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Biomedical subjects

S Schulman

Publications and source records attributed to S Schulman.

At least 127 records · Page 7Linked to original sources

The deamination of adenosine and adenosine monophosphate in Plasmodium falciparum-infected human erythrocytes: in vitro use of 2'deoxycoformycin and AMP deaminase-deficient red cells.

The role of enzymatic deamination of adenosine monophosphate (AMP) and adenosine in the in vitro growth of the malaria parasite Plasmodium falciparum was investigated by means of human red cells deficient in AMP deaminase to which the adenosine deaminase inhibitor 2'-deoxycoformycin was added. Malaria parasites grew normally in red cells lacking one or both of these enzyme activities. As a further probe of adenosine triphosphate (ATP) catabolism, both infected and uninfected RBCs were incubated with NaF (with and without 2'-deoxycoformycin) and the purine nucleotide/nucleoside content was analyzed by high-performance liquid chromatography (HPLC). Uninfected RBCs lacking either AMP or adenosine deaminase were able to bypass the enzyme block and degrade ATP to hypoxanthine. Uninfected RBCs with both deaminases blocked were unable to produce significant quantities of hypoxanthine. On the other hand, infected RBCs were able to bypass blockade of both deaminases and produce hypoxanthine and adenosine. These findings establish that deamination of adenosine and/or AMP are not essential for plasmodial growth. However, further work will be required to elucidate the pathways that permit the parasites to bypass these catabolic steps.

AMP Deaminase↗

Oral surgery in patients with hereditary bleeding disorders. A survey of treatment in the Stockholm area (1974-1985).

The results on the oral surgical management of patients with coagulation disorders at the Karolinska Hospital, Stockholm, during the period 1974-1985 have been compiled and compared with those obtained during the period 1965-1973. The present study included 380 tooth extractions performed in 250 treatment sessions in 107 patients. The incidence of postoperative bleeding and duration of hospitalization were reduced during the period of investigation.

Blood Coagulation Disorders↗

Interaction of ibuprofen and warfarin on primary haemostasis.

It has been stated that ibuprofen can be safely prescribed with concomitant warfarin. The effect of ibuprofen on primary haemostasis was investigated in 20 patients on warfarin for venous thromboembolism. Ibuprofen, 600 mg orally t.i.d., was added for 1 week. Bleeding time, prothrombin time, platelet count and urinalysis for haemoglobin were performed before and 90 minutes after the first dose and after 1 week. The bleeding time was significantly prolonged after 90 minutes (p less than 0.01) and after 1 week (p less than 0.05) and in four cases it was prolonged above the normal range. No clinical side-effects were observed apart from microscopic haematuria and haematoma. Thus, ibuprofen may cause clinical problems in some patients treated with warfarin, particularly in the elderly on complex drug regimens. It is advisable to check the bleeding time a few days after treatment with ibuprofen has been started in patients already on oral anticoagulation, and discontinue the former if the bleeding time is prolonged above the normal range.

Aged↗

Acute effects with reference to thrombogenicity and liver toxicity after injection of different coagulation factor concentrates.

In order to assess thrombogenicity and liver toxicity of different coagulation factor concentrates, antithrombin III, soluble fibrin, alanine aminotransferase (ALAT) and gamma-glutamyl transpeptidase (GT) were measured in samples taken before, 30 min and 24 h after the infusion. Seventy-six studies were performed in 55 patients with haemophilia A (37), B (11) or von Willebrand's disease, type III (7). A sharp rise of soluble fibrin was observed in 2 patients with haemophilia B, indicating that modern factor IX concentrates may still be thrombogenic. A slight increase was also seen after infusion of factor VIII-von Willebrand factor concentrates of low purity. Antithrombin III, ALAT and GT did not change significantly after any of the factor concentrates. The alterations in those parameters did not correlate with the impairment of liver function.

Adult↗

Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy.

