bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in density of calcium‐binding‐protein‐immunoreactive GABAergic neurons in prefrontal cortex in schizophrenia and bipolar disorder
Authors: Sakai Tsutomu , Oshima Akihiko , Nozaki Yusuke , Ida Itsuro , Haga Chie , Akiyama Haruhiko , Nakazato Yoichi , Mikuni Masahiko
Published: March 2008

There is evidence that GABAergic neurotransmission is altered in mental disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). The calcium‐binding proteins (CBPs) calbindin (CB), calretinin (CR), and parvalbumin (PV) are used as markers of specific subpopulations of cortical GABAergic interneurons. We examined the postmortem prefrontal cortical region (Brodmann's area 9) of patients with SCZ and BPD, and of age‐matched control subjects, excluding suicide cases. The laminar density of neurons immunoreactive (IR) for three CBPs, namely CB, CR, and PV, was quantified. The densities of CB‐IR neurons in layer 2 and PV‐IR neurons in layer 4 in the SCZ subjects decreased compared with those in the control subjects. When CBP‐IR neurons were classified according to their size, a reduction in the density of medium CB‐IR neurons in layer 2 in SCZ subjects and an increase in the density of large CR‐IR neurons in layer 2 in BPD subjects were observed. These results suggest that alterations in specific GABAergic neurons are present in mental disorders, and that such alterations may reflect the vulnerability toward the disorders.
Transient Blindness Associated with Renal Failure
Authors: Lennon P. A. , Adam W. R. , Bladin P‐ , Coote B. D. , Dawborn J. K. , Greer C. H.
Published: March 2008

Summary: Sudden impairment of vision occurred in five patients with renal failure. In four cases the visual disturbance was attributed to a lesion in the cerebral cortex. In these cases mental confusion and other neurological lesions were present which suggested widespread involvement of the cerebrum. The lesions recovered rapidly suggesting that compression or spasm of cerebral vessels was an important factor in their production. The ocular and neurological signs were largely resolved by correction of the fluid imbalance and control of hypertension but in two cases some visual field defect persisted. In the fifth case visual impairment was initially due to bilateral retinal detachment, later complicated by severe hypertensive retinopathy.
The Relative Contributions of Tubular Reabsorption and Secretion to Urate Excretion in Lead Nephropathy
Authors: Emmerson B. T. , Mirosch W. , Douglas J. B.
Published: March 2008

Summary: Renal tubular reabsorption and secretion of urate have been separately assessed in patients with lead nephropathy by observation of the effect on renal disposition of urate of the drug pyrazinamide, which blocks active tubular secretion of urate. Tubular reabsorption of urate was found to be greater than expected for the degree of renal failure as reflected by the inulin clearance, whereas active tubular secretion of urate was within the range predicted from the plasma urate concentration. As the hypewricaemia of lead nephropathy has been shown to be renal in origin, these results suggest that it is mediated by excessive tubular reabsorption of urate. Though defective tubular secretion of urate has not been demonstrated, more extensive studies over a wide range of plasma urate concentrations would be needed to exclude an additional associated abnormality of the secretory process.
Appearance of Torrential Left to Right Intracardiac Shunt Following Erosion of Stenotic Pulmonary Valve
Authors: Taylor R. R. , Hopkins B. E. , Nicholls T. T. , Matz L. R.
Published: March 2008

Summary: A 30‐year‐old patient had the complex of atrial septal defect, termination of left superior vena cava in left atrium and absence of coronary sinus together with ventricular septal defect and pulmonary valve stenosis. She was symptomatically well with balanced ventricular pressures and small bidirectional intracardiac shunt until erosion of the pulmonary valve occurred. This allowed large left to right shunt flow which induced intractable cardiac failure and led to her death.
Pathophysiology of Parkinson's Disease
Authors: McLeod J. G.
Published: March 2008

Summary: Parkinson's Disease is a disorder of the extrapyramidal system, and its major clinical manifestations are rigidity, tremor and akinesia.

The extrapyramidal system takes origin from the cerebral cortex and from basal ganglia and other subcortical nuclei. It controls movement by its influence on the alpha and gamma motoneurones in the spinal cord through the reticulospinal, vestibulospinal and rubrospinal tracts.

The rigidity of Parkinson's Disease is basically of a plastic type; the cogwheel effect is caused by the superimposed tremor. The increased muscle tone may be caused by an increase in the background gamma efferent activity to the muscle spindles, or by hyperexcitability of the alpha motoneurones.

The frequency of the resting tremor in Parkinson's Disease is 3–5 cycles/sec. It is caused by an imbalance of excitatory and inhibitory activity to the ventrolateral nucleus of the thalamus which results from disease of the substantia nigra and globus pallidus. The spontaneous rhythmical activity is transmitted to the periphery by way of the pyramidal tract and section or disease of this tract will abolish the tremor.

The mechanism of the akinesia, loss of postural control, and gait disturbance in Parkinson's Disease is not clear but is probably related to disease of the substantia nigra, since experimental lesions of the structure result in poverty of movement.
The Past, Present and Future of Surgical Procedures in Parkinson's Disease
Authors: Bleasel Kevin
Published: March 2008

Summary: Effective surgery for the symptoms and signs of Parkinson's Disease began about 1940 when surgery was for the first time directed at the basal ganglia and internal capsule. The initial operations were by open craniotomy and it was not until 1947 that stereotaxic methods originally used by Horsley were applied by Spiegel and Wycis. Their first lesions were made in the ansa lenticu‐laris. From 1953 onwards stereotaxic techniques created lesions in the globus pallidus with success.

