Second Course Of Treatment Research Articles

A Monkey Model of Tardive Dyskinesia (TD)

Three Cebus apella monkeys were treated with biweekly injections of fluphenazine enanthate for 1 year. Two distinct motor syndromes were produced. The first consisted of acute dystonic, dyskinetic, parkinsonian, and akathisia-like reactions, which worsened after each injection, were not exacerbated by drug withdrawal, and could be abolished or prevented with benztropine. The second appeared after cessation of neuroleptic treatment and consisted of abnormal movements very similar to those of patients with tardive dyskinesia (TD). This syndrome was abolished completely by reinstitution of fluphenazine treatment. One monkey was given a second and third course of fluphenazine, each course lasting 4 weeks. The second syndrome was seen after but not during each course and remained robust for a longer period after the third than after the first or second courses of treatment. We conclude that the first syndrome is analogous to the early appearing extrapyramidal symptoms of neuroleptic-treated patients and that, according to preliminary evidence, reversible TD may turn into irreversible TD with continued periods of on and off neuroleptic treatment.

Results of re-irradiation for cerebral metastases.

After an initial course of radiation, 56 patients with cerebral metastases had their brain retreated at least once for recurrent neurologic symptoms. The most common primary was from either the lung or breast. The frequent symptoms were headache, weakness, seizures, visual problems, and/or mental changes. Forty-two (75%) of these patients responded to the second course of treatment. The median duration of response was 10 weeks and median survival was 14 weeks.

Effect of interferon therapy on circulating lymphocytes in humans.

The effect of interferon treatment on both lymphocyte subpopulation numbers and function was studied in two groups of patients who were being treated systemically with 0.5 to 1.0 x 10(7) units of human leukocyte-derived interferon (HulFN-alpha) daily. Patients with nodular lymphocytic, poorly differentiated non-Hodgkin's lymphoma (NLPD) were given interferon for 30 days and those with chronic hepatitis B infection were treated in cycles for 4 to 7 days. In both patient groups, B lymphocytes numbers were reduced during treatment, but T lymphocyte numbers were unaffected. T lymphocyte responses, measured by blast transformation to herpesvirus antigens were generally low before treatment in NLPD patients. The responses were restored after termination of therapy. In two NLPD patients given two courses of treatment separated by a 3 month interval, the restored T lymphocyte responses were inhibited during the second course of treatment. In patients with chronic hepatitis B virus infection, lymphocyte blast transformation to the viral antigens were also depressed during treatment compared to pretreatment responses. Changes in lymphocyte responses to phytohemagglutinin and pokeweed mitogen were not observed in either patient group.

