Aretaeus on migraine and headache.

Aretaeus of Cappadocia's classification of headache has been referred to for many centuries. Several Latin translations and an English translation (1856) of his books have been published in the past. We translated the pertinent texts on headache from the Greek text as published by Hude in 1958. In this paper, we present an annotated translation preceded by an outline of contemporary knowledge of headache from Celsus' De Medicina. Although symptomatic headache was most probably involved in the types of headache identified by Aretaeus and the making of retrospective diagnoses is hazardous, the terms heterocrania and cephalea may be compared with what today we would call migraine and tension type headache respectively.

Convulsions due to increased permeability of the blood-brain barrier in experimental cerebral malaria can be prevented by splenectomy or anti-T cell treatment.

Experimental cerebral malaria (ECM) can be induced in C57B1 mice by infection with Plasmodium berghei K173 parasites. Behavioral changes shortly before they die of ECM may reflect disturbance of the integrity of the blood-brain barrier (BBB). Folic acid elicits strong convulsive activity if the permeability of the BBB is increased. Administration of folic acid to mice during development of ECM induced convulsions. Interventions known to prevent fatal outcome from ECM, such as splenectomy or treatment with anti-CD4 or anti-CD8 monoclonal antibodies, also prevented sensitivity to folic acid-induced convulsions. In addition, infected mice with ECM and sensitive to folic acid-induced convulsions, recovered from this sensitivity after treatment with anti-T cell antibodies within 4 h. These data suggest that disturbance of the permeability of the BBB can be reversed and depends on the involvement of T cells.

Depletion of CD4+ or CD8+ T-cells prevents Plasmodium berghei induced cerebral malaria in end-stage disease.

The role of T-cells in development of experimental cerebral malaria was analysed in C57B1/6J and C57B1/10 mice infected with Plasmodium berghei K173 or Plasmodium berghei ANKA by treatment with anti-CD4 or anti-CD8 mAbs. Mice were protected against cerebral malaria (CM) when anti-CD4 or anti-CD8 mAbs were injected before or during infection. Even in mice in end-stage disease, i.e. with a body temperature below 35.5 degrees C, treatment with anti-CD4 or anti-CD8 antibodies or the combination protected against CM, whereas chloroquine treatment was completely ineffective in inhibiting further development of the cerebral syndrome.

Attenuated immunogenic parasites are essential in the transfer of immunity to virulent Plasmodium berghei.

A less virulent parasite of Plasmodium berghei K173 was isolated that induced immunity against the more virulent parasite. Immunity to this parasite but not to the virulent one, could be transferred by immune spleen cells but not by immune lymph node cells. However, the immune spleen cells did transfer immunity to the virulent strain if accompanied by infection with viable parasites of the less virulent strain, but only if they were allowed to proliferate for a period of 1 week before challenge with the virulent strain. Immune spleen cells could survive two cycles of mouse to mouse transfer. The induction of immunity by transfer of immune spleen cells was associated with the production of anti-parasitic antibody.

Is Recormon less painful than Eprex after subcutaneous administration?

In this study, we examined the differences in pain score after subcutaneous injection of the epoetin preparations Eprex and Recormon. Patients (n = 30) received 5 injections Eprex and 5 injections Recormon in a randomized double-blind sequence. 10 Min after receiving the injection the patient was asked to complete a visual and a verbal analogue scale and two descriptive scales. The results of 25 patients were used for statistical evaluation. The overall results indicate that there are significantly more patients reporting pain after subcutaneous injection of Eprex than after Recormon (11 versus 2 patients, p less than 0.05; McNemar test). 12 Patients reported no differences in pain. 43 Out of 123 injections Eprex and 69 out of 125 injections Recormon caused no pain (p less than 0.01; chi 2 9.455). For 4 patients Recormon was significantly (p less than 0.05) less painful than Eprex. It can be concluded that Recormon may be a less painful alternative for individual patients reporting pain after subcutaneous injection of Eprex.

[The patient exhibited; clinical demonstration and clinical lessons in the Nederlandsch Tijdschrift voor Geneeskunde]. / De patiënt tentoongesteld; klinische demonstratie en klinische les in het Nederlandsch Tijdschrift voor Geneeskunde.

The evolution of clinical demonstrations and of the illustrations is discussed, with reference to the importance of sharpening observation as a medical method. It is especially in the section 'Clinical Lessons' in the Nederlandsch Tijdschrift voor Geneeskunde that the way in which the patient is shown in illustrations is considered in detail, including the question to what extent limits were imposed on what was considered permissible in illustrations.

The need for live parasites for long-term immunity in malaria.

