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Biomedical subjects

G M Harrison

Publications and source records attributed to G M Harrison.

At least 19 recordsLinked to original sources
PubMed2006

The influence of CD44v3-v10 on adhesion, invasion and MMP-14 expression in prostate cancer cells.

The expression of certain CD44 variants has been linked with metastasis and tumour progression. In particular, high molecular weight forms of CD44 show restricted expression in tumours and may correlate with tumour development and metastasis. In this study, we examined the expression of CD44 variants in prostate cancer cell lines: the invasive PC-3 and DU-145, low invasive LNCaP, and two non-invasive prostate epithelial cell lines. PC-3 prostate cancer cells were transfected with a high molecular weight CD44 variant isoform, CD44v3-v10, isolated from non-invasive prostate epithelial cell lines. These transfected cells (PC-NIVO) were assessed using in vitro invasion, tumour-endothelial, growth, and migration assays. The expression of MMP-14 was examined using SDS-PAGE and Western blot analysis. Transfected PC-3 cells (PC-NIVO) were found to be less adherent to endothelial cells and had significantly reduced invasiveness compared to wild-type PC-3 or control cells. In addition, tumour cell adhesion to endothelial cells and invasiveness was increased after exposure to HGF/SF, and can be blocked by the presence of anti-CD44 antibodies. Further investigation revealed a reduction in the expression of MMP-14 in PC-NIVO cells, but not in PC-3 or control cells. In conclusion, non-invasive prostate epithelial cells express a high molecular weight CD44 isoform, CD44v3-v10, which may counteract the standard isoform function of CD44 by reducing adhesion and invasion of endothelium by prostate tumour cells through negation of the MMP-14 function.

Cell Adhesion↗
PubMed2001

Use of formalin-fixed, propidium iodide-stained human leukocytes as a standard for enumerating CD4+ T lymphocytes in a single-platform assay.

A new, inexpensive method is described that enables lymphocytes to be enumerated very precisely. Normal leukocytes were simultaneously stained and fixed with a propidium iodide-paraformaldehyde solution. The preparation obtained (CellBeads) was used as an internal standard for cell enumeration by flow cytometry and was stable at 4 degrees C for at least 60 days. Unlike synthetic beads, the CellBeads behaved similarly to normal cells during red blood cell lysis and cell washing procedures. When known numbers of CellBeads were added to whole-blood samples and the numbers of CellBeads and lymphocytes were determined, highly reproducible and accurate enumerations were obtained-far more so than when synthetic beads were used. This inexpensive method is suitable for routine use.

CD3 Complex↗
PubMed1997

Hemoptysis: a 10-year retrospective study.

BACKGROUND: Hemoptysis is uncommon in pediatric practice. We reviewed 10 years of experience with hemoptysis in a tertiary pediatric hospital to identify patient characteristics and predictors of mortality. METHODS: Patients were divided into four age groups (0 to 5, 6 to 10, 11 to 20, and >20 years). Hemoptysis was defined as mild (<150 mL/day), large (150 to 400 mL/day), or massive (>400 mL/day). Fever was defined as >/=38.5 degrees C. RESULTS: A total of 228 patients (115 males and 113 females) with 246 episodes of hemoptysis were identified and grouped according to primary diagnosis. There were 149 patients in the cystic fibrosis (CF) group, 37 in the congenital heart disease (CHD) group, and 42 in the Other group. Age was significantly higher in the CF group compared with the CHD and Other groups. Length of stay was significantly prolonged in the CF group compared with the Other group. The overall mortality was 13%. After initial analysis, mortality predictors were age, amount of hemoptysis, receipt of blood products, and fever. After stratification, we found: 1) in the >20-year age group, there was a difference in mortality when comparing CF patients with CHD patients; 2) for patients who received blood products, there were differences in mortality in patients with CF, CHD, and Other diagnoses; 3) for patients who received blood, there were differences in mortality only for the 0- to 5-year age group; and 4) the amount of hemoptysis was predictive for mortality only in CHD patients. CONCLUSIONS: Hemoptysis presented in young adult CF patients and in adolescent CHD patients. Young adult CF patients with hemoptysis had a higher risk of mortality compared with young adult CHD patients. The amount of hemoptysis predicted mortality only for CHD patients. Receiving blood products was predictive of mortality for all patients.

Adolescent↗
PubMed1996

Urge incontinence in elderly people: factors predicting the severity of urine loss before and after pharmacological treatment.

