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Biomedical subjects

P Howard

Publications and source records attributed to P Howard.

At least 55 records · Page 3Linked to original sources
PubMed1996

Myocarditis in mice and guinea pigs experimentally infected with a canine-origin Borrelia isolate from Florida.

OBJECTIVE: To characterize the pathogenic potential of a unique Borrelia isolate obtained from a dog from Florida (FCB isolate). DESIGN: Prospective experimental infection. ANIMALS: 32 preweanling Swiss Webster mice and 12 adult male Hartley guinea pigs were injected intraperitoneally with 10(5) spirochetes. PROCEDURE: Mice were used as controls and blood recipients, and at 3- to 4-day intervals, 1 control mouse and 2 infected mice were necropsied, tissues were cultured, and a recipient mouse was inoculated with blood. Guinea pigs were randomized to 4 groups and inoculated intradermally with 10(0), 10(2), 10(3), or 10(4) spirochetes. For 48 days, clinical, hematologic, serologic, and microbiologic tests were performed on them, after which they were necropsied. RESULTS: In mice, spirochetemia was detectable between postinoculation days (PID) 3 and 13, and seroreactivity to homologous antigen was detectable during PID 10 through 31. Compared with control mice, infected mouse spleens were 2 to 3 times larger. Histologic lesions included lymphoid hyperplasia, neutrophilic panniculitis, epicarditis, and myocarditis, with intralesional spirochetes detected from PID 3 through 6. During PID 10 through 31, nonsuppurative epicarditis developed. Signs of illness and hematologic abnormalities were not observed in guinea pigs, despite isolating spirochetes from blood during PID 7 to 27. When necropsied on PID 48, histologic lesions included lymphoid hyperplasia and lymphocytic plasmacytic epicarditis. CONCLUSIONS: The FCB isolate causes spirochetemia, lymphoid hyperplasia, dermatitis, and myocardial injury in Swiss Webster mice and can be transmitted by blood inoculation. In Hartley guinea pigs, the isolate causes spirochetemia, lymphoid hyperplasia, and epicarditis. Documentation of disease in mice, guinea pigs, and, presumably, dogs raises the level of concern that the FCB isolate might be pathogenic for man and other animal species.

Animals↗
PubMed1995

The QTc interval, autonomic neuropathy and mortality in hypoxaemic COPD.

Patients with hypoxaemic chronic obstructive pulmonary disease (COPD) have a subclinical autonomic neuropathy. Autonomic neuropathy has been associated with a prolonged electrocardiograph QTc interval and risk of ventricular arrhythmias and death. We studied cardiovascular autonomic nerve function and QTc interval at rest and during stress (a valsalva manoeuvre) in 34 patients with hypoxaemic COPD who were followed up after 2 yr. Seventeen patients had a subclinical autonomic neuropathy (group AN) and the remaining 17 were normal (group C). Group AN were significantly more hypoxaemic (PaO2 7.3 +/- 0.3 compared to 9.2 +/- 1.8, P < 0.05), had a lower FEV1 and had a longer QTc at rest (0.43 +/- 0.01 compared to 0.40 +/- 0.01, P < 0.01) and at peak valsalva (0.44 +/- 0.01 compared to 0.41 +/- 0.01, P < 0.05). When analysed after 2 yr, there were two deaths in group C and seven deaths in group AN. The QTc was abnormal > 0.44s at rest and at peak valsalva stress in five of group AN, three of these five patients died. QTc was normal at rest but abnormal at peak valsalva stress in eight further patients. This included three further patients from group AN of whom two had died and five group C patients which included both the group C deaths. The presence of autonomic neuropathy and QTc prolongation (> 0.44s) at rest was significantly associated (P < 0.05). Likewise QTc prolongation at the peak of a valsalva stress was significantly associated with death at 2 yr follow-up (P < 0.01) with an odds ratio of 11.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System Diseases↗
PubMed1995

Microsatellite instability in squamous cell carcinoma of the head and neck.

