[Free formaldehyde determination in cosmetic products by the HPLC method]. / Oznaczanie wolnego formaldehydu w srodkach kosmetycznych z zastosowaniem wysokosprawnej chromatografii cieczowej.

In order to standardize the analytical methods and procedures with the ones used in the EU, a method of free formaldehyde determination in cosmetic products preserved with formaldehyde donors, recommended by Commission Directive (90/207/EEC of 4th April, 1990), has been tested. The free formaldehyde level is determined by HPLC using post column derivatisation with acetylacetone. Formaldehyde content was determined in 44 fortified samples of cosmetic emulsions and shampoos. Recoveries ranged from 94.8-97.5%. Relative Standard Deviation 1-2.3%.

[Hair colorants]. / Preparaty do barwienia wlosów.

The properties, mode of action and its duration of the preparations used for hair dyeing are described, together with their chemical components, and also preparations of herbal origin. The chemical reactions are described in detail which lead the development of a color polymer occurring during hair dyeing. The studies are presented which are used for toxicological assessment of the raw materials which are the components of the colorants, and the list is included of hair colorants permitted for use in Poland.

[Formaldehyde determination using the colorimetric method with acetylacetone. II. Formaldehyde determination in cosmetic emulsions and certain household products]. / Oznaczanie formaldehydu w przedmiotach uzytku metoda kolorymetryczna z acetyloacetonem. Czesc II. Oznaczanie formaldehydu w emulsjach kosmetycznych i wybranych wyrobach chemii gospodarczej.

Total formaldehyde content was determined by the colorimetric method with acetylacetone in cosmetic emulsions and household products. The commercial products not containing formaldehyde were fortified with 150 micrograms of the investigated compound. Recovery in this method was 93.3-102.6%. The method was found useful in routine determinations of formaldehyde in cosmetics and household products and can be used by the State Sanitary Inspections.

[Determination of formaldehyde using the colorimetric method with acetylacetone. I. Determination of formaldehyde in selected cosmetic products]. / Oznaczanie formaldehydu w przedmiotach uzytku metoda kolorymetryczna z acetyloacetonem. Czesc I. Oznaczanie formaldehydu w wybranych srodkach kosmetycznych.

Total formaldehyde content was determined by the colorimetric method with acetylacetone in shampoos and foam baths. The commercial products containing formaldehyde were fortified with a solution of this compound of various amounts. Recovery in this method was 91.7-98.7%. The method was found useful in routine determinations of formaldehyde in shampoos and foam baths and can be used by the State Sanitary Inspection.

Germ cell tumors in children: gonadal and extragonadal.

Sixty-three pediatric patients with germ cell tumors are presented with details of symptoms, histological findings, staging, serological markers, treatment, and response to therapy. The primary sites were: ovarian 32, testicular 17, presacral 7, mediastinal 3, intraabdominal 2, vaginal 1, and right inguinal canal 1. These patients were treated with T2 (sequential use of dactinomycin, doxorubicin, vincristine, and cyclophosphamide, with or without radiation), T6 (combination chemotherapy with cyclophosphamide, bleomycin, dactinomycin, doxorubicin, methotrexate, vincristine), or VAB treatment protocols (velban, dactinomycin, bleomycin, cisplatin). The cure rate for stage I ovarian and testicular germ cell tumors was 100%; for stage III, all primary sites, 82% and for stage IV, all primary sites, 75%. Histology was prognostic in ovarian tumors of the immature malignant teratoma type; the neural type immature teratoma, grades II and III, had the worst prognosis. Initial debulking surgery in combination with chemotherapy and radiation plays an important role in germ cell tumors. Stages II, III, and IV germ cell tumors require aggressive treatment with surgery, radiation, and chemotherapy. For stage I patients, with primary ovarian malignant tumor, cure with surgery alone can be achieved in 50% of the cases and in testicular tumors in about 70% of the patients. For those with stage I and elevated serological markers, it is feasible to follow these markers and give no treatment until there is evidence of persistent elevation or a rise in titers after an initial fall. In those without elevated serological markers, one should take into consideration the size of the tumor and the histological type before taking the "wait and see" approach. These stage I tumors are highly curable when they first present but, if allowed to recur, chemotherapy may not offer the patient such a favorable response and cure rate.

Phase I trial of homoharringtonine in children with refractory leukemia.

Continuous infusion of homoharringtonine was administered to 17 children with refractory leukemia. Ten children with acute lymphoblastic leukemia received a total of 18 courses and seven children with acute nonlymphoblastic leukemia had a total of 13 courses. Doses were escalated from 1.65 to 8.5 mg/m2 for 5-10 consecutive days. Side effects included mild nausea and vomiting and transient changes in liver enzymes. Mucositis and diarrhea were more frequently seen at higher dose levels. Grade 3 hypotension and pain were seen at doses of 7 mg/m2 for 10 days. This is considered to be the maximum tolerated dose in this limited phase I trial. None of these previously heavily treated patients achieved a marrow remission.

