Maternal hyperphenylalaninemias in healthy Czech population of pregnant women: 30 years experience with screening, prevention and treatment.

INTRODUCTION: The increased level of phenylalanine (Phe) in maternal blood--hyperphenylalaninemia (mHPA) has a detrimental effect on the early development of healthy foetus (1965). The toxic effect causes spontaneous abortion or retards intrauterine growth, skeletal malformation, cardiac anomalies can appear. However the most frequent are microcephaly, mental retardation and hypotrophy. PATIENTS AND METHODS: Simultaneously with the introduction of obligatory "Newborn Screening Program" in CR also the facultative screening for mHPA was introduced ("Maternal Hyperphenylalaninemia Preventive Screening Program"). Since 1975 till now 222,990 healthy pregnant women (16-47 yrs) from city Prague and its area (cca 2 mil. inh.) have been screened for increased Phe in blood by Efron's chromatographic screening test (1964); Phe cut off value: 240 micromol/l. Nonfasting venous blood has been taken in 2nd-3rd month of pregnancy during the first antenatal visit. All positive cases have been verified with quantitative Phe estimation on amino acid analyzer incl. pterines analysis in urine. For differentiation of detected mHPAs the Güttler's scheme (1980) has been used. Mutations for Phe-hydroxylase gene analyzed by restriction enzyme digestion after Guldberg (1994). RESULTS: The average incidence of mHPA detected at the beginning of pregnancy was found 1:8675. The major part (65.3%) of all detected mHPA belongs to mild or moderate form of phenylketonuria (PKU) with most frequent PAH gene mutations R408W, Y414C, IVS11 nt8g-a, R158Q, IVS12ntlg-a and R261Q. 19.2% corresponds to atypical or classical PKU with prevailing mutation R408W. Only in 15.3% were detected non-PKU (persistent HPA) with mutations R408W, Y414C, IVS12ntlg-a, IV11nt8g-a and A403V. 28 offsprings born from pregnancies on low-phenylalanine diet (LPD) introduced at least 2 months before the conception and during the whole pregnancy show normal psychomotoric development. In 7 offsprings without LPD or after delayed introducing or on PLD or badly monitored showed malformations (microcephaly, hypotrophy, skeletal malformations) or died. DISCUSSION: Relatively high incidence of mHPA detected in healthy population of pregnant women of Prague area differs from findings of Buist (1989) or Levy (1994) from American pregnant women screened for mHPA from umbilical blood. We consider that screening performed at the beginning of pregnancy from nonfasting venous blood is more effective compared to umbilical blood from two reasons: the Phe level in maternal blood is increased during first trimester of pregnancy due to succing effect of placenta in comparison to decreased Phe level at the end of labour. Umbilical blood for screening of mHPA is not quite suitable to detect the atypical or mild forms of Phe disturbances which prevailed in our Slavonic population of pregnant women. (Tab. 5, Fig. 7, Ref. 16.)

[Helicobacter heilmanii, a spiral bacterium, in gastric mucosa biopsies]. / Spirálová bakterie Helicobacter heilmannii v biopsiích zaludecní sliznice.

Interest in possible microbiological causes of gastritis has increased significantly since the discovery of Helicobacter pylori (Hp). Recently a spiral bacterium named Helicobacter heilmannii (Hh) was described in association with chronic gastritis in adult and pediatric patients. Comparisons between these two organisms, as well as the literature on Hh, have also been reviewed. The incidence of Hh gastritis is far lower than that of Hp gastritis. Concomitant infections by Hh and Hp are very rare. It is very probable that Hh gastritis is transmitted from domestic animals or pets to humans. The frequency of Hh gastritis (11/6059 cases, 0.18%) in authors' material was similar to that reported in Western Europe. The role of touch cytology has been becoming more and more significant recently in the diagnosis of mucosal infections of the GIT.

