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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 163 records · Page 9Linked to original sources
PubMed1995

Immunosuppressive therapy in bone marrow aplasia: the stroma functions normally to support hematopoiesis.

In aplastic anemia (AA) patients responsive to antilymphocyte globulin (ALG) therapy, abnormalities in both stroma and progenitor cell (PC) pool have been described. The relevance of each pathophysiologic defect was characterized in 16 individuals, and data were compared to results from seven normal volunteers. Bone marrow mononuclear cells were split into two fractions. Stromal layers (SL) were prepared from the first, and a CD34+ enriched population was obtained by immunomagnetic selection from the second. In cross-culture experiments, 1 x 10(4) of the latter from patients or controls were seeded on preformed SL, and adhesive PC were scored for the formation of blast colonies (CFU-Bl) on day 5 of culture. Nonadherent progenitors were recovered and quantitated in a standard clonogenic assay (CFU-GM). There were significantly fewer CD34+ cells in the AA group (median 0.65%, SD 0.39%, vs. 1.62%, SD 1.4%; p = 0.002). No morphological or cytologic differences between normal and aplastic SL were detected. Both equally supported the growth of CFU-Bl from normal progenitors (mean 117, SD 20.4, and 103.1, SD 30.4), while this value was reduced for the aplastic PC (mean 41.06, SD 42.9; p = 0.0002, exact two-tailed test). Similarly, the AA nonadherent PC had a decreased CFU-GM growth (mean 142.6, SD 104.8, vs. mean 361.7; SD 91.3), with a lower total clonogenic output (p = 0.0009). We conclude that aplastic stroma appropriately supports the growth of normal progenitors, whereas the depressed clonogenicity of the corresponsing population derived from AA is unrelated to their attachment to SL but intrinsic to the CD34+ cells, whether adherent or not.

Adolescent↗
PubMed1995

A cost-to-benefit analysis of blood products used during the initiation of an orthotopic liver transplantation programme.

Orthotopic transplantation is the treatment of choice for selected patients with end-stage post-necrotic and cholestatic liver diseases. These individuals typically have disturbed haemostasis, which reflects both impaired hepatic synthesis of clotting factors and disseminated intravascular coagulation compounded by large-volume transfusions of blood products occasionally required during surgery. The latter contribute significantly to the cost of this procedure, but may approximate the cumulative consumption of that required for the support of patients in liver failure. Perspective is provided by prospective analysis of data from the first 10 patients in the current programme. There were striking, if transient, intra-operative changes in standard laboratory parameters of coagulation and fibrinolysis; all patients were readily controlled with replacement therapy administered according to serial haemostatic measurements combined with clinical judgement. In most patients these values had stabilised within 24 hours of surgery. Those with post-necrotic liver cirrhosis had the most marked degrees of hepatic dysfunction, reflected in more profound haemostatic disturbances; these patients required the largest amounts of blood products. Inclusive median costs for the first year were estimated at R35,000 and for the first 5 years at R60,000, with 80% of the patients expected to be alive between 5 and 10 years later and enjoying an excellent quality of life. These figures contrast with those estimated for optimal medical and non-transplant surgical management following variceal bleeding as a major complication of liver disease (R30,000 for the first year and R70,000 at 3 years). In addition, the latter patients would usually be unable to work and have a poor quality of life with minimal likelihood of survival beyond this point. We conclude that with a multidisciplinary approach in an academic centre, surgical replacement of the irreversibly damaged liver in properly selected patients is no more expensive and has a better outcome than acceptable alternative approaches.

Adult↗
PubMed1994

Perioperative administration of a single dose of conjugated oestrogen to uraemic patients is ineffective in improving haemostasis.

