PLATELET THROMBOPLASTIC FUNCTION IN POLYCYTHÆMIA AND THROMBOCYTHÆMIA

The platelet thromboplastic function levels in patients with primary disease of the bone marrow (polycythæmia vera and primary thrombocythæmia) were compared with the findings in patients whose polycythæmia or thrombocytosis was due to a definable underlying disorder. Of the patients with untreated polycythæmia vera, irrespective of the platelet count, 71% showed reduced platelet thromboplastic function, compared with only 12% of patients with secondary polycythæmia which was uncomplicated by either renal or liver disease. Similarly, the platelet thromboplastic function level was reduced in 100% of patients with untreated primary thrombocythæmia, compared with 47% of patients with elevated platelet numbers secondary to other associated diseases. The platelet thromboplastic function test was therefore useful in differentiating between primary and secondary polycythæmia. Normal platelet thromboplastic function virtually excluded a myeloproliferative disease (thrombocythæmia) in patients with raised platelet counts, irrespective of other hæmatological changes. The effect of ³²P in the two conditions due to primary disease of the bone marrow was to produce a rise towards normal platelet thromboplastic function. It is considered that the platelet defect in primary thrombocythæmia is a qualitative one, and not, as has been reported by others, a quantitative anticoagulant effect of high in-vitro platelet numbers.     

BLOOD-CELL CYCLES IN POLYCYTHÆMIA VERA

Two patients with polycythæmia vera were studied in order to determine whether blood-cell cycles were present. Neutrophil and platelet cycles were found in one and a reticulocyte cycle in the other. The findings suggest that control of cell production by the marrow is partly retained in polycythæmia vera. In contrast to the findings in chronic granulocytic leukæmia, no evidence was found for slowed cellular maturation.     

CYTOGENETIC STUDIES IN CHRONIC GRANULOCYTIC LEUKÆMIA

A review of the literature shows that the Philadelphia (Ph¹) chromosome is present in cells from a majority of patients with chronic granulocytic leukæmia, including 19 presented here. An adequate explanation has been found for the failure to demonstrate the Ph¹ chromosome in all but four cases in the literature. The Ph¹ chromosome has only rarely been reported in other myeloproliferative disorders, and never in other conditions. The positivity in the myeloproliferative disorders is discussed and the probability that the few reported cases are atypical examples of chronic granulocytic leukæmia is considered. The diagnostic value of cytogenetic studies in prognosis and therapy is considered. The conclusion is reached that such studies are of definite but limited value. Theoretical implications of the Ph¹ chromosome are discussed with particular reference to the stem cell, leucopoiesis and chromosome 21, the inter-relationship of the myeloproliferative disorders and the pathogenesis of chronic granulocytic leukæmia.     

THALASSÆMIA MINOR IN AUSTRALIANS OF NORTHERN EUROPEAN EXTRACTION: A REPORT OF FIVE FAMILIES

Five families of heterozygous beta (type 1) thalassæmia minor with elevated hæmoglobin A₂ values and no “known” Mediterranean ancestry are presented. Four families are of Anglo-Saxon origin, and one family is of German descent. All five propositi and an isolated sixth patient with an elevated hæmoglobin A₂ value were referred with hypochromic microcytic anæmia unresponsive to iron therapy. The purpose of this paper is to draw attention to the incidence of thalassæmia minor in Northern Europeans resident in Australia, and to emphasize the importance of full investigation of all cases of iron refractory hypochromic microcytic anæmia, to avoid the over-treatment with iron of persons with thalassæmia minor.     

