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Biomedical subjects

G E Phillips

Publications and source records attributed to G E Phillips.

At least 19 recordsLinked to original sources

Improving cervical cytology screening in a remote, high risk population.

OBJECTIVE: To evaluate the use of the ThinPrep method to reduce rates of unsatisfactory Papanicolaou (Pap) smears in women in remote communities. DESIGN: Prospectively collected samples were split and screened conventionally and by ThinPrep at the Queensland Cytology Service. PATIENTS: Three hundred women having cervical smears taken by a Mobile Women's Health Service nurse or at the antenatal and sexual health clinics of a remote north Queensland community. MAIN OUTCOME MEASURE: Number of Pap smears reported as unsatisfactory for evaluation and requiring a repeat smear request. RESULTS: 17.3% of conventionally prepared smears were technically unsatisfactory, compared with 6.3% prepared with ThinPrep. The overall rate of unsatisfactory smears was only 4.3% when both ThinPrep and conventional smears were assessed for a combined report. CONCLUSION: A significant reduction in the proportion of unsatisfactory Pap smears is possible with the ThinPrep method. Targeted use of ThinPrep in communities with high rates of unsatisfactory smears may prove cost-effective.

Adolescent↗

Airway response of children with primary ciliary dyskinesia to exercise and beta2-agonist challenge.

In primary ciliary dyskinesia (PCD), chest physiotherapy for airway clearance is essential. Exercise and inhaled beta2-agonists can produce bronchodilation thereby augmenting physiotherapy. However, both can also cause bronchoconstriction, and the effects of these stimuli in PCD are not known. In a preliminary study, the mean coefficients of variation for forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) in children with PCD were determined. They were 5.4%, 4.4% and 8.4%, respectively. Twelve children with PCD and 12 normal children performed pulmonary functions under resting conditions; during and after a validated treadmill exercise test; and before and 15 min after 200 microg of inhaled salbutamol. At baseline, FEV1, FVC, forced mid-expiratory flow (FEF25-75%) and PEFR were significantly reduced in the PCD group compared with the control group. Exercise produced a significant increase in PEFR in the PCD group. There was no significant difference between the groups in response to salbutamol. Within the PCD group, exercise produced a significantly greater increase in PEFR than beta2-agonist therapy. In conclusion, in children with primary ciliary dyskinesia there is evidence of obstructive pulmonary disease. In these children, exercise is a more potent stimulus for bronchodilation than by inhaled beta2-agonists. Enhancement of airway clearance may best be achieved by encouraging patients to exercise before physiotherapy rather than by inhaling beta2-agonists, but the effects of each should be assessed for each individual before instigating treatment.

Administration, Inhalation↗

Holding the baby: head downwards positioning for physiotherapy does not cause gastro-oesophageal reflux.

The head-downwards tipped position for physiotherapy has been claimed to exacerbate gastro-oesophageal reflux (GOR) in infants with cystic fibrosis (CF). This was investigated using lower oesophageal pH monitoring during physiotherapy. Twenty-one infants (age range 1-27 months) with respiratory disorders (CF=11), undergoing lower oesophageal pH monitoring were recruited. Subjects received two physiotherapy episodes in random order, A/B or B/A, 12 h apart. A began the gravity-assisted positioning head downward tip for: right lower lobe, middle lobe, left lower lobe and lingula; then supine with no tip for anterior segments of the upper lobes followed by apical segments of upper lobes in a sitting position. B was in the reverse order. Intermittent chest clapping was carried out for 4 min in each position by a physiotherapist blinded to the pH data. During episode A, the median change in pH from baseline was -0.32 (range -2.07 to +1.0) in non-CF subjects (NS) and -0.52 (range -2.7 to +0.52) in CF subjects (p<0.02). During episode B, the median change in non-CF subjects was -0.1 (NS; range - 1.7 to -0.15) and in CF subjects was -0.05 (NS; range -0.67 to +0.5). There was no order effect for positioning. In the CF subjects the sitting position was twice as likely to have the lowest pH measurement during physiotherapy than the other positions (p<0.04). In conclusion, the head-downward tipped positioning for physiotherapy treatment neither induces nor aggravates gastro-oesophageal reflux. There is no justification for routinely changing the way in which infant physiotherapy is carried out.

