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Biomedical subjects

P D Morris

Publications and source records attributed to P D Morris.

At least 19 recordsLinked to original sources
PubMed2004

Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life.

BACKGROUND: Low serum testosterone is associated with several cardiovascular risk factors including dyslipidaemia, adverse clotting profiles, obesity, and insulin resistance. Testosterone has been reported to improve symptoms of angina and delay time to ischaemic threshold in unselected men with coronary disease. OBJECTIVE: This randomised single blind placebo controlled crossover study compared testosterone replacement therapy (Sustanon 100) with placebo in 10 men with ischaemic heart disease and hypogonadism. RESULTS: Baseline total testosterone and bioavailable testosterone were respectively 4.2 (0.5) nmol/l and 1.7 (0.4) nmol/l. After a month of testosterone, delta value analysis between testosterone and placebo phase showed that mean (SD) trough testosterone concentrations increased significantly by 4.8 (6.6) nmol/l (total testosterone) (p = 0.05) and 3.8 (4.5) nmol/l (bioavailable testosterone) (p = 0.025), time to 1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing increased by 74 (54) seconds (p = 0.002), and mood scores assessed with validated questionnaires all improved. Compared with placebo, testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor alpha with delta values of -0.41 (0.54) mmol/l (p = 0.04) and -1.8 (2.4) pg/ml (p = 0.05) respectively. CONCLUSION: Testosterone replacement therapy in hypogonadal men delays time to ischaemia, improves mood, and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor alpha.

Androgens↗
PubMed2001

Evidence for a functional monomeric form of the bacteriophage T4 DdA helicase. Dda does not form stable oligomeric structures.

The active form of many helicases is oligomeric, possibly because oligomerization provides multiple DNA binding sites needed for unwinding of DNA. In order to understand the mechanism of the bacteriophage T4 Dda helicase, the potential requirement for oligomerization was investigated. Chemical cross-linking and high pressure gel filtration chromatography provided little evidence for the formation of an oligomeric species. The specific activity for ssDNA stimulated ATPase activity was independent of Dda concentration. Dda was mutated to produce an ATPase-deficient protein (K38A Dda) by altering a residue within a conserved, nucleotide binding loop. The helicase activity of K38A Dda was inactivated, although DNA binding properties were similar to Dda. In the presence of limiting DNA substrate, the rate of unwinding by Dda was not changed; however, the amplitude of product formation was reduced in the presence of increasing concentrations of K38A Dda. The reduction was between that expected for a monomeric or dimeric helicase based on simple competition for substrate binding. When unwinding of DNA was measured in the presence of excess DNA substrate, addition of K38A Dda caused no reduction in the observed rate for strand separation. Taken together, these results indicate that oligomerization of Dda is not required for DNA unwinding.

Adenosine Triphosphatases↗
PubMed2001

Unwinding of unnatural substrates by a DNA helicase.

Helicases separate double-stranded DNA into single-stranded DNA intermediates that are required during replication and recombination. These enzymes are believed to transduce free energy available from ATPase activity to unwind the duplex and translocate along the nucleic acid lattice. The nature of enzyme-substrate interactions between helicases and duplex DNA substrates has not been well-defined. Most helicases require a single-stranded DNA overhang adjacent to duplex DNA in order to initiate unwinding. The strand containing the overhang is referred to as the loading strand whereas the complementary strand is referred to as the displaced strand. We have investigated the interactions between a DNA helicase and the DNA substrate by replacing the displaced strand with a nucleic acid mimic, peptide nucleic acid (PNA). PNA is capable of forming duplex structures with DNA according to Watson-Crick base pairing rules, but contains a N-(2-aminoethyl)glycine backbone in place of the deoxyribose phosphates. The PNA-DNA hybrids had higher melting temperatures than their DNA-DNA counterparts. Dda helicase, from bacteriophage T4, was able to unwind the DNA-PNA substrates at similar rates as DNA-DNA substrates. The results indicate that the rate-limiting step for unwinding is relatively insensitive to the chemical nature of the displaced strand and the thermal stability of oligonucleotide substrates.

Adenosine Triphosphatases↗
PubMed2001

Biotin-streptavidin-labeled oligonucleotides as probes of helicase mechanisms.

