[Effect of the tumor promoter phorbol myristate acetate (PMA) on cell-mediated immunity. IV. PMA-induced modulation of mouse dendritic cell function]. In the present study we investigated the in vitro effects of the tumor promoter phorbol myristate acetate (PMA) on the accessory function of mouse spleen dendritic cells (DC) in mitogenesis. The effects of the PMA, a protein kinase C (PKC) activator, depended on dose. If pretreated with < 50 ng/ml of PMA for 3 h, DC activity was enhanced by about two-fold; whereas > or = 200 ng/ml of PMA decreased DC activity with an inhibition rate about 50% (in early response DC activity showed a moderate increase). Our results indicate that the function of DC, a potent accessory population, can be further enhanced by a low dose of PMA. This is circumstantial evidence that DC activity can be up-regulatal via PKC activation. That a high dose of PMA inhibits DC activity might be a mechanism by which PMA promotes carcinogenesis.


[Studies on human cervical carcinoma cell line. II. Establishment of HGPRT- cell line CC-80IAR2 and its biological characteristics]. An HGPRT- cell line, CC-801AR2, was established from cloned human cervical carcinoma cell line CC-801 by using MNNG to induce cell mutation and 8-azaguanine (8-AG) to select the 8-AG resistant cells. The deficiency of HG-PRT in CC-801AR2 cells was proved by enzyme activity assay. This cell line was very sensitive to HAT medium. It was very similar in biological characteristics to CC-801, especially in that it retained its tumorigenicity when transplanted into nude mice. CC-801AR2 can therefore be used in somatic cell hybridization and gene transfer experiments.


[Flow cytometric analysis of surface antigens on liquid nitrogen-stored cells]. A high non-specific fluorescence background imposes serious interference on a flow cytometer in surface antigen assay for those cells stored in liquid nitrogen. The non-specific fluorescence comes from dead and dying cells, the permeability of whose membrane has been increased so that the fluorescence reagent can enter into the cells. To solve this problem, liquid nitrogen-stored PBMNC and Raji cells were screened on different gatings for surface antigen stained with fluorescence. It was observed that the high fluorescence background as well as debris can be gated out by means of gating on FALS, angle 90 degrees angle and PRFL. As a result, the percentage of surface antigen positive cells determined was close to that assayed in fresh samples.


[The preparation and clinical use of a radioimmunoassay CA125 kit for the diagnosis of epithelial ovarian cancer]. A self-made radioimmunoassay CA125 kit (using OC125 monoclonal antibody ascites offered by Dr. Bast Laboratory which was purified, solidified and labelled with 125I) was used for serum determination in 80 patients with epithelial ovarian cancer and in 40 standard antigen samples. The results demonstrated a statistically significant correlation between our self-made CA125 kit and an imported CENTOCOR CA125 kit (P < 0.001). Clinical experience before operation in 40 patients with epithelial ovarian cancer, 34 with endometriosis and 39 with other malignant ovarian tumors suggested that the self-made CA125 kit was more sensitive in diagnosing epithelial ovarian cancer than the other two diseases. Post-operative follow-up in 86 non-recurrent cases and 101 recurrent cases showed a 96% positive predictive rate and 91% negative predictive rate. It is concluded that self-made CA125 kit is very useful in monitoring epithelial ovarian cancer.


[A case of acute lymphocytic leukemia transformed from malignant lymphoma]. We report a case of malignant lymphoma in a 15-year-old male. He had erythema and nodular lesions, hepatomegaly, and splenomegaly with high fever for one month. Laboratory examination revealed a normal blood routine test, a few lymphomatic cells in the bone marrow, and histopathologic changes characteristic of malignant lymphoma in a skin biopsy. Two months later, a second bone marrow examination showed 90% prolymphoblasts. The peripheral blood count revealed WBC 108 x 10(9)/L; among these, prolymphoblasts accounted for 92%. The patient was diagnosed as acute lymphocytic leukemia, and died 2 days later. The diagnosis and transformation from malignant lymphoma to acute lymphocytic leukemia are discussed.


[Application of 3 dimensional computer tomography to maxillofacial surgery]. Three dimensional CT examination is a recently developed technique. Nine patients suffering from traumatic and developmental abnormalities were examined with this new method and the results were satisfying. Applying this technique, we routinely obtain a set of equal spaced, nonoverlapping, high resolution CT scans of the maxillofacial deformities. It provided a condition for facilitating surgical planning and improving quantitative of postoperation evaluation.


[The nerve fiber projection of trigeminal ganglion cell to dental pulp, dentine and periodontal membrane in the rat]. The nerve fiber projection of the trigeminal ganglion cell to dental pulp, dentine and periodontal membrane was investigated with the technique of anterograde radioautographic neuroanatomical tracing (ARNT) in the rat. Results showed that the innervation in dentine and pulp was not uniform. The nerve endings were most numerous in the pulp horn, and in the tubular dentine of the cusp and cervical regions. In the periodontal membrane, both large- and small-diameter nerve fibers were found. And at least part of the innervation in the periodontal membrane was of trigeminal ganglion origin.


[Chronic obstructive parotitis: a report of 92 cases]. This article presents 92 cases (117 diseased parotid glands) of chronic obstructive parotitis with studies by clinical, sialographical, sequential quantitative scintigraphy methods and with investigation of the treatment. The nature of this disease is that various local factors cause obstruction of saliva flow resulting in recurrent swelling of parotid, in which the main feature in sialography is irregular dilatation of the main duct and branch duct. Sialographical manifestations can be divided into four types. Conservative, operative therapy and injection into diseased gland with 1% methyl violet are introduced to treat this disease. Long follow-up findings show that type I in sialography can be cured by conservative method, but other types to not respond to this method and should be treated by other methods, such as parotidectomy. We have used 1% methyl violet to treat cases who have swelling of parotid after conservative therapy. It is considered to be a simple, practical and good method and should only be used in this disease. There are no other side effects except swelling of parotid for a few weeks. Especially it can be used to treat the anterior part of main duct left over by parotidectomy, which still gives off purulent discharge.


[Study on the recovery of 4 types of cultured cell after contacting varieties of dental casting alloys]. Four types of cultured cell (Gin-1, Chang Liver, HEP-2 and L-929) were used in vitro to determine the cytotoxicity of 12 Chinese-Japanese Dental Casting Alloys from cell recovery ability. A new cytocompatibility detecting method--cell recovery test was established and recommended. This method can be able to observe the state of cell recovery through self growth cycle, diminish the side-effect of dead cell and its products on the living cells, nearly mimic the environment in vivo and study the inherited toxicology of cells. The application of computer photo-pattern analysis technique can acquire the objective and accurate data directly.


[Clinical observation of the superoxide dismutase (SOD) and lipid peroxide (LPO) changes in oral-maxillofacial surgical patients]. This article reports examination of superoxide dismutase (SOD) activity in RBC and lipid peroxide (LPO) content in the plasma of the oral-maxillofacial operation patients. The results showed that the LPO content in postoperation ascended remarkably compared with pre-operation (P < 0.001) and that the SOD activity rose also (P < 0.05). It was discovered that the difference of LPO content between the pre-operation and post-operation was closely relative with the difference of SOD activity, the operative time and the operation method (intra- or extra-oral approach). The results demonstrated that the operative damage resulted in the increasing of the reactivity of superoxide radical and LPO and that the rising of SOD activity was probably the compensation of the body.


[Binding of Actinomyces viscosus to collagen]. The ability of collagen adsorbed on apatitic surfaces to promote adhesion of A. viscosus was studied. Treatment of hydroxyapatite (HA) with human type I or type III collagen strongly promoted adhesion of A. viscosus LY7. TEM observations revealed that A. viscosus also attached to fibrils prepared from human type I collagen. The alpha(2) polypeptide derived from type I collagen exhibited moderate activity in promoting binding. Mutans of A. viscosus which possess type I fimbriae, but not type 2 fimbriae or no fimbriae, also bound to collagen-treated HA. This suggests that the adhesin responsible was associated with type I fimbriae, strains of A. israelii and A. odontolyticus also exhibited strong binding to collagen-treated HA. The avidity of Actinomyces species for collagen would seem to be partially responsible for the high proportions of these organisms found on root surfaces.