Of 455 acute nonlymphocytic leukemia (ANL) patients who underwent marrow transplantation, 95 (21%) relapsed a median of 6.5 months posttransplantation and 62 received further treatment. Twenty achieved remission. Success of therapy was related to the length of time from marrow transplant to relapse and to the use of cytarabine (Ara-C) and daunomycin. Aggressive chemotherapy for patients relapsing within 100 days of marrow transplant was associated with a high incidence of early death (six of 14 patients) and a low probability of remission (one of 14). Of 23 patients who relapsed in excess of 1 year from marrow transplant, 15 achieved a complete remission. The median disease-free survival is 6 months (range, 0.4 to 53+ months). Acute lymphocytic leukemia (ALL) recurred in 130 of 366 patients (36%), and 94 received further therapy. Fifty-two achieved a remission. Remissions were more common in late relapse patients (greater than 1 year from transplantation): 65% v 7% for those relapsing within 100 days from transplant (P less than .05). Testicular relapse occurred in 11 patients and was the sole site of relapse in seven. Three are alive and free of disease 58 to 109+ months after relapse. The median survival for the treated patients is 10.5 months (range, 5 to 109+ months). We propose that reinduction be attempted in all patients relapsing greater than 1 year from marrow transplantation. Ara-C and daunomycin should be employed in the treatment of ANL. The decision for treatment of patients relapsing earlier than 1 year should be made on an individual basis.

Adult↗

Incidence of symptoms and AIDS in 146 Swedish haemophiliacs and blood transfusion recipients infected with human immunodeficiency virus.

The times from infection with the human immuno-deficiency virus (HIV) to the onset of the first clinical symptom and the development of AIDS were studied prospectively in 98 haemophiliacs and 48 blood transfusion recipients infected with the virus. Patients were followed up for a median of 61 months after infection, the dates of infection being either known exactly or estimated from the interval between the last negative and first positive HIV antibody test result. The rate of progression to AIDS was significantly higher for the transfusion recipients than for the haemophiliacs. The difference in time to the occurrence of the first clinical symptom was less pronounced between the two groups, though pointing in the same direction. The results suggest that on average roughly half of all patients positive for HIV will develop some clinical sign or symptom within five to six years after infection.

Acquired Immunodeficiency Syndrome↗

HIV isolation and antigen detection in infected individuals and their seronegative sexual partners.

We have examined 39 couples, each consisting of one HIV-seropositive index case and one seronegative sexual partner. HIV isolations, HIV antigen (HIV-Ag) tests and HIV antibody tests were performed on samples from these 78 individuals. Results were compared with those of 68 unselected individuals. Neither HIV, nor HIV-Ag was detected in any of the seronegative individuals. HIV-Ag tests, but not HIV isolations showed positive results with a significantly lower frequency in symptomatic index cases than in unselected patients with symptoms. This indicates that the absence of HIV-Ag in the serum may be correlated with a low level of contagiousness.

Adult↗

Haemorrhagic and thromboembolic complications versus intensity of treatment of venous thromboembolism with oral anticoagulants.

In order to assess the recommended therapeutic interval with the prothrombin complex analysis, using Stago Prothrombin-complex Assay (SPA) as the reagent, a retrospective multicentre study was performed to obtain clinical documentation. All thromboembolic and haemorrhagic complications during secondary prophylaxis after venous thromboembolism in 272 patients were recorded and related to the intensity of the oral anticoagulation. Six thromboembolic complications in patients without a malignant disease occurred at SPA levels greater than or equal to 28%, confirming that the limit of the therapeutic range, determined by the risk of thromboembolic recurrences, should be set at an SPA level of 25% (international normalized ratio, INR = 2.0), at least in venous disease. Major haemorrhages occurred mainly at SPA levels less than 10% (INR greater than 4.0), unless underlying risk factors were present, thus setting the other limit of the therapeutic range. However, an adjustment of this limit to SPA = 15% (INR approximately 3.0) is suggested, since it would lead to further reduction of haemorrhage and is advisable in most patients with venous thromboembolism.

Adult↗

The adaptation of Plasmodium falciparum to oxidative stress in G6PD deficient human erythrocytes.

