Adjuvant small field pelvic radiation for patients with high risk, stage IB lymph node negative cervix carcinoma after radical hysterectomy and pelvic lymph node dissection. A pilot study.

BACKGROUND: After radical hysterectomy and pelvic lymph node dissection, an identifiable subgroup of patients with International Federation of Gynecology and Obstetrics Stage IB lymph node negative cervix carcinoma remains at high risk of pelvic recurrence. This study attempted to determine whether postoperative small field of pelvic radiation can improve the disease free survival (DFS) of this high risk group of patients without producing significant morbidity. METHODS: Between 1991 and 1995, after radical surgery, 25 patients with Stage IB lymph node negative cervix carcinoma were considered to be at high risk of pelvic recurrence on the basis of tumor dimension, depth of stromal invasion, and the presence of lymph-vascular space invasion. All had a score >/= 120 as determined by the Gynecologic Oncology Group (GOG) study. These patients received 50.4 gray of adjuvant radiation to a small central pelvic field and were followed prospectively. A Kaplan-Meier 5-year DFS curve was generated. A log rank analysis produced an estimated log rank P value (est P value) by comparing the 5-year DFS of the patients in the current study with the 5-year DFS of the corresponding high risk group of the GOG study (observation only). The morbidity of small field pelvic radiation was recorded. RESULTS: Among the 25 patients who received small field pelvic radiation, the mean GOG score was 166 (range, 120-263) and the mean follow-up was 32 months (range, 12-64 months). There was 1 recurrence (4%) recorded at 16 months. The log rank analysis demonstrated a significant improvement in the 5-year DFS for the group who received adjuvant small field pelvic radiation (est P value = 0.005) when compared with the DFS of the high risk GOG patients who were observed postoperatively. Four cases of minor morbidity were recorded: lymphedema (three cases) and mild rectal incontinence (one case). No major morbidity was reported. CONCLUSIONS: With low morbidity, adjuvant small field pelvic radiation appears to improve significantly the 5-year DFS of patients with high risk, lymph node negative Stage IB cervical carcinoma. However, this pilot study requires verification.

Purification and characterization of the imidazoleglycerol-phosphate dehydratase of Saccharomyces cerevisiae from recombinant Escherichia coli.

The HIS3+ gene of Saccharomyces cerevisiae was overexpressed in Escherichia coli and the recombinant imidazoleglycerol-phosphate dehydratase (IGPD) purified to homogeneity. Laser-desorption and electrospray m.s. indicated a molecular ion within 2 units of that expected (23833.3) on the basis of the protein sequence, with about half of the polypeptide lacking the N-terminal formylmethionine residue. IGPD initially purified as an apoprotein was catalytically inactive and mainly a trimer of M(r) 70,000. Addition of Mn2+ (but not Mg2+) caused this to assemble to an active (40 units/mg) enzyme (Mn-IGPD) comprising of 24 subunits (M(r) 573,000) and containing 1.35 +/- 0.1 Mn atoms/polypeptide subunit. An enzyme with an identical activity and metal content was also obtained when the fermenter growth medium of recombinant Escherichia coli was supplemented with MnCl2, and IGPD was purified through as Mn-IGPD rather than as the apoenzyme and assembled in vitro. Inhibition by EDTA indicated that the intrinsic Mn2+ was essential for activity. The retention of activity over time after dilution to very low concentrations of enzyme (< 20 nM) indicated that the metal remained in tight association with the protein. A novel continuous assay method was developed to facilitate the kinetic characterization of Mn-IGPD. At pH 7.0, the Km for IGP was 0.10 +/- 0.02 mM and the Ki value for inhibition by 1,2,4-triazole, 0.12 +/- 0.02 mM. In contrast with other reports, thiols had no influence on catalytic activity. The activity of Mn-IGPD varied with enzyme concentration in such a way as to suggest that it dissociates to a less active form at very low concentrations. Significant inhibition by the product, imidazole acetol phosphate, was inferred from the shape of the progress curve. Titration with, the potent competitive inhibitor, 2-hydroxy-3-(1,2,4-triazol-1-yl)propyl phosphonate indicated that Mn-IGPD contained 0.9 +/- 0.1 catalytic sites/protomer. The activity nearly doubled in the presence of high concentrations of Mn2+; the apparent Ks for stimulation was 20 microM. The basis of this effect was obscure, since there was no corresponding increase in the titre of active sites. Neither was there a discernable shift in the values of Km or Ki (above), although exogenous Mn2+ did reduce the optimum pH for kcat, from 7.2 to 6.8. On the basis of a single site/subunit, the maximum rate of catalytic turnover at 30 degrees C was 32 s-1.

Allergic contact sensitivity to thiuram compounds in a hemodialysis unit.

An outbreak of dermatitis among patients in a hemodialysis unit was traced to thiuram compounds, most likely coming from the hemodialysis apparatus itself. Eight of the 21 patients in the facility had allergic contact sensitivity to various thiuram compounds. Testing of patients from other hemodialysis units, in which different hemodialysis equipment was used, did not disclose sensitivity or dermatitis. In the affected patients, allergic contact sensitization of the skin probably resulted from the systemic circulation of an antigen during hemodialysis.