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Biomedical subjects

W J Hall

Publications and source records attributed to W J Hall.

At least 109 records · Page 6Linked to original sources

A role for endogneous prostaglandins in the short-circuit current responses to osmolal changes in isolated frog skin.

1. Reduction in osmolality of the Ringer solution bathing the morphological inside of frog skin (by lowering the NaCl concentration) caused a significant increase in sodium transport as measured by the short-circuit current. Pretreatment of the skin with acetylsalicylic acid (2.5 x 10(-4)M) abolished the short-circuit current and open-circuit potential responses to osmolal change.2. The output of prostaglandin-like material from isolated frog skin was increased by incubating the skin in hypotonic Ringer solution.3. The cyclic AMP levels of isolated frog skin were also increased by a reduction in the osmolality of the Ringer fluid bathing the skin.4. Prostaglandin-like material was released both by the separated epithelial and dermal layers of frog skin and the output from both layers, on a unit wet weight basis, did not differ.5. The output of prostaglandin-like material from the separated layers of the skin was substantially greater than from whole skin. Indomethacin (6 x 10(-6)M) reduced the output of this material by more than 90% from both layers.6. The release of prostaglandin-like material from the separated layers of the skin was not altered by a reduction in osmolality of the bathing medium.7. It is concluded that a reduction in the osmolality of the solution bathing frog skin stimulates prostaglandin production and that the increased level of prostaglandins stimulates transepithelial sodium transport by stimulating cyclic AMP accumulation. It is also concluded that the response to osmolal change can only occur in intact skin since separation of the epithelial and dermal layers abolished the increase in the release of prostaglandin-like material to osmolal change. The site of the increased prostaglandin production and the exact nature of the stimulus remain to be determined.

Animals↗

Heterozygous alpha-1-antitrypsin deficiency and respiratory function in children.

We evaluated 224 children from Rochester, New York, families in which at least one parent was heterozygous for alpha-1-antitrypsin (AAT) deficiency by protease inhibitor (Pi) typing. The childhood population included, of the two major heterozygote Pi types, 75 Pi type MS children and 37 Pi type MZ children. This population was evaluated by means of a standardized respiratory questionnaire, physical examination, and pulmonary function tests. Maximal expiratory flow volume curves were obtained with subjects breathing both air and a helium-oxygen mixture. Total pulmonary resistance by the method of forced oscillations was measured at 3, 5, 7, and 9 cps. No differences in respiratory symptoms or physical findings were seen in Pi type MZ and MS children compared to Pi type MM children. However, when pulmonary function tests were evaluated by a matched-pair analysis designed to minimize other genetic and environmental risk factors, Pi type MZ subjects demonstrated statistically significant differences in forced expiratory flow rates and in increased frequency-dependent characteristics of total pulmonary resistance. These abnormalities are similar to those previously described in adult Pi type MZ subjects, and suggest that physiologic abnormalities associated with AAT deficiency are present early in life.

Adolescent↗

Aortoduodenal fistula. Primary repair with saphenous vein patch graft.

A successful primary repair of a fistula between the proximal aortic suture line and duodenum was performed in a 47-year-old man with the use of a saphenous vein patch graft with omental interposition between the aortic repair and the duodenum. Massive local and parenteral antibiotics were given. The patient remains completely well 3 1/2 years later.

Aortic Aneurysm↗

Endogenous prostaglandins, adenosine 3':5'-monophosphate and sodium transport across isolated frog skin.