It has recently been found that growth of P. falciparum in human G6PD deficient red cells is impaired in vitro; however, the inhibition is overcome after two or three growth cycles. There is evidence to suggest that the parasite can produce its own G6PD enzyme which may compensate for the lack of host enzyme and could account for the resumption of normal growth in G6PD deficient host cells. It is unclear whether the parasite enzyme can enable the host cell to resist oxidative stress as normal cells do. To answer this question, P. falciparum was grown in vitro in: (a) normal red cells, (b) G6PD deficient red cells for one growth cycle only, (c) G6PD deficient cells for a minimum of five cycles. All groups were then challenged with acetylphenylhydrazine (APH) which served as an oxidative stress. Both G6PD (A-) and Mediterranean deficient types were studied. The results show a two-fold increase in resistance to oxidative stress by parasites adapted to G6PD-Mediterranean deficient host cells as compared to unadapted ones, but the parasite-red cell system remains 4 times more sensitive to APH than normal infected cells. In parasitized G6PD (A-) red cells, evidence of adaptation could be seen in the growth curves, but no detectable increase in resistance to APH was found in adapted parasites. It is concluded that the role of the parasite G6PD is not likely to be mainly related to oxidative stress resistance and therefore other functions of this enzyme should be investigated.

Adaptation, Biological↗

HIV-serology and lymphocyte subsets in relation to therapy and clinical development in haemophiliacs.

389 Swedish patients with haemophilia A, B or von Willebrand's disease were examined for HIV-1 antibodies. T-cell subsets were measured in 260 of them. HIV-1 antibodies were found in 98 of these patients. Of the 199 patients with severe or moderate haemophilia A, 44% were seropositive. They had seroconverted between 1979 and 1983. HIV-1-seropositive patients had significantly decreased numbers of CD4 cells and increased numbers of CD8 cells. The seronegative haemophilia A patients had significantly increased numbers of CD8 cells. The T-cell subsets were followed for a median of 40 months in 73 seropositive patients. All groups of patients, at different clinical stages, showed decreasing numbers of CD4 cells. The most pronounced decrease was seen in the patients who developed AIDS, followed by the group which developed HIV-related signs or symptoms. HIV antigen in serum and antibody pattern in Western blot and ELISA were followed in 89 patients. HIV-1 antigen was present and p24 antibodies were lacking in 11% and 13% of asymptomatic subjects, in 13% and 20% of patients with persistent generalized lymphadenopathy, in 33% and 38% of patients with other HIV-related signs or symptoms and in 5/6 of the AIDS patients, respectively. In conclusion, the decrease of CD4 cells and the presence of HIV antigen and/or absence of p24 antibodies were found to be prognostic markers for HIV disease.

Acquired Immunodeficiency Syndrome↗

Feasibility and efficacy of weekly intraarterial cisplatin in locally advanced (stage III and IV) head and neck cancers.

Thirty-five consecutive patients with primary unresectable head and neck cancers were considered eligible for protocol treatment with neoadjuvant intraarterial cisplatin. External carotid artery catheterizations were technically feasible in 29 patients (83%). Twenty-five patients with 28 primary tumors received intraarterial cisplatin, 100 mg/m2, every seven to 14 days for three cycles. The most common toxicity was nausea and vomiting. Ipsilateral hemialopecia, transient VII nerve palsy, and blurring of vision seem to be unique to this route of administration at this dose. A complete response was seen at the primary tumor site in nine of 28 (32%), with 14 of 28 partial responses (50%). In evaluating both primary tumor and nodal disease, five of 25 patients achieved a complete response and 15 of 25 a partial response. In previous reports, one complete response was observed in 74 patients with head and neck cancer treated with neoadjuvant intravenous (IV) cisplatin every 3 weeks. The overall response of 82% reported here is comparable to that reported with combination chemotherapy and suggests an advantage to the arterial administration of cisplatin when possible in the neoadjuvant setting.

Carotid Artery, External↗

No evidence for vertical transmission in children born to HIV seropositive male haemophiliacs.

In order to evaluate the risk of HIV transmission during conception or pregnancy from seropositive male haemophiliacs to their children, we have investigated the families of 8 HIV antibody positive haemophilia A patients. HIV antibodies could be demonstrated in 1/9 mothers after delivery of her second child, whereas all the other mothers tested were seronegative. Of the 14 children studied at least 7 must have been conceived when the father was already seropositive. HIV antibodies were tested for in 6 of these 7 children; all were negative. All 14 children are healthy and free from clinical signs of HIV infection. We conclude that the overall risk of perinatal HIV transmission in haemophilic families should be low and this knowledge may be invaluable in family counselling.

Acquired Immunodeficiency Syndrome↗