Pediatric phase I trial and pharmacokinetic study of trimetrexate.

Trimetrexate, a new nonclassical antifolate, was evaluated in a phase I trial in children with refractory cancer including nine with acute leukemia and 21 with solid tumors. The drug was administered as an i.v. bolus injection weekly for three doses, and courses were repeated every 28 days. The dose ranged from 35 to 145 mg/m2. Thirty patients who received a total of 33 courses were evaluable for toxicity, including 19 who were evaluable for hematological toxicity. The maximally tolerated dose for patients with a solid tumor and leukemia was 110 mg/m2. The dose-limiting toxicities were myelosuppression, mucositis and a pruritic, diffuse maculopapular rash. Other side effects observed included transient, mild elevations of serum transaminases, mild nausea and vomiting, and a local phlebitis at the site of injection at higher dose levels. A single patient with delayed drug clearance had evidence of renal toxicity with a transient increase in serum creatinine. The pharmacokinetics of trimetrexate were studied in 25 patients over the entire dose range. There was considerable interpatient variability in total drug clearance (range 9.2 to 215 ml/min/m2) and half-life (2.1 to 20 h). There was a suggestion of a correlation between plasma concentration at 24 h and the development of hematological toxicity at the highest dose level. Trimetrexate was cleared primarily by biotransformation with renal clearance accounting for only 10% of total clearance. Two metabolites of trimetrexate which inhibit the enzyme dihydrofolate reductase were identified in the urine. One of these appears to be a glucuronide conjugate.

Phase I and clinical pharmacological study of 4-demethoxydaunorubicin (idarubicin) in children with advanced cancer.

We conducted a phase I and pharmacokinetic study of i.v. idarubicin, a new anthracycline analogue, in 42 evaluable children 1-19 years old. Twenty-seven had leukemia and 15 had various solid tumors. The drug was administered in escalating doses of 10 to 40 mg/m2/course in 3 equal fractions over 3 consecutive days at 14- to 21-day intervals. Myelosuppression and mucositis were the limiting toxicities for short-term administration. Nausea, vomiting, and elevation of liver enzymes and bilirubin were the other toxicities encountered. Peak toxicity occurred 2 weeks after drug administration with median recovery by day 24. All but 4 patients with solid tumors had prior anthracyclines. Mild cardiac function changes without clinical symptoms were observed in 17 of 35 patients measured by serial cardiac evaluations. In addition, there were 4 patients with congestive heart failure. On postmortem examination, 4 patients had changes consistent with anthracycline cardiomyopathy at a prior median total anthracycline dose of 175 mg/m2. The maximum tolerated dose for patients with solid tumors was 15 mg/m2 course in 3 divided doses. Patients with leukemia tolerated 30 mg/m2/course. Six of 15 evaluable patients with acute lymphoblastic leukemia who received greater than or equal to 30 mg/m2 idarubicin achieved a remission (M1 marrow status). The plasma clearance of idarubicin fits a 3-compartment model with a harmonic mean half-life of 2.4 min, 0.6 h, and 11.3 h for alpha, beta, and gamma phases, respectively. Idarubicinol was the only metabolite detected in the plasma and it accumulated during the 3 days of therapy. Idarubicin is similar to daunorubicin in pharmacology and toxicity. While the cardiotoxic dose still must be delineated, the complete remission achieved in multiple relapsed patients with acute lymphoblastic leukemia indicate promising activity in at least that disease.

Carboplatin and recurrent childhood brain tumors.

Carboplatin, a cisplatin analogue, was administered as an intravenous (IV) one-hour infusion in a 4-consecutive weekly dose schedule to 44 patients with recurrent childhood brain tumors. Twenty-four patients were registered on our phase I, and 20 on our phase II studies. The maximum tolerable dose derived from our phase I study was 210 mg/m2/wk in patients with solid tumors, and the recommended dose for subsequent pediatric phase II studies was 175 mg/m2/wk. This dose was administered to 14 patients in the phase I and all 20 patients in the phase II study. Nine of 36 (25%) evaluable patients in the combined studies experienced objective responses for a median duration of 10+ months. Seven of nine responders had received prior cisplatin. Disease-specific response rates were as follows: medulloblastoma, six of 14 (43%) with three complete (CR) and three partial responses (PR); pineoblastoma, one of one (PR); germinoma, one of two (CR); and brainstem glioma, one of eight (13%) (PR). Carboplatin had mild emetic effects but no significant auditory or renal toxicity. Thrombocytopenia (less than 49,000) was encountered in nine of 28 (32%) evaluable trials at a dose of 175 mg/m2/wk. Because of its low potential for auditory, renal, and emetic toxicity, ease of administration, and high disease-specific activity, carboplatin deserves further study in multiagent phase II and III trials, especially in chemotherapy-sensitive diseases such as medulloblastoma.