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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 19 recordsLinked to original sources
PubMed1992

A reinvestigation of thirty three fragile(X) families using probe StB12.3.

We have reinvestigated 33 fragile X families using probe StB12.3. In 31 families the affected individual showed an insert while in 2 families no insert was detected. The insert fell into two size categories: small (less than 0.5 kb); and large (greater than 0.6 kb) accompanied by methylation of an EagI site. All individuals of either sex having a small insert were fra(X) negative and intellectually normal, while all males having a large insert were fra(X) positive and intellectually impaired. Females having a large insert were either fra(X) positive or negative and either intellectually normal or impaired. No new mutation was found. All daughters of males with a small insert had a small insert; females with a large insert produced males and females who had a large insert, while females with a small insert had offspring with either a large or a small insert. However, females with a small insert tended to fall into one of two categories: either they had only children with a small insert or only children with a large insert, there being only one exception to this rule. We found four unexpected small inserts, two in unrelated spouses and two in female carriers who proved to be compound heterozygotes, indicating that they had inherited an insert from both their parents. These observations suggest that individuals with a small insert must be not uncommon in the general population.

DNA Probes↗
PubMed1992

Splenectomy in the chronic myeloproliferative syndromes. A retrospective risk-versus-benefit analysis.

The effect of splenectomy on the course of the chronic myeloproliferative syndromes was retrospectively analysed and compared in 96 patients who underwent this procedure and 195 who did not. The operation had a 4% mortality and a 47% morbidity rate, mainly attributable to haemorrhage, infection and respiratory complications. While splenectomy conferred benefit in certain selected cases with hypersplenism, there was no significant overall improvement in the postoperative haematological values and no influence on the rate of blastic transformation. Splenectomy did not improve survival in the group as a whole, or in any subset (P greater than 0.5). In the non-splenectomy group, only a minority of patients experienced massive progressive splenomegaly and in most individuals the spleen size varied little from the time of presentation to death. Splenectomy in patients with the chronic myeloproliferative syndrome carries a significant mortality and has a high morbidity, does not reduce the rate of blastic transformation and has no influence on survival. The majority of patients on conventional therapy do not experience the discomfort of massive splenomegaly during the course of their disease and the routine use of this operation is inappropriate.

Adolescent↗
PubMed1992

Antilymphocyte globulin and high-dose methylprednisolone improve survival in patients with aplastic anaemia without additional financial costs.

The cost-benefit ratio in the treatment of aplastic anaemia with antilymphocyte globulin (ALG) combined with high-dose methylprednisolone (HDMP) was retrospectively compared with supportive palliative treatment alone. Over a 4-year period financial cost, response rate, survival and performance status was documented in 26 consecutive patients receiving this regimen. Outcome was favourable in 69% (group 1; N = 18) and in 13 comprehensive expenditure data were available. In the remainder (group 2; N = 8) treatment failed and they were considered to be the equivalent of a no-treatment population. Here hospital charges were analysed both with and without inclusion of ALG and HDMP. Over the 1-year study period, no significant difference in the median expenditure was found between group 1 at R19 281 (range R35 657-13 379) and group 2 at R18 522 (range R22 449-16 951). The median number of admissions for group 1 was one and for group 2 three, requiring a median of 19 and 20 days of hospitalisation respectively. At the end of the 1-year study period 19 of 26 patients were alive (73%), 69% having responded. At this time, 16 of the 18 patients in group 1 had returned to their previous occupations, but this had not been possible for any of the 8 in group 2. In suitably selected patients who do not have an allogenic bone marrow transplant option the expenditure on ALG and HDMP is both medically and economically sound and the combination can be recommended as a valuable treatment option.

Anemia, Aplastic↗
PubMed1992

Method for the safe and rapid pretransfusion warming of stored blood: an in vitro and in vivo evaluation of a radiofrequency (RF) instrument.

Inadvertent hypothermia due to massive infusion of stored blood can be prevented by pretransfusion warming. One approach is the heating of individual packs by means of electromagnetic conduction, which is a method safely used over the last 25 years. The prototype instrument, which has now been re-engineered, can effectively raise the temperature of a unit of blood to approximately 33 degrees C in less than 3 minutes. Using this new model, we found, in vitro, a modest increase in free plasma haemoglobin, but this was not accompanied by any change in potassium or lactic dehydrogenase levels and the mean red cell fragility was unaltered. In vivo, the survival of autologous red cells that had been stored for 33 days and then infused as a concentrate, having a mean haematocrit of 0.60, was measured at 24 hours and 21 days. Each donor acted as his own control. In paired studies, pretransfusion radiofrequency heating was shown to have no deleterious effect when compared to measurements using the unwarmed blood pack. It is concluded that this method can be recommended as safe.

Adult↗
PubMed1992

Molecular cloning, characterization and purification of ornithine carbamoyltransferase from Mycobacterium bovis BCG.