[An experimental study of dan sheng improving the mandibular bone fracture healing]. Sixty-four rabbits were used in this study, experimental bone defects were made in notch of the mandibular bone angle. Dan sheng was used in experimental groups. A pieces of bone at the edge of the defect was taken and observed by electron microscope in different period. The results were as follows: 1. The amount of osteoblast increase clearly. 2. The synthesis of protein was vigorous in fibroblast appeared as nuclear depression, nucleoli locating at one side and formation of endoplasmic reticulum bubble. as Therefore, we think that dan shen would take a role of improving the mandibular bone fracture healing.


[A preliminary study on cross anastomoses between facial and accessory nerves and reconstruction of motor unit]. In a new operating model, the buccal branch of facial nerve of rabbits, which originally controls the muscles composed of small motor units (MU), was transposed and cross-anastomosed with the accessory nerve which controls the sternocleidocephalic muscle composed of larger MU. One year later, fine filaments of facial nerve were dissected and stimulated, electrophysiological and biomechanic examinations of single MU in sternocleidocephalic muscle were carried out; the total number and percentage of 3 types of muscle fiber were counted according to polyhistochemical and histological methods as we reported formerly; the motor fibers were counted according to nerve AChE direct-coloring method and the innervation ratio was calculated. The results showed that the facial innervation ratio increased by 2.2 to 4.4-fold. That the largest value of TwT recorded in one of single MUs reached to 112.9 mN, suggested that the number of muscle fibers innervated by this facial nerve axon was much more than it did. That there was no type grouping phenomenon appeared in polyhistochemical examination implied that the facial nerve fibers regenerated along the old route offered by original MU, which tended to reneurotize all of muscle fibers of the original MU.


[Flow cytometric analysis of squamous cell carcinoma of the oral and maxillofacial region]. Fifty fresh tissue samples and fifty paraffin embedded specimens from squamous cell carcinoma of the oral and maxillofacial region were analyzed for nuclear DNA content and cell kinetics by flow cytometry (FCM). Mean DNA index (DI) was 1.154, and 59% of them showed aneuploidy patterns. Mean S phase cell population, which represents the "proliferative activity", was 22.62%. With the increase of surgical stage, aneuploid population rose from 51.7% to 82.8%, and with the increase of histology grade, it rose from 54.17% to 71.4%. S phase cell population also showed a tendency to increase with the increase of surgical stage or histology grade, and in those with cervical metastasis. The results indicate that nuclear DNA analysis by FCM is quite useful as a supplement to histology diagnosis and evaluation of malignant grade of squamous cell carcinomas of the oral and maxillofacial region.


[Skin tests in patients with history of anaphylactic reaction to penicillin]. Skin tests including immediate patch test (IPT), skin prick test (SPT), or intradermal test (IT) with penicillin G(PenG) and SPT with benzylpenicilloyl human serum albumin (BPO) were done in 54 patients with history of anaphylactic reaction to penicillin or shock of unknown cause. 26 patients with penicillin allergy were diagnosed. BPO specific IgE measured with ELISA gave a lower positive rate in detecting penicillin allergy as compared with the tests mentioned above. The results of skin tests in 26 patients showed that IPT with 500 IU/ml of PenG was not only accurate but also safe. Because no skin injury occurred and PenG residue could be washed out, the amount of PenG penetrated into skin is very small, thus, adverse reactions were very few. It is recommended that IPT with PenG in 500 IU/ml concentration is performed at the beginning of skin tests. If negative, SPT and then IT both with a solution of 500 IU/ml concentration are carried out, until a positive reaction occurs. This procedure is relatively accurate, simple and safe.


[Relationship between levamisole and encephalitis syndrome]. The results of a cohort study of 92,346 labour population for probing the relationship between levamisole (LMS) and encephalitis syndrome was reported. There were five patients suffering from the disease in an exposed group (E) of 10,911 people within two months after taking LMS as an anthelmintic for mass treatment, the incidence of the disease is 4.58/10,000. The nonexposed population was divided into two control groups the first group (N1) includes 37,990 people living in the mass treatment villages and the other group (N2) consists of 43,445 people living in the adjoining villages without mass treatment. None in the two control groups suffered from the syndrome or any other encephalitis-like disease within the same period. Statistical tests for the differences between E and either N1 or N2 separately is highly significant. (between E and N1: P = 0.000553, P < 0.001; between E and N2: P = 0.000325, P < 0.001). The overall attributable risk (AR) is 45.8/100,000 and that for female is 93.8/100,000. However, the difference between the incidence rates of the disease in female and male is not statistically significant (P > 0.025). It is shown that LMS is obviously the causative factor of the disease.


[Clinical study of 76 cases of counterattack induced by acute organic phosphorus pesticides intoxication]. 76 cases of counterattack induced by acute organic phosphorus pesticides intoxication were analysed. The activity of cholinesterase did not show a significant difference before the counterattack as compared to that after the counterattack (P > 0.05). The average dosage of atropine for pre-atropinization was 58.6 +/- 2.7 mg/h and it was 203.9 +/- 17.7 mg/h between the post-counterattack and the second atropinization (P < 0.01). Compared the mortality in reaching and non-reaching the second atropinization was 22.8% VS 100% (P < 0.01). The survival rate was 37.5% in collaborating blood transfusion cases and 20.6% in noncollaborating ones (P > 0.05). We also studied on the treatment, mechanism, precursory symptoms, causes of death, degrees of intoxication and pesticide types etc.


[Randomized clinical controlled cross-over trial (RCT) in the prevention of blood transfusion febrile reactions with small dose hydrocortisone versus anti-histamines]. RCT was used in 73 patients who had experienced blood transfusion febrile reactions. For further two transfusions Benadryl was used before the first transfusion and hydrocortisone before the second in 36 patients. In the other group of 37 patients hydrocortisone was administered before the first the and Benadryl before the second transfusion. The effective rate of preventing transfusion febrile reactions with Benadryl (72.6%) was not significantly different from that with hydrocortisone (86.3%).


[Gene diagnosis and successful reversion in a patient with preleukemia]. According to the FAB classification, a patient (case 1) could not be diagnosed as MDS-RA, although she had clinical features of MDS, as compared with another patient (case 2) who was diagnosed as RAS and had abnormal karyotype (20q- and 5q-) of bone marrow (BM) cells. BM cells of the two patients were SCD (sister chromatid differentiation) negative. Rearrangement of c-erbB and c-erbA was found in the genome of the BM cells in both patients, when southern blot hybridization was performed with probe v-erbB+A. Therefore, case 1 could be diagnosed as preleukemia. During a period about 3 years of treatment with the drug stanozolol in case 1 there was good effect and successful reversion was obtained. She had then normal hematologic and cytogenetic patterns of BM and PB and the rearrangement of c-erbB of BM cells also disappeared. She has worked for two years since then. The mechanism of effective treatment and successful reversion was discussed briefly. Probe v-erbB was shown to be useful in investigation of gene diagnosis of preleukemia or MDS (shown elsewhere).


[Relation between left ventricular mass indexes and cardiac function in hypertensive patients: an approach with Doppler echocardiography]. 73 age-matched hypertensive patients, 46 men and 27 women, were divided into the four groups according to left ventricular mass indexes (LVMI) and normal control groups were established correspondingly. Doppler and M-mode echocardiography were used to assess the systolic and diastolic functions of left ventricle (LV) and the alterations of heart construction. It was shown that when the LVMI increased slightly, the internal dimension and systolic function of LV had no significant change, but the diastolic function became abnormal and the left atrium enlarged. When the LVMI increased significantly, both the left atrium and left ventricle enlarged and the systolic and diastolic functions of LV were impaired. It is concluded that increase of LV mass may be present in the early stage of hypertension and left atrial enlargement is an early sign of left ventricular diastolic dysfunction, which occurs before systolic dysfunction in the patients with essential hypertension.


