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Biomedical subjects

J Stack

Publications and source records attributed to J Stack.

At least 19 recordsLinked to original sources
PubMed2000

Development and application of a GFP-FRET intracellular caspase assay for drug screening.

Apoptosis is a crucial biological process, and activation of caspase endoproteases is essential for proper regulation and execution of apoptosis. Because caspases also appear to be central players in several pathological states, there is a practical need within the biopharmaceutical research community for facile, noninvasive cellular assays for the discovery of compounds that modulate caspase activity. Tandem molecules of green fluorescent protein (GFP) stably expressed within cells can serve as a genetically encoded sensor of protease activity. Using this technology, we have developed a stable cellular system for the screening of agents that modulate activation of the caspase cascade. This assay technology allows for the real-time monitoring of apoptosis in situ, using conventional fluorescent plate reader detection. By applying this assay system to an actual compound screen, small-molecule inducers of cell apoptosis were reliably identified. Follow-up pharmacology confirmed that the rank-order potency of primary hits using the intracellular GFP assay corresponded to that found using a conventional, cell lysis-based assay method.

Amino Acid Sequence↗
PubMed2000

Weight change in older depressed patients during acute pharmacotherapy with paroxetine and nortriptyline: a double-blind randomized trial.

The authors examined weight change in 32 elderly patients treated for 12 weeks with either nortriptyline or paroxetine during acute-phase pharmacotherapy. Random assignment to treatment and double-blind assessment of weight change were performed, including ascertainment of premorbid (i.e., pre-depression) weight. Pretreatment severity of depression was correlated with weight loss during the depressive episode and depression-related weight loss, in turn, correlated with weight regained during antidepressant treatment. There was no differential weight change associated with nortriptyline vs. paroxetine. Rather, subjects in both groups approximated their premorbid weights by 12 weeks of acute-phase pharmacotherapy with either agent. However, additional investigation of weight change during continuation and maintenance pharmacotherapy is necessary and would be clinically useful for the long-term management of elderly patients with depression.

Aged↗
PubMed1999

Surfactant protein B deficiency: clinical, histological and molecular evaluation.

Congenital alveolar proteinosis due to surfactant protein B deficiency is an inherited disease which results in severe respiratory failure in term infants soon after birth. The pathophysiologic basis of this disease is now known to be an inability to synthesise adequate quantities of normally functioning surfactant protein B. We report a male infant with fatal respiratory failure of neonatal onset, and histopathological features typical of those seen in congenital alveolar proteinosis. Molecular analysis of genomic DNA revealed two mutations, the 'common' 121ins2 mutation in exon 4, and a novel 2bp frameshift mutation in exon 5. We believe this is the first Australian case of surfactant protein B deficiency confirmed by molecular analysis.

Alleles↗
PubMed1999

A double-blind randomized comparison of nortriptyline and paroxetine in the treatment of late-life depression: 6-week outcome.

BACKGROUND: Some studies have suggested that selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The objective of this study was to compare the 6-week outcome of treatment with nortriptyline and paroxetine in older patients with a major depressive episode. METHOD: A double-blind randomized comparison of nortriptyline and paroxetine was conducted in 80 elderly (mean +/- SD age = 75.0 +/- 7.4 years) psychiatric inpatients and outpatients who presented with a major depressive episode. Dropout and response rates were compared in patients who began or completed treatment. Rates of response of inpatients and patients with melancholic depression were also compared. RESULTS: Over 6 weeks, there were no significant differences in dropout rates due to side effects (nortriptyline, 14% vs. paroxetine, 19%) or for any reason (27% vs. 33%). Similarly, there were no significant differences between the rates of favorable response to nortriptyline or paroxetine (intent-to-treat analysis, 57% vs. 44%; completer analysis, 78% vs. 66%). Analyses restricted to inpatients or to patients with melancholic depression yielded similar results. CONCLUSION: Nortriptyline and paroxetine appear to have similar efficacy and tolerability in the acute (6-week) treatment of older depressed patients, including hospitalized patients and those with melancholic features.

Age Factors↗
PubMed1996

Tendon shift in hallux valgus: observations at MR imaging.