Irving Cooper working from a different approach started in 1952 to cause lesions by deliberate occlusion of the anterior choroidal artery, the effectiveness of this depended upon the creation of a lesion in the globus pallidus, internal capsule and thalamic region. Cooper perfected a technique for making chemical lesions in the globus pallidus and later in the lateral ventral nucleus of the thalamus and refined this technique by developing a cryoprobe, which had the advantage of making an initially reversible lesion so that with the patient conscious possible complications could be anticipated and avoided.

At the present time stereotaxic surgery for Parkinson's Disease is a predictable procedure, having a low mortality provided proper case selection is carried out pre‐operatively.

Surgery is effective in abolishing rigidity in 90% of cases and tremor in 75% of cases. It has no effect on the brady‐kinesia and no effect on the bulbar disturbances such as softness of speech or dysarthria. In fact, these may be worsened, particularly in operations on the dominant hemisphere. Disturbances of gait such as locking of gait, slow stumbling gait and disturbances of balance in the form of forward or backward running are not influenced by surgery.

The contra‐indications to surgery are dementia, severe bulbar disturbances, particularly diminished voice volume, and poor health. Hypertension is not necessarily an absolute contra‐indication.

The ideal candidate for surgery is a patient who is still active and employable, who has rigidity predominantly affecting the intrinsic muscles of the hand and who has predominantly unilateral symptoms and signs. Age is better assessed on the physiological age of the patient rather than on an absolute value and patients in early 70's have been successfully operated upon.

Surgery must be directed towards relieving the actual disability of the patient and not merely to the attempted cure of an unsightly tremor. It is likely that there will always be a place for surgery for unilateral disability followed by L‐dopa medication, to control the more generalised features when they arise.
A Summary of Overseas Experience with L‐dopa in Parkinson's Disease
Authors: Fisher A. G.
Published: March 2008

Summary: The use of L‐dopa in the treatment of Parkinson's Disease was based on two observations. The induction of Parkinsonism in man during treatment with reserpine and the reduction in the striatal dopamine in patients dying with involutional and post‐ence‐phalitic Parkinson's Disease.

Experience in using L‐dopa in several overseas centres was surveyed, while the significance of the side‐effects produced by the drug was appraised.

Improvement in the disabling symptoms of the disease was noted in approximately 70 to 80 per cent of patients during extended treatment with L‐dopa.
Clinical Experiences in Oral Antidiabetic Therapy with Sulphonylureas and Biguanides
Authors: Schöffling K.
Published: March 2008

1. Glibenclamide is a highly potent and nontoxic antidiabetic drug.

2. Many patients classified as secondary failures under tolbutamide have shown satisfactory results when given glibenclamide. However, it is still to be determined how long this improvement will last.

3. The three‐year study which has been reported gives evidence of the high potency and the efficacy of glibenclamide.

4. The use of sulphonylureas in combination with biguanides enlarges the group of diabetics who can be treated orally. At present, this combined treatment represents progress in oral therapy.
Pulmonary Function During Clinical Remission of Asthma How Reversible is Asthma?*
Authors: Cade J. F. , Pain M. C. F.
Published: March 2008

Summary: The frequency, range and severity of functional abnormalities during complete clinical remission of asthma were studied in 57 patients. Ninety per cent had abnormal tests, the usual pattern being impaired ventilatory capacity, hyperinflation, maldistribution of ventilation, ventilation/blood‐flow inequality and hyperventilation with norm‐al arterial oxygen tension and gas transfer. If spirometry had been used as the sole screening procedure, nearly one third of patients with abnormal function would have been missed. The measurement of lung volumes appeared to be the most practical way to detect these latter patients. Since there is a poor relation between symptoms and functional abnormalities in asthma, laboratory measurements are an important adjunct to clinical assessment. Although asthma is generally regarded as reversible airways obstruction, the extent of reversibility appears to be frequently incomplete.
Long‐Term Use of Oral Contraceptives: A Study of Chromosomes and Lymphocyte Transformation††
Authors: Fitzgerald P. H. , Pickering Alison F. , Ferguson Deborah N. , Hamer J. W.
Published: March 2008

Summary: Findings from 17 women who had unbroken histories of oral contraceptive use covering 4.5 years or longer were compared to a control group of 18 women, approximately matched for age, who had never used oral contraceptives.

Anomalies of chromosome number and structure in blood lymphocytes, cultured for 48 hours with PHA, did not differ between the two groups. Lymphocyte transformation in response to PHA, as measured by mitotic index and cell uptake of tritiated thymidine, was reduced in oral contraceptive users compared to controls.
Enteric Disease in Young Australian Aborigines
Authors: Gracey Michael
Published: March 2008

Summary: The clinical features are presented of two hundred and fifty‐one (251) Aboriginal infants and children with diarrhoea treated over a recent two‐year period.

Clinical evidence of malnutrition was present in 40 per cent of these patients and 37 per cent were anaemic. Sugar intolerance complicated the clinical course in one‐quarter of the cases. More than one‐half of the patients had enteric pathogens in their stools; they included a wide variety of intestinal parasites and enteropathogenic bacteria.

