Biomedical subjects

R L Hall

Publications and source records attributed to R L Hall.

At least 19 recordsLinked to original sources

PubMed2005

A procedure for the safety evaluation of natural flavor complexes used as ingredients in food: essential oils.

A scientifically based guide has been developed to evaluate the safety of naturally occurring mixtures, particularly essential oils, for their intended use as flavor ingredients. The approach relies on the complete chemical characterization of the essential oil and the variability of the composition of the oil in the product intended for commerce. Being products of common plant biochemical pathways, the chemically identified constituents are organized according to a limited number of well-established chemical groups called congeneric groups. The safety of the intake of the each congeneric group from consumption of the essential oil is evaluated in the context of data on absorption, metabolism, and toxicology of members of the congeneric group. The intake of the group of unidentified constituents is evaluated in the context of the consumption of the essential oil as a food, a highly conservative toxicologic threshold, and toxicity data on the essential oil or an essential oil of similar chemotaxonomy. The flexibility of the guide is reflected in the fact that high intake of major congeneric groups of low toxicologic concern will be evaluated along with low intake of minor congeneric groups of significant toxicological concern (i.e., higher structural class). The guide also provides a comprehensive evaluation of all congeneric groups and constituents that account for the majority of the composition of the essential oil. The overall objective of the guide is to organize and prioritize the chemical constituents of an essential oil in order that no reasonably possible significant risk associated with the intake of essential oil goes unevaluated. The guide is, however, not intended to be a rigid checklist. The Flavor and Extract Manufacturers Association (FEMA) Expert Panel will continue to evaluate each essential oil on a case by case basis applying their scientific judgment to insure that each natural flavor complex is exhaustively evaluated.

Animals↗

PubMed2004

Safety evaluation of natural flavour complexes.

Natural flavour complexes (NFCs) are chemical mixtures obtained by applying physical separation methods to botanical sources. Many NFCs are derived from foods. In the present paper, a 12-step procedure for the safety evaluation of NFCs, 'the naturals paradigm', is discussed. This procedure, which is not intended to be viewed as a rigid check list, begins with a description of the chemical composition of the commercial product, followed by a review of the data on the history of dietary use. Next, each constituent of an NFC is assigned to one of 33 congeneric groups of structurally related substances and to one of three classes of toxic potential, each with its own exposure threshold of toxicological concern. The group of substances of unknown structure is placed in the class of greatest toxic potential. In subsequent steps, for each congeneric group the procedure determines the per capita intake, considers metabolic pathways and explores the need and availability of toxicological data. Additional toxicological and analytical data may be required for a comprehensive safety evaluation. The procedure concludes with an evaluation of the NFC in its entirety, also considering combined exposure to congeneric groups. The first experiences with the use of this procedure are very promising. Future safety evaluations of larger numbers of NFCs will indicate the usefulness of the system, either in its present form or in a form modified on the basis of experience.

Animals↗

PubMed2003

Haematological safety of antipsychotic drugs.

Haematological abnormalities are frequently encountered during treatment with antipsychotic drugs. Most of these are mild and of no clinical significance. In the case of many, there is often difficulty in establishing a cause-and-effect relationship between the drug and the abnormality. However, in a small minority of patients, hazardous, potentially life-threatening haematological effects can occur due to a combination of pharmacological and host factors. These include leucopenia and agranulocytosis. Although such effects are rare, it is essential that they are diagnosed and managed promptly. In this paper, the authors review the haematological adverse effects and safety of antipsychotic drugs and present a strategy for prevention.

Agranulocytosis↗

PubMed2001

Acquired Factor VIII autoantibody: four cases demonstrating the heterogenous nature of this condition and problems involved in diagnosis and treatment.

The development of an autoantibody to human Factor VIII is rare and presents many problems for diagnosis and treatment. We have seen several cases at our institution recently with widely heterogenous clinical and laboratory presentations. A wide range of treatment modalities were used in these cases with no gold standard of treatment or widely accepted guidelines existing. This has prompted us to examine all cases of this condition presenting at Fremantle Hospital over the last decade. We describe four cases which demonstrate the heterogeneity of this condition and its treatment and review the recent literature on the subject.

Adult↗

PubMed2001

Na+ transport in normal and CF human bronchial epithelial cells is inhibited by BAY 39-9437.

