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Biomedical subjects

N Jacobsen

Publications and source records attributed to N Jacobsen.

At least 19 recordsLinked to original sources

Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy.

About 30% of adults with acute lymphoblastic leukemia (ALL) and 20% to 40% of children and adults with acute myelogenous leukemia (AML) never achieve remission, even with intensive chemotherapy. Most die of resistant leukemia, often within 6 months or less. In this study of 126 patients with resistant ALL or AML, allogeneic bone marrow transplants from HLA-identical siblings produced remissions in 113 of 115 (98%) evaluable patients. The 3-year probability of leukemia-free survival was 21% (95% confidence interval, 15% to 29%). Leukemia-free survival was similar in ALL (23%, 12% to 40%) and AML (21%, 14% to 31%). Only 3 of 27 patients at risk relapsed more than 2 years posttransplant.

Adolescent

[Acquired severe aplastic anemia. Therapeutic effect and prognosis after allogeneic bone marrow transplantation].

During 1980-1988 bone marrow transplantation was performed in 14 patients with acquired severe aplastic anemia. Twelve of these patients had HLA identical and two patients incompatible family donors. Two patients died before marrow engraftment. Twelve patients engrafted 12-30 days after marrow transplantation with continued normal marrow function. The actuarial probability for long term survival was found to be 67% after HLA identical allogeneic sibling marrow transplantation. The longest time of observation was 9 years and the patient is still alive. All deaths occurred during the first six months posttransplant. It is concluded that the serious prognosis for patients with SAA has improved if the patients have the possibility for allogeneic HLA identical family donor transplantation.

Adolescent

Perceived side effects of biomaterials in prosthetic dentistry.

The present questionnaire survey of side effects of biomaterials in prosthodontics had a response rate of 64%. There were occupational health problems associated with a variety of dental materials, especially acrylic resins, eugenol-containing materials, and elastomer impression materials. Most reactions were mild to moderate dematoses of the fingers or hands, but one prosthodontist had to cease practice due to a severe allergic reaction to acrylic resin materials. Of the respondents, 8% had experienced reactions to latex gloves. Nondermatologic reactions seemed to be transient, affecting the eyes, respiratory pathways, or occasionally causing generalized symptoms. These reactions were mainly attributed to vapors from acrylic resin monomers or cyanoacrylates. Adverse reactions in patients, tentatively estimated to be one out of 300, were observed by 40% of the prosthodontists, mostly as intraoral reactions. Acrylic resins, eugenol-containing cements, base metal alloys, mercury, gold, polyether/epimine based materials, and tissue conditioners were cited as causes. Skin contact with the dentists' latex gloves elicited extraoral reactions in some patients.

Biocompatible Materials

Increased frequencies of the CD29 and CD57 markers and decreased frequency of CD45RA within CD4+ and CD8+ subsets after allogeneic bone marrow transplantation in man.

Two monoclonal antibodies, anti-CD45RA and anti-CD29, reciprocally divide the CD4+ and CD8+ lymphocytes into CD4+ CD45RA+, CD4+ CD29+, CD8+ CD45RA+ and CD8+ CD29+ subsets. The CD4+ CD45RA+, CD4+ CD29+ and CD8+ CD45RA+ possess suppressor-inducer, helper-inducer and suppressor-effector functions respectively. Since the role of these subsets has not been established after allogenic bone marrow transplantation we studied lymphocyte subpopulations in 12 patients 45-227 days after the procedure. The fraction of CD4+ lymphocytes was significantly (P = 0.0005) decreased to 20 +/- 9% versus 43 +/- 3% in controls. Within the CD4+ compartment, we found an increase in the fraction of CD4+ cells that co-expressed CD29 (CD29+/CD4+) to 92 +/- 10% versus 48 +/- 15% (P = 0.008) in controls and a concomitant decrease in CD45RA+/CD4+ to 16 +/- 12% versus 56 +/- 25% (P = 0.008). Patients were also noted to have an increase in the percentage of CD8+ lymphocytes to 41 +/- 5% compared to 23 +/- 4% in controls (P = 0.0004). Examination of the CD8+ subsets revealed a significant increase in the CD29+/CD8+ fraction to 97 +/- 3% versus 64 +/- 2% in controls (P = 0.008) and a decrease in the CD45RA+/CD8+ fraction to 36 +/- 11% versus 70 +/- 21% (P = 0.008). The number of cells co-expressing CD57 were also determined within the CD4+ and CD8+ subsets. In patients CD57+/CD4+ were increased to 29 +/- 7% versus 1 +/- 1% in controls (P = 0.04), and CD57+/CD8+ to 49 +/- 12% versus 23 +/- 9% (P = 0.02). Since CD29+ and CD57+ cells have a poor capability for IL-2 production and proliferation this shift in subset distribution may account for some of the defects in cellular immunity seen within the first year after allogeneic bone marrow transplantation.

