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Biomedical subjects

G Miller

Publications and source records attributed to G Miller.

At least 109 records · Page 6Linked to original sources
PubMed1998

Total or subtotal gastrectomy for gastric carcinoma? A study of quality of life.

The aim of this study was to compare quality of life after total gastrectomy (TG) with that after subtotal gastrectomy (STG) for gastric carcinoma. The value of the routine use of TG de principe in the treatment of gastric carcinoma, wherever the tumor may be sited in the stomach, remains controversial. The advocates of TG contend that when it can be performed safely, with relatively low operative mortality and morbidity, it yields better long-term survival than STG. Most surgeons, however, believe that the routine use of TG increases both operative mortality and morbidity and the risk of nutritional deficiency in the long term, without improving survival. TG may also be associated with poorer outcome in terms of quality of life (QOL), but the evidence for this is tenuous. Forty-seven consecutive patients who had undergone potentially curative (R0) gastric resection for carcinoma were studied: 26 had undergone TG and 21 STG. A radical D2 lymph node dissection had been performed in each, and all patients were free from recurrence at the time of the study. QOL was measured before operation and 1, 3, 6, and 12 months after operation by means of five questionnaires to measure functional outcome: the Rotterdam symptom checklist (RSCL), the Troidl index, the hospital anxiety and depression (HAD) scale, activities of daily living score, and Visick grades. Before operation there was no significant difference in QOL between the two groups of patients. At 1 year after operation, however, patients who had undergone STG had a significantly better QOL than patients who had undergone TG: Their median RSCL score was lower (10 versus 19 respectively, p < 0.05), and their Troidl index was higher (11 versus 9 respectively, p < 0.05). The QOL of patients who underwent STG was also significantly better after operation than it had been before operation, whereas the QOL of the TG group was not significantly better after operation than before operation. The QOL of patients was found to be significantly better after STG than after TG for gastric carcinoma. Because operative mortality is greater and long-term survival is no better after TG than after STG, the latter is recommended as the treatment of choice for tumors of the distal stomach.

Activities of Daily Living↗
PubMed1998

Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy.

OBJECTIVE: The objective was to obtain preliminary pharmacokinetic data for acyclovir from gravid women receiving herpes simplex virus suppressive therapy with the acyclovir prodrug valacyclovir. STUDY DESIGN: In a prospective, double-blind trial, 20 women with a history of recurrent genital herpes simplex virus infection and positive herpes simplex virus 2 serologic results were randomly assigned at 36 weeks' gestation to receive oral valacyclovir (500 mg twice daily) or acyclovir (400 mg 3 times daily). Acyclovir pharmacokinetic profiles were obtained after the initial dose (36 weeks) and at steady state (38 weeks). Amniotic fluid samples were obtained during labor and simultaneous umbilical cord and maternal plasma samples were collected at delivery. Laboratory studies were performed to screen for laboratory evidence of toxicity in mothers and infants. RESULTS: Peak acyclovir plasma concentrations (mean +/- standard deviation) were higher in valacyclovir recipients than in acyclovir recipients after the initial dose (3.14 +/- 0.7 microg/mL vs 0.74 +/- 0.6 microg/mL, P < .0001) and at steady state (3.03 +/- 1.0 microg/mL vs 0.94 +/- 0.7 microg/mL, P < .001). The daily area under the curve values were higher in valacyclovir recipients than acyclovir recipients after the initial dose (17.8 +/- 3.6 h x microg/mL vs 7.71 +/- 2.5 h x microg/mL, P < .001) and at steady state (19.65 +/- 6.4 h x microg/mL versus 11.0 +/- 4.5 h x microg/mL, P = .009). There was no significant difference in drug elimination half-life or in time to peak concentration between valacyclovir and acyclovir recipients at either sampling interval. Acyclovir was concentrated in the amniotic fluid; however, there was no evidence of preferential fetal drug accumulation (mean maternal/umbilical vein plasma ratios at delivery were 1.7 for valacyclovir and 1.3 for acyclovir). Valacyclovir was well tolerated, and no significant laboratory or clinical evidence of toxicity was detected. CONCLUSION: In this phase I trial maternal valacyclovir therapy resulted in higher plasma acyclovir levels, with significantly higher peak concentrations and daily area under the curve values, than did acyclovir therapy. Additional trials are needed to further evaluate the safety and efficacy of suppressive valacyclovir therapy during late pregnancy.