OBJECTIVE: This study was undertaken to demonstrate a shift in tendon alignment at the first metatarsophalangeal joint in patients with hallux valgus by means of magnetic resonance imaging. DESIGN: Ten normal feet and 20 feet with the hallux valgus deformity conforming to conventional clinical and radiographic criteria were prospectively studied using magnetic resonance imaging. Correlation was made between tendon position at the first metatarsophalangeal joint and the severity of the hallux valgus deformity. RESULTS: There is a significant shift in tendon position at the first metatarsophalangeal joint of patients with hallux valgus. The insertion of the abductor hallucis tendon is markedly plantarward and the flexor and extensor tendons bowstring at the first metatarsophalangeal joint compared with patients without the deformity. The severity of the tendon shift correlates with the hallux valgus angle and clinical severity of the hallux valgus deformity in each case. CONCLUSION: Patients with hallux valgus have a significant tendon shift at the first metatarsophalangeal joint which appears to contribute to development of the deformity.

Case-Control Studies↗
PubMed1996

Predicting mandibular invasion in mouth cancer.

This study assesses the role of orthopantomography, computerized tomography and intra-operative assessment in predicting the presence and extent of mandibular invasion by mouth tumours. Forty patient's with squamous carcinoma of the oral cavity and oropharynx were studied. All had pre-operative orthopantomography and computerized tomography as well as intra-operative assessment of mandibular invasion and these factors were compared with the actual histological invasion to assess the role of each test. This study found that negative radiology is useful for excluding cortical invasion and as might be expected is of no real value in excluding periosteal invasion, a positive orthopantomogram accurately predicts invasion at least into the cortex, however, a positive CT must be judged cautiously due to false positives and intra-operative assessment by an experienced operator is a useful adjunct to radiology.

Adult↗
PubMed1995

Lymphoma and Hashimoto's thyroiditis.

Development of malignant lymphoma in Hashimoto's thyroiditis is well documented. A case of tracheal invasion by a lymphoma which accompanied Hashimoto's disease is described. The clinical and diagnostic difficulties which were encountered are presented. The magnetic resonance imaging (MRI) findings which have not been reported previously are outlined.

Humans↗
PubMed1994

Hallux valgus, first metatarsal pronation and collapse of the medial longitudinal arch--a radiological correlation.

In a previous study we developed a model to assess first metatarsal pronation based on the position of the inferior tuberosity of its base and showed a significant relationship between first metatarsal pronation and the intermetatarsal angle (r = 0.69, p < 0.001). The present study was undertaken to correlate first metatarsal pronation with the height of the medial longitudinal arch in an attempt to define the clinical significance of this new finding. The weight-bearing anteroposterior and lateral radiographs of the feet of 50 patients (100 feet; 36 females patients of mean age 38 years, 14 males patients of mean age 40 years) were reviewed, and in each case, the patient's age, sex, intermetatarsal angle, amount of first metatarsal pronation and medial longitudinal arch angle were recorded by independent observers. A significant relationship was demonstrated between first metatarsal pronation and the height of the medial longitudinal arch (r = 0.93, p < 0.0001). Less marked association was observed between intermetatarsal angles and first metatarsal pronation (r = 0.71, p < 0.001). Multivariate analysis of patient age, sex, intermetatarsal angle and medial longitudinal arch angle against metatarsal pronation showed that the single most dominant variable affecting metatarsal pronation was the height of the medial longitudinal arch.

Adult↗
PubMed1994

Magnetic resonance imaging in pigmented villonodular synovitis.

The magnetic resonance imaging (MRI) appearance of pigmented villonodular synovitis of the knee is described for three patients. In the images for one patient diffuse areas of low signal intensity reflecting hemosiderin deposits suggested the diagnosis. For another patient with the diffuse form of the condition but minimal hemosiderin deposition, identification of diffuse synovial proliferation in the MRI images guided diagnostic percutaneous biopsy. For the third patient, who had localized pigmented villonodular synovitis, MRI after administration of a gadolinium chelate facilitated identification of localized synovial proliferation and guided diagnostic arthroscopic biopsy. The authors discuss the value of MRI in the diagnosis of all forms of this uncommon condition and the various signal characteristics that it may produce.