LEUCOCYTES CONTAINING BACTERIA IN PLAIN BLOOD FILMS FROM PATIENTS WITH SEPTICÆMIA

A search for infected cells was made with the low power (× 10 or × 20) objective in plain blood films from patients known to have, or suspected of having, septicæmia. It was found that scanning of a film in this way for a short time will detect even small concentrations of infected cells. Infected leucocytes occurred in highest concentration in the first drop of blood issuing from the previously unmanipulated ear lobe. They occurred most frequently in films in which there was also an increase in mononuclear cells containing inclusions of corpuscular origin, and were found whether or not the patient had recently been given apparently effective antibiotic treatment. Consideration is given to the requirements for a diagnosis of septicæmia from the presence of infected cells in blood films and the distinction of bacteria from other structures in leucocytes which may resemble them. A search for infected leucocytes in a plain blood film of the first drop of blood from the ear lobe appears to be a useful procedure in routine investigation of patients who may have septicæmia.     

AN EVALUATION OF NUCLEAR ARYL SULPHATASE ACTIVITY AS AN AID TO THE CYTOLOGICAL DIAGNOSIS OF ACUTE LEUKÆMIA

A cytochemical method for the detection of aryl sulphatase in the nuclei of cells was applied to bone marrow smears of 16 children and two adults with leukæmia. Four children with an acute undifferentiated leukæmia were found to have nuclear aryl sulphatase, as seen in acute lymphatic leukæmia. The clinical course of these patients has been similar to that seen in acute lymphatic leukæmia. It is suggested that this test will facilitate a cytological diagnosis in acute leukæmia, particularly in those cases found to be undifferentiated by other criteria.     

HEPATIC FUNCTION IN PATIENTS WITH HYPOXÆMIA DUE TO CHRONIC PULMONARY DISEASE

The effects of chronic hypoxæmia on hepatic function were appraised by routine liver function tests and by a prolonged BSP infusion procedure in patients with chronic pulmonary disease unaccompanied by heart failure. Despite the presence of hypoxæmia sufficient to severely limit exercise, hepatic function was unimpaired. Abnormalities in hepatic function described previously in patients with chronic pulmonary disease by others may have been due to accompanying heart failure.     

SOME CLINICAL AND CHEMICAL MANIFESTATIONS OF ALCOHOL-INDUCED HYPERLIPÆMIA

Some of the clinical features and the values of the plasma lipids of 10 subjects with alcohol-induced hyperlipæmia are presented. The finding of lactescence in samples of fasting plasma from subjects who had been drinking heavily led to the establishment of the diagnosis. The presenting symptoms were abdominal pain in seven cases, coronary heart disease in two and recurrent xanthomatosis in one cases. Pancreatitis was found in three cases, marked hepatomegaly subsiding rapidly after admission of the subjects to hospital in seven, and transient hyperglycæmia in four. The very high concentrations of plasma triglyceride and cholesterol fell rapidly when alcohol intake was stopped. The frequency of finding and the pathogenesis of this disorder are discussed.     

AN ASSESSMENT OF RED CELL SURVIVAL IN IDIOPATHIC UNCONJUGATED HYPERBILIRUBINÆMIA (GILBERT'S SYNDROME) BY THE USE OF RADIOACTIVE DIISOPROPYLFLUOROPHOSPHATE AND CHROMIUM

Red cell survival was determined in 20 patients with idiopathic unconjugated hyperbilirubinæmia without overt signs of hæmolysis (Gilbert's syndrome) by means of a double isotope technique with the use of diisopropylfluorophosphate (DF³²P) and chromium (⁵¹Cr) simultaneously. Red cell life span was significantly reduced in 42% of patients. However, the degree of hæmolysis was not sufficient to produce hyperbilirubinæmia in persons with normal hepatic function. The incidence of familial involvement in patients with reduced red cell survival was not significantly different from that in patients with normal red cell survival. Similarly, there was no difference between the groups with respect to symptomatology, age of onset of jaundice, or results of laboratory investigations. It is concluded that the hyperbilirubinæmia in this syndrome is more likely to be due to a defect in hepatic handling of bilirubin than to compensated hæmolysis. This defect appears to occur whether or not there is a reduced red cell survival. It remains to be shown why some patients with this syndrome have a reduced red cell survival while others do not.     