The clinical pattern of diarrhoeal illnesses seen so commonly in young Aborigines resembles that seen in under‐privileged communities in developing countries. Improvement of this situation will depend on elevation of the presently unsatisfactory standards of living, nutrition, education and hygiene in the Aboriginal population.
Medullary Ischaemia in Experimental Analgesic Nephropathy—The Pathogenesis of Renal Papillary Necrosis*
Authors: Nanra Ranjit S. , Chirawong P. , Kincaid‐Smith Priscilla
Published: March 2008

Summary: Medullary blood flow has been assessed in 29 analgesic‐fed rats and nine matched control animals and has been correlated with renal medullary histological changes and tests of glomerular and tubular function. The animals were gavage‐fed a variety of common non‐steroid anti‐inflammatory analgesic compounds over 20 weeks. Medullary perfusion was significantly reduced in analgesic‐fed animals and was further lowered in animals subjected to hypovolaemic shock. Dehydration, however, did not appear to influence medullary blood flow in analgesic‐fed rats. Medullary ischaemia appeared to be the earliest analgesic induced renal damage and developed before histological renal papillary necrosis. Ischaemia correlated with tests of medullary dysfunction — renal concentrating capacity and sodium conservation, but not with tests of glomerular function. On the basis of these findings the pathogenesis of analgesic induced renal papillary necrosis is discussed.
Leucocyte Histamine Release Studies and Skin Tests with Aggregated γ‐Globulin in Hypogammaglobulinaemia
Authors: Schumacher M. J. , Ellis E. F.
Published: March 2008

Summary: The leucocytes of nine children and adolescents with hypogammaglobulinaemia were tested in vitro for histamine release in response to heat‐aggregated human γ‐globulin. In this system, no histamine release was demonstrable in any of the subjects. Hypogammaglobulinaemic subjects did not differ from controls in their skin reactivity to heat‐aggregated human γ‐globulin, and the cutaneous response to this material could be blocked by an antihistamine, chlorpheniramine.

The results suggest that systemic reactions to aggregated γ‐globulin in patients with immunological deficiency are unlikely to be mediated by intravascular histamine release.
Effect of Prednisolone and Salicylic Acid on Ionic Fluxes across the Human Stomach
Authors: Ivey K. J. , Parsons C. , Weatherby R.
Published: March 2008

Summary: Effect of prednisolone and salicylic acid on ionic fluxes across the human stomach. K. J. Ivey, C. Parsons and R. Weatherby, Aust. N.Z. J. Med., 1975, 5, pp. 408–412.
Successful Use of Combination Chemotherapy in Pure Red Cell Aplasia Associated with Malignant Lymphoma, Histiocytic Type
Authors: Hunt F. A. , Lander C. M.
Published: March 2008

Summary: Successful use of combination chemotherapy in pure red cell aplasia associated with malignant lymphoma, histiocytic type. F. A. Hunt and C. M. Lander, Aust. N.Z. J. Med., 1975, 5, pp. 469–471.
Assessment of Cardiovascular Side Effects of Therapeutic Doses of Tricyclic Anti‐depressant Drugs
Authors: Vohra Jitu , Burrows Graham D. , Sloman Graeme
Published: March 2008

Summary: An assessment of the side effects of therapeutic doses of tricyclic anti‐depressant drugs was attempted in 32 patients with depressive illness. The patients studied had no evidence of clinical heart disease or hypertension and were not receiving any other drugs.

Moderate increase in heart rate and mild prolongation of atrioventricular conduction occurred. No significant effect on the corrected QT interval or blood pressure was found. There was no correlation between the increased heart rate, prolongation of the atrioventricular conduction time (PR interval) and plasma nortriptyline levels measured in 20 out of 32 patients.
Cobalt Chloride in the Treatment of Refractory Anaemia in Patients undergoing long‐term Haemodialysis
Authors: Bowie E. A. , Hurley P. J.
Published: March 2008

Summary: E. A. Bowie and P. J. Hurley, The effect of oral cobalt chloride on the anaemia of patients undergoing long‐term haemodialysis therapy was investigated in 14 patients taking 25 mg then 50 mg daily. After eight weeks of treatment the mean haematocrit increase in 11 patients completing the trial was 23% of the original level and the 51Cr‐red cell volume had increased by 20%. The 51Cr red cell half‐life lengthened after treatment in six patients and the 59Fe plasma half‐time shortened in ten patients. After treatment, evidence of increased erythropoietic activity was seen in the bone marrow of five patients. No evidence was found of thyroid or liver dysfunction but three patients developed transient loss of hearing demonstrated by audiometry. Cobalt chloride appears to be helpful in the management of some uraemic patients with refractory anaemia.
Hepatitis B Antigen, Auto‐antibodies and Liver Disease in a Haemodialysis and Transplantation Unit
Authors: Campion E. C. , Wangei A. G. , Lawrence J. R.
Published: March 2008

Summary: This study concerns hepatitis B antigen and antibody, (HBAg and HBAb) auto‐antibodies and liver disease in a renal haemodialysis and transplantation unit between February, 1970 and December, 1972. Fourteen per cent of patients on maintenance haemodialysis, 25% of renal transplant recipients, and 5% of the staff were HBAg positive during this period. Three family members of antigen positive patients developed hepatitis; all were either antigen or antibody positive.
Guillain Barré Syndrome during the Pre‐icteric Phase of Acute Type B Viral Hepatitis
Authors: Ng P. L. , Powell L. W. , Campbell C. B.
Published: March 2008

