Search PubMed⌕ Search

Biomedical subjects

A Brook

Publications and source records attributed to A Brook.

At least 19 recordsLinked to original sources
PubMed1999

Benign parotid hypertrophy on +HIV patients: limited late failures after external radiation.

PURPOSE: Although 8-10 Gy of external radiation therapy for +HIV associated parotid hypertrophy has achieved high response rates, the responses were transient with only 1/12 of patients retaining cosmetic control at median follow-up procedures of 9.5 months. Retreatment for failures after 8-10 Gy has also been unsatisfactory. Having shown that 24 Gy of external radiation therapy for benign parotid hypertrophy produced more durable cosmetic control than 8-10 Gy, we now report on longer follow-up periods on a group of patients receiving 24 Gy. MATERIALS AND METHODS: Twenty +HIV patients with clinical and radiographic evidence of lymphoepithelial lesions of the parotid were treated with 24 Gy of external radiation therapy using daily 1.5 Gy fractions; parallel opposed technique and 6 MV photons were used in 19 patients, and unilateral electron treatment was performed for one patient. RESULTS: With a mean follow-up period of 24 months, the cosmetic control appears durable. We have had no late failures past 24 months. Two patients have complained of modest xerostomia. There was no correlation with size of the cyst and eventual cosmetic result. CONCLUSIONS: Twenty-four Gy produces durable parotid control for HIV associated lymphoepithelial lesions of the parotid glands in +HIV patients. Failures after 2 years are uncommon and the side effects have been tolerable.

Female↗
PubMed1999

A genetic screen for modifiers of E2F in Drosophila melanogaster.

The activity of the E2F transcription factor is regulated in part by pRB, the protein product of the retinoblastoma tumor suppressor gene. Studies of tumor cells show that the p16(ink4a)/cdk4/cyclin D/pRB pathway is mutated in most forms of cancer, suggesting that the deregulation of E2F, and hence the cell cycle, is a common event in tumorigenesis. Extragenic mutations that enhance or suppress E2F activity are likely to alter cell-cycle control and may play a role in tumorigenesis. We used an E2F overexpression phenotype in the Drosophila eye to screen for modifiers of E2F activity. Coexpression of dE2F and its heterodimeric partner dDP in the fly eye induces S phases and cell death. We isolated 33 enhancer mutations of this phenotype by EMS and X-ray mutagenesis and by screening a deficiency library collection. The majority of these mutations sorted into six complementation groups, five of which have been identified as alleles of brahma (brm), moira (mor) osa, pointed (pnt), and polycephalon (poc). osa, brm, and mor encode proteins with homology to SWI1, SWI2, and SWI3, respectively, suggesting that the activity of a SWI/SNF chromatin-remodeling complex has an important impact on E2F-dependent phenotypes. Mutations in poc also suppress phenotypes caused by p21(CIP1) expression, indicating an important role for polycephalon in cell-cycle control.

Animals↗
PubMed1999

The utility of bone scans in rheumatology.

PURPOSE: Bone scanning is the most common diagnostic imaging service requested by Australian rheumatologists, who order $50,000 (Australian) worth of bone scans annually. METHODS: To determine why rheumatologists request bone scans and how they affect their patient management, the authors administered a two-part prospective survey before and after every bone scan ordered by four rheumatologists during a 6-month period in 1996. RESULTS: A total of 136 bone scans were requested. The primary indications for scanning were to confirm a clinical diagnosis (38%), to exclude a diagnosis (34%), and to localize the site of pain (17%). The common diseases that rheumatologists were attempting to confirm or exclude with bone scanning were inflammatory arthritis, malignancy, and fracture. However, the most common provisional and final diagnosis was soft tissue rheumatism (18%), followed by inflammatory arthritis (15%) and osteoarthritis (11%). Bone scans were successful in excluding a diagnosis in 87% and confirming a diagnosis in 80%. In 32%, bone scans altered the clinical diagnosis, and in 43% they changed the course of disease management. Bone scan results prevented further investigations in 60%.

Adolescent↗
PubMed1998

A phase I clinical trial of prolonged infusion of hydroxyurea in combination with hyperfractionated, accelerated, external radiation therapy in patients with advanced squamous cell cancer of the head and neck.

