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Biomedical subjects

P Howard

Publications and source records attributed to P Howard.

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

Asbestos exposure, lung cancer and asbestosis.

The relationship between asbestos exposure, lung cancer and asbestosis is reviewed. Studies have demonstrated the risk of lung cancer to be raised in asbestos-exposed workers whether asbestosis is present or not. Although increasing exposure increases the risk of disease, variability in estimation of fibre levels and in subject susceptibility should be borne in mind. Consensus opinion recommends that attribution of lung cancer to asbestos exposure should be based on clinical and occupational histories. The risk of lung cancer in those who both smoke and are exposed to asbestos is increased in a multiplicative way, putting subjects at very great risk.

Animals↗
PubMed1999

Cost-minimization analysis of CHOP, fludarabine and rituximab for the treatment of relapsed indolent B-cell non-Hodgkin's lymphoma in the U.K.

The optimal therapy for patients with relapsed indolent B-cell non-Hodgkin's lymphoma is unclear. Combination chemotherapy such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or purine analogues including fludarabine are frequently used and the anti-CD20 monoclonal antibody rituximab has recently been licensed for use. However, no comparative studies of these therapies have been reported. Since relapsed indolent B-cell NHL is generally regarded as incurable with current therapies, the place of each of these therapies is likely to be determined by their relative efficacy, toxicity and cost. We undertook a literature review and a retrospective analysis of patients receiving combination chemotherapy for relapsed indolent B-cell NHL at our institution to determine the response rates and the duration of response when treated with CHOP or fludarabine. Reported response rates and median response duration for these regimens are similar, and similar to those reported in phase II studies of rituximab. A cost minimization analysis was therefore conducted. The per patient costs for the treatment of drug-related adverse events were pound 5049 for CHOP, pound 2953 for fludarabine and pound 109 for rituximab. When costs of a full course of each treatment were compared, the costs per patient for CHOP, fludarabine and rituximab were pound 7210 (pound 5975-8445), pound 10022 (pound 8917-11126) and pound 6080 (pound 5892-6267) respectively. In this preliminary analysis, rituximab appeared to have a similar efficacy rate to CHOP and fludarabine, but had significantly fewer adverse events and a lower total cost per patient. These data require confirmation in a prospective randomized study with formal assessment of cost-effectiveness.

Ambulatory Care↗
PubMed1998

A comparative study of the 1992 and 1997 recovery positions for use in the UK.

In April 1997 the ILCOR Basic Life Support advisory statements were announced in conjunction with changes to the recovery position for use in the UK. This study compared the new and old positions by using a questionnaire to assess how well each position satisfied the ILCOR statements. The study was carried out over six different hospital trusts by eight resuscitation training officers. Each tutor alternately taught the 1992 or 1997 recommended positions. After the practical session each student completed a questionnaire on ease of learning and use of the position, as well as other factors such as spinal stability. They were also asked to score the position when they were placed in recovery by other students. Their competency was assessed using the ALS criteria. Over the duration of the study 687 forms were suitable for analysis. For every question there was a significant trend in favour of the 92 position, with students finding the technique easier to learn and use, simpler for positioning for CPR and with less spinal movement during rolling. Possible sources of bias such as previous training, tutor or staff grade made no statistical difference to the results. When performed competently the 1997 position appears to cause less brachial compression, but other problems with learning or use of the 97 position outweigh this advantage. The 1992 position currently provides the best compromise between ease of use, spinal stability and other factors, and better satisfies the ILCOR advisory statements.

Attitude of Health Personnel↗
PubMed1998

Respiratory symptoms among glass bottle workers--cough and airways irritancy syndrome?