1. Sodium transport across isolated frog skin, as measured by the short-circuit current, was decreased by acetylsalicylic acid, mefenamic acid, paracetamol and phenylbutazone. Indomethacin (6 X 10(-6) M) had a biphasic effect on the short-circuit current: a transient increase followed by a sustained decrease. 2. The release of prostaglandin-like material from the skin was reduced by acetylsalicylic acid and indomethacin. Paracetamol caused a significant reduction in the short-circuit current response of the skin to low doses of arachidonic acid, but the response to the highest dose tested was not significantly altered. 3. Indomethacin (6 X 10(-6) M) increased the sensitivity of the skin to applied prostaglandin E1. The other prostaglandin synthetase inhibitors did not have this effect. Indomethacin (6 X 10(-6) M) also enhanced the effect of antidiuretic hormone on the short-circuit current. 4. Indomethacin (30 X 10(-6) M) increased the short-circuit current and diminished the response to applied prostaglandin E1. 5. In sulphate Ringer, theophylline increased the short-circuit current and diminished the response to prostaglandin E1. 6. Prostaglandin E1 increased the levels of cyclic AMP in frog skin and these increases preceded the increases in short-circuit current. There was a seasonal variation in the level of cyclic AMP in the skin: the levels in winter exceeded those in summer. There was also a seasonal variation in the cyclic AMP response to prostaglandin E1: the winter response was greater than that in summer. 7. Indomethacin (6 X 10(-6) M) had a biphasic effect on cyclic AMP levels in the skin, an initial increase followed by a decrease. Indomethacin also potentiated prostaglandin E1 stimulated cyclic AMP accumulation. 8. Theophylline increased cyclic AMP levels in the skin and potentiated prostaglandin E1 stimulated cyclic AMP accumulation. 9. Pre-treatment of the skin with theophylline reversed the effects of cyclic AMP on the short-circuit current and open-circuit potential. 10. It is concluded that endogenous prostaglandins help to maintain sodium transport across isolated frog skin and that the effects of E-type prostaglandins on the short-circuit current are mediated by increased cyclic AMP levels. The transient increase in short-circuit current and the increased skin sensitivity caused by indomethacin (6 X 10(-6) M) are attributed to inhibition of phosphodiesterase activity. The failure of theophylline to potentiate the short-circuit current response of the skin to prostaglandin E1 is attributed to alteration of cyclic AMP action on the skin by theophylline.

Acetaminophen↗

Pulmonary mechanics after uncomplicated influenza A infection.

Pulmonary mechanics were evaluated in 13 nonsmoking adults with acute, uncomplicated influenza A/Port Chalmers/73(H3N2) virus infection. Subjects had no evidence of lower respiratory tract involvement on physical examination. Viral and/or scrologic evidence of influenza infection was established for all subjects. Physiologic measurements included forced expiratory rates by spirometry and total pulmonary resistance (RT) measured at 3, 5, 7, and 9 cycles per sec by the oscillometric technique. Subjects were studied at time of acute illness and at 1, 3, and 5 weeks thereafter. Spirometric measurements were initially normal in all subjects and did not change significantly throughout the study. Elevated RT measured at 3 cycles per sec and an abnormal degree of frequency dependence of RT, determined by comparing RT at 3 cycles per sec to RT at 9 cycles per sec, were initially present in 10 of 13 subjects. All 7 of these subjects initially abnormal who were tested 7 days after the onset of illness had abnormal frequency dependence. At 3 weeks, 7 of the 10 subjects initially abnormal continued to have frequency dependence of RT. All but 2 subjects reverted to normal levels by 5 weeks. Frequency dependence of RT indicates that acute influenza infection produces uneven time constants in the airways. A generalized increase in peripheral airway resistance or localized compliance changes could account for these abnormalities. Because these abnormalities persisted well beyond the period of clinical illness, these data imply that asymptomatic mechanical dysfunction of the lungs is a frequent sequela to acute influenza A virus infection. RT measured by the oscillometric method was a suitable noninvasive method for detecting abnormal airway time constants in these subjects with acute upper respiratory diseases.

Adult↗

The prevalence of alpha-antitrypsin heterozygotes (Pi MZ) in patients with obstructive pulmonary disease.

