Macrophage and microglial cell immunoreactivity for PrP(c) in a random post-mortem population.
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Humans↗
Biomedical subjects
J Carter
Publications and source records attributed to J Carter.
High grade abnormalities following an 'inconclusive' smear.
OBJECTIVE: The National Health and Medical Research Council (NHMRC) recommends a report of 'inconclusive possible high grade epithelial abnormality', but many laboratories only report 'inconclusive' with reference to any possible high grade disease elsewhere in the report. This study was performed to determine possible reasons for cytological difficulties resulting in this category of report and to determine the rate of significant disease within this category. DESIGN: Retrospective record review. Clinical details were extracted without patient-identifying data. SETTING: Gynaecological Oncology Department, King George V/Royal Prince Alfred Hospital. POPULATION: Two hundred patients referred with the cytological abnormality. MATERIALS AND METHODS: An adequate colposcopic diagram documenting size, distribution and grade of lesion was required. All patients had colposcopy with management according to colposcopic and histological results as appropriate to their disease. OUTCOME MEASURES: Colposcopic features, topography and size of any lesion, histological results, treatments performed and subsequent review of untreated patients. RESULTS: Colposcopy found high-grade lesions in 43% and carcinoma in 1%. Histopathology found 49% and 4% respectively. Treatment was performed in 124 patients. Inflammation was found in 27%, a small lesion in 43% and endocervical disease in 21%. CONCLUSIONS: The high rate of endocervical disease, inflammation and small lesions may explain the cytological difficulties leading to an 'inconclusive' result. The authors believe that the term 'inconclusive' alone does not adequately convey the high level of risk faced by these patients.
Adolescent↗
Pulse-exposure effects of selected insecticides to juvenile Australian crimson-spotted rainbowfish (Melanotaenia duboulayi).
Laboratory toxicity studies were conducted in southeastern Queensland, Australia, to determine the acute lethal effects of a 1-h pulse exposure of selected insecticides to adult and juvenile (<72 h old) crimson-spotted rainbowfish, Melanotaenia duboulayi (Castlenau). In addition, to its ecological significance, this native fish is a predator of mosquitoes. Two organophosphate (OP) compounds (temephos and pirimiphos-methyl), an entomophathogenic bacterium (Bacillus thuringiensis variety israelensis [Bti]) and two insect growth regulators (IGRs) (s-methoprene and pyriproxyfen) were evaluated. Although none of the five insecticides were acutely toxic to adult M. duboulayi under the test conditions, temephos and pirimiphos-methyl were found to be toxic to juveniles, with 24 h pulse exposure LC50 values of 27 and 15 microg/liter (ppb), respectively. Of the two OPs, pirimiphos-methyl was the most toxic, with a lethal dose ratio (pulse exposure LC50 temephos/ pulse exposure LC50 pirimiphos-methyl) of 1.8 (95% CL 0.5-6.4). These pulse exposure LC50 values represented 40 and 4.5% of the estimated environmental concentrations (EEC) for a 15 cm deep water body, respectively. Bti and the two IGRs had no acute toxic effects at up to 10 and 12.5 times the EEC, respectively. Accordingly, in the interests of environmental conservation and integrated pest management (IPM), preference should be given to the latter three insecticides for control of mosquito larvae in juvenile M. duboulayi habitat.
Animals↗
Combined whole tumor cell and monophosphoryl lipid A vaccine improved by encapsulation in murine colorectal cancer.
