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Biomedical subjects

F Alexander

Publications and source records attributed to F Alexander.

At least 55 records · Page 3Linked to original sources
PubMed1990

Characterization of skin lesions in mice following intradermal inoculation of Haemophilus ducreyi.

Twelve strains of H. ducreyi, which included two reference strains, were each inoculated intradermally into the flanks of CBA mice. All strains produced self-limited lesions which were macroscopically and microscopically typical of those seen in chancroid. Pustular nodules, about 5mm in diameter, developed at all inoculation sites by the second day when 10(7) organisms were inoculated. Approximately half of these lesions ulcerated and all had regressed by 2 weeks. Smaller nodules developed at about half the sites from the second to the fifth day when 10(6) or 10(5) organisms were given, but these did not ulcerate. No lesions were seen when 10(3) organisms were inoculated. Organisms were recovered from the lesions up to 11 days after inoculation. Specific H. ducreyi antigen, sought by a monoclonal antibody test, was detected in lesions up to 15 days following inoculation. Heat-killed organisms of H. ducreyi also produced nodules and ulcers although these were slightly smaller than those which developed after inoculation of viable bacteria. Similar lesions to those caused by H. ducreyi were produced after intradermal inoculation of about 10(8) viable or killed Neisseria gonorrhoeae organisms. Treatment of mice with ceftriaxone had little or no effect on the subsequent development of H. ducreyi-induced lesions. These findings indicated that the lesions were not produced specifically by viable H. ducreyi organisms. Ulcers were also produced following intradermal inoculation of purified lipopolysaccharide (LPS) from H. ducreyi or N. gonorrhoeae, but not by cell-free filtrates prepared from H. ducreyi cultures indicating a possible role for LPS in the pathogenesis of ulcerative skin lesions.

Animals↗
PubMed1990

Severity of salpingitis in mice after primary and repeated inoculation with a human strain of Chlamydia trachomatis.

Groups of inbred female mice of strains CBA or C3H were infected genitally with a pathogenic human strain of Chlamydia trachomatis (N.I.1, serovar F) known to produce salpingitis and infertility in mice. Mice were inoculated under the ovarian bursa or directly into the uterine cavity with chlamydiae (test groups) or with sucrose-phosphate transport medium (control groups) before being challenged with chlamydiae by the same route 12-17 weeks later. Twenty-five pairs of test and control animals were killed from 7 to 77 days after challenge and oviductal inflammatory changes, recovery of organisms, and antibody responses were compared in the two groups. Salpingitis in the mice infected previously (tests groups) was more severe than in the controls in 56% of comparisons, the same in 24% and less severe in 20%. However, despite the increase in the severity of disease, shedding of C. trachomatis from the lower genital tract was less prolonged after rechallenge or did not occur. Salpingitis occurred in spite of the almost certain presence of pre-existing serum antibody, and accelerated and accentuated antibody response in the rechallenged mice. Furthermore, the continued existence of high titres of antibody was not associated with less severe disease. Thus, the results reveal that previous exposure to chlamydiae does not prevent salpingitis and suggest that its severity is influenced by cell-mediated immune mechanisms.

Animals↗
PubMed1989

Natural history of in situ breast cancer in a defined population.

The entire experience of in situ breast cancer in Alberta from 1953 to 1984 was examined. Of 243 patients coded, 226 were available for review by a panel of three pathologists. In 149 cases the diagnosis of in situ disease was confirmed. One hundred and eight patients had 109 ductal carcinomas in situ, 38 patients had lobular carcinomas in situ, with 3 patients having both. A multitude of treatments was used, ranging from local excision to radical mastectomy. Survival at a mean of 6 years follow-up was equal in all groups, with only two patients with a confirmed diagnosis of ductal carcinoma in situ dying from clinically suspected systemic disease. In patients treated by local excision, ipsilateral cancers were seen in 12% of ductal carcinoma in situ patients who had local excision and 13% of patients with lobular carcinoma in situ. Contralateral metachronous invasive cancers were seen in 6% of ductal carcinoma in situ patients and 3% of lobular carcinoma in situ patients. No lymph node involvement was seen in any of these patients, either with prophylactic dissection or in follow-up. The conclusion reached was that both in situ lesions are similar in their clinical course. Lymph node dissection is not necessary. Pathologic review is critical for accurate studies, with a change in diagnosis of 36% of diagnoses. Treatment does not appear to affect prognosis. The most appropriate treatment needs to be determined in prospective randomized trials.