Adolescent

Occupational health complaints and adverse patient reactions as perceived by personnel in public dentistry.

A questionnaire survey on health complaints experienced by personnel in public dentistry was undertaken in 1979 and repeated in 1988/89. The reply rates were about 80% and 83%. In both surveys, about one half of the personnel reported occupation-related health complaints, a majority of which were dermatoses of hands and fingers. The dermatoses were attributed to seasonal air quality problems, or to contact with chemically active substances relevant to hygienic measures, treatment patterns, or other activities connected with the running of a dental clinic. The majority of the dermatoses were probably irritative. Some presumably hypersensitivity reactions occurred after handling of dental materials. Latex gloves, which were in general use only at the time of the last survey, seemed to have prevented some dermatoses formerly attributed to handwashing procedures. However, latex gloves per se had also induced dermatoses. Non-dermatological ailments of a transient nature comprised eye, respiratory, or systemic reactions and were connected with volatiles from X-ray liquids, methylmethacrylate monomer, and disinfectants. Adverse patient reactions occurred at a frequency of about one per 2600 treated patients. The observations comprised skin reactions (head/face), gingival/mucosal ulcerations, and sometimes systemic/urticarial reactions. The reactions were associated with the use of local anesthetics, orthodontic appliances, and other biomaterials. Two reactions were related to contact with the dentists' latex gloves.

Adult

Toxic effects of dental materials.

Dental materials and clinical accessories may potentially cause adverse reactions in dentists, auxiliaries or patients. The introduction of new dental materials and a general awareness of adverse effects has been accompanied by an increase in the number of complaints related to dental treatment and to occupational exposure. Resin-based materials with various monomers, used as restorative composite materials, orthodontic adhesives and appliances, prosthodontic resins and impression materials, have all been involved. Reactions to metals used in extra-oral appliances in orthodontics seem to be relatively frequent, but few reactions have been reported following the use of other alloy systems. Some reactions may be due to toxic or allergic effects, but some are unexplained. Adverse reactions to any substance will usually be detected first in a setting where the exposure is greatest. This also holds true for dentistry, where some of the adverse reactions may be due to lack of knowledge about the toxic, irritant and allergenic properties of dental materials.

Allergens

[2 fatal cases of pneumococcal septicemia after bone marrow transplantation].

Patients with bone-marrow transplants have an increased risk of developing fulminant pneumococcal infections for years after transplantation. In order to illustrate this, two cases of fetal pneumococcal septicaemia in patients with bone-marrow transplants are described. Self-medication with penicillin in case of fever is recommended.

Adult

Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation.

Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of developing chronic GVHD within three years posttransplant was 46% +/- 3% (95% confidence interval). The most important risk factor for chronic GVHD was acute GVHD. The 3-year probabilities of chronic GVHD were 28% +/- 3%, 49% +/- 5%, 59% +/- 6%, 80% +/- 9%, and 85% +/- 15% for persons with grades 0, I, II, III, and IV acute GVHD, respectively (P less than .0001). Among patients with no or grade I acute GVHD, recipient age greater than 20 years, use of non-T-cell depleted bone marrow, and alloimmune female donors for male recipients predicted a higher risk of chronic GVHD. When all three adverse risk factors were present, the probability of chronic GVHD was 62% among persons with no prior acute GVHD and 85% among those with grade I acute GVHD. Among patients with grade II through IV acute GVHD, no other risk factor predicted chronic GVHD. These data identify individuals who might benefit from treatment strategies aimed at changing the incidence of chronic GVHD.

Acute Disease

A European multicenter study of chronic graft-versus-host disease. The role of cytomegalovirus serology in recipients and donors--acute graft-versus-host disease, and splenectomy.

A group of 466 leukemic bone marrow transplanted patients were reported from 17 European bone marrow transplantation teams. Of these, 285 survived more than 3 months and could be evaluated for chronic GVHD. The cumulative incidence of chronic GVHD was 32% two years after BMT. The following factors were statistically significantly associated with chronic GVHD in bivariate analysis: high donor and recipient age, splenecacute GVHD, pretransplant seropositivity to CMV among the recipients and the donors, and donor seropositivity to 3 or 4 different herpesviruses, compared with 0-2, prior to BMT. In multivariate analysis pretransplant recipient CMV seropositivity in combination with donor CMV seropositivity prior to BMT (P = 0.0006), a previous grade II-IV acute GVHD (P = 0.001), and splenectomy (P = 0.01) were significantly associated with chronic GVHD. Thus, in addition to acute GVHD, CMV immune donor cells may be triggered by latent CMV in the recipient, which may play a role in the triggering of chronic GVHD. The possible role of splenectomy in GVHD is also discussed.