Helicases use the energy from ATP hydrolysis to catalyze formation of single-stranded nucleic acids by unwinding double-stranded nucleic acids. The ATP-dependent reaction can be broken down into at least two steps: melting of the duplex and translocation of the enzyme along the nucleic acid lattice. Each step presents difficulties for study because clear end points for the reactions are not always available. For example, translocation involves the movement of the enzyme from one point along the lattice to a new position, with no net change in chemical structure of the nucleic acid. Hence, new assays have been developed in which the nucleic acid is modified to contain a "protein block" that impedes translocation of the enzyme. To prepare such protein blocks, biotin-streptavidin has been used due to the ease with which the biotin can be incorporated into nucleic acids by chemical synthesis. Several applications of oligonucleotides labeled with biotin-streptavidin for the study of helicase mechanisms are described.

Biotin↗
PubMed1999

DNA helicases displace streptavidin from biotin-labeled oligonucleotides.

Helicases are enzymes that use energy derived from nucleoside triphosphate hydrolysis to unwind double-stranded (ds) DNA, a process vital to virtually every phase of DNA metabolism. The helicases used in this study, gp41 and Dda, are from the bacteriophage T4, an excellent system for studying enzymes that process DNA. gp41 is the replicative helicase and has been shown to form a hexamer in the presence of ATP. In this study, protein cross-linking was performed in the presence of either linear or circular single-stranded (ss) DNA substrates to determine the topology of gp41 binding to ssDNA. Results indicate that the hexamer binds ssDNA by encircling it, in a manner similar to that of other hexameric helicases. A new assay was developed for studying enzymatic activity of gp41 and Dda on single-stranded DNA. The rate of dissociation of streptavidin from various biotinylated oligonucleotides was determined in the presence of helicase by an electrophoretic mobility shift assay. gp41 and Dda were found to significantly enhance the dissociation rate of streptavidin from biotin-labeled oligonucleotides in an ATP-dependent reaction. Helicase-catalyzed dissociation of streptavidin from the 3'-end of a biotin-labeled 62-mer oligonucleotide occurred with a first-order rate of 0.17 min-1, which is over 500-fold faster than the spontaneous dissociation rate of biotin from streptavidin. Dda activity leads to even faster displacement of streptavidin from the 3' end of the 62-mer, with a first-order rate of 7.9 s-1. This is more than a million-fold greater than the spontaneous dissociation rate. There was no enhancement of streptavidin dissociation from the 5'-biotin-labeled oligonucleotide by either helicase. The fact that each helicase was capable of dislodging streptavidin from the 3'-biotin label suggests that these enzymes are capable of imparting a force on a molecule blocking their path. The difference in displacement between the 5' and 3' ends of the oligonucleotide is also consistent with the possibility of a 5'-to-3' directional bias in translocation on ssDNA for each helicase.

Bacteriophage T4↗
PubMed1996

Golf cart related injuries in a North Carolina island community, 1992-4.

OBJECTIVES AND METHODS: The use of electric golf carts for roadway transportation is increasing in many regions of the United States, but injuries associated with the operation of these vehicles have not been previously described. In response to reports of golf cart related injuries in a North Carolina island community, we reviewed ambulance call report (ACR) information to identify and describe all injuries related to golf cart operation in this community in 1992-4. We also conducted telephone interviews with the subset of injured people who consented to be contacted. SETTING: Bald Head Island, North Carolina. RESULTS: Twenty two people were included in the case series, and 55% of these provided interview information to supplement ACR data. Fifty nine per cent of the 22 injured people were injured when they fell from a moving golf cart; of those injured in this manner, all with available information on seating position were passengers (rather than drivers). Eighty six per cent received immediate medical treatment at a mainland hospital. Thirty two per cent of injury incidents occurred among children aged 10 or younger. Forty per cent of injured adults were known to have been drinking alcohol before their injuries occurred, while alcohol was not known to have been involved in any of the children's injuries (in terms of drinking either by children or by accompanying adults). CONCLUSIONS: In settings where golf carts are used for road transportation, their users and traffic safety officials should be aware of potential safety hazards associated with the use of these vehicles, and installation of appropriate occupant restraints should be considered seriously.

