Treatment of cutaneous T-cell lymphoma with extracorporeal photopheresis monotherapy and in combination with recombinant interferon alfa: a 10-year experience at a single institution

BACKGROUND: Extracorporeal photopheresis is a pheresis-based therapy that permits the direct targeting of psoralen-mediated photochemotherapy to circulating pathogenic T cells. Although photopheresis is currently used to treat cutaneous T-cell lymphoma (CTCL), limited data are available regarding overall response rates and durability of responses among patients with advanced disease. Furthermore, little is known about the effectiveness and tolerability of combined regimens employing other biologic response modifiers including interferon alfa. OBJECTIVE: Our purpose was to determine the efficacy of photopheresis among 41 patients with the clinical and laboratory diagnosis of CTCL; the majority of patients had stage III or IV disease with the presence of circulating malignant T cells. METHODS: A retrospective chart review during a 10-year period at a single university hospital was performed for all patients receiving either photopheresis monotherapy on two consecutive days every 4 weeks (one cycle) and for an additional 12 patients who also received interferon alfa 1.5 to 5 million U subcutaneously three to five times weekly. RESULTS: Thirty-one of 41 patients (76%) were treated for six or more cycles. The remaining 10 were treated with less than six cycles because of rapidly progressing disease (n = 6), death unrelated to CTCL (n = 2), or withdrawal from treatment (n = 1); one of the 10 patients had only received five cycles of treatment but is still receiving therapy. Twenty-eight of the 31 patients treated for six or more cycles received photopheresis alone. Among the 28, seven patients (25%) had a complete remission, 13 (46%) had a partial remission defined as more than 50% clearing of skin disease, and eight (29%) did not respond to treatment. The presence of Sézary cells in the peripheral blood was associated with a favorable response. Median time to treatment failure was 18 months, whereas median survival from initiation of therapy was 77 months and from the time of diagnosis exceeded 100 months. Nine of these 28 patients went on to receive combination therapy with interferon alfa and, in some cases, other agents. Among these nine patients, five had an enhanced clinical response to the combination therapy compared with treatment with photopheresis monotherapy. The combined regimen was well tolerated. CONCLUSION: These results indicate that patients with advanced CTCL can achieve a high response rate for an extended period with photopheresis and that interferon alfa combined with photopheresis is a well-tolerated regimen that appears to produce higher response rates than photopheresis alone.     

Testing your older patient's thyroid function

Thyroid disease cannot be diagnosed through any single test. Normal aging does affect the values of some test parameters in the elderly. When interpreting laboratory test results in the elderly, careful consideration should be given to gender, concurrent acute or chronic illness, nutritional and mental status, as well as possible recent administration of iodinated radiocontrast media and drug therapy. When these factors have been excluded and preliminary routine thyroid function are abnormal or marginally suspect, the usual standards for younger adults, slightly modified, should suffice for diagnosing both hypo-and hyperthyroidism. Patients with complications may require special measurements of serum FT4 and FT3 levels as well as the TSH and T3 response to TRH. These tests will provide additional supportive diagnostic assistance.     

Milia restricted to the eyelids

The present study was performed to estimate the prevalence of Rett syndrome in Fukui prefecture by sending questionnaires to special classes (classes for handicapped children in schools for normal children) and schools for mentally/physically handicapped children, and observing children suspected of having this syndrome on the basis of answers to the questionnaire. The subjects were girls aged 6-14 years who were attending 11 special classes and 7 schools for handicapped children. The prevalence of Rett syndrome was estimated to be 0.22 per 10,000 girls aged 6-14 years in Fukui prefecture, as of April 1, 1993. The prevalence noted in this study was lower than those found in previous studies in Japan and Western countries.     