HYPONATRÆMIA AND RENOVASCULAR HYPERTENSION

A case of traumatic renal artery thrombosis in which the patient developed the hyponatnemic hypertensive syndrome is described. Decreased vascular sensitivity to angiotensin, grossly elevated plasma renin levels, hypertension and hyponatræmia returned to normal after unilateral nephrectomy. Sequential renin and electrolyte studies indicated that this syndrome was caused by the pressor and natriuretic actions of high circulating levels of renin and angiotensin. No evidence could be found to support the suggestion that the high renin levels were secondary to sodium depletion. A positive result to a phentolamine test was recorded, leading to initial problems in diagnosis. The patient is normotensive and well three years after this episode.     

AN ANALYSIS OF HYPOPLASTIC ANÆMIA WITH SPECIAL REFERENCE TO THE USE OF OXYMETHOLONE (”ADROYD“) IN ITS THERAPY

Eight of II patients with refractory anæmia, who required regular blood transfusions to maintain their hæmoglobin level, gave a dramatic clinical and hæmatological response to oxymetholone. Analysis of bone marrow aspirates revealed an overall increase in erythropoietic tissue and mitotic indices following successful treatment with oxymetholone. A significant increase in the incidence of karyomeres was noted in the red-cell precursors in some patients with hypoplastic anæmia. This was interpreted as reflecting abnormalities in mitosis similar to the effects seen after irradiation. Possible factors in the ætiology of aplastic anæmia are discussed.     

CYTOGENETIC STUDIES IN FAMILIAL LEUKÆMIAS

Familial aggregation of chronic granulocytic leukæmia is rare and even the occurrence of chronic granulocytic leukæmia in onto member of a family and another type of leukæmia in a close relative is very uncommon. When such instances occur they provide an opportunity for ascertaining if the Philadelphia chromosome (Ph¹), characteristic of chronic granulocytic leukæmia, is ever an inherited rather than an acquired anomaly. The possible existence of a special liability to other chromosomal aberrations can be investigated in such families. In a man with chronic granulocytic leukæmia whose mother had died of the same disease, the Ph¹ was identified in bone marrow cells and in 50% of the dividing cells of peripheral blood cultured during a period of relapse. No Ph¹-positive cells were identified in a culture of subcutaneous fibroblasts, and so it may be assumed that in this patient the Ph¹ was an acquired and not an inherited chromosomal abnormality. The Ph¹ was not present in cultures of peripheral blood leucocytes or of subcutaneous fibroblasts from a girl with acute leukemia whose father died of chronic granulocytic leukæmia. These studies provide further evidence of the status of the Philadelphia chromosome as an acquired cytogenetic anomaly.     

STUDIES CONCERNING A COMPUTER ANALYSIS OF PATIENTS WITH PRIMARY,SECONDARY OR STRESS POLYCYTHÆMIA

Previously published hæmatological data concerning patients with primary, secondary or stress polycythæmia have been analysed by digital computer. The mathematical model utilized is presented, and the results of the analysis have been related to the clinical and laboratory findings. It is emphasized that different mathematical methods of treating the data may produce variable results. Accordingly, the results of computer analysis should be regarded critically and with an awareness of the limitations of the mathematical methods involved. Complex data are often assembled under less than ideal conditions for subsequent computer analysis. However, the present study concerning previously published hæmatological data indicates that such material may be amenable to certain statistical techniques provided that the subsequent computer results are interpreted carefully. It is further emphasized that computer analysis of any medical data must involve close cooperation between clinician and mathematician if the resultant information is to be regarded as accurate.     

