Changes in serum immunoglobulin levels during phenytoin treatment of epilepsy

Immunoglubulin concentrations were determined by radial immunodiffusion in sera from 15 epileptic patients before and during phenytoin therapy. Three reaction patterns were recorded: Two patients developed IgA deficiency (less than 0.05 mg/ml) during the first 3-4 months of treatment. Both patients also had a decrease in serum IgG and IgM, but no significant fall or increase in serum IgE. The IgA deficiency state was apparently reversible, since normalization of serum levels occurred after withdrawal of phenytoin. Five patients developed a 35-80 per cent reduction in serum IgA. In these patients, the decline in serum levels of IgG and IgM was inconsistent. Eight patients showed no significant fluctuations in serum immunoglobulins during phenytoin treatment. When a fall in serum IgA occurred, it did not correspond to a fall in serum or in red cell folate. Mean serum IgG was lower (9.37 mg/ml) in epileptic patients who had taken phenytoin for less than 1 year and had a low IgA, than in patients who had taken phenytoin for 10 years or more (11.50 mg/ml).     

Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin

AIMS: To evaluate absorption of protein-bound and unbound cyanocobalamin before and during treatment with omeprazole, and cobalamin levels in patients on long-term treatment with omeprazole. METHODS: In eight former duodenal ulcer patients absorption of unbound and protein-bound cobalamin was determined by measuring 24-h urinary excretion of unbound 58Co-cyancobalamin or protein-bound 57Co-cyanocobalamin during a modified Schilling test. Tests were performed before and during treatment with 20 mg and 40 mg omeprazole daily for 9 days. Serum cobalamin levels were assessed in 25 patients with gastro-oesophageal reflux disease (GERD) before and during long-term maintenance therapy with omeprazole. Mean treatment duration was 56 months (range 36-81 months). RESULTS: Urinary excretion of unbound cobalamin was unchanged with both dosages of omeprazole. Excretion of 57Co-cyanocobalamin, however, decreased significantly during treatment with both 20 mg omeprazole (mean +/- S.E.M.: 1.31 +/- 0.20 vs. 0.54 +/- 0.17%; P < 0.02) and 40 mg omeprazole (1.25 +/- 0.26 vs. 0.29 +/- 0.06%; P < 0.02). Mean serum cobalamin levels (+/- S.E.M.) before and during therapy with omeprazole in GERD patients were 298 +/- 27 and 261 +/- 16 pg/mL (normal range 180-900 pg/mL), respectively (P = N.S.). CONCLUSIONS: Absorption of protein-bound, but not unbound, cyanocobalamin is decreased when measured by a modified Schilling test during treatment with omeprazole. However, no change in serum cobalamin levels was observed in patients with GERD after treatment with omeprazole for up to 7 years.     

Comparison among delayed-type skin tests, serum IgE levels and peripheral blood CD4 in HIV-positive patients

Three groups of HIV-positive men and a control group of healthy subjects were evaluated simultaneously by delayed-type skin tests with recall antigens detection of CD4 cell counts in peripheral blood and the IgE serum levels. Delayed-type skin test reactivity and CD4 cell counts in peripheral blood decreased while IgE serum levels increased as immune imbalance progressed with the worsening of HIV infection (p = 0.003 between controls and HIV-positive patients). The existence of atopy did not significantly influence IgE serum levels in the groups of HIV-positive patients (p < 0.2). Candidin appeared as a useful antigen in the delayed-type skin tests considering that it was the only antigen that remained positive with low values of CD4 cell counts (< or = 250/mm3). The detection of serum IgE levels as well as the performance of delayed-type skin tests with recall antigens are useful tools to evaluate immunological status whereas the number of CD4 in peripheral blood is critical for determining the initiation of antiretroviral therapy.     

Elevated C3-proactivator serum levels in patients with chronic polyarthritis

The C3-Proactivator (C3-PA) and the C3 and C4 complements were determined by radio-immuno diffusion in the serum of 72 patients with definite or classical rheumatoid arthritis, 51 patients with osteoarthrosis and 42 healthy subjects. C3-PA and C4 levles were significantly higher in the serum of patients with rheumatoid arthritis than in the control group (C3-PA in 72%, C4 in 37% of the RA patients). There was also a significant difference between seropositive und seronegative cases. Elevation of both components was more frequently found in patients with seronegative rheumatoid arthritis than in the seropositive cases. However, the C3-PA serum level is not correlated with the ESR. Also an elevation of the C3-PA serum level is not specific for rheumatoid arthritis, it is also found in other inflammatory diseases as well as after surgery.     

