Targeted Infusions of Supradose Cisplatin With Systemic Neutralization for Carcinomas Invading the Temporal Bone

In an attempt to improve the dismal prognosis for patients with advanced cancer involving the temporal bone, a regional chemotherapy technique was piloted as part of the multimodality therapy for such patients. Rapid supradose cisplatin infusions selectively delivered to the lesion were given to 14 patients with carcinoma involving the temporal bone. Concurrent systemic cisplatin neutralization was achieved with sodium thiosulfate which permitted the use of cisplatin dose intensity regimens equivalent to fivefold the conventional amount. Four patients received chemotherapy alone, four had concomitant irradiation, and six had subsequent irradiation and/or temporal bone surgery. All patients tolerated the chemotherapy without significant complications or toxicity.

All three of the patients with previously untreated disease responded to chemotherapy (2 Crs, 1 PR); three of the seven patients with recurrent disease responded to chemotherapy; and all four patients treated with chemoradiation had a complete response (including one patient with recurrent disease). The median follow-up time was 19 months (range, 5 to 63 months). Nine of the 14 patients are alive, including the 4 who were treated with targeted chemoradiation.

The use of targeted high-dose chemotherapy for patients with malignant skull base lesions offers hope for improved outcome, particularly when this regimen is given simultaneously with radiation.

     

Absolute linkage of celiac disease and dermatitis herpetiformis to HLA-DQ

This report shows the absolute genetic linkage of celiac disease (CD) to the HLA-DQ region, and supports the fact that dermatitis herpetiformis (DH) follows the same pattern of HLA-mediated susceptibility in extensive series of Caucasian Spanish patients. Ninety-five percent of CD (201 of 212) and 100% of DH (55) patients could produce DQã1*0501-DQβ1*02 heterodimers. Negative CD patients for this combination were mostly DR4-DQ8 (DQA1*03-DQB1*0302) (9 of 11), along with a restricted number of complementary chromosomes. Comparison of observed and expected DQA1-DQB1 genotype distributions (Hardy-Weinberg equilibrium) showed that the excess of patients with DQB1*02 in double doses would be the consequence for which this allele should be complemented by DQA1*0501. Homozygosity for DQA1*O501 would restrain susceptibility to CD and DH.     

Parathyroid hormone resistance and B cell lymphopenia in propionic acidemia

The mechanisms of hypocalcemia, recurrent infections and hypogammaglobulinemia associated with metabolic decompensation of propionic acidemia due to propionyl-CoA carboxylase deficiency have not been defined. A 7-week-old infant with this disorder presented with severe hypocalcemia and B cell lymphopenia during an episode of metabolic acidosis and hyperammonemia. Hypocalcemia (1.1 mmoll ¹) was associated with elevated serum intact parathyroid hormone (122 ng 1 ¹), hyperphosphatemia, hypophosphaturia and hypercalcuria, indicating parathyroid hormone resistance. B cell lymphopenia (20 cells μl^-1) was associated with transient neutropenia, anemia and subsequent hypogammaglobulinemia (IgG < 294mgdl^-1, IgM < 8mgdl^-1, IgA < 8mgdl ¹), while T cells were normal. Parathyroid hormone resistance and B cell lymphopenia resolved following treatment with hemodialysis, diet and carnitine. These complications may be due to interference with parathyroid hormone renal tubular action and B cell maturation/proliferation by accumulated organic acids.     

Penetration of hematoporphyrin derivative into rat brain and intracerebral 9L glioma tissue

Summary Brain and glioma tissue levels of tritiated hematoporphyrin derivative (³H-HPD) were measured in normal and 9L intracerebral glioma-bearing rats at 24 hours following administration of³H-HPD 2–20 mg/kg and at 24–120 hours after³H-HPD 10 mg/kg. Levels of³H-HPD in blood, liver, spleen and muscle were also measured.Tissue levels of³H-HPD increased progressively as the dose was increased. In animals given 10 mg/kg, gradual decreases in tissue levels occurred between 24 and 72 hours but thereafter remained stable. The³H-HPD level in gliomas was consistently 2–3 × greater than in brain tissue, despite changes in dosage and time interval. High levels of activity were measured in normal brain tissue at all dosage levels, and subsequent clearance of the³H-HPD from brain, glioma, and other tissues was slow; at 120 hours after administration of 10 mg/kg, approximately 50% of the 24 hour level was still present.These results indicate that although a dose- and time-independent preferential uptake of hematoporphyrin derivative occurs in intracerebral gliomas, persistent high levels may be present in the surrounding brain. The disadvantages of using hematoporphyrin derivative rather than its individual components in studies of HPD uptake and photosensitization in the brain are discussed.     

A light-driven rhythm in neurotensin-like immunoreactivity in the chicken retina

Purpose: To determine if the pattern of release of neurotensin from the enkephalin-, neurotensin- and somatostatin-like immunoreactive amacrine cells in response to light and dark is the same as that of the enkephalins and somatostatin. Methods/Results: Both the enkephalins and somatostatin are released at high rates in the dark and at lower rates in the light, and these rate changes are reflected in increasing intracellular levels of the peptides in vivo in the light and decreasing levels in the dark The levels of neurotensin-like immunoreactivity show a similar diurnal light-driven and non-circadian rhythm in vivo. Conclusion: This implies that the actual release rates of neurotensin follow the same patterns as those demonstrated in vitro for the enkephalins and somatostatin.     

BRIEF HOSPITALIZATION : RESULTS OF TWO-YEAR FOLLOW UP

Brief hospitalization contributes to quicker and more effective recovery in psychiatric practice. It also leads to a progressive change in the pattern of mental morbidity. Two-year follow-up of patients treated with this technique indicates that recovery is sustained, and relapse/wastage rate is low. There is need for further research in this significant aspect of military medicine.KEY WORDS: Follow-up studies, Hospitalization, Length of stay, Outcome assessment     

Clinical and endocrine effects of megestrol-acetate in women with pretreated advanced breast-cancer

Megestrol acetate (MA) is one of the most widely used progestins in the palliation of advanced breast cancer, but its optimal dose level has yet to be defined. Forty-six women with progressive advanced disease were given MA according to a monthly loading-dose-schedule (320 mg/day orally) followed by standard-dose maintenance (160 mg/day). Most of the patients had been heavily pretreated with endocrine and/or chemotherapy; all the cases were evaluable. The response rate was 20% (95% CI: 9-31%), with 9 subjects achieving PR. The median time to response was 3 months (range 2-11), the median response duration being 3 months (range 3+-12+). After a median follow-up period of 8 months (range 7-16), only 3 of the patients achieving PR are still on treatment. No increased toxicity or potentially detrimental endocrine effects were observed and all of the patients showed good compliance to treatment. Although the loading-dose schedule used in the present series proved to be feasible, it does not appear to provide any clinical advantage over standard-dose MA treatment.