PERNICIOUS ANIEMIA: INCIDENCE AND SIGNIFICANCE OF CIRCULATING ANTIBODIES TO INTRINSIC FACTOR AND TO PARIETAL CELLS

Intrinsic factor antibody was present in 54% and parietal cell antibody in 91% of 95 patients (26 men and 69 women) with Addisonian pernicious anæmia. The incidence of intrinsic factor antibody of 82% in 17 patients tested more than 10 years after diagnosis was significantly higher than the incidence of 47% in 78 patients tested within 10 years of diagnosis. The incidence of parietal cell antibody showed no significant variation with the duration of diagnosed pernicious anæmia. It is suggested that given sufficient time all patients with pernicious anæmia may develop detectable circulating antibody to intrinsic factor.     

CLINICAL AND METABOLIC STUDY OF ALCOHOLIC HYPERLIPIDÆMIA

In a survey of identifiable causes of hypertriglyceridæmia, alcoholic excess seemed to be remarkably common. Accordingly, the mechanism and clinical features of alcoholic lipæmia have been studied in thirteen patients. Alcohol did not decrease peripheral uptake of triglyceride from plasma, as assessed by the intravenous fat-tolerance test. It is suggested that alcohol increases hepatic secretion of lipoprotein, inducing hyperlipidæmia in individuals predisposed by having a relatively low ability to clear triglyceride from plasma.     

DEFECT OF CELL-MEDIATED IMMUNITY IN PATIENTS WITH IRON-DEFICIENCY ANÆMIA

Tests on peripheral blood lymphocytes from twelve subjects with iron-deficiency anæmia revealed an impairment of lymphocyte transformation and migration inhibition factor production on stimulation with candida antigen and purified protein derivative. The intradermal injection of these antigens produces a delayed-hypersensitivity skin reaction in only a minority of iron-deficient subjects. The data suggest that iron deficiency may be a factor in the production or potentiation of immunodeficient states.     

An Evaluation of Aryl Sulphatase Activity in Leukæmic Cells

A histochemical method for demonstrating aryl sulphatase activity in haemic cells has been applied to 22 cases of leukæmia of different types. The difference in distribution of activity in myeloid and lymhatic cells, which has been suggested as an aid in the classification of acute leukæmias, has not been confirmed.     

BENIGN SICKLE-CELL ANÆMIA

Clinical, hæmatological, genetic, chemical, and oxygen-affinity studies have been carried out on a group of 18 Shiite Saudi Arabians with sickle-cell anæmia. Apart from occasional attacks of mild musculo-skeletal pain they are well and have few of the complications which are usual in the sickling disorders. The unusually mild course of the illness is attributable, at least in part, to a genetically determined ability to produce large amounts of fetal hæmoglobin.     

INTESTINAL LYMPHANGIECTASIA WITH HYPOMAGNESÆMIC TETANY

This report concerns a patient suffering from intestinal lymphangiectasia, and recurrent tetany not responding to calcium and vitamin D. Hypomagnesæmia was demonstrated, and the tetany was relieved by magnesium therapy. Measurement of the plasma ionized calcium content showed it to be in the tetanic range. This returned to normal after magnesium infusion, and the tetany was relieved concurrently with this.     

THROMBO-EMBOLISM AND INCREASED PLATELET ADHESIVENESS IN POST-SPLENECTOMY THROMBOCYTOSIS

Platelet count data have been obtained from patients suffering from various types of hereditary hæmolytic anæmia, sideroblastic anæmia and thalassæmia, and from hæmatologically normal controls. One-third of the patients studied had been subjected to splenectomy. Patients with persistent anæmia after splenectomy developed post-splenectomy thrombocytosis. The percentage of platelets which were adhesive was increased after splenectomy irrespective of whether anæmia and thrombocytosis persisted. Six of the 25 patients with persistent post-splenectomy thrombocytosis developed thrombo-embolic complications. On the other hand, signs or symptoms of thrombo-embolism were not observed in any of 21 patients who had normal platelet counts after splenectomy, or in 72 patients suffering from similar disorders who had not been subjected to splenectomy. The cause of the high incidence of thrombo-embolic complications in patients with continuing anæmia after splenectomy is not completely understood, but it seems likely that thrombocytosis and increased platelet adhesiveness may play a part.