Adolescent↗
PubMed1995

Lifetime excess risk of death from lung cancer for a U.S. female never-smoker exposed to environmental tobacco smoke.

There is considerable evidence that exposure to environmental tobacco smoke (ETS) in the home increases the risk of lung cancer in female nonsmokers. A risk assessment was conducted to estimate the lifetime excess risk of death from lung cancer for a U.S. female never-smoker exposed to ETS in different settings. Relative risks for social and occupational exposures were calculated using a relative risk of 1.185 for home exposure (calculated from a recent metaanalysis of U.S. studies) and the results of studies that compare home exposure to exposures outside the home. Each relative risk was used to convert lung cancer mortality rates for U.S. female never-smokers into a lifetime excess risk, using a formula which accounts for competing causes of death. The excess risk for home exposure is 6.5 x 10(-4) (6.5 excess deaths per 10,000 never-smokers). For social and overall workplace exposures, excess risks range from 1.4 x 10(-4) to 3.6 x 10(-4) and from 9.8 x 10(-6) to 1.4 x 10(-4), respectively. Exposures in offices, restaurants, and bars result in excess risks that range from 1.5 x 10(-4) to 9.0 x 10(-4). All of these estimates are greater than an acceptable risk level of 10(-6). The results of this analysis support efforts to restrict or eliminate smoking in public places and work sites.

Aged↗
PubMed1995

Eosinophilia-myalgia syndrome: a long-term follow-up study.

In this case-series analysis, of 34 patients originally identified with eosinophilia-myalgia syndrome (EMS), 31 survivors were followed-up by yearly telephone interviews. We ascertained type, duration, and severity of symptoms and whether certain patient characteristics were associated with illness improvement. At a median of 3.6 years after onset, 3 patients (8.8%) had died. Two (5.9%) were well, 7 (20.6%) were improved, and 22 (64.7%) reported either no change or worsening overall condition compared to 1 year prior. Musculoskeletal and neurologic symptoms predominated. The prevalence of several symptoms, including muscle cramps, joint pain, and cognitive symptoms, increased over the course of study. Age, sex, peak eosinophil count, early prednisone use, and usual dose or duration of L-tryptophan use were not associated with significant improvement. We conclude that for the majority of patients, EMS is a chronic illness having a major impact on life-style 3.6 years after onset. The chronic, often worsening pattern of illness suggests an ongoing pathogenetic mechanism.

Adult↗
PubMed1994

The risk of dying in alcohol-related automobile crashes among habitual drunk drivers.

BACKGROUND: Reports suggest that people who drive while intoxicated by alcohol may do so repeatedly. We hypothesized that persons arrested for driving while impaired might be at increased risk for death in an alcohol-related motor vehicle crash. To evaluate this possibility, we studied the deaths of drivers in alcohol-related motor vehicle accidents in North Carolina over a 10-year period. METHODS: We compared drivers who died in motor vehicle crashes from 1980 through 1989 and who had blood alcohol concentrations of at least 20 mg per deciliter (4.3 mmol per liter), referred to as the case drivers, with those who died in crashes but had blood alcohol concentrations below 20 mg per deciliter, referred to as the control drivers. We identified case drivers and control drivers through the state Medical Examiner System. We then searched North Carolina driver-history files for the five years before each death to identify arrests for driving while impaired. RESULTS: We linked a total of 1646 case drivers and 1474 control drivers to their driver-history files. Case drivers were more likely than control drivers to have been arrested for driving while impaired (26 percent vs. 3 percent). After we controlled for potential confounding variables, case drivers 21 to 34 years of age were 4.3 times more likely (95 percent confidence interval, 2.7 to 6.8) than control drivers to have been arrested for driving while impaired; case drivers 35 years of age or older were 11.7 times more likely (95 percent confidence interval, 6.8 to 20.1). The strength of the association appeared to increase with the number of prior arrests. Case drivers were also more likely than the general population of currently licensed drivers to have been arrested. CONCLUSIONS: Arrests for driving while impaired substantially increase the risk of eventual death in an alcohol-related crash. Aggressive intervention in the cases of people arrested for driving while impaired may decrease the likelihood of a future fatal alcohol-related crash.

