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PubMedDate not supplied

Neurosyphilis, or chronic heavy metal poisoning: Karen Blixen's lifelong disease.

BACKGROUND: Since the 1490s, the treatment of syphilis has consisted of heavy metals--first mercurial and later arsenic and bismuth preparations. Tabes dorsalis, as described by Duchenne in the 1850s, is made up of various characteristic neurologic symptoms. "Gastric crises," sudden stabbing pains followed by vomiting and diarrhea, was originally included by Duchenne, but later, syphilologists disputed its relevance to syphilis. Poisoning by heavy metals, including mercury, may produce similar pain reactions and tabes-like neurologic symptoms. METHODS: According to an earlier published pathography, the Danish author Karen Blixen (1885-1962), also known under the pseudonym Isak Dinesen, suffered from a lifelong disease described as tabes dorsalis. She got syphilis in 1914 and took mercury pills for a year, after which she experienced a severe mercurial intoxication. The Wassermann reaction (WR) in peripheral blood was positive only once, in 1915, before treatment with arsphenamine (Salvarsan), which she received during hospitalization in Copenhagen in 1915 to 1916. Her spinal fluid was examined several times from 1915 to 1956. Apart from an increased number of cells in 1915, the fluid remained unremarkable and the WR was always negative. RESULTS AND CONCLUSIONS: It was postulated that her illness, ending with a cachectic state, was the result of heavy metal poisoning from the various treatments and not a monosymptomatic tabes dorsalis with negative serology.

Arsenicals↗
PubMed1975

[Histomorphology of the liver by damage with phenolisatine-containing laxatives (Recurrent chronic cholangiohepatitis)].

In the case of 36 female patients who were anamnestically known to have taken laxatives, semiquantitative histological investigations with laparoscopically obtained liver needle biopsies were effected after the exposition with preparations containing phenolisatine. The time gap until exposition was 12 to 24 h (16 cases), 48 h (8 cases), 72 to 96 h (4 cases) and 7 to 14 days (4 cases). The histological result after the exposition is an acute cholangiolitis of the allergic-hyperergic type with edema and a dense eosinophile infiltration of the portal fields with destruction of the epithelium of preformed bile ducts and portally proliferated ductles. In addition, the parenchyma of the liver shows a pleomorphism of the cells in form and colour with a cellular edema and with disseminated acidophilic necroses and necrobioses of the individual cells as well as with little reactive proliferation of the Kupffer's cell. After a period of 8 days the acute process has more or less subsided. Also, in the majority of cases there are histological signs of an aggressive chronic hepatitis of type IIa, partially in the active stage with piece-meal necroses and partially stabilized or in the process of healing. A transition to the picture of hepatitic cirrhosis is possible. In serious cases the picture of a chronic non-purulent destructive cholangitis can be simulated by the hepatocellular and canalicular damage. Thirty-one bioptic pre-examinations from the same results, whereby the acute cholangiolitical exacerbation can be attributed to an exposition of the patients themselves. The clinical picture of the phenolisatine damage in its entirety is induced by medication and is described as a recurrent chronic cholangiohepatitis. Similarities exist between the liver damages caused by chlorpromazine and arsphenamine. When medication is discontinued, the morphologic substrate recedes leaving behind an inactive fibrosis or cirrhosis. The formal and known causal pathogenetic connections are discussed with regard to this clinically important liver disease. Guidelines are then given for histological diagnosis of this damage caused by medication. 14% of the female patients with a histological picture of aggressive chronic hepatitis and hepatitic cirrhosis are affected by this type of liver damage.

Adult↗
PubMed2006

The contributions of Paul Ehrlich to infectious disease.

Paul Ehrlich (1854-1915) is nowadays considered a pioneer in a number of medical fields, and in the course of time his role in the establishment and development of disciplines such as histology, immunology, oncology and haematology has been acknowledged. Aim of this historical note is to illustrate, in the area of chemotherapy, the special importance of this brilliant scientist whose 150th anniversary of birth occurred in 2004. Already as a medical student, Ehrlich was obsessed by structural organic chemistry and dyes, and, continually studying these issues, he elaborated his theory regarding the discovery of a "magic bullet", able to specifically destroy tumour cells and micro-organisms. In practice he applied methylene blue to the treatment of malaria patients, following his intuition that such a dye could destroy parasites. However, his culminating achievements in the chemotherapic field, reached even at the expense of his health, were the concept of the one-dose treatment of Helicobacter pylori infection, and the creation of arsphenamine (compound 606, or Salvarsan), the first really effective compound in controlling human syphilis. Within the many and various contributions of Ehrlich to the development of experimental and clinical medicine, a special mention of his experimental studies and clinical applications in the area of chemotherapy is essential, since his achievements in this biomedical area remain a paramount legacy in the history of the therapy of infections.