Analysis of Variance↗

Further observations on histological changes at the ureteroileal junction in ileal conduits.

Seventy-two ureteroileal anastomoses taken from ileal conduits removed from 62 patients were examined histologically to characterize the range of mucosal and stromal changes at these sites. All 72 demonstrated variable amounts of subepithelial chronic inflammation and fibrosis. Other histological features included: cystic spaces lined by transitional epithelium (N = 29; 40%; average diameter 1.2 mm); cystic spaces lined by mixed intestinal/transitional epithelium (N = 5; 7%; average diameter 0.77 mm); and cystically dilated intestinal glands (N = 21; 29%; average diameter 0.24 mm). The latter were associated with overgrowth by transitional epithelium, which had prevented mucus drainage. Twenty-one (29%) had mucus pools with no epithelial lining (average diameter 1.2 mm), and polypoidal protrusions into the lumen of the anastomosis were found containing mucus pools (N = 4; 6%; average diameter 1.4 mm), transitional-lined cysts (N = 5; 7%; average diameter 2.2 mm), and mixed intestinal/transitional-lined cysts (N = 2; 3%; average diameter 2.5 mm). Focal rupture of dilated intestinal glands with interstitial pooling of mucus was not uncommon, and marked dystrophic calcification was found in 1 case within a large collection of extracellular mucus. This series confirms that inflammation, fibrosis, and glandular overgrowth by transitional epithelium are common occurrences at ureteroileal anastomosis sites. Subsequent gland rupture may result in sizable accumulations of interstitial mucus, and rarely in marked dystrophic calcification.

Adolescent↗

Pathologic features of the ureteroileal anastomosis in ileal conduits in childhood.

Ileal conduit urinary diversions are associated with a high incidence of late complications often requiring major revision surgery. Although the etiology of the late complications is not always clear, there may be unilateral or bilateral hydroureteronephrosis, with the conduits showing narrowing and stricture formation with villous atrophy, chronic inflammation, and fibrosis. Histologic review of 20 ureteroileal anastomoses from 12 patients showed variable degrees of chronic changes. In addition, cystically dilated intestinal glands were noted in six anastomoses, transitional epithelial-lined cysts were noted in nine, aggregated pools of mucus were noted in four, mixed transitional and intestinal epithelial-lined cysts were noted in two, and polypoid lesions with mucus pools or cysts projecting into the lumen were noted in five. Twelve cysts measured over 1 mm in diameter; six measured over 2 mm. These histologic features may result from overgrowth of intestinal glands by transitional epithelium, with subsequent gland dilatation, rupture, and mucus pooling. It is possible that the larger "cysts" and "polyps" may have contributed to the ureteroileal obstruction, a finding that may have bearing on other types of urinary tract reconstructions using bowel segments.

Adolescent↗

Leiomyosarcoma of the saphenous vein in a child with 12-year follow-up.

Leiomyosarcomas of the vasculature are exceedingly rare tumors in childhood. The case of a 2-year-old girl who underwent three local excisions with two courses of adjuvant chemotherapy over 3 years for a leiomyosarcoma of a saphenous vein tributary is described. Follow-up over the following 9 years has shown no evidence of further recurrence or metastases suggesting that cure has been achieved. Treatment options are discussed and pertinent literature is reviewed.

Antineoplastic Combined Chemotherapy Protocols↗

High prevalence of human papillomavirus transcripts in all grades of cervical intraepithelial glandular neoplasia.