Accidents, Traffic↗
PubMed1994

Hurricane-related emergency department visits in an inland area: an analysis of the public health impact of Hurricane Hugo in North Carolina.

STUDY OBJECTIVE: To evaluate the public health impact of a hurricane on an inland area. DESIGN: Descriptive study. SETTING: Seven hospital emergency departments. PARTICIPANTS: Patients who were treated from September 22 to October 6, 1989, for an injury or illness related to Hurricane Hugo. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Over the two-week study period, 2,090 patients were treated for injuries or illnesses related to the hurricane. Of these, 1,833 (88%) were treated for injuries. Insect stings and wounds accounted for almost half of the total cases. A substantial proportion (26%) of the patients suffering from stings had a generalized reaction (eg, hives, wheezing, or both). Nearly one-third of the wounds were caused by chain saws. CONCLUSION: Hurricanes can lead to substantial morbidity in an inland area. Disaster plans should address risks associated with stinging insects and hazardous equipment and should address ways to improve case reporting.

Adolescent↗
PubMed1992

Choosing criteria to screen for specific medical conditions from nonspecific sources: an application to injury surveillance.

The authors examine an approach for identifying which criteria to use when screening for persons with a relatively rare medical condition. They considered various subsets of an inclusive set of criteria by examining the statistical effectiveness per unit cost of deleting various criteria using three statistical measures of effectiveness. An application to injury surveillance, where categories of the patient's chief complaint were used for screening via emergency department logs, illustrates two implications of the approach. First, deletion priorities may differ somewhat by effectiveness measure. When using sensitivity to measure statistical efficiency, the tendency is first to drop the larger categories with the smaller proportions of injury. On the other hand, using specificity to gauge effectiveness calls for large categories with the highest injury rates to be deleted first; while for a measure of effectiveness derived from relative bias, the tendency is first to drop those categories with the fewest injuries. Second, an unequivocal set of criteria may not emerge, thus forcing one to decide among options. The authors suggest several rationales for making this decision.

Cost-Benefit Analysis↗
PubMed1991

Respiratory symptoms and pulmonary function in chicken catchers in poultry confinement units.

To evaluate the respiratory consequences of working in poultry confinement units, we completed a cross-sectional epidemiologic study of respiratory symptoms and pulmonary function in 59 chicken catchers. The results were compared to a published reference standard of nonexposed blue-collar workers. Chicken catchers reported a high rate of acute symptoms associated with work in poultry houses. They also reported statistically significant higher rates for chronic phlegm (39.0%) and chronic wheezing (27.1%) than nonexposed blue-collar workers. Chicken catchers had significant decrements over a work shift in forced vital capacity (-2.2%) and forced expiratory volume in 1 sec (-3.4%), and there was suggestive evidence that they had decreased preshift pulmonary function compared with nonexposed blue-collar workers. These results indicate that chicken catchers are at risk for respiratory dysfunction and emphasize the need to develop measures to minimize their exposure to respiratory toxicants in poultry confinement units.

Air Pollutants, Occupational↗
PubMed1991

Clinical and epidemiological features of neurotoxic shellfish poisoning in North Carolina.

BACKGROUND: In October 1987, a red tide due to P. brevis affected the North Carolina coast for the first time. The purpose of our study was to describe the clinical and epidemiological features of neurotoxic shellfish poisoning (NSP), an illness caused by eating shellfish contaminated with the neurotoxins of P. brevis. METHODS: Active surveillance was established for cases of NSP. A descriptive study of the NSP cases was then completed. RESULTS: Forty-eight persons, who had eaten oysters at 20 meals, met the case definition. A variety of gastrointestinal tract and neurological symptoms were reported. The illnesses were generally mild and of short duration, and there were no deaths. Forty-one (85 percent) affected persons lived in five communities located within a 70-kilometer area along the coast. Cases occurred from October 27 to December 9; 27 (56 percent) of the cases occurred before the first closure of affected shellfish waters on November 2. There was a significant increase in the illness attack rate with an increase in the number of oysters eaten. CONCLUSIONS: Routine monitoring of coastal waters for P. brevis is needed to facilitate earlier recognition of red tides, closure of affected areas, and education of the public before substantial exposure to contaminated shellfish occurs.