[Immunohistochemical study of hepatitis E virus antigen in liver tissues from patients with type E hepatitis]. Hepatitis E virus antigen (HEV Ag) has been identified in liver tissues of 6 out of 14 patients with type E hepatitis by direct immunoperoxidase staining, using anti-HEV-IgG-HRP. HEV Ag was found to be diffusive or inclusive in the cytoplasm of hepatocytes were scattered and isolated, but might aggregate in some parts where the liver damage was severe. We found that lymphocyte invaded the HEV Ag positive hepatocyte. These phenomena suggest that the liver damage is related to immunoreaction. HEV Ag was not found in the liver tissues of stillborn fetus and newborn baby from woman patients with hepatitis E. To detect HEV Ag in liver with direct immunoperoxidase method, using anti-HEV-IgG-HRP is more efficient than using anti-HEV-IgM-HRP.


[Immunodiagnosis of tuberculous meningitis]. The detection of special anti-mycobacterial antibodies in cerebrospinal fluid (CSF) were evaluated. Among all the common coated antigens, it was found that PPD was the most potential one. Seven detecting methods were compared. It is shown that the classic ELISA technique is worth recommending. The results of the experiments, revealed that absorbance method was better than titration method, IgG antibody was more sensitive than IgM antibody and the sensitivity rate of IgM was not related with the course of the disease. The factors which influenced the levels of IgG antibody to mycobacterial antigens include focal signs and abnormal CT findings. False positive results were found in detecting anti-mycobacterial antibodies in a few cases. Immunodiagnosis was an useful method in diagnosing tuberculous meningitis and this study has provided ample theoretical basis for popularizing this technique.


[Is the renal dopamine involved in the sodium retention in the nephrotic syndrome?]. Urinary dopamine (DA) and sodium excretion in patients with nephrotic syndrome (NS) were studied under various sodium loading in metabolic ward. Twenty patients and 10 age-matched normal volunteers were enrolled in this study. When they were on a low-salt diet (34 mmol/d), urinary excretion of DA and sodium in patients with heavy edema were much lower than that in normal controls, while in patients with mild or without edema, urine DA and sodium excretion did not decrease significantly, but were not mobilized on sodium loading (170 mmol/d), and the plasma renin activity and aldosterone were not completely suppressed as well. The decrement of urine DA excretion was independent of Ccr or the severity of renal tubule lesions, but was associated with the severity of proteinuria. When the proteinuria reduced, urine DA and sodium excretion increased. From the above observations, we might assume that the abnormal retention of sodium and water in NS was due partly to a failure to mobilize DA in the kidney and the change of the physical environment in renal tubule caused by heavy proteinuria was responsible for it.


[Resistant rate to antibiotics in Tian Tan Hospital for 3 years]. The resistance to antibiotics of the 985 clinical isolates collected in Tian Tan hospital was studied. The results showed that S. aureus had a resistant rate of more than 90% to penicillin and was also highly resistant to erythromycin. Methicillin resistant Staphylococcus Aureus (MRSA) was isolated in 15.6% of all the isolates with S. aureus. The isolation rate of MRSA is lower than that in other countries or districts of West Pacific Area. K. pneumonia and other Gram negative bacilli had a resistant rate of 0.6% to amikacin and P. aeruginosa was all sensitive to Polymyxin-B.


Transpupillary thermotherapy (TTT) by infrared irradiation of choroidal melanoma. We studied the destructive effect of hyperthermia at sub-photocoagulation level of 45-60 degrees C on melanomas. Optimal conditions for spreading of heat into tissue are a wavelength of 700-900 nm, a temperature of 45-60 degrees C, an exposure time of 1 minute or more, and a beam diameter of several millimeters. In hamsters with subcutaneous melanomas we obtained a tumour necrosis of 6 mm depth at 60 degrees C and one minute exposure time. We performed transpupillary thermotherapy (TTT) with a diode laser at 810 nm in patients with choroidal melanomas prior to enucleation. Treatment is based on the fortunate situation that irradiation at this wavelength combines optimal tissue penetration with a low absorption by clear ocular media of 5% or less. In 3 TTT-treated eyes histopathology showed a depth of necrosis of 0.9, 3.4, and 3.9 mm. TTT may become a new useful treatment modality for choroidal melanoma but its ultimate value has yet to be assessed.


Lamellar excimer laser keratoplasty: reproducible photoablation of corneal tissue. A laboratory study. We examined the depth of ablation of the recipient bed with different counts of oscillations of excimer laser beam, to determine the correlation between planned and real depth. The ablation rate per oscillation was tested preoperatively by blackened photographic paper of defined thickness and thus was calculated to be 5 microns. Forty pig eyes were used for the first study. Each eight eyes were ablated in the planned depth 100 microns, 200 microns, 300 microns, 400 microns and 500 microns. The corneal thickness was measured with an ultrasonic pachymeter before and after the procedure. The depth measured after the photoablation was 99.4 +/- 36.4 microns for 100 microns planned depth, 186.7 +/- 55.3 microns for 200 microns, 298.4 +/- 68.5 microns for 300 microns, 373.9 +/- 65.7 microns for 400 microns and 480.1 +/- 59.3 microns for 500 microns. Comparing the depth measured after the photoablation to planned depth, there was a significant correlation (correlation coefficient: R = 0.93; p < 0.0001). Five other corneas trephinated from pig cadaver eyes were ablated from the endothelial side to the desired thickness (100 to 500 microns) of lamellar graft. In a second step a donor mask was placed onto the cornea and a laser light spot was led until perforating on all sides. The lamellar keratoplasty was completed by suturing the corneal graft into the bed. Macroscopic and microscopic examination of sutured eyes after fixation showed a good fit of wound margins and stromal interface. These results indicate that excimer laser is useful for reproducible corneal photoablation in lamellar keratoplasty.


Alfentanil/promazine versus meperidine/promazine as a sedative regimens during local analgesia for cataract operation. The influence of two intravenous (IV) sedative regimens on intra-ocular pressure (IOP) was investigated in conjunction with retrobulbar local analgesia. Forty patients of either sex, and similar age with body weight within 40-90 kg were allocated equally and randomly to two groups: Group A (alfentanil/promazine) and group M (meperidine/promazine). Measurement of IOP, systolic pressure, pulse rate, respiratory rate, PaCO2, PaO2 and O2 saturation were made before operation, after premedication, after IV sedation and post-operatively. In the Alfentanil group there was significantly stronger decrease of IOP (p < 0.001). In group A the IOP dropped from 18.1 +/- 3.2 mm Hg to 10.3 +/- 2.7 mm Hg, i.e. 43%, while in group M the reduction IOP was from 17.6 +/- 3.5 mm Hg to 12.6 +/- 1.9 mm Hg, i.e. 28.4%. Meperidine caused a significant increase in PaCO2 (4.2 +/- 0.3 mm Hg), however this increase was not sufficient to cause the IOP alterations. The oxygen saturation was lower in group M (decreased by 1.5 +/- 1% in group M versus decrease by 1.0 +/- 1.2% in group A). Cardiovascular parameters were more stable in group A. In conclusion the alfentanil regimen produced a better reduction of the IOP with excellent sedation, operative condition and least anaesthetic side effects.


Visual acuity following treatment of bilateral congenital cataracts. Several studies have indicated that operation during the first months of life in children with dense congenital cataract improves the final visual acuity. In the current study seven otherwise healthy children operated on before the age of fifty-six days are compared with seven children operated on after the age of three months. The patients were followed by a team consisting of a paediatric ophthalmologist, a contact lens optician and an orthoptist. They were treated with contact lenses, spectacles with near addition and occlusion therapy when needed. Visual acuity was initially tested with preferential looking technique and later with Snellen optotypes. In the early treated group the visual development was almost normal with a final visual acuity of 20/20, while in the late treated group no patient obtained better visual acuity than 20/100. The findings indicate that dense congenital cataract should be treated before the age of three months.


