Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

Fluorimetric assay of rufloxacin in serum and in pharmaceutical formulations

A simple and rapid fluorimetric method for the determination of 9-fluoro-10-[N-(4′-methyl)piperazinyl]-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-d,e][1–4]benzothyazin-6-carboxylic acid hydrochloride (MF 934), in serum and in pharmaceutical formulations, has been developed based on its strong fluorescence, in 0.1 N H₂SO₄, at 526 nm (excitation wavelength at 340 nm). The procedure which involves the direct dilution of the sample requires only a few minutes and the sample volume is only 20–100 μl of serum, depending on the drug concentration. Tedious sample preparation procedures such as extraction, deproteinization, or centrifugation are not necessary. The minimum concentration that can be detected is 0.3 ng ml⁻¹, the standard curve in 0.1 N H₂SO₄ was found to be linear from 0.005 to 1.5 μg ml⁻¹ and from 0.01 to 0.07 g in plasma after dilution with 0.1 N H₂SO₄.     

Plastic surgery for the management of palmoplantar keratodermia (Palmoplantoneoplasty)

Keratodermia is an incurable genetic and regional disease located in the palmar and plantar regions. The author reports his experience with five cases of palmoplantar keratodermia that were treated by grafting onto the soles and the palms skin taken from the calves and the thighs.     

Mass spectrometric identification of urinary and plasma metabolites of 2-(6'-carboxyhexyl)-3-n-hexylcyclohexylamine, a new antiaggregating agent.

The compound IBI-P-05006, 2-(6'-carboxyhexyl)-3-n-hexylcyclohexylamine, is an antiaggregating agent under development. IBI-P-05006 is an in vitro inhibitor of platelet aggregation. The biotransformation of this compound has been studied in the dog and rat. We present here a study on the metabolites of IBI-P-05006 found in dog and rat urine, and in dog plasma. Analyses were done by gas chromatography-mass spectrometry. In dog urine 15 metabolites were identified. Some of them were also found in dog plasma and in rat urine. The unmetabolized drug was found only in plasma. 10 different hydroxylated metabolites were characterized. The hydroxyl groups were introduced in the hexyl chain in positions omega-4, omega-3, omega-2, omega-1 and omega.     

Velamentous cord insertion into the lower third of the uterus is associated with intrapartum fetal heart rate abnormalities.

OBJECTIVES: To evaluate the accuracy of sonographic identification of the site of umbilical cord insertion (CI) at 18-20 weeks of gestation, to compare the sensitivities for detection of a velamentous cord insertion (VCI) secondary to a CI into the anterior, posterior or fundal wall, and to compare the intrapartum complications secondary to VCI into the upper, middle or lower third of the uterus. METHODS: As part of the routine ultrasound scan at 18-20 weeks' gestation we evaluated abnormal CI (VCI and marginal CI) and the location of the CI in the uterus in 3446 pregnancies. In cases of abnormal CI, the location of the CI was further classified as being in the upper, middle or lower third of the uterus. After delivery, the placenta and the umbilical cord were examined and intrapartum complications were compared with the location of the CI. RESULTS: The values for antenatal detection of VCI were: sensitivity, 25 of 40 (62.5%); positive predictive value, 25 of 25 (100%); and negative predictive value, 3406 of 3421 (99.6%). The sensitivity for cases in which the CI was located on the anterior wall was 12 of 13 (92.3%); when it was located on the posterior wall, the sensitivity was 11 of 22 (50.0%); and when it was fundal the sensitivity was 2 of 5 (40.0%). Variable decelerations were frequently observed with a VCI. In lower VCI cases, non-reassuring fetal heart rate patterns and emergency Cesarean sections occurred with a higher frequency than in cases with upper or middle VCI (P < 0.01). After delivery, the length of the aberrant vessels in cases of VCI by pathologic examination was 3.9 +/- 3.3 cm in the upper third, 4.7 +/- 4.6 cm in the middle third, and 10.6 +/- 6.8 cm in the lower third; thus, the aberrant vessel length was significantly greater when the CI was in the lower third of the uterus (P = 0.024). CONCLUSION: We have demonstrated that VCI with a lower CI site and with longer aberrant vessels is associated with various intrapartum complications. This finding has the potential for improving perinatal outcome.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Metabolism and pharmacokinetics of p-(3,3-dimethyl-1-triazeno) benzoic acid in M5076 sarcoma-bearing mice

Summary The pharmacokinetics of the anticancer agent p-(3,3-dimethyl-1-triazeno) benzoic acid (pCOOH-DMT), a drug now in phase I clinical trial in Europe, was investigated in C57 Bl female mice with M5076 reticulum-cell sarcoma that were treated i.v. with 200 mg/kg pCOOH-DMT. The drug disappeared from plasma with a terminal half-life of about 2.5 h. Plasma clearance was approximately 6 ml/min per kg. Distribution studies showed some differences in drug levels in different tissues. The highest levels were found in the tumor, liver, kidney and lung; lower levels were found in the spleen and gut, and the lowest, in the brain. The N-desmethyl derivative of pCOOH-DMT was not detectable in plasma or tissues of mice treated with the drug. Therefore, the previous evidence of low N-demethylation of pCOOH-DMT was confirmed. pCOOH-DMT glucuronide was identified by mass spectrometry and quantified by high-performance liquid chromatography (HPLC) in plasma, tissues and urine samples. pCOOH-DMT glucuronide appears to be the major urinary metabolite of pCOOH-DMT in mice. Another metabolite identified by mass spectrometry and quantified by HPLC in some tissues and urine was pCOOH-DMT glycinate.Abbreviations DTIlC 5-(3,3-dimethyl-l-triazeno)imidazole-4-carboxamide - pCOOH-DMT p-(3,3-dimethyl-l-triazeno)benzoic acid - pCOOH-MMT p-(3-methyl-l-triazeno)benzoic acid - pCONH₂-DMT p-(3,3-dimethyl-l-triazeno)carboxamide - BSTFA N,O-bis(trimethylsilyl)trifluoroacetamide - TMCS trimethylchlorosilane - TLC thin-layer chromatography - FAB fast atom bombardment - EI electron impact - M5 M5076 reticulum-cell sarcoma - t_1/2 beta-half-life - C₀ concentration time 0 - AUC area under the concentration vs time curve - Cl total clearance - V volume of distribution     

Prenatal diagnosis of a complete mole coexisting with a dichorionic twin pregnancy: case report

A complete mole coexisting with dichorionic twins was diagnosed by the combined use of sonography and chorionic villus sampling at 10 weeks gestation. The pregnancy resulted in the death of one fetus at 31 weeks from presumed feto-maternal haemorrhage, while the other fetus survived in good condition. A summary of the available literature, combined with this report, reveals a total of seven pregnancies with twins and a coexistent complete mole. Only two out of 14 fetuses survived. Maternal complications included one case of pre-eclampsia and one persistent trophoblastic tumour. Accurate diagnosis of complete mole is possible by genetic analysis of chorionic villi obtained with standard transabdominal sampling. Twins with a coexistent complete mole will usually undergo miscarriage. However, fetal survival is possible and the maternal risks seem limited. A concomitance between gestational trophoblastic disease and the occurrence of feto-maternal haemorrhage is observed.