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Biomedical subjects

P Gibson

Publications and source records attributed to P Gibson.

At least 55 records · Page 3Linked to original sources

Serum free medium increases expression of markers of differentiation in human colonic crypt cells.

In colitis, colonic epithelial cells have a shortened life span but show normal or increased expression of phenotypic markers of differentiation. This study examined the effect of differing culture conditions on the expression of such markers in colonic crypt cells. Crypt cells were enzymatically isolated from macroscopically normal large bowel mucosa resected because of neoplasia, inflammatory bowel disease or non-neoplastic non-inflammatory conditions. Cells cultured in the presence of serum exhibited a doubling of the rate of protein synthesis (measured by 14C-leucine uptake; p < 0.001) compared with autologous cells cultured in the absence of serum without evidence of loss of cell viability (assessed by 51Cr release from prelabelled cells) or of change in the rate of cell proliferation (assessed by total DNA content and 3H-thymidine uptake). Irrespective of the underlying colonic disease, crypt cells cultured in the absence of serum exhibited increased expression of phenotypic markers of differentiation compared with those cultured with serum: the rate of glycoprotein synthesis relative to that of protein synthesis increased by a mean of 59% and the cellular expression of brush border glycoproteins, alkaline phosphatase, and carcinoembryonic antigen significantly increased. The effects seen could not be mimicked by addition of dexamethasone or insulin to serum free medium. Thus, under less optimal (serum free) culture conditions, colonic crypt cells express phenotypic markers of differentiation at an accelerated rate suggesting that unfavourable microenvironmental conditions themselves are probably in part responsible for the normal or increased expression of such markers in colitis.

Alkaline Phosphatase↗

Secretion of urokinase and plasminogen activator inhibitor-1 by normal colonic epithelium in vitro.

Urokinase is a neutral protease whose major site of action is the external surface of the plasma membrane of cells and whose major function seems to be modulation of cell adhesion, such as that which occurs during cell migration. This study aimed to determine whether colonic epithelium is involved with the urokinase system. The contents of urokinase and one of its specific inhibitors, plasminogen activator inhibitor-1, were measured in culture supernatant and cell homogenates of isolated human colonic crypt cells. The amounts of both factors increased in supernatants over 24 hours, and approximately twice the amount was found in supernatants than in autologous cell homogenates. The secretion of both factors was similar in serum free and serum containing media. Northern blot analysis showed that messenger ribonucleic acid specific for urokinase and plasminogen activator inhibitor-1 was present in colonic crypt cells and that expression over 18 hours of culture was increased 12 fold for urokinase type plasminogen activator and two to fourfold for the inhibitor compared with values found in autologous freshly isolated cells. Urokinase activity was detected in crypt cell homogenates and supernatants indicating that it was present in excess of its inhibitors. Control experiments indicated that the epithelial cells themselves were responsible for the observations and excluded artefactual effects of the isolation procedure. In conclusion, isolated human colonic epithelial cells secrete urokinase and at least one of its specific inhibitors. Further investigation of the role of urokinase in the physiology and pathophysiology of colonic epithelium is indicated.

Blotting, Northern↗

Association between availability of non-prescription beta 2 agonist inhalers and undertreatment of asthma.

OBJECTIVE: To determine whether the availability of beta 2 agonist inhalers without prescription leads to undertreatment of asthma. DESIGN: Cross sectional study of adequacy of treatment in asthmatic subjects who purchased beta 2 agonist inhalers and subjects who obtained inhalers by prescription. SETTING: Community pharmacies in New South Wales, Australia. SUBJECTS: 403 eligible consecutive asthmatic subjects aged 13 to 55 purchasing salbutamol metered dose inhalers over the counter or by prescription; 197 attended for follow up and spirometry and 139 returned 14 day symptom, peak flow, and medication diaries. MAIN OUTCOME MEASURES: Severity of asthma assessed on frequency of day time and night time wheezing, frequency of inhaler use, and peak expiratory flow rates. Adequacy of treatment according to published guidelines. RESULTS: Of the 139 patients who completed the diary 83, (60%) purchased their inhalers without prescription and 83 were undertreated. The characteristics of patients in the prescription and purchasing groups were similar. Multiple logistic regression analysis identified use of non-prescribed salbutamol as being associated with a 2.9-fold increase in the odds of undertreatment (95% confidence interval 1.3 to 6.8). Smoking increased the odds of undertreatment (3.3, 1.2 to 9.5) and use of a peak flow meter reduced the odds (0.11, 0.04 to 0.34). Adjustment for frequency of consultation made use of non-prescription salbutamol insignificant (1.4, 0.55 to 3.8). Attitudes to services provided by doctors and pharmacists were favourable and not associated with undertreatment. CONCLUSION: Over the counter purchase of salbutamol is associated with infrequent consultation with doctors and undertreatment of asthma.