Summary: A 54‐year‐old man presented with the Guillain Barré syndrome (GBS) during the pre‐icteric phase of acute type B viral hepatitis. This neurological syndrome has been infrequently described in the clinical course of viral hepatitis but only once previously during the prodromal period. Deposition of circulating immune complexes of the HBsAg have been implicated in the pathogenesis of arthritis, nephritis and poly‐arteritis associated with type B viral hepatitis. Although the relationship of GBS to type B viral hepatitis is uncertain, a similar immunopathological mechanism may be involved.
The Significance of HL‐A W27 in Ankylosing Spondylitis and Reiter's Syndrome with Three Family Studies
Authors: Cross R. A. , Rigby R. , Dawkins R. L.
Published: March 2008

Summary: So as to test the diagnostic significance of tissue typing in an Australian population the HL‐A antigens of forty‐seven patients with Ankylosing Spondylitis and six patients with Reiter's Syndrome were compared with those found in three hundred and six controls. Since HL‐A W27 was found in 92% of the patients with Ankylosing Spondylitis and all patients with Reiter's Syndrome it is concluded that these diagnoses should be questioned if this antigen cannot be demonstrated. In three family studies it was apparent that Ankylosing Spondylitis only occurred in those who had inherited HL‐A W27 so that the absence of the antigen may help to identify those family members who will not develop the disease. Notwithstanding the association demonstrated the data argue against a close and simple linkage between the antigen and these diseases.
Salicylate Therapy and Drug Interaction in Rheumatoid Arthritis
Authors: Barraclough D. R. E. , Muirden K. D. , Laby B.
Published: March 2008

Summary: Salicylate therapy and drug interaction in rheumatoid arthritis.
The Pituitary‐testicular Response to Luteinising Hormone Releasing Hormone Administration to Normal Men*
Authors: de Kretser D. M. , Burger H. G. , Hudson B. , Keogh E. J.
Published: March 2008

Summary: The pituitary‐testicular response to luteinising hormone releasing hormone administration to normal men.

The response of the pituitary and testis in normal men to the injection of LH‐RH has been studied using single intravenous doses of either 25 μg or 100 μg.

Serum LH levels rose with both doses but significant elevation of plasma testosterone was evident only following 100 μg of LH‐RH. Though testosterone levels were elevated within 60 minutes, peak responses occurred from 4–12 hours post‐injection. The rise in serum FSH levels was small or absent at 25 μg but was clearly present following 100 μg LH‐RH, in general rising more slowly than LH levels but persisting for a longer period.
Detection of Synovial Cysts by Transmission‐emission Scintigrams Following Intra‐articular 169Yb‐DTPA
Authors: Adiseshan N. , Johnson F. L. , Buttfield I. H.
Published: March 2008

Summary: A new simple and safe technique for the detection of synovial cysts is described. This investigation employs combined transmission‐emission scintigraphy following intra‐articular injection of 169Yb‐DTPA. Twenty‐two joints were investigated in 18 patients. A high degree of correlation was found between clinical findings and the results of this investigation. The major advantages of this method are low local radiation to synovial linings, adequate visualisation of periarticular soft tissue, and small volumes required for intra‐articular injection.
Ectopic Adrenocorticotrophic Hormone Production and Neoplasm
Authors: Pinerua R. F. , Dunn C. M.
Published: March 2008

Summary: Three patients presented with severe hypokalaemic, hypochloraemic alkalosis, muscle weakness and later cutaneous pigmentation. There were few signs of Cushing's syndrome. Two had bronchial and one pancreatic neoplasm. Plasma cortisol and urinary steroid metabolites were extremely elevated and synacthen stimulation showed significant adrenal capacity even with adrenal metastases. Aminoglutethamide reduced plasma cortisol in two patients.
Changing Results of Treatment of Infarction in a Coronary Care Unit
Authors: Sloman J. G. , Penington Christina , Hunt D. , Duffield Anne
Published: March 2008

Summary: Changing results of treatment of infarction in a coronary care unit.

A comparison has been made between the first 300 patients admitted from 1963 to 1967 to the Coronary Care Unit (CCU) of The Royal Melbourne Hospital with transmural cardiac infarction, and two groups of similar numbers admitted in 1969 and 1974. While the age spectrum and duration of stay of survivors in the Unit has remained similar, there has been a reduction in mortality, most marked in the most recent group of patients. The improvement was seen in all age groups, but was statistically significant only in the patients under 50 years and over 70 years. The reduction occurred in both sexes and was most evident in the patients admitted with severe cardiac infarction.

The improvement in results of treatment is due in part, at least, to improvements in management introduced since 1963.
Plasma Heparin Concentrations during Subcutaneous Heparin Therapy
Authors: Pitney W. R. , Deant Shirley
Published: March 2008

Summary: Plasma heparin concentrations during subcutaneous heparin therapy.

Plasma heparin concentrations were measured at two‐hourly intervals following the subcutaneous injection of varying doses of heparin. With doses of 5000 and 10,000 units, peak plasma concentrations were seen most commonly four hours after the injection. There was a wide range of peak values at both dose levels with considerable overlap and no correlation could be shown between plasma heparin concentration and the age, sex or weight of the individual. Traces only of heparin could be detected in the blood after a WOO unit injection. Comparable results were obtained up to six hours after the injection with either the calcium or sodium salts of heparin.
Smooth Muscle‐associated Contractile Protein in Human and Experimental Acute Leukaemias*
Authors: Toh B. H. , Muller H. K. , Cauchi M. N.
Published: March 2008

Summary: Smooth muscle‐associated contractile protein in human and experimental acute leukaemias.