Adult↗
PubMed1989

Randomisation by cluster and the problem of social class bias.

For randomised population trials the unit of randomisation is normally the individual person. In some situations, however, investigators take other groups as basic unit and one such design is cluster randomisation. Considerable attention has been given to this design recently in statistical and epidemiological literature. The Edinburgh randomised trial of breast cancer screening is an example which takes general practices as clusters of patients. The experience of this trial is reported here. Mortality from all causes, cardiovascular disease and lung cancer over the first 5 year period of follow up are examined. We found that spurious mortality differences were present in the analyses, which do not allow for socio-economic status. From examination of methods of adjusting for this, we conclude that allowance can be made at the analysis stage, and it is intended that this approach will be adopted when breast cancer mortality is analysed in the Edinburgh trial. Nevertheless, we recommend that for future studies with outcome related to socio-economic status, randomisations which use this design be stratified by socio-economic criteria where this is feasible.

Bias↗
PubMed1989

Corticosteroid treatment and prognosis in pulmonary eosinophilia.

The acute and long term responses to corticosteroid treatment in 65 patients with pulmonary eosinophilia have been reviewed. Of the 247 episodes of pulmonary eosinophilia that were documented during a median follow up period of 14 years, 186 were treated with prednisolone. Complete clearing of chest radiographic infiltrates occurred in 65% of the 247 episodes, partial clearing in 25%, and no response in 9%. Blood eosinophil counts were monitored during 194 episodes and returned to normal in 72%, decreased in 19%, and remained raised in 9%. Complete radiological clearing and a reduction in blood eosinophil counts were more common in episodes treated with prednisolone. Long term prednisolone was given to 28 of the 33 patients with allergic bronchopulmonary aspergillosis (mean 7.4 mg/day for 11 years) and to 29 of the 32 "non-aspergillosis" patients (mean 8.1 mg/day for 4.6 years). Initial pulmonary function, measured between episodes, was worse in patients with allergic aspergillosis than in those without (mean % predicted: FEV1 57% v 83%, vital capacity (VC) 76% v 88%). During a mean follow up period of 12 years neither group displayed further decline in FEV1 or VC.

Acute Disease↗
PubMed1988

In vitro activity of eight antimicrobial agents against non-penicillinase-producing gonococci isolated in Munich.

The susceptibility of 119 strains of Neisseria gonorrhoeae isolated in Munich in 1986 to eight antibiotics was assessed. Although some degree of resistance to penicillin and tetracycline, as well as high minimum inhibitory concentrations (MIC) of spectinomycin, were observed, all the strains were sensitive to ciprofloxacin, enoxacin, fleroxacin, cefotaxime, and FCE 22250.

Anti-Bacterial Agents↗
PubMed1987

Atresia of the esophagus. New trends in the management of high-risk neonates.

Once the reconstruction of esophageal atresia in infancy was reported, immediate repair became standard practice. High-risk infants carry an operative mortality of 30% to 80%. Staged surgical procedures were introduced to improve survival. "Delayed" reconstruction of esophageal atresia in selected cases has been reported to improve survival and eliminate staged surgical procedures. Between 1982 and 1986, 21 newborns were diagnosed as having esophageal atresia. Eight infants (32%) underwent "immediate" repair. In 13 infants repair was "delayed" for seven to 252 days. Four neonates with "pure" esophageal atresia underwent primary anastomosis, one was awaiting surgery, and another died in the postnatal period. As more high-risk infants survive the perinatal period, surgical reconstruction must be planned to maximize operative survival. The goal of delayed management of esophageal atresia is to restore intrinsic esophageal continuity.

Abnormalities, Multiple↗
PubMed1987

The effect of fenoldopam, a dopaminergic agonist, on renal hemodynamics.