High incidence of asymptomatic urogenital infection in patients with uveitis anterior. Acute anterior uveitis (AAU) may be associated with systemic infectious or inflammatory disease. We examined 92 patients with the first attack of acute anterior uveitis; all patients were free of any extraocular symptoms. A thorough clinical examination did not reveal any systemic underlying disease. In the course of microbiological examination, however, a high incidence of asymptomatic infection of the urethra and/or cervix with ureaplasma urealyticum, chlamydia trachomatis and mycoplasma hominis was found. Infections with ureaplasma were significantly more frequent in patients with AAU when compared with a sex- and age-matched control group. There was no statistically valid association of these infections with the HLA-B27 phenotype in the patients. The higher rate of urogenital infections in patients with AAU may reflect a higher rate of sexual promiscuity. Transmission of infectious agents seems to be one possible factor in the pathogenesis of AAU.


Long-term results of systemic chemotherapy for ocular cicatricial pemphigoid. Ocular cicatricial pemphigoid (OCP) is a chronic, progressive, blinding, autoimmune disease that scars mucous membranes. We studied the long-term outcome in 104 consecutive patients (average follow-up: 4 years) to determine whether complete remission could be achieved following a course of treatment with immunosuppressive drugs. We found that prolonged periods of remission off therapy are maintained in about one third of OCP patients. Follow-up must be continued for life as relapse occurs in approximately one third of cases. Those who relapsed regained disease control readily upon reinstitution of therapy and did not deteriorate to more advanced cicatrization. Sex, age, initial degree of inflammation and the incidence of extraocular involvement did not bear a prognostic significance. The mechanism which underlies the differing responses to therapy is not yet known.


Gonioscopic changes in eyes with posterior chamber intraocular lenses. The aim of this study is to determine the effects of posterior chamber implantation on angle structures. First, without previous knowledge of the position of lens haptics, 360 degrees gonioscopy was performed and any changes in the angle structures were recorded. Then, the pupil was dilated to determine the exact position of the intraocular lens haptics. The apposition of peripheral iris to angle structures or, at least, the narrowing of the angle corresponding to the lens haptic position was observed in almost all of the 117 examined eyes, with no difference found between bag and sulcus implantation. Peripheral anterior synechia overlying the lens haptic was observed in 49 (41.8%) of 117 eyes. Interestingly, we also noted that there was marked and well-limited clumping of pigment in the angle at 6 o'clock position in 67 (57.2%) of 117 eyes. In conclusion, we feel that posterior chamber intraocular lenses are not completely innocuous to the angle structures.


Binocular contrast summation and inhibition in amblyopia. The influence of the interocular difference on binocular contrast sensitivity. The monocular contrast sensitivity loss in amblyopia is well documented. We investigated the influence of interocular sensitivity difference on binocular contrast sensitivity in amblyopia. Monocular and binocular contrast sensitivity functions of six amblyopes (three strabismic and three anisometropic) were measured. The monocular contrast sensitivity loss depended on the type of amblyope. Anisometropic amblyopes generally showed high frequency losses. Strabismic amblyopes showed losses at both low and high spatial frequencies. Binocular performance was assessed in terms of binocular ratios (binocular/non-amblyopic). A binocular ratio greater than 1 indicates binocular summation (binocular > monocular) while a ratio less than 1 shows binocular inhibition (binocular < monocular). In all subjects, the binocular ratio depended on the difference between the amblyopic and the non-amblyopic eye. Minimal interocular difference produced binocular summation, the magnitude of which decreased as the difference between the two eyes increased. Further increases in the monocular difference produced binocular inhibition. Anisometropic amblyopes showed a greater degree of binocular summation at low spatial frequencies compared to strabismic amblyopes. Both types of amblyopes showed binocular inhibition at high spatial frequencies. Clinical implications of binocular summation and inhibition in amblyopia are discussed.


Myopia progression in young school children and intraocular pressure. Studies of the literature have given the impression that intraocular pressure (IOP) may influence the refractive error (RE); the reason being that the IOP in some studies is higher among myopic subjects than among emmetropes and hypermetropes. The progression of myopia was studied in 49 children, aged 9-12 years, over a period of 2 years. The rate of progression was 1.14 D/2 years and the IOP 16.6 mmHg. Comparison of the rate of progression between children with an IOP above 16 mmHg and those with an IOP of 16 mmHg or less showed a statistically significant difference: 1.32 D/2 years as compared to 0.86 D/2 years. These results are supported by ultrasound measurement of the axial length. The author recommends that measurement of IOP should be included in the design of studies of myopia progression. The reason for this is, that it would appear that those persons most at risk of developing higher degrees of myopia have a high IOP.


Retinal oscillatory potential abnormalities in patients with chronic renal failure, before and after dialytic treatment. Nineteen patients with chronic renal failure were studied, oscillatory potentials (OPs) being recorded shortly before and after dialytic treatment. Mean values of either onset latency (O1 latency) and duration of the complex (O1-N4 inter-peak latency) were found to be significantly longer in patients than in controls (p < 0.001). Most of the patients (12) showed a pathological prolongation of latency (> 2.5 SD). Amplitude changes also affected OPs, but earlier components were reduced to a lesser degree than the later ones, as shown by statistical analysis. Moreover, seven patients showed an almost complete loss of O3 and O4 peaks. Latency changes may be transiently reversed by dialysis, suggesting a functional impairment of the retinal response; the loss of later components is a more persistent abnormality probably related with a structural damage.


Twice daily 4% Sodium Cromoglycate vs. 2% Sodium Cromoglycate used four times daily in seasonal (grass pollen) allergic conjunctivitis. It is well established that 2% Sodium Cromoglycate is an effective treatment for a number of allergic eye diseases. It has been shown to be non-toxic. It can be used longterm and in serious allergic problems it is a useful adjunctive therapy to steroids. The main problem with Sodium Cromoglycate is that the recommended dosage is a four times daily application and patient non-compliance is common. One of the main objectives of any therapy is to reduce the frequency of dosage and the current study has been designed to investigate the efficacy of a 4% solution of Sodium Cromoglycate, used twice daily, versus a 2% solution used four times daily in seasonal allergic conjunctivitis. A multicentre study, therefore, was carried out to assess the efficacy of both drugs and to assess any possibility of side effects. In addition, a unit dose was used, thus eliminating preservatives and it was used specifically in seasonal allergic conjunctivitis in the pollen season. This study showed that 4% Sodium Cromoglycate used twice daily was at least as affective as 2% Sodium Cromoglycate used four times daily.


Potassium iodide and acrylamide fluorescence quenching studies on gamma-crystallins of human lenses in development and aging. gamma 1-, gamma 2- and gamma 3-crystallin (corresponding to gamma s-, gamma C- and gamma D-crystallin respectively) of human fetal, 2 year and 20+ year old lenses are separated by Sephadex gel chromatography. Iodide and acrylamide are used to quench the tryptophane fluorescence of sub-gamma-crystalline fractions and Ksv and fa values are calculated. The results show that iodide has no clear quenching effects on all gamma-crystallins, the quenching effects of acrylamide on the tryptophan fluorescences of gamma 1-, gamma 2- and gamma 3-crystallin from lenses of the same age have little differences, and the quenching rates of tryptophane fluorescences of gamma 1-crystallin decreases and that of gamma 2- and gamma 3-crystallin increase with age. These results indicate that all tryptophan residues in these three gamma-crystallins lie in hydrophobic environments of molecule and their exposure degree is in the order gamma 2 < gamma 3 < gamma 1. The tryptophan exposure of gamma 2 and gamma 3 increase (gamma 2 > gamma 3) and of gamma 1 decrease with age. The age related change of gamma 1 may be related to the changing of structure or containing of new constituents. Although the tryptophan exposure in gamma 3 is higher than that in gamma 2, the change of structure with age in gamma 2 is more prominent than in gamma 3.