Cervical biopsy specimens containing cervical intraepithelial glandular neoplasia (CIGN) were examined for the presence of human papillomavirus (HPV) RNA transcripts by in situ hybridization with iodine 125-labeled riboprobes. HPV RNA was detectable in 95.2% of biopsy specimens. HPV 16 RNA was present in 12, HPV 18 in 27, and both in 1 of the 42 cases examined. Among HPV-positive cases, HPV RNA was detectable in all grades of CIGN and, in three cases, in glands displaying only minimal nuclear abnormality insufficient for a diagnosis of CIGN. Patients with HPV RNA-positive CIGN were younger than those with negative findings for HPV, and patients with less severe grades of CIGN showed a trend toward a younger age of presentation than patients with severe glandular lesions. Increasing grades of CIGN may reflect progressive stages in the development of cervical adenocarcinoma, and this progression may closely involve HPV gene expression from its earliest stages.

Adult↗

Differing prevalence of human papillomavirus RNA in penile dysplasias and carcinomas may reflect differing etiologies.

Penile intraepithelial neoplasias grade 3 (PIN 3) and penile carcinomas were examined for the presence of human papillomavirus (HPV) RNA transcripts by in situ hybridization using 125I-labeled RNA probes. Human papillomavirus transcripts were detected in all 10 PIN 3 lesions not associated with invasive malignant conditions but were present in only 29% of penile carcinomas (9 of 26 squamous cell carcinomas and none of 5 verrucous carcinomas). Human papillomavirus RNA-positive penile cancers were significantly more likely to exhibit adjacent PIN 3 lesions than were HPV-negative tumors, and PIN 3 lesions adjacent to tumors always contained the same HPV-RNA type as was present in the invasive tumor. The development of most penile cancers may be unrelated to HPV infection. Future epidemiologic studies of the role of sexually transmitted factors in the development of penile carcinoma should distinguish between HPV-positive and HPV-negative penile cancers.

Adult↗

Transcription patterns of human papillomavirus type 16 in genital intraepithelial neoplasia: evidence for promoter usage within the E7 open reading frame during epithelial differentiation.

Human papillomavirus (HPV) type 16 transcription was analysed by in situ hybridization using 125I-labelled subgenomic riboprobes, from 26 genital intraepithelial neoplastic (IN) lesions, in formalin-fixed biopsies from 18 different cases. Distinct transcription patterns separable by the presence or absence of late gene transcription were detected. In 12 lesions, late gene expression was absent; HPV transcripts corresponding to the E6 and E7 open reading frame (ORF) were detectable in all basal cells and were usually evenly distributed through all layers of the epithelium. Transcripts corresponding to the E1, E2 and E2/E4 ORFs were present in nine of 12 lesions and displayed a similar distribution. In 14 lesions late gene transcripts were present. E6 and E7 transcripts were detectable basally in all but one lesion. The levels of E7 but not E6 transcripts were markedly increased in the superficial cells of differentiating epithelia, with an identical distribution and at similar levels to those of the E2/E4 transcript. We propose that the most abundant transcript in genital IN lesions containing late gene expression is an E7/E1 [symbol: see text] E2/E4 transcript corresponding to that reported in HPV-6/11 condylomata and which is derived from a similar promoter within the E7 ORF.

Cell Transformation, Neoplastic↗

Increased age and mortality associated with cervical carcinomas negative for human papillomavirus RNA.

Attempts to relate presence and type of human papillomavirus in cervical carcinoma with prognosis have yielded conflicting results. To further investigate this relation, the association between survival of cervical cancer patients after diagnosis and the presence of human papillomavirus (HPV) RNA within the tumour was assessed retrospectively. Formalin-fixed biopsy specimens from 212 patients with cervical carcinoma who had been followed for up to 6 years were tested by in-situ hybridisation with 125I-labelled riboprobes. HPV-RNA-positive women were 11.9 years younger than HPV-negative women at diagnosis (p less than 0.001). Case-fatality rates from cervical cancer rose with absence of HPV RNA, age at diagnosis, or FIGO stage. Multivariate analysis confirmed that absence of detectable HPV RNA and advanced FIGO stage were independent risk factors. No differences in survival between HPV types 16, 18, 31, or 33 were seen. These observations suggest that cervical carcinoma patients fall into two groups--a younger, HPV-RNA-positive group, with a better prognosis, and an older, HPV-RNA-negative group with poorer prognosis. Treatment regimens for the two groups may need to differ.

