Polymorphism in the pertussis toxin promoter region affecting the DNA-based diagnosis of Bordetella infection

The pertussis toxin (PT) promoter region is a frequently used target for DNA-based diagnosis of pertussis and parapertussis infections. The reported polymorphism in this region has also allowed discrimination of species in mixtures with several Bordetella species by their specific PCR amplicon restriction patterns. In the present study, we investigated the degree of polymorphism in order to confirm the reliability of the assay. Five different sequence types of the amplified 239- or 249-bp region were found among the 33 Bordetella pertussis, B. parapertussis, and B. bronchiseptica American Type Culture Collection reference strains and patient isolates analyzed. According to the sequences that were obtained and according to the PT promoter sequences already available in the databases, restriction enzyme analysis with TaqI, BglI, and HaeII, which gave four different patterns, can be performed to reliably identify B. pertussis, B. parapertussis, and B. bronchiseptica.     

Long-term follow-up in patients treated with electrochemotherapy for non-melanoma skin cancer in the head and neck area

Background: Electrochemotherapy (ECT) is a cancer treatment modality where the intracellular accumulation of chemotherapeutic agents is enhanced by an applied electrical field.

Aims/Objectives: To evaluate the long-term efficacy, safety and functional outcome after ECT treatment in high-risk non-melanoma skin cancer (NMSC) with curative intent.

Materials and methods: Seven patients with SCC or BCC in the head and neck area were treated with ECT with intratumoral bleomycin administration.

Results: Five patients were cured by ECT as a mono-modality treatment after a median 10-year follow-up period. Two patients had recurrences and/or persisting tumors after treatment that required salvage surgery and radiotherapy. In two patients, the eye was spared with no visual impairment. In another patient, full facial nerve function was spared.

Conclusions: ECT can be a curative as well as an organ and function-sparing mono modality treatment in high-risk NMSC.

Significance: Today ECT is mostly used as a palliative treatment. Its curative potential should be further investigated. Randomized studies comparing ECT with standard treatment is needed. Hopefully, this small study can encourage such studies.     

Total body potassium measurements in 230 patients. A study of potassium depletion.

Three groups of patients with suspected potassium depletion were studied. Twenty-nine obese patients were observed before and up to 1 year after an intestinal shunt operation. During the first week after operation they lost almost 3 grams of potassium per day. The percentage potassium loss was much larger than the percentage weight loss. A significant decrease of serum potassium was also noted during the first week after operation. In contrast to the total body potassium, however, the serum potassium remained within normal limits in all patients except two. Fourteen patients subjected to a cardiac operation also showed a significant decrease of total body potassium concentration 1 week after operation. The serum potassium remained within normal limits. In 187 patients with suspected potassium depletion the total body potassium had been measured, and the results were examined retrospectively. In 38 of these patients the measured total body potassium was outside a 94% confidence interval for an individually predicted value, even though 26 of these 38 patients were taking oral potassium chloride tablets. In 23 of these 38 patients two or three risk factors - hypoalbumin-emia, treatment with diuretics, and treatment with digitalis - were present simultaneously, and in 10 patients one factor was present. Only 8 of the 38 patients had a low serum potassium value. It may therefore be concluded that the total body potassium measurement, when compared with an individually predicted value, seems to be more sensitive in estimation of potassium depletion than the commonly used serum potassium method.     

Absent clinical effects of retinoic acid and isoretinoin treatment in the myelodysplastic syndrome

Ten patients with the myelodysplastic syndrome (eight with anemia, two with granulocytopenia, four with thrombocytopenia) were given etretinate (ER) and retinoid acid (RA). No correlation was seen between the RA effect in vitro and its clinical effect. No effect was seen of the ER-treatment or of the RA-treatment on anemia, thrombocytopenia or the abnormal karyotype seen in three patients. In three of eight patients given RA a decreased blast cell percentage in the bone marrow was seen, and in two of these there was also a normalization of the in vitro bone marrow cell colony formation. We found no clinical effect of ER and only a minimal one of RA.     

Phase I pharmacologic study of a new Vinca alkaloid: navelbine

Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week.