Adolescent↗
PubMed1994

A weight on children's minds: body shape dissatisfactions at 9-years old.

Although adolescent dieting is common, comparatively little is known about its developmental course. The present study investigated the self-perception and body shape satisfaction of 9-year old girls and boys in different weight categories. Two hundred and thirteen girls and 166 boys from three schools completed assessments of body-esteem, self-esteem, body shape preference and dietary restraint. The children's body weight and height were also measured. The heaviest children expressed the most discontent, having a low body-esteem, a desire for thinness and higher levels of dietary restraint. However, this desire for thinness and associated dieting motivation was apparent in some children in all weight categories. Furthermore, this pattern was more characteristic of girls than boys. By the age of nine, girls and boys already differ in their body shape satisfaction and differ in their body shape aspirations. Initiatives to reduce obesity should acknowledge these early and strongly-held gender differences or risk promoting the unwarranted pursuit of thinness by girls.

Body Constitution↗
PubMed1993

Radiographic features that enable assessment of first metatarsal rotation: the role of pronation in hallux valgus.

This study describes a method of detecting first metatarsal pronation on the basis of the movement of the inferior tuberosity of the base of 20 cadaveric first metatarsals at 0 degrees, 10 degrees, 20 degrees and 30 degrees pronation. On pronation, the inferior tuberosity of the base of the first metatarsal moved lateral to the mid-line axis. At 10 degrees, the tuberosity pointed to the junction of the inner third and outer two-thirds of a line between the midpoint and lateral tubercle of the base. At 20 degrees, it pointed to the junction of the inner two-thirds and outer third of that line. At 30 degrees, it pointed to the outer margin of the lateral third. Using these features, the amount of first metatarsal pronation in 100 consecutive weight-bearing views of feet was recorded and plotted against the corresponding intermetatarsal angles in those feet. Four of 43 patients with an intermetatarsal angle of less than 9 degrees had pronation greater than 10 degrees, 48 of 57 patients with an intermetatarsal angle greater than 9 degrees had pronation greater than 10 degrees (P < 0.001). As intermetatarsal angles increase, the amount of first metatarsal pronation increases (r = 0.69). Pronation and varus deviation of the first metatarsal are linked; both alter the tendon balance maintaining proximal phalanx alignment and lead to the development of hallux valgus.

Hallux Valgus↗
PubMed1993

Role of magnetic resonance imaging in the assessment of spinal injuries.

Magnetic Resonance Imaging (MRI) examination was carried out on 44 patients who had spinal injuries with neurological involvement. The technique provided valuable information about the nature of the injuries and, in particular, about the state of the spinal cord. The appearances of the cord on MRI ranged from normal, to oedema, to more severe damage such as cord haemorrhage or transection or, in later cases, myelomalacia. The appearance of the cord on MRI correlated strongly with both the severity of the neurological deficit and also the degree of subsequent recovery. In the assessment of the acute spinal injury, MRI has been shown to be a good prognostic indicator; it may also help to identify which patients are likely to benefit from early decompression.

Acute Disease↗
PubMed1993

Bipolar affective disorder prior to the onset of multiple sclerosis.

The frequent association of affective disorder and multiple sclerosis raises important aetiological and clinical considerations. Reported here are seven patients who presented with symptoms of multiple sclerosis and who had a preceding history of bipolar affective disorder. The hypothesis that bipolar illness may be the initial manifestation of multiple sclerosis is discussed with reference to relevant clinical and epidemiological research on the topic.

Adult↗
PubMed1992

Abnormalities of cerebral structure in schizophrenia on magnetic resonance imaging: interpretation in relation to the neurodevelopmental hypothesis.

The nature of abnormalities of cerebral structure evident in schizophrenia on magnetic resonance imaging is considered in relation to the neurodevelopmental hypothesis of the disorder. While schizophrenic patients showed increased ventricular volume, the extent of increase with age was comparable with that evident in controls and was unrelated to duration of illness. Conversely, cortical atrophy was evident only in patients, and this increased markedly with age and duration of illness. Such findings could be suggestive of two distinct pathophysiological processes in schizophrenia, but a schema for their reconciliation with the neurodevelopmental hypothesis is elaborated.

Adult↗