Biomedical subjects

D Perkins

Publications and source records attributed to D Perkins.

At least 19 recordsLinked to original sources

PubMed2005

Progressive spontaneous unilateral enlargement of the breast twenty-two years after prosthetic breast augmentation.

Late spontaneous enlargement of the breast is a rare complication after prosthetic breast augmentation. It has been intermittently described in the literature over the last 24 years but its exact aetiology remains unknown. Several possible aetiologies have been proposed. We present a case of a 46-year-old female who developed spontaneous asymmetrical breast enlargement 22 years post-bilateral breast augmentation without any known precipitating factors. Radiographic imaging revealed a periprosthetic collection occupying 70% of the volume inside the capsule. Initial recommendations for capsulectomy and removal of the breast implant were delayed for a year by the patient who subsequently represented with ongoing enlargement of the affected breast. Pathological findings revealed an intact silicone implant surrounded by laminated blood clot, similar in appearance to a chronic subdural haematoma. The literature is reviewed and the possible pathophysiological mechanisms of this unusual condition discussed.

Breast↗

PubMed2003

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design.

Adolescent↗

PubMed2003

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. II. Baseline characteristics of the "prodromal" sample.

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.

Adolescent↗

PubMed2003

The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) functions as a dominant regulator of apoptosis in hippocampal neurons involving activation of the ERK survival pathway and upregulation of the antiapoptotic protein Bag-1.

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) can trigger or block apoptosis in a cell type-dependent manner. We have recently shown that the protein kinase activity of the large subunit of the HSV-2 ribonucleotide reductase (R1) protein (ICP10 PK) blocks apoptosis in cultured hippocampal neurons by activating the extracellular signal-regulated kinase (ERK) survival pathway (Perkins et al., J. Virol. 76:1435-1449, 2002). The present studies were designed to better elucidate the mechanism of ICP10 PK-induced neuroprotection and determine whether HSV-1 has similar activity. The data indicate that apoptosis inhibition by ICP10 PK involves a c-Raf-1-dependent mechanism and induction of the antiapoptotic protein Bag-1 by the activated ERK survival pathway. Also associated with neuroprotection by ICP10 PK are increased activation/stability of the transcription factor CREB and stabilization of the antiapoptotic protein Bcl-2. HSV-1 and the ICP10 PK-deleted HSV-2 mutant ICP10DeltaPK activate JNK, c-Jun, and ATF-2, induce the proapoptotic protein BAD, and trigger apoptosis in hippocampal neurons. c-Jun activation and apoptosis are inhibited in hippocampal cultures infected with HSV-1 in the presence of the JNK inhibitor SP600125, suggesting that JNK/c-Jun activation is required for HSV-1-induced apoptosis. Ectopically delivered ICP10 PK (but not its PK-negative mutant p139) inhibits apoptosis triggered by HSV-1 or ICP10DeltaPK. Collectively, the data indicate that ICP10 PK-induced activation of the ERK survival pathway results in Bag-1 upregulation and overrides the proapoptotic JNK/c-Jun signal induced by other viral proteins.

Activating Transcription Factor 2↗

PubMed2002

The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) blocks apoptosis in hippocampal neurons, involving activation of the MEK/MAPK survival pathway.