Cells from ten human myeloblastic leukaemias and from spontaneous rat myeloblastic and lymphoblastic leukaemias were examined by indirect immunofluorescence with human serum containing smooth muscle antibody. Strong positive cell outline staining of blast cells was seen in cryostat sections of rat leukaemic lymph nodes, spleen and liver. In cell smears of human and rat leukaemias, cell outline fluorescence was restricted to cells in close contact with each other. Membrane immunofluorescence tests of suspensions of viable leukaemic cells were negative. Specificity of the immunofluor‐escent staining reaction was established by failure to obtain staining with normal serum, or with smooth muscle antibody serum neutralized by homogenates of smooth muscle or extracts containing actin derived from smooth muscle. These observations suggest that smooth muscle‐associated microfilaments are present in leukaemic blast cells and that expression of the antigen is dependent on cell‐ cell contact. The presence of this antigen may facilitate leukaemic infiltration of tissues.
Hereditary Thrombocytopathy: A Familial Bleeding Disorder due to Impaired Platelet Coagulant Activity
Authors: Ardlie N. G. , Coupland W. W. , Schoefl G. I.
Published: March 2008

Summary: Hereditary thrombocytopathy: A familial bleeding disorder due to impaired platelet coagulant activity.
Spirometric Values for Normal Perth Children aged Six to Twelve Years
Authors: Morton A. R. , Fitch K. D. , Blankstay B. A. , Streatfield P. J.
Published: March 2008

Summary: Spirometric values for normal Perth children aged six to 12 years.
Effect of Prostaglandin E2 on the Healing of Gastric Ulcers: A Double‐Blind Endoscopic Trial
Authors: Fung Wye‐Poh , Karim Sultan M. M.
Published: March 2008

Summary: Effect of prostaglandin E2 on the healing of gastric ulcers: A double‐blind endoscopic trial. Wye‐Poh Fung and Sultan M. M. Karim, Aust. N.Z. J. Med., 1976. 6, pp. 121–122.

A double‐blind trial was performed to assess the effect of prostaglandin E2 on the healing of gastric ulcers. The prostaglandin preparation was given orally in doses of 1 mg, 6 hourly for two weeks to ten subjects with proven gastric ulcer. The control group consisted of ten subjects with proven gastric ulcer, without prostaglandin treatment. Gastric ulcer healing was assessed endoscopically with a duodenofiberscope. The maximum diameter of the ulcer crater was determined endoscopically just before and after two weeks of treatment. In the prostaglandin group, complete healing was seen in two cases, considerable healing (50% and more) in three cases, and the overall mean healing rate was 42%. In the control group, complete healing was seen in none, considerable healing in one case, and the overall mean healing rate was 14.3%. The difference, statistically, was significant. The results show that prostaglandin E2 is effective in promoting the healing of gastric ulcers.
Essential Hypertension—The Starting Point for Improved Drug Treatment
Authors: Boyd G.W.
Published: March 2008

Summary: Essential hypertension—The starting point for improved drug treatment.

Hypertension is a common disease and plays an important role as a potentially remediable contributor to cardiovascular causes of death in the community. In moderate to severe hypertension recent treatment has improved morbidity and mortality substantially, but it is disappointing that despite this myocardial infarction still stands as an important cause of death. In this regard it is encouraging that beta adrenergic blockade may be useful not only in lowering blood pressure, but also possibly in reducing independently the risk of myocardial infarction and/or sudden death in some patients. In mild hypertension the number of patients is large and the possible beneficial effect of treatment less well‐established, so that there is a clear need for further research in order to define patients at relatively high risk in this group.
The Pharmacokinetic Characteristics of Beta‐Receptor Antagonists in Man—Similarities and Differences of Clinical Relevance
Authors: Riess W. , Brechbühler S. , Theobald W.
Published: March 2008

Summary: The pharmacokinetic characteristics of beta‐receptor antagonists in man—Similarities and differences of clinical relevance.

The aliphatic partial structure common to the beta‐receptor antagonists leads to similar products of their biotransformation. The main qualitative and quantitative differences of the metabolism of the compounds of this class, however, rest in the nature of their aromatic or heterocyclic substituents.

The physico‐chemical properties of the beta‐blockers appear to be predominantly responsible for the extent of metabolic degradation and for the distribution in the body, especially for the binding to proteins. As a consequence of their different biological disposition the clinically relevant systemic bioavailabilities of the various beta‐blockers from oral doses differ drastically.

Practolol maintains an extreme position among all other compounds: It is most hydrophilic, it is not bound to proteins, it is metabolized least, but cleared renally in unchanged form to 85% of the dose. Despite its extremely high systemic bioavailability, relatively high daily doses were required for therapy. The receptor sensitivity for practolol has been rated 2 to 3 powers of 10 lower than of propranolol.

Comparative pharmacokinetic assessment of beta‐receptor antagonists requires quantitative analytical data in clinically representative groups of patients. This has been demonstrated by respective studies with oxprenolol. The intra‐and inter‐individual systemic bioavailability, the differential analysis of plasma and erythrocytes, the multiexponential elimination kinetics, and their possible dependence on the dose have been studied as clinically relevant pharmacokinetic characteristics.

The continuing attempt of the pharmaceutical industry to optimize the properties of beta‐blockers also has taken advantage of the slow release principle in oral dosage forms as shown by the example of oxprenolol.