To test the hypothesis that Na+ transport in human bronchial epithelial (HBE) cells is regulated by a protease-mediated mechanism, we investigated the effects of BAY 39-9437, a recombinant Kunitz-type serine protease inhibitor, on amiloride-sensitive short-circuit current of normal [non-cystic fibrosis (CF) cells] and CF HBE cells. Mucosal treatment of non-CF and CF HBE cells with BAY 39-9437 decreased the short-circuit current, with a half-life of approximately 45 min. At 90 min, BAY 39-9437 (470 nM) reduced Na+ transport by approximately 70%. The inhibitory effect of BAY 39-9437 was concentration dependent, with a half-maximal inhibitory concentration of approximately 25 nM. Na+ transport was restored to control levels, with a half-life of approximately 15 min, on washout of BAY 39-9437. In addition, trypsin (1 microM) rapidly reversed the inhibitory effect of BAY 39-9437. These data indicate that Na+ transport in HBE cells is activated by a BAY 39-9437-inhibitable, endogenously expressed serine protease. BAY 39-9437 inhibition of this serine protease maybe of therapeutic potential for the treatment of Na+ hyperabsorption in CF.

Biological Transport↗

PubMed1999

Hydrodynamic properties of mucins secreted by primary cultures of guinea-pig tracheal epithelial cells: determination of diffusion coefficients by analytical ultracentrifugation and kinetic analysis of mucus gel hydration and dissolution.

We have used two different approaches to determine hydrodynamic parameters for mucins secreted by guinea-pig tracheal epithelial cells in primary culture. Cells were cultured under conditions that promote mucous cell differentiation. Secreted mucins were isolated as the excluded fraction from a Sepharose CL-4B gel filtration column run under strongly dissociating conditions. Biochemical analysis confirmed the identity of the high molecular weight material as mucins. Analytical ultracentrifugation was used to study the physical properties of the purified mucins. The weight average molecular mass (Mw) for three different preparations ranged from 3.3 x 10(6) to 4.7 x 10(6) g/mol (corresponding to an average structure of 1-2 subunits), and the sedimentation coefficient from 25.5 to 35 S. Diffusion coefficients ranging from 4.5 x 10(-8) to 6.4 x 10(-8) cm2/s were calculated using the Svedberg equation. A polydispersity index (Mz/Mw) of approximately 1.4 was obtained. Diffusivity values were also determined by image analysis of mucin granule exocytosis captured by videomicroscopy. The time course of hydration and dissolution of mucin was measured and a relationship is presented which models both phases, each with first order kinetics, in terms of a maximum radius and rate constants for hydration and dissolution. A median diffusivity value of 8.05 x 10(-8) cm2/s (inter-quartile range = 1.11 x 10(-7) to 6.08 x 10(-8) cm2/sec) was determined for the hydration phase. For the dissolution phase, a median diffusivity value of 6.98 x 10(-9) cm2/s (inter-quartile range = 1.47 x 10(-8) to 3.25 x 10(-9) cm2/sec) was determined. These values were compared with the macromolecular diffusion coefficients (D20,w) obtained by analytical ultracentrifugation. When differences in temperature and viscosity were taken into account, the resulting D37,g was within the range of diffusivity values for dissolution. Our findings show that the physicochemical properties of mucins secreted by cultured guinea-pig tracheal epithelial cells are similar to those of mucins of the single or double subunit type purified from respiratory mucus or sputum. These data also suggest that measurement of the diffusivity of dissolution may be a useful means to estimate the diffusion coefficient of mucins in mucus gel at the time of exocytosis from a secretory cell.

Animals↗

PubMed1999

52-Week oral gavage chronic toxicity study with ubiquinone in rats with a 4-week recovery.

Potential ubiquinone (CoQ10; a natural fermentation product) toxicity was assessed in rats administered CoQ(10) by oral gavage for 1 year at 100, 300, 600, and 1200 mg/(kg day). No adverse changes in mortality, clinical signs, body weight, food consumption, or clinical pathology results occurred. CoQ(10) had elimination half-lives ranging from 10.7 to 15.2 h. At 1200 mg/(kg day), a high incidence of orange, granular, lumenal exudate in nasal turbinates occurred; microscopically, findings similar to those in the turbinates were occasionally observed in small granulomas within lung alveoli. A dose-related increased incidence of vacuolated macrophages (mesenteric lymph nodes) and vacuolated hepatic periportal cells was noted. Neither were associated with tissue damage or organ dysfunction, so they were not considered to be adverse. The nasal turbinate and lung findings were probably secondary to incidental exposure to crystallized test material. Overall, CoQ(10) was well tolerated by male and female rats at dose levels up to 1200 mg/(kg day).

Administration, Oral↗

PubMed1999

Comparison of two methods to assess the intake of flavouring substances.

