Showing papers by "St Bartholomew's Hospital published in 1976"

Graphic representation of pain.

Abstract: Of the different types of visual analogue and graphic rating scales tested in a series of experiments, only two were satisfactory: these were the visual analogue scale and the graphic rating scales used horizontally with the words spread out along the whole length of the line. Other types of scale used gave distributions of results which were not uniform. Unusual distribution of results occurred when patients selected a position adjacent either to descriptive terms or preferred numbers. In some experiments, the distribution of results was determined by the nature of the experiment. Alternation of the ends of a scale did not affect the results. The behaviour of the graphic rating scale was different in patients accustomed to completing it and in those not so accustomed. The results of pain severity measured by these methods showed a very good correlation with pain severity measured by the simple descriptive pain scale. Changes in visual analogue scores also correlated well with changes in simple descriptive pain scores. The visual analogue and graphic rating scales were more sensitive than the traditional simple descriptive pain scale. Most patients could readily use visual analogue and graphic rating scales despite having no previous experience. The failure rate was slightly lower with the graphic rating method. Use of these scales is the best available method for measuring pain or pain relief.

Preparation and properties of mitochondria derived from synaptosomes.

Abstract: A method has been developed whereby a fraction of rat brain mitochondria (synaptic mitochondria) was isolated from synaptosomes. This brain mitochondrial fraction was compared with the fraction of "free" brain mitochondria (non-synaptic) isolated by the method of Clark & Nicklas (1970). (J. Biol. Chem. 245, 4724-4731). Both mitochondrial fractions are shown to be relatively pure, metabolically active and well coupled. 2. The oxidation of a number of substrates by synaptic and non-synaptic mitochondria was studied and compared. Of the substrates studied, pyruvate plus malate was oxidized most rapidly by both mitochondrial populations. However, the non-synaptic mitochondria oxidized glutamate plus malate almost twice as rapidly as the synaptic mitochondria. 3. The activities of certain tricarboxylic acid-cycle and related enzymes in synaptic and non-synaptic mitochondria were determined. Citrate synthase (EC 4.1.3.7), isocitrate dehydrogenase (EC 1.1.1.41) and malate dehydrogenase (EC 1.1.1.37) activities were similar in both fractions, but pyruvate dehydrogenase (EC 1.2.4.1) activity in non-synaptic mitochondria was higher than in synaptic mitochondria and glutamate dehydrogenase (EC 1.4.1.3) activity in non-synaptic mitochondria was lower than that in synaptic mitochondria. 4. Comparison of synaptic and non-synaptic mitochondria by rate-zonal separation confirmed the distinct identity of the two mitochondrial populations. The non-synaptic mitochondria had higher buoyant density and evidence was obtained to suggest that the synaptic mitochondria might be heterogeneous. 5. The results are also discussed in the light of the suggested connection between the heterogeneity of brain mitochondria and metabolic compartmentation.

Inhalation of benzpyrene and cancer in man.

Abstract: Both cigarette smoke and polluted urban air contain very small amounts of benzo[a]pyrene, or BaP, a substance which is carcinogenic to experimental animals if relatively large amounts are applied in certain ways such as skin painting or subcutaneous injection. This suggested the possibility that the BaP in cigarette smoke might account for the high degree of association between cigarette smoking and lung cancer, and it suggested the possibility that BaP poliution of urban air might perhaps increase the risk of lung cancer. Some years ago Wynder and Hoffman found an average of 2.5 pg of BaP in the smoke from 100 American cigarettes smoked mechanically.' The average amount has dropped considerably in more recent years. Based upon this, it would appear that even during a lifetime of heavy cigarette smoking, the concentration of BaP per square centimeter of bronchial tissue over which it might be spread would be extremely small as compared with the dose required to produce skin cancer in mice. The concentration of BaP in the air of large American cities is reported to vary from about 0.3 to 6.0 pgl1,OOO cubic meters in summer and from 6.0 to as high as 74.0 in winter.* The air of British cities is more heavily contaminated with BaP. In some British cities, in winter it varies from 73.0 to as high as 170.0 pgl1,OOO cubic meters of air.g During the course of a year, nonsmokers living in some of these cities probably inhale far more BaP than do heavy cigarette smokers living in rural areas of America. Even so, the amount is extremely low as compared with the amount required to produce skin cancer in susceptible strains of mice, surface area being taken into consideration, Largely because of interest in the possible effects of small amounts of BaP in cigarette smoke and in urban air, we decided to study mortality from lung cancer and other causes among people with very heavy occupational exposure to BaP in air. Roofers and waterproofers are such a group. Sawicki collected air samples in the vicinity of men working in pitch roofing operations and found 14,000 pg of BaP/ 1,000 cubic meters of air (see TABLE 1 ) . Even higher amounts were found in air samples collected close to where a roofer was attending a kettle of hot pitch. Thus it would appear that roofers working with hot pitch are exposed to far greater amounts of BaP than are heavy cigarette smokers living in urban areas.