Geriatric patients with urge incontinence lose different amounts of urine and respond differently to treatment. Identification of factors predicting the amount of urine loss before or after treatment might help to select therapy. We have sought such factors in 41 elderly patients (23 women and 18 men), mean age 79 years with established urge incontinence that was urodynamically proven to be associated with detrusor hyperreflexia, who were treated with oxybutynin chloride. Urine loss was measured by 24-hour monitoring (mean 378 g/24 hour). Demographic, psychosocial, behavioral, cortical, circulatory, urodynamic, and urological factors were studied before and after treatment. Multiple regression analysis showed that, before intervention, factors predicting the amount of urine loss were fluid intake, voiding frequency, and impaired orientation on cognitive testing. After intervention, urine loss was significantly smaller (mean 259 g/24 hour). Different factors predicted the amount of this persistent incontinence: underperfusion of the cerebral cortex, reduced bladder sensation, and (again) impaired orientation. The analysis confirms that the severity of geriatric urge incontinence associated with detrusor hyperreflexia, particularly incontinence that is resistant to anticholinergic therapy, depends on cortical factors, that bladder sensation plays an important role, and that therapeutic manipulation of fluid intake and voiding frequency may offer a modest reduction in urine loss (e.g., about 40 g/day).

Aged↗
PubMed1994

Cerebral aetiology of urinary urge incontinence in elderly people.

We have examined 73 elderly incontinent patients (mean age 79 years) and 27 continent subjects (mean age 78 years) of similar cognitive status. Among the incontinent patients, 20 were shown objectively to have urge incontinence with normal bladder filling sensation, 14 had objectively demonstrated urge incontinence with reduced bladder sensation, and 39 had other types of incontinence. We compared cognitive function (by Mini-mental State Examination: MMSE) and regional brain perfusion (by SPECT scanning) in these four groups. Patients with objectively demonstrated urge incontinence and reduced bladder sensation stood out as being different from the rest: their mean MMSE score was significantly lower than that of any of the other three groups; perfusion of the frontal cortex was significantly poorer than that in the continent and other incontinent groups; global cortical perfusion was significantly poorer than in the other incontinence groups. This was not found in patients with urge incontinence and normal bladder sensation. The observations support the hypothesis that in elderly people urge incontinence with reduced bladder sensation can be a consequence of cortical neuropathy, especially in the frontal lobes.

Aged↗
PubMed1994

Urinary incontinence in the elderly: the brain factor.

Recent research has shown that urge incontinence is common in the elderly and is often combined with reduced bladder sensation. It is associated with cognitive impairment and with underperfusion of the frontal lobes of the cortex. To test for an expected preferential association with particular aspects of cognitive function, 47 incontinent patients (25 men and 22 women, median age 78 y) underwent cognitive testing, 24-hour monitoring of bladder function and videourodynamics. Median CAMCOG score was 72/107. Median urine loss in 24 h was 36 g (range 11-1347 g). 17 patients had urodynamic proof of urge incontinence, 8 with normal and 9 with reduced bladder sensation. Impaired orientation in time was more strongly associated with proven urge incontinence than overall cognitive impairment; it was the only significant predictor (P < 0.00005). Praxis, calculation ability, abstract thinking or recent memory were less closely involved. Thus dysfunction of the frontal cortical lobes and impairment of temporal orientation appear to constitute a "brain factor" underlying geriatric urge incontinence, particularly in combination with reduced bladder sensation.

Aged↗
PubMed1993

Relationship of fluid intake to voluntary micturition and urinary incontinence in geriatric patients.

The aim of this study was to investigate, in a group of geriatric inpatients with established incontinence, the relationships among urine loss, voided volumes, frequency of voiding, and fluid intake. The investigated included 128 patients: 76 women and 52 men, with a median age of 79 years. One-half had significant cognitive impairment. Patients underwent 24-hr monitoring of fluid intake, urine loss, and voiding, as well as conventional videourodynamic testing. Diurnal and nocturnal voiding frequencies were significantly but relatively weakly related to fluid intake. Diurnal and nocturnal voided volumes were more closely related, however, to the fluid intake. There was a strong and easily interpretable relationship among nocturnal voided volume, nocturia, cystometric bladder capacity, and evening fluid intake. Sixty of 128 patients had urodynamically proven urge incontinence, and this group was studied separately. They were more cognitively impaired and had significantly greater urine loss and smaller fluid intake than was true of the other incontinent patients. Urine loss was significantly related to fluid intake in this group. Nocturnal urine loss increased by an average of 28 ml/dl of evening fluid intake and decreased by 17 ml/dl voided at night. These results suggest that nocturnal toileting and evening fluid restriction may reduce nocturnal urine loss by a small but useful amount in carefully selected older patients with severe urge incontinence.

Aged↗
PubMed1993

Effect of transurethral resection of the prostate on detrusor instability and urge incontinence in elderly males.

