Search PubMed⌕ Search

Biomedical subjects

J Smyth

Publications and source records attributed to J Smyth.

At least 37 records · Page 2Linked to original sources
PubMed2000

Medicine and story: a novel clinical panorama arising from a unitary mind/body approach to physical illness.

Since 1987, all patients referred by family physicians for internal medicine consultation at the Institute for Integrative Health Studies (Christchurch, New Zealand) have been assessed by the author from both physical (normative internal medicine) and psychological (psychodynamic, interpersonal, object relations, and self psychological) perspectives. Depending upon the material emerging in each case, the treatment options available for the particular disorder, and patient preferences, many patients have gone on to mind/body oriented discussions or psychotherapy with the author (detailed in Broom 1997), or with one of a team of therapists supervised by the author. This clinical experience, mixing internal medicine and psychotherapy approaches to physical illnesses (with or without organic findings), points to the following: (1) Profound connections between the patients' perceptions of their life-events and experience and the development of illness in both organic and nonorganic illnesses; (2) a rich fund of information in the patients' verbal language about the meaning of the illnesses; (3) the crucial importance of clinical attunement to macro- and micro-life events surrounding symptom emergence; and (4) the decisive role a clinician's implicit paradigm of "personhood" plays in patient care. This paper broadly outlines the presuppositions for this integrative clinical approach, and illustrates the approach with case material. Additionally, it summarizes the kinds of listening, and other skills, that have proved clinically useful. In all, the material illustrates that a combination of orthodox biomedical approaches and a "story approach" (which focuses on meaning leading to illness) offers considerable potential benefits to patients with physical symptomatologies including those with organic findings.

Adult↗
PubMed1999

The differential impact of training stress and final examination stress on herpesvirus latency at the United States Military Academy at West Point.

In this study, we searched for evidence for reactivation of three latent herpesviruses, Epstein-Barr virus (EBV), herpes simplex virus type-1 (HSV-1), and human herpesvirus 6 (HHV-6), in West Point cadets experiencing two different stressors. Blood samples were obtained from cadets before and after a 6-week training period known as "Cadet Basic Training" (CBT), at a baseline prior to final examinations, and then once again during the week of final examinations. Antibody titers to latent HSV-1, EBV, and HHV-6 were determined as a measure of the steady-state expression of latent virus. EBV virus capsid antigen (VCA) IgG antibody titers were unchanged in blood samples obtained prior to and immediately after CBT. However, EBV antibody titers were significantly higher in the blood sample obtained during examination week than in the baseline period before examination; they were also higher than antibody titers before/after CBT. None of the serum samples were positive for EBV VCA IgM antibodies, indicating that the changes in antibody titers to EBV were not associated with recent EBV infections in the class. No significant changes in antibody titers to HSV-1 or HSV-6 were found over the identical time periods, including examination week. Academic stress but not CBT modulated the steady-state expression of latent EBV, resulting in the reactivation of latent virus. The same stressors, however, did not affect the steady-state expression of latent HSV-1 or HSV-6, at least as measured by changes in antibody titers. The data provide additional evidence of the impact of different psychological stressors on the steady-state expression of latent herpesviruses.

Adult↗
PubMed1999

Inhibition of transforming growth factor alpha (TGF-alpha)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868.

The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01CDDP. Transforming growth factor alpha (TGF-alpha)-stimulated growth was completely inhibited by concentrations > or =0.3 microM in the PE01 and PE04 cell lines and by > or =0.1 microM in SKOV-3 cells. TGF-alpha inhibition of PE01CDDP growth was reversed by concentrations > or =0.1 microM ZM 252868. TGF-alpha-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations > or =0.3 microM, completely inhibited TGF-alpha-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 microM ZM 252868 in PE01, SKOV-3 and PE01CDDP cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor.

Cell Division↗
PubMed1999

The sequential modular curriculum for oral health personnel: an evaluation of the Fijian experience after five years.