Human foetal pituitary peptides and parturition.

Abstract: THE pituitary gland produces a family of related peptide hormones (Fig. 1). Adrenocorticotrophic hormone (ACTH), β-lipotropic hormone (β-LPH) and possibly γ-lipotropic hormone (γ-LPH) are produced by the pars distalis. α-Melanocyte stimulating hormone (α-MSH), β-melanocyte stimulating hormone (β-MSH) and corticotropin-like intermediate lobe peptide (CLIP)1, however, are thought to be formed in the pars intermedia2, their being found only in those species in which this structure can be distinguished. They have not been identified in man3. The human foetus, however, does develop a rudimentary pars intermedia which involutes shortly after birth4. We present, for the first time, evidence for the occurrence of peptides resembling α-MSH and CLIP in the human foetal pituitary in the second half of pregnancy, and we suggest that these peptides are the dominant hormones of foetal life, only replaced by ACTH before parturition.

Blast Crisis of Chronic Myeloid Leukaemia (CML): II. CELL SURFACE MARKER ANALYSIS OF ‘LYMPHOID’AND MYELOID CASES

Abstract: SUMMARY. Fourteen cases of Philadelphia chromosome (Ph1) positive chronic myeloid leukaemia in blast transformation have been investigated using cell surface markers. Morphologically eight cases were lymphoid and the remainder myeloid in appearance. All cases were negative with surface markers for thymocytes and T and B lymphocytes. Five of the lymphoid cases reacted with an antiserum specific for acute lymphoid leukaemia (ALL) of non-T non-B type and were also weakly reactive with a lymphocyte reactive antiserum. A sixth patient, whose blast cells were anti-ALL negative (ALL-) at presentation, subsequently developed central nervous system leukaemia with anti-ALL positive (ALL+) blast cells in the CSF. In all cases the leukaemic blast cells showed greatly diminished expression of cholera toxin receptors when compared to granulocytic cells from the chronic phase of CML. This parallels weak or negligible expression of the cholera toxin receptor in ALL and AML. These results suggest that the blastic phase of CML may involve different cellular derivatives of a pluripotential stem cell in which the primary malignant/genetic changes reside. The blast crisis of CML can therefore be heterogeneous with respect to cellular expression and in a significant proportion of patients involves a cell which is by membrane markers and morphological criteria indistinguishable from that seen in the common form of ALL. In these cases the Philadelphia chromosome may be the only distinguishing cellular characteristic.

Protein absorption and ammonia production: the effects of dietary protein and removal of the colon.

Abstract: 1. The effect of increasing dietary protein content on the amount of faecal nitrogen was measured in six normal subjects and five subjects without functioning colons (three with ileostomy and two with ileo-rectal anastomosis). 2. There was a significant inontent in the subjects without functioning colons. 3. In normal subjects with intact colons, faceal N content was found to be lower than that in subjects without colons, and furthermore there was no significant variation with diet. 4. The source of the increase in faecal N with increased dietary protein content in subjects without functioning colons is discussed and the significance of these findings in relation to the efficiency of protein absorption is considered.

