Influence of previous gold toxicity on subsequent development of penicillamine toxicity.

The incidence of penicillamine toxicity was determined in 250 patients who had never previously received gold, 76 patients who had received gold without toxic reaction, and 79 patients with a previous history of gold toxicity. The results suggest that there may be a higher incidence of penicillamine toxicity in patients who have previously shown toxic reactions. The interval between stopping the gold and starting the penicillamine did not influence incidence of toxicity. The development of a rash during gold treatment does not seem to influence the development of a rash during penicillamine treatment, but patients who have had proteinuria or bone-marrow depression during gold treatment may have an increased likelihood of developing a similar side effect with penicillamine.     

Allogeneic bone marrow transplantation as primary therapy for chronic myelomonocytic leukemia

This is the first report of a successful bone marrow transplantation for chronic myelomonocytic leukemia. A 41-year-old woman with chronic myelomonocytic leukemia received, as primary treatment, a novel preparatory regimen consisting of high dose fractionated total body irradiation and high dose VP-16 chemotherapy followed by allogeneic marrow transplantation from her histocompatible brother. The patient is now more than two years after marrow transplantation with normal blood counts and a normal bone marrow which is of donor type. For younger patients with this disease who have a histocompatible sibling donor, bone marrow transplantation may represent a valid therapeutic option with curative potential.     

Transient pancytopenia. A report from the International Agranulocytosis and Aplastic Study

From a population-based study on the incidence of potentially drug-associated blood dyscrasias 28 cases were identified with pancytopenia. Who recovered within 90 days after diagnosis. Early recovery occurred more frequently in patients showing normal or increased cellularity of the bone marrow than in patients with bone marrow hypoplasia. Median recovery times of leukocytes were 14 and 10 days and of platelets 21 and 9 days in patients with and without bone marrow hypoplasia, respectively. Age and sex distribution were similar in both groups. Of 28 patients, 11 reported a period of fever before onset of pancytopenia. Sixteen patients in whom information on drug use was available had taken a median of 4 drugs before the onset of symptoms that were related to pancytopenia. From these results we present the hypothesis that transient pancytopenia with or without marrow hypoplasia can be the expression of the same type of bone marrow injury and that drugs or viral infections should be considered as etiological factors.     

Penicillamine in Rheumatoid Disease: A Long-term Study

Eighty-five patients with rheumatoid disease were treated with penicillamine, and 69 completed more than one year''s treatment. The main reason for discontinuing penicillamine in the 16 patients who withdrew was adverse reaction. The number of adverse reactions, however, declined when patients were given lower maintenance doses of penicillamine. In those who tolerated the drug the results of treatment were good. To prevent side effects the drug should be introduced gradually and maintenance doses should be the lowest which produce a satisfactory response. Urine should be monitored for protein and blood for changes in platelet and white cell counts at frequent intervals throughout treatment.     

Recombinant interferon-alpha, but not interferon-gamma is effective therapy for essential thrombocythemia

Recombinant interferon-gamma with a starting dose of 0.5 mg 3x/week subcutaneously, was administered to 6 patients with essential thrombocythemia (median platelet count 1172 X 10(9)/l, range 602-1564). Four of the patients had received alkylating agents previously. Hematological remission, defined as a decrease in platelet counts to less than or equal to 350 X 10(9)/l, was observed in none of these patients. Subsequently 4 of these 6 patients, supplemented by 2 others were treated with interferon-alpha 2c at a dose of 5 X 10(6) U daily subcutaneously. Five patients showed hematological remission. In case of hematological remission the interferon-alpha doses was reduced to 5 X an thereafter to 3 X weekly 5 X 10(6) U. During an observation period ranging from 12-41 weeks platelet counts remained normal in all patients. Side-effects were mild and consisted of fever, myalgias, malaise and itching occurring mainly during the first month of treatment. No dose adaptation was required. The patients treated previously with interferon-gamma experienced the side effects from this drug less tolerably than those from the alpha-compound. These observations suggest that recombinant interferon-alpha may be an effective drug in treating essential thrombocythemia resulting in a sustained response.     

Myoclonus associated with treatment with high doses of morphine: the role of supplemental drugs.