It is important to assess the intake of flavouring substances in order to be confident that exposure to the substance from its intended use presents no significant risk. A number of methods exist to estimate intake of food ingredients. Two such methods, one using a detailed dietary analysis based on food consumption and composition and one using 10 times the annual volume of use on a per capita basis (per capita x 10), were compared for their precision and practicality in assessing the intake of 10 flavouring substances. The detailed dietary analysis method of determining exposure resulted in good estimates of the distribution of intakes across the population, as well as patterns of intake of individuals. This method is both expensive and labour intensive. The per capita x 10 method yields results that, compared with those obtained by detailed dietary analysis, tend consistently to overstate exposure. Thus, this method is a conservative and practical approach to assessing exposure to flavouring substances and other food ingredients.

Diet↗

PubMed1998

Oral toxicity and carcinogenicity studies of sucrose acetate isobutyrate (SAIB) in the Fischer 344 rat and B6C3F1 mouse.

Sucrose acetate isobutyrate (SAIB), a food additive used as a flavour emulsion stabilizer in citrus-based soft drinks, was evaluated for chronic toxicity in B6C3F1 mice and Fischer 344 rats. SAIB dissolved in acetone was blended into NIH07 rodent diet at concentrations that were adjusted weekly during the first 12 to 18 months of the studies so that ingested dose levels per kg body weight were constant. Groups of 20 rats per sex were given dose levels of 0.0, 0.0, 0.5, 1.0 and 2.0 g SAIB/kg body weight for 1 yr, and groups of 50 rats per sex were given dose levels of 0.0, 0.0, 0.5, 1.0 and 2.0 g SAIB/kg body weight for 2 yr. Mice were fed dose levels of 0.0, 0.0, 1.25, 2.5 and 5.0 g SAIB/kg body weight for 2 yr. The highest doses fed, equivalent to dietary concentrations of approximately 5%, were considered to be the maximum concentrations that could be fed without risk of nutritional deficiencies. Depressions in body weight gain were noted, particularly in female rats during the first 12 to 18 months of the studies. Recovery during the last quarter of the 2-yr study suggests that the reduced body weight gain was nutritional rather than SAIB-related. There were no differences in survival between SAIB-treated rats or mice and controls. Decreased body weight gains, primarily in females, but less consistent than those in the rat, were noted in the 2-yr mouse study. No signs of toxicity were observed in clinical chemistry, haematology, organ weights, gross necropsy findings or light microscopy studies in the 1- or 2-yr rat studies. Electron microscopic examinations of liver sections from high dose level rats from the 1-yr study also revealed no effects of SAIB treatment. There were no significant increases in benign or malignant tumours in the long-term rat or mouse carcinogenicity studies. The lowest no-observed-adverse-effect level (NOAEL) was 2 g SAIB/kg body weight derived from the 1- and 2-yr chronic toxicity studies in the rat.

Animal Feed↗

PubMed1998

High-level expression of Amsacta moorei entomopoxvirus spheroidin depends on sequences within the gene.

Spheroidin (SPH) is the most highly expressed gene of the entomopoxvirus isolated from Amsacta moorei (AmEPV). The level of expression of poxvirus genes is believed to be governed in large part by the promoter. Poxvirus promoters generally consist of approximately 40 bp which frequently terminate at the 3' end with a translation initiating TAAATG sequence. We have examined the requirements for high levels of SPH gene expression by constructing AmEPV recombinants containing either the SPH promoter or the late vertebrate poxvirus promoter derived from the cowpox virus A-type inclusion (ATI) gene. In addition, we have examined SPH promoter derivatives which extend beyond the 3' TAAATG to include 2 or 20 bp of the 5' coding sequence of the SPH gene. Examination of insect cells infected with these AmEPV ATI-lacZ or SPH-lacZ recombinants suggests that ATI-lacZ expression begins 12 h before and is essentially complete prior to any SPH-lacZ expression, allowing functional distinction between the ATI and SPH promoters and implying that different factors regulate the two promoters within the insect environment. SPH promoter-regulated expression is significantly enhanced within infected insect cells by including the additional 20 bp of the N-terminal SPH coding sequences as part of the promoter. However, when any of the SPH promoter constructs, including those containing the downstream sequences, were inserted into vaccinia virus, only very low levels of beta-galactosidase expression were observed. These results imply that downstream coding sequences within the SPH gene enhance SPH gene expression only within the insect environment.

Animals↗

PubMed1997

Characterization of a DNA topoisomerase encoded by Amsacta moore entomopoxvirus.