The beta‐receptor antagonists belong to one of the youngest classes of pharmaceuticals. Pharmacokinetic and metabolic data for the different representatives of this class have been generated in different laboratories with different approaches and different techniques. Therefore, full comparative documentation is still incomplete.
Pharmacodynamic Studies on the Antihypertensive Effectiveness of Beta‐Blocking Drugs
Authors: Taylor S. H.
Published: March 2008

Summary: Pharmacodynamic studies on the antihypertensive effectiveness of beta‐blocking drugs.

Beta‐adrenoceptor antagonists are effective antihypertensive agents in the majority of patients with uncomplicated essential hypertension. Their antipressor activity is greater on systolic than diastolic pressure and greatest during dynamic exertion. Their circulatory effects are maximum within 1–2 hours of ingestion and the antipressor effects of a single dose are detectable for over eight hours. Both the immediate and long‐term blood pressure lowering effects of these drugs are dose related. The reduction in exercise systolic pressure is related to the logarithm of the dose of each drug; the reductions in pressure at rest follow no simple mathematical function. There is wide individual variation in the plasma concentrations achieved after a given oral dose, although the averaged values follow a linear regression. There are wide discrepancies between plasma concentration profile and magnitude and duration of antihypertensive activity; blood pressure lowering activity persists for significantly longer than the drug is detectable in plasma. The antihypertensive effects of the beta‐blocking drugs are enhanced during chronic administration without habituation. Their effects are specific but independent of the immediate presence of the drug, i.e. blood pressure lowering activity persists after clearance of the drug from the body. The ancillary pharmacological properties of these drugs neither augment nor detract from their antihypertensive potency, although the possession of intrinsic vasodilator activity enhances reduction in the blood pressure standing at rest. Beta‐blocking drugs add a new dimension to antihypertensive treatment in their specific potential to reduce the coronary consequences of the disease.
Blood Pressure Variability in Patients on Beta‐Blockers
Authors: West M. J. , Honour A. J. , Sleight P. , Littler W. A.
Published: March 2008

Summary: Blood pressure variability in patients on beta‐blockers.

The direct arterial blood pressure was monitored over 24 hours in unrestricted untreated patients in order to obtain the average pressure and standard deviation over 24 hours. The standard deviation was taken as the index of variability of pressure. In eight subjects the study was repeated three months after commencement of treatment with a beta‐adrenergic blocking agent (tolamolol, 300 mg/day). In these subjects tolamolol resulted in a fall in mean blood pressure from 107 to 92 mmHg (P < 0.05) and a fall in heart rate from 82 to 70 beats per minute (P ≤ 0.01). The variability in blood pressure, however, was unaffected by treatment.
A Beta‐Blocker‐Based Antihypertensive Drug Program Guided by Age and Renin
Authors: Bühler F. R. , Lütold B. E.
Published: March 2008

Summary: A beta‐blocker‐based antihypertensive drug program guided by age and renin.

From analyses of the effectiveness of beta‐blocker monotherapy in relation to the patient's age and to pre‐treatment renin determinations an antihypertensive drug program is proposed in which beta‐blockers form the cornerstone.

Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%), or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall into two categories: younger patients with fairly mild hypertension and older patients with more severe hypertension and signs of renal disease.

The antihypertensive efficacy of beta‐blocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, beta‐blockers normalized blood pressure (≤ 95 mmHg diastolic) in three‐quarters of the younger than 40‐year‐olds, in about half of those aged 40–60 years, but in only 20% of those aged over 60 years.

On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state while those with a normal or high renin—for a given age and elevated pressure—have a relatively increased adrenergic nervous activity.

Because the beta‐blockers have a potent suppressive action on the renin‐angiotensin system—and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms—their antihypertensive mode of action may be linked to an important extent, though not exclusively, to renin suppression.
The Vasodilator—Beta‐Blocker Interaction—Some Determinants of its Clinical Success
Authors: Zacest R.
Published: March 2008

Summary:The vasodilator—beta‐blocker interaction—Some determinants of its clinical success.

A number of structurally dissimilar compounds, sharing the ability to induce vasodilatation have come into clinical usefulness as antihypertensive drugs. Their successful utilisation often depends critically on an appropriate combination with diuretics and beta‐blockers. Beta‐blockers can specifically inhibit the reflex cardiac stimulation which otherwise may limit the tolerability and haemodynamic value of these drugs. A synergistic antihypertensive effect has been demonstrated with hydrallazine and propranolol and possibly exists with other combinations.

Generally, vasodilators are not first‐line drugs in chronic therapy but are best added to beta‐blockers.

Variations of the dose‐response and the time‐course of effect are stressed as being important determinants of a successful interaction.
Centrally Acting Alpha‐Adrenoceptor Agonists in Hypertension: Mechanisms and their Role in Therapy
Authors: Dollery C. T.
Published: March 2008

Summary: Centrally acting alpha‐adrenoceptor agonists in hypertension: Mechanisms and their role in therapy. C. T. Dollery, Aust. N.Z. J. Med., 1976, 6, pp. 88–94.