Feasibility of reducing L-thyroxine dose in patients with a suppressed serum TSH

A total of 748 patients on L-thyroxine with a suppressed serum TSH were requested to reduce their dose and this was achieved in 601 patients. Thyroxine dosage was reduced by 25 or 50 micrograms of L-thyroxine and patients were reviewed six months later. Of all 601 patients, 54.4% remained with a suppressed serum TSH despite dose reduction and in 5.8% an elevated serum TSH resulted. 25 micrograms reductions and 50 micrograms reductions were equally likely to result in an detectable but non-elevated serum TSH (42.8% vs 34.1% ns) but 25 micrograms reductions were less likely to result in an elevated serum TSH (3.8% vs 10.0% p < 0.01). Only 7/601 patients in the study (1.2%) appeared to require a dose of over 150 micrograms. If dose reduction is thought to be necessary for patients with a suppressed serum TSH, we would recommend 50 micrograms reductions if the original dose is 200 micrograms or more, and 25 micrograms reductions if the original dose is 175 micrograms or less.     

Evaluation of CA 15-3 serum levels in breast cancer patients

A case of opacity in the fetal gallbladder was diagnosed by ultrasound. The lesion resolved spontaneously in the postnatal period. Careful follow-up ultrasound examinations are necessary for fetal cholelithiasis in the pre- and postnatal periods, and conservative management is mandatory.     

A patient showing increased T3 and T4 levels due to ALP-interfering substances and heterophilic antibody

A 73-year-old male, who underwent resection of soft palate cancer and was under treatment for esophageal ulcer at our medical department, complained of palpitation. On the suspicion of hyperthyroidism, enzyme immunoassay (EIA) was performed. T3 and T4 were increased, and FT4 and TSH were normal. However, T3 and T4 measured again by radioimmunoassay (RIA) were normal. Therefore, the patient serum was examined for interfering substances such as antibody against bovine intestinal alkaline phosphatase (ALP) and heterophilic antibody. Substances interfering with ALP and anti-rabbit IgG human antibody were detected. It is necessary to consider the possible presence of these substances when results of EIA are evaluated.     

Triiodothyronine (T3) and thyroxine (T4) levels in Rana curtipes during development and metamorphosis

During premetamorphosis, levels of circulating triiodothyronine (T3) and thyroxine (T4) were below the limits of detection of RIA. They became detectable in late prometamorphic stages. A gradual increase in T3 and T4 was observed during this period. A sharp rise in hormone levels was apparent at the onset of metamorphic climax. Peak levels of both hormones were found at Taylor-Kollros stage XXI. The T3 reached a peak level of 101.4 ng/dl, about 3 fold increase over the level at prometamorphosis. Thereafter the circulating hormones (particularly T4) decreased rapidly and reached levels similar to prometamorphic stages. Significant high levels of thyroid hormones (T3 and T4) in metamorphic climax suggest that like other anurans, elevation of these hormones is required for normal metamorphosis in R. curtipes tadpoles.     

Vitamin E serum levels in patients with leukemia, lymphoma and myeloma

The serum alpha-tocopherol levels were determined in a group of 182 patients with hematological neoplasms: 87 lymphoid or myeloid leukemias, 65 lymphomas and 30 myelomas. The levels did not differ from those of controls, when compared either globally or for diagnosis. Low alpha-tocopherol serum levels were observed in 6 patients (3.3%).     

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.     

Radioimmunoassay for 3,3',5'-triiodothyronine (reverse T3, R-T3) in unextracted human serum

Highly specific antibodies against 3,3',5'-triiodothyronine (reverse T3, R-T3) have been produced in rabbits. The crossreaction with T4 is about 0.05%. A radioimmunoassay for R-T3 in unextracted serum was developed. ANS is used for blocking the binding of tracer and endogenous R-T3 to TBG. The sensitivity to the assay is 0.06 ng/ml plasma. The mean normal R-T3 concentration is 0.20 ng/ml. Thyrotoxic patients show elevated levels; in most hypothyroid patients R-T3 concentrations are below the detection limit.     

