Renal tubular acidosis in the Silver-Russell syndrome

Several patients with the Silver-Russell syndrome (SRS) attending our Genetics Clinic were diagnosed as having persistent metabolic acidosis. Since this abnormality has not been reported previously in the SRS, we reexamined 33 SRS patients to evaluate the frequency and type of metabolic acidosis, the clinical and laboratory findings, and the growth pattern in SRS patients with and without metabolic acidosis. Among them, 14 had a consistent decrease in HCO levels. Renal studies in acidotic patients showed urine pH of 5.8 and 24 h urine calcium of <2.4 mg/kg/24 h; serum creatinine, excretion of glucose, and aminoacids were normal, as were renal ultrasound and excretory urography findings. These data supported the diagnosis of renal tubular acidosis, probably type II; the patients were treated with oral bicarbonate and acidosis was corrected successfully. Clinical manifestations were similar in acidotic and non-acidotic patients. The nutritional indices at diagnosis and at last evaluation (at least 8 months after diagnosis) were abnormally low in all patients; however, acidotic patients, treated with bicarbonate, showed an improvement of nutritional status particularly in the weight/height index, although the difference between groups after follow-up did not reach statistical significance. We suggest that metabolic acidosis due to renal tubular acidosis, probably type II, may occur in children with the SRS and should be looked for and treated in all patients. © 1995 Wiley-Liss, Inc.     

Suppression of Experimental Allergic Encephalomyelitis in Rats Exposed Nocturnally to Magnetic Fields

After inoculation with spinal cord and complete Freund's adjuvant, female Lewis rats were exposed to weak, 7 Hz complex magnetic fields or to the control condition. The computer-generated magnetic field, whose amplitude varied from 15 nT to 60 nT every 6 to 12 sec, was presented for 6 min every hour between midnight and 0800 of the scotophase. In two replicates of the experiment, the rats exposed to the field displayed statistically significant suppression relative to sham-field controls (effect size=55%) of the overt symptoms of experimental allergic encephalomyelitis which included hindleg paralyses.     

Pilot study of a visitor volunteer programme for community elderly people receiving home health care

There is a need to evaluate community support programmes for elderly people. In this randomized control trial (RCT), we determined the effectiveness of 'friendly visitors' in a volunteer programme of a visiting nurses organization in Southern Ontario, Canada. The Volunteer Friendly Visitor Programme was developed to support elderly people receiving homemaking and nursing care in the community. Volunteers are screened, trained, interviewed and matched to homebound elderly clients for general interest, visit expectations and personality. Volunteers spend three to four hours on average per week with clients socializing in mutually agreed-upon ways. The nursing staff identified clients who were lonely for this additional support. These newly-referred clients were randomly allocated to receive a friendly visitor or not for six weeks. Those receiving the volunteer visitor improved in life satisfaction and two social support measures: worth and social integration. Thus, the addition of volunteer visitors to planned homemaking and nursing care made a difference for elderly in the community.     

Treating allergic rhinitis in pregnancy. Safety considerations.

Allergic rhinitis affects approximately one-third of women of childbearing age. As a result, symptoms ranging from sneezing and itching to severe nasal obstruction may require pharmacotherapy. However, product labels state that medications for allergic rhinitis should be avoided during pregnancy due to lack of fetal safety data, even though the majority of the agents have human data which refute these notions. We present a systematic and critical review of the medical literature on the use of pharmacotherapy for the management of allergic rhinitis during pregnancy. Electronic databases and other literature sources were searched to identify observational controlled studies focusing on the rate of fetal malformations in pregnant women exposed to agents used to treat allergic rhinitis and related diseases compared with controls. Immunotherapy and intranasal sodium cromoglycate (cromolyn) and beclo-methasone would be considered as first-line therapy, both because of their lack of association with congenital abnormalities and their superior efficacy to other agents. First-generation (e.g. chlorpheniramine) and second-generation (e.g. cetirizine) antihistamines have not been incriminated as human teratogens. However, first-generation antihistamines are favoured over their second generation counterparts based on their longevity, leading to more conclusive evidence of safety. There are no controlled trials with loratadine and fexofenadine in human pregnancy. Oral, intranasal and ophthalmic decongestants (e.g. pseudoephedrine, phenylephrine and oxymetazoline, respectively) should be considered as second-line therapy, although further studies are needed to clarify their fetal safety. No human reproductive studies have been reported with the ophthalmic antihistamines ketorolac and levocabastine, although preliminary data reported suggest no association between pheniramine and congenital malformations. There are no documented epidemiological studies with intranasal corticosteroids (e.g. budesonide, fluticasone propionate, mometasone) during pregnancy; however, inhaled corticosteroids (e.g. beclomethasone) have not been incriminated as teratogens and are commonly used by pregnant women who have asthma. In summary, women with allergic rhinitis during pregnancy can be treated with a number of pharmacological agents without concern of untoward effects on their unborn child. Although the choice of agents in part should be based on evidence of fetal safety, issue of efficacy needs to be addressed in order to optimally manage this condition.     