Administration, Inhalation↗

Acute myopathy in status asthmaticus.

An acute myopathy complicating life-threatening asthma has been reported with increasing frequency. We present a further 3 patients with this complication. Each patient had nerve conduction studies, electromyography and muscle biopsy performed. The records of a cohort of 12 patients, ventilated in an intensive care unit over a 16 month period, were reviewed. Eleven out of the 12 patients developed an elevated creatine kinase level (median 1311 U/L, range 185-9973 U/L) and 4 developed symptomatic weakness. The myopathy of status asthmaticus is not a homogeneous clinicopathological entity. Although myopathy is the predominant feature, there is a neuropathic component in some patients. Full recovery is usual. The combination of corticosteroids and neuromuscular blocking agents has been proposed as the possible cause of the complication.

Acute Disease↗

Cholelithiasis in infants with Down syndrome. Three cases and literature review.

Only four cases of cholelithiasis have been reported in patients with Down syndrome and none in Down syndrome infants. The cases of three Down syndrome infants (all males) with cholelithiasis are reported. Each exhibited different fetal complications, and in each, Down syndrome was diagnosed at birth. Gallstones apparently were congenital (a rarity) in one infant, since they were detected on the first day of life. Cholelithiasis was an incidental finding in another of the infants when, at 12 weeks old, he had renal ultrasonography because of a urinary tract infection. The third infant was 4 months old when sonographic studies revealed a gallstone. Despite the confirmation of cholelithiasis in all three infants, none has since had any signs or symptoms that suggest the need for intervention. Cholelithiasis is probably more common in Down syndrome infants than has been supposed, but whether Down syndrome infants with gastrointestinal (GI) malformations are more likely to have gallstones than are children with similar GI malformations but with normal karyotypes is unknown.

Cholelithiasis↗

Noninvasive detection of the morphologic and hemodynamic changes during normal pregnancy.

To characterize the morphologic and hemodynamic changes during normal pregnancy, serial echocardiographic measurements (n = 210) of left ventricular (LV) dimensions and mass (M-mode), volumes and ejection fraction (two-dimensional), stroke volume, and cardiac output (Doppler: aortic, apical, and suprasternal) were performed in 15 patients (mean age 30 years) beginning as early as 12 weeks of gestation, at 2-week intervals through delivery, and up to 12 weeks postpartum. Left atrial size increased from 3.4 +/- 0.4 (SD) to 3.8 +/- 0.4 cm near term, decreasing to 3.4 +/- 0.5 cm postpartum (p = 0.006 overall). LV mass changes correlated with increases in body weight. No consistent significant changes in LV volumes and ejection fraction were observed. LV outflow tract cross-sectional area increased significantly from 3.0 +/- 0.2 cm2 at baseline to 3.5 +/- 0.3 cm2 near term, decreasing to 3.2 +/- 0.3 cm2 postpartum (p less than 0.002 for both). Heart rate increased from 70 +/- 7 to 77 +/- 10 beats/min near term decreasing to baseline postpartum (p less than 0.02 for both). Accordingly, cardiac output increased significantly, as detected from both the apical and suprasternal positions averaging from 4.7 +/- 0.6 to 6.5 +/- 1.5 l/min near term, returning to 4.3 +/- 0.6 l/min postpartum (p less than 0.0005 for both). Thus, in normal pregnancy, left atrial size increases significantly without significant changes in LV dimensions, volumes, and ejection fraction. Increased LV mass is related to increased body weight. Cardiac output changes result from increased heart rate and an increase in LV outflow area, which contributes to increased stroke volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prevalence of HPV cervical infection in a family planning clinic determined by polymerase chain reaction and dot blot hybridisation.