Effect of chronic treatment with octreotide nasal powder on serum levels of growth hormone, insulin-like growth factor I, insulin-like growth factor binding proteins 1 and 3 in acromegalic patients

Octreotide nasal powder is a delivery system of the somatostatin analogue developed to overcome the inconvenience of repeated subcutaneous administrations. Eight patients with clinically active acromegaly were treated for three months with octreotide nasal powder which was administered at the initial dosage of 0.125 mg tid, doubling the dosage up to 2 mg tid in order to obtain a mean GH value below 5 micrograms/l during 8 daytime hours. In 4 of these patients, treatment was prolonged till the sixth month. Blood samples were taken on days 15, 29, 43, 55, 90, 120, 150, 180 for GH, IGF-I, IGFBP-3, IGFBP-1 and insulin measurements. Before treatment, mean daytime GH and morning IGF-I serum levels were both increased but not correlated with each other. Serum IGFBP-3 levels were higher than normal and positively correlated with those of GH, IGF-I and insulin. Insulin levels were elevated and positively correlated with those of GH but not with those of IGF-I and IGFBP-1. Serum IGFBP-1 levels were in the low normal range and not correlated with any of the other parameters. Treatment with octreotide nasal powder induced in all patients a marked decrease of GH which lowered below 5 micrograms/l in 7/8 patients and IGF-I levels, which fell within the normal range in 1 patient. Serum IGFBP-3 and insulin concentrations decreased by 26% and 71%, respectively, and those of IGFBP-1 underwent an only transient increase in 5/8 patients. Opposite changes of insulin and IGFBP-1 levels, with a decrease of the former followed by an increase of the latter were noted during the 8 hours following an octreotide nasal insufflation. During chronic octreotide treatment, positive correlations were found between GH and IGF-I, GH and IGFBP-3, IGF-I and IGFBP-3, insulin and IGFBP-3 and insulin and IGF-I. An improvement of the clinical picture was registered in all patients after a few days of octreotide nasal powder administration. Treatment was well tolerated, with only mild side effects and no significant changes in the nasal mucosa, and the patients' compliance was excellent.     

Long-term followup of all patients with muscle invasive (stages T2, T3 and T4) bladder carcinoma in a geographical region

PURPOSE: We studied the relationship between long-term survival and treatment of stages T2, T3 and T4 bladder carcinoma in an unselected patient population. MATERIALS AND METHODS: A total of 680 patients with the initial diagnosis of bladder carcinoma in 1987 to 1988 in Western Sweden was prospectively registered and followed until 1994. Of these patients 107 had stage T2 to T3 and 41 had stage T4 disease. RESULTS: Of the patients with stage T2 to T3 disease 30 (mean age 66) underwent radical cystectomy, 33 (mean age 75) full dose radiotherapy and 44 (mean age 81) nonradical therapy (mainly transurethral resection of the bladder). The 5-year crude survival rates were 33, 15 and 14%, respectively. Of the patients with stage T4 disease 6 (mean age 61) underwent radical cystectomy, 9 (mean age 73) full dose radiotherapy and 26 (mean age 81) nonradical therapy (mainly transurethral resection of the bladder). All except 1 patient died of disease within 4 years. CONCLUSIONS: More than 60% of the patients in the cohort were considered unsuitable for radical cystectomy and their survival was poor, whether treated with full dose radiotherapy or transurethral resection of the bladder alone.     

A simple and rapid thyroxine radioimmunoassy (T4-RIA) in unextracted human serum; a comparison of T4-RIA and T4 displacement assay, T4(D), in normal and pathologic sera