Acupuncture for Everything Else

Analgesia is only one aspect of acupuncture. Various Chinese medical texts claim that nearly 300 kinds of diseases can be treated effectively with acupuncture. Among them are: malaria, hypertension, acute appendicitis, acute perforation of gastric ulcer, ulcer, bronchitis, asthma, arthritis, benign thyroid adenoma, syringomyelia, paraplegia, myopia, optic fundus bleeding and optic atrophy. The Institute of Acupuncture and Moxibustion in Beijing. an affiliate of the Academy of Traditional Chinese Medicine, is one of the places where research on the effects and mechanisms of acupuncture with regard to several of these diseases is being carried out. We are doing theoretical research in the light of modern medicine, says Wang Xuetai, head of the institute. But this is not the way it has always been. U.S. researchers who visited China in the early 1970s reported that much of what the Chinese called research was not research as we know it but rather simple, unstructured clinical trial and error. Today, from what we could see, the Chinese seem to be seriously interested in backing up what they are doing with hard research data. During our visit to the acupuncture institute we saw clinical treatment of and experimental data relating to coronary heart disease and gastroptosis (an abnormal downward displacement of the stomach). Chest pain with symptoms of deathlike pallor, dyspnea and difficult breathing signifies heart disease with derangement of liver. [Acupuncture I Points chosen should be Xingjian and Taichong.... Pain in chest, pain in the heart aggravated in exertion with complexion unaltered means pulmonary heart disease. Points taken should be Yuji, Taiyuan. The Chinese cite these passages from The Cannon of Medicine, a Chinese medical classic published more than 2,400 years ago. as evidence that acupuncture therapy for coronary heart disease and angina pectoris has a timehonored history. In recent years the Chinese have been conducting research in the hope of demonstrating the efficacy of such treatment. One major study made systematic observations of 631 angina pectoris patients who had been treated with acupuncture. Included in the study were 436 males and 195 females, mostly laborers between 40 and 60 years of age. These patients had complained of heart pain for two years or more, and complications included hypertension, chronic myocardial infarction, bronchitis, cerebral accidents and diabetes. All had failed to respond to either traditional Chinese herbal medicine or to modern Western medicine. The Chinese report that acupuncture treatments were successful in relieving symptoms in nearly 70 percent of the cases. Treatment consists of inserting needles at various points and either manipulating them or applying an electric current to them for 20 minutes. This therapy is applied every day or two in an out-patient clinic, and 10 sittings constitute one course of treatment. The interval between courses of treatment is 3 to 5 days, and observations are made during three courses of treatment. The Chinese report that effective results usually appear during the first or second course of treatment. In 219 of 506 patients suffering from angina pectoris, symptoms were markedly improved after acupuncture treatment. Another 242 cases showed moderate improvement, and 45 (8.9 percent) showed no improvement. More than 85 percent of the patients who had used glyceral nitrate prior to acupuncture treatment either stopped or reduced use of the drug after treatment. More than 70 percent of the patients who had been disabled by their condition were able to go back to fullor part-time work. Electrocardiogram readings are made before, during and after the treatment regimen. Of 631 cases, 583 showed abnormal ECG readings prior to acupuncture treatment. After treatment 146 showed marked improvement, 244 moderate improvement, 181 no improvement and 12 were worse. The total effective rate, as shown by ECC measures, is 66.9 percent, but follow-up studies indicate that improvement in ECG usually appears much later than do improvements in symptoms. In addition to relief of heart pain, the Chinese claim that acupuncture therapy has beneficial effects on associated symptoms: relief from suppressive feelings in the chest in 88 percent of the cases; from heart palpitations, 80 percent; from dyspnea (difficulty breathing) 86 percent. Officials at the acupuncture institute say, We Patient with cardiovascular disease and hypertension (above) gets acupuncture needles in legs. The long needle inserted down patients stomach is treatment for gastroptosis.

The Treatment of an Obsessive-Compulsive Girl in the Context of Malaysian Chinese Culture

The case history, treatment and follow-up of a thirteen-year-old girl with obsessive-compulsive neurosis of six months duration are reported. Results show that behaviour modification techniques were effective though a second course of treatment was required. Her illness and its treatment by behaviour therapy in relation to the Malaysian Chinese culture is discussed.

Systemic miconazole treatment of a patient with chronic granulomatous mucocutaneous candidiasis

Miconazole given intravenously and orally was evaluated in the treatment of a patient with drug-resistant, chronic, widespread horny candida lesions. Marked clinical improvement occurred after 4 weeks of the first course of treatment, in which 400 mg of miconazole per day was given intravenously. After 3 months no signs of the disease were apparent. The patient remained free of symptoms for 3 months, after which the lesions recurred and a second course of treatment, with 200 mg of miconazole per day intravenously, was started. A prompt clinical clearing was seen within 3 weeks, after which the miconazole (1 000 mg per day) was given orally. During oral administration of the drug a limited degree of recurrence of horny patches occurred. Systemic miconazole seems to be the drug of choice in the treatment of systemic chronic mucocutaneous candidiasis.

Estrogen-Progestogen Treatment Enhances the Ovulatory Response to Clomiphene in Amenorrheic Patients

Nineteen anovulatory subjects who initially did not respond to clomiphene were treated with Cycloprogynova (11 tablets containing 2 mg of 17 β-estradiol valerate and 10 tablets containing 2 mg of 17 β-estradiol valerate plus 0.5 mg of D, L-norgestrel) through three or four cycles and subsequently received 100 mg of clomiphene for 5 days during three cycles. Of the 19 patients, 9 conceived during the first course of therapy and 2 patients became pregnant after a second application. Another 11 anovulatory patients who initially failed to ovulate during several courses of clomiphene therapy were treated with a combination of clomiphene and cycloprogynova. Of these 11 patients, 1 patient conceived during the first course of treatment, 3 patients conceived during the second course of treatment, and 2 patients conceived during the third course of treatment. Another 10 women who had long-lasting amenorrhea and did not respond to luteinizing hormone-releasing hormone (LH-RH) with an elevation of serum gonadotropin levels were treated with Cycloprogynova for 3 months. During the third application of the steroid preparation, 7 of the 10 subjects responded to LH-RH. The data combine to suggest that Cycloprogynova exerts a sensitizing action, at least in part, on pituitary responsiveness and may mediate the clomiphene effect, most likely at the pituitary level. It is concluded that Cycloprogynova should be considered as a back-up therapeutic tool when clomiphene is used for induction of ovulation.