Genomic instability or microsatellite instability (MI) in simple repeated sequences was initially recognised in colonic carcinomas and subsequently in other tumours. MI has been associated with mutations in genes concerned with replication and DNA repair. We investigated 34 microsatellite markers in squamous cell carcinoma of the head and neck (SCCHN). Fifty-six tumours, were studied, of which 25 were investigated with ten or more microsatellite markers. In this study we consider two or more microsatellite alterations in a tumour to be diagnostic of MI. We demonstrated that 7/25 (28%) of the tumours had MI at two or more loci and three of these tumours exhibited evidence of 20 or more loci with MI. No correlations were found between MI and previous treatment, site, histological differentiation, positive nodes at pathology, a history of alcohol intake or survival. MI has been demonstrated in T1N0 stage tumours, indicating that these changes may occur early in the disease process. A negative correlation was found between MI and a history of smoking (P = 0.02). Two or more markers of MI were found in three of four non-smokers compared with one of 13 in the smoking group of patients, which suggests a novel mechanism of carcinogenesis in non-smokers.

Carcinoma, Squamous Cell↗
PubMed1995

Allelotype of squamous cell carcinoma of the head and neck: fractional allele loss correlates with survival.

Allelic imbalance or loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour-suppressor genes. We have undertaken an extensive allelotype of 80 specimens of squamous cell carcinoma of the head and neck (SCCHN) using 145 polymorphic microsatellite markers on 39 chromosome arms. Allelic imbalances were found most frequently on chromosome arms 3p, 9p, 17p and 18q with over 45% LOH and imbalances on 1p, 1q, 2p, 5q, 6p, 6q, 8p, 8q, 9q, 11q, 13q, 17q and 19q were found in more than 20% of SCCHN. These LOH data were analysed against a range of clinicopathological parameters which included previously untreated and previously treated tumours; correlations were found between LOH on 9q and nodes at pathology (P = 0.02) and between histopathological grade and LOH on 12q (P = 0.02) and 13q (P = 0.01). In the group of previously untreated tumours, a correlation was found between site of tumour and LOH on 3p (P = 0.019), and 8p (P = 0.029), while TNM staging correlated with LOH on 3p (P = 0.019) and 17p (P = 0.016). Fractional allele loss (FAL) was calculated for 52 tumours with LOH data on nine or more chromosomal arms and found to have a median value of 0.22 (range 0.0-0.80). Correlations were found between FAL > median value and nodes at pathology (P = 0.01) and tumour grade (P = 0.06), demonstrating that advanced tumours with lymph node metastasis often had LOH at multiple sites. FAL > median value was found to correlate with a poor survival (P < 0.03) and, furthermore, FAL > median value correlated with poor survival in the previously untreated patients (P < 0.019). These results indicate that assessment of the accumulation of genetic damage, as provided by allelotype data, provides a useful molecular indicator of the tumour behaviour and clinical outcome.

Alleles↗
PubMed1995

Effect of fenspiride on pulmonary function in the rat and guinea pig.

1. Fenspiride is an anti-inflammatory agent that may have a role in reversible obstructive airways disease. Small, but significant, improvements have been seen in airways function and arterial oxygen tension in patients with mild chronic obstructive pulmonary disease. These changes have been attributed to the anti-inflammatory properties of the drug. However, airways function can be improved by other means, e.g. improved ventilation/perfusion ratio or reduced airways resistance. The possibility that fenspiride may have actions other than anti-inflammatory was investigated in two animal species. 2. In the rat, actions on the pulmonary circulation were investigated in the isolated perfused lung, but fenspiride proved to be a poor pulmonary vasodilator, showing only a small reversal of the raised pulmonary artery pressure induced by hypoxia. 3. Ventilation was measured in the anaesthetized rat using whole-body plethysmography. Fenspiride caused no increase in ventilation or changes in arterial blood gases. However, a profound hypotensive action was observed with high doses. 4. The possibility that a decrease in airways resistance (R(aw)) might occur with fenspiride was investigated in anaesthetized guinea pigs. Capsaicin (30 mumol/l) was used to increase baseline R(aw) through bronchoconstriction. Fenspiride gave a dose-dependent partial reversal of the raised R(aw), and its administration by aerosol proved as efficacious as the intravenous route. In addition, the hypotensive side-effect found with intravenous injection was alleviated by aerosolized fenspiride.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1995

Hormonal, renal, and autonomic nerve factors involved in the excretion of sodium and water during dynamic salt and water loading in hypoxaemic chronic obstructive pulmonary disease.