Acyclovir↗
PubMed1998

Long-term salivary effects of single-dose head and neck irradiation in the rat.

The effect of a single dose of X-irradiation (either 2.5, 5, 7.5, 10 or 15 Gy) to the head and neck region on parotid and submandibular gland function in rats was evaluated for up to 1 year. No animal receiving 15 Gy survived the entire study. Animals receiving > or = 7.5 Gy showed significantly less increase in body weight over time. Average wet weights of both gland types were reduced with as little as 2.5 Gy. Pilocarpine-stimulated parotid salivary flow was diminished significantly at 12 months for each radiation-dose group. Significant salivary flow reductions from submandibular glands were seen at > or = 7.5 Gy at this same time-point. These results show that a single radiation exposure of as low as 2.5 Gy to the head and neck region of rats can cause significant long-term alterations in salivary gland function.

Analysis of Variance↗
PubMed1998

Pseudomonas aeruginosa necrotizing fasciitis: a case report.

A renal transplant recipient with necrotizing fasciitis due to Pseudomonas aeruginosa is presented. Only three other cases of necrotizing fasciitis due to this organism have been found in the literature. This is the first case of P. aeruginosa necrotizing fasciitis in a renal transplant patient to be reported. Prompt diagnosis, enabling treatment with appropriate antibiotics and early surgical intervention, was the key factor in his recovery.

Fasciitis, Necrotizing↗
PubMed1998

Initial experience with a physiologic morcellating resectoscope.

A new physiologic morcellating resectoscope allows operative hysteroscopy to be performed with a physiologic distention medium, thus reducing the risk of dilutional hyponatremia and cerebral edema secondary to excessive absorption of nonphysiologic fluid. To study this new technology, we gathered in vitro data with the SL resectoscope with dual-function electrode (FemRx, Sunnyvale, CA). Coupled to a standard monopolar electrosurgery unit and operating in normal saline or Ringer's lactate solution, extirpated uteri showed equivalent depth of tissue necrosis with this new physiologic morcellating resectoscope as with a conventional monopolar resectoscope used in an electrically nonconductive fluid.

Electrocoagulation↗
PubMed1998

Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA.

Huntington disease (HD) is an adult-onset, autosomal dominant inherited human neurodegenerative disorder characterized by hyperkinetic involuntary movements, including motor restlessness and chorea, slowing of voluntary movements and cognitive impairment. Selective regional neuron loss and gliosis in striatum, cerebral cortex, thalamus, subthalamus and hippocampus are well recognized as neuropathological correlates for the clinical manifestations of HD. The underlying genetic mutation is the expansion of CAG trinucleotide repeats (coding for polyglutamines) to 36-121 copies in exon 1 of the HD gene. The HD mRNA and protein product (huntingtin) show widespread distribution, and thus much remains to be understood about the selective and progressive neurodegeneration in HD. To create an experimental animal model for HD, transgenic mice were generated showing widespread expression of full-length human HD cDNA with either 16, 48 or 89 CAG repeats. Only mice with 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction with neuron loss and gliosis in striatum, cerebral cortex, thalamus and hippocampus. These animals represent clinically relevant models for HD pathogenesis, and may provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders.

Animals↗
PubMed1998

Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome.

Gorlin (or nevoid basal cell carcinoma) syndrome is characterized by a variety of clinical problems including generalized overgrowth of the body, cysts, developmental abnormalities of the skeleton and a predisposition to benign and malignant tumors. The syndrome results from germline mutations of the human homolog of the drosophila segment polarity gene patched (ptc). Here we report that mice heterozygous for ptc develop many of the features characteristic of Gorlin syndrome and that they exhibit a high incidence of rhabdomyosarcomas (RMS), the most common soft-tissue sarcoma in children. The downstream signalling partner of ptc, gli1, was overexpressed in all RMSs analyzed, indicating that abnormal signalling of the ptc-gli1 pathway may be common for the various tumors associated with the syndrome. igf2, implicated in the formation of RMSs, was also overexpressed, suggesting cross-talk between the ptc and igf2 pathways in tumorigenesis. Developmental defects in Gorlin syndrome resemble those induced by ionizing radiation. We show that ptc heterozygous mice exhibit increased incidence of radiation-induced teratogenesis. This suggests a role for ptc in the response to ionizing radiation and provides a model for both the systemic (developmental) and stochastic (cancer) abnormalities observed in Gorlin syndrome.