Detrusor instability is common in men with evidence of outflow obstruction due to benign prostatic hypertrophy and typically reverses in about two thirds of patients after transurethral resection of the prostate (TURP). It is also common among the elderly without outflow obstruction and may lead to urge incontinence. To determine whether TURP has an effect on detrusor instability and urge incontinence in elderly men, or whether these abnormalities are due to other age-associated changes, 12 males (mean age 80 years) with urge incontinence or frequency and urgency of micturition, and symptomatic benign prostatic hypertrophy, were studied by 24-hour monitoring of incontinence and videourodynamic examination, before and after TURP; 7/12 patients were significantly cognitively impaired. Preoperatively, all patients showed detrusor instability, which reversed postoperatively in only one patient, a significantly smaller proportion than that consistently reported in younger patients. Preoperatively, 11/12 patients were incontinent. After TURP, 8/11 patients had an improvement in the amount of incontinence, by up to 458 g in 24 hours. Those who improved had been urodynamically more severely obstructed preoperatively. Those with the most improvement were also cognitively impaired. We conclude that, in the geriatric population, detrusor instability and urge incontinence may be the result of age-associated changes and not secondary to obstruction. Detrusor instability is likely to persist following TURP. Preoperative urodynamic assessment of obstruction in the incontinent male with benign prostatic hypertrophy may be useful since the severity of incontinence responds well to TURP if there is marked obstruction. Cognitive impairment should not be a deterrent to operation.

Aged↗
PubMed1993

Polypharmacy and its effect on urinary incontinence in a geriatric population.

The relationship between medication and incontinence was studied retrospectively in 128 elderly patients enrolled in an incontinence study. Patients were taking up to 18 non-topical medications but most of these were unlikely to have a significant urological effect. Nevertheless, 62% of patients were receiving, for other medical problems, up to 4 drugs which could potentially affect the lower urinary tract. These were classified by their mode of action. The most common types of urologically active medication, apart from diuretics, were calcium channel blockers, used by 21% of patients, and tricyclic antidepressants, used by 12%. The urodynamic findings in patients on different types of medication were compared. Patients with urodynamically proven urge incontinence who were on calcium channel blockers had significantly less urine loss than those not on the drug. Tricyclic antidepressants have been used in the treatment of urge incontinence; in this study urine loss was less severe among those receiving tricyclics, although the differences were not significant. A few patients on beta-blockers apparently had more severe urge incontinence. Drugs prescribed to the elderly for non-urological medical problems can affect the lower urinary tract and may have some effect, either beneficial or adverse, on incontinence.

Adrenergic beta-Antagonists↗
PubMed1992

Characteristics of urinary incontinence in elderly patients studied by 24-hour monitoring and urodynamic testing.

Characteristics of urinary incontinence have been studied in 100 elderly incontinent patients using invasive video-urodynamics and noninvasive 24-h monitoring of incontinence, fluid intake, voiding and residual urine. Incontinence was of the urge type in 51 patients, including 24 with reduced bladder sensation. Noninvasive 24-h monitoring showed satisfactory reproducibility and high sensitivity (88%) for detecting urine loss. Urodynamically proven urge incontinence, especially in combination with reduced sensation, and recent bacteriuria were associated with severe urine loss on 24-h monitoring. On 24-h monitoring, urine output was significantly larger at night and nocturia was common. In urge incontinence urine loss was predominantly nocturnal and the amount depended significantly on the previous evening's fluid intake and on nocturia. Noninvasive 24-h monitoring showed that post-void residual was common and was often largest in the early morning. It also yielded many free-voiding flow curves. Normal flow curves with small residual urine make dysfunction of voiding itself unlikely. Thus noninvasive monitoring provides information about incontinence and voiding that is suitable for designing intervention and management strategies. Invasive testing may be necessary however to confirm the urodynamic type of incontinence or suspected voiding dysfunction.

Aged↗
PubMed1991

Incontinence in the elderly: objective demonstration and quantitative assessment.

Subjective and objective methods of demonstrating incontinence and assessing its severity have been compared in a group of elderly patients with a high incidence of severe urge incontinence. It was found that 24-h in-patient monitoring of urine leakage was the most sensitive method of demonstrating incontinence, with videourodynamic testing almost as good. In comparison, a 1-h pad test was poor. Visual inspection during physical examination seldom demonstrated leakage. For quantitative assessment of severity, 24-h monitoring gave the most reproducible results; it was also able to reveal significant changes in severity in response to pharmaceutical treatment. A 1-h pad test was less reproducible and suggested changes that were only poorly consistent with 24-h monitoring. The subjective responses of the patients were not useful in assessing changes in the severity of incontinence. Twenty-four hour monitoring thus stands out as a superior method of demonstrating and assessing incontinence.

Aged↗
PubMed1991

Toxicity of colistin in cystic fibrosis patients.