In 1993 a new sequential modular curriculum was introduced for the training and education of oral health personnel in Pacific Island countries. The five-year model provided a multi-stage course with the opportunity to exist at the level of dental hygienist after two years, dental therapist or dental technologist after three years and dental surgeon after five years. After five years' experience the principles involved in the introduction of such a curriculum have been confirmed as educationally sound. The model may also be useful for introduction in other countries providing its structure and the details of individual modules are tailored to local social, cultural and demographic needs.

Curriculum↗
PubMed1998

Stressors and mood measured on a momentary basis are associated with salivary cortisol secretion.

Effects of past, current, and anticipated naturalistic daily stressors and of affect on salivary cortisol levels were examined. Participants (120) reported on stressors and affect 6 x /day in response to a preprogrammed wristwatch. Twenty min after each assessment they took a sample of saliva for cortisol analysis. Both the experience of a current stressor and anticipating a stressor were associated with increased salivary cortisol levels. Average increases in cortisol were relatively low, but inter-individual variability in this response existed. Stressors also were associated with lower positive affect and higher negative affect. Negative affect was associated with higher cortisol levels and positive affect was associated with lower cortisol levels. Daily stressors were not significant predictors of cortisol secretion when affect was controlled. Momentary assessment of daily stressors and of salivary cortisol proved to be a useful tool for examining psychoendocrinological processes in the natural environment.

Adult↗
PubMed1997

Phase II trial of the oral platinum complex JM216 in non-small-cell lung cancer: an EORTC early clinical studies group investigation.

BACKGROUND: JM216 is a new oral platinum complex with dose-limiting toxicity myelosuppression, now undergoing phase II evaluation. PATIENTS AND METHODS: JM216 was evaluated as first line therapy in non-small-cell lung cancer. Seventeen patients received 120 mg/m2/day for five days repeated every three weeks. RESULTS: Toxicity was manageable, the commonest side-effects being nausea, vomiting, diarrhoea, constipation and asthenia. Myelososuppression was generally grade < 2 and there were no cases of neutropenic sepsis or bleeding. Thirteen patients were fully evaluable for response. No sustained objective responses were reported. One patient was reported as stable disease had a partial response after three courses but was progressing again after four. An additional five patients had stable disease (46.2%). CONCLUSIONS: Although some patients may have had useful palliation, JM216 did not appear to have significant antitumour activity in non-small-cell lung cancer.

Administration, Oral↗
PubMed1997

Efficient multiplication of a Semliki Forest virus chimera containing Sindbis virus spikes.

Using the Semliki Forest virus (SFV) and Sindbis virus (SIN) cDNAs we have constructed recombinants in which the spike genes were exchanged. Analyses of expression showed that the SFV/SIN(spike) RNA directed efficient assembly of infectious virus, whereas the reciprocal SIN/SFV(spike) RNA was completely unable to assemble virus. This was apparently due to a defective capsid-spike interaction.

Amino Acid Sequence↗
PubMed1996

Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam.

BACKGROUND: This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O + D) with metoclopramide plus dexamethasone plus lorazepam (M + D + L) over three consecutive courses of cisplatin chemotherapy. PATIENTS AND METHODS: This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4 mg bd orally. M + D + L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M + D + L). RESULTS: On the first course chemotherapy, O + D was significantly superior to the M + D + L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P = 0.014). This was maintained over the three treatment cycles; 38% of O + D and 20% of M + D + L patients remained free of emesis (P = 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O + D group (48%) than in the M + D + L (26%, P = 0.003). The most commonly occurring adverse events in the O + D group were constipation (25%) and headache (19%). In the M + D + L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M + D + L group. Despite the inclusion of lorazepam, 14% of patients in the M + D + L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. CONCLUSION: This study show that O + D is significantly more effective and better tolerated than M + D + L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.

