Arsenical Therapy Research Articles

Efficacy of imidacloprid 10%/moxidectin 2.5% spot on (Advocate®, Advantage Multi®) and doxycycline for the treatment of natural Dirofilaria immitis infections in dogs

Heartworm infection (also known as dirofilariosis due to Dirofilaria immitis) in dogs causes chronic pulmonary disease that, if left untreated, can lead to right-side congestive heart failure. Currently, the only registered drug for adulticide therapy in dogs with heartworm disease (HWD) is melarsomine dihydrochloride. The recent targeting of the bacterial endosymbiont Wolbachia, through antibiotic therapy of the infected host, has offered an interesting alternative for the treatment of HWD. Recent reports of the adulticide activity of an ivermectin/doxycycline combination protocol has lead the American Heartworm Society (AHS) to include in its guidelines that, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period might be considered. In the present study, 20 dogs with confirmed natural D. immitis infection were included following owner consent. Fourteen dogs were treated with a topical formulation containing 10% w/v imidacloprid and 2.5% w/v moxidectin (Advocate®, Advantage Multi®, Bayer), monthly for nine months, associated to doxycycline (10 mg/kg/BID) for the first 30 days. Six dogs were treated with melarsomine (Immiticide®, Merial) (2.5 mg/kg) at enrollment, followed one month later by two injections 24 h apart.The presence of circulating antigens and the number of microfilariae (mf) were evaluated at the moment of enrollment and then at 1, 2, 3, 4, 5, 6, 7, 8, 12, 18, 24 months post enrollment. Echocardiogram and radiographs were performed at month 0, 6, 12, 18, 24.Monthly moxidectin combined with 30 days of doxycycline eliminated circulating microfilariae within one month, thus breaking the transmission cycle very quickly. Furthermore, dogs treated with the combination protocol started to become negative for circulating antigens at 4 months from the beginning of treatment and all except one were antigen negative at 9 months. All dogs treated with melarsomine were antigen negative by 5 months from the beginning of the treatment. No dogs showed worsening of pulmonary patterns or criteria indicative of pulmonary hypertension 12 to 24 months after. For the criteria mf concentration, antigen concentration, radiography and echocardiography at 12, 18 and 24 months the non-inferiority for the moxidectin group could be proven for a non-inferiority margin of 15% for the rate difference. Dogs treated with moxidectin and doxycycline became negative for microfilariae and antigens sooner when compared to melarsomine in the present study and to dogs treated with doxycycline combined with ivermectin in studies previously published.

Wolbachia, doxycycline and macrocyclic lactones: New prospects in the treatment of canine heartworm disease

Melarsomine dihydrochloride (Immiticide®, Merial) is the only approved adulticidal drug for the treatment of canine heartworm disease (HWD). However, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period, which targets the bacterial endosymbiont Wolbachia, might be considered. There are published reports on the efficacy of ivermectin and doxycycline in both experimentally and naturally infected dogs, but no data on the use of other macrocyclic lactones (MLs) with a similar treatment regime. Preliminary results of studies in dogs show that a topical formulation of moxidectin, the only ML currently registered as a microfilaricide, is also adulticidal when combined with doxycycline. It is not yet known if the efficacy of these combination therapies is due to pharmacokinetic synergism. A recent study showed that serum levels of doxycycline in dogs treated with the combination protocol were not statistically different compared to dogs treated with doxycycline alone. However, lungs from dogs treated with the combination therapy showed a marked reduction in T regulatory cells, indicating that treatment efficacy may be due to a heightened immune response against the parasite. Further studies are necessary to evaluate the long-term clinical outcome of combination protocols and to establish the most efficient treatment for HWD in dogs.