Herpes simplex virus type 1 (HSV-1) and HSV-2 trigger or counteract apoptosis by a cell-specific mechanism. Our studies are based on previous findings that the protein kinase (PK) domain of the large subunit of HSV-2 ribonucleotide reductase (ICP10) activates the Ras/MEK/MAPK pathway (Smith et al., J. Virol. 74:10417, 2000). Because survival pathways can modulate apoptosis, we used cells that are stably or transiently transfected with ICP10 PK, an HSV-2 mutant deleted in ICP10 PK (ICP10DeltaPK) and the MEK-specific inhibitor U0126 to examine the role of ICP10 PK in apoptosis. Apoptosis was induced by staurosporine or D-mannitol in human (HEK293) cells or HEK293 cells stably transfected with the ICP10 PK-negative mutant p139 (JHL15), as determined by morphology, DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage. HEK293 cells stably transfected with ICP10 (JHLa1) were protected from apoptosis. ICP10 but not p139 protected neuronally differentiated PC12 cells from death due to nerve growth factor withdrawal, and apoptosis (determined by TUNEL) and caspase-3 activation were seen in primary hippocampal cultures infected with ICP10DeltaPK but not with HSV-2 or a revertant virus [HSV-2(R)]. The data indicate that ICP10 has antiapoptotic activity under both paradigms and that it requires a functional PK activity. The apoptotic cells in primary hippocampal cultures were neurons, as determined by double immunofluorescence with fluorescein-labeled dUTP (TUNEL) and phycoerythrin-labeled antibodies specific for neuronal proteins (TuJ1 and NF-160). Protection from apoptosis was associated with MEK/MAPK activation, as evidenced by (i) increased levels of activated (phosphorylated) MAPK in HSV-2- but not ICP10DeltaPK-infected cultures and (ii) inhibition of MAPK activation by the MEK-specific inhibitor U0126. MEK and MAPK were activated by infection with UV-inactivated but not antibody-neutralized HSV-2, suggesting that activation requires cellular penetration but is independent of de novo viral protein synthesis.

Animals↗

PubMed2001

The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches.

Schizophrenia is commonly considered a neurodevelopmental disorder that is associated with significant morbidity; however, unlike other neurodevelopmental disorders, the symptoms of schizophrenia often do not manifest for decades. In most patients, the formal onset of schizophrenia is preceded by prodromal symptoms, including positive symptoms, mood symptoms, cognitive symptoms, and social withdrawal. The proximal events that trigger the formal onset of schizophrenia are not clear but may include developmental biological events and environmental interactions or stressors. Treatment with antipsychotic drugs clearly ameliorates psychotic symptoms, and maintenance therapy may prevent the occurrence of relapse. The use of atypical antipsychotic agents may additionally ameliorate the pathophysiology of schizophrenia and prevent disease progression. Moreover, if treated properly early in the course of illness, many patients can experience a significant remission of their symptoms and are capable of a high level of recovery following the initial episode. Because the clinical deterioration that occurs in schizophrenia may actually begin in the prepsychotic phase, early identification and intervention may favorably alter the course and outcome of schizophrenia.

Acute Disease↗

PubMed2001

Administration of pentoxifylline during allergen sensitization dissociates pulmonary allergic inflammation from airway hyperresponsiveness.

Asthma, a chronic inflammatory disease characterized by intermittent, reversible airflow obstruction and airway hyperresponsiveness (AHR), is classically characterized by an excess of Th2 cytokines (IL-13, IL-4) and depletion of Th1 cytokines (IFN-gamma, IL-12). Recent studies indicating an important role for Th1 immunity in the development of AHR with allergic inflammation suggest that Th1/Th2 balance may be important in determining the association of AHR with allergic inflammation. We hypothesized that administration of pentoxifylline (PTX), a phosphodiesterase inhibitor known to inhibit Th1 cytokine production, during allergen (OVA) sensitization and challenge would lead to attenuation of AHR in a murine model of allergic pulmonary inflammation. We found that PTX treatment led to attenuation of AHR when administered at the time of allergen sensitization without affecting other hallmarks of pulmonary allergic inflammation. Attenuation of AHR with PTX treatment was found in the presence of elevated bronchoalveolar lavage fluid levels of the Th2 cytokine IL-13 and decreased levels of the Th1 cytokine IFN-gamma. PTX treatment during allergen sensitization leads to a divergence of AHR and pulmonary inflammation following allergen challenge.

Aerosols↗

PubMed2001

Penile incarceration: a wrapping technique.

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Constriction, Pathologic↗

PubMed2001

The Illawarra Coordinated Care Trial: better outcomes with existing resources?