Animals↗
PubMed1998

The development of general practice standards in Australia. Royal Australian College of General Practitioners.

The Royal Australian College of General Practitioners has spent 4 years developing a set of entry standards which define the minimum features of general practices expected for the mid-1990s. The project design followed a slow, iterative process, with several opportunities for wide consultation with professional, consumer and Government groups. The draft standards were piloted in 25 volunteer practices, modified and then field-tested in 200 randomly selected practices representing urban and rural practices. Results of this field testing showed that the standards had content validity and that reliable measures were possible using triangulation from several data sources. The current version of the standards has been distributed widely for voluntary application in Australian general practices from early 1997.

Australia↗
PubMed1998

High prevalence of antibodies to human herpesvirus 8 in relatives of patients with classic Kaposi's sarcoma from Sardinia.

A survey for antibodies to a recombinant small viral capsid antigen (sVCA) of human herpesvirus type 8 (HHV-8) was conducted in Sardinia, one of the world's highest incidence areas for classic Kaposi's sarcoma (KS). Prevalence of antibodies to HHV-8 sVCA was greatest in patients with KS (95%), followed by family members (39%) and a Sardinian control population age- and sex-matched to the relatives (11%). Within families, prevalence of antibodies was about equal among spouses, children, and siblings of KS patients, a finding that raises the possibilities of intrafamilial person-to-person or vertical transmission. Antibodies were detected 2-3 times more frequently in males than in females. The data show that prevalence of antibodies to HHV-8 sVCA correlates with the distribution of classic KS in a high- incidence area. Clustering of seroprevalence within some families suggests the presence of familial risk factors for active HHV-8 infection.

Age Factors↗
PubMed1998

Have you heard the latest rumor about...? Solution-focused therapy as a rumor.

This essay treats solution-focused therapy as a rumor. Solution-focused therapy is a series of stories that members of diverse therapist communities tell one another. Our version of this rumor stresses how solution-focused therapy is a job involving language games, political relations, and ethical issues. We use this starting point to tell a story that links solution-focused therapy to Wittgenstein's philosophy of language, and to aspects of postmodernist social thought. We also discuss how solution-focused therapy is organized as a politics of possibilities.

Humans↗
PubMed1998

Safety of salivary gland-administered replication-deficient recombinant adenovirus in rats.

We have examined the safety of a replication-deficient recombinant adenovirus administered at a single, high dose intraductally to rat submandibular glands or systemically via the femoral vein. The virus used directed the synthesis of human aquaporin-1, a water channel protein, and is termed AdhAQP1. Comparisons were made 1 and 9 days post-infection with animals administered either a similar virus encoding no transgene or the viral suspension buffer. Animals were specifically not given anti-inflammatory drugs to impede the well-known immunopathologic response to recombinant adenoviral administration. Serum chemistries and hematological parameters were monitored. Rats were subjected to complete gross necropsy and selected tissues were evaluated by histopathology. Most clinical chemistry and hematology values were within normal ranges; however, evidence of inflammation (e.g., elevated lactic dehydrogenase, total leukocyte count) was seen. Gross pathology was normal, as was histopathology, excepting rare focal areas of necrosis. The results show that intrasalivary gland or intravenous AdhAQP1 administration leads to low levels of toxicity in rats.

Adenoviridae↗
PubMed1998

The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes.