Adult↗
PubMed1996

A randomized phase II study with two schedules of the novel indoloquinone EO9 in non-small-cell lung cancer: a study of the EORTC Early Clinical Studies Group (ECSG).

In a multicentre randomized trial of the EORTC-ECSG, we have treated 38 chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) with EO9, a novel bio-reductive alkylating indoloquinone. The drug was given at two different dose schedules by a single bolus i.v. injection: arm A 12 mg/m2 weekly and arm B 22 mg/m2 every three weeks. All together 185 courses were administered (145 in arm A and 40 in arm B). The major toxicity was reversible proteinuria more frequently occurring in the three-weekly schedule (arm A 34.5% vs. arm B 62.5%). Creatinine elevation, fluid retention and pericardial or pleural effusion were also recorded in a limited number of patients. Other common toxicities more frequent in the three-weekly administration were asthenia (21% vs. 35% of cycles), nausea (15% vs. 27.5% of cycles) and vomiting (5% vs. 17.5% of cycles). Toxicities were mainly of grade I and II. No responses have been observed. Five patients (26%) on arm A and eight (53%) on arm B experienced stable disease. These doses and schedules of EO9 do not yield activity in NSCLC.

Adult↗
PubMed1996

Spiroplasma diminutum sp. nov., from Culex annulus mosquitoes collected in Taiwan.

Initially, strain CUAS-1T (T = type strain), which was isolated from a frozen triturate of Culex annulus mosquitoes collected in Taiwan, was thought to be a member of spiroplasma group VII. This placement was based on the spiroplasma deformation test titer observed when strain CUAS-1T spiroplasmas were tested with Spiroplasma monobiae MQ-1T antiserum. The results of subsequent reciprocal spiroplasma deformation, metabolism inhibition, and growth inhibition tests clearly revealed that strain CUAS-1T is not serologically related to previously described spiroplasma groups (groups I to XXIV) and thus is a representative of a new group, group XXV. Strain CUAS-1T was characterized by using the minimal standards for mollicute species descriptions. During logarithmic-phase growth, strain CUAS-1T cells are characteristically very short helices with 1.5 to 2 helical turns (1 to 2 microns), highly motile, and bounded by a single trilaminar membrane and form granular colonies with satellites when the organism is grown aerobically on MID medium containing 1.6% agar. Growth in MID broth occurs at temperatures ranging from 10 to 37 degrees C, and the optimum temperature is 30 degrees C. Substrate utilization tests revealed that cholesterol is required for growth, that glucose is hydrolyzed, and that arginine is not hydrolyzed both in the presence and in the absence of glucose. The genome of strain CUAS-1T is 1,080 kbp long, and the guanine-plus-cytosine content is 26 +/- 1 mol%. On the basis of the results of our studies we propose that strain CUAS-1T (group XXV) should be placed in a new species, Spiroplasma diminutum. Strain CUAS-1 (= ATCC 49235) is the type strain of S. diminutum.

Animals↗
PubMed1995

Double-blind, randomized, placebo-controlled Canadian multicenter trial of two doses of synthetic surfactant or air placebo in 224 infants weighing 500 to 749 grams with respiratory distress syndrome. Canadian Exosurf Neonatal Study Group.

In a multicenter, double-masked, placebo-controlled rescue trial conducted at 12 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 224 infants with birth weights of 500 to 749 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio of less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to the infants continuing to receive mechanical ventilation. Infants were stratified at study entry by birth weight and gender. Infants receiving synthetic surfactant showed significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7. In the group randomized to synthetic surfactant, significant improvements were seen in oxygen requirements at the first time point measured (2 hours; p = 0.02), in the alveolar-arterial oxygen tension gradient by the second time point measured (6 hours; p = 0.03), and in mean airway pressure after 6 hours. Overall mortality at 28 days was not significantly different in the two groups (50% vs 46%, air placebo group vs synthetic surfactant group; p = 0.586). Similarly, neither the incidence of bronchopulmonary dysplasia (37% vs 30%, air placebo group vs synthetic surfactant group; p = 0.089) nor the incidence of survival without BPD through 28 days (17% vs 26%, respectively; p = 0.070) was significantly different in the two groups. No significant differences in the incidence of safety-related outcomes or in adverse effects such as apnea or pulmonary hemorrhage were noted. These findings indicate that rescue therapy with synthetic surfactant results in physiologic improvements in very tiny premature infants, but improvements in overall mortality or other complications of respiratory distress syndrome were not documented in the sample evaluated.