Visceral Leishmaniasis Acquired in Greece

Reported is a case of visceral leishmaniasis acquired in Greece by a 3-year-old American child. Untreated, this protozoan infection causes a high mortality. Specific treatment is available, making early recognition of the illness important. This child's infection responded dramatically to a course of sodium antimony gluconate. Repeat bone marrow cultures demonstrated persistent organisms and a second course of treatment was required. Monitoring of his response to therapy suggested that serial bone marrow cultures and the neutrophil response may be sensitive means for following the course of this infection.

THERAPY EXPERIENCES WITH HERPES SIMPLEX ANTIGEN “LUPIDON G”

ABSTRACTDuring the last years a relative high incidence of recurrent herpes simplex genitalis has been observed in Jakarta. A total number of 58 adult male and female patients suffering from herpes progenitalis and of herpes on the mons veneris, gluteal region or thighs were treated with “Lupidon G.”* “Lupidon G” is a HSV (herpes simplex virus) type 2‐antigen, to be injected subcutaneously according to a fixed treatment schedule. The first course consists of 12 subsequent weekly injections (1st–3rd month), followed by a second course of 8 fortnightly injections (4th–5th month). This paper will discuss the factors contributing to proneness of individuals to the disease, the average duration of the herpes, the prior treatment, frequency of the relapses and the coincidence with other diseases.Twelve patients terminated before completion of the course of treatment or did not come back for control. In 46 patients a follow‐up during 6–12 months revealed the following clinical results: excellent 34.8% (16 cases), good 52.2% (24 cases), and inefficacious 13.0% (6 cases), all after the first course. Two patients of the last group were cured after a second course of treatment. Trivial side‐effects occured on the site of injection in 3 patients (6.5%).

Luteinizing Hormone-Releasing Hormone for Induction of Follicular Maturation and Ovulation in Women with Infertility and Amenorrhea

Five patients with primary infertility and secondary amenorrhea who did not respond to clomiphene with a gonadotropin or estrogen surge were treated with 500 mug of luteinizing hormone, follicle-stimulating hormone-releasing hormone (LH-RH), self-administered subcutaneously every 8 hours for 14 days. Of four patients who responded to this treatment, three showed follicular maturation, ovulation, and menses, although the luteal phase was deficient; in the fourth patient, follicular maturation and menses occurred without evidence of ovulation. For their second course of treatment these four patients were given LH-RH with the addition of human chorionic gonadotropin when the urinary estrogen levels indicated follicular maturation. All four patients responded with ovulation, an adequate luteal phase, and menses, without clinical indication of ovarian hyperstimulation. These results suggest that LH-RH may be a better alternative to human menopausal gonadotropin in the treatment of anovulatory infertility.

Treatment of Paget's Disease of Bone with Porcine Calcitonin: Clinical and Metabolic Responses

The clinical and metabolic responses of 12 patients with painful Paget's disease have been assessed before, during and after an 18-day course of treatment with purified porcine calcitonin, 160 MRC units i.m. daily. The indices of response included relief from pain, changes in concentration of serum alkaline phosphatase, calcium, magnesium, electrolytes and plasma inorganic phosphate; balance studies of calcium, phosphate, magnesium and in some cases sodium and potassium were undertaken. Urinary excretion of hydroxyproline was also measured. Remission of pain was complete in 11 of 15 courses of treatment. Coexistent osteoarthrosis was considered to be responsible where remission was incomplete. The mean duration of remission of pain was 12 months. Three patients who received a second course of treatment achieved further remission of pain. Side effects were not troublesome. Serum levels of alkaline phosphatase decreased to 67 per cent of the initial reading and the degree of suppression depended on the initial alkaline phosphatase activity. Urinary hydroxyproline correlated closely with the activity of serum alkaline phosphatase before, during and after treatment. The ratio of serum alkaline phosphatase:hydroxyproline excretion rose at the start and at the termination of treatment. Retention of calcium and inorganic phosphate occurred during the early phase of treatment only. Withdrawal of treatment resulted in a rebound retention of calcium and inorganic phosphate. The degree of calcium retention after treatment correlated with the level of plasma inorganic phosphate prevailing before treatment. The efficacy of these short courses of calcitonin are discussed and the metabolic observations related to theories of bone remodelling at a cellular and hormonal level.