[Value of peroperative biopsy in the diagnosis and treatment of musculoskeletal tumors.]. / Význam peroperacní biopsie v diagnostice a lécbe nádoru pohybového ústrojí

In the period 1982-1992 the authors have performed 1276 peroperative biopsies from frozen sections in 607 patients with suspect diagnosis of a musku-loskeletal tumor. In 174 a diagnosis of a primary malignant tumor was established, in 166 of a benigne tumor, in 53 of metastasis, in 104 of a tumor-like lesion, in 33 of an inflamation. In 77 patients (12,6 %) it was not possible to establish peroperatively the diagnosis and it became necessary to wait for the definite histological examination. Gaining a peroperative histological diagnosis makes an immediate start of preoperative chemotherapy in osteosarcoma and Ewing's sarcoma possible. In chondrosarcoma a definite surgical procedure in the same operation becomes possible. Establishing a metastatic lesion leads to indication of a less radical procedure. The examinations were performed in a histological laboratory in the area of operating theatres. Some principles for performing biopsy are given. Key words: peroperative biopsy, muskuloskeletal tumors, early treatment.

[Aggressive chondroblastoma]. / Agresívní chondroblastom.

The authors report three observations of rather extensive aggressive chondroblastoma and draw attention to difficulties of histological diagnosis, which result out of a less typical histological picture, in which signs of differentiation into cartilaginous tissue may be missing. Differential diagnosis may be facilitated by proper recognition of the cytologic character of chondroblasts by the positivity of S-100 protein, and by proving characteristic properties of chondroblasts in electronmicroscopic examination. In treating this type of tumors an increased risk of local recurrence (in one of our patients) and aggressive behaviour to surrounding tissues should be considered, exceptionally pulmonary metastases may develop, as was the case in one of our presented patients.

Multilocular pigmented villonodular synovitis in a child (case report).

A case of multilocular pigmented villonodular synovitis in a child is described. It is an uncommon disorder, slowly progressive. Investigation, diagnosis and treatment are very difficult.

[Use of cement plugs in the care of giant cell bone tumors]. / Aplikace cemetové plomby pri osetrování obrovskobunecného kostního nádoru.

The classical giant cell tumor represents a problem as the clinical, radiological and histological parameters not always exclude the tendency to local recurrences, rarely also to metastases. Surgical treatment of this tumor is characterized by a relatively high percentage of local recurrences. In the years 1965-1987 patients with 72 giant cell tumors were treated within the Prague Team for Bone Tumors. In 1980 the existing results were revised in 37 patients operated on to that time and the therapeutical scheme was changed by the introduction of new methods mainly the application of bone cement. While in 17 patients we have primarily operated on in the years 1965-1980 recurrence occurred in 36 per cent, in the period 1981-1987 in 32 patients primarily operated on the recurrence amounted to 9.4 per cent, i.e. it occurred in three patients. In these three patients it was the case of excochleation and primary filling by autografts. In 13 cases of the application of bone cement for the filling of the defect after the removal of the tumor there was no recurrence. In the average interval of 1 year since the operation bone cement was substituted by author allografts. In case of an extensive resection of greater part of the joint the application proved right of the massive allografts, fixed by stable osteosynthesis, exclusively in some cases also the application of a special tumorous endoprosthesis in the area of the hip, knee and shoulder.

[Mesenchymal chondrosarcoma]. / Mezenchymální chondrosarkom.

Five mesenchymal chondrosarcomas of the bones, soft tissues and the orbit were subjected to histological and electronmicroscopic examination. In all instances the authors found in addition to the differentiated cartilaginous component extensive areas formed by round or spindle-shaped non-differentiated mesenchymal elements which on electron microscopic examination had a striking resemblance with Ewing's Sarcoma cells or resembled fibroblasts. The vascular portions present in all examined tumours reminded of the structure of a haemangiopericytoma. Osteoplasia found in soft tissue tumours had a non-tumourous character.

[Parosteal osteosarcoma]. / Parosteální osteosarkom.

Six parosteal osteosarcomas were described in patients of the age of 20-72 years. They grew on the surface of long bones forming sessile lobulated firm foci. Prevailing histological structure in most cases was that of a differentiated osteoplastic sarcoma with regular bone trabeculae and connective tissue in between. Less differentiated and more cellular regions were scanty. Tumours destroyed corticalis in two cases and spongiosa in one of them. Tumours recurred in two patients but secondaries were not spotted.