OBJECTIVE--To estimate the prevalence of important side effects in patients with malignant disease who were receiving high doses of morphine as part of their palliative treatment. DESIGN--Data on patients were collected over 12 months. SETTING--Two palliative care units in Western Australia. PATIENTS--19 Patients with malignant disease who were receiving morphine either subcutaneously or orally as the main analgesic. 10 Patients receiving a total daily dose of morphine of at least 500 mg orally or 250 mg parenterally were enrolled in the study. The other 9 patients were enrolled after an important problem thought to be related to the morphine had been identified. All of the patients were taking drugs to supplement the treatment. INTERVENTIONS--The dose of morphine or route of administration, or both, was changed in three patients. MAIN OUTCOME MEASURE--Determination of the prevalence of side effects in the patients. Assessment of the relation of any side effects with the supplemental drugs taken by the patients. MAIN RESULTS--Plasma morphine and electrolyte concentrations were measured and a full history taken for each patient. Thirteen of the 19 patients had an important side effect; 12 of them had myoclonus and one had hyperalgesia of the skin. Plasma morphine concentrations were similar in patients with and without myoclonus, ranging from 158 to 3465 nmol/l and 39 to 2821 nmol/l respectively. Eight of the patients with side effects were taking an antipsychotic drug concurrently compared with none of those without side effects. A greater proportion of patients with side effects were taking the antinauseant drug thiethylperazine (6/13 v 2/6) and at least one non-steroidal anti-inflammatory drug (10/13 v 2/6), whereas a smaller proportion were taking a glucocorticosteroid (3/13 v 4/6). The estimated prevalence of important side effects in the total population of patients receiving palliative treatment in the two units was 2.7-3.6%. CONCLUSIONS--Myoclonus as a side effect of treatment with morphine is more likely to occur in patients taking antidepressant or antipsychotic drugs as antiemetics or as adjuvant agents or non-steroidal anti-inflammatory drugs for additional analgesia. If a patient develops myoclonus the best approach may be to change the supplemental treatment.     

Long survival in acute myelogenous leukaemia: an international collaborative study.

A group of 82 adult patients with acute myelogenous leukaemia had survived in continuous first remission for more than three years was studied. These long-surviving patients were being treated at 12 referral centres in Europe and the USA, and they were compared with other patients with acute myelogenous leukaemia from 10 of these centres. There was no clear difference in the amount of induction chemotherapy or the time taken to achieve remission. Immunotherapy was not found to improve chances of long-term survival. The 82 patients were also compared with a group of 115 patients who had no appreciable difference in the number of blood or marrow myeloblasts between these two groups at presentation, but the long survivors had significantly higher initial platelet counts and were slightly younger. The long survivors also tended to have a lower total white cell count at presentation and lower granulocyte counts; there was no obvious explanation for these differences. Eight of the 82 patients relapsed from three to four years after remission and two (of 69 patients) after four to five year. Thereafter relapse was rare, and it seems likely that some of the 40 patients who have survived for five years or more are cured.     

Sensitivity to Rifampicin: Incidence,Mechanism, and Prevention

Five out of 200 patients taking rifampicin 900 mg twice weekly and three out of 91 patients taking rifampicin who attended an immunology clinic developed intolerance to the drug. Antibodies to rifampicin, which were found in most cases, decreased steadily after the end of treatment but were detectable for up to 16 months. The dose of rifampicin and the blood levels are predominating factors in the occurrence of reactions. Thus the dose should be reduced in patients in whom rifampicin blood levels rise abnormally. When it is important to continue rifampicin treatment despite intolerance antibody titres within 24 hours after administration of the drug must be measured to find when they are lowest, which determines the “unreactive period,” and when a further dose may be safely given.     

Diagnosis of pseudomembranous colitis.

Twenty-eight patients with histologically proved pseudomembranous colitis have been seen in one hospital since July 1975. All patients with the disease had received antibiotics, six for infections not requiring operations; the other 22 cases all occurred after major surgery. All the patients had diarrhoea; six patients also had fever with clinical signs of sepsis, and three had abdominal pain thought to be due to anastomotic dehiscence after colonic resection. Pseudomembranous colitis was associated with white blood counts over 15 000/mm3 in 17 patients and albumin concentrations of less than 30 g/1 in 18. Pseudomembranous colitis was an incidental finding at necropsy in two of six patients who had not had an operation. Of the 22 patients who had had major surgery, nine died from this complication; in all except two of these cases the diagnosis was made only at necropsy. If pseudomembranous colitis is suspected on clinical grounds or if there is an unexplained complication after colorectal surgery repeat sigmoidoscopy and testing for faecal toxins should be carried out to establish the diagnosis so that prompt supportive treatment can be given.     

