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Biomedical subjects

M Prentice

Publications and source records attributed to M Prentice.

At least 19 recordsLinked to original sources

Portopulmonary hypertension in decompensated cirrhosis with refractory ascites.

BACKGROUND: The prevalence of portopulmonary hypertension (PPHTN) in patients with cirrhosis and refractory ascites is unknown. Its presence may preclude patients from receiving a transjugular intrahepatic portosystemic shunt or liver transplantation as a definitive treatment for their end stage cirrhosis. PURPOSE: To determine the prevalence, possible aetiological factors, and predictive factors for the development of PPHTN in these patients. METHODS: Sixty two patients (53 males, nine females; mean age 54.5 (1.4) years) with biopsy proven cirrhosis and refractory ascites underwent angiographic measurements of pulmonary and splanchnic haemodynamics. Endothelin 1 levels were measured from the pulmonary artery. Forty nine patients underwent radionuclide angiography for measurements of central blood volume, pulmonary vascular, and cardiac chamber volumes. Forty seven patients also underwent two dimensional echocardiography for measurements of cardiac structural and functional parameters. Cardiac output, and systemic and pulmonary vascular resistance were calculated. RESULTS: Ten patients (16.1%) fulfilled the criteria for PPHTN (mean pulmonary artery pressure >/= 25 mm Hg and pulmonary vascular resistance >/= 120 dynxs/cm(5)), with significantly higher mean right atrial (15.4 (1.2) v 7.9 (0.5) mm Hg; p<0.001), and right ventricular pressures (24.7 (1.5) v 14.7 (0.6) mm Hg; p<0.001), and endothelin 1 levels (3.04 (0.40) v 1.98 (0.12) pg/ml; p=0.02). No significant differences in any of the other parameters measured were detected between the two groups. A right atrial pressure of >/= 14 mm Hg had a 83% positive predictive value for the presence of PPHTN. CONCLUSIONS: Portopulmonary hypertension is common in cirrhosis with refractory ascites, possibly due to excess endothelin 1 in the pulmonary circulation. An elevated right atrial pressure >/= 14 mm Hg predicts the presence of PPHTN, which may be helpful in deciding management options in these patients.

Ascites↗

Conservative treatment as an option in the management of pancreatic pseudocyst.

BACKGROUND: Management of pancreatic pseudocysts is associated with considerable morbidity (15-25%). Traditionally, pancreatic pseudocysts have been drained because of the perceived risks of complications including infection, rupture or haemorrhage. We have adopted a more conservative approach with drainage only for uncontrolled pain or gastric outlet obstruction. This study reports our experience. PATIENTS AND METHODS: A consecutive series of 36 patients with pancreatic pseudocysts were treated over an 11-year period in one district general hospital serving a population of 310,000. This study group comprised of 19 men and 17 women with a median age of 55 years (range, 10-88 years). Twenty-two patients had a preceding attack of acute pancreatitis whilst 12 patients had clinical and radiological evidence of chronic pancreatitis. The aetiology comprised of gallstones (16), alcohol (5), trauma (2), tumour (2), hyperlipidaemia (1) and idiopathic (10). RESULTS: All patients were initially managed conservatively and intervention, either by radiological-assisted external drainage or cyst-enteric drainage (by surgery or endoscopy), was only performed for persisting symptoms or complications. Patients treated conservatively had 6 monthly follow-up abdominal ultrasound scans (USS) for 1 year. Fourteen of the 36 patients (39%) were successfully managed conservatively, whilst 22 patients required intervention either by percutaneous radiological drainage (12), by endoscopic cystogastrostomy (1) or by open surgical cyst-enteric anastomosis (9). Median size of the pancreatic pseudocysts in the 14 patients managed conservatively (7 cm) was nearly similar to that of the 22 patients requiring intervention (8 cm). The most common indications for invasive intervention in the 22 patients were persistent pain (16), gastric outlet obstruction (4), jaundice (1) and dyspepsia with weight loss (1). Although one patient required surgery for persistent pain, no other patients required urgent or scheduled surgery for complications of untreated pancreatic pseudocysts. Two of the 12 patients treated by percutaneous radiological drainage had recurrence of pancreatic pseudocysts requiring surgery. Two patients developed an intra-abdominal abscess following cyst-enteric drainage of pancreatic pseudocysts and one patient had a pulmonary embolism. On the mean follow-up of 37.3 months, one patient with alcoholic pancreatitis died 5 months after surgical cyst-enteric bypass. CONCLUSIONS: These results suggest that many patients with pancreatic pseudocysts can be managed conservatively if presenting symptoms can be controlled.

