Treatment of Hereditary Spherocytosis in Peromyscus by Radiation and Allogeneic Bone Marrow Transplantation

An inherited disease of the bone marrow identical in its pathophysiologyto human hereditary spherocytosis has been described in the deer mouse,Peromyscus maniculatus. As Peromyscus are not inbred and of distinct individually-specific histocompatibility, they provide an experimental model system for the use of hemopoietic allotransplantation in the treatment of hereditary diseases of the erythron. Ninety adult mice were exposed to otherwise 100per cent lethal doses of x-rays and then inoculated intravenously with 20 to60 million nucleated marrow cells. Marrow was transplanted on a one-to-onedonor recipient basis in four combinations of phenotypes: normal to normal;spherocytic to normal; spherocytic to spherocytic; and normal to spherocytic.Mortality and pathology were similar in all groups. Thirty per cent of the hostsdied as a direct result of the irradiation within 20 days. Another 30 per centsubsequently succumbed to secondary disease presumably of graft-against-hostorigin, bringing the overall mortality to 60 per cent at the end of 10 weeks. At3 months, however, the hematologic status of the survivors, nearly withoutexception, was of donor phenotype: Genetically spherocytic recipients of normalmarrow contained normal red cells; conversely, wild type recipients of spherocytic marrow had assumed the mutant phenotype. Evidence of chronic grafthost interaction was obtained. By 7 months, six mice in the spherocyticto normal transplant group had reassumed the host hematologic phenotype, but only one animal in the normal to spherocytic group reverted to themutant phenotype.

Submitted on May 24, 1966 Accepted on July 18, 1966     

Applications of ammonium formate-catalytic transfer hydrogenation.

Dehalogenation of chlorine bound to aromatic nuclei has been achieved using ammonium formate-catalytic transfer hydrogenation (AF-CTH) techniques. The use of deuterated ammonium formate as the transfer agent in the CTH process when performed in a deuterated solvent medium results in the predominant formation of the labeled product. Thus, ND₄+ DCOO^- - CTH of [D-Ala², p-ClPhe⁴]-Leu-enkephalin in 80% CD₃COOD/D₂O yielded [D-Ala², Phe (4D)⁴]-Leu-enkephalin. Levels of D-incorporation were measured by fast atom bombardment-mass spectrometry (FAB-MS) and/or by ¹³C n.m.r. spectroscopy. Using D-labeled and unlabeled ammonium formate in stoichiometrically similar reactions, it was concluded that the hydrogenation exhibited a primary kinetic isotope effect. Reactant and product concentrations were determined by amino acid analysis and reversed phase HPLC.     

Patient Acceptance of the Implantable Cardioverter Defibrillator in Ventricular Tachyarrhythmias

Besides surgical problems, recipierifs of implantable cardioverter defibrillators (ICDs) are faced with psychological and social adjustments. Successful ICD therapy is influenced by the patients' perceived concerns regarding device, discharge, changes in life style, and complications. In order to assess patients' acceptance of the ICD, the psychological profile of 57 consecutive patients was evaluated using a specifically designed questionnaire and the State Trait Anxiety Inventory (STAI). The results showed that 20 patients staled fear of ICD discharge, 12 patients revealed physical discomfort due to the device, and limited quality-of-life occurred in 8 patients. Fifty-five of 57 patients answered that it was worth having an ICD device implanted, 30 (53%) patients returned to active life, and 56 (98%) would advise another patient to undergo implantation if necessary. Overall, there was only a slight, but insignificant, decrease in the level of anxiety within the total patient population after ICD implantation. However, a comparison of two subgroups indicated that the state of anxiety was significantly higher in patients < 50 years of age as well as in patients having received > 5 shocks versus those > 50 years of age and having experienced < 5 shocks. In general, the acceptance of the ICD as a tool in managing life-threatening ventricular tachyarrhythmias is high. Besides the increased survival rate, quality-of-life and patient acceptance are important criteria for successful ICD therapy.     

Variants of red cell ǵlucose-6-p-hosphate dehydroǵenase amonǵ Asiatic Indians

Among one hundfed and one unrelated Asiatic Indian males living in the Pacific north-west, five G-6-PD-deficient individuals were identified. The enzyme of three of these individuals was indistinguished elctrophoreticaly and biochemically from the Mediterranean type of deficiency. These individuals originated from the north-western parts of the Indian subcontinent. The enzyme of one individual and that of his subsequently studied beother (G-6-PD Kerala) was found to be simialr to G-6-PD Seattle by k_m G-6-P, k_m TPN, pH optimum, utilization of 2d-g-6P and Gal-6-P and electrophoretic migration rate in Tris buffer, pH 8.8. Electrophoresis on TEB buffer (pH 8.6) however, showed this variant to be different from G-6-PD Seattle, The desirability of using multiple electrophoretic methods in the elucidation of new variants is emphasized by these observations. The third abmormal G-6-PD (G-6-PD West Bengal) was unlike other mutations previously described in having higher-than normal k_m TPN and lower-than-normal k_m G-6-P and a slow electrophoretic mobilty. The identification of the Mediterranean type of G-6-PD deficiency in the north-western part of the Indian subcontinent, together with histrorical and molecular considerations, suggests affiinities of Mediterranean, Near Eastern, and North-west Indian populations.     