Treatment of Epilepsy

The main clinical types of epilepsy and their treatment are described. The treatment of choice in petit mal epilepsy is trimethadione (Trimedone) 0.3 g., three to six times a day, or acetazolamide (Diamox) 125-250 mg., three to four times a day. Phenobarbital is usually given as well to prevent grand mal seizures. Diphenylhydantoin sodium (Dilantin Sodium), 100 mg., and/or phenobarbital, 30-100 mg., three to four times a day, is recommended in patients with focal and grand mal epilepsy. Psychomotor automatisms are a form of focal seizure. Primidone (Mysoline), in doses of 125-250 mg. two to three times a day, is a very useful anticonvulsant in patients with myoclonic features, psychomotor automatisms and grand mal seizures. Primidone should be started in small doses. Drug reactions, especially cerebellar ataxia in the case of diphenylhydantoin and blood dyscrasias in the case of some drugs, should be recognized. Excessive drowsiness can be avoided by proper dosage and proper timing of drug administration. Patients should be seen regularly at least two to three times a year. The objective of treatment is to achieve optimum control of seizures by using the appropriate drug in adequate dosage. Social adaptation is good in the majority of patients, who should be encouraged to carry on their life independently, usually free to marry and have children. Attention to special occupational hazards has to be considered. Education of employers and employees is often necessary. Special work arrangements are occasionally indicated for selected patients. Patients should be seizure-free for two to three years before permission is given to drive an automobile.     

Changes of the blood lymphocyte subpopulations and their functions following 131I treatment for nodular goitre and 32P treatment for polycythemia vera

The blood lymphocyte population was examined in 34 patients who were treated with 131I for toxic or atoxic nodular goitre. One to three doses of 300-550 MBq of 131I were administered at 1-week intervals. Lymphocyte counts were found to be significantly reduced at both 1 and 6 weeks after treatment. This decrease was accompanied by a changed composition of the lymphocyte subpopulations. The frequency of lymphocytes expressing membrane receptors for C'3 (EAC-rosette forming cells) was significantly reduced at 1 and 6 weeks following 131I administration. At 6 weeks there was a small but statistically significant increase of the frequency of T cells as identified by Leu 1 monoclonal antibodies. This was essentially due to an increased proportion of helper/inducer T cells as identified by Leu 3 monoclonals. 131I treatment also decreased the capacity of lymphocytes to secrete immunoglobulins (Ig) when stimulated with pokeweed mitogen (PWM). The greatest effect was observed for IgM. Secretion of IgG and IgA were less reduced. Mitogenic stimulations of lymphocytes with phytohemagglutinin (PHA) and concanavalin A were not significantly changed. It is concluded that these findings, with the exception of mitogen reactivity, are largely similar to those occurring following external radiation therapy for cancer. It is suggested that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by beta-rays. The effect of 32P treatment on the blood lymphocyte population was examined in 16 patients with polycythemia vera. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as identified by monoclonal antibodies against total T cells (Leu 1 and 4), helper/inducer (Leu 3) and suppressor/cytotoxic T cells (Leu 2), were slightly decreased. Moreover, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were impaired. Following a single oral dose of 32P (150-305 MBq), which normalized the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40 per cent 12 weeks after treatment. Examination of subsets demonstrated that the proportion of B-cells, as identified by B1 monoclonal antibodies, was decreased by the highest relative extent. On the other hand, lymphocytes expressing the above-mentioned T cell markers were somewhat increased. 32P treatment markedly increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in agreement with the finding that serum concentrations of Ig were reduced after treatment.     

Additional comments on migraine therapy

The symptoms and clinical management of alcohol, barbiturate and benzodiazepine withdrawal syndromes are discussed in this article. People who suffer alcohol withdrawal should be admitted to hospital if they have medical or surgical complications or severe symptoms; supportive care and pharmacotherapy, especially diazepam loading, are the essential components of treatment. Barbiturate withdrawal requires pharmacotherapy and admission to hospital for patients who have taken more than 0.4 g/d of secobarbital or an equivalent amount of another barbiturate for 90 days or longer, or 0.6 g/d or an equivalent dose for 30 days or longer, or who have had withdrawal seizures or delirium; phenobarbital loading is recommended. Regular benzodiazepine therapy that has lasted at least 3 months should be gradually stopped. Short-acting agents should be replaced with long-acting ones, such as diazepam, to avoid withdrawal symptoms. Most of these patients can be managed on an outpatient basis.     

Adverse reactions to frusemide in hospital inpatients.