A genomic library of Mycobacterium bovis BCG has been constructed by cloning DNA partially digested with Sau3A into the Escherichia coli expression vector pAS1. The gene coding for ornithine carbamoyl-transferase (EC.2.1.3.3; OTCase), hereafter referred to as argF, was isolated from the library by complementation of a double argF-argI mutant of E. coli and its sequence was determined. The translation initiation codon used, GTG, was identified by comparing the amino acid sequence deduced from the gene with the N-terminal sequence of the corresponding purified protein. On this basis, the M. bovis BCG OTCase monomer consists of 307 amino acid residues and displays about 44% identity with other OTCases, the most closely related homologue being the anabolic enzyme of Pseudomonas aeruginosa. The native enzyme has an estimated molecular mass of 110 kDa, suggesting a trimeric structure as is the case for most of the anabolic OTCases known from various organisms.

Amino Acid Sequence↗
PubMed1992

Erythropoietic adaptations to endurance training.

Erythropoietic adaptations involving the oxygen dissociation curve (ODC) and erythropoietin production have been implicated in the etiology of reduced blood haemoglobin concentrations in sportspersons (known as sports anaemia). A significant increase in the half-saturation pressure indicating a right-shift in the ODC was measured in 34 male [25.8-27.4 mmHg (3.44-3.65 kPa)] and 16 female (25.8-27.7 mmHg (3.44-3.69 kPa)] trained distance runners (P less than 0.01 for both genders) after completing a standard 42-km marathon. Erythrocyte 2,3-diphosphoglycerate concentrations measured concurrently were unaltered by exercise, although consistently higher in the female compared to the male athletes (P less than 0.05). The serum erythropoietin (EPO) concentrations of 15 male triathletes (26.3 U.ml-1) were significantly lower than those of 45 male distance runners (31.6 U.ml-1; P less than 0.05). However, the mean serum EPO concentrations of male and female athletes engaged in a variety of sports were not different from those of sedentary control subjects of both sexes (26.5-35.3 U.ml-1). Furthermore, the serum EPO concentrations were unaltered after prolonged strenuous exercise in 20 male marathon runners. These data suggest that the haematological status of these endurance athletes is in fact normal and that the observed shift in the ODC, while providing a physiological advantage during exercise, has no measurable effect on the erythropoietic drive.

2,3-Diphosphoglycerate↗
PubMed1992

Epidemiology of acute leukaemia in the Cape Province of South Africa.

Of 535 consecutive cases of acute leukaemia diagnosed in the Cape Province between 1978 and 1985, demographic data are incomplete in 75 black patients and they have had to be excluded from the spatial analysis. Of the remaining 460 cases, 223 (48.5%) occurred in white patients and 237 (51.5%) in those of mixed ancestry, classified as coloureds according to the Population Registration Act No. 30 of 1950. The average incidence was 2.12, 1.37 and 0.58/100,000 for whites, coloureds and blacks respectively. There was no temporal trend in the incidence of acute leukaemia between the three race groups. The median age for whites was 30 years and for the coloureds was 15 years, which is comparable to the 16 years for the black patients. The two-peak age distribution for leukaemia was seen in the white group, but was absent in the other two groups. This is accounted for by a different distribution in non-lymphoblastic as opposed to lymphoblastic subtypes. Furthermore, there was a disproportionately high frequency of acute progranulocytic leukaemia in the black patients, whereas the white and coloured groups were similar. There was a single, clearly defined macro-scale cluster restricted to white patients in Statistical Region 17 (SR-17). This exploratory study provides the first epidemiologic data for acute leukaemia in the Cape Province. It needs to be extended in order to verify these observations under more controlled circumstances and to seek evidence for some environmental factors that may account for the geographical cluster.

Acute Disease↗
PubMed1992

'Sports anemia'--a real or apparent phenomenon in endurance-trained athletes?

In order to critically define the apparently widespread condition 'sports anemia', the red cell indices and iron status of male distance runners and triathletes, and female distance runners and ballet dancers were compared to non-exercising controls of both sexes. The mean hemoglobin (Hb) levels of all groups were within the normal ranges and there was no difference between the athletic and control groups of each sex. The mean serum ferritin (SF) concentration of the male distance runners (79.8 micrograms/l) was significantly lower than that of the triathletes (123.5 micrograms/l) and controls (138.3 micrograms/l). Iron deficiency (SF less than 12 micrograms/l, % saturation less than 18%) was evident in 3.3% and 5% of the male and female runners respectively, and 3.3% of the ballet dancers. Iron deficiency anemia (abnormal red cell indices and iron status) occurred in only 1.7% and 3.3% of the male and female distance runners respectively, and 3.3% of the dancers. However, 7 (11.7%) each of the male and female distance runners and 6 (20.0%) of the ballet dancers recorded hemoglobin values lower than the normal range of 140 g/l and 120 g/l for males and females respectively. This anomaly can be explained by a significantly expanded plasma volume in endurance-trained individuals, causing a 'pseudoanemia'. We conclude therefore that athletes are at no greater risk for developing a frank anemia than the non-exercising population, and that the term 'sports anemia' is misleading, as it does not describe a specific clinical entity.