An investigation into variability in the therapeutic response to deferiprone in patients with thalassemia major

Data suggest a large variability in the effectiveness of the orally active iron chelator, deferiprone, in inducing a sustained decrease in body iron to concentrations compatible with the avoidance of complications from iron overload. We analyzed 19 patients with thalassemia major who were undergoing long-term therapy with deferiprone (75 mg/kg/day every 8 hours). In seven of the 19 patients, hepatic iron concentration had been reduced or maintained at less than 7 mg/g of dry weight liver tissue, associated with no evidence of iron-induced toxicity (group A). In the remaining 12, hepatic iron concentration had either stabilized at higher than 7 mg/g of dry weight liver tissue, or increased to such concentrations during therapy with deferiprone (group B). We studied in these patients determinants that may explain such variability, including initial hepatic iron concentrations, compliance, transfusion index, pharmacokinetic characteristics of deferiprone, and plasma vitamin C status. Patients in group B showed significantly decreased plasma vitamin C concentrations compared with those in group A, who demonstrated normal levels (0.04 mg/dl [0.04-0.19 mg/dl] and 0.62 mg/day [0.44-1.05 mg/day], respectively; p = 0.02). A significant difference in apparent volume of distribution (Vd/F) had developed between the groups over time, with a higher Vd/F in group B (1.66 [0.681, group A] and 3.16 [0.811, group B]; p = 0.006). Group B had started with hepatic iron concentrations that were significantly higher than those of group A, a difference that became more pronounced over time. In the initial analysis, serum ferritin concentrations were also higher in group B. The two groups did not differ in the remaining factors. The initial hepatic iron concentrations predicted the slope of change in this value. Regression analysis suggested that patients with initial hepatic iron concentration of less than or equal to 7.22 mg/g of dry weight liver tissue are unlikely to further decrease while taking deferiprone 75 mg/kg/day. Vitamin C deficiency developed in patients in group B over time. Vitamin C is an important biologic cofactor that plays a role in the distribution of iron. The trend of increase in Vd/F of deferiprone over time may imply a compartment shift of iron stores to one less accessed by deferiprone. This study confirmed the effectiveness of deferiprone in heavily iron-loaded patients and provided evidence that its effectiveness decreases in proportion to liver iron load.     

Urine fingerprinting: detection of sample tampering in an opiate dependency program

Methadone treatment programs commonly monitor patient compliance by screening urine samples for drugs of abuse. Our experience suggests that re-submission of urine samples (for example, providing a urine sample that is either not that of the patient or was previously submitted) is often used as a method of sample tampering. We have developed an algorithm that combines urine sodium, chloride, creatinine and pH values with urine drug screening results to effectively detect resubmitted samples. Given the widespread use of urine drug screening in drug and alcohol rehabilitation programs, we believe this technique has significant practical benefits. This technique may also have an application in forensic identification of duplicate samples.     

Pharmacokinetics of arginine butyrate in patients with hemoglobinopathy

Recent reports have demonstrated improvement in the clinical status and hemoglobin levels with use of intravenous arginine butyrate in patients with homozygous β-thalassemia and sickle cell disease.

To allow optimalization of therapy, we conducted pharmacokinetic studies in nine patients, five with sickle cell disease and four with β-thalassemia, treated with continuous intravenous infusion of arginine butyrate.

The disappearance of the drug after discontinuation was characterized by a biphasic elimination with an initial rapid phase followed by a slower phase. Redistribution was noted in five of the patients after 11.2 ± 4.0 min. The short half life was the result of both rapid clearance rate of 93.6 ± 31.9 ml/kg/min and small Vc (0.21 ± 0.26 l/kg) and Vss (0.31 ± 0.37 l/kg).

While preliminary results of the effectiveness of arginine butyrate are encouraging with a rise of γ-globin mRNA and F reticulocytes in some patients, the rapid elimination of this agent will probably limit its current use to administration by continuous infusion.     

Kraepelin-oriented research-diagnosable schizophrenia,mania, and depression in schneider-negative schizophrenics

Summary The rigorous neo-Kraepelinean research criteria of the St. Louis/ Iowa and Taylor groups were applied to case record data of 116 first admissions of Schneider-negative schizophrenics—that is, those without first-rank symptoms (FRSs)—hospitalized in a strongly Schneider-oriented German University Psychiatric Clinic from 1962 to 1971. This sample had a total of 45.7% (53 cases) of psychiatric illness diagnosable by research methods. Indeed, only 31% (36 cases) of Schneider-negative schizophrenics turned out to have research-positive Kraepelin-oriented schizophrenia; and of these, 21 fulfilled both sets of research criteria for schizophrenia. It is important that 14.6% (17 cases) of Schneider-negative schizophrenia consisted of research-diagnosable affective disorder, with mania making up 5.2% and depression 9.4% of this figure. The findings suggest that a sample of Schneider-oriented schizophrenia without FRSs as routinely diagnosed in Germany does not seem to represent a clear-cut homogeneous and uncontaminated group of schizophrenics.     

Postmortem redistribution of morphine in rats.

Because morphine is often found in the postmortem (PM) blood samples of patients treated with or abusing the drug, its causation in death has to be considered. The possibility of PM redistribution of the opioid drug has not been studied previously. We treated adult Wistar rats with 4 mg/kg of morphine i.m. and measured cardiac cavity levels at the time of death, by killing (2 h postdose) 24 and 96 h PM. Morphine concentrations rose from 41.4 +/- 13.2 ng/ml at death to 111.9 +/- 66.6 ng/ml at 24 h (p = 0.00036), with no additional increase at 96 h (98.7 +/- 21.7 ng/ml). After death there was accumulation of endogenous substances cross-reacting with the morphine radioimmunoassay. Although these attribute only 3% to total accumulation of morphine, they may complicate interpretation of morphine "readings" in patients who had not received the drug. Our study suggests that after death there is substantial redistribution of morphine. Elevated PM levels cannot necessarily by interpreted as representing antemortem concentrations.