked potential in normal subjects.

The effect of enteric-coated sodium valproate on 10 normal volunteer subjects was evaluated using simple reaction times, the visual evoked potential (VEP), and EEG sleep recording. Placebo, low-drug (500 mg), high-drug (1,000 mg), and withdrawal conditions were investigated. No significant treatment effect was found for simple reaction time nor was there any significant effect on either the latency or the amplitude of the VEP. Sleep recordings were analysed visually and also using an automated technique consisting of simple period analysis. The automated sleep results suggested that there was a decrease in rapid eye movement activity and an increase in delta activity under the high-drug condition. The visually analysed data did not reach significance, although they followed the same trends as those analysed automatically. It is possible that the automated results reflect an EEG frequency change rather than a change in the sleep cycle itself caused by treatment with sodium valproate.

Adult↗
PubMed1991

The role of cirrhosis in memory functioning of alcoholics.

The effects of alcoholism and liver disease on memory functioning in alcoholics were studied by comparing four groups: normal healthy controls, alcoholics without liver disease, alcoholics with biopsy-confirmed cirrhosis, and nonalcoholics with postnecrotic cirrhosis. Memory capacity was evaluated employing the Benton Visual Retention Test (BVRT), the Rey-Osterreith Complex Figure Test, Digit Span, and the Brown Peterson four-word short-term memory test. A 2 x 2 ANOVA revealed significant main effects for both alcohol and cirrhosis on Digits Forward and the total score on the Brown Peterson test. Additionally, there were significant main effects for cirrhosis on the BVRT. The Brown Peterson test was analyzed using a repeated measures 2 x 2 ANOVA. Significant effects for cirrhosis were observed at all three interpolation periods. The effects for alcohol approached significance at the 30-sec (most difficult) interpolation period. Analysis of error patterns on the Brown Peterson test indicated that overall omission errors were most commonly made among all groups. Significant effects were found for alcohol on omissions and intrusion, while the cirrhosis factor yielded significant effects for phonemic, perseverative, and omission errors. This study demonstrates the importance of liver disease underlying the etiology of memory impairments in alcoholics. The results confirm our earlier findings that neuropsychologic deficits seen in alcoholics may be the result of the combination of alcohol abuse and liver disease.

Adult↗
PubMed1975

Electroencephalographic and behavioral changes associated with papaverine administration in healthy geriatric subjects.

A double-blind cross-over procedure was used to evaluate the effects of papaverine hydrochloride on the electroencephalogram (EEG), cognition, mood and psychologic test performance of 10 healthy geriatric volunteers. During the two-week period, each subject was tested four times: before and after receiving papaverine and before and after receiving placebo. Period analysis revealed that a 300-mg dose of papaverine (Pavabid Plateau Caps) increased EEG alpha activity (8-13 cycles per second) and decreased the beta2 range (27-40 cps). Baseline values for six mood factors, short-term memory, complex problem solving, and attention were not altered significantly by either drug or placebo. Results of the Subject Paced Digit Symbol Substitution Test indicated that papaverine may produce some improvement in simple cognitive functioning. No adverse effects were associated with the use of papaverine.

Alpha Rhythm↗
PubMed1997

Circadian rest-activity rhythms in demented and nondemented older community residents and their caregivers.