BACKGROUND: Whole autologous colon cancer vaccines in combination with various adjuvants have been used in both animals and humans. At this writing, vaccine regimens have been initiated in humans 3 to 6 weeks postoperatively. This delay between tumor resection and vaccination gives surviving tumor cells an opportunity to establish themselves. Vaccine administered either preoperatively or immediately after surgery, in theory, should be more effective. However, surgery-related immunosuppression may diminish the effectiveness of pre-operative or early postoperative vaccines. This problem may be overcome by limiting postoperative immunosuppression via the use of minimally invasive methods. Alternatively, the impact of the vaccine may be improved by encapsulating the vaccine, plus adjuvant, which in theory, should extend exposure time. Encapsulation of cancer vaccines in polysaccharide particles has not yet been studied. The goal of this study was to determine whether vaccine encapsulation, preoperative vaccination, and early postoperative vaccination affected the tumor burden. In addition, laparotomy and carbon dioxide insufflation were compared. METHODS: Vaccine was prepared from ultraviolet-irradiated C26 colon cancer cells in combination with monophosphoryl lipid A, either in suspension or entrapped in alginate beads. The C26 cell line and syngeneic BALB/c mice were used for all the studies. Tumor volumes were determined after excision of the tumors 2 weeks after inoculation in these studies. RESULTS: Encapsulated vaccine was more effective than the standard liquid vaccine. Significantly smaller tumors were noted in mice receiving encapsulated vaccine than in either the control group (p <0.01) or the liquid vaccine group (p <0.05). The use of a preoperative encapsulated vaccine was associated with significantly smaller tumors after laparotomy, pneumoperitoneum, or anesthesia alone when the tumors were established immediately after surgery. With an already established tumor, encapsulated vaccine, when given in the early postoperative period to mice that had undergone laparotomy or anesthesia alone was associated with significantly smaller tumors that those found in control animals. CONCLUSIONS: The incorporation of a whole-cell vaccine and monophosphoryl lipid A into alginate beads increases the efficacy of pre-operative and early postoperative tumor vaccines in the setting of both laparotomy and Carbon dioxide pneumoperitoneum. The use of perioperative vaccines may prove to be an effective way to immunize patients with cancer undergoing surgery.
Adenocarcinoma↗
Pneumocystis carinii cytochrome b mutations are associated with atovaquone exposure in patients with AIDS.
This retrospective cohort study was conducted to determine whether Pneumocystis carinii cytochrome b gene mutations in patients with AIDS and P. carinii pneumonia (PCP) are associated with atovaquone exposure. Portions of the P. carinii cytochrome b genes that were obtained from 60 patients with AIDS and PCP from 6 medical centers between 1995 and 1999 were amplified and sequenced by using polymerase chain reaction. Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matched with 45 patients with no atovaquone exposure. Cytochrome b coenzyme Q binding site mutations were observed in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=.018). There was no difference in survival 1 month after treatment between patients with or without cytochrome b mutations (P=.14). Thus, cytochrome b mutations are significantly more common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of these mutations remains unknown.
Acquired Immunodeficiency Syndrome↗
Maternal uniparental heterodisomy for chromosome 2: detection through 'atypical' maternal AFP/hCG levels, with an update on a previous case.
We report a case of maternal uniparental disomy 2, detected through routine screening of placental karyotypes following the finding of 'atypical' AFP/hCG levels in the second trimester, with intrauterine growth retardation (IUGR) but otherwise normal outcome at term. Although the child remained small, subsequent early physical and mental development has also been normal. Additionally, we report long-term follow-up of an earlier case, again with relatively normal physical and mental development. The significance of atypical AFP/hCG results and the predictive value of prenatal testing for UPD2 in trisomy 2 confined placental mosaicism (CPM) cases are discussed.
Adult↗
Hybrid laparoscopic flexure takedown and open procedure for rectal resection is associated with significantly shorter length of stay than equivalent open resection.
PURPOSE: Laparoscopic-assisted, sphincter-saving resection (largest incision < 7 cm) of the middle and distal rectum is technically very difficult and, with regard to cancers, has not been demonstrated to be oncologically safe. The hypothesis of this retrospective study is that a hybrid operation that combines laparoscopic and open methods would be associated with short-term outcome benefits compared with open surgery results for patients undergoing sphincter-saving proctectomy. METHODS: A total of 31 hybrid and 25 fully open rectal resection patients were compared in this retrospective review. All patients had splenic flexure takedown and rectal anastomosis. The hybrid approach consisted of laparoscopic splenic flexure takedown (with or without partial rectal mobilization and devascularization) followed by completion of the procedure via infraumbilical midline laparotomy. The indication was neoplasm in 87 percent of hybrid patients and in 68 percent of open patients. The majority of tumors were located between 4 and 10 cm from the dentate line. RESULTS: Fifty-eight percent of hybrid and 68 percent of open patients had low anterior or coloanal resections, and 48 percent of hybrid and 64 percent of open patients underwent temporary diversion via ileostomy. The mean hybrid midline incision length was 11 cm compared with 24 cm for open patients (P < 0.0001). The neoplastic specimens were similar with regard to margins and lymph node harvest. Similar complication rates were noted in both groups. Nonsignificant benefits for hybrid patients (0.9-1.2 days) were seen with regard to length of time until toleration of liquid or solid diet and first flatus. Hybrid patients experienced their first bowel movements 4.1 days vs. 5.7 days for the open group (P = 0.03). Mean length of stay was significantly shorter for hybrid patients (6.1. days) than for open patients (11.1 days; P = 0.0006). CONCLUSION: This preliminary retrospective study suggests that a combined hybrid laparoscopic and open approach to sphincter-saving proctectomy permits a similar resection as open methods and may be associated with a length-of-stay benefit and more rapid return of bowel function. Prospective studies will be needed before any firm conclusions can be drawn.