Glass bottle workers have been shown to experience an excess of respiratory symptoms. This work describes in detail the symptoms reported by a cohort of 69 symptomatic glass bottle workers. Symptoms, employment history and clinical investigations including radiology, spirometry and serial peak expiratory flow rate records were retrospectively analyzed from clinical records. The results showed a consistent syndrome of work-related eye, nose and throat irritation followed after a variable period by shortness of breath. The latent interval between starting work and first developing symptoms was typically 4 years (median = 4 yrs; range = 0-28). The interval preceding the development of dysponea was longer and much more variable (median = 16 yrs; range = 3-40). Spirometry was not markedly abnormal in the group but 57% of workers had abnormal serial peak expiratory flow rate charts. Workers in this industry experience upper and lower respiratory tract symptoms consistent with irritant exposure. The long-term functional significance of these symptoms should be formally investigated.

Adult↗
PubMed1998

Diarrhoea morbidity in children in the Asaro Valley, Eastern Highlands Province, Papua New Guinea.

A morbidity study of diarrhoea covering 1926 children aged less than 5 years was carried out in Goroka town and the Lowa and Asaro Census Divisions, Eastern Highlands Province between 1986 and 1989. The study involved weekly demographic surveillance of the total population and morbidity surveillance of children by lay reporters who enquired about the presence or absence on any of the preceding 8 days of a range of symptoms associated with diarrhoeal and respiratory diseases. A three-day symptom-free period was used to define distinct episodes of diarrhoea. The average number of episodes/child-year for all children in the study population was 3.0. Boys suffered a significantly higher incidence of diarrhoea under 48 months of age than girls (4.4 episodes compared to 3.6/child-year). Incidence was highest among those aged 6-17 months (5.5/child-year) with a rapid decline after age 35 months. Incidence of diarrhoea was highest in the more remote Asaro Census Division and was higher in periurban areas than in Goroka town. Incidence also varied significantly between villages, some villages experiencing up to 10 times the incidence of diarrhoea found in Goroka town. The incidence of diarrhoea was significantly higher in January than at other times of year. Duration of diarrhoea varied with age, the longest duration being an average of 4.7 days in the 12-17 months age group. In order to reduce diarrhoea morbidity, it is necessary to improve access to water, encourage improved hygiene practices and breastfeeding and warn people about the risks of sleeping with pigs.

Age Distribution↗
PubMed1998

Damp housing and asthma.

An allergic disposition has long been recognized as a risk factor for asthma. However, it has been suggested that, irrespective of genetic factors, exposure to environmental agents is of major importance in the development of asthma. In industrialized countries, people spend most of their time indoors and so environmental conditions inside the home may play an important role in asthma development. A review of studies examining the relationship between housing conditions and health in general or, more specifically, the relationship between respiratory symptoms/asthma and damp housing and mould has been carried out. These studies have shown that damp housing conditions are associated with increased prevalence of respiratory symptoms and asthma. The severity of asthma increases with an increasing quantity of dampness and mould in the home. It is suggested that damp conditions may, by a number of mechanisms, increase the allergenic burden so resulting in the development of asthma.

Adolescent↗
PubMed1997

The C2 domain of the ubiquitin protein ligase Nedd4 mediates Ca2+-dependent plasma membrane localization.

Neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) is a ubiquitin protein ligase (E3) containing a hect domain, 3 or 4 WW domains, and a putative C2 domain. We have recently demonstrated an association between the WW domains of Nedd4 and the proline-rich PY motifs (XPPXY) of the epithelial Na+ channel, as well as with PY motifs of several other proteins. The role of the putative C2 domain of Nedd4 has not been elucidated. Here we show that Nedd4, endogenously expressed in Madin-Darby canine kidney cells, was redistributed from the cytosolic to the particulate fraction in response to ionomycin plus Ca2+ treatment. A similar treatment of polarized Madin-Darby canine kidney cells led to an apical and lateral membrane localization of Nedd4, as determined by immunostaining and confocal microscopy. The C2 domain of Nedd4, expressed as a glutathione S-transferase (GST) fusion protein, was sufficient to bind cellular membranes in a Ca2+-dependent manner. Moreover, this GST-Nedd4-C2 domain was able to mediate Ca2+-dependent interactions with phosphatidylserine, phosphatidylinositol, and phosphatidylcholine liposomes in vitro. An epitope-tagged Nedd4 lacking its C2 domain and stably expressed in Madin-Darby canine kidney cells failed to mediate the Ca2+-induced plasma membrane localization seen in wild-type (epitope-tagged) Nedd4. These results indicate that the putative C2 domain of Nedd4 acts as a bona fide C2 domain which binds phospholipids and membranes in a Ca2+-dependent fashion and is involved in localizing the protein primarily to the apical region of polarized epithelial cells in response to Ca2+.