The Illawarra Coordinated Care Trial was one of nine Australian trials undertaken to see whether different models of coordinated care could improve the health of people with multiple service needs within existing resources. This paper summarises the findings of an extensive local evaluation and discusses the impact of the trial on clients and service providers. It examines the main findings related to the principal trial hypothesis and points to lessons that might inform the next round of trials.

Aged↗

PubMed1999

Evaluation of biomarker modulation by fenretinide in prostate cancer patients.

An NCI-sponsored, phase II trial of N-(4-hydroxyphenyl)- retinamide (4-HPR) in patients with organ-confined prostate cancer in the period prior to radical prostatectomy was carried out. Thirty-seven men with the histologic diagnosis of prostate cancer planning to have radical prostatectomy entered the study after informed consent and were given 4-HPR (or matching placebo) as a single daily dose (two 100-mg capsules of 4-HPR or two capsules of placebo daily) for 3 weeks prior to surgery. Four men dropped out for unrelated reasons. Thirty-three men completed the study. At the time of surgery, repeat biopsies of the prostate were performed to study the effects of the drug on potential surrogate endpoint biomarkers (SEBs) of malignancy within the tissue. The panel of potential SEBs of malignancy include p53, cytomorphometric indices, ploidy, PNCA, erbB-2, erbB-3, EGF receptor, TGF-alpha tumor-associated glycoprotein-72, fatty acid synthetase and Lewis Y antigen. Twenty-three patients had matching pre- and posttherapy lesions and were considered informative. Results from the patients indicate significant differential expression of biomarkers in pretreatment specimens of uninvolved prostatic tissue (normal-appearing epithelia) prostatic intraepithelial neoplasia (PIN) and prostate cancer. The mean erbB-2 expression was 0.58 in uninvolved vs. 1.04 in PIN (p = 0.002); while the mean erbB-2 expression was 1.35 in prostate cancer (p = 0.0007, uninvolved vs. prostate cancer). A similar pattern of increased biomarker expression between uninvolved and PIN or prostate cancer tissues can be observed for EGF receptor (mean = 1.21, 1.87 and 1.76 for uninvolved, PIN and prostate cancer, respectively) and erbB-3 (mean = 0.81, 1.59 and 1.30 for uninvolved, PIN and prostate cancer, respectively). There were no statistically significant differences in biomarkers observed in the 4-HPR-treated patients when compared with placebo-treated control patients. There was a posttreatment up-regulation of biomarkers observed in both groups of patients. This observation is most likely explained by an effect due to the diagnostic sextant biopsy equally affecting both groups of patients. Results from this study do not demonstrate a chemoprevention effect of 4-HPR on tissue-based SEBs at the dose given.

Adenocarcinoma↗

PubMed1998

Comparison of morbidity of outpatient general anesthesia administered by the intravenous or inhalation route.

PURPOSE: This study compares the morbidity between subjects receiving general anesthesia either by an intravenous or inhalation route for the extraction of impacted third molars in an outpatient setting. PATIENTS AND MATERIALS: Forty ASA Class I subjects, 21 females and 19 males (age range, 17 to 43 years), who presented for the extraction of four impacted third molars, were studied. Subjects were alternately assigned to receive general anesthesia either by the intravenous route (group I) or the inhalation route via an endotracheal tube (group II). The parameters for comparison included psychomotor recovery, cardiovascular changes 20% above or below baseline, the frequency of nausea and vomiting perioperatively and at 48 hours, occurrence of laryngospasm and bronchospasm, the frequency of sore throat both perioperatively and at 48 hours, procedure time, and recovery time. The Trieger dot test was administered to patients at three different intervals to evaluate psychomotor recovery. All parameters were recorded for each subject and compared both within and between groups. RESULTS: There was no statistical difference found between groups I and II with regard to psychomotor recovery, the frequency of nausea and vomiting, bronchospasm, laryngospasm, or median recovery time (P < .05). However, there was greater variability in both elevation and depression of blood pressure from baseline in the intubated subjects (P < .05). These deviations were both expected and easily managed. The probability of sore throat was greater in the intubated subjects (P < .05) than the nonintubated subjects. Procedure time, although a weak association, was nonetheless found to be significantly greater for the intubated group than for the intravenous group (P < .05). SUMMARY: The results show greater cardiovascular variability, increased probability of sore throat, and slightly lengthened procedure time with the administration of general anesthesia by an inhalational route via an endotracheal intubation. However, there was no difference with regard to psychomotor recovery, recovery time, the probability of nausea and vomiting, or incidence of laryngospasm or bronchospasm.