The transition of Epstein-Barr virus (EBV) from latency into the lytic cycle is associated with the expression of two immediate-early viral genes, BZLF1 and BRLF1. Overexpression of ZEBRA, the product of BZLF1, is sufficient to disrupt latency in B lymphocytes and epithelial cells by stimulating expression of lytic cycle genes, including BRLF1. The BRLF1 product Rta functions as a transcriptional activator in both B lymphocytes and epithelial cells. However, Rta has recently been reported to disrupt latency in an epithelial specific manner (S. Zalani, E. Holley-Guthrie, and S. Kenney, Proc. Natl. Acad. Sci. USA 93:9194-9199, 1996). Here we demonstrate that expression of Rta is also sufficient for disruption of latency in a permissive B-cell line. In HH514-16 cells, transfection of Rta leads to synthesis of ZEBRA, viral DNA replication, and late gene expression. However, Rta by itself is less potent than ZEBRA in the ability to activate most early and late lytic cycle genes. In light of previous work implicating ZEBRA in the activation of Rta, we suggest a cooperative model for EBV entry into the lytic cycle. Expression of either BZLF1 or BRLF1 triggers expression of the other immediate-early factor, and together these activators act individually or in synergy on downstream targets to activate the viral lytic cycle.

B-Lymphocytes↗
PubMed1998

A functionally distinct TATA box required for late progression through the Epstein-Barr virus life cycle.

During EBV infection, lytic DNA replication activates late gene expression in trans via an uncharacterized pathway. In this study, we mapped the target of this regulatory cascade to a variant TATA box (TATTAAA) and the 3' flanking region within the core promoter of the BcLF1 gene. The inherent late activity of this core promoter is, surprisingly, disrupted by a heterologous enhancer, suggesting that late gene expression is regulated through core promoter sequences located in a transcriptionally inert environment.

B-Lymphocytes↗
PubMed1998

Detection of the low density lipoprotein receptor gene PvuII intron 15 polymorphism using the polymerase chain reaction: association with plasma lipid traits in healthy men and women.

We have used anchored PCR to amplify and sequence 1400 bp of the 15th intron of the Low Density Lipoprotein (LDL) receptor gene, and have determined oligonucleotides and conditions for the genotyping of the previously reported PvuII polymorphism. The cutting site (CAGCTG) is created by the transition of a CpG to a TpG within the sequence CAGCCG at a position roughly 600 bp 5' from the splice acceptor site of exon 16. Genotype was determined in three population-based samples of healthy individuals. In a group of 318 men and women from Iceland the frequencies of the Intron-15 T (cutting) allele was 0.23 (95% CI, 0.19-0.28) and was similar in men and women. In two groups of men from England (n = 385) and Scotland (n = 320), the frequency was similar, being 0.23 (0.19-0.27) and 0.25 (0.22-0.28) respectively. Individuals who were homozygous for the T allele had lower levels of total-cholesterol triglycerides and apolipoprotein B, than those with other genotypes, and in the combined group of UK men this effect reached statistical significance; compared to the C/C group, the T/T group had 6% lower cholesterol (p = 0.02) and 15% lower triglycerides (p = 0.03). The lowering effect associated with the T/T genotype was greater in men who were in the lowest tertile of body mass index (< 25 kg/m2) and for the trait of apoB levels, this genotype x obesity interaction was statistically significant (p = 0.01). We thus confirm the association between this allele and lower levels of plasma lipid levels previously reported. The availability of a PCR-based method to detect this polymorphism will facilitate further investigation of the impact of LDL-receptor gene variation in determining lipid levels.

Alleles↗
PubMed1998

Disseminated histoplasmosis in an Atlantic bottlenose dolphin (Tursiops truncatus).

An approximately 37-yr-old female Atlantic bottlenose dolphin (Tursiops truncatus) died after a 4-mo illness characterized by intermittent anorexia, lethargy, mild neutrophilic leukocytosis, and mild nonregenerative anemia. At necropsy, the lungs were diffusely consolidated, and histopathology of the lungs revealed severe pneumonia with macrophages containing clusters of numerous yeast cells. Inflammatory lesions and yeast also were found in pulmonary, mediastinal, prescapular, and duodenal lymph nodes, spleen, liver, kidneys, urinary bladder, pancreas, right adrenal gland, and the pyloric stomach. Histomorphology, fungal culture, and polymerase chain reaction analysis indicated that the fungus was Histoplasma capsulatum var. capsulatum. This is the first report of histoplasmosis in a cetacean.

Animals↗