Adolescent↗

Endocervical cancer is associated with an increase in the ligands and receptors for transforming growth factor-beta and a contrasting decrease in p27(Kip1).

OBJECTIVE: The aim of this study was to investigate the relationship between the expression of the TGF-beta ligands and TGF-beta receptors to the expression of p27(Kip1), a TGF-beta-regulated gene, in endocervical cancer. METHODS: To examine the expression of TGF-beta and p27(Kip1) in malignant transformation of the uterine endocervix, a panel of 23 formalin-fixed and paraffin-embedded human cervical specimens, including 8 with benign endocervical glands, 8 with cervical adenocarcinoma in situ, and 7 with cervical adenocarcinomas, was used. Tissues were immunostained with polyclonal antibodies that react specifically with TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-beta RI, TGF-beta RII, and p27(Kip1). RESULTS: Immunostaining for TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-beta RI, TGF-beta RII, and p27(Kip1) was detected in normal endocervix, with the TGF-betas showing weak cytoplasmic staining, while p27(Kip1) showed strong nuclear staining. Expression of TGF-beta increased significantly upon neoplastic transformation with the TGF-beta ligands and receptors showing strong cytoplasmic staining in adenocarcinoma in situ compared to normal endocervix. Interestingly, expression of TGF-beta was lower in adenocarcinoma than in adenocarcinoma in situ, but still significantly higher than in normal endocervix. TGF-beta 2 and TGF-beta 3 showed higher levels of immunostaining than TGF-beta 1 in adenocarcinomas. In contrast, p27(Kip1) protein expression decreased with progressive malignancy, with lower p27(Kip1) protein levels detected in adenocarcinoma than in adenocarcinoma in situ, while normal endocervix showed the highest level of p27(Kip1) protein expression. CONCLUSION: Elevated expression of the TGF-beta ligands and receptors is found in both cervical adenocarcinoma in situ and adenocarcinoma compared to normal endocervix. In contrast, a progressive decrease in p27(Kip1) occurs upon neoplastic transformation of the normal endocervix to cervical adenocarcinoma. These results suggest that neoplastic transformation of the endocervix may be related to dysregulation of TGF-beta and p27(Kip1) seen as an elevation of TGF-beta and a reduction of p27(Kip1) expression that may lead to loss of cell cycle control.

Activin Receptors, Type I↗

The high-pathogenicity island of Yersinia enterocolitica Ye8081 undergoes low-frequency deletion but not precise excision, suggesting recent stabilization in the genome.