Air↗
PubMed1995

Isolation of Arcobacter butzleri from a neonate with bacteraemia.

We describe the case of a neonate with bacteraemia from whom the recently described organism Arcobacter butzleri was isolated. This appears to be the first report of the organism causing neonatal infection. Clinical details suggest that the infection was contracted in utero, although the mother showed no evidence of disease before delivery. Treatment of the preterm infant was ultimately successful in resolving the infection but the organism proved resistant to a wide range of antibiotics. Similar patterns of antibiotic resistance were also observed in 39 reference and field strains of the genus Arcobacter. These findings, combined with available data on the distribution of Arcobacter species, suggest that these organisms may be important human pathogens. Optimized methods for their isolation and identification are therefore required so as to ascertain their role in human disease.

Bacteremia↗
PubMed1995

The 6-kilodalton membrane protein of Semliki Forest virus is involved in the budding process.

Alphavirus genomes encode a small hydrophobic protein of 6 kDa (the 6K protein) that is expressed as part of a large polyprotein containing the sequences of the two virus transmembranal glycoproteins which form the spikes of the infectious particle. Although made in amounts equivalent to those of the glycoproteins, very little of the 6K protein is found in secreted infectious virions. The role of this protein in virus replication and structure has been studied by use of a variety of mutationally altered forms of 6K, which yield phenotypically distinct viruses. A complete deletion of the gene encoding the 6K protein (delta 6K) of Semliki Forest Virus (SFV) has been constructed from an SFV infectious cDNA and the transcribed RNA-produced progeny virus that closely resembled the normal virus (P. Liljeström, S. Lusa, D. Huylebroeck, and H. Garoff, J. Virol. 65:4107-4113, 1991). Further studies of this mutant have now been performed, and they show that growth of delta 6K has a strong dependency on its host cell, varying from 2 to 50% of the rate of formation of the wild-type SFV. Mammalian cells are much more defective than insect and avian cells in replication of the delta 6K mutant. This mutant is not defective in formation and transport of the glycoproteins or in production of nucleocapsids, which accumulate at the plasma cell membrane in infected BHK cells. The major defect, thus, is in the final assembly and budding of new virus. In BHK cells infected with the delta 6K strain, a relatively large fraction of the total infectious virus formed can be recovered by osmotic lysis of exhaustively washed cells. Infectious SFV totally lacking 6K is identical to wild-type SFV in the early stages of virus replication, i.e., binding and uptake. The particles themselves are more thermolabile than those of wild-type SFV, suggesting that the 6K protein may be a part of the structure of wild-type virus or that the slower budding leads to an altered configuration of the trimeric spikes. These data support other studies that implicate the 6K protein as an important but nonessential component in the assembly and budding of the alphavirus particle, perhaps by affecting the packing of the glycoproteins and their interactions with membrane lipid.

Animals↗
PubMed1994

Assembly and entry mechanisms of Semliki Forest virus.