CONTROL OF PYRUVATE AND β‐HYDROXYBUTYRATE UTILIZATION IN RAT BRAIN MITOCHONDRIA AND ITS RELEVANCE TO PHENYLKETONURIA AND MAPLE SYRUP URINE DISEASE

Abstract: —The effects of the amino acids (phenylalanine, valine, leucine and isoleucine) which accumulate in phenylketonuria (PKU) and maple syrup urine disease (MSUD), and their analogue α-keto acids (phenylpyruvate, α-keto isovalerate, α-keto isocaproate, α-keto-β-Me valerate) have been studied on rat brain mitochondrial respiration. Both phenylpyruvate and α-keto isocaproate specifically inhibited the oxidation of pyruvate plus malate and β-hydroxybutyrate plus malate by rat brain mitochondria in the presence of ADP. However, no inhibitory effects of similar concentrations of phenylpyruvate or α-keto isocaproate were observed on the isolated semipurified pyruvate or β-hydroxybutyrate dehydrogenases from rat brain mitochondria. The transport of pyruvate and β-hydroxybutyrate across the brain mitochondrial membrane was studied by both uptake and exchange of radioactively labelled substrates. Both these processes were inhibited by phenylpyruvate and α-ketoisocaproate. The results are interpreted as providing evidence for both pyruvate and β-hydroxybutyrate translocases across the brain mitochondrial membrane, and that the inhibition of these systems by phenylpyruvate and α-keto isocaproate may be important lesions in phenylketonuria and maple syrup urine disease respectively.

Effect of epidural analgesia on the glycoregulatory endocrine response to surgery.

Abstract: Plasma concentrations of glucose, insulin, glucagon, cortisol, growth hormone and prolactin were measured repeatedly in ten females undergoing abdominal hysterectomy during general anaesthesia. In addition to general anaesthesia five of the patients had continuous epidural analgesia effective for the first 26 postoperative hours. Plasma glucose was elevated during surgery and postoperatively, but not in patients having epidural analgesia. Insulin was low and unchanged in both groups. Glucagon was unchanged and similar in both groups. Cortisol was lower during surgery in the epidural group, but not postoperatively. Growth hormone increased during surgery in four of five patients receiving general anaesthesia alone, but no changes were observed in the epidural group. Prolactin was greatly elevated in all patients immediately after induction of anaesthesia and then fell rapidly during surgery, similarly in both groups. It is concluded that epidural analgesia can inhibit the hyperglycaemic response to surgical stress, but this effect cannot be uniformly correlated to changes in peripheral plasma levels of insulin, glucagon, cortisol, growth hormone or prolactin.

Blast Crisis of Chronic Myeloid Leukaemia (CML): I. PRESENTATION SIMULATING ACUTE LYMPHOID LEUKAEMIA (ALL)

Abstract: SUMMARY. Seven patients presenting as an acute leukaemia caused difficulty in diagnosis. The lymphoid appearance of the blast cells either initially or during treatment suggested acute lymphoid leukaemia (ALL). In each case the Philadelphia chromosome was shown to be present thus suggesting that these cases were examples of chronic myeloid leukaemia (CML) presenting in blast crisis without a detectable chronic phase. The implications of these findings are discussed and the difficulty in achieving a precise diagnosis in the acute leukaemias is emphasized. Cytogenetic analysis should be carried out whenever the type of acute leukaemia present is of critical importance.

Steroid‐induced atrophy in an animal and human model

Abstract: SUMMARY A ratchet-controlled micrometer screw gauge has been used to measure the changes in skin thickness produced by topical corticosteroids. Measurable thinning of the mouse ear followed repeated daily application of corticosteroids. This response in the animal was used to assess the atrophic potential in a variety of standard formulations. The same compounds were applied to human skin and the changes in thickness measured. Patterns of response and the rank order of thinning obtained from the animal model were found to parallel closely the human results.

Autonomic actions and interactions of mianserin hydrochloride (Org. GB 94) and amitriptyline in patients with depressive illness.

Abstract: The clinical pharmacology of mianserin hydrochloride was studied in patients suffering from a primary depressive illness after steady-state plasma concentration of the drug had been achieved. The results were compared with those found with amitriptyline in both open and double-blind studies. The two drugs are equally effective in their antidepressive effect. Mianserin hydrochloride appears to be free of anticholinergic effects as assessed by the measurement of salivary volume, pupil diameter and the interactions with guanethidine and thymoxamine on the pupil. No peripheral adrenergic interaction as studied by the tyramine dose-pressor-response test were observed in patients treated with mianserin hydrochloride (20 mg three times daily).