BACKGROUND: Preclinical data suggested that sustained inhibition of the anabolic enzyme, ribonucleotide reductase (RR), by hydroxyurea (HU) may be critical for the anticancer effects of the drug. A phase I trial of continuous infusion HU with concomitant hyperfractionated, accelerated radiation therapy (CHU-CHRT) was initiated to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of HU in patients with locally advanced squamous cell carcinoma (SCC) of the head and neck. METHODS: Patients were required to have histologically-documented and radiographically-staged locally advanced SCC of the hypopharynx (AJC stages II, III or IV), oropharynx (AJC stage IV), or oral cavity (AJC stage IV) not amenable to reasonable surgical resection. Eligible patients had adequate bone marrow, hepatic, and renal function and had to give informed consent. Concomitant, hyperfractionated, accelerated radiation therapy (CHRT) consisted of 1.2 Gy BID (6 hour minimum interfraction interval) on weekdays and 1.2 Gy delivered daily on the weekends to a total tumor dose of 74.4 Gy. Continuous infusion hydroxyurea (CHU) was administered at 0.25-0.375 mg/m2/min as a continuous intravenous infusion daily for 5 days with weekends days off for the duration of the radiation therapy. The dose of HU was increased by 0.125 mg/m2/min between dose levels until DLT was reached in 2/6 patients. If the primary had a complete clinical response and biopsies were negative, planned neck dissections were performed. RESULTS: Fifteen patients were enrolled and are evaluable. The initial dose level, 0.25 mg/m2/min was tolerated by 3/3 patients. At 0.375 mg/m2/min, 3/6 patients experienced grade 3-4 infections, with one patient having a non-fatal, subendocardial infarction. At 0.313 mg/m2/min, no patient experienced DLT. CONCLUSION: The MTD for CHU-CHRT was 0.313 mg/m2/min. The toxicities were primarily mucosal and a phase II study is in progress.

Adult↗
PubMed1998

Blepharitis.

Explore the source record for details and available documents.

Adult↗
PubMed1997

The world according to hedgehog.

Members of the Hedgehog family of signaling molecules mediate many important short- and long-range patterning processes during invertebrate and vertebrate development. In the fly, a single hedgehog gene regulates segmental and imaginal disc patterning. In contrast, in vertebrates a hedgehog gene family is involved in the control of left-right asymmetry, polarity in the central nervous system (CNS), somites and limb, organogenesis, chondrogenesis and spermatogenesis. Here, we review recent experiments addressing the function of the various Hedgehog members during invertebrate and vertebrate development.

Animals↗
PubMed1997

Papillary endolymphatic sac tumors: CT, MR imaging, and angiographic findings in 20 patients.

PURPOSE: To determine the computed tomographic (CT), magnetic resonance (MR) imaging, and angiographic findings of papillary endolymphatic sac tumors. MATERIALS AND METHODS: Clinical and imaging studies in 20 patients (aged 17-65 years) with histopathologically proved papillary endolymphatic sac tumors were retrospectively reviewed. Patients underwent CT (n = 18), MR imaging (n = 15), or angiography (n = 12). CT scans were evaluated for bone erosion and calcification; MR images, for signal intensity, enhancement patterns, and flow voids; and angiograms, for tumoral blood supply. RESULTS: All tumors were destructive and contained calcifications centered in the retrolabyrinthine region at CT. The MR imaging appearance varied with lesion size; 12 of 15 tumors showed increased signal intensity at T1-weighted imaging. The high-signal-intensity area was circumferential in lesions 3 cm or smaller and was scattered throughout the lesion in advanced tumors. Only tumors larger than 2 cm had flow voids. The blood supply arose predominantly from the external carotid artery. Large tumors had additional supply from the internal carotid and posterior circulation. CONCLUSION: Papillary endolymphatic sac tumors are destructive, hypervascular lesions that arise from the temporal bone retrolabyrinthine region. Increased signal intensity at unenhanced T1-weighted MR imaging is common and may help distinguish these lesions from more common, aggressive temporal bone tumors.

Adenocarcinoma↗
PubMed1996

E2F-induced S phase requires cyclin E.

Both the heterodimeric transcription factor, E2F, and the G1 cyclin, cyclin E, are required for the G1-S transition at the start of the metazoan cell cycle. It has been established that cyclin E can act as an upstream activator of E2F. In addition to this action, we show here that cyclin E has an essential role in DNA replication distinct from activating E2F. We have created transgenic Drosophila capable of inducible, ectopic production of E2F activity. Simultaneous overexpression of both Drosophila E2F subunits, dE2F and dDP, in embryos stimulated the expression of multiple E2F-target genes including cyclin E, and also caused the initiation of S phase. Mutation of cyclin E prevented the initiation of S phase after overexpression of dE2F/dDP without affecting induction of target gene expression. Thus, E2F-directed transcription cannot bypass loss of cyclin E in Drosophila embryos.

Animals↗
PubMed1996

Requirements for dE2F function in proliferating cells and in post-mitotic differentiating cells.

The transcription factor E2F is a target of the retinoblastoma tumor suppressor protein (pRB) and may mediate pRB regulation of S phase entry in mammalian cells. The recent identification of mutant alleles of the Drosophila E2F gene (dE2F) has shown that dE2F is required for embryogenesis. dE2F-mutant embryos lack a co-ordinated program of gene expression which accompanies S phase entry and DNA synthesis declines to levels that are barely detectable. We have investigated the role of the dE2F gene at later stages of development. dE2F is expressed in several larval tissues and is required for cell proliferation in the eye imaginal disc. Surprisingly, dE2F expression persists in post-mitotic cells of the eye disc of third-instar larvae. The loss of dE2F function in these cells causes a novel phenotype, characterized by loss of photoreceptors and abnormal rhabdomere cell morphology. These results show that dE2F is required at multiple stages of development and suggest that E2F may have an important function in post-mitotic cells in addition to its role during cell proliferation.