Adenocarcinoma↗

Differing characteristics of human papillomavirus RNA-positive and RNA-negative anal carcinomas.

Anal carcinomas were tested for the presence of human papillomavirus (HPV) RNA transcripts by in situ hybridization using 125I-labeled RNA probes. The HPV transcripts were detected in 73.2% of 41 nonglandular anal carcinomas but in none of six anal or 11 rectal adenocarcinomas. In anal nonglandular carcinomas, no difference in the percentage of tumors that were HPV RNA positive was observed between tumors classed as basaloid carcinomas or squamous cell carcinomas. Patients with HPV RNA-negative tumors were significantly older (9.2 years) than those with HPV RNA-positive tumors. Anal intraepithelial neoplasia Grade 3 in the surrounding epithelium was seen in 14 of 25 assessable HPV RNA-positive tumors and in none of nine assessable HPV RNA-negative tumors. Anal tumors may include two separate clinical and biologic groups distinguished by their dependence, or lack of dependence, on HPV RNA expression for maintenance of the neoplastic state.

Adenocarcinoma↗

Presence and distribution of human papillomavirus sense and antisense RNA transcripts in genital cancers.

RNA transcription in eight human papillomavirus (HPV) type 16-positive genital carcinomas and in two cervical squamous cell carcinoma (SCC)-derived cell lines was analysed by in situ hybridization using 125I-labelled subgenomic riboprobes. Transcripts corresponding to the E6 and E7 open reading frames were always present, except within the keratinizing layers of differentiated SCCs. Intranuclear E1 gene transcripts were detectable in both cell lines and some tumours whereas E2/E4 transcripts were absent from five of seven assessable tumours, suggesting transcription from integrated viral DNA. When mRNA sense riboprobes were used as controls, no signal was seen in the two cell lines; however, three tumours contained a focal, intense nuclear RNase-sensitive signal using mRNA sense riboprobes. This antisense RNA signal mapped across the whole genome including the noncoding region. In one tumour, the presence of antisense RNA was independently confirmed by using E7 and E2/E4 RNA probes of both orientations in RNase protection assays. Transcription of antisense RNA may be a natural feature of some HPV-positive genital tumours and its possible role in modulating cell behaviour in vivo requires further investigation.

Carcinoma, Squamous Cell↗

Two unusual tumours of the gastrointestinal tract in a patient with tuberous sclerosis.

A 16 year old girl with an established diagnosis of tuberous sclerosis presented with a 1 year history of swelling of the left cheek. A 2 cm diameter tumour was excised which showed histological features of a solid variant of a minor salivary gland basal cell adenoma. One year later during laparotomy and excision of multiple renal angiomyolipomas, a 5 cm diameter subserosal tumour was found at the hepatic flexure of the colon. Examination of biopsy material revealed a leiomyoma. This case is presented to demonstrate two tumours that have not to the authors' knowledge been previously described in a young patient with tuberous sclerosis. Although the association may be coincidental, these tumours could represent two rare associations of tuberous sclerosis.

Adenoma↗

Neonatal necrotizing enterocolitis: a cause of gastric metaplasia in the mid-ileum.

Following neonatal necrotizing enterocolitis in a premature Aboriginal baby, a stricture developed in the distal small intestine. At laparotomy a 1.0 cm stricture was found in a 25 cm thick-walled, oedematous segment of the mid-ileum. Biopsy demonstrated antropyloric-type ectopic mucosa and, therefore, the oedematous segment was removed. The resected specimen contained several distinct areas of flat antropyloric gastric mucosa as well as ileal mucosa. Although no acid-producing cells could be demonstrated, mucosal ulceration was prominent in several areas. Scanning electron microscopy demonstrated gastric pits. Immunoperoxidase technique for gastrin failed to demonstrate gastrin-containing cells. It is believed that this mucosa represents a metaplasia that has been induced in response to mucosal damage, which in turn was initiated by necrotizing enterocolitis. It is believed this would represent the first reported case.

Choristoma↗