Comparative studies of the carbohydrate of human gamma-crystallins from fetal and adult lenses with agglutinins. Using gel chromatography of Sephadex G-75 superfine connected with Sephadex G-50 fine column, three human gamma-crystallins (gamma 1, gamma 2, gamma 3) could be obtained. Seven agglutinins (LCA, SBA, DBA, PNA, BSL, RCA and UEA) were used to detect the sugar of sub-gamma-crystallins, which had been transferred to nitrocellulose membrane and finally stained with ABC reagents and the substrate of HPR. These results suggested that gamma 2- and gamma 3-crystallins contain sugar, but gamma 1-crystallin has no sugar. There is a decrease of carbohydrate of gamma 2 and gamma 3 as the development of the lens (esp. the former). It was postulated that in gamma-crystallins (gamma 2, gamma 3) the sugar components helped stabilizing the molecular structure (folding polypeptide, prevent protein breaking). The sugar components decreased with age by the post-translation modification.


Posterior chamber IOL implantation in traumatic cataract with injured complications. Twenty-five cases of posterior chamber IOL implantation in traumatic cataract with complications associated with primary injury were reported. The operating methods were described and the post-operative complications were discussed. Seventy-two percent of patients have the correct vision over 20/40. It is suggested that the posterior chamber IOL can be implanted in traumatic cataract with some injured complications.


Modern surgical treatment of congenital subluxated lenses. Traditional surgical management of subluxated lenses is usually associated with a high incidence of operative and postoperative complication and a poor visual outcome. We treated a series of 14 patients (26 eyes) whose visual acuity could not be improved with optical correction (phakic or aphakic) with modern microsurgery and automated suction-cutting devices. Preoperative visual acuity ranged from 0.05 to 0.3. Improvement in post-operative visual acuity was documented in all operated eyes, ranging from 0.4 to 1.0 during a follow-up period ranging from 6 to 59 months (medium 43 months). The only complication was a small accidental cut in the pupillary border in three eyes. Other complication did not occur.


Retinoma and phthisis bulbi of retinoblastoma. 1. Clinical and genetic analysis. Retinoma and phthisis bulbi of retinoblastoma are rare entities found in retinoblastoma patients and their relatives. Eleven cases of phthisis bulbi of retinoblastoma and 9 cases of retinoma were identified from 1966 to 1991 in our center. The clinic data show that retinoma and phthisis bulbi are closely related to the retinoblastoma gene. Enucleation should be carried out as soon as possible without hesitation for the phthisis of eyes with retinoblastoma. Genetic counseling and frequent observation should be paid attention to retinoma patients and their offspring. The mechanism of retinoma developed is discussed. We propose that the diversity of second mutation might be the cause of retinoma.


Quantitative evaluation of flicker ERG waveforms in low vision patients. Flicker electroretinograms (FERGs) of 30Hz were recorded for 46 eyes (23 cases) of low vision, including 38 eyes with retinal diseases and 8 eyes with optic neuropathy, and for 39 normal eyes (33 cases). The recorded wave forms were analysed by two methods: (1) to measure the peak to peak amplitude and pseudophase directly, and (2) to measure the amplitude and phase of fundamental response component (30Hz) by discrete Fourier transform (DFT). The abnormality ratios between these two methods were compared in low vision patients. All the eyes with optic neuropathy showed normal flicker ERG, the abnormality ratios of directly measured amplitude and the amplitude by DFT were 60.9% in 28 eyes and 71.7% in 33 eyes with retinal diseases respectively, the difference being no statistically significant (P > 0.05), while the abnormality ratios of directly measured pseudo-phase and the phase by DFT were 60.9% in 28 eyes and 82.6% in 38 eyes with retinal diseases respectively, the difference being statistically significant (P < 0.05). These results suggest that FERGs are an objective way to test the retinal function, and DFT for flicker ERGs are more useful in quantitative evaluation of the retinal function.


The spectral VEP in normal subjects and dichromats. The spectral VEP in 13 normal subjects (25 eyes), four cases (8 eyes) of protanopes and 8 cases (15 eyes) of deuteranopes were tested. In normal subjects, the shortest latencies of N1, P1, N2 were in 560 nm and the greatest amplitudes of N1-P1 and P1-N2 were 560-570 nm, around which the latencies were delayed and the amplitudes were decreased as the wavelengths of stimulative light increased or decreased gradually. The spectral VEP pattern of deuteranopes was similar to the normal subjects. In the protanopes, the shorter latencies of N1,P1,N2 and greater amplitudes of N1-P1, P1-N2 appeared in 520-530 nm and 570 nm, forming the two-thoughs and two-peaks shapes, with the shortest latencies and the greatest amplitudes in 520-530 nm. There were statistically significant differences of amplitudes and/or latencies in some wavelengths between the protanopes and normals and between the deuteranopes and normals.


Visual functions and trace element metabolism in tobacco-toxic optic neuropathy. Visual functions and nutrition metabolic characteristics were studied in 8 subjects (16 eyes) with tobacco-toxic optic neuropathy (TTON). Their visual functions tested by psychophysical and electrophysiologic methods showed that 1: 1. central vision diminished in 16 eyes, 2. dyschromatopsias were found in 14 tested eyes, 3. bilateral symmetrical central or cecocentral scotomas were the visual field characteristics in all cases, 4. PVEP were severe abnormal in 3 spatial frequencies in all cases and 56.3% of 15' checkboard PVEP showed flat responses, which indicated the impairment of optic nerve dominated by the central field. However, the preserved visual responses could be obtained by FVEP test in 14 tested eyes even though their visual acuity were between the range of 0.02-0.2 and flat PVEP responses. The II and III wave latencies of primary stage were more prolonged than those of control group (P < 0.01), which further indicated the preferential demyelination corresponding to the papillomacular bundles, 5. ERG showed slightly attenuated amplitudes in 5 of 8 tested eyes, which indicated the secondary and mild retinal lesion. On the other hand, TTON occurred on a background of long-term, heavy smoking, drinking, emaciation and malnutrition bodies with low serum zinc level.


Effects of qingkailing on experimental allergic uveitis in rabbits. Experimental allergic uveitis (EAU) in rabbits was induced by single intraocular injection of bovine serum albumin (BSA). The average of protein concentration in aqueous humor of untreated group of rabbits was 14.33 +/- 1.21 mg/ml and the count of tritiated thymidine (3H-TdR) incorporated into lymphocyte T was 3,987 +/- 1,156cpm/10(6). The specific antibody responses to BSA in the serum and the aqueous were 0.508 +/- 0.034 and 0.369 +/- 0.019 (OD) respectively. Meanwhile, the effect of Qingkailing on EAU was observed in comparison with dexamethasone as the positive control. The inflammatory reactions of rabbits treated with Qingkailing were remarkably diminished clinically and pathologically. The amount of protein concentration in aqueous of the treated rabbits was 5.79 +/- 2.19 mg/ml (P < 0.01) and the count of 3H-TdR incorporation was 2,455 +/- 981cpm/10(6) (P < 0.05). The responses of antibody in the serum and the aqueous were 0.414 +/- 0.059 and 0.253 +/- 0.041 (P < 0.01) respectively. Our observations indicate that Qingkailing has a positive therapeutic effect on EAU in the rabbits and sustain the suggestion that this drug is capable of suppressing immune and phlogistic reactions.