The effect of percutaneously absorbed steroids on hypothalamic‐pituitary adrenal function after intensive use in in‐patients*

Abstract: Hypothalamic-pituitary-adrenal (HPA) axis function has been monitored in adults and children who required intensive treatment of their skin disease with topical corticosteroid preparations while in hospital. Evidence of mild suppression of the HPA axis was seen in adults when the more potent topical steroids were used, but recovery of function was rapid when the intensive treatment ceased. In children suppression was still present in twelve of sixteen cases on the 2nd day after treatment with 0-1% betamethasone 17-valerate ointment had stopped, yet in nine cases treated in a comparable manner with 1% hydrocortisone acetate ointment, there was no evidence of impaired HPA axis function.

A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe.

Abstract: 1. A convenient method of preparation of jack-bean urease (EC3.5.1.5) involving covalent chromatography by thiol-disulphide interchange is described. 2. Urease thus prepared has specific activity comparable with the highest value yet reported (44.5 +/- 1.47 kat/kg, Km = 3.32 +/- 0.05 mM; kcat. = 2.15 X 10(4) +/- 0.05 X 10(4)s-1 at pH7.0 and 38 degrees C). 3. Titration of the urease thiol groups with 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) and application of the method of Tsou Chen-Lu [(1962) Sci. Sin. 11, 1535-1558] suggests that the urease molecule (assumed to have mol.wt. 483000 and epsilon280 = 2.84 X 10(5) litre-mol-1-cm-1) contains 24 inessential thiol groups of relatively high reactivity (class-I), six 'essential' thiol groups of low reactivity (class-II) and 54 buried thiol groups (class-III) which are exposed in 6M-guanidinium chloride. 4. The reaction of the class-I thiol groups with 2-Py-S-S-2-Py was studied in the pH range 6-11 at 25 degrees C(I = 0.1 mol/l) by stopped-flow spectrophotometry, and the analogous reaction of the class-II thiol groups by conventional spectrophotometry. 5. The class-I thiol groups consist of at least two sub-classes whose reactions with 2-Py-S-S-2-Py are characterized by (a) pKa = 9.1, k = 1.56 X 10(4)M-1-s-1 and (b) pKa = 8.1, k = 8.05 X 10(2)M-1-s-1 respectively. The reaction of the class-II thiol groups is characterized by pKa = 9.15 and k = 1.60 X 10(2)M-1-s-1. 6. At pH values 7-8 the class-I thiol groups consist of approx. 50% class-Ia groups and 50% class-Ib groups. The ratio class Ia/class Ib decreases an or equal to approx. 9.5, and at high pH the class-I thiol groups consist of at most 25% class-Ia groups and at least 75% class-Ib groups. 7. The reactivity of the class-II thiol groups towards 2-Py-S-S-2-Py is insensitive to the nature of the group used to block the class-I thiols. 8. All the 'essential' thiol groups in urease appear to be eeactive only as uncomplicated thiolate ions. The implications of this for the active-centre chemistry of urease relative to that of the thiol proteinases are discussed.

Clinical significance of plasma chlorpromazine levels I. Plasma levels of the drug, some of its metabolites and prolactin during acute treatment

Abstract: Seventeen acute psychotic patients were studied in the course of chlorpromazine (CPZ) treatment. Blood samples were taken weekly both before and two hours after the morning CPZ dose. Plasma levels of CPZ, CPZ sulphoxide (CPZ SO) monodesmethylated CPZ (NOR1CPZ) and 7-hydroxy CPZ (7OH CPZ) were estimated by gas chromatography. Plasma prolactin, luteinizing hormone, testosterone and oestrogens were measured by radioimmunoassay. Six of the seven patients who showed no clinical improvement had plasma CPZ levels equal to or higher than those of patients who improved. 'Non-responders' has a greater proportion of CPZ SO in pre-dosage samples. The occurrence of parkinsonian side effects was associated with a mean plasma CPZ of greater than 50 ng/ml and a mean plasma prolactin of greater than 30 ng/ml two hours after dosage. The elevation of prolactin preceded the onset of parkinsonian symptoms by 1-2 weeks. There was a significant positive correlation between mean plasma prolactin and mean plasma CPZ levels. The prolactin response may prove a useful index of the central antidopaminergic effect of neuroleptic drugs.