We have identified an Amsacta moorei entomopoxvirus (AmEPV) gene encoding a DNA topoisomerase. The 333-amino acid AmEPV topoisomerase displays instructive sequence similarities to the previously identified topoisomerases encoded by five genera of vertebrate poxviruses. One hundred nine amino acids are identical or conserved among the six proteins. The gene encoding AmEPV topoisomerase was expressed in bacteria and the recombinant enzyme was partially purified. AmEPV topoisomerase is a monomeric enzyme that catalyzes the relaxation of supercoiled DNA. Like the vaccinia, Shope fibroma virus, and Orf virus enzymes, the AmEPV topoisomerase forms a covalent adduct with duplex DNA at the target sequence CCCTT decreases. The kinetic and equilibrium parameters of the DNA cleavage reaction of AmEPV topoisomerase (Kobs = 0.08 sec-1; Kcl = 0.22) are similar to those of the vaccinia virus enzyme.

Amino Acid Sequence↗

PubMed1997

Sodium chloride increases the ciliary transportability of cystic fibrosis and bronchiectasis sputum on the mucus-depleted bovine trachea.

Mucus retention in the lungs is an important feature of several respiratory diseases (Regnis, J.A., M. Robinson, D.L. Bailey, P. Cook, P. Hooper, H.K. Chan, I. Gonda, G. Bautovich, and P.T.P. Bye. 1994. Am. J. Respir. Crit. Care Med. 150:66-71 and Currie, D.C., D. Pavia, J.E. Agnew, M.T. Lopez-Vidriero, P.D. Diamond, P.J. Cole, and S.W. Clarke. 1987. Thorax. 42:126-130). On the mucus-depleted bovine trachea, the ciliary transport rate of sputum from patients with cystic fibrosis and bronchiectasis of other causes was slow, but the rate was doubled by increasing the sodium chloride content by 90 mM. Increasing the sputum osmolality by inspissation or by the addition of nonelectrolytes had a similar effect. The viscoelasticity of sputum, but not the bovine ciliary beat frequency, was markedly saline dependent over the pathophysiological range. This suggests that low mucus salinity, not (as is generally assumed) its under-hydration, contributes to its retention in bronchiectasis due to cystic fibrosis and other causes, probably by affecting its rheology. It also indicates how the genetic defect in cystic fibrosis might lead to impaired mucus clearance. Therapies that increase the osmolality of lung mucus might benefit patients with mucus retention.

Animals↗

PubMed1997

Transient, nonlethal expression of genes in vertebrate cells by recombinant entomopoxviruses.

The group B entomopoxvirus (EPV) from Amsacta moorei (AmEPV) productively infects only insect cells. A series of AmEPV-lacZ recombinants was constructed in which the lacZ gene was regulated by either late (the AmEPV spheroidin or the cowpox virus A-type inclusion [ATI]) or early (the AmEPV esp [early strong promoter; derived from a 42-kDa AmEPV protein] or the Melolontha melolontha EPV fusolin, fus) virus promoters. When the AmEPV recombinants were used to infect vertebrate cells, beta-galactosidase expression occurred (in >30% of the cells) when lacZ was regulated by either the fus or esp early promoters but not when lacZ was regulated by the late promoters (spheroidin or ATI). Therefore, AmEPV enters vertebrate cells and undergoes at least a partial uncoating and early, but not late, viral genes are expressed. Neither viral DNA synthesis nor cytopathic effects were observed under any infection conditions. When an AmEPV recombinant virus containing the Aequorea victoria green fluorescent protein gene (gfp) under the control of the esp promoter was used to infect vertebrate cells at a low multiplicity of infection, single fluorescent cells resulted, which continued to divide over a period of several days, ultimately forming fluorescent cell clusters, suggesting that vertebrate cells survive the infection and continue to grow. Therefore, AmEPV may prove to be a highly efficient, nontoxic method of gene delivery into vertebrate cells for transient gene expression.

Animals↗

PubMed1997

Replacement of the lateral malleolus of the ankle joint with a reversed proximal fibular bone graft.

Infrequently, prior reports have described the use of the ipsilateral proximal fibula to replace an absent distal fibula caused by either trauma, infection, or resection for tumor. This is a 27-year follow-up of a 12-year-old patient who lost the distal 7.5 cm of her fibula secondary to trauma. The soft tissue defect was replaced early by an abdominal flap and the bone defect was eventually replaced with 7.5 cm of proximal fibula. The lateral ankle ligaments were reconstructed with the peroneus brevis, and the ankle joint has remained stable. Although traumatic arthrosis has progressed slowly, the patient at age 39 has a relatively painless, mobile ankle joint.

