Blanka Schaumann

Effects of Carbamazepine on Human Chromosomes

Summary: The effect of carbamazepine (CBZ) on human chromosomes was studied in an effort to determine its mutagenic potential. Analysis of chromosome breakage, sister chromatid exchanges (SCE), and cell cycle studies were performed in peripheral lymphocyte cultures. The in vivo studies failed to detect any significant increase of chromosome aberrations or SCE or any slowing of the cell cycle. A significant dosedependent increase in chromosome aberrations but not in SCE was observed in the in vitro analyses. No correlation was observed between chromosome breaks and SCE in either the in vivo or in vitro studies. The negative in vivo results indicate an absence of detectable chromosome‐damaging effects of CBZ used in monotherapy in human subjects.

Comparative effects of phenytoin and/or phenobarbital treatment on sister chromatid exchange

Summary: The potential of the widely prescribed antiep‐ileptic drugs (AEDs) phenytoin (PHT) and phenobarbital (PB) to interact with genetic material was tested using sister chromatid exchange (SCE) assay. Thirty adult male patients with epilepsy receiving long‐term AED therapy (16 with PHT, 6 with PB, and 8 with combined PHT and PB therapy) and 30 healthy controls were selected for the study of SCE frequencies in peripheral lymphocytes. The patients and controls were carefully screened and matched for sex, age, and smoking habits. All potential probands with exposure to factors known or suspected of affecting the SCE frequencies were excluded. Statistical analyses did not show any significant differences between the SCE rates of PHT‐ and/or PB‐treated patients and controls, indicating a lack of mutagenicity of the tested drugs as expressed by induction of SCE on adult recipients. Smoking, however, affected the SCE levels considerably. The smokers had higher SCE frequencies than the nonsmokers, both among patients and controls. Caffeine consumption was also associated with SCE increases in patients but not in controls.

Dermatoglyphics in trisomy 8 mosaicism

SummaryDermatoglyphic data on a patient with trisomy 8 mosaicism and of his immediate family are reported and compared with those of other known cases of trisomy 8 and other unidentified C trisomies. Similarities of the dermatoglyphics of trisomy 8 and unidentified C trisomy cases suggest that at least some of the latter represent chromosome 8 trisomy or its mosaicism. These similarities include arch patterns on the fingertips, low total finger ridge count, high palmar and plantar pattern intensity, simian creases and bilateral arches on the great toes.

Sister chromatid exchanges in adult epilepsy patients on valproate monotherapy

Sister chromatid exchanges (SCE) were studied in peripheral lymphocyte cultures of 13 adult male patients with epilepsy treated chronically with valproate (VPA) and in their matched controls. No statistically significant differences in SCE level were found between the patient and control groups, indicating a lack of mutagenic potential of VPA within the therapeutic dose range.

Lack of Sister Chromatid Exchange Induction in Phenytoin-Treated Patients with Epilepsy

Summary: Phenytoin (PHT) has been suspected of having a mutagenic effect with chronic administration, but the existing evidence is equivocal. Contradictory results have been obtained using different testing systems. Sister chromatid exchange (SCE), a sensitive indicator of geno‐toxic environmental influences, has been used in only a few limited studies of PHT users, with varying results. The present study was designed to evaluate the potential mutagenicity of PHT in a more objective and reliable way than has been done previously. Following careful screening procedures, 16 adult male patients with epilepsy receiving long‐term PHT monotherapy and 16 healthy controls were selected for a study of SCE frequencies in peripheral lymphocytes. The patients and controls were matched for sex, age, and smoking habits. Strict exclusionary criteria were observed, including all factors known to affect or suspected of affecting the SCE frequencies. Statistical analyses did not reveal any significant differences between the SCE rates of PHT‐treated patients and controls, indicating a lack of PHT mutagenicity as expressed by induction of SCE in adults.

