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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 1,117 records · Page 62Linked to original sources

Campylobacter pyloridis in peptic ulcer disease: microbiology, pathology, and scanning electron microscopy.

After the recent successful isolation of spiral organisms from the stomach this paper presents the bacteriological and pathological correlation of gastric antral biopsies from 51 patients endoscopied for upper gastrointestinal symptoms. Campylobacter pyloridis was cultured from 29 patients and seen by either silver staining of the biopsy or scanning electron microscopy in an additional three. The organism was cultured from 23 of the 33 (69%) patients with peptic ulcer disease and from within this group 17 (80%) of the 21 patients with duodenal ulceration. It was cultured only once from the 12 normal biopsies in the series but from 27 of the 38 (71%) biopsies showing gastritis. C pyloridis was also cultured from five out of seven of the 14 endoscopically normal patients, who despite this had biopsy evidence of gastritis. It was the sole organism cultured from 65% of the positive biopsies and scanning electron microscopy invariably revealed it deep to the surface mucus layer. C pyloridis persisted in the three patients with duodenal ulcers after treatment and healing. The findings support the hypothesis that C pyloridis is aetiologically related to gastritis and peptic ulceration though its precise role still remains to be defined.

Campylobacter↗

Treatment delay in patients with bladder tumours.

Previous work has shown that the hospitals are the most important source of delay in treatment of bladder cancer rather than the patient or the general practitioner. We have studied referral of patients for investigation and treatment in the North West Region using data from the cancer registry. Delay in treatment for this disease is appreciably longer than for the other common cancers we have studied. Various factors associated with speed of treatment are discussed.

Adult↗

The teaching of medical ethics.

Students at Newcastle are exposed to patients during their first week at medical school and attached to a family within the first month. The object is to sensitise them to patients as people rather than vehicles of disease. Medical ethics is introduced as part of the multidisciplinary Human Development, Behaviour and Ageing Course by a lecturer who shows a film which poses an ethical problem. At subsequent tutorials led by the Department of Family and Community Medicine's general practitioner lecturers the subject is discussed as ethical issues arise in the course of their work.

Bioethical Issues↗

The effect of procaterol treatment on beta-adrenergic bronchodilation and polymorphonuclear leukocyte responsiveness.

Procaterol is a new and effective beta-adrenergic bronchodilator. To determine if procaterol administration could cause tachyphylaxis, airway and leukocyte beta-adrenergic function were monitored in 10 patients with asthma during two 4-wk, double-blind treatment periods, each preceded by a 2-wk beta-agonist washout. Treatment periods were randomized to placebo or procaterol (2 wk, 0.1 mg/day; 2 wk, 0.2 mg/day). At each 7 biweekly evaluations, the patient's cumulative bronchodilator dose-response to inhaled isoproterenol (0.1 to 0.64%) was measured, and venous blood was collected to quantitate, in vitro, the polymorphonuclear leukocyte (PMN) beta-adrenergic receptor's 125Iodo-cyanopindolol (125I-CYP) ligand binding and the PMN cyclic AMP response to isoproterenol and procaterol. Neither the airway nor leukocyte beta-adrenergic characteristics were changed during placebo treatment. Procaterol treatment reduced (p less than 0.05) the maximal 125I-CYP binding to PMN membranes but only during the initial 2 wk at low dosage. The percent PMN cyclic AMP increase to procaterol (10(-5) M) was also significantly (p less than 0.05) less during active treatment (141 +/- 40%) than during washout (256 +/- 24%) or placebo (257 +/- 32%). In contrast, procaterol treatment did not alter the acute isoproterenol bronchodilation response as measured by either the percent improvement in FEV1 or the dose required to produce 50% maximal bronchodilation. The duration of bronchodilation was not measured. Therefore, although procaterol therapy of asthma is associated with decreased PMN beta-adrenergic function, airway smooth muscle function appears not to be altered.

Adult↗

Aortic coarctation in the first three months of life. An anatomopathological study with respect to treatment.

