Cytogenetic studies of bone marrow and extramedullary tissues and clinical course during metamorphosis of chronic myelocytic leukemia

Of 33 consecutive patients with chronic myelocytic leukemia, examined during metamorphosis, 82% showed chromosome abnormalities in addition to the Ph1. Aberrations most frequently encountered were +8 (39%), +22q - (30%), and i(17q) (18%). Translocations other than the Ph1 were observed in four cases and - Y clones in four cases. Discrepancies in the cytogenetic pattern between bone marrow and extramedullary tissues or blood were noted in a total of 15 patients. In six cases, transformation occurred in extramedullary organs at a time when it was not present in the marrow. In three cases the bone marrow transformation was preceded by a lymph node blastic infiltrate; in one case, by a skin infiltrate; and in one case, by a subdural blastoma. Clonal abnormalities additional to the Ph1 were identified in the tumor tissue from all these cases. Patients with primary extramedullary transformation tended to have a lower median age at onset of metamorphosis, shorter survival, and higher incidence of chromosome abnormalities than the cases without extramedullary involvement. Patients with only Ph1-positive cells and no other anomalies had a slightly longer duration of metamorphosis and longer total survival. Basophilia and thrombocytopenia were more marked in cases with i(17q) than in the rest of the series.     

Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

Assessment of biomaterials as components of a reciprocating dialyser during canine dialysis

A recently reported device, the sorbent suspension reciprocating dialyser (SSRD), was investigated for use as a test system for biocompatibility of dialyser components. The device is easy to assemble and operate, and allows minimal blood contact with foreign material outside of dialyser components. Its constant pressure/ variable flow rate operation allows quantification of degree of clotting of dialyser versus time. The effect of heparinization of the blood distribution gaskets (BDG) of the device on performance and dialyser lifetime was investigated. Heparin was bound to the surface of polyethylene gaskets by immersion in a solution of tridodecylmethylammonium chloride (TDMAC)-heparin complex for several hours. Gaskets were then assembled in an SSRD which was then used for experimental dialysis in dogs with AV shunts. Dialysers assembled using non-heparinized gaskets were used as controls. Blood coagulation tendency was quantified by the activated clotting time (ACT) and partial thromboplastin time (PTT), and these values correlated with the rate of clotting of the device. Heparinization of the gaskets resulted in the prevention of clotting in the dialyser until the final minutes of dialysis in all cases, in contrast to the constant decay of blood fill volume and evidence of clotting in the non-heparinized cases. However, dialyser lifetime was not significantly increased by gasket heparinization. At normal initial values of ACT (80–95 s) dialyser clotting occurred in 10–15 mia In tests with non-heparinized gaskets and systemically heparinized dogs, values obtained in the ACT test were observed to decrease during dialysis, indicating the disappearance of heparin from the blood. Both ACT and PTT tests show promise as predictors of dialyser lifetime.     

Studies of the antigenicity and allergenicity of phospholipase A2 of bee venom.

The antigenic and allergenic properties of phospholipase A2 (PLA2) and whole bee venom were compared by measuring the IgG and IgE antibody responses in animals and man. Precipitating antibodies raised in rabbits and reaginic and other antibodies raised in mice reacted about equally with both bee venom and PLA. The majority of human sera containing bee venom-specific IgE also contained PLA-specific IgE, although in somewhat lower titers. Similarly, most human sera with significant amounts of total antibodies reacting with bee venom also had antibodies reacting with PLA. Histamine and SRS-a release from leukocytes of sensitive patients followed challenge with whole bee venom and PLA in the majority of instances. However, mediator release from several patients' cells was obtained with bee venom only. These studies suggest that although PLA is a major allergen and antigen in bee venom, significant exceptions in patients' reactivity may limit its potential diagnostic and therapeutic usefulness.     

Leukocyte histamine release in Hymenoptera-allergic patients. Correlation with skin test reactivity and changes following hyposensitization therapy

We have studied 46 Hymenoptera-allergic patients and 11 nonallergic controls by grading the severity of their sting reaction, determining their skin test reactivity, and performing human leukocyte histamine release with a commercial mixed stinging insect extract. A significant correlation was found between increasing severity of sting reaction and increasing skin test reactivity (p < 0.001). In $\text{41}\text{46}$ allergic patients from 15 to 100 per cent release of total cellular histamine occurred, whereas in the 11 nonallergic controls no greater than 10 per cent release of total cellular histamine was observed. Skin test reactivity correlated significantly with cell sensitivity in the allergic patients (p < 0.001). Following hyposensitization therapy, cell sensitivity generally did not change, but significant increases in antigen-neutralizing capacity (A.N.C.) of allergic serum did occur in $\text{11}\text{15}$ Hymenoptera-allergic patients.     