Adolescent

The role of biomaterials as occupational hazards in dentistry.

Many of the biomaterials and auxilliary products used in dentistry are chemically and biologically reactive and may be of concern in occupational safety programmes. Observations from 1936 to 1975 indicated that most occupational problems were related to skin contact with procaine, soaps, eugenol, iodine, formalin, phenol, and other disinfectants. Methyl methacrylate monomer was identified as an irritant and allergen in the later part of this period. Investigations from 1975 to 1985 indicated that disinfectants and detergents were still important causes of dermatoses, whereas reactions to procaine had been replaced by reactions to pantocaine. Furthermore, adverse reactions to methyl methacrylate monomer and to elastomeric impression materials had replaced the former iodine, tricresol and eugenol reactions. In recent studies the frequency of occupation-related dermatoses varied from 21 per cent to 43 per cent, depending on the prevailing material usage in the various specialties. Reactions to local anaesthetics seemed to have disappeared. Transient, irritative reactions of the eyes and airways have been observed, mostly associated with exposure to volatiles from resin-based materials, X-ray chemicals and cleansers. The occupational problems related to biomaterials in dentistry seem to have been fairly constant over the years, reflecting the type of materials in common use, and with dermatological disorders being a tenacious companion. Neuropathological conditions in dental technicians have been associated with prolonged exposure to vapours of methyl methacrylate monomer. The more recent extensive use of volatile resin-based materials, and the use of protective gloves seems to have created new problems that need to be investigated.

Biocompatible Materials

Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients. The Nordic Bone Marrow Transplantation Group.

Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogenic bone marrow transplantation for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma in first to fourth remission or during relapse. Multifactorial analysis was performed according to Cox with fixed pretransplant covariates and post-transplant cytomegalovirus (CMV) infection and graft-versus-host (GVHD) as time-dependent covariates. Advanced stage of leukemia at the time of transplantation was an important risk factor for subsequent relapse. Furthermore, the study confirmed a graft-versus-leukaemia (GVL) activity associated with chronic GVHD, including de novo chronic GVHD (intensity factor 0.08, p = 0.004). In a model excluding chronic GVHD, female donor-to-male recipient (a risk factor for GVHD), was associated with decreased post-transplant relapse risk (intensity factor 0.3, p = 0.008), suggesting that an allo-reaction against a minor transplantation antigen (Hy) may mediate antileukaemic activity. A decrease of the relapse risk by a factor 0.18 was observed in recipients with AML as well as ALL when the donor was CMV seropositive (p = 0.0002). This effect was restricted to patients who had laboratory evidence of post-transplant CMV infection. When CMV infection occurred and donor was seropositive the relapse risk was reduced by a factor 0.035. The effect was not mediated through an increased occurrence of grade 2-4 acute or chronic GVHD and could not be explained by a statistical bias due to censoring of patients who died in remission. Rather, donor CMV immunity was associated with GVHD independent GVL activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

A role of herpes virus serology for the development of acute graft-versus-host disease. Leukaemia Working Party of the European Group for Bone Marrow Transplantation.

Pretransplant herpes virus serology and acute graft-versus-host disease (GVHD) were studied in 379 leukaemic bone marrow transplant (BMT) recipients and their HLA-identical sibling donors. In logistic multivariate regression analysis pretransplant seropositivity to three or more different herpes viruses among the recipients was the only significant factor associated with grade II-IV acute GVHD (p = 0.03). If this factor was excluded, older donor age (p less than 0.001), absence of T cell depletion (p less than 0.001), pharmacological immunosuppression by monotherapy of methotrexate or cyclosporin versus a combination therapy of both (p = 0.002), and seropositivity to three or more herpes viruses among the donors (p = 0.03) prior to BMT, were also significantly associated with acute GVHD. The data indicate that latent herpes viruses in the host may act as minor histocompatibility antigens or by other means to trigger acute GVHD.

Adolescent

Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera.

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.

Acquired Immunodeficiency Syndrome

Occupational health problems and adverse patient reactions in orthodontics.