OBJECTIVE: Disruptive nocturnal behaviors (DNBs) of older people often threaten the caregiving arrangements on which their community tenure depends. Dementing disorders are especially prone to result in disrupted sleep and agitated behaviors ("sundowning"). The objective here was to develop an objective correlate of DNBs, by which their severity and effects on caregivers can be measured. DESIGN: Quantitative comparison of subjective sleep and motor activity patterns in older people and their caregivers. It was hypothesized that older people with reported DNBs would be more motorically active at night than their caregivers. SETTING: Subjects' homes. PARTICIPANTS: Twenty-five demented and 18 nondemented older day-care participants and their paired caregivers. MEASUREMENTS: Older subjects and caregivers simultaneously kept daily sleep logs and recorded wrist motor activity every .5 minute for 9 days. A novel method was devised to identify and exclude from analysis periods when the activity monitor was not being worn. Such periods were common. Activity data were analyzed by computing hourly means and by fitting cosine models by least squares. RESULTS: Demented older people were not significantly more active at night than their caregivers, though group differences varied by time of night. They were significantly less active in the daytime than were their caregivers. Nondemented older people were significantly more active at night than their caregivers and were as active by day as their caregivers. The caregivers of demented and nondemented older people had similar rest-activity patterns. The mean amplitudes of cosine models were smaller in the older adults. Acrophases (peaks) fell between 2 and 3 pm and did not differ significantly among the groups. CONCLUSIONS: As a result of increased nighttime motor activity and decreased daytime activity, rest-activity rhythms were flatter in older adults than in caregivers. This was not explained fully by age and does not necessarily imply that the output of a circadian pacemaker was low. Decreased daytime activity may have resulted from deficient physical stimulation or frailty. Frailty may also explain why nighttime activity was not more elevated in the demented older people. Increased nighttime activity is probably explained by depression, sleep-schedule disturbances, restless legs, or other sleep disorders. Judging by their shared variations of activity, caregivers interacted mainly with the demented older people at bedtime and at rising time in the morning.

Aged↗
PubMed1995

Crevicular fluid osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as markers of rapid bone turnover in periodontitis. A pilot study in beagle dogs.

The objective of this study was to correlate the levels of 2 putative markers of bone metabolism, namely osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), to the progression of experimental alveolar bone loss in the beagle dog. 36 control sites and 36 experimental sites in 2 beagle dogs were assessed longitudinally at 2-week intervals for gingival crevicular fluid (GCF) osteocalcin and ICTP levels during a 6-month observation period. Analysis of osteocalcin and ICTP in GCF was performed by RIA. During the study, bone-seeking radiopharmaceutical uptake (BSRU) of 99mTc-MDP was assessed monthly; standardized radiographs were taken at 2-week intervals. The results showed osteocalcin and ICTP levels in GCF increased significantly (p < 0.05) by 2 weeks following initiation of disease. This increase preceded significant increases in BSRU by 2 weeks and radiographic evidence of bone loss by 4 weeks. BSRU was significantly elevated (p < 0.05) at experimental sites as compared to controls at 4 and 8 weeks post-disease initiation. Osteocalcin in GCF peaked 8 and 10 weeks after ligature placement in experimental sites at levels nearly 10-fold greater than contralateral paired control sites. ICTP levels in GCF remained elevated throughout the entire disease progression phase. Following the removal of ligatures, both GCF osteocalcin and ICTP levels dropped precipitously approaching control values. Osteocalcin revealed overall a positive predictive value (PPV) and negative predictive value (NPV) for future bone loss during disease progression of 0.87 and 0.34, respectively, while ICTP showed both high PPV and NPV of 0.87 and 0.91 respectively. Results from this study in the dog model indicate that osteocalcin and especially ICTP relate to indices of active periodontal bony destruction and suggest that these molecules may serve as predictive markers for future alveolar bone loss.

Alveolar Bone Loss↗
PubMed2005

Analysis of the crown fractures and crown-root fractures due to dental trauma assisted by the Integrated Clinic from 1992 to 2002.

The purpose of this study was to analyze crown fractures and crown-root fractures due to dentoalveolar trauma, treated in the Integrated Clinic comprehensive dental care at Aracatuba School of Dentistry (UNESP), from January 1992 to July 2002. The data were obtained from files of trauma cases. On the analysis period, 293 patients had crown fractures or crown-root fractures, in 605 teeth. Sixty-nine percent were males and 31% were females. Adolescents between 11 and 18 years old were the most prevalent group (41.6%) and the maxillary arch was the most commonly traumatized (83%). The most commonly affected tooth was the maxillary central incisor (58.3%). The most frequent causes were falls from bicycles (30.8%). It was concluded that the reality of the local service is similar to the published data.

Accidental Falls↗
PubMed1976

Biofeedback control of migraine: a pilot study.

A group of six subjects was trained, using biofeedback procedures, in the voluntary regulation of hand temperature as a means of controlling migraine attacks. The training procedure and its relationship to migraine activity is described. Daily records of migraine activity were kept during base-line, training, and follow-up periods. Analysis of this data revealed statistically and clinically significant improvement on several indices of migraine activity. Evidence for a concomitant improvement in the ability of subjects to produce voluntary increases in hand temperature is presented.