Chronic fatigue syndrome (CFS) associated with Staphylococcus spp. bacteremia, responsive to potassium arsenite 0.5% in a veterinary surgeon and his coworking wife, handling with CFS animal cases

Chronic fatigue syndrome (CFS) in human patients remain a controversial and perplexing condition with emerging zoonotic aspects. Recent advances in human medicine seem to indicate a bacterial etiology and the condition has already been described in horses, dogs, cats and birds of prey in association with micrococci-like organisms in the blood. To evaluate the possibility of a chronic bacteremia, a veterinary surgeon (the author) and his coworking wife, both diagnosed with CFS and meeting the CDC working case definition, were submitted to rapid blood cultures and fresh blood smears investigations. Blood cultures proved Staph-positive and micrococci-like organisms in the blood were repeatedly observed in the 3-year period preceding the arsenical therapy, during which several medicaments, including antibiotics, proved unsuccessful. Following treatment with a low dosage arsenical drug (potassium arsenite 0.5%, im., 1 ml/12 h, for 10 days) both patients experienced complete remission. At the post-treatment control made 1 month later, micrococci had disappeared from the blood, and the CD4/CD8 ratio was raising.

Clinical investigation of chronic diseases: Its successful pursuit in an outpatient setting

With the great discoveries made during the first decade of the 20th century in relation to syphilis—transmission to animals, identification of the spirochete, the Wassermann test and Ehrlich's introduction of Salvarsan—the clinical and experimental aspects of this disease underwent a dramatic change. Knowledge directly applicable to treatment was gained by studies of immunity and of the principles of arsenical therapy in animal models of the disease. In 1915 the Johns Hopkins Hospital made a major innovation by establishing a syphilis clinic where the disease could be studied clinically and experimentally. This led to more effective care of patients and to important new knowledge of the disease. With the discovery that penicillin was treponemicidal, the prospect of eliminating syphilis as a major disease problem seemed at hand. This did not eventuate, but in the early 1950s there was such a dramatic decline in the number of new cases that the syphilis clinic at Johns Hopkins was reorganized. The clinical and epidemiologic facilities that had been created for the study and management of this single disease were utilized to investigate other chronic diseases and finally to form the base for a pioneering program in medical genetics.

Case 91-1961

Presentation of Case First admission. A forty-four-year-old woman, gravida 8, para 8, entered the hospital because of vaginal bleeding. The patient had normal menstrual periods until two years previously, when they became irregular. On the day of entry a single episode of sudden, profuse vaginal bleeding occurred. The patient received an incomplete course of arsenical therapy seventeen years previously because of positive Hinton and Wassermann tests. Her intake of alcohol had been excessive for many years. An umbilical hernia appeared several months before admission, and she lost 17 pounds in weight during the six months before entry. There was . . .

Antibiotics in early syphilis and in syphilis complicated by pregnancy.

THE RENEWED interest in syphilotherapy that began with Ehrlich, who at first believed that arsphenamine could eradicate syphilis with one injection, has continued with the hope that some such quick cure could be found. Pollitzer 1 and, in more recent years, Chargin 2 believed that by giving arsenical treatments daily for a few days or by administering large doses in a slow but continuous drip method one could obtain a cure. However, serious reactions due to intensive arsenical therapy were reported, and in a few instances death occurred. When Mahoney and co-workers 3 reported that injections of penicillin were curative and caused no reactions, it was felt that the ultimate safe cure had been found. It was soon noted that the 600,000 units originally used was not sufficient for cure, and relapses were frequent. Even with the dose increased to 1,200,000 and 2,400,000 units, too many recurrences were noted. It

Tick-borne relapsing fever in Somaliland with special reference to the blood sedimentation rate.

Abstract 1. (1)|An account of the clinical features and complications of tick-borne relapsing fever in Somaliland has been given. 2. (2)|The Kahn test was negative in the eight cases examined. 3. (3)|In this series, neutrophilia was the exception rather than the rule. 4. (4)|B.S.R. estimations were made during, and for several weeks after, attacks. There was a tendency to a raised rate for several weeks after an attack, and to fluctuation in the B.S.R. without any corresponding clinical signs of activity. 5. (5)|It is believed that a latent infection persists in the body (possibly the brain) for a considerable period after all clinical signs have disappeared. An analogy is drawn to the latency and neurotropic character of Treponema pallidum . 6. (6)|Arsenical therapy was of benefit in some areas, while proving of no value whatsoever in other districts, the explanation probably being the occurrence of arsenic-resistant strains of spirochaetes in certain localities. 7. (7)|Penicillin did not prevent relapses.