Operation for coarctation in infancy is a lifesaving procedure, but it still carries a high mortality and is followed frequently by recurrence of stenosis. This is especially true when the procedure is performed in the first 3 months of life. To determine a correlation, if any, between anatomy of coarctation and surgical procedures, we have studied a series of 42 autopsy specimens from patients younger than 3 months who had aortic coarctation. We found that concepts of coarctation based solely on a discrete lesion or isthmic hypoplasia were simplistic. The anatomy was much more complex, the findings being relevant to surgical techniques currently in use (resection and end-to-end anastomosis, subclavian flap aortoplasty). Of equal significance in the cases we studied to the presence of a shelf of ductal tissue within the aortic lumen or hypoplasia of a segment of the arch was the finding of "waist" lesions. In these cases the wall of the aorta was constricted to form the obstruction. Such "waists" coexisted with discrete shelves or with shelves and isthmic narrowing. While we recognize the danger of extrapolating from autopsy findings to predict clinical results, our observations suggest that surgical procedures might best be tailored to the precise anatomy present. It seemed that in may cases a subclavian flap procedure offered the best chance of success. Cases with anatomy suitable for resection and end-to-end anastomosis were less frequent. Percutaneous angioplasty seemed at best to offer only palliative options in limited cases.

Age Factors↗

A randomized trial of antihuman thymocyte globulin versus murine monoclonal antihuman T-cell antibodies as immunosuppressive therapy for aplastic anemia.

A prospective randomized trial was undertaken to compare the efficacy and toxicity of murine antihunman T-cell monoclonal antibody (mcAb) therapy to that of horse antihuman thymocyte globulin (ATG) in the treatment of severe aplastic anemia (AA). Patients were randomized into one of the two treatment groups as well as to receive or not receive androgens. Median duration of aplasia prior to treatment was 1.5 and 2.2 months for the mcAb and ATG groups, respectively. One of 12 patients who received mcAb therapy had a partial response, whereas four of 13 patients receiving ATG had a complete or partial response. Of the 11 patients who failed mcAb treatment, six were subsequently treated with ATG and two improved. Ten of 13 patients who received ATG are surviving compared with seven of 12 patients who received mcAb. Toxicity of mcAb therapy was less than that of ATG. Future studies are needed to determine whether mcAbs known to be immunosuppressive are of benefit as therapy for patients with AA.

Adolescent↗

Recent advances in the use of microspheres for targeted therapy.

In recent years the concept of using small colloidal particles for the selective delivery of drugs has been explored experimentally using a variety of different physical systems (for example, phospholipid vesicles (liposomes), triglyceride emulsions, albumin microspheres) and routes of administration. In such studies the aim has been to target a potent pharmacological agent on an organ or tissue site, thereby reducing adverse reactions and side-effects, or to provide a means of controlled release. The design of appropriate delivery systems must take into account the nature of the target and physiological barriers to targeting as well as factors such as drug loading and drug release, stability of the carrier system and its biocompatibility and biodegradation. Targeting with microspheres can be divided into passive methods that rely upon physiological and physicochemical determinants such as entrapment in capillary beds (lungs - particle size) or uptake by phagocytic cells (liver-surface characteristics), an active method whereby the particle is directed to a specific site through the use of surface coatings (surfactants, glycolipids, monoclonal antibodies) or a material sensitive to an external influence. Candidate systems presently under study are described. These include lipid emulsions for intravenous administration and microspheres for intra-articular delivery.

Adrenal Cortex Hormones↗

Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase.

The mechanism of porphyrin accumulation by tumours is not yet established. If metabolism aids porphyrin elimination, tumours, unlike normal tissues, may not metabolize porphyrins used clinically, such as proto-, haemato-, OO'-diacetyl-haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin. Proto-, haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin are substrates for the mitochondrial enzyme ferrochelatase (EC 4.99.1.1), which can form haem analogues from exogenous porphyrins. The Km values for proto-, haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin are 11, 22 and 23 microM respectively. However, OO'-diacetyl-haematoporphyrin is an effective competitive inhibitor with Ki of 11 microM. Hepatic ferrochelatase specific activity is 5.9 and 5.5 nmol of haem/h per mg of protein respectively in normal Buffalo rat and in those bearing the extrahepatic Morris 7288C hepatoma, and is only 0.13 nmol/h per mg in the hepatomas. Therefore low ferrochelatase activity in cancerous cells may provide one means whereby some porphyrins accumulate in tumours, and the ability of certain porphyrins to act as ferrochelatase inhibitors may provide another.

Animals↗

Homozygous cystinuria in New South Wales. A study of 110 individuals with cystinuria ascertained by methods other than neonatal screening.