Adult↗
PubMed1979

Effect of environmental parameters on the biodegradation of oil sludge.

A laboratory study was conducted with the aim of evaluating and optimizing the environmental parameters of "landfarming", i.e., the disposal by biodegradation in soil of oily sludges generated in the refining of crude oil and related operations. Oil sludge biodegradation was monitored by CO2 evolution and by periodic analysis of residual hydrocarbons. The parameters studied were soil moisture, pH, mineral nutrients, micronutrients, organic supplements, treatment rate, teratment frequency, and incubation temperature. Oil sludge biodegradation was optimal at a soil water-holding capacity of 30 to 90%, a pH of 7.5 to 7.8, C:N and C:P ratios of 60:1 and 800:1, respectively, and a temperature of 20 degrees C or above. Addition of micronutrients and organic supplements was not beneficial; sewage sludge interfered with hydrocarbon biodegradation. Breakdown of the saturated hydrocarbon (alkane and cycloalkane) fraction was the highest at low application rates, but higher application rates favored the biodegradation of the aromatic and asphaltic fractions. An application rate of 5% (wt/wt) oil sludge hydrocarbon to the soil (100,000 liters/hectare) achieved a good compromise between high biodegradation rates and efficient land use and resulted in the best overall biodegradation rate of all hydrocarbon classes. Frequent small applications resulted in higher biodegradation than single large applications. Two 100,000-liter/hectare (255 barrels per acre) or four 50,000-liter/hectare oil sludge hydrocarbon applications per growing season seem appropriate for most temperate zone disposal sites.

Bacteria↗
PubMed2000

Depletion of lymphocytes and diminished cytokine production in mice infected with a highly virulent influenza A (H5N1) virus isolated from humans.

Previously, we observed that several virulent influenza A (H5N1) viruses which caused severe or fatal disease in humans were also lethal in BALB/c mice following dissemination of the virus to solid organs, including the brain. In contrast, one particular human H5N1 virus was nonlethal in mice and showed no evidence of systemic spread. To compare H5N1 viruses of varying pathogenicity for their ability to alter the mammalian immune system, mice were infected with either influenza A/Hong Kong/483/97 (HK/483) (lethal) or A/Hong Kong/486/97 (HK/486) (nonlethal) virus and monitored for lymphocyte depletion in the blood, lungs, and lymphoid tissue. Intranasal infection with HK/483 resulted in a significant decrease in the total number of circulating leukocytes evident as early as day 2 postinfection. Differential blood counts demonstrated up to an 80% drop in lymphocytes by day 4 postinfection. In contrast, nonlethal HK/486-infected mice displayed only a transient drop of lymphocytes during the infectious period. Analysis of lung and lymphoid tissue from HK/483-infected mice demonstrated a reduction in the number of CD4(+) and CD8(+) T cells and reduced synthesis of the cytokines interleukin-1beta and gamma interferon and the chemokine macrophage inflammatory protein compared with HK/486-infected mice. In contrast, the cytokine and chemokine levels were increased in the brains of mice infected with HK/483 but not HK/486. Evidence of apoptosis in the spleen and lung of HK/483-infected mice was detected in situ, suggesting a mechanism for lymphocyte destruction. These results suggest that destructive effects on the immune system may be one factor that contributes to the pathogenesis of H5N1 viruses in mammalian hosts.

Animals↗
PubMed1990

Conditional expression of RPA190, the gene encoding the largest subunit of yeast RNA polymerase I: effects of decreased rRNA synthesis on ribosomal protein synthesis.