Treatment of trichuriasis with a new drug, mebendazole.

Effectiveness of mebendazole, a new anthelminthic drug recommended for treatment of Trichuris trichiura infection, was evaluated in 50 children attending a pediatric outpatient clinic in New York City. Mebendazole, 100 mg. administered orally twice daily for three days resulted in an apparent cure of 48 children. Posttreatment stools of the remaining two children had a substantial reduction in the number of eggs. A second course of treatment, identical to the first, led to the elimination of eggs in the stool specimens of these two children. Mebendazole appears to be an effective drug against Trichuris trichiura.

Comparison of daily with twice-weekly injections of follicle-stimulating hormone for treatment of failure of ovulation

Ten patients with anovulation were investigated in 24 courses of treatment to compare daily with twice-weekly injections of follicle-stimulating hormone (FSH). Human pituitary FSH (CP1) with a ratio of FSH to luteinizing hormone (LH) of about 5.1 was given in 12 courses of treatment, and human menopausal gonadotropin††Humegon, Organon Laboratories, Limited, Morden, Surrey, England. (HMG) with a ratio of FSH to LH of about 1 to 1 was given in the other 12. A balanced experimental design was used. The different methods of treatment could not be compared on the basis of the pregnancies because there were too few of them. The doses of HMG and of CP1 required to produce a positive response in excretion of total estrogen were the same for twice-weekly injections as for daily injections, indicating that both preparations were as effective when given in twice-weekly doses as in daily doses. Daily injections of CP1, however, produced a significantly greater rate of increase of excretion of total estrogen than did twice-weekly injections of CP1, implying that twice-weekly injections are less likely to result in multiple pregnancies. This effect did not occur with HMG. It was found that on average 56 per cent more HMG was required to obtain a positive response in the second course of treatment than in the first. This did not occur with CP1. This effect was probably due to the different ratios of FSH to LH in the 2 preparations.

Cutaneous cryptococcosis. A sentinel of disseminated disease.

In four cases of disseminated cryptococcosis with central nervous system (CNS) involvement, cryptococcal cutaneous lesions developed two to eight months before the diagnosis of disseminated cryptococcosis with meningitis was made. In all four patients, there was cultural or strong clinical evidence of multisystem involvement in addition to the presenting skin lesions and CNS involvement. All four patients were treated with amphotericin B intravenously. In two patients, a single course of drug therapy produced long-term apparent cure, while in the remaining two, clinical and cultural relapse occurred, resulting in death in spite of a second course of treatment. The recognition of cutaneous cryptococcal disease should alert the clinician to the probability of disseminated cryptococcosis. Repeated careful cultural studies of the cerebrospinal fluid, urine, prostatic secretions, and sputum should be performed for early diagnosis and appropriate therapy.

Follow-up of Patients with Chronic Pulmonary Histoplasmosis Treated with Amphotericin B

The late results of chronic pulmonary histoplasmosis treated with amphotericin B are of interest because of the chronic relapsing character of the disease. A total of 89 cases from four hospitals were reviewed according to a uniform plan. Of 56 cases that were observed repeatedly for an average of four years and four months, 48 (86 percent) were either well or died of causes other than histoplasmosis. Eighteen were well and working. Nineteen had inactive histoplasmosis and were not working. Six patients relapsed, but responded to a second course of treatment. Five cases died and had no active histoplasmosis at autopsy. The remaining eight patients (14 percent) had unsatisfactory results. These chronic pulmonary histoplasmosis cases treated with amphotericin B supply data covering longer time periods than those derived from controlled observations of early results reported elsewhere.