The purpose of the present investigation was to study the nature and frequency of adverse reactions to materials and procedures among orthodontists and their patients. A questionnaire about this topic was mailed to practicing members of the Norwegian Orthodontic Society, of which 137 (about 75%) responded together with 127 chairside assistants. About half of the orthodontic personnel had experienced adverse reactions. The majority of the problems were dermatoses, comprising dryness, redness, itching, thickening, reduced tactile sensitivity, fissuring, soreness/desquamation and pain of hands and fingers. The residual were respiratory reactions, eye reactions or reactions of a general nature. Many of the dermatoses were of moderate severity, attributed to (seasonal) air/ventilation associated problems. Other frequent causes were hand washing procedures, work involving composites and acrylics (orthodontists), or work involving model materials, alcoholic disinfectants, latex gloves, alignates etc. (assistants). For both groups the most severe dermatological reactions were associated with unspecified allergies, acrylics and composites. Non-dermatological reactions also reflected the different working pattern and exposure to materials in orthodontics; acrylic monomer topping the list. The orthodontists had observed 425 patients with dermal reactions and 67 patients with intraoral/systemic reactions, indicating a prevalence of about 1 per cent. Dermal reactions included redness, eczema, itching and fissuring in facial, neck or perioral areas, mostly attributed to metallic parts of extraoral appliances, with some exceptions (elastics, neck pillows, head caps). Intraoral reactions consisted of redness, soreness and swelling of the oral mucosa, gingiva and/or lips and were associated with metal brackets, labial wires, bonding procedures or acrylic appliances.

Adolescent

Specific depletion of mature T lymphocytes from human bone marrow.

An effective method for specific depletion of mature T lymphocytes from human bone marrow mononuclear cells (BMMC) with preservation of prethymic T cells and natural killer (NK) cells is presented. The BMMC were incubated with F101.01, a monoclonal antibody recognizing an epitope of the T-cell receptor-CD3 complex, and subsequently with immunomagnetic beads. Flow cytometric analysis demonstrated that mature T cells were efficiently depleted and that NK cells and prethymic T cells were preserved in the BMMC. Furthermore, T cell-mediated immune reaction as measured by thymidine incorporation after stimulation with phytohaemagglutinin was abolished, whereas NK activity as measured by 51Cr release using K562 as target cells was preserved. Recovery of colony-forming units of granulocyte-macrophages was 60-70%.

Bone Marrow

Occupational health problems and adverse patient reactions in periodontics.

The purpose of the present survey was to assess the nature and extent of adverse reactions to materials and procedures among personnel in periodontal practice and their patients. A questionnaire was mailed to practicing members of the Swedish Society of Periodontists. A total of 85, about 65%, responded together with 44 dental hygienists and 64 chairside assistants. 42% had experienced adverse reactions. The majority of complaints were related to dermatoses of the hands and fingers. The remainder were respiratory or eye reactions. A specifical problem characteristically involving the hygienists, was musculoskeletal stress reactions. Many of the dermatoses were of moderate severity, and were associated with seasonal, air-ventilation problems or were unexplained. The most severe reactions were reported by atopic persons. The reactions were attributed to hand washing procedures, the use of latex gloves and other disposable personal equipment such as face masks and caps. Reactions attributed to dental materials or local anaesthetics, characteristic of other reports from general dental practice, were absent. The survey indicated that personnel in periodontal practice have problems similar to many other categories of health personnel. Patient reactions were encountered at a frequency of 1 every other year per periodontist. The majority were intraoral reactions to chlorhexidine mouthrinses. Other patient reactions were associated with exposure to latex gloves, eugenol-containing periodontal packs, methacrylates and nickel-containing instruments. 2 instances of anaphylactoid reactions to latex gloves were encountered.

Adult

[Causes of interruption of dental studies and subsequent change in careers].

During recent years an increasing number of dental students at the University of Oslo used prolonged student time and graduated with mediocre results, or interrupted studies without graduation Jacobsen, Acta Odontol Scand 45:399-408, 1987). The present investigation aimed at clarifying the reasons for interrupted studies and at getting information about subsequent career. Semistructured questionnaires on curricular and socioeconomic causes for drop-out and on subsequent career were mailed to 98 persons who had quit dental studies during a 10-year period. Free comments on circumstances relevant to their drop-out were encouraged. The following findings are based on 68 replies (69 per cent): Sixty-three students (93 per cent) quit dental school for different curricular reasons, a majority of which was "more interest in other subjects". Contributory factors of socioeconomic nature, mostly future unemployment concern, were often mentioned. Forty-five (66 per cent) later graduated with university degrees in medicine, economics, veterinary medicine, science, technology, law etc, and the remainder, except two persons, finished up to 4 years of studies at regional colleges or similar institutions. Free comments focused on curricular, pedagogical, and social shortcomings at the dental faculty. The findings indicated that a large majority of the students who dropped out did so for lack of stimulation by the dental curriculum and not for lack of academic potential. Only a few students quit because, in their own description, they were immature for university studies at the time, or because they had "academic" difficulties with the early science/biology courses or with the preclinical technique courses.

Adult