Experimental work in animals has shown that both methyldopa and clonidine lower the blood pressure predominantly by an action on the central nervous system. This action is due to alpha‐adrenoceptor stimulation by clonidine and by alpha‐methyl‐noradrenaline. The evidence for a central site of action for these drugs in man is indirect but persuasive. Both drugs lower blood pressure and heart rate without causing much postural or exercise hypotension. Sympathetic responses like the overshoot of pressure following Valsalva's manoeuvre are reduced but not abolished. Failure of ejaculation in the male is much less common than with drugs that are known to blockade sympathetic adrenergic neurones in the periphery.
Pathology, Aetiology and Pathogenesis of Analgesic Nephropathy*
Authors: Nanra R. S.
Published: March 2008

Summary: 1. The initial site of damage in analgesic abuse is the renal medulla and the characteristic lesion is renal papillary necrosis. The papillary necrosis appears to be an ischaemic infarct. The cortical lesion of chronic interstitial nephritis is a non‐specific change and secondary to obstruction to tubules in the necrotic medulla.

2. Medullary perfusion and the concentration mechanism appear to be important factors in the genesis of renal papillary necrosis.

3. Experimental and clinical studies suggest that abuse of compound analgesics containing aspirin, phenacetin and caffeine result in renal papillary necrosis and the clinical syndrome of analgesic nephropathy. In the APC mixture aspirin appears to be the major nephrotoxic agent while phenacetin plays a synergistic but secondary role in the renal nephrotoxicity.
The Significance of Lowered Jejunal Disaccharidase Levels
Authors: Jennings W. , Rowland R. , Hecker R. , Gibson G. E. , Fitchf R. J. , Reid D‐ P‐
Published: March 2008

Summary: The significance of lowered jejunal disaccharidase levels. W. Jennings, R. Rowland, R. Hecker, G. E. Gibson, R. J. Fitch and D. P. Reid, Aust. N.Z. J. Med., 1976, 6, pp. 556–560.

Disaccharidase estimations on 115 consecutive jejunal biopsies are reported. The patients were divided into four groups:

1. Normal jejunal biopsy light microscopy, not milk intolerant, 82 cases.

2. Normal jejunal biopsy light microscopy, milk intolerant, eight cases.

3. Patients with giardiasis, 11 cases.

4. Coeliac disease patients, 14 cases. The lowest disaccharidase levels were found in coeliac disease, with giardiasis cases showing intermediate levels. Poor correlation of lactase levels with milk intolerance was found. Three cases in Group 1 showing lowered lactase levels were given metronidazole and showed remission of clinical symptoms, raising the possibility that they had undiagnosed infections with Giardia lamblia.
Effect on Respiration of Diazepam, Chloropromazine and Haloperidol in Patients with Chronic Airways Obstruction
Authors: Tandon M. K.
Published: March 2008

Summary: Effect on respiration of diazepam, chloropromazine and haloperidol in patients with chronic airways obstruction. M. K. Tandon, Aust. N.Z. J‐ Med., 1976, 6, pp. 561–565.

The effect on respiration of diazepam, haloperidol and chloropromazine in patients with chronic airways obstruction was studied on ten patients by the modified rebreathing method of ventilatory response to carbon‐dioxide. The two parameters of the ventilatory response studied were:

(a) the slope expressed as litres/minute/ mmHg C02 and

(b) minute ventilation at a computed pCO? 57 mmHg (VE 57).

A significant decrease in either of these parameters indicated respiratory depression. Following administration of 10 mg diazepam intramuscularly to ten patients a significant depression of respiration was observed in five patients. Administration of 50 mg chloropromazine intramuscularly to eight patients significantly depressed respiration of three patients. A significant depression of respiration was not observed in any of the ten patients given 5 mg haloperidol intramuscularly. These results indicate that the lack of significant respiratory depression from an intramuscular injection of 5 mg of haloperidol to patients with severe chronic airways obstruct/on makes it a safer drug, for the management of acute psychotic episodes in such patients, than 50 mg of chloropromazine or 10 mg of diazepam given intramuscularly.
The Haemolytic Uraemic Syndrome and Oral Contraceptives
Authors: Jackson B. , Clarkson A. R. , Seymour A. E.
Published: March 2008

Summary: The Haemolytic uraemic syndrome and oral contraceptives. B. Jackson, A. R. Clarkson and A. E. Seymour, Aust. N.Z. J. Med., 1976, 6, pp.580–582.

A case of haemolytic uraemic syndrome is described in a young woman in whom the illness was apparently precipitated by the change from a low to a high oestrogen containing oral contraceptive agent.
The Role of Immune Complexes in the Pathogenesis of Disease
Authors: Andrews B. S. , Penny R.
Published: March 2008

Summary: The role of immune complexes in the pathogenesis of disease. B. S. Andrews and R. Penny, Aust. N.Z. J. Med., 1976, 6, pp. 591–602.

Circulating antigen‐antibody complexes are incriminated in the pathogenesis of autoimmune and inflammatory disease, and more recently malignancy.

Extensive knowledge of the immuno‐pathological reactions has evolved from the study of experimental serum sickness in animals and of the potential aetiological agents (e.g. viruses) from spontaneous immune complex diseases in animals.

Numerous techniques, both direct and indirect, have now been described to identify immune complexes in serum, though no single technique will identify regularly immune complexes in all clinical situations, nor will it demonstrate the pathogenicity of the immune complex in a given patient.

Human disorders with a definite immune complex basis (glomerulonephritis, systemic lupus erythematosus, rheumatoid arthritis) and others with a possible immune complex basis (e.g. cutaneous vasculitis) are presented.