BACKGROUND: Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop sodium and water retention and a subclinical autonomic neuropathy. The possibility that these might be associated has been investigated. METHODS: The ability of 24 patients with COPD to excrete a 6 ml/kg 2.7% intravenous saline or 15 ml/kg oral water load was studied and changes in plasma electrolyte levels, osmolality, plasma aldosterone and vasopressin levels, urinary volume and sodium content, glomerular filtration rate, renal blood flow, and cardiovascular autonomic nerve function were measured. Patients were divided into groups of eight: those in group A (controls) had mild COPD with a Pa02 of > 9 kPa and no oedema, patients in group B were more hypoxaemic but had never been oedematous, whilst those in group C were hypoxaemic and mildly oedematous at the time of the study. RESULTS: Patients in groups B and C excreted less sodium and water during saline loading and a lesser proportion of the water load. Patients in group C had a reduction in renal blood flow and glomerular filtration rate and all had a subclinical autonomic neuropathy, which was also found in three patients in group B. Their plasma aldosterone level was raised but did suppress appropriately on saline loading. Vasopressin levels were abnormally raised for the osmolality in patients in group C and in those with autonomic dysfunction throughout the water load and at 240 minutes after the salt load. Sodium and urine excretion was highly correlated with autonomic dysfunction, aldosterone levels at time zero, and renal blood flow. The 11 patients with autonomic dysfunction were more likely to be oedematous, more hypoxaemic, excreted much less urine and sodium, had lower glomerular filtration rate and renal blood flow, and higher aldosterone and vasopressin levels than the remaining patients. CONCLUSIONS: In patients with COPD the inability to excrete sodium and water is multifactorial. This is the first study to show that autonomic dysfunction is at least associated and might play an important part in the impaired sodium and water homeostasis seen in patients with severe COPD.

Aged↗
PubMed1995

Antitussive and antibronchoconstriction actions of fenspiride in guinea-pigs.

Fenspiride is a nonsteroidal anti-inflammatory agent, which we have previously shown to have an in vivo antibronchoconstrictor action in guinea pigs. We have currently studied this action using the constrictors Substance P, neurokinin A, citric acid and capsaicin in anaesthetized guinea-pigs. Fenspiride has also been reported to produce a subjective improvement in cough in patients. We have used a conscious guinea-pig model of cough as a more definitive method to study the effect of fenspiride on capsaicin- and citric acid-induced cough. Aerosolized fenspiride (1 mg.mL-1) caused a 58% reversal of capsaicin-induced bronchoconstriction; and i.v. fenspiride (1mg.kg-1) a 45% reversal of citric acid induced bronchoconstriction. Substance P- and neurokinin A-induced bronchoconstriction were unaffected by 1 mg.kg-1 i.v. fenspiride. Aerosolized fenspiride (1, 3 and 10 mg.mL-1) administered for 4 min reduced citric acid (300 mM) induced cough, but 0.1 mg.mL-1 was without effect. Pretreatment with aerosolized fenspiride (10 mg.mL-1) caused a shift in the citric acid dose response curve to the right. For citric acid-induced cough, the duration of action of aerosolized fenspiride (10 mg.mL-1) was found to be 5 and 15 min post-treatment. Aerosolized capsaicin (30 microM) induced cough was also reduced by 3 and 10 mg.mL-1 aerosolized fenspiride, but no significant effect was found with 1 mg.mL-1. We conclude that aerosolized fenspiride reduces capsaicin- and citric acid-induced bronchoconstriction as well as induced cough in guinea-pigs in vivo. Whether a pathway common to both cough and bronchoconstriction is the site of action of fenspiride remains to be established. We postulate that fenspiride, acting as an antitussive and antibronchoconstrictor agent, would be beneficial in the clinical situation for those patients with hyperresponsive airways.

Acetates↗
PubMed1994

Effects of angiotensin converting enzyme inhibition on sodium excretion in patients with hypoxaemic chronic obstructive pulmonary disease.