Fetal and postnatal development of palmar, plantar, and digital pads, and flexion creases of the rat (Rattus norvegicus)

Fetal development of the hands and feet of rats was investigated to determine the feasibility of using rats as an experimental model for studying the factors influencing early development of the hands and feet, and especially the dermatoglyphics in humans. Eighty rat fetuses of 14–21 days gestational age and 80 newborn rats of 0–7 days of age were used to study the morphological features of the palmar, plantar, and digital areas and to determine the timing of appearance and the location of the volar pads and flexion creases. Comparisons between analogous developmental stages of rat and human fetuses demonstrate striking similarities in overall fetal development. Marked differences, however, were found between rat and human fetuses in the timing of developmental milestones and in some morphological features. The results indicate that rats can serve as a useful experimental model in studies of the utility of the epidermal ridge configurations and flexion creases in medical disorders, provided that the differences in the timing of development are taken into consideration.

Dermatoglyphic Pattern Configurations

Numerous investigators have proposed rules, principles, and definitions that allow reliable analyses of dermatoglyphics. The earlier proposals have been reviewed by Cummins and Midlo (1961). Their monograph served as the most comprehensive guide to dermatoglyphic analysis for more than three decades.1 When a relationship was reported between unusual dermatoglyphic features and certain chromosomal abnormalities, interest in dermatoglyphic analysis increased rapidly. The widespread interest in this field and a need for a standardized dermatoglyphic terminology stimulated an international symposium. As a result, a “Memorandum on Dermatoglyphic Nomenclature” was published (Penrose, 1968). The memorandum listed and defined dermatoglyphic features, outlined accepted methods of dermatoglyphic analysis, and provided a nomenclature that was intended to serve as a universal standard. The more subtle aspects of dermatoglyphics, which were previously dealt with in detail by Cummins and Midlo (1961) were not included in the memorandum.

Embryogenesis and Genetics of Epidermal Ridges

Dermal ridge differentiation takes place early in fetal development. The resulting ridge configurations are genetically determined and influenced (or modified) by environmental forces. There is a paucity of knowledge concerning the developmental mechanism that determines ultimate epidermal ridge patterns but a relationship to the fetal volar pads clearly exists because ridge patterns form at the sites of these pads.

Developmental Aspects of Human Palmar, Plantar, and Digital Flexion Creases

Unusual, extra of missing flexion creases have been reported in individuals with various medical disorders. Examples of such associations include the single transverse palmar flexion crease (“simian line”) and Sydney crease in Down syndrome (Beckman, Gustavson, & Norring 1962; Purvis-Smith & Menser 1968), “sandal” crease on the soles in Down syndrome (Penrose 1963) and the Rubinstein-Taybi syndrome (Rubinstein 1969; Filippi 1972), single interphalangeal crease on digit V in Down syndrome (Penrose 1931), trisomy 18 (Schaumann & Alter 1976; Hodes, Cole, Palmer, & Reed 1978) and partial trisomy 9p (Rodewald 1979), and missing distal interphalangeal flexion creases in a mentally retarded individual (Aue-Hauser 1979). Occasionally, unusual flexion creases are present in normal, healthy individuals (Davies & Smallpeice 1963; Alter 1970; Plato, Cereghino, & Steinberg 1973; Komatz, Daijo, & Yoshida 1978; Wertelecki 1979). The clinical significance of the flexion crease anomalies, however, is not well appreciated, mainly because of the limited understanding of the normal crease development (Lacroix, Wolff-Quenot, & Haffen 1984; Kimura and Kitagawa 1986; Stevens, Carey, Shah, & Bagley 1988; Kimura & Schaumann 1988). To fill this gap, we have studied the embryonal development and the morphology of the flexion creases on the surfaces of the palms, soles and digits in human fetuses.

Genotoxicity evaluation in patients on phenobarbital monotherapy by sister chromatid exchange

The potential of phenobarbital to interact with DNA has been studied using the sister chromatid exchange (SCE) assay in peripheral lymphocytes of nine adult male patients with epilepsy and of their matched controls. All patients were otherwise healthy individuals, treated chronically with phenobarbital in monotherapy. No statistically significant differences in SCE levels were found between the patient and control groups. Smoking was associated with increased SCE frequencies. The experiment was repeated with five available patients, using a slightly modified methodology. Although different SCE scores were obtained, the results of both tests were comparable.