Muscarinic acetylcholine receptors in Torpedo electric organ: effect of guanine nucleotides

The effect of guanine nucleotides on the binding properties of presynaptic muscarinic receptors has been studied in a membrane preparation from the electric organ of Torpedo marmorata by measuring the competitive displacement of the radiolabelled antagonist, [3H]quinuclidinyl benzilate, by nonradioactive muscarinic ligands. The binding of the antagonists, atropine, scopolamine and pirenzepine was to a single class of sites [slope factors (pseudo Hill coefficients) close to 1] and was unaffected by 0.1 mM GTP. The binding of the N-methylated antagonists, N-methylatropine and N-methyl-scopolamine was more complex (slope factors less than 1) but also insensitive (N-methylatropine) to 0.1 mM GTP. Agonist binding was complex and could be resolved into two binding sites with relatively high and low affinities. The proportion of high-affinity sites varied with the nature of the agonist (15-80%). Agonist binding was depressed by 0.1 mM GTP, and the order of sensitivity was oxotremorine-M greater than carbamoylcholine greater than muscarine greater than acetylcholine greater than arecoline greater than oxotremorine. The binding of pilocarpine, a partial agonist, was unaffected by GTP. With carbamoylcholine as a test ligand the GTP effect on agonist binding was half-maximal at 12 microM. GDP and guanylylimidodiphosphate produced comparable inhibition of carbamoylcholine binding, but GMP and cyclic GMP were ineffective, as were various adenine nucleotides. Analysis of agonist binding in terms of a two-site model indicates that the predominant effect of guanine nucleotides is to reduce the number of sites of higher affinity.     

Dosimetry of rhenium-186-labeled monoclonal antibodies: methods, prediction from technetium-99m-labeled antibodies and results of phase I trials

Rhenium-186 is a beta-emitting radionuclide that has been studied for applications in radioimmunotherapy. Its 137 keV gamma photon is ideal for imaging the biodistribution of the immunoconjugates and for obtaining gamma camera data for estimation of dosimetry. Methods used for determining radiation absorbed dose are described. We have estimated absorbed dose to normal organs and tumors following administration of two different 186Re-labeled immunoconjugates, intact NR-LU-10 antibody and the F(ab')2 fragment of NR-CO-02. Tumor dose estimates in 46 patients varied over a wide range, 0.4-18.6 rads/mCi, but were similar in both studies. Accuracy of activity estimates in superficial tumors was confirmed by biopsy. Prediction of 186Re dosimetry from a prior 99mTc imaging study using a tracer dose of antibody was attempted in the NR-CO-02 (Fab')2 study. Although 99mTc was an accurate predictor of tumor localization and the mean predicted and observed radiation absorbed doses to normal organs compared favorably, 186Re dosimetry could not be reliably predicted in individual patients. The methods described nevertheless provide adequate estimates of 186Re dosimetry to tumor and normal organs.     

Direct vs indirect blood pressure at rest and during isometric exercise in normal subjects

Systolic and diastolic blood pressures were measured by intraarterial means and by auscultation. Comparisons were made with simultaneously determined intraarterial catheter and auscultation measurements. Five healthy males were measured at rest and during handgrip and deadlift isometric exercises, utilizing small and large muscle mass. The data suggest that indirect systolic blood pressure is highly correlated with the direct method at rest, during handgrip and deadlift (0.8, 0.9 and 0.91 respectively) isometric exercises. Indirect diastolic blood pressure correlates well with intraarterial at rest (0.7) and during the isometric handgrip bout which utilized small muscle mass (0.8). As for the deadlift manoeuvre, the correlation coefficients between the indirect and direct methods were low. These results suggest that when utilizing large muscle mass during isometric deadlift exercise, the indirect method is not valid for assessment of diastolic blood pressure.     

A G-protein-coupled 130 kDa phospholipase C isozyme, PLC-beta 4, from the particulate fraction of bovine cerebellum

A 130 kDa PLC isozyme was purified from the particulate fraction of bovine cerebellum. This PLC was recognized by a polyclonal antiserum generated against the purified 97 kDa PLC-beta 4. Reconstitution of the purified 130 kDa PLC with the membranes of C6 Bu-1 cells in the presence of GTP gamma S or AlF4- resulted in PLC activation as well as the association of PLC with the membranes. Both the association and activation were revoked when the membrane was washed with 2 M KCl. The 97 kDa PLC-beta 4 did not associate with membranes. These data suggest that the 130 kDa PLC is the intact form of PLC-beta 4 the activity of which is likely to be regulated by a G-protein on the membrane.