An increased incidence of intermediate deficiency of serum alpha1-antitrypsin resulting from Pi phenotype MZ has been reported in patients with chronic obstructive pulmonary disease (COPD) by some laboratories but not confirmed by others. Prevalence of Pi MZ was determined in patients with COPD among 502 subjects referred to a pulmonary function testing laboratory in a region with low concentrations of air pollutants. Control prevalences were obtained from 930 randomly selected subjects in the same community as well as from patients without COPD referred to the laboratory. Depending on criteria used to define COPD, 155 to 306 subjects had COPD. Pi MZ prevalence in subjects with COPD varied from 1.5 to 4 times the prevalence in the community control group and in the patients without COPD. This difference approached significance or was significant. Because Pi MZ was present in only 3.5 to 4.5 per cent of patients with COPD, Pi MZ is not a major factor in the etiology of COPD in this community. The higher incidence of Pi MZ inpatients with COPD reported by other investigators may be explained by small sample size, bias in selection of study or control population groups, or the development of COPD from interaction between Pi MZ and air pollutants or other factors not present in this community.

Adult↗

Pulmonary abnormalities in intermediate alpha-1-antitrypsin deficiency.

Pulmonary function studies were carried out in a group of asymptomatic nonsmoking adults with intermediate alpha-1-antitrypsin deficiency who were attending an early disease detection unit in Rochester, N. Y. All subjects were identified by specific protease inhibitor (Pi) typing. Fifteen MZ and 14 MS subjects who had never smoked cigarettes were matched by sex and age to MM controls. Spirometry, static lung volumes, and single breath-diffusing capacity were identical in all Pi type groups with no statistically significant differences noted. Maximal expiratory flow volume curves were obtained in all subjects. MZ subjects demonstrated statistically impaired maximal flow rates at 75%, 50%, and 25% of vital capacity compared to their MM controls. Total pulmonary resistance by the oscillometric method was measured at 3, 5, 7, and 9 cycle/s in the same subjects. Increased frequency dependence of resistance (defined as the difference between total pulmonary resistance at 3 cycle/s and 9 cycle/s) was observed in MZ subjects compared to MM controls. No differences were noted by this method in MS-MM pairs. The data suggest that detectable mechanical abnormalities are present in subjects with the MZ phenotype, even in the absence of established risk factors such as cigarette smoking and high air pollution.

Female↗

Amantadine effect on peripheral airways abnormalities in influenza. A study in 15 students with natural influenza A infection.

Amantadine HCl administration has resulted in accelerated resolution of influenza A illness. Prolonged abnormalities in pulmonary function have been described in uncomplicated influenza A. To study the effect of amantadine on these changes, we evaluated young adults with documented natural influenza A with clear chest examinations and X rays. Subjects received placebo or amantadine in random, double-blind fashion. Physiologic studies included maximal expiratory flow volume curves with air and helium-oxygen mixtures. Air flow rates were unchanged in all subjects throughout. Initially, both groups showed comparable decreases in mean helium-oxygen maximal expiratory flow rates. The amantadine group showed accelerated physiologic improvement: significant increase in helium-oxygen flow rates occurred within 7 days (P less than 0.05). The rate of improvement in the helium-oxygen flow rates in the placebo group was not statistically significant. These studies confirm peripheral airways dysfunction after uncomplicated influenza A and suggest that amantadine is associated with accelerated resolution of this dysfunction.

Adult↗

Person-to-person spread of Salmonella typhimurium after a hospital common-source outbreak.

In September, 1973, diarrhoea caused by Salmonella typhimurium developed in 32 people in a Maine hospital. Both epidemiological and microbiological evidence indicated that raw egg beaten in milk ("egg-nog") was responsible for the infection. However, 6 patients and 8 employees had not had egg-nog, and their illness developed after the source of infection had been recognised and removed. Most of these people had had direct contact with an infected patient, and presumably acquired the infection by person-to-person spread. It is concluded that person-to-person spread of S. typhimurium can occur in hospitals and can be a hazard to patients and staff.

Adult↗

The role of prostaglandins in cholinergic neurotransmission in the guinea pig.