Adolescent↗
PubMed1992

Dietary iron deficiency and sports anaemia.

In order to determine whether dietary inadequacies can explain the sub-optimal iron status widely documented in endurance-trained athletes, the food intake records of Fe-deficient and Fe-replete distance runners and non-exercising controls of both sexes were analysed. In all the male study groups the mean dietary Fe intake met the recommended dietary allowances (RDA; > 10 mg/d (US) Food and Nutrition Board, 1989). However, both female athletes and controls failed to meet the RDA with regard to Fe (< 15 mg/d) and folate (< 200 micrograms/d). There was no difference in the total Fe intakes of Fe-deficient and Fe-replete athletes and the controls of each sex. However, Fe-deficient male runners, but not female runners, consumed significantly less haem-Fe (P = 0.048) than their comparative groups. This suggests that the habitual consumption of Fe-poor diets is a factor in the aetiology of athletes' Fe deficiency.

Adult↗
PubMed1992

Doxycycline and hepatotoxicity.

The hepatotoxicity of tetracyclines is well known. If microvesicular steatosis due to a high dose of tetracycline has virtually disappeared, it can also be observed with other drugs belonging to the tetracycline family. To our knowledge, hepatotoxicity induced by doxycycline has never been reported. In our patient, the abrupt onset of hepatic failure, five days after the start of doxycycline and the rapid normalization after the drug was stopped, leads to suspect a causal relationship between doxycycline and liver insufficiency. We must however be careful before concluding, because our patient received also acetylsalicylic acid and paracetamol, two other potential hepatotoxic drugs.

Adult↗
PubMed1992

Treatment of acute lymphoblastic leukaemia (ALL).

Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

Adolescent↗
PubMed1992

Serum erythropoietin concentrations in symptomatic infants during the anaemia of prematurity.

A comparison was carried out between a series of neonates who weighed less than 1500 g at birth and received red cell transfusions for symptomatic anaemia of prematurity (group 1, n = 14) and controls of similar gestational age and weight, who remained well and were not transfused during their nursery stay (group 2, n = 10). Mean (SD) haemoglobin concentrations at birth were 163 (12) g/l and 183 (17) g/l (p = 0.004), respectively. Transfusion resulted in significantly better weight gain in six infants who had been growing poorly:mean (SE) 8.8 (2.8) g/day improved to 23.3 (2.1) g/day (p less than 0.002). Geometric mean (SD) serum immunoreactive erythropoietin (SiEp) concentrations (17.7 (1.3) U/l) for the whole group of infants were similar to those of normal adults (17.4 (4.7) U/l) despite considerably reduced haemoglobin values. There was a significant inverse correlation between haemoglobin and log SiEp concentrations in the infants requiring transfusion (r = -0.43; p less than 0.01), but this was not apparent in the untransfused babies. Moreover, at haemoglobin concentrations below 120 g/l the mean (SE) SiEp concentration of 20 (1.08) U/l in group 1 was significantly higher than in group 2 (14 (1.06) U/l; p = 0.002). These data suggest that an increased concentration of SiEp early in the course of the anaemia of prematurity helps to identify those infants who would benefit from red cell transfusions, but that clinical criteria, although ill defined, do so equally well.

2,3-Diphosphoglycerate↗
PubMed1992

Plasmacyte-reticulum cell satellitism in multiple myeloma associated with amyloidosis.

A novel morphological feature is described in a patient with myeloma and associated amyloidosis: characteristic clustering (satellitism) of neoplastic plasma cells around macrophages in bone marrow aspirates. Although described in myeloma cell culture, as far as is known, this is the first description of this phenomenon in a patient. This unique association may partly explain the origin of amyloid deposition in tissues and organs.

Aged↗
PubMed1992

A complex rearrangement associated with sex reversal and the Wolf-Hirschhorn syndrome: a cytogenetic and molecular study.

We report a male infant referred with multiple congenital abnormalities consistent with the Wolf-Hirschhorn syndrome. Cytogenetic analysis showed a chromosome complement of 46,XX with a deletion of 4p15.2----4pter and its replacement by material of unknown origin. The patient was positive for a number of Yp probes including SRY, the testis determining factor, and in situ hybridisation localised the Yp material to the tip of the short arm of one X chromosome. Using pDP230, a probe for the pseudoautosomal region, and M27 beta, which recognises a locus in proximal Xp, the material translocated on to 4p was identified as originating from the short arm of the paternal X chromosome. The most reasonable explanation for this complex rearrangement is two separate exchange events involving both chromatids of Xp during paternal meiosis. An aberrant X-Y interchange gave rise to the sex reversal and an X;4 translocation resulted in additional, apparently active Xp material and a deletion of 4p which produced the Wolf-Hirschhorn phenotype.

Adult↗