ELECTROENCEPHALOGRAPHIC STUDIES OF THE ENCEPHALOPATHIES

HEMORRHAGIC during arsenical therapy for syphilis was comparatively rare until the advent of rapid treatment methods, several years ago. The incidence of this complication was reviewed by Glaser, Imerman and Imerman, 1 who pointed out that the mortality rate in this complication was 76 per cent. Dorothy Russell, 2 Scheinker 3 and others have noted that the cognomen hemorrhagic is really a misnomer and that perivascular necrotic phenomena may be the only notable feature present, rather than the outpouring of red cells. Engel 4 and his associates, in their studies on delirium, have emphasized the importance of serial electroencephalograms in the evaluation of the degree of clinical and anatomic recovery. In their investigation of a case of acute arsenical encephalopathy they stressed the degree of change in the electroencephalogram, rather than the appearance of any particular wave frequency. Their method was essentially one of quantitative analysis, in which they

A case of periarteritis nodosa of the central nervous system.

This is a clinical and pathological report on an unusual case of periarteritis nodosa in which the disease was confined chiefly to the brain and spinal cord. The diffuseness, variability and intermittency of the neurological signs and symptoms over a period of two years, in the absence of many of the more usual somatic manifestations of periarteritis nodosa, was responsible for the nature of the disorder not being diagnosed before death. Mental symptoms were prominent throughout the last year of illness. T.A.B. pyrexial therapy coincided with a marked remission in physical and mental symptoms, whilst arsenical therapy appeared to precipitate the terminal exacerbation of symptoms.

Tick-borne relapsing fever in somaliland with special reference to the blood sedimentation rate

1. (1)|An account of the clinical features and complications of tick-borne relapsing fever in Somaliland has been given. 2. (2)|The Kahn test was negative in the eight cases examined. 3. (3)|In this series, neutrophilia was the exception rather than the rule. 4. (4)|B.S.R. estimations were made during, and for several weeks after, attacks. There was a tendency to a raised rate for several weeks after an attack, and to fluctuation in the B.S.R. without any corresponding clinical signs of activity. 5. (5)|It is believed that a latent infection persists in the body (possibly the brain) for a considerable period after all clinical signs have disappeared. An analogy is drawn to the latency and neurotropic character of Treponema pallidum. 6. (6)|Arsenical therapy was of benefit in some areas, while proving of no value whatsoever in other districts, the explanation probably being the occurrence of arsenic-resistant strains of spirochaetes in certain localities. 7. (7)|Penicillin did not prevent relapses.

The Early Diagnosis of Infective Hepatitis in Syphilitic Patients Undergoing Arsenical Therapy

The Early Diagnosis of Infective Hepatitis in Syphilitic Patients Undergoing Arsenical Therapy

Postarsenical Encephalopathy in the Treatment of Syphilis in Women

AT LEAST 60 per cent of adults receiving arsenical antisyphilitic therapy who develop postarsenical encephalopathy are pregnant women. The mortality in this most serious complication in the treatment of syphilis approaches 70 per cent. Postarsenical encephalopathy, the term considered most apt, has also been described under the following titles: cerebral purpura, serous apoplexy, hemorrhagic encephalitis, pericapillary encephalorrhagia, medullary perivascular necrosis and toxic encephalitis. There is a widespread lack of familiarity with this cause of death in 1.3 per cent of the total number of patients treated by the massive five-day arsenical course.1 Postarsenical encephalopathy was the cause of 9.5 per . . .