BACKGROUND: Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop cor pulmonale with sodium and water retention. The sodium retention has been explained as a result of increased plasma levels of aldosterone. If this was true angiotensin converting enzyme (ACE) inhibition would be expected to lower plasma levels of aldosterone and improve the renal excretion of sodium. METHODS: Six patients with stable hypoxaemic COPD (PaO2 < 8.0 kPa) and a history of an oedematous exacerbation received an intravenous hypertonic saline load (6 ml/kg body weight of 2.7% saline over one hour) before and while taking 4 mg/day perindopril, an ACE inhibitor, for one month. Aldosterone, antidiuretic hormone (ADH), plasma and urine electrolyte levels, osmolality, and volume were measured over four hours. The repeatability of the saline load test was assessed in six patients with a similar severity of hypoxaemic COPD. For comparison the saline load test was also performed in six patients with mild COPD. RESULTS: The hypertonic saline load test results were repeatable. Perindopril reduced the mean (SD) plasma level of aldosterone from 142 (88) pg/ml to 54 (24) pg/ml at 0 minutes before the saline infusion, and from 64 (35) pg/ml to 30 (17) pg/ml after the infusion without improving the urinary volume or sodium excretion. Before starting treatment with perindopril 43.7 (6.9) mmol (20%) of the sodium load was excreted compared with 49.6 (7.9) mmol (22% of load) when taking perindopril. Patients with mild COPD excreted more sodium (77.6 (21.4) mmol (38.7% of load)) despite having similar plasma aldosterone levels to those in the patients receiving perindopril. CONCLUSIONS: Patients with stable hypoxaemic COPD have an impaired ability to excrete sodium which is not improved by the administration of an ACE inhibitor. ACE inhibition lowered the plasma level of aldosterone without improving sodium excretion. This suggests that the inability of patients with hypoxaemic COPD to excrete sodium is not caused by their increased plasma levels of aldosterone.

Aged↗
PubMed1994

Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary artery pressure is elevated in patients with advanced chronic obstructive pulmonary disease (COPD). Release of atrial natriuretic peptide (ANP) is increased in pulmonary hypertension and this hormone may both selectively vasodilate pulmonary vessels and inhibit pulmonary vascular remodelling. The hypothesis that ANP has a physiological role in protection of the pulmonary circulation from pressure overload, and that it may be beneficial in patients with COPD, has been examined. METHODS: Ten patients with hypoxic COPD were infused for 30 minute periods with saline followed by ANP at 0.4, 2, and 10 pmol/kg/min respectively via a pulmonary artery catheter whilst monitoring haemodynamics and oxygenation. RESULTS: Levels of immunoreactive ANP (irANP) increased from a mean (SD) of 23 (15) pmol/l to a maximum of 94 (41) pmol/l. Neither systemic blood pressure, cardiac output nor total systemic vascular resistance showed any correlation with irANP levels. There were negative correlations between levels of ANP and mean pulmonary artery pressure which fell from 28.7 to 25.9 mm Hg, pulmonary artery wedge pressure which fell from 6.5 to 4.6 mmHg, and total pulmonary vascular resistance which fell from 489 to 428 dynes s cm-5. There was a small fall in PaCO2 from 6.2 to 5.9 kPa, whilst venous admixture and oxygen delivery both increased non-significantly. CONCLUSIONS: At these pathophysiological concentrations there was evidence that ANP selectively reduced right ventricular afterload. These data support the hypotheses that increased plasma levels of ANP may be beneficial in hypoxic COPD, and that endogenous ANP may ameliorate pulmonary hypertension in humans.

Aged↗
PubMed1994

Home treatment for chronic respiratory insufficiency: the situation in Europe in 1992. The European Working Group on Home Treatment for Chronic Respiratory Insufficiency.

The search for improved quality of life and a reduction in health care costs is leading to the development of home treatment. The organization of home treatment for chronic respiratory patients in 13 European countries was evaluated at the end of 1992 by means of a questionnaire. Switzerland and the Association Nationale pour le Traitement A Domicile de l'Insuffisance Respiratoire Chronique (ANTADIR) in France maintain registers for patients on oxygen therapy, mechanical ventilation and sleep disorders. Sweden and Poland have a national register for patients receiving oxygen. In other countries, some information can be obtained from the National Health Service or the commercial provider. Oxygen concentrators are used preferentially in all countries except Italy, Denmark, Spain and The Netherlands. Home ventilator treatment is generally performed by volume-cycled ventilators. National prescription rules exist in some parts of Spain, Switzerland and Belgium. In other countries, such as Germany, prescriptions rely on recommendations elaborated by specialists or international guidelines. Service and equipment are provided by national organizations, health services, commercial companies or hospitals. Home supervision of the patient is performed by a nurse and/or a doctor and equipment maintenance by a technician. Important differences exist between countries in Europe in home treatment of chronic respiratory disease. Comparative analysis should help achieve uniform standards and provide a basis for future research.

Costs and Cost Analysis↗
PubMed1994

A survey of sexually transmitted diseases in five STD clinics in Papua New Guinea.