The overall prevalence of human papillomavirus (HPV) cervical infection in 131 women attending a family planning clinic was 7% (HPV 6/11, 16, 18, 31) by dot blot hybridisation, 53% (HPV 11, 16, 31) by polymerase chain reaction (PCR), and 56% by the two methods combined. HPV 16 and 18 were the commonest types (4% each) by dot blot, HPV 16 (39%) by PCR. Fifteen percent of subjects had mildly abnormal cervical cytology (grades 1A, 2A, or 3). There was no significant correlation between cytological abnormality and HPV positivity, or between cytological or HPV status and other postulated risk factors for cervical neoplasia. It is concluded that PCR is considerably more sensitive than dot blot DNA hybridisation in detecting HPV cervical infection in such a "low risk" setting, where HPV copy number may be low. Firm conclusions cannot be drawn from our results regarding a causal role for HPV or other factors in the development of cervical neoplasia.

Adolescent↗

Prenatal diagnosis of duplication cyst of the pylorus.

The first description of the antenatal appearance of a duplication cyst of the pylorus is presented. Prior to the infant's delivery, the possibility that this intra-abdominal cystic mass represented a choledochal cyst was also strongly considered. The antenatal detection of this cystic mass allowed close neonatal surveillance and timely surgical intervention prior to the onset of serious neonatal complications. The embryogenesis of duplication cysts of the gastrointestinal tract and bronchopulmonary foregut malformations is reviewed. The clinical utility of the prenatal diagnosis of such fetal gastrointestinal anomalies is also discussed.

Adult↗

Complications associated with central venous catheters inserted in critically ill neonates.

OBJECTIVE: To assess the incidence and spectrum of complications associated with central venous catheter (CVC) placement in the critically ill infant. DESIGN: A prospective study of all babies hospitalized in a neonatal intensive care unit (NICU) from January 1989 to December 1989. Potential risk factors associated with infection were evaluated by a case-control comparison. SETTING: Conducted at a university-affiliated, tertiary care community hospital. PATIENTS: Neonates requiring intensive care and a central venous catheter. Controls consisted of noninfected babies. RESULTS: Of 263 critically ill neonates, only 13 (4.9%) required a CVC insertion. Seventeen CVCs were placed in these 13 neonates for a total duration of 600 days (median, 32 days/cannula). Fifteen (88%) of these cannulas had one or more complications during its catheter life including dislodgement or leakage (53%), occlusion or thrombosis (47%), infections (29%), or minor bleeding (12%). Five babies (29%) developed 6 episodes of bloodstream infection including 3 sporadic cases due to Staphylococcus epidermidis and a cluster of fungemia due to Malassezia furfur associated with lipid emulsion therapy. Infants with a CVC-associated infection were a younger gestational age (24 weeks versus 32 weeks, p = .04) and weighed less at birth (580 g versus 1285 g, p = .02). The overall rate of bloodstream infection was one episode per 100 days of catheter use. CONCLUSIONS: CVCs may be lifesaving to a critically ill neonate, but complications occur frequently. Use must be restricted to infants in whom alternate delivery routes of intravenous therapy or support are otherwise unavailable.

Birth Weight↗

Value of positive technetium-99m leucocyte scans in predicting intestinal inflammation.

The value of positive scans of autologous 99mTc-labelled leucocytes in the detection of intestinal inflammation was assessed in 29 patients with known inflammatory bowel disease and a high probability of intestinal inflammation and 58 with a low probability of intestinal inflammation comprising 37 with intestinal symptoms and 21 with suspected abscess. Autologous leucocytes were labelled with 99mTc using either of the established methods. In patients with inflammatory bowel disease, 3/13 with ileocaecal and 1/11 with colonic accumulation of 99mTc were incorrectly diagnosed in that there was no histological evidence of inflammation in those regions. In the low probability patients, all 26 positive images were false positives: there were 19 in the ileocaecal and 7 in colonic regions and no differences between the two subgroups. False positives were more common in low probability than high probability patients (p = 0.011). The results were independent of the 99mTc cell labelling technique used. Three false positive patients also had normal scans for 111In-labelled granulocytes. The time of first detection of 99mTc in the bowel was earlier in true than in false positive patients (92% v 33% within 1 h, p = 0.008), the false positive rates in the first hour of imaging being 5% in high and 15% in low probability patients. In 99mTc scintigraphy, the appearance of the isotope in the intestine occurs commonly in the absence of inflammation irrespective of the cell labelling technique used. In high probability patients, imaging at 1 h can more reliably discriminate true from false positives and retain clinical usefulness. In low probability patients specificity remains unacceptable and 99mTc-labelled leucocyte scanning in these patients is of little value as a positive predictor of intestinal inflammation.

Adolescent↗