Fenoldopam, a dopaminergic agonist, was administered intravenously to 18 healthy male subjects in doses ranging from 0.025 to 1.0 microgram/kg/min for 2 hours. Three subjects were studied in a three-way crossover of fenoldopam at doses of 0.025, 0.10, and 0.50 microgram/kg/min. Fenoldopam decreased diastolic blood pressure and increased pulse rate without changing systolic blood pressure. Fenoldopam produced dose-related increases in para-aminohippuric acid clearance up to 75% at the 0.50 microgram/kg/min dose. This increase in renal blood flow was accompanied by increases in urine volume, water, and solute excretion; glomerular filtration rate was unchanged. Doses greater than 0.25 microgram/kg/min caused flushing and nasal congestion. The dopamine receptor antagonist metoclopramide (0.1 mg/kg/hr) did not block the systemic hemodynamic effects of fenoldopam but attenuated the increase in para-aminohippuric acid clearance. Fenoldopam plasma levels achieved steady state between 30 and 120 minutes after the start of the infusion and were linear with respect to infusion rate. Our findings show that intravenous fenoldopam causes systemic arteriolar vasodilation, accompanied by renal vasodilation and increased sodium excretion.

Adult↗
PubMed1987

Effect on the endocrine system of a new dopaminergic agent, ibopamine.

Ibopamine, an oral dopaminergic and adrenergic agent, was given to 19 healthy men to investigate the effect of this dopamine analogue on carbohydrate metabolism. In a three-part study six subjects received ibopamine alone, seven subjects were pretreated with metoclopramide (a dopamine antagonist), and six subjects received phentolamine (an alpha-receptor antagonist) and propranolol (a beta-receptor antagonist) to study the specific mechanisms involved. In these single-blind, controlled, randomized studies, effects on fasting glucose, insulin, glucagon, and prolactin were evaluated. Ibopamine, 300 mg, produced a statistically significant increase in fasting glucose and insulin levels but had no effect on glucagon or prolactin levels. Pretreatment with metoclopramide or phentolamine did not block these effects, but pretreatment with propranolol significantly (P less than 0.05) blunted the increase in fasting glucose and insulin levels. These findings indicate that, unlike other dopaminergic agonists, administration of ibopamine results in increased glucose levels without affecting glucagon. The effect on glucose is mediated through stimulation of beta-adrenergic receptors.

Adult↗
PubMed1987

Proteolytic processing of avian sarcoma and leukosis viruses pol-endo recombinant proteins reveals another pol gene domain.

Three pol gene products have been identified in avian retroviral particles: the full-length 95-kilodalton (kDa) beta chain of reverse transcriptase and two proteolytic cleavage products of beta, a 63-kDa reverse transcriptase alpha chain derived from the amino terminus of beta and a 32-kDa (pp32) endonuclease from its carboxy terminus. By using molecularly cloned retroviral DNA and synthetic oligonucleotides to introduce initiator ATGs and codons corresponding to the authentic N termini, we constructed two bacterial-expression clones; one clone contains the entire pol gene, and the other contains the region encoding the pp32 domain. A 99-kDa protein was synthesized in Escherichia coli by the full-length clone, and a 36-kDa protein was synthesized by the endonuclease domain clone. The recombinant proteins exceeded the size of both the mature viral beta chain and the pp32, respectively, by approximately 4 kDa. These larger sizes, however, are consistent with predictions from the DNA sequence of the pol gene. Processing of the recombinant pol proteins was examined by using p15 protease purified from virus particles and antisera directed against synthetic peptides corresponding to three domains in pol. Proteolytic digestion of the 99-kDa product with p15 produced a 63-kDa protein that comigrated on polyacrylamide gels with the alpha chain of reverse transciptase and a 36-kDa fragment that comigrated with the endonuclease domain product. Further digestion of the 36-kDa protein yielded a 32-kDa protein that comigrated with viral pp32 endonuclease. Thus, we concluded that two p15-sensitive sites exist in pol. Cleavage at the previously identified site produces alpha, and cleavage at the newly discovered site removes approximately 4 kDa from the C terminus of the primary protein product. Since the 36-kDa protein was also detected in protein isolated from virus particles, it seems probable that processing at the C-terminal site is a normal step in the production of mature beta and pp32 endonuclease products.