Comparison between isoprenaline infusions and bolus injections to assess β-adrenoceptor function in man,with special reference to cardiac contractility and the influence of autonomic reflexes

The present study was performed to characterize cardiovascular responses to isoprenaline and the influence of autonomic reflexes on these reponses. Nine healthy volunteers received infusions and bolus injections of isoprenaline before and after ‘autonomic blockade’ produced by intravenous atropine 0.04 mg kg^-1 and clonidine 300 μg. Heart rate, blood pressures, systolic time intervals and various echocardiographic measures of cardiac contractility were registered. No significant differences in responsiveness to isoprenaline were seen when infusions were repeated on the same day without ‘autonomic blockade’. After ‘blockade’, Δ responses at 1 nmol 1^-1 isoprenaline (infusions) were increased for diastolic blood pressure and decreased for systolic blood pressure and stroke volume. Bolus injections of 2 μg isoprenaline caused enhanced Δ responses after ‘autonomic blockade’ of diastolic blood pressure, left ventricular diameter in systole, ventricular circumferential fibre shortening, mean posterior wall velocity (V_{mean pw}), stroke volume, systemic vascular resistance, electromechanical systole (QS₂) and pre-ejection period. Systolic blood pressure decreased, in contrast to a small increase without ‘blockade’. These findings are explained by differences in haemodynamic effects of isoprenaline and by the dependence of responses on reflexes when isoprenaline is administered in different ways. When heart rate was increased by bolus doses of atropine, in the presence of β-blockade (propranolol), pre-ejection period and left ventricular diameter in systole were unaffected, and V_{mean pw} and ventricular circumferential fibre shortening showed only small increases (compared with alterations induced by isoprenaline). However, left ventricular ejection time, QS₂ and ejection time (by echocardiography), were markedly dependent on heart rate alterations. Thus, pre-ejection period, left ventricular diameter in systole V_{mean pw} and ventricular circumferential fibre shortening are parameters which can be useful in order to evaluate cardiac β-adrenoceptor sensitivity in vivo in man.     

Plasma steroid concentrations during alternate-day treatment with prednisone

Plasma steroid concentrations were measured in asthmatic children 24 and 48 hours after administration of alternate-day treatment with prednisone, and the results were compared with those of control patients who did not receive corticosteroid treatment as well as those of patients who were treated with prednisone each day. It was found that 24 hours after administration of prednisone in any dose, plasma steroid concentrations were significantly lower than those of the control group. The degree of suppression in plasma steroid concentration was less marked in patients who received treatment on alternate days than in those who received the same doses of prednisone each day. Within 48 hours after administration of alternate-day treatment, plasma steroid concentrations approached the values observed in the control group and were independent of the magnitude of the prednisone dose. Although alternateday steroid treatment was associated with transient and incomplete suppression of pituitary-adrenal function, patients whose therapy was changed from a daily to an alternate-day regimen sometimes exhibited prolonged suppression of adrenal cortical function.     

Functional inhibition and release: unilateral tachistoscopic performance and stereoelectroencephalographic activity in a case with left limbic status epilepticus

During prolonged nonconvulsive unilateral left limbic status epilepticus, a natural model of functional hemispheric inhibition, we performed two tachistoscopic experiments, a lexical decision task associated with a RVF (left hemisphere) superiority and a facial matching task associated with a LVF (right hemisphere) superiority. We found that epileptic activity in the left hemisphere, especially rhythmic high-frequency "tonic" discharges, inhibited performance on the lexical task but not on the facial matching task. This suggests that only cognitive activity in the discharging hemisphere is inhibited. Strikingly, the best performance of the right hemisphere was obtained while the left hemisphere was most inhibited, suggesting a functional balance of inhibition and release.     

Ejaculatory incompetence: a theoretical formulation and case illustration

Three theoretical formulations of ejaculatory incompetence have been proposed in the literature. They include: (1) aversive conditioned inhibition of the ejaculatory reflex, (2) an "autosexual" orientation associated with discrepant levels in the cognitive and physiological dimensions of sexual arousal, and (3) a discriminative learning model. These three models are discussed in relation to their theoretical and therapeutic implications. Clinical data supporting the discriminative view is presented.     

The discovery of neuronopathy and neuropathy as a cause of progressive paralysis in childhood. The historical origins of modern differential diagnosis in neuromuscular disease

The concept of the differential diagnosis has a central place in all clinical medicine. In neurology and paediatrics, evolution of thought concerning the differential diagnosis of the child presenting with symptoms of neuromuscular disease was far in advance of similar diagnostic approaches to problems of infectious, infective and neoplastic disease; and as such forms a significant historical model for the development of modern clinical approaches to the sick or disabled child. The account presented in this paper provides a detailed historical review of the development of thought relating to the causes of neuromuscular disease. Nosological developments concerning diseases of the motor unit can be conveniently classified into three periods: (a) a "state of the art" period to 1850; (b) 1850-1890 - a period of parallel and interdependent advances in both normal neuro-anatomy and neurophysiology, and diseases recognized as variations from such norms. In this era Duchenne was the first to write about the differential diagnosis of the progressive muscular paralysis in childhood; and Gowers was the first to write specifically on the hereditary transmission of this group of diseases; (c) in 1891 was described the first case of childhood neuronopathy recognized as such, and with this development was ushered in the modern era of clinical differential diagnosis of childhood neuromuscular disease. The "splitters" have won the great debate concerning the clinical approach to neurological diseases. The continual further refining of an exact diagnosis is the only way in which a realistic prognosis can be forecast, correct genetic counseling can be offered, and (if the condition is treatable) optimal therapy can be introduced.