Adult↗
What treatments patients seek after inpatient care: a follow-up of 24 patients with anorexia nervosa.
BACKGROUND: To determine the kind of treatment patients with anorexia nervosa (AN) seek for their eating disorder following hospitalization. METHOD: Twenty-four women previously treated in the Toronto General Hospital were interviewed to determine the nature and amount of treatment received following discharge. RESULTS: Mean age: 31 years (SD=9.18). Mean body mass index (BMI) at assessment: 19.97 (SD=4.00). All had seen at least one or more professionals, mainly family doctors and psychiatrists, within the first 6 months. Mean hours of treatment: 85. Eighty-eight per cent had taken psychotropic medication (most commonly antidepressants). Symptomatic and asymptomatic patients did not differ in amount of treatment received. CONCLUSIONS: Regardless of their symptom state, AN patients continue to use the health system heavily following weight restoration. Their aftercare is thus essential for ongoing maintenance treatment and to prevent relapse, and training primary-care physicians to provide it may be one way to contain health care costs.
Adult↗
Monitoring vital signs in a bone marrow transplant unit: are they needed in the middle of the night?
Monitoring vital signs (VS) is a routine procedure in bone marrow transplant (BMT) units, but such monitoring can interfere with sleep. We hypothesized that middle of the night (MON) monitoring may not be needed in all patients. Charts of 20 consecutive patients who underwent BMT were reviewed for MON monitoring to determine the frequency with which monitoring resulted in a nursing intervention, call to the physician or change in treatment by the physician. Charts were also reviewed for day time events, which could predict the need for monitoring at night. MON monitoring was done on 457 of the 543 nights evaluated, 148 nursing interventions were performed during these 457 nights (32%) of which only 20 (4%) were the result of monitoring VS. In five instances, the nurse called the physician as a result of monitoring VS and in three of these five instances, the treatment was changed. The only day time event that was significantly associated was fever (P = 0.0002). There was also a trend for CNS events (P = 0.057) to be associated with MON intervention. Larger, prospective studies need to be done to accurately identify day time risk factors that can predict the need for night time monitoring.
Adult↗
New insights into the role of zinc in the respiratory epithelium.
Over the past 30 years, many researchers have demonstrated the critical role of zinc (Zn), a group IIb metal, in diverse physiological processes, such as growth and development, maintenance and priming of the immune system, and tissue repair. This review will discuss aspects of Zn physiology and its possible beneficial role in the respiratory epithelium. Here we have detailed the mechanisms by which Zn diversely acts as: (i) an anti-oxidant; (ii) an organelle stabilizer; (iii) an anti-apopototic agent; (iv) an important cofactor for DNA synthesis; (v) a vital component for wound healing; and (vi) an anti-inflammatory agent. This paper will also review studies from the authors' laboratory concerning the first attempts to map Zn in the respiratory epithelium and to elucidate its role in regulating caspase-3 activated apoptosis. We propose that Zn, being a major dietary anti-oxidant has a protective role for the airway epithelium against oxyradicals and other noxious agents. Zn may therefore have important implications for asthma and other inflammatory diseases where the physical barrier is vulnerable and compromised.
Animals↗
Synaptic pathology in prefrontal cortex is present only with severe dementia in Alzheimer disease.