Amino Acid Sequence↗
PubMed1997

A molecular and FISH approach to determining karyotype and phenotype correlations in six patients with supernumerary marker(22) chromosomes.

In a cytogenetic, molecular, and clinical study of patients with autosomal supernumerary marker chromosomes (SMC), 6 out of 72 (8.3%) were shown by fluorescence in situ hybridisation (FISH) to be derived from chromosome 22. PCR microsatellite analysis and FISH using primers and cosmids from proximal 22q showed 3 of the 6 to contain euchromatin. The first, a de novo nonmosaic bisatellited, dicentric SMC, was acsertained in a patient with cat eye syndrome and Duane anomaly. Microsatellite analysis showed the SMC was maternal in origin with euchromatin extending to D22S427, i.e., proximal to the DiGeorge syndrome critical region (DGSCR). The second, a nonmosaic bisatellited, dicentric marker, was found in a child with severe hypotonia and developmental delay and had been inherited from the patient's phenotypically normal father. FISH showed the SMC to contain euchromatin extending into the DGSCR. The third, a de novo SMC, was ascertained antenatally and was shown to contain 22q euchromatin extending distal to the DGSCR. The 19-week terminated fetus was phenotypically normal at autopsy. Two of the three SMC(22)s not containing detectable proximal 22q euchromatin were ascertained coincidentally in phenotypically normal individuals, whereas the third, the only mosaic with a minority euploid cell line, was found in a patient with mild developmental delay. These results suggest that SMC(22)s devoid of proximal 22q euchromatin are not associated with adverse phenotypic effects whereas SMC(22)s containing euchromatin may be found in individuals with phenotypes ranging from cat eye syndrome to normal.

Chromosome Aberrations↗
PubMed1997

Expression of microfibrillar proteins by bovine bladder urothelium.

OBJECTIVES: To determine the occurrence and potential function of proteins composing elastic microfibrils in the developing bovine bladder. METHODS: Monospecific antibodies, generated against two well-characterized microfibrillar proteins, microfibril-associated glycoprotein (MAGP) and fibrillin-1 (FBN1), were used in immunohistochemical analysis of full-thickness frozen sections of fetal bovine bladder. The localization of these two antibodies was compared with that of anti-type IV collagen antibody. Adjacent serial sections were stained for routine light microscopy. Cultured urothelial cells were fixed in 3.7% formaldehyde and permeabilized with 0.5% Triton X-100 before immunoanalysis. Control reactions used either preimmune serum or a monoclonal antibody to a nonmatrix protein. Poly(A+) ribonucleic acid was isolated from cultured urothelial cells and subjected to Northern analysis using specific complementary deoxyribonucleic acid probes for MAGP and FBN1. RESULTS: Both MAGP and FBN1 are expressed by the urothelium and are found in association with the underlying basement membrane, as visualized by their co-localization with type IV collagen. Furthermore, urothelial cells in culture continue to express both microfibrillar proteins. CONCLUSIONS: The developing bovine urothelium expresses major microfibrillar protein components. The role of these microfibrils in the urothelium remains to be determined, but they may have an important anchoring function.

Animals↗
PubMed1997

Skin flap closure by dermal laser soldering: a wound healing model for sutureless hypospadias repair.