Highly pathogenic strains of Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica are characterized by the possession of a pathogenicity island designated the high-pathogenicity island (HPI). This 35- to 45-kb island carries an iron uptake system named the yersiniabactin locus. While the HPIs of Y. pestis and Y. pseudotuberculosis are subject to high-frequency spontaneous deletion from the chromosome, we were initially unable to obtain HPI-deleted Y. enterocolitica 1B isolates. In the present study, using a positive selection strategy, we identified three HPI-deleted mutants of Y. enterocolitica strain Ye8081. In these three independent clones, the chromosomal deletion was not limited to the HPI but encompassed a larger DNA fragment of approximately 140 kb. Loss of this fragment, which occurred at a frequency of approximately 5 x 10(-7), resulted in the disappearance of several phenotypic traits, such as growth in a minimal medium, hydrolysis of o-nitrophenyl-beta-D-thiogalactopyranoside, Tween esterase activity, and motility, and in a decreased virulence for mice. However, no precise excision of the Ye8081 HPI was observed. To gain more insight into the molecular basis for this phenomenon, the putative machinery of HPI excision in Y. enterocolitica was analyzed and compared to that in Y. pseudotuberculosis. We show that the probable reasons for failure of precise excision of the HPI of Y. enterocolitica Ye8081 are (i) the interruption of the P4-like integrase gene located close to its right-hand boundary by a premature stop codon and (ii) lack of conservation of 17-bp att-like sequences at both extremities of the HPI. These mutations may represent a process of HPI stabilization in the species Y. enterocolitica.

Animals↗

The 102-kilobase unstable region of Yersinia pestis comprises a high-pathogenicity island linked to a pigmentation segment which undergoes internal rearrangement.

Several pathogenicity islands have recently been identified in different bacterial species, including a high-pathogenicity island (HPI) in Yersinia enterocolitica 1B. In Y. pestis, a 102-kb chromosomal fragment (pgm locus) that carries genes involved in iron acquisition and colony pigmentation can be deleted en bloc. In this study, characterization and mapping of the 102-kb region of Y. pestis 6/69 were performed to determine if this unstable region is a pathogenicity island. We found that the 102-kb region of Y. pestis is composed of two clearly distinct regions: an approximately 35-kb iron acquisition segment, which is an HPI per se, linked to an approximately 68-kb pigmentation segment. This linkage was preserved in all of the Y. pestis strains studied. However, several nonpigmented Y. pestis strains harboring an irp2 gene have been previously identified, suggesting that the pigmentation segment is independently mobile. Comparison of the physical map of the 102-kb region of these strains with that of strain 6/69 and complementation experiments were carried out to determine the genetic basis of this phenomenon. We demonstrate that several different mechanisms involving mutations and various-size deletions are responsible for the nonpigmented phenotype in the nine strains studied. However, no deletion corresponded exactly to the pigmentation segment. The 102-kb region of Y. pestis is an evolutionarily stable linkage of an HPI with a pigmentation segment in a region of the chromosome prone to rearrangement in vitro.

Bacterial Outer Membrane Proteins↗

The leg ulcer resource team: a standard of care.

A leg ulcer resource team was formed to introduce and implement a standard of care for patients with leg ulcers. An audit of the standard following implementation showed that 82% of ulcers had been classified correctly, diagnostic tools had been used in 78% of cases and a clear rationale for care given in 86%. However, accurate identification of patient needs in the care plan occurred in only 39% of cases, and only 60% of care plans had ulcer size and site recorded. Patient education was also a problem--25% of patients did not know what type of ulcer they had and only 43% could describe care of their ulcer or identify risk factors associated with leg ulceration.

Community Health Nursing↗

Characterization of a large chromosomal "high-pathogenicity island" in biotype 1B Yersinia enterocolitica.

Pathogenic Yersinia spp. can be subdivided into highly pathogenic (high-pathogenicity) and low-pathogenicity strains. Several genes specific for the high-pathogenicity strains are clustered on a chromosomal fragment designated a "high-pathogenicity island" (HPI). In the present work, the HPI of biotype 1B strain Ye 8081 of Y. enterocolitica was characterized. We demonstrate important differences from the HPI of Y. pestis. The HPI of Y. enterocolitica is smaller (45 kb) and is not flanked by insertion sequences. A copy of the gene coding for the tRNA-Asn is present at one extremity of the HPI and may, as in uropathogenic Escherichia coli, participate in the excision of the island. In addition to the genes encoding the yersiniabactin-pesticin receptor and the high-molecular-weight protein 2, four repeated sequences are present on the HPI of Y. enterocolitica. At least two of them are insertion elements: previously described IS1328 and newly characterized IS1400. Comparison of the HPI of strain Ye 8081 with that of other Y. enterocolitica strains of biotype 1B indicates that most of the island is conserved, apart from 15 kb at the left-hand end which is variable, especially in the region where three repeated sequences are clustered.