Adult↗

PubMed1996

The Amsacta moorei entomopoxvirus spheroidin gene is improperly transcribed in vertebrate poxviruses.

The Amsacta moorei entomopoxvirus (AmEPv) spheroidin is the most highly expressed late viral gene product in infected insect cells. However, when a cassette containing the spheroidin gene and putative promoter was inserted into cowpox (CPV) or vaccinia viruses, only very low levels of spheroldin gene expression were observed. Primer extension analysis suggests much lower spheroidin gene transcript levels than seen either for the highly expressed CPV A-type inclusion gene or for the spheroidin gene within infected insect cells, indicating that in vertebrate cells, the spheroidin promoter functions poorly if at all. Examination of the spheroidin mRNA synthesized in recombinant CPV shows that the 5' start site of the spheroidin transcript was also unexpectedly imprecise and upstream (approximately 31 bp) of the well-defined start site normally observed in AmEPV-infected insect cells. Sequencing of the 5' terminus of the CPV recombinant spheroidin mRNA suggested that 5' poly(A), a characteristic feature of late poxvirus mRNAs and spheroidin mRNA derived from insect cells, was absent, despite the presence of the typical vertebrate poxvirus late promoter consensus sequence, TAAATG. Our results indicate that insect and vertebrate poxvirus promoters may not be universally interchangeable and imply that there are regulatory features of gene expression unique to the infected insect cell environment.

Animals↗

PubMed1996

Centrocentral anastomosis with autologous nerve graft treatment of foot and ankle neuromas.

Painful neuromatas in the foot and around the ankle can be difficult to treat. Five patients of clinically and histologically proven neuromas underwent centrocentral union with autologous transplantation. Three patients had previous toe amputations involving multiple operations. One patient had failed multiple operative treatments for Morton's neuroma in his 3rd web space. One patient had a neuroma in his superficial peroneal nerve caused by a gun shot wound. All patients but one showed definitive subjective and objective improvement after centrocentral union with the interposed autologous nerve graft. The patient with "recurrent" Morton's neuroma had the least improvement. This technique can be recommended as an alternative for the prevention of painful stump neuromata.

Adult↗

PubMed1996

Plantar fibromatosis: treatment of primary and recurrent lesions and factors associated with recurrence.

Plantar fibromatosis is a benign but often problematic foot disorder which, when surgically treated, is difficult to eradicate. The purpose of this investigation was to identify epidemiologic factors associated with disease recurrence and to determine which method of treatment most successfully eliminated recurrence. A retrospective review of surgical pathology reports and clinical histories from 1979 to 1993 was performed to identify all patients who underwent surgery for plantar fibromatosis at our institution during that time. Thirty-three feet of 30 patients were identified with a minimum 2-year follow-up. Seventeen feet underwent surgery for primary lesions, and 4 of 10 that had local excision, 1 of 3 that had wide excision, and 2 of 4 that had subtotal fasciectomy (with or without skin grafting) had recurrence. All 16 feet in patients presenting with recurrent lesions had undergone prior local excision at other institutions. When combined with patients from our institution who underwent a second procedure, 21 feet had surgery for recurrent plantar fibromatosis. Of these, three of four had further recurrence when treated with local or wide excision. In feet with recurrences treated with subtotal fasciectomy, only 4 of 17 had recurrence after the first attempt at such treatment. Average follow-up for all patients was 7.7 years, and all patients with postoperative recurrences showed evidence of disease within 14 months after surgery (mean, 6.9 months). Factors identified with an increased risk for recurrence were multiple nodules, bilateral lesions, and positive family history. In treating recurrent disease, subtotal fasciectomy was more effective than local or wide excision. This study identified factors associated with a significant likelihood of postoperative recurrence in treating plantar fibromatosis and found subtotal fasciectomy to provide the most successful treatment in eradicating disease in recurrent cases.

Adolescent↗

PubMed1996

Magnetic resonance imaging in the evaluation of heel pain.

This study demonstrates magnetic resonance findings in 16 patients (25 heels) with heel pain. Sixteen of 25 (64%) studies demonstrated abnormalities which could be related to the etiology of their heel pain. Eleven of 16 abnormal scans demonstrated thickening of the plantar aponeurosis with associated fibrosis (7 of 11), and a tear of the flexor digitorum brevis (1 of 11). One study demonstrated changes in the heel pad consistent with fluid. The other four abnormal studies demonstrated changes thought to be consistent with bilateral fibrous calcaneonavicular coalitions, subtalar arthrosis and tenosynovitis of the posterior tibial, flexor digitorum longus, and flexor hallucis longus tendons.

Adult↗