The synthesis of ribosomal proteins (r proteins) under the conditions of greatly reduced RNA synthesis were studied by using a strain of the yeast Saccharomyces cerevisiae in which the production of the largest subunit (RPA190) of RNA polymerase I was controlled by the galactose promoter. Although growth on galactose medium was normal, the strain was unable to sustain growth when shifted to glucose medium. This growth defect was shown to be due to a preferential decrease in RNA synthesis caused by deprivation of RNA polymerase I. Under these conditions, the accumulation of r proteins decreased to match the rRNA synthesis rate. When proteins were pulse-labeled for short periods, no or only a weak decrease was observed in the differential synthesis rate of several r proteins (L5, L39, L29 and/or L28, L27 and/or S21) relative to those of control cells synthesizing RPA190 from the normal promoter. Degradation of these r proteins synthesized in excess was observed during subsequent chase periods. Analysis of the amounts of mRNAs for L3 and L29 and their locations in polysomes also suggested that the synthesis of these proteins relative to other cellular proteins were comparable to those observed in control cells. However, Northern analysis of several r-protein mRNAs revealed that the unspliced precursor mRNA for r-protein L32 accumulated when rRNA synthesis rates were decreased. This result supports the feedback regulation model in which excess L32 protein inhibits the splicing of its own precursor mRNA, as proposed by previous workers (M. D. Dabeva, M. A. Post-Beittenmiller, and J. R. Warner, Proc. Natl. Acad. Sci. USA 83:5854-5857, 1986).

Base Sequence↗
PubMed2004

Tissue invasiveness and non-acidic pH in human candidiasis correlate with "in vivo" expression by Candida albicans of the carbohydrate epitope recognised by new monoclonal antibody 1H4.

BACKGROUND: The morphogenetic conversion between yeast and hyphal growth forms appears to be crucial in the pathogenesis of invasive candidiasis, and can be regulated by environmental signals such as extracellular pH. AIMS: To characterise the epitope recognised by monoclonal antibody 1H4, and to evaluate the expression of its corresponding epitope in Candida albicans cells under different conditions of pH and temperature, and "in vivo", in tissue samples from patients with human candidiasis. METHODS: Monoclonal antibody 1H4 was generated against the 58 kDa cell wall mannoprotein of C albicans (mp58), and was further characterised by immunoblot analysis, periodate treatment of the antigenic preparations, and agglutination experiments of C albicans strains 3153A, SC5314, and 412, cultured under different environmental conditions (growth media and pH). An immunohistochemical study was performed in 24 human tissue samples from patients with mucocutaneous and systemic candidiasis. RESULTS: 1H4 recognises a pH sensitive carbohydrate epitope on the surface of C albicans cells, and this epitope is not restricted to mp58, but is shared with other cell wall mannoproteins. Immunohistochemical findings indicated that expression of the 1H4 epitope on C albicans cells in tissue sections from human candidiasis correlates with tissue invasion and pH of the niche. 1H4 immunoreactivity was also found in candida remnants within macrophages. CONCLUSIONS: The fact that 1H4 epitope expression selectively identifies invasive forms of C albicans, in addition to candida remnants within macrophages, supports its potential value in the diagnosis and management of human candidiasis.

Animals↗
PubMed1997

Asthma mortality in Australia 1920-94: age, period, and cohort effects.

STUDY OBJECTIVE: To investigate asthma mortality during 1920-94 in Australia in order to assess the relative role of period and birth cohort effects. DESIGN: Asthma mortality (both sexes) was age standardised and examined for changes over time. The data were also examined for age, period, and cohort (APC) effects using Poisson regression modelling. SETTING: National Australian mortality data. PARTICIPANTS: Population (both sexes) aged 15-34 years, 1920-94. MAIN RESULTS: Age adjusted period rates indicate an increase in asthma mortality during the 1950's, and increases and subsequent falls (epidemics) during the mid 1960s and late 1980s. APC modelling suggested an increasing cohort effect (adjusted for both age and period) from the birth cohort 1950-54 onwards. Period effects (adjusted for age and cohort) are characterized by an increase in the 1950s (possibly due to changes in diagnostic labelling), minimal or no increases in the mid 1960s and late 1980s (where period peaks had been noted when data were adjusted for age only), and declines in mortality risk subsequent to the periods where age-period analysis had noted increases. Thus, in Australia, some of the mid 1960s epidemic in asthma deaths, and all of the late 1980s mortality increase, seem to be attributable to cohort effects. CONCLUSIONS: The increase in asthma mortality cohort effect is consistent with empirical evidence of recent increases in prevalence (and presumably incidence) of asthma in Australia, and suggests the need for more research into the underlying environmental aetiology of this condition.

Adolescent↗
PubMed1999

Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects.

OBJECTIVE: To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy. METHODS: A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased. RESULTS: Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences. CONCLUSION: For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.

Adult↗
PubMed2000

Self reported symptoms and inhibition of acetylcholinesterase activity among Kenyan agricultural workers.