Amino Acid Sequence↗

Osteopenia as a feature of the androgen insensitivity syndrome.

OBJECTIVE: The syndrome of androgen insensitivity, a paradigm of a hormone resistance syndrome, manifests as failure of masculinization despite normal or high concentrations of serum testosterone. The defect in these 46 XY patients resides in the androgen receptor gene, with consequent defective androgen action and abnormal sexual differentiation. We sought to evaluate whether the adverse sequelae of androgen resistance may extend to skeletal tissue by measuring bone mineral density in six patients with androgen insensitivity. DESIGN: A cross-sectional retrospective study. MEASUREMENTS: Bone mineral density was measured by means of a Dexa (Hologic QDR 1000 scanner). The diagnosis of androgen insensitivity was confirmed in each patient by karyotype and assay of sex hormones. RESULTS: The five adult patients with androgen insensitivity had been exposed to both defective androgen action and variable periods of oestrogen deficiency. The latter resulted from the low circulating oestrogen concentrations (for premenopausal females) before gonadectomy and inadequate oestrogen replacement after gonadectomy. All five adults with androgen insensitivity had osteopenia in both the lumbar spine (T-score -1.52 to -3.85) and femoral neck (T-score -1.34 to -4.91). CONCLUSIONS: Osteopenia in patients with androgen insensitivity may relate to defective androgen action, oestrogen deficiency or a combination of the two. These observations have implications for the management of patients with androgen insensitivity and may provide insight into the effects of androgens on the female as well as the male skeleton.

Adolescent↗

Leukemia care.

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Adolescent↗

A partnership with minority populations: a community model of effectiveness research.

This paper describes a community-based approach, including a partnership of an academic medical institution and a high-risk, urban, African-American population, directed at decreasing premature morbidity and mortality and enhancing health and functional status. The intervention approach is based on a model of community-based leadership and "ownership" of interventions and programs to enhance sustainability of effective approaches, and it follows specific stages to assure appropriate assessment and evaluation. Initial efforts were directed at the control of hypertension and were coordinated through decentralized mayor's stations in Baltimore, Maryland. This approach was successful in significantly enhancing control of hypertension and reducing related morbidity and mortality. Over time, an enhanced partnership has been coordinated through churches in the community and organized around a program entitled "Heart, Body, and Soul." Current efforts are directed at the major risk factors and preventable and/or controllable problems in the population, such as hypertension, smoking, obesity, diabetes, hyperlipidemia, and cervical and breast cancer. Key components include the training of neighborhood health workers to provide screening, counseling, monitoring, support, and follow-up; enhanced access to care; training of high school students as health counselors; and use of media to promote healthier life-styles.

Academic Medical Centers↗

Ectopic beta-human chorionic gonadotropin production by a dermoid cyst.

Benign cystic teratomas of the ovary (dermoid cysts) are common in women in the 20- to 40-year-old age group; 10% of these teratomas are bilateral. There have been reports of hormone production by dermoid cysts, particularly thyroid-stimulating hormone. We report the first case to our knowledge, of ectopic human chorionic gonadotropin production by a dermoid cyst.

Adult↗

Isolated unilateral hypoglossal nerve palsy due to a chondroid chordoma.

A case is described of an isolated unilateral hypoglossal nerve palsy due to a tumour which was removed surgically from the hypoglossal canal. The pathological findings showed the features of a chondroid chordoma. This case is unusual because intracranial causes of isolated unilateral hypoglossal nerve palsies are rare, and because the chondroid chordoma had arisen laterally, either close to or within the hypoglossal canal.

Chordoma↗