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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 307 records · Page 17Linked to original sources

Emergency caesarean section and symptomatic immune thrombocytopenic purpura.

A 24-year-old woman presented in labour with profound purpuric bleeding due to idiopathic immune thrombocytopenia. She was assessed as requiring immediate caesarean section for cephalopelvic disproportion and foetal distress. In view of her platelet count of 21 x 10(9)/L she was prepared with intravenous methylprednisolone, isovolaemic plasma exchange, and infusion of 400 mg/kg of gammaglobulin and 5 x 10(11) allogeneic platelets. Six hours after commencing the procedure, at a time when her platelet count was 97 x 11(9)/L, she went uneventful operation and with no further therapy this level subsequently reached 175 x 10(9)/L, at which time an uneventful operation was performed. The mother and her normal, full-term infant have been discharged; both are well and at follow-up have normal platelet counts. This experience illustrates that major surgery can safely be undertaken in severely thrombocytopenic patients, even as an emergency procedure, using this regimen.

Adult↗

The comparison of gammaglobulin to steroids in treating adult immune thrombocytopenia. An interim analysis.

Symptomatic immune thrombocytopenia is a life-threatening situation which is conventionally treated in the adult with prednisone, although subsequent splenectomy is frequently unavoidable. Recently, high-dose intravenous gamma-globulin has been reported to be an effective alternative option, particularly in children. To determine the role of this agent in adults a controlled prospective trial has been undertaken. Previously untreated patients with immune thrombocytopenia were randomised to compare oral prednisone (1 mg/kg/day: Group 1: n = 13) to high-dose intravenous gamma-globulin (400 mg/kg on days 1 through 5: Group 2: n = 7), or a combination of both agents given on the same schedule (Group 3: n = 12). The time from diagnosis to commencement of treatment, initial platelet counts, age and sex were comparable in the three groups. At this interim analysis there has been no mortality, but one patient has suffered a cerebrovascular accident. Objective response, defined as a platelet count greater than 50 x 10(9)/l, was achieved in a median of 5, 5 and 3 days, whereas the time taken to reach peak counts were 9, 5 and 7 days, respectively. The relapse rates, percentage of patients subsequently requiring splenectomy for control of symptomatic bleeding and the postoperative course was comparable between the three groups. These data, although preliminary, re-emphasize differences between the paediatric and adult forms of immune thrombocytopenia and also suggest in the latter patients a need for caution before advocating replacement of prednisone by gammaglobulin as the primary form of treatment.

Adult↗

Conjunctival melanocytic lesions in children.

Seventy-one conjunctival melanocytic proliferations in patients 20 years of age or younger were examined. Sixty-five (91.5%) were nevi; there were three cases (4.2%) of racial or acquired melanosis, and three patients were identified who had malignant melanoma of the conjunctiva. The melanoma patients are presented in detail, and additional cases of conjunctival melanoma in children and adolescents reported in the literature are reviewed to determine factors that might influence prognosis. The number of cases is so small, however, that factors cannot be identified with confidence. Follow-up data are presented. Conjunctival nevi are relatively common in children, and appear to carry no risk for the development of melanoma during childhood. However, -conjunctival melanomas do occur rarely in children and have a variable prognosis.

Adolescent↗

Superparamagnetic iron oxide: pharmacokinetics and toxicity.

The pharmacokinetics (distribution, metabolism, bioavailability, excretion) and toxicity (acute and subacute toxicity, mutagenicity) of a superparamagnetic iron oxide preparation (AMI-25), currently used in clinical trials, were evaluated by 59Fe radiotracer studies, measurements of relaxation times, the ability to reverse iron deficiency anemia, histologic examination, and laboratory parameters. One hour after administration of AMI-25 to rats (18 mumol Fe/kg; 1 mg Fe/kg), 82.6 +/- 0.3% of the administered dose was sequestered in the liver and 6.2 +/- 7.6% in the spleen. Peak concentrations of 59Fe were found in liver after 2 hr and in the spleen after 4 hr. 59Fe slowly cleared from liver (half-life, 3 days) and spleen (half-life, 4 days) and was incorporated into hemoglobin of erythrocytes in a time-dependent fashion. The half-time of the T2 effect on liver and spleen (24-48 hr) was shorter than the 59Fe clearance, indicating metabolism of AMI-25 into other forms of iron. IV administration of AMI-25 (30 mg Fe/kg) corrected iron-deficiency anemia and showed bioavailability similar to that of commercially available IV iron preparations within 7 days. No acute or subacute toxic effects were detected by histologic or serologic studies in rats or beagle dogs who received a total of 3000 mumol Fe/kg, 150 times the dose proposed for MR imaging of the liver. Our results indicate that AMI-25 is a fully biocompatible potential contrast agent for MR.

Animals↗

The chronic leukaemias.