Prostaglandins have contrasting effects on neurotransmission at different cholinergic nerve endings. This is a report on the role of prostaglandins in a number of cholinergic preparations from the guinea pig. In the isolated ileum PGE1 (2 X 10(-10) to 5 X 10(-8) M) potentiated the response to electrical stimulation of the cholinergic nerves. PGE1 (10(-7 M) caused an increase in tone followed by a period of transient inhibition of twitch height. Responses to simulation of the ileum with drugs were not potentiated by PGE1. Responses of atropinized or plexus-free muscle to electrical stimulation were also not potentiated by PGE1. Acetylsalicylic acid (2.5 X 10(-4) M) diminished the twitch response and the output of acetylcholine from the ileum. Both effects were reversed by PGE1. Qualitatively similar observations were made on the trachea. It is concluded that prostaglandins facilitate acetylcholine release in the ileum and trachea. PGE1 diminished the effect of vagal stimulation on the heart rate. The response to stimulation of the phrenic nerve was not affected.

Acetylcholine↗

Neoplasms in persons treated with x-rays in infancy: fourth survey in 20 years.

The incidence of neoplastic disease was determined by a mail survey of 2,872 young adults given X-ray treatments in infancy and of their 5,005 nonirradiated siblings. Newly diagnosed benign and malignant neoplasms appeared more frequently in the irradiated subjects than in their siblings or the age- and sex-matched general population of upstate New York. Only thyroid neoplasms occurred in sufficient numbers to permit statistical analysis for the effects on incidence of sex, age, and dose, and of being in a high-risk group (sub-group C). Thyroid cancers developed earlier in life than did benign neoplasms, especially in boys; benign goiters occurred after smaller doses, predominantly in females. Females had a greater risk of developing thyroid cancer than males--2,3 times for females of all ages and 5 times for young adults. Except for young adult females, there was no definite age effect. The risk of cancer (but not of benign goiter) was proportional to the thyroid dose, with a linear risk coefficient of 2.5/year/million people exposed to 1 rad for the entire irradiated population and 4.0 for subgroup C. The high risk of thyroid cancer in subgroup C may be the result of the high percentage of Jews, who had a 3.4-fold greater risk than non-Jews. Young adult Jewish females had a 17-fold increased risk. An incidental observation was an apparent increased incidence of asthma and rare diseases with abnormal immunologic features in the irradiated population.

Adolescent↗

Effect of calcium and vasopressin on the response of frog skin to prostaglandin E1.

1. Prostaglandin E(1) increases sodium transport as measured by short circuit current (SCC) across isolated frog skin whereas calcium, added to the external Ringer fluid, decreases sodium transport. To help establish the site of action of prostaglandin the possible interaction of these two agents on sodium transport has been examined.2. The effect of a standard dose of prostaglandin (0.5 x 10(-6)M) on the short circuit current was tested on paired skins with either zero or high calcium (22.4 mM) in the external Ringer fluid. In ten experiments the responses to prostaglandin (expressed in muA/cm(2)) were not significantly affected by external calcium.3. In another series of experiments the chelating agent, EGTA, was included in calcium-free external Ringer in order to promote greater depletion of skin calcium. The response of these skins to the standard dose of prostaglandin was of the same order of magnitude as that of control skins. The response was not sustained in contrast to that of normal skins and skins in high-calcium fluids.4. In a further series of experiments the reverse procedure was adopted whereby the response of the skin to low and high doses of calcium in the external Ringer was recorded in control conditions and when the skin had responded fully to twice the standard dose of prostaglandin. In addition, the calcium-sensitive current was calculated for each skin in both circumstances. The latter was unchanged on addition of prostaglandin, and graded doses of calcium caused the same degree of inhibition of the short circuit current.5. The results show no interaction between external calcium and prostaglandin and also no need for external calcium in prostaglandin stimulation of sodium transport.6. The findings do not support the concept of chelation by prostaglandin of calcium from critical sites on the skin as the primary mechanism of its action on sodium transport. The results closely parallel those of a similar type of study into the relationship between vasopressin and external calcium on frog skin also.7. When frog skin has responded fully to either prostaglandin E(1) or vasopressin, it shows no response to the other, although removal of calcium from the external Ringer fluid causes a further increase in short circuit current.8. Vasopressin causes a further increase in short circuit current in skins treated with prostaglandin F(1alpha). Prostaglandin F(1alpha) may be a weaker agonist on frog skin than either vasopressin or prostaglandin E(1).

Animals↗