Radial keratotomy: eleven-year experiences. During the period from 1980 to 1991, Radial Keratotomy (RK) had been done by the author under topical anesthesia in more than 10,000 cases, mostly on both eyes at the same time. Those patients had myopia with a preoperative refractive error between 1.5 and 20.0 diopters (D). The surgical technique consisted of 4, 8, 16 incisions using a diamond knife with micrometer and the diameter of the central clear zone was mostly 3.0 mm and determined by preoperative refractive error. Many different procedures were tried to improve the effect of RK, including redeepening intentional microperforations at 1.5 mm, 3 mm, 5 mm distance from the corneal center. But these procedures had no significant effect 6 months after the operation. Complications such as infection, glaucoma, cataract, etc. were almost none. Results of RK on long term follow up showed hyperoptic tendency, and the visual fluctuation were none or minimal.


[Biomechanical testing of DIAKOR implants by photoelastic stress analysis]. Diakor aluminium oxide implants of different forms and sizes have been investigated and compared by photoelastic stress analysis. On forming the conditions of investigations the authors aimed at the modelization based upon the physiological direct implant-bone contact, installing implants having resin that is optically double refractive. In the sample results show a move advantageous stress relation at multi grooved implants of extended dimensions.


[Effect of betadine as a mucosa-disinfectant]. According to the previous data in the literature, the Betadine is an effective disinfectant in daily practice so its spreading is much desirable. The Betadine considerably decreases the oral flora. Its use may be advisable in case of dental and oral surgical interventions, before local anaesthesia, and in the perioperative period to support the oral hygiene.


[Genetic subjects in Hungarian dental literature]. The author classifies the Hungarian dental publications on genetical aspects into the following groups: 1. tooth and dental arch characteristics, disorders and illnesses, 2. oral cavity and surrounding area characteristics, disorders and illnesses, 3. mandible and surrounding bone characteristics, disorders and illnesses, 4. hereditary illnesses involving oral symptoms, 5. summarizing publications.


[The effect of fluoridated milk on caries reduction over 12 years]. The aim of the study was to assess the caries-preventive effect of fluoridated milk after 12-years of consumption, including 2 years interruption. DMF mean values of 162 institutionalized children aged 7-to 14 years were compared with DMF mean values of 139 institutionalized control children of the same age. The children consumed 200 ml milk daily, implemented with 0.4 mg -0.75 mg F(-)--depending on their age--between 1979-1984, after 2 years interruption they got fluoridated milk or cocoa-milk twice a week during 10 years. In the test group the ratio of caries-free children averaged more than 10%. The caries prevalence in the permanent dentition showed statistically significant reduction. The caries reduction regarding all groups was 36.78% in case of DMF-T, and 40.02% of DMF-S. According to our results the consumption of fluoridated milk in institutionalized children proved to be effective also in the long run.


[Importance of the styloid process syndrome in the differential diagnosis of facial pain]. The reported 2 cases of processus styloideus syndrome deserve attention because of their rarity. In the case of complains of uncertain origin and radiating chiefly into the tongue also the processus styloideus syndrome is to be taken into consideration. With the surgical treatment, after having the diagnosis, a well treated illness can be separated from the group of those illnesses in which the main problem is facial pain.


[Familial occurrence of Gorlin-Goltz syndrome]. A case of familial Gorlin-Goltz syndrome is described from the clinical point of view. The importance of early diagnosis, adequate treatment and care are emphasized.


[The use of a radial osteocutaneous flap in mandibular reconstruction]. The authors make known the indications and method of the free osteocutaneous forearm flap. They have established from the literature data, and by their own experience of 4 cases, that the use of free osteocutaneous forearm flap seems to be the most ideal method when the bone defect is not bigger than 6-8 cm and only the replacement of mucosa is required.


[Preparing dental radiographs without film. Radiovisiography]. In dental practice it was with the Radiovisiography system that a dental X-ray picture can be made without film and development time. The radiation load of patients decreases from 62%- to 94% compared to dental film. The regulation of the contrast and the light intensity of the electronic picture makes the further evaluation of the exposure possible.


[Toxicological implications of amalgams]. Nowadays hard attacks have been launched by the media against the use of dental silver amalgams. Different diseases are attributed to dental amalgams mostly because of their mercury contents. These claims are based mainly on suppositions without controlled scientific studies. The amount of mercury vapour from amalgam restoration achieves--not even in adverse conditions--the quarter of the daily mercury intake by food. Their total value which might be harmful to health is under the level approved by the WHO thus we don't have to deal with its effect. We can reduce the mercury evolved from amalgam restorations with gamma 2 phase free amalgam and capsule amalgam application.


[Isolated aplasia of the upper cuspids and its orthodontic management]. A multi-band appliance was used to space-closure after the deciduous canines were extracted. The upper first molars got a ring the other teeth direct brackets. The mesial movement was achieved with rubber band pull.


[Free radial forearm flap in the reconstruction of the mouth floor after removal of a tumor by pull-through method]. Free radial forearm flap was used to replace the tissue defect caused by pull-through operation for cancer of the mouth in 13 cases. There was no total or partial flap failure. The greatest advantage of the method is that the restriction of the tongue movement is less when compared to the results of other methods since the thin forearm flaps are well adaptable and are of a pliable nature. The newly developed lower alveolar crest makes the prosthetic rehabilitation possible.


[Evaluation of treating neonates with surfactants for respiratory distress syndrome. I. Importance of gas exchange]. Twenty seven preterm babies enrolled in a European Multicentre Trial (Curosurf 4) were treated with surfactant Curosurf (Chiesi Farmaceutici, Italy). Mean gestational age was 30.7 weeks (range 26-36), and mean birthweight 1617 g (960-2790 g). Curosurf was given as a rescue therapy in babies with severe RDS between 2-72 hours after birth. Indications for treatment were: clinical and radiological diagnosis of RDS, need for mechanical ventilation and arterial to alveolar oxygen tension ratio < 0.22. Umbilical arterial catheterisation and written parental consent were obtained before trial entry. The results are given for all treated babies and have not been analysed according to the dose of Curosurf. In the first hour after treatment there were mean increases in PaO2 of 27.4 mm Hg (3.6 kPa), and oxygen saturation of 8.2%, a mean decrease in PaCO2 of 15.0 mm Hg (3.3 kPa) and mean increases a/A ratio of 0.1. It was possible to reduce mechanical ventilation one hour after Curosurf instillation: inspired oxygen concentration was decreased by a mean of 12.3%, peak inspiratory pressure by 4.3 cm H2O, and frequency by a mean of 5.6 per minute. It is concluded that there are immediate beneficial effects of Curosurf in preterm babies with severe RDS.


[Evaluation of pulmonary flow through the aortic and pulmonary valves of the fetus during normal pregnancy from 20 to 41 weeks of gestation with two dimensional doppler (2dd)]. Doppler data have been analysed in 49 cases for aortic valve and 35 cases for pulmonary valve. For both valves V max, V mean, Aortic Flow and Pulmonary Flow were measured and compared with gestational age. V max A = 0.85 +/- 0.23 m/s, V max P = 0.72 +/- 0.14 m/s, (p < 0.01); V mean A = 0.28 +/- 0.08 m/s, V mean P = 0.24 +/- 0.06 m/s, (p < 0.02); A Flow = 699 +/- 285 ml/min, P Flow = 740 +/- 310 ml/min, and 275 +/- 100 ml/min/kg for aortic valve and 322 +/- 120 ml/min/kg for pulmonary valve (p > 0.05). There was statistical significant correlation between aortic and pulmonary flow and gestational age and there was no correlation between max velocity and gestational age for these valves.


[Kidney function in pregnant women with primary arterial hypertension]. Investigations covered 64 women in the III trimester of pregnancy. In this group 34 were with diagnosed primary arterial hypertension (examined group), and 30 were apparently healthy (control group). In both groups the blood serum concentrations of creatinine, urea, uric acid and electrolytes were determined. Creatinine clearance and acid-base balance were determined in these cases also. In 24 hours urine samples the NH4+, H+, Na+ and K+ ions concentrations were established. Impaired kidney function was shown in the patients from the examined group.