OBJECTIVES: Laser tissue soldering (LTS) with the diode laser and human albumin-hyaluronate-indocyanine green solder is a safe and effective method of providing an immediate leak-free closure during hypospadias repair. In this report, we compare the physiology, histology, and immunohistochemistry of wound healing following LTS and suturing in a rat skin flap model. METHODS: A 4 x 5-cm skin flap was raised and bisected (4 cm) on the dorsum of 48 Sprague-Dawley rats. The central wound was either closed from a dermal approach by suturing or LTS or left open, and studied at 0, 3, 5, 7, 10, 14, and 21 days postoperatively. An intraoperative comparison was made between suturing and LTS with respect to operative time. Postoperatively, flaps were excised for tensiometric analysis, and sections were stained with hematoxylin-eosin to define wound architecture. Resting skin temperature, laser exposed temperature without solder, and maximum temperature with solder (one drop) were measured at the level of the deep dermis, superficial striated muscle layer, and within the solder. Mean peak temperatures were recorded during a 1-minute laser activation time. RESULTS: Mean continuous suturing time (4.9 +/- 1.1 minutes) was significantly (P < 0.001) faster than either LTS (7.7 +/- 0.77 minutes) or discontinuous suturing (8.2 +/- 0.62 minutes). Two seromas (sutured) and two instances of partial wound dehiscence (1 sutured, 1 LTS) were noted. Tensile strength was increased significantly (P < 0.001) for up to 5 days in the LTS group, but was equal to suturing at 7 and 10 days. Immediate tensile strength after LTS was equivalent to a 7-day healed wound. At 14 days, wounds initially left open and those closed by LTS were stronger than sutured wounds (P < 0.05). There was no evidence of thermal injury or foreign body reaction in the LTS group. Solder was incorporated within the dermis in all wounds at 21 days. Laser activation of solder resulted in significant increases in temperature at all three tissue levels: 65.0 +/- 5.2 and 69.9 +/- 6.8 degrees C in the deep and superficial skin (no significant difference between the two), and 101 +/- 15.6 degrees C within the solder (P < 0.001 versus superficial and deep skin). CONCLUSIONS: Our results indicate that sutureless dermal LTS of skin flaps provides increased tensile strength for up to 7 days, with relatively greater tensile strength provided within the first 3 days. Our laser technique does not appear to alter the normal wound healing process. Rather, solder-tissue interaction initially, and extracellular matrix infiltration of solder later, provide the basis for improved wound strength. For hypospadias repair using skin flaps, these wound attributes may permit sutureless surgery.

Animals↗
PubMed1997

Lizards as hosts for immature Ixodes scapularis (Acari: Ixodidae) in North Carolina.

Previously archived museum specimens of lizards collected throughout North Carolina were examined for Ixodes scapularis (Say). Lizards (n = 1,349) collected in 80 of North Carolina's 100 counties were examined. Lizards with ticks were collected in 23 (29%) of the 80 counties from which lizards were examined. I. scapularis was detected on 8.7% (n = 117) of the lizards and was the sole species of tick obtained from lizards. Immature ticks were most frequently found on the southeastern five-lined skink, Eumeces inexpectatus, and the eastern glass lizard, Ophisaurus ventralis. Larvae were most frequently found on the six-lined racerunner, Cnemidophorus sexlineatus. One C. sexlineatus harbored 177 larvae and 2 nymphs. Nymphs were most frequently observed on E. inexpectatus. The majority of counties (chi 2, P < 0.01) where ticks were found on lizards were in the Coastal Plain.

Animals↗
PubMed1997

Comparison of outcome measures for patients with chronic obstructive pulmonary disease (COPD) in an outpatient setting.