Pulmonary exacerbations of cystic fibrosis associated with strains of Pseudomonas aeruginosa that are resistant to multiple antibiotics are becoming increasingly common. The search for treatment alternatives continues and may include the reexamination of older antibiotics. Colistin sulfate is a polypeptide antibiotic with good activity against P. aeruginosa. Although its use was largely discontinued in the early 1970s because of reports of frequent renal and neurologic toxicity, intravenous colistin is often prescribed at our institution for patients with P. aeruginosa resistant to multiple-drug therapy. We prospectively monitored 19 patients during 21 courses of colistin therapy to identify the character and incidence of this agent's toxicity. Only one case of renal toxicity occurred. Six cases of neurotoxicity occurred, which were characterized by perioral paresthesia, ataxia, or both. The rate of intolerable renal adverse effects secondary to colistin therapy was appreciably lower among these patients than that reported previously for other patients. It appears that intravenous colistin can be considered for cystic fibrosis patients with strains of P. aeruginosa that are resistant to more commonly used antibiotics.

Adolescent↗
PubMed1987

Central venous catheters in older children.

This report discusses the safety of 89 cuffed, Silastic (Dow Corning, Midland, MI) catheters placed in children between the ages of 1 and 18, a group that may be considered high risk on the basis of age. The overall complication rate was once every 288 days, three times more often than in published results in adults, but less often than in other pediatric series. The sepsis rate of once each 1236 days was almost twice the adult rate. Thirty (35%) of the catheters were used at home, accounting for 85 per cent of the total catheter use. Among this group, the overall complication rate was only once every 815 days, three times less frequent than in comparable adult series. The complication rate due to sepsis was once each 2444 days, the same as noted in adults. Whereas these catheters may be more hazardous overall in this age group, home usage appears to be safer than expected. These catheters are well accepted by this age group and their use, particularly among outpatients, should not be restricted for fear of an unacceptably high complication rate.

Adolescent↗
PubMed1985

Home negative pressure ventilation: report of 20 years of experience in patients with neuromuscular disease.

Twenty years of experience using negative pressure devices (NPD) at home to ventilate 40 patients with neuromuscular disease is presented. The purpose of the study was to determine the costs, complications, and clinical outcome of this form of respiratory support, and to ascertain the reasons for failure to institute effective negative pressure ventilation (NPV) in nine patients. Emerson tank respirators, used mainly to rest respiratory muscles at night, and intermittent positive pressure breathing machines were used by 98% of patients at an average equipment cost of +2,700 annually. Patients in whom NPV was initiated on an elective rather than emergent basis saved an average of +12,000 during their initial hospitalization. Life table analysis shows a five-year survival of 76%, and a 10-year survival of 61%. Complications were minor and occurred at an average rate of less than one per year per patient at home on NPV. Failure to achieve satisfactory NPV in nine patients was associated with age (six patients were younger than 3 years of age), or severe thoracocervical scoliosis, which prevented proper fitting of the NPD. For reasons of safety, economy, and quality of life, NPV at home is the preferred treatment for patients having neuromuscular disease who need respiratory assistance.

Adolescent↗
PubMed1985

Outcome of home mechanical ventilation in children.

A retrospective study of the outcome of home mechanical ventilation in 54 children with chronic respiratory insufficiency was conducted. The children's ages ranged from 4 months to 18 years. Tracheostomies and positive pressure ventilation were used in 33 patients, and negative pressure ventilation in 21 patients. Nine patients were eventually weaned from the ventilator, including three quadriplegic patients in whom electrophrenic stimulation subsequently was used. Over 20 years, there were 17 deaths, including three from ventilator disconnection. Life table analysis showed 1-year survival to be 84%, and 5-year survival 65%. Home mechanical ventilation, with patients cared for by family and friends, cost less (average less than $1000/mo) than registered nurse or hospital care (average $16,000/mo). There was no significant difference in the number of deaths between patients cared for by registered nurses 24 hours a day and those cared for by family and friends. Home mechanical ventilation may be a reasonably safe and cost-effective alternative to prolonged hospitalization for the ventilator-dependent child.

Adolescent↗
PubMed1983

Home positive-pressure ventilation. Twenty years' experience.

We studied retrospectively 26 adults and 21 children with chronic respiratory failure whose condition was managed at home using positive-pressure ventilators in order to ascertain the outcome, benefits, and complications of this form of management. Twenty-six (55 percent) of the patients had injuries to the spinal cord. Among the 47 patients, nine were eventually weaned from the ventilator, and two died at home because of disconnection from their ventilators. Using life-table analysis, projected three-year survival was 74 percent for patients without spinal injury and 63 percent for patients with spinal injury. Mortality was greater for children than for adults. For a majority of patients, the cost of management at home was significantly less than management in the hospital, depending largely on the level of nursing care required. We suggest that mechanical ventilation at home may be a reasonable alternative to prolonged hospitalization for medically stable ventilator-dependent adults and children.

Adolescent↗