[Kidney function in pregnant women with hypertension in the course of chronic kidney disease]. In 53 pregnant patients in the III trimester of pregnancy kidney function investigations were carried. The group consisted of 23 patients with chronic kidney diseases with superimposed arterial hypertension (examined group) and of 30 healthy pregnant women (control group). In the examined group an increase of blood-serum urea, uric acid and creatinine concentrations were demonstrated. In these women the blood pH was decreased also. The urinary excretion of NH4+ and H+ ions was decreased, the excretion of Na+ and K+ was normal.


[Alpha-amylase in serum and urine of women with hypertension during the III trimester of pregnancy]. The urinary and blood serum activity of alpha-amylase was tested in 34 women with arterial hypertension in the III trimester of pregnancy (examined group). The results were compared with a control group of healthy women (35 urine samples and 108 blood-serum samples). In both groups other biochemical examinations were carried additionally (the serum creatinine, urea, uric acid, electrolytes and the acid-base balance levels were established). In the examined group an increased activity of the alpha-amylase in the blood serum was demonstrated.


[Activity of alpha-amylase in serum and urine of pregnant women with diabetes mellitus type I]. The investigations covered 33 women in the III trimester of pregnancy with diagnosed, insulin-dependent diabetes mellitus, and 108 healthy women in the control group. The alpha-amylase activity was measured in the blood-serum and urine samples using the Caravay technique. An increased activity was demonstrated in the blood-serum samples in the examined group. The values were not related to the levels of glycemia. The urinary alpha-amylase activity was similar to that in the control patients. No coincidence between the activity and glycemia or acetone levels could be demonstrated.


[Threats of infectious factors in the uterine neck regarding chlamydia trachomatis in imminent premature deliveries]. The research concerned threats of infections factors to a endocervix in imminent premature deliveries. It was ascertained that Chlamydia (C) trachomatis is the most frequent pathogenic factor, which occurred in 41.8% of cases. The premature delivery occurred in 16.3% of women with positive C. trachomatis test results.


[Levels of thyroid hormones and thyrotropic hormone in serum of women with perimenopausal arterial hypertension]. Test carried out in 96 women aged between 43 to 55 years (50.46 +/- 4.7), who did not take any drugs during the last 3 months. The women were divided into two groups: premenopausal and early postmenopausal. Each group was subdivided according to blood pressure: with normal pressure and with arterial hypertension. The concentration of T4, T3 and TSH were measured using a radioimmunologic method. The saturation of carrier proteins was established with the T3/test, the result of which was used to divide T4 and T3 and to obtain FT4I and FT3I respectively. It was found that women with arterial hypertension have significantly higher (p < 0.001) TSH concentration. The concentration T3 and FT3I were significantly higher (p < 0.01) in women with arterial hypertension in the postmenopausal period.


[Excretion of free catecholamines in urine and activity of some enzymes involved in catecholamine metabolism with arterial hypertension during menopause]. This study was performed in 60 women aged between 47-55 years (mean age 50.46 +/- 1.7), divided into two groups: premenopausal and postmenopausal. Each group was subdivided according to arterial pressure: with normal pressure and arterial hypertension. Daily urinary excretion of catecholamines was determined according to method of Euler and Lishajko, the activity of dopamine--beta-hydroxylase in serum according to Nagatsu et al. The activity of catechol-O-methyltransferase in erythrocytes according to Axelrod et al., the activity monoamineoxidase in serum according to Wurtman et al. Daily urinary excretion of vanilmandelic acid determined according to Pisano et al. It was found that women with menopausal arterial hypertension have significantly greater urinary excretion of adrenaline and noradrenaline (p < 0.001) in the premenopausal period, and adrenaline (p < 0.01) in the postmenopausal period. The activity of dopamine-beta-hydroxylase did not differ from the control group. The activity of COMT in erythrocytes of women and MAO in serum of women with menopausal arterial hypertension was significantly lower. Daily urinary excretion of vanillinmandelic acid in women with menopausal arterial hypertension was significantly lower.


[Changes of pituitary hormone concentration during vasomotor disorders, in blood serum of women during the early phase after surgical castration]. The behaviour of the concentration of the selected pituitary hormones during hot flushes at women after a surgical castration was evaluated. The inquiry concerned 42 women 46.7 +/- 3.4 years old, with a regular menstruation till the hysterectomy and the adnexectomy due to sexual organs diseases. The inquiry contained a determination, by means of radioimmunological methods, of the concentration of the hormones: LH, FSH, PRL, HGH, TSH in the blood serum taken at women 48 hours before the operation, on the 8th day after the intervention and 5 min after the hot flushes apparition. At the same time, the finger skin temperature and the pulse rate was taken. The rise in the finger skin temperature by 1.2 degrees C and the mean rise in the pulse rate by 11.3 beats/min during hot flushes were noticed. An important increase of the LH and HGH concentration during hot flushes was also observed.


[Myomectomy through the vagina--routine treatment or still a rarity?]. The description and initiation of a method of myomectomy through vagina at 12 women in reproductive age has been done. In succeeding steps of operation special attention on difficulties and facilities during these surgical interventions has been made. Myomectomy through vagina shortened the time of the operation diminished the loss of blood and postoperative complications. The postoperative cicatrix on the abdominal wall has not been left by this method of operation.


[Clinical picture of tumors from the mesoblastoma group in women]. Yolk Sac Tumor (YST) originating from the primitive reproductive cells reminds with its microscopic construction a gallbladder or an endodermal sinus thus the name endodermal sinus tumor, Yolk sac tumor, mesoblastoma vitellinum Teilum. There have been presented here two cases of YST of different locality with unusual development of one of them and rapid course in the both cases. In both discussed cases the survival period exceeds 3 months. Both patients are still alive and the period from the day of diagnosis and operation is in one case 26 months and in the second one 11 months.


[The management of subarachnoid hemorrhage in pregnancy]. Subarachnoid haemorrhage (SAH) from an intracranial aneurysm or arteriovenous malformation is a grave complication of pregnancy. Authors critically analyzed 12 cases of verified SAH during pregnancy from an 11 identified and 1 unidentified cerebral vascular malformation. Aneurysms were responsible for SAH in 7, and arteriovenous malformations in 4 patients. Subarachnoid haemorrhage occurred during I trimester in 2, II trimester in 3, III trimester in 6 patients and after cesarean delivery in 1 case. We conclude that the decision to operate after SAH during pregnancy should be based upon neurosurgical principles, whereas the cesarean delivery should be done in every pregnant patient with SAH.


[Pharmacokinetic examination of theophylline in pregnancy in cases of fetal anoxia]. The purpose of the investigation was to determine the effects of pregnancy on theophylline pharmacokinetics and to clarify the clinical effect of theophylline treatment in cases of threatened anoxemia of foetus. The study was carried out in 15 pregnant women between 28 and 32 weeks of pregnancy with chronic anoxemia of the foetus. The women obtained Aminophyllinum "Polfa" 250 mg (201.3 mg of theophylline) every 12 hours for 4 days to achieve the steady-state of theophylline. After the first dose the drug concentration reached the level of theophylline in range of 12.05 +/- 4.57 micrograms/ml in 15 minutes to 3.62 +/- 0.74 micrograms/ml in 12 hours. The subsequent doses increased the concentration and in steady-state the concentration fluctuates between 21.48 +/- 10.00 micrograms/ml and 6.20 +/- 1.56 micrograms/ml, what coincides with established therapeutic range of theophylline (10-20 micrograms/ml). Elimination of the drug was characterised by calculation of the elimination rate constant and drug-clearance. Both parameters are higher after a single administration what suggest the accumulation of theophylline after multiple drug administration by the saturation of enzymes taking part in metabolism of the drug. Attention should be paid higher values of half-life in pregnancy in comparison with those obtained previously in healthy volunteers. Comparative investigations of the level of theophylline in amniotic fluid in relation to maternal blood in steady-state showed a high correlation between these two values (r = 0.7867, p < 0.006). The proportion of the concentration of theophylline in relation to that in maternal blood is about 60% (0.5978 +/- 0.1599).(ABSTRACT TRUNCATED AT 250 WORDS)