Out of 2580 medical inpatients included in a drug-surveillance programme, 585 (22.7%) were treated with frusemide. Of these, 123 (21.0%) had a total of 177 adverse reactions. The most common were hypovolaemia (85 cases), hyperuricaemia (54), and hypokalaemia (21). Most reactions were mild, and only three patients had potentially life-threatening effects. The incidence of adverse reactions increased significantly with daily dose, occurring in 47 patients (13.5%) given up to 40 mg, 42 (26.3%) given up to 80 mg, and 34 (43.6%) given over 80 mg (P less than 0.001). There was no clear association between side effects and a raised blood urea concentration on admission, confirming that treatment with frusemide is not more hazardous in patients with renal failure. Frusemide is a safe and highly effective diuretic. Nevertheless, in view of the potential seriousness of volume depletion, dosage should probably begin at 20 rather than 40 mg daily.     

Does the order of second-line treatment in rheumatoid arthritis matter?

In a prospective study 88 patients, with rheumatoid arthritis who had stopped taking gold, penicillamine, or levamisole were randomly allocated to one of the alternative drugs and followed up for a minimum of one year. Concurrent studies of the effects of gold, penicillamine, and levamisole prescribed in 123 patients as the first second-line drug were used for comparison. No difference in toxicity or efficacy between primary and secondary use of gold or penicillamine was identified. Variation in the toxicity of levamisole could in part be accounted for by changes in the dose regimen over the four years of study. The length of the treatment-free interval between drugs did not influence subsequent development of toxicity. These results suggest that an adverse reaction to one of the three second-line drugs studied should not prejudice the selection of another.     

Inactivation of Salmonellae on Chilled and Deep Frozen Broiler Carcasses by Irradiation

Chilled and deep-frozen broiler carcasses were examined for total counts of salmonellae using pooled samples taken from 76 batches each of five birds. By means of a most probable number technique (MPN) it was found that counts expressed/100 g of skin or /500 ml of thaw water varied between < 2 and 1400 with 90% being < 100. Irradiation of carcasses using a dose of 250 krad was found to be highly effective in destroying salmonellae whether the birds had been chilled or deep-frozen.     

Lithium Treatment Aggregates the Adverse Effects on Erythrocytes Subjected to Arsenic Exposure

The present study was designed to investigate the effects of lithium treatment on red blood cells which were given arsenic exposure. Long-term lithium therapy is being extensively used for the treatment of bipolar disorders. Arsenic is a group I carcinogen and a major toxic pollutant in drinking water that affects millions of people worldwide. Male SD rats were segregated into four groups, viz. normal control, lithium treated, arsenic treated, and lithium + arsenic treated. Lithium was supplemented as lithium carbonate at a dose level of 1.1 g/kg diet for a period of 8 weeks. Arsenic was given in the form of sodium arsenite at a dose level of 100 ppm in drinking water, ad libitum, for the same period. Lysates of red blood cells were used to investigate the effects of lithium and arsenic treatments on anti-oxidant enzymes, reduced glutathione (GSH), and lipid peroxidation (LPO) levels. Various hematological parameters, activities of Na⁺ K⁺ ATPase and delta-aminolevulinic acid dehydratase (δ-ALAD) were also assessed. A significant reduction was observed in the activities of antioxidant enzymes, GSH levels, total erythrocyte counts, Na⁺ K⁺ ATPase, and ALAD enzyme activities in lysates of red blood cells when exposed either to lithium or arsenic. In addition, a significant increase in the levels of malondialdehyde (MDA), lymphocytes, neutrophils, and total leukocytes was also observed following lithium as well as arsenic treatments. However, when arsenic-treated rats were subjected to lithium treatment, a pronounced alteration was noticed in all the above parameters. Therefore, we conclude that lithium supplementation to the arsenic-treated rats enhances the adverse effects on red blood cells and therefore use of lithium may not be medicated to patients who are vulnerable to arsenic exposure through drinking water. It can also be inferred that adverse effects of lithium therapy may get aggravated in patients thriving in the arsenic-contaminated area.

     

Atopy does not predispose to RSV bronchiolitis or postbronchiolitic wheezing.