RELATION BETWEEN THIAMINE AND ARSENICAL TOXICITY

SINCE the introduction of arsphenamine in 1909, the severe reactions of the central nervous system associated with arsenical therapy have been of paramount significance in the treatment of syphilis. Up to 1935, 158 such reactions have been reported in the literature. 1 Of the 158 cases, there were 120 resulting in death, 76 per cent mortality. Intensive arsenotherapy has been used extensively since 1939, but with constant apprehension because of the increased danger of cerebral complications. Thomas and Wexler 2 stated that the incidence of cerebral symptoms was about 1 per cent in all quick methods of treatment. The treatment of syphilis with penicillin is still in the experimental stage, and it will be years before the true value of penicillin therapy can be determined. Already a high percentage of relapses have occurred, although toxic reactions are practically nonexistent. It would seem that treatment with penicillin alone does not appear

Renal damage resulting from idiosyncrasy to neoarsphenamine

1.1. A review of the available literature reveals the relative infrequency of severe renal reactions following arsenical therapy.2.2. A case is presented of severe nephrosis accompanied by purpura and gastrointestinal reaction which followed the administration of a small dose of neoarsphenamine.3.3. Despite the severity of the reaction nearly complete recovery has occurred in this case.4.4. The renal injury in this instance is thought to have been due to a sensitivity reaction. Clinically, the manifestations were similar to those of nephrosis caused by bichloride of mercury and accompanying sulfonamide sensitivity.

Haemorrhagic Encephalopathy after Arsenical Therapy

Haemorrhagic Encephalopathy after Arsenical Therapy

The Bone Marrow in the Five-Day Treatment of Syphilis

SummaryThe intensive arsenical therapy used in the 5-day treatment of syphilis produces no demonstrable effect on the bone marrow of patients who have no individual idiosyncrasy to arsenical drugs. Cases of primary and secondary syphilis in which there is no change in the peripheral blood picture have a distribution of cell types in the bone marrow which is within the normal limits of variation.

FACTORS WHICH MAY INFLUENCE SENESCENCE

Excerpt In any discussion of the factors which may influence senescence, consideration must be given to clinical observations and research and to animal experimentation. Unfortunately there has bee...

BISMUTH HEPATITIS

For many years extensive use has been made of bismuth compounds in the treatment of syphilis. Hepatitis due to bismuth, however, has only recently received general recognition. The failure to realize that hepatitis may result from the use of the drug is in a large measure due to the common tendency to attribute jaundice occurring during bismuth therapy to either relapse of the disease, intercurrent infection or previously received arsphenamine. Attention was first directed to bismuth as the cause of hepatitis by Langernon, Paget and Devriendt, 1 who in 1932 reported 13 cases in which jaundice was presumably due to bismuth. Langernon and his associates believed, however, that bismuth is not hepatotoxic in the sense that the arsphenamines are but that it has rather a nonspecific effect on the liver already damaged by syphilis, alcohol or previous arsenical therapy. The occasional occurrence of hepatitis presumably due to bismuth is likewise

SUPERFICIAL PUNCTATE KERATITIS IN MILIAN'S ERYTHEMA OF THE NINTH DAY

Milian in 19171and again in 19202described an of the body appearing between the seventh and the twelfth day after arsenical therapy and designated this occurrence erythema of the ninth As a clinical entity this early erythematous reaction is becoming firmly established by its characterization as a relatively short, acute illness in which fever with or without chill, a self-limited rash, tonsillitis, pharyngitis and cervical adenitis are noted on the seventh to the twelfth day after injections of trivalent arsenic compounds. Ocular complications of arsenical therapy have been frequently reported, including acute inflammatory reactions involving any or all of the ocular tissues. However, except for the case report of Thomas and Canizares,3the literature contains practically no references to these ocular disorders as part of ninth day erythema, although it is probable that some have occurred from the seventh to the twelfth day. That

Quinine iodobismuthate in the treatment of syphilis complicating pregnancy

1.1. A group of 34 pregnant syphilitic women were treated with quinine iodobismuthate by the intramuscular injection of 2 c.c. of a 10 per cent suspension in oil once a week.2.2. Only 26 or 76.5 per cent of the total group were discharged with living apparently healthy children. Six babies were stillborn, one died neonatally, while another developed evident signs of syphilis.3.3. Among 20 women who received 6 or more treatments, 4 (20 per cent) had stillbirths, while among 12 women in whom treatment was started before the sixth lunar month, 3 (25 per cent) had stillbirths.4.4. From a comparison with other groups of syphilitic pregnant women observed in this clinic it is concluded that quinine iodobismuthate afforded little protection to the pregnancy, and was markedly inferior to arsenical therapy.