Management of immune complex disorders is based on removal of the initiating agent if known (e.g. infection, drug, malignancy) or the use of non‐specific antiinflammatory therapy. Specific immunotherapy, in practice and theory, is discussed.
The Effect of Verapamil on Experimental Myocardial Ischaemia with a Particular Reference to Regional Myocardial Blood Flow and Metabolism*
Authors: Smith H. J. , Singh B. N. , Norris R. M. , Nisbet Heather D. , John M. B. , Hurley P. J.
Published: March 2008

Summary: The effects of verapamil on epicardial ST segment elevation, regional myocardial metabolism and collateral blood flow were studied in open‐chest anesthetized dogs following left anterior descending coronary artery occlusion. Collateral blood flow was measured by radioactive microspheres (15 ± 5 μ diameter) and regional metabolism was studied by measuring lactate concentration in venous blood draining the infarcting myocardium. Verapamil (0–2 mg/kg intravenously) produced a significant reduction (50–60%) in the epicardial ST elevation when it was given before coronary occlusion; when administered 15 minutes after coronary occlusion and infusion continued for two hours, it minimized (30–40%) ST segment elevation, and prevented the fall in cardiac index and rise in systemic resistance found in the untreated animals in which the ST segment remained persistently elevated. Changes in epicardial ST segment occurred without alterations in the QRS duration. Verapamil had no effect on either the total collateral blood flow or the relative distribution of flow to the endocardial and epicardial halves of the ischemic ventricular myocardium. No significant differences were found between the levels of lactate in blood sampled from small epicardial veins at the center of the infarct when the control animals were compared with those treated with verapamil.
Lack of Relationship between Viruses and Human Diabetes Mellitus
Authors: Samantray S. K. , Christopher S. , Mukundan P. , Johnson S. C.
Published: March 2008

Summary: Antibodies titres against Coxsackie‐B (CB) and mumps virus (MV) were determined in 180 normal subjects and two groups of diabetics, 236 with diabetes of recent onset (DRO) and 108 with diabetes of long duration (DLD). Positive antibody titres to these viruses were found more frequently in controls than in diabetics. In fact, the percentage of positive titres was significantly less than in controls in several instances particularly in juvenile onset diabetes of long duration. These data suggest that CB and MV are not causally related to human diabetes mellitus.
Plasma Disappearance of Intravenously Injected Radiolabeled Glycocholic Acid in Patients with Liver Disease
Authors: Sewell R. B. , Hoffman N. E. , Ireton H. J. C. , Smallwood R. A.
Published: March 2008

Summary: The plasma disappearance of an intravenously injected tracer dose of glycocholic acid (glycine‐1‐14Cy was compared in patients with and without diffuse hepatocellular disease. No difference was found between the two groups of patients. We conclude that this test is not a sensitive index of the presence of significant liver disease.
Cholesterol and Phospholipid: Influence of Body Weight on the Output of Lipids in Mesenteric Lymph
Authors: Tall A. R. , Mistilis S. P. , Shields R. J.
Published: March 2008

Summary: In ageing humans there is accumulation of cholesterol in adipose tissue, muscle and other organs. In human obesity increased synthesis of cholesterol has been demonstrated.

In order to ascertain possible endogenous sources of lipids, the output of cholesterol, phospholipid and triglyceride from the bile and small intestine was studied in rats in relationship to body weight.

The output of lipid in mesenteric lymph showed an a/most two‐fold increase in the heaviest rats. Small intestinal concentrations of phospholipid and unesterified cholesterol rose significantly with increase of body weight. Output of cholesterol and phospholipid in bile was found to be related to body weight and total bile salt output.

The increased lipid content of mesenteric lymph may reflect lipid synthesis in the small intestine, as well as increased absorption from biliary sources, and contribute to cholesterol accumulation in obese rats.

Although there are major differences between human and rat cholesterol metabolism, the intestine is a major source of endogenous cholesterol in both species, and could be part of the source of the* additional cholesterol load in obese humans.
A Case of Myxoedema Coma Successfully Treated by Low Dose Oral Triiodothyronine
Authors: Graham J. J. , Harding P. E.
Published: March 2008

Summary: Myxoedema coma is fortunately rare and is probably rarer in a warm climate such as Australia. It carries a high mortality rate. Its correct management is still a controversial issue. A case of severe myxoedema coma who was successfully treated is described. Thyroid hormone was replaced in the form of triiodothyronine given orally in doses of 20–40 ng/day. There was an improvement in body temperature within six hours of the first dose; this was accompanied by a brisk fall in serum CPK and cholesterol with a rapid rise of plasma T3 into the euthyroid range. There was a defect in water excretion which was rapidly reversed as renal function returned to normal. Review of the literature suggests that low dose oral therapy with T3 is a satisfactory form of initial management.
Tissue Antigens: Autoantigens, Ailoantigens, Xenoantigens and Neoantigens*
Authors: Whittingham S. , Mackay I. R.
Published: March 2008

Summary: The subject of Clinical Immunology is developing hand in hand with a wide and rapidly moving area of laboratory technology. The result is a better understanding of autoimmune disease, tissue transplantation rejection, foetal‐maternal incompatibility, allergic disease, immunodeficiency disorders, adverse reactions to drugs, aberrant responses to bacterial and viral infections, and growth and spread of malignant cells. Basic to this understanding is the need to appreciate the character and composition of natural substances which act as immunogens and elicit antibodies. These substances have, according to their origin, been classified as autoantigens, ailoantigens, xenoantigens and neoantigens. This review summarizes our knowledge relating to such antigens, emphasizing those aspects relevant to human disease and pointing to the major gaps that future research must bridge.