Biomedical subjects
Publications and source records attributed to D Djawari.
We report on a 48-year-old patient who had increasingly suffered from impotence since 20 years. Since three years, aspermatism had been additionally noted. Androgenic dysfunction was attributed to low plasma testosterone and high prolactin levels. As the cause, we diagnosed prolactinome growing downward the pituitary sella. Our therapy comprised neurosurgery as well as combined oral administration of bromocriptin.
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The present randomized, placebo-controlled double-blind multicenter study included a population of 36 subjects with frequent recurrences (at least once a month) of herpes labialis. Most of the patients had failed to respond adequately to previous treatment with other therapeutic tools, including acyclovir. Either 50 mg of thymopentin or of placebo was administered 3 times a week, by the subcutaneous route, for 6 weeks. Subsequently, the patients were observed for nearly 6 months on the average. The results achieved with thymopentin for the individual parameters were significantly superior to those obtained with placebo; thus significant improvement was seen in patients on thymopentin in the duration of the longest symptomfree period (prolonged from 2.1 weeks to 20.9 weeks, p = 0.000), in the number of relapses (reduced from 1.6 to 0.4 episodes/month, p = 0.001), and in the total duration of herpes symptoms per month (shortened from 2.0 to 0.3 weeks, p = 0.000). Placebo treatment also resulted in considerable improvement (p less than 0.05 or 0.01), but was significantly inferior to the improvement obtained with thymopentin. The longest symptomfree period in the placebo group was prolonged from 2.4 to 11.2 weeks. The number of relapses per month was reduced from 1.4 to 0.8, and the total duration of herpes symptoms per month from 2 to 0.9 weeks. The results of intergroup analyses, in which the observed parameters and the improvement achieved in either group were compared, significantly favored thymopentin treatment. The effect of thymopentin was in all but one parameters superior to that of placebo and highly significant (p less than 0.01).
This paper presents longitudinal clinical and immunological findings in a patient with a life-long history of pluriorificial pyoderma vegetans, a disease characterized by a distinct immunodeficiency of T lymphocytes. After treatment with thymopentin, 50 mg s.c. three times weekly for 12 weeks, the number of T lymphocytes in peripheral blood normalized, while other impaired immunological functions failed to improve, however. The most impressive observation was the significant clinical improvement of the patient's condition.
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Comparative in vivo examinations of skin (cutaneous pathergy test, skin window technique over 24 h according to Rebuck) were carried out in 12 patients with Behçet's disease (BD) and in 13 healthy volunteers serving as controls. 10 out of 12 patients at active phases of BD showed a positive papular (-pustular) skin reactivity to needle prick or venepuncture. These 10 patients simultaneously revealed an increased chemotactic activity of polymorphonuclear leukocytes (PMNL) in vitro. In the controls all pathergy tests were negative and chemotaxis of PMNL was within normal range. The proportion of PMNL initially coming up to 100% in the skin window preparations, very rapidly decreased in patients with BD as compared to a distinctly slower drop in the controls. Conversely to the number of PMNL, the skin window cellular pattern was built up by monophagocytic cells replacing the PMNL. The phenomenon of 'rapid depletion of PMNL', from skin window can be considered an additional hint on the functional disturbance of the PMNL involved in the pathogenesis of BD.
Twenty-seven patients suffering from long-standing, severe, recurrent herpes simplex (14 labial and 13 genital) who had not responded adequately to prior therapy were recruited for this open, monitored study. They were treated with thymopentin 50 mg subcutaneously three times weekly for a period of 6 weeks. Clinical controls were performed once a week and then again 6 weeks after cessation of therapy; laboratory investigations were done at time points 0, 3, and 6 weeks. Additionally, information was collected with regard to the clinical course during the following year. Thirteen of 14 patients with labial infection and 10 of the 13 with genital herpes improved markedly (p less than 0.05) as shown by decrease in the relapse rate of at least 50%, shorter relapse episodes, and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than 4 months after cessation of therapy. These favorable results were paralleled by a statistically significant increase in the T cell helper/suppressor ratio. This finding indicates that thymopentin acts as an immunodomulator; it is assumed that the activation of T helper cells induces-presumable via interleukin 2-the proliferation of cytotoxic T lymphocytes and natural killer cells which play a major role in the natural immune defense. No serious side effects of thymopentin were recorded.
62 patients suffering from recurrent herpes simplex, with ten out of them showing postherpetic erythema multiforme, have been investigated with special reference to histocompatibility standardisation. In comparison with a control group (n = 170), our patients revealed a high and statistically significant level of HLA-B5 (p less than 0,01). Postherpetic erythema multiforme seems to be associated with HLA-A9.