Amino Acid Sequence↗
PubMed1987

Short term variability in FEV1 and bronchodilator responsiveness in patients with obstructive ventilatory defects.

Short term variability in FEV1 and responsiveness to inhaled bronchodilator were measured in 150 patients with obstructive ventilatory defects. The range of initial FEV1 was 0.5-4.71 and the natural variability over a 20 minute period when expressed in absolute terms was similar over the entire range, and differed insignificantly from that found in normal subjects. The increase in FEV1 and vital capacity (VC) required to exclude natural variability with 95% confidence in these patients was 160 ml and 330 ml respectively. Natural variability when expressed in percentage terms was negatively correlated with the level of FEV1 recorded. The analysis of changes in FEV1 and VC after administration of bronchodilator used absolute and percentage criteria for response. The number of responders differed considerably according to the criterion used. In those defined by the absolute criterion as responders there was no evidence that size of response was related to level of FEV1. Percentage criteria have traditionally been used to identify responses to bronchodilator that may be clinically useful, while absolute criteria, although statistically valid, have not been favoured. Reappraisal of the criteria used and their limitations and implications is required.

Adolescent↗
PubMed1987

Effects of isoproterenol-induced tachycardia on myocardial blood flow and glycogen in the fetal lamb.

In utero tachycardia is a cause of fetal congestive heart failure and fetal hydrops. We investigated the effects of isoproterenol-induced tachycardia (IIT) on cardiac output and its distribution, on myocardial blood flow and intramyocardial blood flow distribution as well as on regional myocardial glycogen in 8 chronically prepared, near-term fetal lambs and 3 control twins (for myocardial glycogen only). Blood flows were measured by the radioactive microsphere method, myocardial glycogen by an enzymatic method. In animals with IIT (heart rate 200-280), cardiac output (excluding lung flow) increased from 0.399 to 0.544 ml/g/tissue/min (+36%), blood flow to the carcass increased from 0.19 to 0.32 ml/g/tissue/min (+68%) and myocardium increased from 2.31 to 7.72 ml/g/tissue/min (+234%), while kidney blood flow decreased from 1.34 to 0.72 ml/g/tissue/min (-46%). The normal intramyocardial blood flow distribution and predominance of flow to the endocardium of both ventricles was preserved during IIT. In the three sets of twins, glycogen was lower in the right (RV) and left (LV) ventricular walls of each animal stressed by IIT (mean RV = 0.19, mean LV = 0.44) than of its unstressed twin (mean RV = 0.75, mean LV = 0.70). Furthermore, a metabolic acidemia (mean pH 7.21, mean BE -8.4) developed in the stressed animals. Although we were unable to demonstrate regional myocardial ischemia at the maximal fetal heart rates achieved by isoproterenol infusion, our data suggest that metabolic acidemia and myocardial glycogen depletion are consequences of severe inotropic and chronotropic stress in the fetal lamb.

Animals↗
PubMed1986

Comparative pathology of prevalent and incident cancers detected by breast screening. Edinburgh Breast Screening Project.

In the Edinburgh Breast Screening Project 210 cancers were detected from commencement in 1979 up to December, 1984. By this time the full initial cohort had completed at least 3 visits and a proportion had attended for up to 5 visits, so pathological characteristics for prevalent and incident cancers could be compared. The main differences are in distribution of histological type of cancer, detection of occult invasive disease, and lymph-node positivity among incident tumours. Only the first of these was statistically significant. This evaluation shows that cancer detection by screening in Edinburgh conforms with screening theory, in which detection of good prognosis tumours is favoured at the prevalence screens, and faster growing, aggressive tumours are found at the incidence screens. Qualitative histopathology may provide a better measure than standard quantitative judgments of size and lymph node status to compare the varieties of cancer detected by screening programmes and to understand the biology of the disease.

Aged↗