Administration, Inhalation↗

PubMed1998

Control and accountability in the NHS market: a practical proposition or logical impossibility?

Before the imposition of the NHS internal market, systems of accountability and control were far from adequate and could be criticized on a number of grounds. The market was offered as a panacea to address these inadequacies. However, in practice there have only been partial improvements which could have been achieved without the imposition of the market. The market also creates new problems and a number of crises and scandals seem to be addressed at the political level by pleas to utilize resources more effectively. These pleas mean that more and more the focus is turning back to central planning in the provision of care and further away from so-called market mechanisms. The NHS "managed" market has been imperfect and will continue to be so. Argues that there is no alternative but to return to the planned provision of health care in order to improve on accountability and control in the NHS. Hopefully the adverse impact of the market on clinicians and others will force a more rational reappraisal of the fundamental raison d'être of the NHS and the need for those involved in the delivery of services, at all levels, to be more openly accountable.

Contract Services↗

PubMed1998

Illinois Dental Anesthesia and Sedation Survey for 1996.

Dentists in the state of Illinois who possess a permit to administer sedation or general anesthesia were surveyed. A 71% response rate was achieved. Of the respondents, 86% held permits for deep sedation/general anesthesia and 14% held permits for parenteral conscious sedation. By practice specialty, 84% were oral and maxillofacial surgeons, 11% were general dentists, 5% were periodontists, and fewer than 1% were dental anesthesiologists. Advanced Cardiac Life Support training was possessed by 85% of the respondents. The most common anesthesia team configuration (82%) was a single operator-anesthetist and two additional assistants. Only 4% reported use of a nurse anesthetist, and 2% used an additional MD or DDS anesthesiologist. The vast majority (97%) of the practitioners do not intubate in the office on a routine basis. Supplemental oxygen was used by 81% of the respondents whenever intravenous agents were used. A total of 151,335 anesthetics were administered during the year. One mortality occurred in a patient with an undisclosed pre-existing cardiac condition. Four other events were reported that required medical intervention or hospital evaluation; however, no permanent injuries were reported. Other practice characteristics were described.

Anesthesia, Dental↗

PubMed1998

Vaccine-induced remission of severe chronic arthritis.

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Arthritis↗

PubMed1997

Evidence for the involvement of the Gli gene family in embryonic mouse lung development.

Murine Gli, Gli2, and Gli3 are zinc finger genes related to Drosophila cubitus interuptus, a component of the hedgehog signal transduction pathway. In the embryonic lung, all three Gli genes are strongly expressed at the pseudoglandular stage, in distinct but overlapping domains of the mesoderm. Expression of Gli and Gli3, but not of Gli2, is subsequently downregulated at the canalicular stage, coincident with a decline in the expression of sonic hedgehog (Shh) and the hedgehog receptor gene, patched (Ptc). Overexpression of Shh in the lung results in increased levels of Ptc mRNA. Gli, but not Gli2, is also upregulated, suggesting a differential involvement of the Gli genes in the regulation of Ptc by SHH during lung development. Gli3 is not upregulated by Shh overexpression. However, its importance for lung development is shown by the finding that Gli3XtJ embryos, homozygous for a mutation involving a deletion of the Gli3 gene, have a stereotypic pattern of abnormalities in lung morphogenesis. The pulmonary defects in these embryos, consisting of localized shape changes and size reductions, correlate with normal Gli3 expression. Thus, our data indicate that one of the Gli genes, Gli3, is essential for normal lung development, and that another, Gli, can be placed downstream of Shh signaling in the lung.