The first multicentre survey of sexually transmitted diseases (STDs) performed in Papua New Guinea was conducted in STD clinics in five towns, Port Moresby, Goroka, Rabaul, Lae and Daru, from September 1989 to May 1990. Infections with Neisseria gonorrhoeae and Chlamydia trachomatis (alone or in combination) were common. Penicillinase-producing N. gonorrhoeae (PPNG) represented 44% of all gonococcal isolates but significant intrinsic resistance to penicillin was not found. Of the other antibiotics tested, significant elevation of minimum inhibitory concentration (MIC) was common only for tetracycline, although no high-level tetracycline resistance was detected. C. trachomatis was detected by direct immunofluorescence (DIF) in 26% of 210 males and 27% of 64 females. 10% (21/210) of males and 11% (7/64) of females were both DIF positive for C. trachomatis and culture positive for N. gonorrhoeae. Of 203 males and 78 females tested, 5% and 12%, respectively, had serological evidence of current syphilis infection. Clinically, genital ulcer disease was most commonly due to syphilis, donovanosis or genital herpes, while specific vaginal infections were commonly seen in female patients attending Port Moresby and Lae STD clinics.

Anti-Bacterial Agents↗
PubMed1994

Survey on domiciliary oxygen by concentrator in England and Wales.

Long-term oxygen therapy is initiated in England and Wales by the patient's family doctor, sometimes at the request of a hospital consultant. Guidelines for therapy exist but are not mandatory. We wish to investigate the numbers and types of patients being treated under this regimen, the method of treatment and how they responded to their oxygen dose. We therefore interviewed and tested patients at the inception of therapy in six of the nine prescribing areas of the whole country, during August 1990 and February 1991. Main outcome measures were diagnoses, daily duration and flow prescribed, arterial oxygen saturation (SaO2) breathing air and improvement in arterial oxygen saturation on prescribed oxygen. Most patients both in summer and winter reported diagnoses of chronic bronchitis (45%) or emphysema (50%), in addition to other conditions. Most were male (58%), and most (72%) were over retirement age. Roughly half (45%) were house-bound, but only 28 (6%) were totally bedridden. Three quarters (77%) reported that a hospital consultant had told them how much oxygen to use, and in all diagnostic groups mean prescriptions exceeded 15 h.day-1 and 2 l.min-1. However, only half (54%) of the patients with complete measurements had basal arterial oxygen saturation of 90% or less at the start of treatment, together with a satisfactory improvement in arterial oxygen saturation on the prescribed flow of oxygen. In conclusion, patients are usually prescribed adequate regimens but little attempt is made to ensure that prescription is appropriate or response satisfactory. Resources continue to be used for treating patients without ensuring that they benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Autonomic nerve dysfunction in COPD as assessed by the acetylcholine sweat-spot test.

Patients with hypoxic chronic obstructive pulmonary disease (COPD) have evidence of a subclinical parasympathetic autonomic neuropathy, with apparent preservation of sympathetic function. However, these cardiovascular-respiratory tests might have been biased by concomitant chest disease, the acetylcholine sweat-spot test avoids this bias. This sweat-spot test assesses sympathetic nerve function, it relies upon the fact that denervated sweat glands do not produce sweat. 35 patients with hypoxaemic COPD and seven age matched normal subjects were studied. Following intradermal injection of 0.1 of 1% acetylcholine into the dorsum of the feet, the number of sweatglands able to respond in a given surface area was recorded. Cardiovascular autonomic nerve function, arterial oxygen and carbon dioxide tensions, lung function and cigarette consumption were also recorded. The acetylcholine sweat-spot test was highly repeatable in eight COPD patients, no person with normal or frankly abnormal function being wrongly assigned. The age matched control subjects had normal acetylcholine sweat-spot scores and cardiovascular autonomic tests. The acetylcholine sweat-spot test was abnormal in 24 patients, borderline in 8 and normal in 3 patients. The abnormal sweat-spot test group had significant worse FEV1, arterial blood gases and autonomic function. The acetylcholine sweat-spot score correlated with the severity of arterial hypoxaemia (r = 0.78, p < 0.001) and with the parasympathetic cardiovascular tests (r = 0.80, p < 0.001). In conclusion, patients with hypoxaemic COPD have a parasympathetic cardiovascular and a peripheral sympathetic autonomic neuropathy. The acetylcholine sweat-spot test is repeatable, easy to perform and a sensitive indicator for autonomic dysfunction in breathless individuals with COPD.

Acetylcholine↗