The slow progression of both chronic granulocytic and lymphocytic leukaemia, when compared to their acute counterparts, has been used as an argument to support less aggressive therapy or even, in some instances, a watch-and-wait policy. This conservative approach is bolstered by a number of observations including the ease with which haematologic control can initially be achieved, the older age of patients with the lymphocytic variant and the paucity of controlled data showing that long disease-free survival or cure can result from the use of aggressive treatment. Given these circumstances, it is not surprising that many such individuals are managed outside specialised centres using a variety of agents and schedules, both of which may, on occasions, be inappropriate. Accumulating evidence suggests a need to reconsider these practices since cure is now possible in selected patients with chronic granulocytic leukaemia while the use of multi-drug regimens in the lymphatic form can significantly improve survival. These advances are the result of carefully conducted clinical trials involving many individuals the world over and constitute the basis for advocating early referral to those institutions where all the necessary expertise is available.

Adult↗

Myeloma--the integral role played by the professional nurse.

Myeloma is a malignancy of plasma cells which are terminally differentiated B-lymphocytes. The diagnosis may be made incidentally at routine blood testing, when an abnormality is found in the plasma proteins on electrophoresis. More usually the patients are symptomatic, with bone pain, anaemia, evidence of renal failure, or the metabolic abnormalities associated with increased plasma calcium and urate levels. Effective treatment will extend survival from 7 to approximately 30 months and at the same time improve the quality of life. Treatment is multidisciplinary, prominently involves the professional nurse and may arbitrarily be divided into two stages. Firstly, reversible lesions, such as dehydration and plasma hyperviscosity must be corrected, hypercalcaemia and hyperuricaemia improved and, if necessary, renal dialysis undertaken. Secondly, but of equal importance, is the need for specific therapy to be directed against the tumour itself, and both cytotoxic agents and irradiation have an important role to play. More recently, newer approaches have included high dose chemotherapy and bone marrow transplantation.

Combined Modality Therapy↗

Unusual clinical presentations of intermediate lymphocytic lymphoma.

Three patients with previously unreported presentations of the follicular or mantle zone variant of intermediate lymphocytic lymphoma are described. In each case lymph node histopathology showed the presence of non-neoplastic follicular structures containing germinal centre-like areas and widened mantle zones in which the component small lymphocytes consisted of an admixture of a typical lymphoid cells. The nuclear contour of these cells was irregular or indented and they expressed an IgM lambda phenotype. The patients were typical in being over 50 years of age, anaemic with stage IV disease by virtue of bone marrow involvement, and having generalized lymphadenopathy and marked hepatosplenomegaly. Conversely, the clinical features in each case were unusual, being the nephrotic syndrome due to mesangioproliferative glomerulonephritis in one, extensive lymphomatous involvement of the ileum in the second, and recurrent pneumonia and abscess formation in the third. These associations are further examples of the way in which patients with this unusual lymphoma may present.

Aged↗

Isolation of a new human herpesvirus producing a lytic infection of helper (CD4) T-lymphocytes in peripheral blood lymphocyte cultures--another cause of acquired immunodeficiency?

A new human helper (CD4) T-lymphotropic herpesvirus (HTLHV) was first isolated in February 1985 from the cultured peripheral blood lymphocytes (PBL) of a patient with the acquired immunodeficiency syndrome, and subsequently from the PBL of 1 patient with hairy cell leukaemia and 2 patients with lymphoproliferative disease associated with human T-lymphotropic virus type I infection. The viruses could be serially subcultured in umbilical cord PBL cultures in which they infected helper (CD4) T-lymphocytes producing multinucleate giant cells with intranuclear inclusions followed by cell lysis. Electron microscopy of infected cultures revealed that the isolates were herpesviruses. Specific DNA probing showed that the 4 isolates were related to one another but were distinct from cytomegalovirus, Epstein-Barr virus, Herpesvirus hominis types 1 and 2, and varicella-zoster virus. HTLHV lyses the same target cell as human immunodeficiency virus in PBL cultures suggesting that it may have a similar potential to cause acquired immune deficiency. The development of an unequivocally diagnostic serological test is a priority, so that the epidemiology and pathogenesis of HTLHV infection can be studied.

Acquired Immunodeficiency Syndrome↗

Properties of the transferrin associated with rat intestinal mucosa.

The transferrin that is isolated from washed intestinal mucosal cell preparations consists partly of a fraction that has properties distinguishing it from serum transferrin. The serum transferrin contaminating mucosal preparations, even when fully saturated with iron and in the presence of proteinase inhibitors, also acquires the properties of the mucosal transferrin when the mucosa is homogenised. The mucosal transferrin is modified by a single cleavage of the polypeptide chain yielding a disulphide-linked peptide of 6550 daltons linked to the parent protein by a disulphide bridge. The amino-terminal sequence of the first 11 residues of this peptide could be aligned with both the known rat and human transferrin carboxy-terminal sequences. In both cases the sequence is preceded by a phenylalanine residue (residue 622 of human transferrin). This suggested that a mucosal chymotryptic enzyme was responsible even though rat transferrin is not susceptible to alpha-chymotrypsin if fully iron-saturated. Since transferrin mRNA is not found in the intestinal mucosa it must be imported from the serum. It remains uncertain whether the modified transferrin is present naturally and plays a role in iron absorption but these findings do indicate the eventual fate of any transferrin imported into an intestinal cell.

Amino Acid Sequence↗