The excessive bleeding that occurs in uraemic patients undergoing surgery is reported to be reversed by at least one schedule of prior oestrogen administration. To assess this possibility a single intravenous injection of 25 mg of the conjugated hormone was given to ten uraemic patients undergoing regular haemodialysis and randomly compared to eight matched patients who received only the diluent. Two hours later there was no reduction in bleeding time, improvement in platelet aggregation, nor an increase in plasma levels of factor VIII (VIII:C), von Willebrand factor (VWF:Ag), or the factor VIII-related ristocetin cofactor state. Furthermore, there was no reduction in intraoperative blood loss, being a median of 558 +/- 154 (range 225-1,260) mL in the test group and 412 +/- 55 (range 270-555) mL in the control and additional median postoperative portovac drainage was 123 +/- 27 (range 0-170) mL and 153 +/- 41 (range 45-240) mL, respectively. These findings differ from the shortening in bleeding time achieved by others with repeated administration of the same agent, and emphasize the importance of dose and duration of oestrogen therapy when used for this indication.

Adolescent↗
PubMed1994

Intravenous gammaglobulin has no advantages over oral corticosteroids as primary therapy for adults with immune thrombocytopenia: a prospective randomized clinical trial.

Symptomatic immune thrombocytopenia in adults is potentially lethal, and, when conventionally treated with oral corticosteroid agents, approximately two thirds of patients will have some response in platelet count, but this is seldom durable. Since cytotoxic drugs are of limited benefit at this stage, splenectomy becomes necessary in 70% of patients. Intravenous gammaglobulin has been advocated as an alternative to prednisone as the primary form of treatment. A prospective, randomized comparison was carried out between oral prednisone (1 mg/kg/day; group 1; n = 17), high-dose intravenous gammaglobulin (400 mg/kg on days 1 through 5; group 2; n = 13), or a combination of both agents given on the same schedule (group 3; n = 13). The groups were well matched clinically and hematologically. No mortality occurred after initiating therapy, but one patient experienced a cerebrovascular accident. Response, defined as a platelet count greater than 50 x 10(9)/L, was achieved in 82%, 54%, and 92% of patients in groups 1, 2, and 3, respectively, but was only significant between groups 2 and 3 (P = 0.0365). The median times to peak platelet counts were 8.5 days (range 7 to 21 days), 7 (range 5 to 10 days), and 7 (range 3 to 23 days), respectively. Although there was a trend in favor of the steroid-administered groups, relapse was not significantly different, which occurred at a median of 184, 32, and 76 days, respectively, nor was the average time to splenectomy different at 339, 59, and 98 days, respectively. At a minimum of 2 years of follow-up, 5 of 17 in group 1, 2 of 13 in group 2, and 1 of 13 in group 3 had achieved platelet counts of greater than 100 x 10(9)/L and, therefore, did not require splenectomy. In contrast, where this indication was present for failure to respond, 8 of 12 (67%) in group 1, 4 of 8 (50%) in group 2, and 9 of 12 (75%) in group 3 remain in complete remission. Significantly more patients in group 2 than group 3 experienced a relapse (P = 0.0365). It is concluded that in previously untreated adults with symptomatic immune thrombocytopenia, gammaglobulin offers no advantage over conventional corticosteroid administration as the primary form of therapy. Additionally, more intense immunosuppression, resulting from the use of both agents combined, is no better than single agent corticosteroid agents and appears to be an unnecessary and unwarranted expense.

Administration, Oral↗
PubMed1994

Case report: rectal stenosis due to extramedullary haemopoiesis--radiological features.

Although extramedullary haemopoiesis (EMH) is relatively common in myelofibrosis, it is seldom symptomatic and rarely involves the intestinal tract. We report a case in which perirectal infiltrate resulted in clinically symptomatic constipation. The barium enema showed tubular rectal narrowing with mucosal pleating. On computed tomography a poorly marginated soft tissue mass was shown to be replacing the perirectal fat.

Aged↗
PubMed1994

Key operating and financial ratios for Alberta hospitals.

Comparative financial and operating ratios in Canadian hospitals are examined to reveal sources of increased efficiency. The study involved 70 Alberta hospitals, which were divided into three groups: teaching hospitals, regional hospitals and smaller rural hospitals. Data were obtained from HS-1 and HS-2 reports. Hospitals across Canada can calculate their own ratios to give them a general idea of how they compare with the hospitals in this report.