Clinical Significance of Plasma Chlorpromazine Levels II. Plasma Levels of the Drug, Some of Its Metabolites and Prolactin in Patients Receiving Long-Term Phenothiazine Treatment

Abstract: Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolacin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4–6 weeks on placebo and during 6–12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication. Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug.

A comparative study of the effects of glutamate and kainate on the lobster muscle fibre and the frog spinal cord

Abstract: 1 The depolarizing actions of glutamate and its conformationally restricted analogue kainate were investigated on the lobster muscle fibre and the frog spinal cord using intracellular and extracellular recordings, respectively. 2 Bath-applied kainate was less potent than glutamate on the lobster fibre but more potent on the frog cord. From the log-log transformation of dose-response curves it was proposed that more than one glutamate molecule was necessary to activate both the lobster and the frog receptor sites. In the frog, at least three kainate molecules were thought to be required for receptor activation. 3 The ionic dependence of glutamate and kainate responses appeared different for the two tissues. 4 Some possible explanations of the differential tissue sensitivity to kainate are discussed.

The acquisition of Escherichia coli by new-born babies.

Abstract: In discussing the background of these studies the importance of faecal carriage of Gram negative organisms by hospital patients is stressed. In many instances it was shown that transmission is by an oral route. This discussion leads on to an assessment of the dose required forEscherichia coli to implant in the bowel. The difficulties of studying the spread ofE. coli within a faecal specimen are discussed. A number of papers are quoted which show that E. coli are present in the vagina of women and that the acquisition of theseE. coli by babies is related to the length of time that the birth takes, and that there is a relationship between theE. coli found in the faeces of the mothers, the mucus swallowed by the babies at birth and subsequently in the faeces of the babies. Most of the earlier studies quoted deal predominantly with enteropathogenic serotypes, but it was later shown that other serotypes can be similarly acquired by the babies. Although this appears to be the general method by which babies acquire their faecalE. coli, it is well established that they can also be obtained from the environment, hence ward outbreaks of infantile gastroenteritis. Studies on normally delivered babies show that generally two thirds obtain their faecalE. coli from their mothers while the rest appear to pick up environmental strains. Very detailed biochemical and serological studies need to be performed to assess this. Caesarian section babies are generally not likely to become colonized by their mothers' faecalE. coli and studies are described which show that the babies faeces or rectal swabs are usually the first areas colonized and that theE. coli are spread from there. Extensive environmental studies suggest that contaminated hands and uniforms of the nursing staff may be the main vector for transmittingE. coli. There is a wide variety ofE. coli serotypes present in a maternity ward at any time and these are related to the presence of the babies excreting them. A variation in the ability of strains to spread was noted.

Asthma due to inhaled chemical agents--fumes from 'Multicore' soldering flux and colophony resin.

Abstract: Summary Four patients with occupational asthma associated with exposure to soldering flux or hot-melt glue containing pine resin (colophony) were subjected to occupational type inhalation challenge testing. All four gave immediate bronchial reactions to inhalation of the fumes, varying from one breath to 3 min of exposure. The clinical history and provocation test reactions suggest hypersensitivity to colophony fumes.

Sunshine and the geographical distribution of the alleles of the Gc system of plasma proteins.

Abstract: Following the discovery by Daiger et al. (1975) that the Gc proteins of human plasma act as the carriers of vitamin D, the authors have plotted on a world map all available data on the frequency of the allele Gc2, and compared the distribution with that of sunlight. With some exceptions high frequencies of Gc2 correspond to low levels of sunlight and vice versa. Similar comparisons within Ireland show no such relation. The results are discussed in relation to natural selection and the incidence of rickets, due to vitamin D deficiency.