Homozygous cystinuria was ascertained in 110 individuals (44 men) from 78 families because of symptoms in the propositi. The most common renal symptoms were calculi which occurred in 91% of the propositi and in 52% of affected family members. One-third of patients had urinary tract infections. There was a high rate of renal morbidity at an early age; 16 patients had undergone nephrectomy at a mean age of 25 years (range, 12-40 years). Two-thirds of subjects had type I cystinuria on family testing--the same ratio as that reported in a previous study of cases detected by newborn screening in the same population--which eliminates genetic type as a risk factor for stone formation. On the basis of all data, a 62% probability of stone formation by the age of 25 years in patients with cystinuria was estimated. The patients were shorter than Australian controls, and an association between gout and cystinuria was found in adult men.

Adolescent↗

Domain structure of rabbit hemopexin. Isolation and characterization of a heme-binding glycopeptide.

Plasmin preferentially cleaves rabbit hemopexin at a single site, generating two nondisulfide-linked carbohydrate-containing fragments. In contrast, heme-hemopexin is almost totally resistant to this enzyme and is more resistant than the apoprotein to digestion by trypsin, chymotrypsin, papain, subtilisin, and proteinase K as well. Plasmin digestion dramatically shortens the plasma clearance time of the molecule. The larger glycopeptide (I), shown to be derived from the amino terminus of the parent molecule by sequence analysis, has a molecular weight near 35,000 with a pI of 5.0. It binds 1 mol of heme per mol in a manner analogous to intact hemopexin, molecular weight near 60,000 and pI 5.8. The smaller glycopeptide (II) has a molecular weight near 25,000, a pI of 6.4, and does not bind heme. Of the four oligosaccharides of rabbit hemopexin, peptide I contains three oligosaccharides and peptide II contains one. At micromolar concentrations, the two peptides migrate together during centrifugation through sucrose gradients in the presence, but not in the absence, of heme. Peptide I has a far UV circular dichroism spectrum indicating it has some alpha-helical and extensive nonrepeating peptide structures whereas peptide II appears to be almost exclusively in a beta-sheet conformation. Peptide II is responsible for most of the positive ellipticity at 231 nm of native apohemopexin, but the increase in ellipticity at 231 nm characteristic of heme-hemopexin is not seen when peptide I binds heme, even in the presence of peptide II.

Amino Acid Sequence↗

Hemopexin-mediated heme uptake by liver. Characterization of the interaction of heme-hemopexin with isolated rabbit liver plasma membranes.

Plasma membranes isolated from rabbit liver retain the ability to interact specifically with heme-hemopexin. In this system, apohemopexin does not compete effectively with heme-hemopexin for binding. The membranes bind heme-hemopexin complexes with high affinity (KD = 6.8 X 10(-7) M) and with an apparent capacity of 2.3 pmol/mg of membrane protein. These membranes also retain the ability to remove heme from heme-hemopexin. The release of heme reaches a plateau after 15-30 min at 30 degrees C and does not involve metabolic energy, proteolysis of hemopexin or pH gradients. The apohemopexin formed is rapidly released from the membranes. The accumulation of heme is saturable and is affected by pH and temperature with maximum uptake occurring between pH 5.5 and 6.5 and at 30 degrees C. Interestingly, much more heme (approximately 25 pmol/mg of membrane protein) is accumulated than hemopexin at saturation, implying that the receptor can turn over several times and that a heme-binding component exists in the rabbit liver plasma membrane.

Animals↗

Health centres.

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Community Health Centers↗

Specificity of a cytochemical bioassay for arginine-vasopressin and its validation for plasma measurement.

The total Na+/K+ ATP-ase activity of the thick ascending limb of the loop of Henle may be stimulated by arginine-vasopressin (AVP). Lysine-vasopressin (LVP), oxytocin (OT), and arginine-vasotocin (AVT) produce less than 5% of the enzyme activity induced by the same concentration of AVP. Physiological concentrations of a mixture of other hormones with known activity on the kidney (T3, T4, aldosterone, angiotensin II, and OT) did not significantly increase total Na+/K+ ATP-ase activity. Specific AVP antiserum consistently removed greater than 90% of the stimulatory effect of plasma. The concentration of AVP in plasmas from dehydrated subjects was greater than 10 times that of the same subjects hydrated. Intra-assay coefficient of variation was 35% and 52% from 200 microliters and 20 microliters of plasma respectively. The interassay coefficient of variation was 53% and 55% from plasma pools with high and low AVP content.

Animals↗