Animals↗

PubMed1997

Regional cancer cytogenetics: a report on 1,143 diagnostic cases.

The results of studies from a regional cancer cytogenetics diagnostic service are reported. In a 10-year period, 1,143 marrow samples from patients with newly diagnosed leukemia and myelodysplastic syndrome were referred. Successful studies were completed on 992 cases (87%). Among all referred cases, the rates of detection of cytogenetically abnormal clones were 95% for chronic myelogenous leukemia (CML), 54% for acute lymphoblastic leukemia (ALL), 51% for acute myeloid leukemia (ANLL), and 43% for myelodysplastic syndrome (MDS). Of 169 cases of CML studied, 90.5% bore the standard Philadelphia chromosome (Ph), 3.55% had an unusual Ph, and 5.33% were Ph-negative. Among the 59 cases of cytogenetically abnormal MDS, common abnormalities observed were trisomy 8 and changes resulting in loss of material from the long arm of chromosomes 5 and 7, and 20q-. Of the 168 abnormal ANLL, there was a strikingly non-random pattern of aneuploidy, with monosomy 7 and trisomy 8 predominating. Common structural changes observed were changes resulting in loss of material from the long arm of chromosomes 5 and 7, trisomy 8, rearrangements of 11q23, t(15;17), t(8;21), rearrangements of 12q13 and 3q, inversion 16, trisomy 11, Ph, trisomy 21, t(6;9) and t(1;22). The differences between adult and pediatric findings were minor, with the exception of chromosome 5 abnormalities, which were common among adults with ANLL but rare in the pediatric cases. There were 273 ALLs with abnormal cytogenetic findings. There was preferential gain of chromosomes 21, X, 14, 6, 4, 18, 17, and 10 (in decreasing order of frequency) in leukemic clones. Of the 193 ALLs with structural changes, many fell into-well-defined categories with established correlations to FAB subtypes. Common changes in ALL were rearrangements of 9p, 12p, 6q, TCR loci, 11q23, Ig loci, and 8q24, and duplication of 1q, Ph, i(17q), t(1;19), i(9q) and dic(9;12). The detailed documentation of the cytogenetic findings in this relatively large, single-institution study will likely facilitate the further characterization of rare, primary cytogenetic changes associated with leukemias and MDS. From a managed health care perspective, regional cancer cytogenetic services may be cost-effective alternatives to single-institution laboratories.

Adult↗

PubMed1997

Robert B. Forney (1916-1997)

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Journal Article↗

PubMed1996

Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin.

Based on preliminary but variable results with direct DNA transfer into wounds, we evaluated in vivo gene transfer by particle-mediated DNA delivery to rat skin to determine whether overexpression of TGF-beta1 at the site of skin incisions would result in a significant improvement in repair. Optimization of the method with viral promoter-luciferase reporter constructs indicated that expression of luciferase activity persisted up to 5 d and was promoter, pressure, and site dependent (ventral > dorsal). Using cytomegalovirus (CMV)-driven human alpha1-antitrypsin, transgene expression was immunolocalized within keratinocytes of the stratum granulosum at 24 h. We measured tensile strength of skin incisions at 11-21 d in both normal and diabetic rats transfected with TGF-beta1 expression vectors at surgery. Native murine TGF-beta1 under an SV40 promoter produced positive effects, while wound strengthening was more pronounced in diabetic animals using a CMV-driven construct. Transfection of rat skin with constitutively active, mutant porcine TGF-beta1 under the control of the CMV and Moloney murine leukemia virus promoters significantly increased tensile strength up to 80% for 14-21 d after surgery. Transfection 24 h before surgery was more effective. Particle-mediated gene delivery can be used to deliver viral promoter-cytokine expression constructs into rat skin in a safe, efficient, and reproducible fashion. The extent of wound repair, as evidenced by enhanced tensile strength, can be markedly improved in tissues transfected with TGF-beta1 expression constructs.

Animals↗