The interactions of blood pressure, salt intake and angiotensin converting enzyme (ACE) inhibition were investigated in the Dahl salt-sensitive (DS) and salt-resistant (DR) strains of rats. ...Eight-week-old DS and DR (40 of each) were separately randomized to receive a low- (0.4% NaCl) or a high- (8% NaCl) salt diet for 3 weeks. Thereafter the rats were further separated randomly to receive the ACE inhibitor lisinopril (3-8 mg/kg per day) or no drug treatment for 11 weeks. In untreated DS rats blood pressure rose, paralleled by a higher left ventricular mass (ratio left ventricular weight/body weight) irrespective of salt intake. Lisinopril lowered blood pressure to normotensive levels in all groups except DS rats on a high-salt diet, despite doses of up to 100 mg/kg per day, although there was a significant fall in blood pressure. Lisinopril reduced left ventricular mass significantly on the low- but not on the high-salt diet. Plasma renin activity increased on lisinopril treatment in all groups except DS rats on the high-salt diet. Regression of an increased left ventricular mass by ACE inhibition seemed to be impaired by a high salt intake, even when blood pressure was lowered. Therefore, although for regression of left ventricular hypertrophy, reduction of afterload was the leading factor, this might be adversely affected by a high salt intake.
Two patients presenting with mental subnormality and severe emotional lability were examined for possible inborn errors of metabolism. Amino acid and organic acid analyses of their plasma and urine ...revealed a novel and grossly abnormal metabolism of tryptophan. Basal levels of plasma tryptophan were ten times that of controls and the 24-hour urinary excretion of tryptophan was up to 50 times greater than normal. Both patients excreted about 100 times the normal amounts of indoleacetic, indolelactic and indolepyruvic acids. Administration of oral antibiotic to one of the patients to eliminate intestinal bacteria did not result in any reduction in the excretion of the indoleic acids. The results are interpreted in terms of a possible congenital defect in the normal conversion of tryptophan to kynurenine.
Provision of general anaesthesia in areas remote from the operating room creates many difficult challenges especially if required for repeated radiotherapy in the prone position. This case ...illustrates these problems and some innovative solutions.
A nine-year-old girl with medulloblastoma became extremely distressed whenever cobalt radiotherapy was attempted. Sedation with midazolam and high dose propofol infusion failed to achieve satisfactory conditions and caused concerns regarding airway management. The patient received a total of 37 endotracheal anaesthetics in the prone position using isoflurane in oxygen. Activated charcoal was used to scavenge anaesthetic vapors and adequate gas supplies were assured by connecting an "H' size tank to the oxygen pipeline inlet of the anaesthesia machine. Measurement of isoflurane in exhaust gases using gas chromatography confirmed the effectiveness of scavenging. No serious complications occurred related to repeated anaesthesia.
The methods and equipment described permitted safe delivery of repeated inhalation general anaesthesia for radiotherapy. The same methods could be applied to anaesthesia in other remote locations.
The work described in this thesis has been divided into three sections, namely: 1. "The Latent Heat of Sublimation of Carbon and the Heat of Dissociation of Nitrogen." 2. "The Mass Spectra of Camphor ...and Some of its Halogen Derivatives." 3. "Electron Impact Studies on some Chlorinated Benzaldehydes." In Section 1 a study of the ionization and dissoc-riation of the molecules CX4 (X = F,Cl,Br); CHX3, CH2X2, CH3X (X = Cl,Br) and NH3 was undertaken. Appearance potentials of some of the positive ions produced under electron bombardment were obtained for each compound, while a suitable method was devised for the generation of some of the corresponding free radicals and the measure-sment of their ionization potentials. Dissociation processes were then selected to account for the formation of each ion. Combination of the experimental data in the appropriate equations then gave a series of bond dissoc-siation energies from which the heat of atomization of each compound was obtained. Substitution of this heat of atomization in a suitable thermochemical cycle then all:owed a value for the latent heat of carbon (Lc) or the heat of dissociation of nitrogen, D(N2), to be estimated. Prom the results it was concluded that Lc = 7.386 eV., and D(N2) = 9.756 eV. are most likely to be correct. In Section 2, the "Cracking Patterns" of camphor, α-bromo-, α-chloro-, β-bromo-, β-iodo-, α:α-dibromo- and α:β-dibromo camphors are recorded. An attempt was then made to explain the occurrence of the principal peaks of each spectrum in terms of the current theories of the origin of mass spectra and to interpret the differences in the spectra of the seven compounds with the variation in molecular structure. This has been fulfilled with some modicum of success. Plausible mechanisms, based on such generalizations as facile allylic bond fission, ready elimination of CO and the occurrence of rearrange:ments promoted by the relative stabilities of the fragment ions, have been proposed for the production of the more prominent ions observed. It is emphasized that the results of the present work can only give an indication rather than a conclusive proof of the behaviour of the camphor skeleton under electron impact. In Section 3, the appearance and ionization potentials of some of the ions produced in the electron impact induced dissociation of o-, m- and p- chlorobenzalde-:hydes are recorded. The dissociation energies of the bond between CHO and the aromatic nucleus, D(Ar-CHO), was measured in each case, and compared with that of benzaldehyde itself. It was then possible to interpret the results in terms of the Inductive and Conjugative effects of the substituent chlorine atom. The dissociation energies of the corresponding bond in the molecule ion, D(Ar+-CHO), were also obtained. The relationship between D(Ar-CHO) and D(Ar+-CHO) was discussed, resulting in the tentative proposal that a benzaldehyde type molecule ion may undergo ring expansion to give an ionized derivative of tropone.
A sensitive assay method of furosemide in plasma and urine by high-performance liquid chromatography (HPLC) is described. The minimum measurable concentrations of furosemide in plasma and urine were ...0.2 and 5.0 microgram/ml, respectively; whereas the coefficients of variation of furosemide levels were found to be 7.8% for plasma and 2.0% for urine. These are within the acceptably low limits. Hence, the present method of furosemide is sensitive, reproducible, and accurate for therapeutic drug monitoring. The significance of this HPLC assay method is discussed.