BACKGROUND: To assist clinicians and researchers in choosing outcome measures for patients with chronic obstructive pulmonary disease attending routine outpatient clinics, a comparative assessment was undertaken of four questionnaires designed to reflect the patients' perception of their physical and emotional health in terms of their feasibility, validity, reliability, and responsiveness to health change. METHODS: Two condition specific questionnaires, the St George's Respiratory Questionnaire (SGRQ) and Guyatt's Chronic Respiratory Questionnaire (CRQ), and two generic questionnaires, the Short Form-36 Health Survey (SF-36) and Euroqol (EQ), were compared for their discriminative and evaluative properties. Spirometric tests and a walking test were also performed. One hundred and fifty six adults who were clinically judged to have COPD and who attended an outpatient chest clinic were assessed at recruitment and six and 12 months later. Patients were also asked whether their health had changed since their last assessment. RESULTS: Completion rates and consistency between items for dimensions of the SGRQ were lower than for dimensions of the other questionnaires. The distributions of responses were skewed for certain dimensions in all questionnaires except the CRQ. Validity was supported for all instruments insofar as patients' scores were associated with differences in disease severity. The generic questionnaires better reflected other health problems. All instruments were reliable over time. The condition specific questionnaires were more responsive between baseline and first follow up visit but this difference did not persist. While certain dimensions of the SF-36 were responsive to patient perceived changes, this did not apply to the derived single index of the EQ. The rating scale of the EQ, however, provided a quick and easy indicator of change. CONCLUSIONS: Evidence from this study supports the CRQ and the SF-36 as comprehensive outcome measures for patients with longstanding COPD.

Aged↗
PubMed1997

Tick-raccoon associations and the potential for Lyme disease spirochete transmission in the coastal plain of North Carolina.

Raccoons (Procyon lotor) were live-trapped and examined for ticks from July 1990 to July 1993 in the coastal plain of North Carolina on Marine Corps Base, Camp Lejeune, North Carolina (USA). Five species of ixodid ticks were found on 351 (78%) of 449 raccoons. Amblyomma americanum was the most abundant tick found on raccoons. Dermacentor variabilis, Ixodes texanus, and Ixodes scapularis were frequently collected, while Ixodes cookei were rarely collected from raccoons. Tick burdens were not affected by the age, sex, or trap location of captured raccoons. Ticks parasitizing raccoons had varying seasonal patterns of abundance. Amblyomma americanum were generally collected from raccoons year around, but infestation intensities were greatest in summer from June to September. Dermacentor variabilis adults were most abundant in mid-summer while peak numbers of larvae were collected in the fall. Infestation intensities of Ixodes texanus larvae were greatest in fall and winter months while nymphs were most abundant in winter and spring. No males were collected from raccoons, but females were most frequently collected in the spring and declined in abundance in the summer with no specimens collected in the fall or winter. Numbers of 1. scapularis adults appeared to reach peak numbers in the fall while larvae and nymphs were most abundant on raccoons in winter. Spirochetes, Borrelia burgdorferi, were identified in a small percentage (0.2%) of host-seeking A. americanum nymphs and adults, and I. scapularis adults by immunofluorescent antibody assays. Similarly, a small percentage (1.9%) of host-associated A. americanum, D. variabilis, I. texanus and I. cookei contained B. burgdorferi. Borrelia burgdorferi spirochetes were cultured from the blood of 23 (26%) of 87 raccoons.

Animals↗
PubMed1997

Causes of death in patients with COPD and chronic respiratory failure.

Although the factors associated with mortality, such as forced expiratory volume in one second (FEV1), arterial oxygen tension (Pa,O2) and pulmonary arterial pressure, have been well described, there is limited information on the circumstances of death in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the causes and circumstances of death in patients with COPD and chronic respiratory failure (Pa,O2 < 8.0 kPa (60 mmHg) breathing air), treated with long-term oxygen therapy (LTOT). Ten European centres participated in the study and data were collected from patients both during a period of clinical stability and at the time of death. Of the 215 patients evaluated (161 males and 54 females; aged 66 +/- 10 yrs), the major causes of death were: acute on chronic respiratory failure (38%); heart failure (13%); pulmonary infection (11%); pulmonary embolism (10%); cardiac arrhythmia (8%); and lung cancer (7%). Seventy five percent of patients died in hospital. There was no difference in the number of patients who died in the morning, afternoon and night hours. Twenty percent of the total died during sleep and in 26% death was unexpected. A lower arterial carbon dioxide tension (Pa,CO2), less oxygen usage per 24 h, and increased incidence of arrhythmias were seen in those patients who died suddenly. Drug therapy was not related to unexpected death. The majority of patients with chronic obstructive pulmonary disease on long-term oxygen therapy died from chronic or acute on chronic respiratory failure. Prevention and treatment of respiratory failure in patients with chronic obstructive pulmonary disease is likely to have the greatest impact in reducing mortality.