OBJECTIVES: This study was part of the East African pesticides project. The general objective was to assess health hazards posed by handling, storage, and use of pesticides, on agricultural estates and small farms with a view to developing strategies for prevention and control of pesticide poisoning. The aim of this paper is to describe the prevalence of symptoms in this population, to relate levels of inhibition to reported symptoms and evaluate at which levels of inhibition symptoms become increased. METHODS: Complete data were available for 256 exposed subjects and 152 controls from four regions in Kenya. A structured questionnaire on symptoms experienced at the time of interview was given to all subjects and controls. Information was also obtained on sex, age, main occupation, and level of education. Symptoms reported during the high exposure period, were initially clustered in broader symptom categories from reference literature on health effects of pesticides that inhibit cholinesterase (organophosphate and carbamate). Prevalence ratios were estimated for symptoms with changes in cholinesterase activity in serum. RESULTS: Symptom prevalence in exposed subjects was higher during the high exposure period than the low exposure period, although these differences were not significant. Interestingly, a clear and significant change in symptoms prevalence was found in the controls with a higher prevalence in the low exposure period. Analysis of the relation between cholinesterase inhibition and symptoms showed that prevalence ratios were significantly > 1 for respiratory, eye, and central nervous system symptoms for workers with > 30% inhibition. Similar results were found for analyses with the actual level of acetylcholinesterase activity. CONCLUSION: The results suggest the presence of a relation between exposure and acetylcholinesterase inhibition, acetylcholinesterase activity, and respiratory, eye, and central nervous system symptoms. Increased symptom prevalence was found at acetylcholinesterase activities generally considered to be non-adverse.

Acetylcholinesterase↗
PubMed1979

Social distribution of sexually transmitted diseases. A survey of female clinic registrations.

Social and medical data on 1672 female patients attending a venereal disease clinic were recorded over a four-year period. Analysis of these data provided a demographic and social profile of female clinic attenders and indicated considerable variations in patterns of diagnosis between different social categories of patients. The probability of diagnosis of different infections varied according to age, marital state, social class, employment status, and previous record of attendance.

Adolescent↗
PubMed1982

Sputum and ciliary inhibition in asthma.

Twenty-eight sputum samples collected from 20 patients with chronic bronchial asthma of atopic and intrinsic clinical types were incubated with human bronchial explants to study their influence on ciliary motility. Of these, 19 (68%) of the sputa exerted a ciliary inhibitory effect of varying degree in a two-hour period. Analysis of the data indicates that (1) the ciliary inhibitory effect was invariably present when patients produced a distinctive slurry sputum; (2) this occurred more frequently during clinical exacerbations; (3) the induced ciliary inhibition was reversible on removal of the sputum; (4) the intensity of the ciliary inhibitory effect decreased with clinical improvement of the patient; (5) the inhibitory effect was unrelated to the medications used; (6) it was equally common in the atopic and the intrinsic types of asthmatic patients; (7) the effect was not pH dependent or related to the degree of eosinophilia. The ciliary inhibitory factor in sputum was identified as having a molecular weight of 6000-8000. It may play a part in the pathogenesis of asthma and recognition of sputum containing it carries implications for treatment.

Asthma↗
PubMed1985

Duplex carotid sonography: criteria for stenosis, accuracy, and pitfalls.

Both carotid bifurcations were examined in 353 patients over a 20-month interval using a combination of real-time and pulsed Doppler ultrasound (duplex scanning). Angiographic correlation was available in 72 cases. Stenosis of the internal carotid was evaluated using a Doppler input frequency of 5 MHz and a scan angle of 60 degrees. A peak frequency shift of less than 3.5 kHz was found to be a sign of less than or equal to 30% stenosis; 3.5-4 kHz with moderate turbulence suggested 31-50% stenosis, 4-8 kHz 51-90% stenosis, and greater than 8 kHz greater than 90% stenosis. Subtotal stenosis (greater than 95%) was manifested by a frequency shift of less than 8 kHz, but the waveform was totally distorted. Overall accuracy improved from 77% for the first 6 months to 87% for the last 14 months. For stenosis greater than 50%, sensitivity improved from 82% to 97% during this period. Analysis of errors and suggestions for avoiding them are presented.

Carotid Arteries↗