The alphavirus Semliki Forest (SFV) is an enveloped virus with a positive single-stranded RNA genome. The genome is complexed with 240 copies of a capsid protein into a nucleocapsid structure. In the membrane the virus carries an equal number of copies of a membrane protein heterodimer. The latter oligomers are grouped into clusters of three. These structures form the spikes of the virus and carry its entry functions, that is receptor binding and membrane fusion activity. The membrane protein heterodimer is synthesized as a p62E1 precursor protein which upon transport to the cell surface is cleaved into the mature E2E1 form. Recent studies have given much new information on the assembly and entry mechanism of this simple RNA virus. Much of this work has been possible through the construction of a complete cDNA clone of the SFV genome which can be used for in vitro transcription of infectious RNA. One important finding has been to show that a spike deletion variant and a capsid protein deletion variant are budding-negative when expressed separately but can easily complement each other when transfected into the same cell. This shows clearly that enveloped viruses use different budding strategies: one which depends on a nucleocapsid-spike interaction as exemplified by SFV and another one which is based on a direct core-lipid bilayer interaction as shown before to be the case with retroviruses. Another important finding concerns the activation process of the presumed fusion protein of SFV, the E1 subunit. In the original p62E1 heterodimer E1 is completely inactive. Activation proceeds in several steps. First p62 cleavage activates the potential for low pH inducible fusion. Next the low pH which surrounds incoming virus in endosomes induces dissociation of the heterodimeric structure. This is followed by a rearrangement of E1 subunits into homotrimers which are fusion active.

Animals↗
PubMed1994

Docetaxel (Taxotere) in advanced gastric cancer: results of a phase II clinical trial. EORTC Early Clinical Trials Group.

Thirty-seven eligible patients, median age 59 years (range 37-72) and median performance status 1 (0-2), with advanced, untreated, measurable gastric carcinoma were given docetaxel, 100 mg m-2 i.v. over 60 min without premedication, once every 3 weeks. Metastatic sites included the liver in 12 patients and retroperitoneal lymph nodes in 16. Eight of the 33 evaluable patients (24%) achieved a partial remission for a median of 7.5 months (3-11+). An additional 11 patients had stabilisation of disease. The patients received a median of four cycles of docetaxel (range 1-8) for a total of 156 courses. Dose reduction was necessary in 30 cycles; 14 cycles were delayed a mean of 3 days. Haematological toxicity consisted mainly of non-cumulative neutropenia, with a median nadir count of 0.35 x 10(9) l-1 (0.04-1.64) and eight episodes (5%) of leucopenic fever; non-haematological toxicities included alopecia, mild nausea and vomiting and allergic manifestations such as skin rash and pruritus. There were no drug-related deaths. Our data indicate that docetaxel is an active agent in advanced gastric cancer; further clinical investigations seem warranted.

Adult↗
PubMed1994

Absence of ventilatory responses to alternating breaths of mild hypoxia and air in infants who have had bronchopulmonary dysplasia: implications for the risk of sudden infant death.

Infants who have had bronchopulmonary dysplasia (BPD) are at an increased risk of sudden infant death syndrome. Because failure of the cardiorespiratory response to hypoxia is suggested to play a key role in sudden infant death syndrome, we tested the hypothesis that infants who have had BPD have a reduced respiratory chemoreflex response to hypoxia. We examined the reflex respiratory responses to breath-by-breath alternations in fractional inspired oxygen concentration in eight infants who had had BPD (mean gestation = 27 wk, mean postnatal age = 93 d) who were no longer on supplemental oxygen and compared the responses with those of 12 preterm infants who had not required supplemental oxygen or been mechanically ventilated since birth (mean gestation = 30 wk, mean postnatal age = 38 d). For test runs we alternated fractional inspired oxygen concentration through two gas delivery lines between 0.21 and 0.16 on a breath-by-breath basis, and for control runs we alternated the inspirate between the two gas lines with a fractional inspired oxygen concentration of 0.21 in each. Respiration was measured using inductance plethysmography infants with BPD showed no significant differences between test and control responses for any respiratory variable. In contrast, all respiratory variables in the preterm infants showed test responses significantly greater than control. We speculate that the "blunted" chemoreflex respiratory response seen in infants with BPD may predispose them to subsequent respiratory failure, but we do not known which component of the chemoreflex is impaired.

Bronchopulmonary Dysplasia↗