Aged↗
PubMed1996

Reservoir competence of the southeastern five-lined skink (Eumeces inexpectatus) and the green anole (Anolis carolinensis) for Borrelia burgdorferi.

The reservoir competence of two lizard species, the southeastern five-lined skink (Eumeces inexpectatus) and the green anole (Anolis carolinesis), for Borrelia burgdorferi was evaluated. Skinks and anoles were exposed by needle inoculation or tick bite to B. burgdorferi. Xenodiagnosis with larval Ixodes scapularis and culture of tissues were used to asses infection and the ability of infected lizards to infect attached ticks. Both lizard species were susceptible to B. burgdorferi by both routes of exposure. Xenodiagnostic ticks acquired spirochetes while feeding on both species. One tick that dropped from a skink on the ninth day after exposure was infected. The remainder of xenodiagnostic ticks that acquired spirochetes fed three weeks after exposure of the lizards to the spirochete. Lizards remained infectious to attached ticks for at least five weeks. Overall, more than 20% of xenodiagnostic larvae fed on southeastern five-lined skinks acquired spirochetes. Individual skinks infected up to 34% of attached ticks. A smaller proportion of ticks feeding on green anoles became infected. Borrelia burgdorferi recovered from infected lizards retained their infectivity for mammalian hosts. The ability of the lizards to sustain a Borrelia infection and infect attached ticks suggests that they may play a role in the maintenance of spirochete transmission.

Animals↗
PubMed1996

Experimental infection of the raccoon (Procyon lotor) with Borrelia burgdorferi.

The reservoir competence of the raccoon (Procyon lotor) for the Lyme disease spirochete (Borrelia burgdorferi) was evaluated in the laboratory during September 1991 to April 1993. Five raccoons were exposed to spirochete-infected (JD1 and Wisconsin 210 Wise strains) Ixodes scapularis nymphs (20/raccoon). A second feeding of spirochete-infected (Wisconsin 210 Wise strain) nymphs (20/raccoon) was performed with four of the original raccoons. Xenodiagnosis with cohorts of I. scapularis larvae (300/cohort) or nymphs (150/cohort) that were periodically placed on each animal was used to detect infection. We examined 1943 engorged ticks by a indirect immunofluorescence monoclonal antibody assay, but no spirochetes were detected. After exposure to spirochete-infected ticks, blood samples were collected at approximately weekly intervals and ear-skin biopsy samples were taken from each animal every third week. These tissues were placed in Barbour-Stoenner-Kelly media. Spirochetes were isolated in cultures of skin (wk 3, 5, 9, 81, and 83) and blood (wk 5, 8, 9, 11, and 12) of one raccoon and the skin (wk 28 and 31) of another raccoon. Antibody response of each animal was monitored through enzyme-linked immunosorbent assays and immunoblotting of blood serum against B. burgdorferi proteins. Except for one animal, raccoons did not have an antibody response until they were fed upon by a second cohort of infected I. scapularis nymphs. Based on Western blot analyses, raccoons exposed to B. burgdorferi via tick bite responded to the 31- (OspA) and 34-KDa (OspB) antigens. Response to other antigens varied among raccoons. Based on our results raccoons may be inefficient reservoirs for B. burgdorferi. Although some raccoons can become infected with B. burgdorferi, they may not transfer the infection to attached ticks.

Animals↗