Synaptic pathology is proposed to be integral to the clinical expression of Alzheimer disease (AD). Most studies have assessed only the vesicle protein synaptophysin as a measure of synaptic integrity. The interrelationships of synaptophysin, other presynaptic proteins, the cholinergic system, and severity of dementia in AD remain unclear. We studied the presynaptic proteins synaptophysin, syntaxin and SNAP-25, along with choline acetyltransferase (ChAT) activity in prefrontal cortex (BA 46) samples from 18 subjects with AD and 16 controls. Mean values of presynaptic protein immunoreactivities were significantly reduced, by 21%-28%, and ChAT activity was reduced by 41% in the AD groups. Synaptic protein immunoreactivity and ChAT activity were correlated with Mini-Mental State Examination scores obtained 1 yr prior to death. When AD cases were subgrouped into mild/moderate and severe illness at time of death, all differences in presynaptic proteins and ChAT activity were significant between controls and severe cases. However, no significant differences were detected in BA 46 between controls and mild/moderate cases. Considerable synaptic reserve or plasticity remains in BA 46 until the late stages of AD. Synaptophysin and ChAT appear to be more vulnerable in severe AD than are syntaxin or SNAP-25.
Aged↗
Beta-amyloid, neuronal death and Alzheimer's disease.
Alzheimer's disease (AD) is a common neurodegenerative disease that affects cognitive function in the elderly. Large extracellular beta-amyloid (Abeta) plaques and tau-containing intraneuronal neurofibrillary tangles characterize AD from a histopathologic perspective. However, the severity of dementia in AD is more closely related to the degree of the associated neuronal and synaptic loss. It is not known how neurons die and synapses are lost in AD; the current review summarizes what is known about this issue. Most evidence indicates that amyloid precursor protein (APP) processing is central to the AD process. The Abeta in plaques is a metabolite of the APP that forms when an alternative (beta-secretase and then gamma-secretase) enzymatic pathway is utilized for processing. Mutations of the APP gene lead to AD by influencing APP metabolism. One leading theory is that the Abeta in plaques leads to AD because Abeta is directly toxic to the adjacent neurons. Other theories advance the notion that neuronal death is triggered by intracellular events that occur during APP processing or by extraneuronal preplaque Abeta oligomers. Some investigators speculate that in many cases there is a more general disorder of protein processing in neurons that leads to cell death. In the later models, Abeta plaques are a byproduct of the disease process, rather than the direct cause of neuronal death. A direct correlation between Abeta plaque burden and neuronal (or synaptic) loss should occur in AD if Abeta plaques cause AD through a direct toxic effect. However, histopathologic studies indicate that the correlation between Abeta plaque burden and neuronal (or synaptic) loss is poor. We conclude that APP processing and Abeta formation is important to the AD process, but that neuronal alterations that underlie symptoms of AD are not due exclusively to a direct toxic effect of the Abeta deposits that occur in plaques. A more general problem with protein processing, damage due to the neuron from accumulation of intraneuronal Abeta or extracellular, preplaque Abeta may also be important as underlying factors in the dementia of AD.
Alzheimer Disease↗
Evaluation of liquid Bacillus thuringiensis var. israelensis products for control of Australian Aedes arbovirus vectors.
Laboratory bioassay studies were conducted in southeast Queensland, Australia, on the efficacy of Teknar, VectoBac 12AS, and Cybate (active ingredient: 1,200 international toxic units Bacillus thuringiensis var. israelensis [Bti]) against 3rd instars of the arbovirus vectors Aedes aegypti, Ae. notoscriptus, Ae. vigilax, and Ae. camptorhynchus. Probit analyses were then used to determine LD50 (median lethal dose), LD50, and lethal dose ratios (LDR). Aedes aegypti and Ae. notoscriptus, both container-habitat species, tolerated the highest Bti concentrations compared with saltmarsh Ae. vigilax and Ae. camptorhynchus. For example, the LDR for Ae. vigilax versus Ae. notoscriptus exposed to Cybate was 0.14 (95% confidence limit [CL] 0.03-0.61). Similarly, the Cybate LDR for Ae. camptorhynchus versus Ae. notoscriptus was 0.22 (95% CL 0.07-0.70). Teknar produced similar results with an LDR of 0.21 (95% CL 0.04-1.10) for Aedes vigilax versus Aedes notoscriptus. Differences in product efficacy were found when tested against the 2 container-breeding species. Cybate was less effective than Teknar with LDRs of 1.55 (95% CL 0.65-3.67) and 1.87 (95% CL 0.68-5.15) for Aedes aegypti and Ae. notoscriptus, respectively. The significant differences in susceptibility between mosquito species and varying efficacy between products highlight the importance of evaluating concentration-response data prior to contracting with distributors of mosquito control products. This information is crucial to resistance management strategies.