A simple, rapid and accurate thyroxine radioimmunoassay (T4-RIA) in unextracted serum or plasma has been described, and for comparison T4 determinations have also been made by a T4(D) procedure using Abbott Tetrasorb kits. T4-RIA procedure basically involved denaturation of serum to dissociate T4-protein bond, and T4 released was allowed to react with [125I]T4-labeled T4 antiserum elicited by immunizing rabbits against bovine thyroglobulin. The displaced unbound [125I]T4 was rapidly taken up by an anionic resin sponge within 15 min and this sponge [125I]T4 uptake was linearly related to T4 present in standards or serum. The denaturation of serum effected by trichloroacetic acid-sodium hydroxide permitted virtually 100% T4 extraction recovery in normal, pregnancy, hypo- and hyperthyroid sera whereas 72.9-87.6% T4 recovery from normal serum (and with large individual differences) was noted with lower alcohols in T4(D) procedure. Cumbersome and/or tedious steps such as pre-extraction, centrifugation, time consuming bound and unbound hormone separation procedures, etc. are obviated in T4-RIA and the entire assay can be completed in the same tube in approximately an hour. These attributes along with increased sensitivity and specificity and the need for only microamounts of test sera (25-50 mul) in T4-RIA offer distinct advantages over T4(D) procedures, and in simplicity excel even other T4-RIAs. T4-RIA values in physiological and pathological states were highly correlated (r = 0.97) with T4(D) measurements and no differences between these two techniques were found. The reported discrepancies between T4-RIA and T4(D) measurements in human sera and some of the reasons for attributing these inconsistencies to probable methodological errors and variations are discussed.     

Surgical treatment of extratemporal epilepsy: clinical, radiologic, and histopathologic findings in 60 patients

PURPOSE AND METHODS: The aim of this study was to analyze clinical, radiologic, and histopathologic findings in 60 consecutive patients with medically intractable extratemporal epilepsy who were operated on between November 1987 and May 1993. RESULTS: Histologically, there were distinct structural abnormalities in 50 (83%) of the surgical specimens. Signal abnormalities on magnetic resonance imaging (MRI) were present in all patients with neoplastic lesions (n = 17) and in 94% of patients with nonneoplastic focal lesions (n = 32). Overall, structural abnormalities were detected by MRI in 47 (96%) of 49 patients with focal lesions. During a mean follow-up of 4 years, 30 (54%) patients remained completely seizure free, 11 (20%) had < or = 2 seizures per year, seven (12%) showed a seizure reduction of > or = 75%, and eight (14%) had < 75% reduction in seizure frequency. The fraction of seizure-free patients was 12 (80%) of 15 in patients with neoplastic lesions, 16 (52%) of 31 in patients with nonneoplastic focal lesions, and two (20%) of 10 for those without histopathologic abnormalities. The differences in seizure outcome between patients with and without focal lesions were statistically significant (p < 0.05), if seizure-free outcome was compared with persistent seizures. CONCLUSIONS: Focal lesions and particularly neoplasms are associated with improved postoperative seizure control compared with patients without histopathologic abnormalities. We advise caution in considering surgery to treat extratemporal epilepsy in patients who have normal MRI scans, because the outcome with the approach described in this study is poor in such cases.     

Clozapine in long-term treatment of schizophrenic patients

Clozapine has advantages over standard antipsychotics in refractory schizophrenia. Studies on the efficacy of clozapine in the maintenance treatment are sparse and suffer from methodological limitations. Despite this fact clozapine ranked second in a survey dealing with the preference of this antipsychotic in the long-term treatment of schizophrenia. Doctors report on using a mean of 130 mg/d in this indication which is considerably less than the doses used in most of the published long-term trials. The discrepancy between the popularity of clozapine and the lack of sound empirical data on its long-term efficacy is discussed.     

Factors affecting T3 and T4 proficiency testing

Problem areas within a proficiency testing (PT) program are performance evaluation and sample stability. The different units used in the various T3 uptake methodologies make performance evaluation complex. To facilitate this evaluation, a normalization method for T3 uptake performance evaluation has been developed. Sample stability studies for T3 uptake indicate that, at room temperature, sample values increase after storage for about seven days. Room temperature sample stability studies for T4 using a competitive protein binding (CPB) method indicate that the apparent T4 content of pooled serum increases after about one week. Fatty acids are shown to be an interfering substance in the T4 CPB method as well as the T4 radioimmunoassay (RIA) method. This interference increases with a decrease in carbon chain length from C18 to C12 and with an increase in unsaturation of fatty acids. The B/B0 ration for arachidonic acid at a concentration of 0.48 micronMoles per tube is 17.4 in a CPB method and 87.1 in a radioimmunoassay method indicating that the greater effect is in the CPB method. The increase in T3 uptake values are probably also due to the interfering effect of fatty acids.