Twenty-six 8-year-old children who had had respiratory syncytial virus (RSV) bronchiolitis in infancy and their paired controls underwent skin and blood tests to assess the role of immunodeficiency and atopy in the pathogenesis of RSV bronchiolitis and the wheezing that may follow it. There was no difference between patients and controls in prevalence of atopy; positive results of prick tests to common antigens; eosinophil counts; yeast opsonisation defect; C2 deficiency; IgG, IgA, IgM, and IgE concentrations; or IgE antibody to dermatophagoides, timothy-grass pollen, and cat fur. Those of the children who had had RSV bronchiolitis and who continued to wheeze had a slightly higher mean eosinophil count and levels of IgE antibody to dermatophagoides than those who did not wheeze. Exercise-induced bronchial lability, though higher in patients than controls, did not correlate significantly with eosinophil counts or IgE concentrations. The genetic factors predisposing to RSV bronchiolitis and postbronchiolitic wheezing may differ from those predisposing to atopic asthma, though exclusive breast feeding may protect against both.     

COMPLICATIONS OF GOLD THERAPY AND THEIR MANAGEMENT

Early recognition of manifestations of gold intoxication is important to the treatment of such complications. Proper dosage schedules should be followed and blood and urine frequently examined.Most toxic manifestations subside, but those which become worse or which do not subside on withdrawal of the gold should be treated with BAL (2, 3-Dimercaptopropanol).BAL has a toxicity of its own and is painful on injection. Since BAL combines with gold, the therapeutic effect of the metal may be lost after such treatment.The beneficial effects of methionine and methionine plus BAL in treatment of experimentally induced gold intoxication of animals suggests such combined therapy in the treatment of clinical complications of gold poisoning. A schedule of combined antidotes is outlined.     

Complete Blood Counts are Frequently Abnormal 1 Year after Dosimetry-Guided Radioactive Iodine Therapy for Metastatic Thyroid Cancer

ObjectiveRadioactive iodine (RAI) has been associated with hematologic abnormalities. Previous research has shown that even a single dose of RAI can cause changes in the peripheral complete blood count (CBC). It is unclear if the use of dosimetry guidance would prevent the effects of high doses of RAI on bone marrow suppression.MethodsCBC at baseline was compared to a CBC obtained 1 year after the last RAI treatment in 50 thyroid cancer patients that received ≥ 250 mCi RAI during the course of their disease. Cumulative dose, number of treatments, patients’ age, and the use of external beam radiation therapy (EBRT) were considered in the analysis.ResultsWe observed a small but statistically significant decrease in hemoglobin (Hb), hematocrit (Hct), and platelet (Plt) counts at 1 year in 50 patients who had received ≥ 250 mCi RAI. We did not find a significant change in white blood cell count (WBC). Approximately 60% of patients who developed anemia had concomitant WBC and Plt abnormalities. RAI dose, number of treatments, and age at diagnosis did not confer a higher risk of bone marrow suppression.ConclusionHigh cumulative activities of RAI administered under dosimetric guidance are associated with a small but statistically significant decreases in Hb, Hct, and Plt counts. The clinical implications of these changes, if any, are unclear. The benefits obtained with high doses of RAI, when indicated, are likely to outweigh the minimal hematologic risks observed in the present study. (Endocr Pract. 2014;20:213-220)     

Immune, endocrine, and behavioral precursors to breast cancer recurrence: a case-control analysis

BACKGROUND: A period of tumor growth precedes the clinical detection of breast cancer recurrence. We explore immune, endocrine, and behavioral parameters during this period. METHODS: We conducted a phase III clinical trial in which women with surgically treated stage II/III breast cancer (N = 227) were randomized to receive a psychological intervention or assessment-only and then regularly assessed for 10 years. Patients who recurred (R, n = 48) were matched with patients remaining disease-free (DF, n = 48) on demographic and prognostic characteristics, treatment, and duration of disease-free follow-up. Data at three assessment points, occurring, on average, 17, 11, and 4 months before the recurrence was detected clinically, with equivalent time points for the disease-free group, were examined. Mixed-effects models tested for group differences in immune cell counts and function as well as endocrine and behavioral parameters. RESULTS: In the 17 months prior to recurrence detection, patients exhibited higher white blood cell count, neutrophil, lymphocyte, and natural killer cell counts, relative to DF patients. R patients also showed higher cortisol, worse physical functioning, fatigue, and quality of life. Follow-up analyses showed patients with local recurrences to differ from those with distant recurrence, with the former exhibiting elevated natural killer cell cytotoxicity, lymphocyte proliferative response, fatigue, pain, and emotional distress (depression, anxiety), and the latter exhibiting higher neutrophil, lymphocyte, and natural killer cell counts. CONCLUSION: Patients who would recur showed reliable biobehavioral alterations more than a year prior to their diagnosis. This novel observation may contribute to our understanding of the disease relapse processes.