Aedes↗
Cholinergic deficits contribute to behavioral disturbance in patients with dementia.
BACKGROUND: Noncognitive behavioral changes such as depression, aggressive behavior, psychosis, and overactivity occur frequently in patients with dementia, in addition to cognitive impairment, and often determine the need for institutionalization. The biochemical basis of such changes is poorly understood. Clinical trial data indicate that cholinomimetics improve noncognitive behaviors. This study investigated the relationship between markers of the cholinergic and dopaminergic neurotransmitter systems and noncognitive behavioral symptoms assessed during the course of dementing illness. METHOD: Brains from 46 patients with dementia (36 with AD and 10 with mixed or other dementias using Consortium to Establish a Registry for AD criteria) were examined together with 32 normal controls. The patients with dementia had been evaluated every 4 months, often over several years, for cognitive performance (Mini-Mental State Examination) and behavior (Present Behavioral Examination). Concentrations of dopamine (DA) and major metabolites, choline acetyltransferase activity (ChAT), and density (Bmax) of DA D1 receptors in frontal and temporal cortex were studied by radioligand binding protocols. None of the patients was receiving cholinomimetic drugs. RESULTS: ChAT activity, but no other neurochemical markers, was reduced in AD compared with controls. Loss of ChAT activity correlated with cognitive impairment. Lowered ChAT activity also correlated with increasing overactivity in patients with dementia in both frontal and temporal cortex whereas ChAT:DA and ChAT:D1 ratios in temporal cortex correlated negatively with aggressive behavior. CONCLUSIONS: Disturbance of the cholinergic system may underlie both cognitive and some noncognitive behavioral changes in dementia, providing a basis for rational therapy.-1467
Aged↗
Family support for stroke: a randomised controlled trial.
BACKGROUND: Attention is currently focused on family care of stroke survivors, but the effectiveness of support services is unclear. We did a single-blind, randomised, controlled trial to assess the impact of family support on stroke patients and their carers. METHODS: Patients with acute stroke admitted to hospitals in Oxford, UK, were assigned family support or normal care within 6 weeks of stroke. After 6 months, we assessed, for carers, knowledge about stroke, Frenchay activities index, general health questionnaire-28 scores, caregiver strain index, Dartmouth co-op charts, short form 36 (SF-36), and satisfaction scores, and, for patients, knowledge about stroke and use of services, Barthel index, Rivermead mobility index, Frenchay activities index, London handicap scale, hospital anxiety and depression scales, Dartmouth co-op charts, and satisfaction. FINDINGS: 323 patients and 267 carers were followed up. Carers in the intervention group had significantly better Frenchay activities indices (p=0.03), SF-36 scores (energy p=0.02, mental health p=0.004, pain p=0.03, physical function p=0.025, and general health perception p=0.02), quality of life on the Dartmouth co-op chart (p=0.01), and satisfaction with understanding of stroke (82 vs 71%, p=0.04) than those in the control group. Patients' knowledge about stroke, disability, handicap, quality of life, and satisfaction with services and understanding of stroke did not differ between groups. Fewer patients in the intervention group than in the control group saw a physiotherapist after discharge (44 vs 56%, p=0.04), but use of other services was similar. INTERPRETATION: Family support significantly increased social activities and improved quality of life for carers, with no significant effects on patients.
Aged↗
Autozygosity mapping of a seckel syndrome locus to chromosome 3q22. 1-q24.
Seckel syndrome (MIM 210600) is an autosomal recessive disorder of low birth weight, severe microcephaly, and dysmorphic facial appearance with receding forehead, prominent nose, and micrognathia. We have performed a genomic screen in two consanguineous families of Pakistani origin and found that the disorder segregates with markers between loci D3S1316 and D3S3710, which map to chromosome 3q22.1-q24. Analysis using HOMOZ/MAPMAKER gave a maximum LOD score of 8.72. All five affected individuals were homozygous for the same allele, for two adjacent polymorphic markers within the region segregating with the disease, narrowing the region to 12 cM.
Abnormalities, Multiple↗
Childhood obesity. Health schools approach is needed.
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Child↗