Adolescent↗
PubMed1990

Ciguatera fish poisoning: an outbreak associated with fish caught from North Carolina coastal waters.

Ten persons who had eaten at a seafood meal in North Carolina had gastrointestinal and neurologic symptoms suggestive of ciguatera fish poisoning. In five persons, the neurologic morbidity lasted 30 days or longer. The meal included barracuda, dolphin fish (mahimahi), and yellow-fin tuna, all of which were caught in North Carolina coastal waters. Analysis of food-specific attack rates implicated the barracuda as the probable cause of the outbreak. We believe this is the first suspected or confirmed report of ciguatera fish poisoning associated with consumption of fish harvested from mainland US coastal waters outside of Florida. Physicians treating patients with a syndrome resembling ciguatera fish poisoning should inquire about consumption of fish not only from areas where the disease is endemic but also from the southeastern US.

Adult↗
PubMed1989

Chronic lymphocytic leukemia in relation to chemical exposures.

As part of a population-based case-control study carried out in four areas of the United States, 427 cases of chronic lymphocytic leukemia diagnosed between July 1, 1977, and December 31, 1981, and 1,683 controls were interviewed regarding their history of chemical exposure. Respondents were asked if they had ever been "highly exposed" at home, at work, or elsewhere to one or more of a list of chemicals or to any other such substances not on the list. These chemicals were categorized into 20 exposure groups based on chemical composition. Odds ratios were calculated adjusting for age, sex, race, education level, and geographic location by means of unconditional logistic regression. Increased risks were associated with reported past exposure to acid-containing chemicals, "other caustic substances," aliphatic hydrocarbons, and chlorinated hydrocarbons. Because of the large number of exposures investigated in this study, and because of the relatively imprecise means the authors had to assess exposure, further research is needed to verify these findings.

Adult↗
PubMed1987

Human toxocariasis. Review with report of a probable case.

A 23-year-old woman with fever, myalgias, stridor, pelvic cramping, lower abdominal pain, and profound eosinophilia was presumed to have toxocariasis. An enzyme-linked immunosorbent assay titer of 1:64 and an elevated IgE level supported the diagnosis. The patient became asymptomatic without treatment, and the eosinophil count returned to normal over several months. A stool sample from her dog was found to contain Toxocara canis ova, but the patient had no history of geophagia. Presumably, she acquired infection by hand-to-mouth transmission of infectious ova after handling the dog. Toxocariasis from this type of transmission is usually not seen in an adult, but it does occur, as this case demonstrates. Thus, the primary care physician should consider toxocariasis in any patient with a suggestive clinical picture and eosinophilia.

Adult↗
PubMed1986

Toxic substance exposure and multiple myeloma: a case-control study.

By means of a population-based, multicenter case-control investigation, certain toxic substances were evaluated as risk factors for multiple myeloma. Interviews were completed on 698 subjects with newly diagnosed multiple myeloma, and 1,683 controls were selected from the same geographic areas as those of the cases. Respondents were asked if they had ever been "highly" exposed" to one or more of a list of toxic substances or to other substances not on the list. With the aid of a toxicologist, responses were then categorized into 20 exposure groups. Those who reported past exposure to pesticides had an estimated relative risk of 2.6 for multiple myeloma [95% confidence interval (CI) = 1.5-4.6]. Subjects exposed to a variety of compounds commonly used by painters had an estimated relative risk of 1.6 (95% CI = 1.1-2.4). An increased risk also was found for those who were exposed to sources of carbon monoxide (relative risk = 1.8, 95% CI = 1.0-3.2). Associations of borderline statistical significance were found for metals and organically high polymers (plastics and elastomers). No statistically significant associations were seen for exposure to fertilizers; dyes and inks; alkalies; acids; other caustic substances; chemical asphyxiants; aliphatic, chlorinated, or aromatic hydrocarbons; aldehydes and ketones; ethers; esters; oils; dusts; or asbestos.

Adult↗