ACQUIRED RESISTANCE TO TREATMENT WITH ARVIN

2 patients who underwent therapeutic defibrination with ' Arvin ' were found to be refractory to a second course of treatment. Plasma from both neutralised the clotting effect of arvin added in vitro, and a similar abnormality was observed in 2 of 14 other plasma-samples. Resistance to arvin has been demonstrated in 3 of 4 patients treated by the intramuscular route, but in only 1 of 12 patients treated intravenously. It is probable that arvin is weakly antigenic and that resistance is due to the production of antibodies.

Factors involved in treatment failures following oral penicillin therapy of streptococcal pharyngitis

Among 331 children with group A streptococcal pharyngitis who were treated with a 10 day oral regimen of either sodium nafcillin or penicillin V potassium, there were 39 treatment failures. There was no correlation between the incidence of relapse and patient's age, sex, interval between onset of illness and onset of therapy, history of respiratory tract allergy, compliance in completing therapy, concomitant presence of penicillinase-producing staphylococci, or incidence of homologous streptococci in household contacts. There was, however, a significantly higher incidence of relapse in patients harboring M-typable strains, as compared with patients harboring nontypable strains; this was particularly evident for patients with types 3 and 12 streptococci. Among the relapse group, there was no difference in the bacteriologic outcome of those patients who received a second course of treatment as compared with the patients who were not re-treated.

The sensitizing carcinogenic effect of small doses of carcinogen

A short-term contact of the skin of mice with small doses of carcinogens such as 20-methylcholanthrene, 3,4-benzpyrene and 9,10-dimethyl- 1,2-benzanthracene, which as a rule do not induce any tumours during the usual life span of the animals, sensitizes the organism to subsequent applications of one of these carcinogens after an 8–14-week interval. The skin papillomas appear on the site of the repeated applications earlier than in control mice and malignant transformation of these papillomas takes place earlier. The development of papillomas and their malignant transformation also accelerated if the carcinogen is applied during the second course of treatment on areas of the skin far from the place of initial sensitizing (experiment with methylcholanthrene). On the place of sensitizing, where tumours as a rule do not appear, some mice develop papillomas, and even carcinomas, if methylcholanthrene had again been applied on another area of the skin. Similar results were received when the sensitizing of the skin had been followed by subsequent subcutaneous injection of methylcholanthrene. In this case, sarcomas developed earlier than in control mice and tumours of the skin appeared in some animals on the place of sensitizing. The acceleration of papilloma and carcinoma development is also found in experiments with 9,10-dimethyl- 1,2-benzanthracene or benzpyrene when the mice have been previously sensitized with doses of orthoaminoazotoluene, insufficient for hepatomas induction. All the data obtained show that the doses of carcinogens, which are insufficient to induce tumours, increase the susceptibility of the organism to subsequent carcinogenic influences.

Testosterone-induced activation of fibrinolysis in carcinoma of the prostate.

SUMMARYA case is recorded in whom the administration of testosterone, as a preliminary to P32 treatment for the pain of bony metastases, induced a fibrinolytic state which was corrected by giving EACA. No further fibrinolysis occurred even though the testosterone treatment continued. The same events occurred after a second course of treatment. This is the first report of a possible dangerous complication of this valuable treatment of so distressing a condition.My thanks are due to Mr H. F. Anderson, under whose care the patient was admitted, and to Dr J. W. Hamer for the hematological investigations and advice on therapy.

OBSERVATIONS ON THE TREATMENT OF ONCHOCERCIASIS IN AN ENDEMIC AREA OF WESTERN NIGERIA.

Diethylcarbamazine and Antrypol were used in combination in treating 163 ambulant patients suffering from onchocerciasis for periods of 8–10 weeks, in the endemic area of Western Nigeria, and palpable onchocercal nodules were excised when found. Treatment was made difficult by reinfection when patients returned to their home environment, thus emphasizing the urgency of instituting general control measures against S. damnosum in this area. Good results were obtained with the dosage regime employed and 109 patients were discharged as cured on clinical and serological grounds when seen 6 weeks after the completion of treatment. Twenty-five patients received a second course of treatment while 12 others were given a modified course of treatment with diethylcarbamazine alone. The complement-fixation test, with extracts of onchocercal nodules as antigen, was found better than any other diagnostic technique as an objective test of cure during treatment.