Animals↗
PubMed1995

The transcription factor E2F is required for S phase during Drosophila embryogenesis.

Overexpression of the E2F-1 cDNA in mammalian cells disrupts normal control of the cell cycle and drives cells into S phase. Whereas eliminating E2F activity would test its inferred involvement in the G1-S transition, elimination is complicated by the existence of gene families encoding mammalian E2F. Here we identify mutations in a single essential Drosophila gene, dE2F, that encodes a homolog of the mammalian E2F gene family. Embryos homozygous for null mutations of dE2F complete early cell cycles, presumably using maternal contributions of gene products, but DNA synthesis falls to virtually undetectable levels in cycle 17. Mutant embryos also lack the pulses of coordinate transcription of genes encoding replication functions that usually accompany each transition from quiescence to S phase. We conclude that in most cells dE2F is essential for a G1-S transcriptional program and for G1-S progression.

Animals↗
PubMed1995

Explanation in the hermeneutic science.

Using clinical vignettes, we first examine the idea that psychoanalysis is, in Gill's (1991) phrase, a hermeneutic science--hermeneutic because it interprets meanings, scientific because the meaning connections it deals with are also usually causal connections. Next we explore some aspects of the structure of the kinds of explanation distinctive to psychoanalysis. Three kinds are distinguished: conveyance of content explanations, which have been central in the accounts of some recent philosophers of psychoanalysis, and two kinds of explanation in terms of intentionality, in terms, that is to say, of what the psychic states in question are about. One deals with forward-looking states such as wishes, in which the state is about some future, sought-after state of affairs such as a wish-fulfilment; the other deals with backward-looking psychic states such as memories, in which the state to be explained is about some earlier experience, fantasy, or whatever, one often quite unknown to the analysand prior to analysis. The paper concludes by making a quick case for the idea that good explanations in terms of meaning or intentionality often also identify the cause of the psychic states being explained.

Female↗
PubMed1994

DNA-binding and trans-activation properties of Drosophila E2F and DP proteins.

The temporal activation of E2F transcriptional activity appears to be an important component of the mechanisms that prepare mammalian cells for DNA replication. Regulation of E2F activity appears to be a highly complex process, and the dissection of the E2F pathway will be greatly facilitated by the ability to use genetic approaches. We report the isolation of two Drosophila genes that can stimulate E2F-dependent transcription in Drosophila cells. One of these genes, dE2F, contains three domains that are highly conserved in the human homologs E2F-1, E2F-2, and E2F-3. Interestingly, one of these domains is highly homologous to the retinoblastoma protein (RB)-binding sequences of human E2F genes. The other gene, dDP, is closely related to the human DP-1 and DP-2 genes. We demonstrate that dDP and dE2F interact and cooperate to give sequence-specific DNA binding and optimal trans-activation. These features suggest that endogenous Drosophila E2F, like human E2F, may be composed of heterodimers and may be regulated by RB-like proteins. The isolation of these genes will provide important reagents for the genetic analysis of the E2F pathway.

Amino Acid Sequence↗
PubMed1994

Schopenhauer and Freud.

A close study of Schopenhauer's central work, 'The World as Will and Representation', reveals that a number of Freud's most characteristic doctrines were first articulated by Schopenhauer. A thinker always expresses something of his culture, of course, but the parallels to be found between Freud and Schopenhauer go well beyond cultural influence. Schopenhauer's concept of the will contains the foundations of what in Freud became the concepts of the unconscious and the id. Schopenhauer's writings on madness anticipate Freud's theory of repression and his first theory of the aetiology of neurosis. Schopenhauer's work contains aspects of what become the theory of free association. And most importantly, Schopenhauer articulates major parts of the Freudian theory of sexuality. These correspondences raise some interesting questions about Freud's denial that he even read Schopenhauer until late in life.

Freudian Theory↗
PubMed1991

Bowel distress and emotional conflict.

A psychodynamic assessment of 60 women with functional bowel disorder seen at St Mark's, a specialist hospital for disorders of the colon and rectum, has shown that most were trapped in severe emotional conflicts with which they were unable to cope. In many the bodily illnesses appeared to be an expression of these conflicts as well as a defence against experiencing them. The illnesses were then partly, or entirely, emotional conflicts that had become medicalized--emotional conflicts in illnesses clothing. The illnesses, usually precipitated by significant life events, often had their roots in emotional conflicts in infancy or childhood at which time a high proportion of the women had experienced a severe life trauma. The study also indicated that the conflicts that appeared to contribute to the illnesses were associated with emotional difficulties in fulfilling themselves as women.

Adolescent↗
PubMed1989

Streptococcus faecalis arthritis.

Septic arthritis due to Streptococcus faecalis is rare. We describe a case in which synovial biopsy was required for diagnosis and a new longterm antibiotic combination using ciprofloxacin and amoxicillin was successful in treating the infection. Comparison is made with previous reported cases and the usual poor outcome in this condition.

Amoxicillin↗