Alberta↗
PubMed1994

Ambulatory case mix funding systems in Canada.

The implementation of inpatient case mix funding in Alberta and Ontario does not allow for adequate incentives to shift resources to an outpatient basis, where appropriate, or to provide outpatient care efficiently. This paper explores the prospects and problems of further extending case mix tools into this area. The availability of tools to characterize output for day surgery, special clinics and emergency care is surveyed. We conclude that case mix funding is desirable and feasible for ambulatory surgery; however, it is questionable for emergency care and special clinics. However, developments in this area in the United States will continue, and this will likely maintain an interest in Canada.

Alberta↗
PubMed1994

Involuntary stepping after chronic spinal cord injury. Evidence for a central rhythm generator for locomotion in man.

We investigated a pattern of involuntary lower extremity stepping-like movements which recently appeared in a subject with a 17-year history of neurologically incomplete injury to the cervical spinal cord. The movements were rhythmic, alternating and forceful, involved all muscles of the lower extremities and could be reliably evoked by lying the subject down (supine) and extending his hips. Once in this position, the movements continued spontaneously, in the absence of external sensory perturbations, with a step-cycle duration of approximately 3.5 s (0.3 Hz). This rate could be either increased or temporarily halted by specific sensory inputs. Anaesthetizing the subject's right hip joint, in which we found evidence of pathology, led to a marked attenuation of the stepping movements for a period of approximately 15 min. We believe that a combination of (i) preserved but limited supraspinal tonic facilitation, and (ii) abnormal, perhaps noxious afferent inflow from the subject's right hip to the spinal cord may underlie the appearance of this highly unusual and involuntary movement pattern. The striking similarity between the movement and EMG patterns in this subject and those described in many reports using the surgically reduced cat model suggests that we were witnessing the first well-defined example of a central rhythm generator for stepping in the adult human.

Adult↗
PubMed1994

The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination.

We investigated the parent and cell division of origin of the additional sex chromosome in 142 males with a 47,XXY constitution and 50 females with a 47,XXX constitution. In 66 of the 47,XXY males the additional chromosome was paternal in origin and in 76 it was maternal in origin, while among the 47,XXX females only 5 had an additional paternal X chromosome, the remaining 45 having an additional maternal chromosome. Among the 107 maternally derived aneuploids for whom it was possible to determine the cell division of origin, 73 were the result of a mat MI error, 24 the result of a mat MII error and 10 the result of a post zygotic mitotic (PZM) error involving the maternal X chromosome. Among those in which the non-disjunction was attributable to an error at the first meiotic division (MI) we observed three different mechanisms of origin. Approximately 30% were associated with complete absence of recombination (nullichiasmate); approximately 24% were associated with a normal number of recombinant events but an abnormal distribution of exchanges (perturbed recombination), while approximately 45% were associated with a normal number and distribution of recombinant events (normochiasmate). Nondisjunction due to an error at the second meiotic division (MII) was associated with a slight reduction in the total number of recombinant events and an abnormal distribution of exchanges. Thus of the four different meiotic mechanisms of origin, three were associated with an abnormal number and/or distribution of exchange events. There was no evidence of an increased paternal age in the aneuploids of paternal origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1994

The treatment of thrombotic thrombocytopenic purpura: plasma infusion or exchange?

Classic thrombotic thrombocytopenic purpura has substantial mortality and, because the pathogenesis is uncertain, multiple therapies are often used. These include corticosteroids and antiplatelet drugs, with plasma infusion or exchange most dramatically influencing outcome. To compare the relative efficacy of these latter two options, the records of 20 patients were retrospectively analysed. The groups were well matched for size and disease severity and received equivalent volumes of plasma. No significant difference in response rate or survival was demonstrated, although plasmapheresis may be preferable in the presence of impaired renal function with fluid overload.

Adolescent↗