HLA-pattern was analysed in 60 patients with recurrent benign aphthosis (RBA), in another 14 suffering from Behçet's disease (BD) and in 200 healthy individuals, all of German origin. High prevalence rates of HLA-A2, HLA-B5 and HLA-Cw3 haplotypes were found in patients with RBA, yet significant only for HLA-Cw3 (p = 0.01). HLA-B5 was shown in none but two German patients with BD. These results are discussed with particular regard to reports on racial differences of HLA-patterns in the populations of several continents including patients with aphthous disorders.
Treatment resistant recurrent herpes simplex persisting for years in 7 patients was treated with thymopoietin pentapeptide for 6 weeks, 50 mg subcutaneously three times per week. During treatment and follow-up of 6 weeks a pronounced reduction of frequency and duration of recurrences were observed. There was some tendency for normalisation of deranged lymphocyte and granulocyte function. The mode of action of thymopoietin pentapeptide in recurrent herpes simplex remains uncertain. An indirect effect via stimulation of production of interferon may be assumed.
Various micro- and macrophage functions were studied in vitro in 21 patients suffering from lichen ruber planus and in 100 healthy individuals. A slight impairment of chemotactic activity of microphages (12/21) and a reduced capacity of intracellular inactivation of microorganisms in both systems (14/21; 3/12) were found.
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Mycobacterial histiocytosis is a generally fatal disease characterized by abundant amounts of undigested atypical mycobacteria present within tissue macrophages that diffusely infiltrate the affected lymph nodes. The immune functions of a 22-year-old man with infection due to Mycobacterium avium were investigated. Although the patient had a marked increase in serum immunoglobulin levels and detectable antibodies toward mycobacterial antigens, he had no cellular response to these antigens both in vivo and in vitro. There was an elevated proportion of blood cells with the helper/inducer (T4+) phenotype, but these cells showed a markedly decreased response to several T-cell mitogens, as well as to autologous and allogeneic cells. The patient's lymphocytes produced diminished amounts of immune interferon, and there was no detectable interleukin 2 (IL-2) activity after stimulation with phytohemagglutinin (PHA). The proliferative response of T4+ cells to pokeweed mitogen (PWM), however, was normal; 47% of these cells bore the Tac antigen, and the production of IL-2 using PWM was within the normal range. No phenotypical or functional abnormalities were found in peripheral blood monocytes. These findings suggest a dissociation of helper/inducer T-cell functions with intact B-cell help, but an impaired ability to activate tissue macrophages or to produce immune mediators.
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Twenty-four patients suffering from longstanding severe recurrent herpes simplex, who had not responded to prior therapy, were treated with s.c. thymopentin injections 50 mg, three times weekly, over a period of six weeks. They were followed up at weekly intervals over this period and then six weeks later. Moreover, the longest relapse-free period observed in the year after the treatment was recorded in the investigator's documentation. Thirteen of the 14 patients with labial herpes simplex and 10 of the 13 patients with genital herpes simplex improved markedly as shown by a decrease in the relapse rate of at least 50%, shorter episodes of relapse and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than four months after cessation of the therapy. No serious side-effects were observed. Laboratory examinations before, during and after thymopentin did not reveal significant alterations except for an increase in the T-helper/T-suppressor ratio. The effect of thymopentin is assumed to be due to T-helper cell activation resulting in enhanced interleukin-2 production with subsequent proliferation of cytotoxic T lymphocytes and natural killer cells which are capable of producing immune interferon.
This is a report of a 24-year follow-up of a man now 33 years of age, who suffers almost continuously from severe inflammatory lesions of the lips, nose and eyelids, with increased susceptibility to respiratory infections since early childhood. The condition, previously described as "pyo-rhino-blepharo-stomatitis vegetans (McCarthy)", was treated with systemic corticosteroids and antimicrobial agents for years, but failed to improve until the immune status of the patient was checked after withdrawal of the steroids. T lymphocytes were found to be abnormal as to count in peripheral blood and various functional qualities determined in vivo and in vitro. For treatment, levamisole and thymopoietin pentapeptide (TP-5) were given. Subsequently each drug induced rapid and complete clearing of all lesions, but was followed by the recurrence of facial periorificial lesions after drug withdrawal. Change of the regimen by administering either inosiplex orally or commercial calf thymus extract parenterally, remained ineffective. During therapy with levamisole as well as TP-5, the number of T lymphocytes in peripheral blood normalized, yet impaired functions failed to improve. There was an elevated ratio of T-suppressor/T-inducer cells in blood using OKT antibodies. In vitro testing of different functions of polymorphonuclear leucocytes revealed normal results except for a slight decrease of chemotactic activity during levamisole. In view of the long clinical course, the mass of clinical and immunological data collected over decades, and the therapeutic results as a whole, the disease can be characterized as a peculiar type of pluriorificial pyoderma vegetans, caused by a distinct immunodeficiency of T lymphocytes.
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Five patients suffering from recurrent oral aphthae and one patient with Behçet's disease were treated with thymopoetin pentapeptide injections for 6 weeks. Although some immune parameters showed a tendency toward normalization no clinical improvement was observed.