All of the results of the various experiments support a role for living, proliferating parasites in the efficient induction of anti-parasitic as well as anti-disease (CM) immunity. Non-proliferating parasites or material from disrupted parasites are poor or non-antigens in this respect. Three possibilities as to why living parasites are important in immunity could be considered: 1. circulating parasites contain insufficient antigen to induce protective immunity, but sufficient antigen can be produced during proliferation; 2. only circulating parasites arrive at critical places (e.g. parts of the white pulp of the spleen) for the presentation of the important antigen or induction of appropriate signals. 3. Architectural changes are needed (i.e. formation of barrie-cell-complexes) for the immune response to be effective. The first possibility explains why exoantigens, as well as live, proliferating parasites are efficient inducers of anti-CM immunity. Since these immunizations have no effect on parasitemia, additional/other immune reaction(s) are needed for anti-parasitic immunity. The important role of the spleen in malaria and malaria immunity is well-known. The second possibility includes the idea that live, proliferating parasites circulate through the spleen continuously where unsatisfactory or infected erythrocytes are removed rather than in the liver. Injected killed parasites or material from them when present in the circulation is to a larger extent taken up by the Kupffer cells from the liver rather than the spleen. Presence and uptake of parasites in the spleen may provide the critical confrontation and/or delivery of signals necessary for the development of immunity.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired immune responsiveness in Plasmodium berghei immune mice.

Mice immunized against Plasmodium berghei parasites by drug-controlled infection exhibited decreased immunoresponsiveness against rabbit red blood cells (RRBC). Increasing RRBC antigen dose increased responsiveness, but agglutinating anti-RRBC antibodies of the IgG class remained undetectable. Clearance of colloidal carbon from the bloodstream of malaria-immunized mice was not different from controls. Removal of all the persistent parasites from immune mice did not restore responsiveness until 140 days after treatment, suggesting that the parasite per se did not influence responsiveness directly. Because of this, and because of the fact that priming of mice with RRBC before P. berghei immunization was not more effective than priming after immunization, it was concluded that antigen uptake and subsequent presentation were not impaired in P. berghei immune mice, in contrast to infected mice. Anti-RRBC antibodies were detected in serum of P. berghei immune mice, but regulation of responsiveness to RRBC by transfer of such immune mouse serum was not found. Immunoglobulin levels, especially of the IgG2 and IgG3 subclass were elevated in sera of P. berghei immune mice, which indicated an LPS-like polyclonal activation. The results also suggest that during drug-controlled infection, which leads to immunity against infection, a state of B-cell tolerance is induced.

Thin-basement-membrane nephropathy in adults with persistent hematuria.

Thin-basement-membrane nephropathy, also called benign recurrent hematuria, is characterized by diffuse thinning of the glomerular basement membrane and by hematuria. To determine the incidence of thin-basement-membrane nephropathy among patients with idiopathic hematuria, we conducted a prospective study in the nephrology units of three large hospitals in the Netherlands. Eighty normotensive adults without azotemia underwent renal biopsy because of recurrent macroscopic hematuria (n = 26) or persistent microscopic hematuria (n = 54). Idiopathic IgA nephropathy was found in 27 of the 80 patients. Light microscopical examination showed that 42 patients had normal renal tissue. The remaining 11 patients had mesangioproliferative glomerulonephritis (n = 5), interstitial nephritis (n = 3), or focal global glomerulosclerosis (n = 3). Tissue from the 42 patients whose renal biopsy specimens were normal when examined with light microscopy was analyzed morphometrically with electron microscopy to determine the thickness of the glomerular basement membrane. Two subsets of patients were identified by this analysis. In 18, thin-basement-membrane nephropathy was found (mean basement-membrane thickness [+/- SE], 191 +/- 28 nm; normal, 350 +/- 43 nm); all but one of these 18 patients had microscopic hematuria, which persisted during follow-up (median duration, 50 months). (Of the 54 patients who presented with microscopic hematuria, 17 [31 percent] had thin-basement-membrane nephropathy.) The thickness of the glomerular basement membrane was normal in the other 24 patients (361 +/- 69 nm); during follow-up, hematuria disappeared in all 13 of these patients who had macroscopic hematuria, and hematuria resolved in 5 of the 11 patients who had microscopic hematuria. We conclude that in patients with persistent microscopic hematuria, the incidence of thin-basement-membrane nephropathy is similar to that of idiopathic IgA nephropathy. Morphometric analysis of the thickness of the glomerular basement membrane should be included in the workup of adults with persistent microscopic hematuria that is not of urologic origin.

Malarial immunity in pregnant mice, in relation to total and unbound plasma corticosterone.

A pregnancy dependent loss of malarial immunity is accompanied by an (excessive) increase of total as well as free plasma corticosterone. This loss of immunity was largely prevented by adrenalectomy. Moreover, malarial immunity was more sensitive to dexamethasone immunosuppression during pregnancy. Primary infections are more virulent during pregnancy and like in recrudescent mice, cause excessive total and free plasma corticosterone levels. Corticosterone may be considered an immuno-regulatory serum factor during pregnancy, the endocrine regulation of which is disturbed in pregnant, infected mice.

In vitro studies of 5, 10-methylenetetrahydrofolate reductase: inhibition by folate derivatives, folate antagonists, and monoamine derivatives.

Folate monoglutamates and folate antagonists have an inhibitory action on the activity of 5,10-methylenetetrahydrofolate reductase in rat brain. The type of inhibition was studied for dihydrofolic acid using the Lineweaver--Burk transformation. Some of the monoamine alkaloids, the in vitro products of 5,10-methylenetetrahydrofolate reductase, have either a stimulatory or inhibitory effect on the enzyme activity.