Allergy and Immunology↗
PubMed1991

Syphilis, neurosyphilis, penicillin, and AIDS.

Early neurosyphilis, characterized by meningitis, cranial nerve abnormalities, and cerebrospinal accidents, was first described in patients with syphilis who received inadequate courses of arsphenamine. Although more effective, penicillin at conventional doses does not yield treponemacidal levels in the central nervous system and probably does not eradicate the infecting organisms, suggesting that it works synergistically with the host's immune response in preventing neurosyphilis. Neurosyphilis after penicillin therapy was almost unheard of in the United States until it began to appear in human immunodeficiency virus (HIV)-infected patients. Numerous cases of syphilitic meningitis, cranial nerve abnormalities, and strokes have been reported in the past decade; about one-half of reported patients had received penicillin therapy, often within the previous 6 months. Thus, more intensive diagnostic evaluation, perhaps including routine cerebrospinal fluid analysis, more intensive therapy, for example with at least three doses of benzathine penicillin, and far more rigorous follow-up are indicated in HIV-infected subjects with syphilis. Since the efficacy of conventional therapy is now uncertain, novel approaches to treatment deserve systematic evaluation.

HIV Infections↗
PubMed1988

Squamous cell carcinoma arising in Hailey-Hailey disease.

A case of squamous cell carcinoma (SCC) arising in a lesion of Hailey-Hailey disease at the penoscrotal junction is reported. The patient was treated with arsphenamine (Salvarsan 606) early in the disease. It is possible that this carcinogen, as well as friction and the local irritation of long-standing Hailey-Hailey skin lesions, may be the predisposing factors for the development of SCC in this case.

Aged↗
PubMed2005

Thermotropic liquid crystalline drugs.

Crystalline solids are characterized by long-range positional and orientational order in three dimensions, whereas amorphous liquids lack long-range order in any dimension. Liquid crystals (mesophases) show structural, mechanical and optical properties intermediate to those of crystalline solids and the amorphous, liquid state of matter. There are two principle types of liquid crystals: thermotropic liquid crystals (TLCs) and lyotropic liquid crystals (LLCs). TLCs can be formed by heating a crystalline solid or by cooling an isotropic melt of a TLC-forming molecule (mesogen). In the first part of this review the types of liquid crystals are defined and classified and the structural properties of mesogens are explained. In the second part, ten case studies of thermotropic mesomorphous drugs and pharmaceutically relevant molecules (arsphenamine, nafoxidine hydrochloride, L-660711, palmitoyl propranolol hydrochloride, penbutolol sulfate, itraconazole hydrochloride, fenoprofen sodium, fenoprofen calcium, ciclosporin and cholesteryl esters) are presented and their thermotropic mesomorphism is described. The review closes with a brief discussion of the unusual properties of drug mesophases and a potential use of drugs and excipients in this fourth state of matter.

Crystallization↗
PubMed1976

Veno-occlusive disease of the liver after chemotherapy of acute leukemia. Report of two cases.

Two adult male patients with acute leukemia developed a fatal Budd-Chiari-like illness while receiving 6-thioguanine. Both had previously received cytosine arabinoside. Antemortem and postmortem specimens of liver showed changes characteristic of toxic veno-occlusive disease. Similar findings have been described after ingestion of certain plant alkaloids and after treatment with arsphenamine, urethane, and ionizing radiation to the liver. We are unaware of any published reports of veno-occlusive disease of the liver after treatment with either 6-thioguanine or cytosine arabinoside. Although 6-thioguanine was most likely responsible for this syndrome, it is not possible to eliminate cytosine arabinoside as the causative agent. Since both drugs are occasionally used for benign conditions, physicians should be aware of this possible complication.

Acute Disease↗
PubMed1976

Treatment of late benign syphilis: review of the literature.

The English literature on the treatment of late benign syphilis with penicillin was reviewed. To date there have been no controlled randomized therapeutic trials to support the efficacy of this therapy. This disease responds rapidly to all antisyphilitic drugs including arsphenamine and heavy metals. There are ample case reports and 2 major therapy studies which demonstrate the safety and beneficial effects of penicillin in individual patients. Although the exact dosage and duration of therapy are open to speculation, it is wise to treat patients with late benign syphilis with doses of penicillin judged to be effective for concomitant neuro-or cardiovascular syphilis.

Humans↗