Change in HIV-antibody seroprevalence rates in i.v. drug dependent prisoners

In 1985 a high HIV-seroprevalence (44.2%) was found in a cohort of parenteral drug addicted prisoners in Innsbruck, Austria. In a longitudinal study from March 1985 to March 1989 we investigated the epidemiology of HIV-infection as well as possible changes in the drug taking behaviour of this defined population at risk. During the study HIV-seroprevalence rates in drug dependent prisoners showed a statistical decrease to 30%. A concomitant increase in admission to any kind of therapy programmes as well as an increasing change from ‘heavy use’ (mainly taking heroin i.v.) to ‘non-heavy use’ (mainly taking drugs orally) could be noted. The influence of preventive measures, such as comprehensive AIDS-information, special therapy programmes including the methadone substitution programme, and the unrestricted availability of needles and syringes is discussed.     

A Philippino Glucose-6-Phosphate Dehydrogenase Variant (G6PD Union) With Enzyme Deficiency and Altered Substrate Specificity

A variant of glucose-6-phosphate dehydrogenase (G6PD) associated withaltered substrate specificity and severe deficiency of red cell enzyme activitywas found in a Philippino male and in his relatives. The genetic pattern wasconsistent with X-linked inheritance. -Thalassemia was found in the propositusand in several family members, but there was no interaction between G6PDdeficiency and -thalassemia. This G6PD variant has two pH optima, at pH5.5 and pH 9.0, while the normal enzyme is inactive at pH 5.5. The substratespecificity of the variant enzyme is different from any known G6PD variant:2-deoxyglucose-6-phosphate and galactose-6-phosphate are good substrates anddeamino-NADP is a better coenzyme than NADP. Although G6PD activityin the variant red cells was only three per cent of normal, quantitative immunologic neutralization suggested that the specific activity of the variantenzyme might be at least ten per cent of that of the normal enzyme. Thisvariant is named after the place of origin, Gd Union.

Submitted on August 11, 1969 Accepted on October 31, 1969     

Hepatic Glucose-6-Phosphatase Activity in Non-Insulin Dependent Diabetics

ABSTRACT The role of glucose-6-phosphatase (G6Pase) in postreceptional glucose handling in non-insulin dependent diabetics (NIDDs) was investigated by comparing the enzyme values in diagnostic liver biopsy samples with fasting blood glucose (BG), immunoreactive insulin (IRI) and plasma antipyrine half-life (T/2). The NIDDs, treated with sulphonylureas, had elevated serum aminotransferase and alkaline phosphatase values associated with fatty liver with or without fibrosis. G6Pase activity was reduced in the NIDDs compared with subjects who had undergone gallstone surgery (p<0.001), insulin dependent diabetics (p<0.001), and age- and sex-matched non-diabetics (p<0.001). G6Pase was inversely related to BG and antipyrine T/2, but not to IRI or conventional liver function tests. Therapy with phenobarbital and medroxyprogesterone acetate, known inducers, increased G6Pase activity, shortened antipyrine T/2, reduced BG and did not alter IRI, in four NIDDs. Low liver G6Pase activity in NIDDs may hence be one factor underlying the impaired glycemic control.     

EFFECT OF EXTRADURAL ANALGESIA USING BUPIVACAINE AND 2-CHLOROPROCAINE ON INTERVILLOUS BLOOD FLOW DURING NORMAL LABOUR

The effect of lumbar extradural analgmig on intervillous bloodflow (IBF) during labour was studied in 26 healthy parturientsusing an i. v. bolus injection of xenon-133. There was a 19%decrease (n.s.) in mean IBF in six parturients (non-extraduralcontrol group). Mean IBF increased by 37.5% when 0.25% bupivacaine10 ml was used and by 35.2% when 2% 2-chloroprocaine 10 ml wasused (n.s.). When the two extradural groups were combined, themean difference between IBFi and IBF2 was 45± 112 mlmin dl^–1. This increase is statistically significant (P<0.05). The improvement in IBF after extradural block was consideredto be a result of the decreased uterine vascular resistance,as no significant changes were observed in arterial pressure,utenne activity or uterine tone.