[Pharmacokinetic investigations of verapamil used as a concomitant drug in treatment of premature labor]. The study carried out on 35 pregnant women, who were threatened with fenoterol and verapamil by premature delivery. The pharmacokinetics of verapamil have been examined after single dose and in steady state using drug in a dose of 2 x 80 mg/day (15 women) and 3 x 40 mg/day (8 women). Verapamil in a dose of 2 x 80 mg/day induced average steady state concentration in range of 40.6 +/- 7.8 ng/ml to 134.2 +/- 56.9 ng/ml and in a dose of 3 x 40 mg/day 28.9 +/- 5.1 ng/ml to 69.8 +/- 11.2 ng/ml. Since most authors take as optimal therapeutic level of verapamil in blood the range of 100-200 ng/ml, it seems that dosage regimen of 2 x 80 mg/day can be recommended. Additionally, verapamil concentration in maternal blood and in amniotic fluid were determined simultaneously in a group of 12 pregnant women. Verapamil readily penetrates placenta reaching in amniotic fluid about 70% of the concentration observed in maternal blood.


[Use of GnRH analog for induction of gonadotropin ovulatory surge in cycles stimulated by clomiphene citrate and menopausal gonadotropin in an in vitro fertilization program]. In 23 women treated for sterility by the in vitro fertilization method the gonadotropins ovulatory surge was stimulated by applying a GnRH analogue (Busereline). The authors showed that a single injection of GnRH analogue in the cycles stimulated with clomiphene citrate and menopausal gonadotropin causes pituitary output of both LH and FSH which is sufficient for morphological and functional maturity of the oocytes. After such treatment two patients conceived and delivered healthy babies.


[Production of progesterone in short term tissue culture by follicular cells of women]. After volume and content of the follicular cells were determined the concentration of LH, FSH and prolactin was estimated in the ovarian follicular fluid taken during laparotomy of 17 women (ages 14-43). The sixty six hour follicular fluid cells cultures were established and the concentration of the medium progesterone were assessed by means of radioimmunological methods. The ability of cells to produce progesterone was demonstrated in 3/4 of the cases. It has been found that the progesterone producing cells come from the follicles with significantly higher LH and prolactin concentration. The positive correlation was observed between FSH concentration in follicular fluid and culture progesterone production by the cells in 42 and 66 hour of the experiments.


[Surgical treatment of polycystic ovary syndrome. A. Preoperative examinations]. The aim to study was the determination the effect of operative treatment of 31 patients with polycystic ovary syndrome. Before the operation primarily the authors confirmed at the patients the presence of menstrual abnormalities in 96.8%, of infertility in 100%, of hirsutism I. in 9.7%, II. in 61.8%, III. in 29% and the average level of 17-ketosteroids 16.0 +/- 6.9, of DHEA 3.7 +/- 1.5 mg and of estrogens 39.0 +/- 15.1 mcg in 24 urine, of total testosterone 0.98 +/- 0.24, of FSH 3.4 +/- 1.5, of LH 44 +/- 2.4, of prolactin 11.4 +/- 5.4 and of estradiol 0.32 +/- 0.35 ng/ml in blood. On the basis of clinical, hormonal or/and ultrasonographic examinations the diagnosis of the polycystic ovarian disease was performed.


[Surgical treatment of polycystic ovary syndrome. B. Postoperative examinations]. After the wedge resection of the ovaries the authors obtained the normal menses in 100%, the reduction of total testosterone in blood of 41.8% and of 17-KS in urine of 20%, an increase of fertility of 62.5% and in hirsutism a correction only of 12%, the stopping of 12% and no correction of 76%. The authors conclude that the cause of the healing or of the correction is placed in the resection of 3/4 of the changed ovaries with cysts follicles with distinct thecal layer what is accompanied by the reduction of testosterone on average of 41.8%. On contrary a weak correction in hirsutism has the explanation that the existent hirsutism is supported even by the normal level of testosterone in organism.


[FAI in hirsutism of women with polycystic ovary syndrome]. The free androgen index (FAI) was estimated and compared with intensiveness of hirsutism in ten anovulatory women of reproductive age referred for polycystic ovarian syndrome with LH/FSH ratio greater than 3.0. The control group consisted of five ovulatory women. The serum testosterone, SHBG, LH and FSH were measured by radioimmunoassay. The mean plasma level of hormones in the study group was following: T-5.8 +/- 1.9 nmol/l, SHBG - 51.0 +/- 18.0 nmol/l, LH - 18.5 +/- 6.0 mIU/ml, FSH - 5.0 +/- 1.2 mIU/ml, in comparison with the control group: T - 1.4 +/- 0.4 nmol/l, SHBG - 90.0 +/- 11.2 nmol/l, LH - 9.4 +/- 4.8 mIU/ml, FSH - 7.3 +/- 0.9 mIU/ml. FAI was calculated as T/SHBG ratio multiplied by 100. In contrast to the control group the seven times higher FAI did not accompany the intensiveness of hirsutism.


[Uroflowmetry in diagnosis of urinary stress incontinence in women]. The authors' aim was to evaluate the range of uroflowmetry in diagnostics of stress urinary incontinence (sui) in women. The examinations were carried out in 59 women with sui, aged from 35 to 45 years (group I). The control group consisted of 20 asymptomatic women (group II). To evaluate volumes of urine voided during micturition in a unit of time a urological flowmeter UF-1 (produced by COTM, Białystok) was used. Numeric data of flow were analysed, as well as registered curves of flow were ascribed to one of the following flow patterns: normal, multi-peak or interrupted. The conducted studies revealed statistically significant differences in flow values in group I, compared to group II. A more frequent incidence of multi-peak and interrupted flow patterns was found in women with sui, which could be related to a neurogenic component in etiology of the disease.


[Antioxidant agents--importance in neonatology]. The toxic consequences of oxygen therapy may be development some neonatal diseases, for example: retrolental fibroplasia and bronchopulmonary dysplasia. It's now generally believed that oxygen induced cell toxicity is the result of formation of highly reactive free radicals. The greater incidence of these disorders in preterm infants suggest that some aspect of prematurity increases susceptibility of effects of toxic oxygen species. It's proposed the term for these disorders: "oxygen radical diseases of prematurity". Verification of the hypothesis about role of the antioxidant defense mechanisms of neonate may have important implications in the pursuit of the etiology these diseases and in identification of agents that may minimize toxicity associated with oxygen therapy.


[Late vesico-vaginal fistula after colporrhaphy for urinary incontinence]. We present a case of a 65 year-old woman with a late vesicovaginal fistula after colporrhaphy. Too late proper diagnosis of that complication caused perivesical tissue inflammation and led to damage to the urinary bladder, occlusion of the urethra as well as created a massive inflammatory tumor in the minor pelvis, which suggested a cancerous process. Bilateral hydronephrosis forced us to make bilateral nephrostomy. After intensive antiinflammatory therapy, anterior exenteration and Bricker's operation were performed with a finally good effect.


Factors influencing the cadmium body burden in a population study. The cadmium body burden, as estimated from 24-h urinary cadmium (Cd-U), was determined in 1523 non-occupationally exposed subjects living in five areas of Belgium. It increased with age until 55-65 years in both sexes and thereafter decreased slightly. It was higher in smokers but was inversely associated with alcohol consumption and social class. In men only, it was also positively correlated with body mass index. After the menopause, women showed a significant increase in 24-h Cd-U independently of the other factors. In addition, the cadmium body burden was independently associated with place of residence in both sexes. Highest levels of Cd-U were found in subjects living in an area with soils heavily polluted by cadmium.


Ten-year follow-up of biological monitoring of cadmium-exposed workers. In this study, 105 workers exposed to cadmium for over 10 years were subjected periodically to environmental monitoring, biological monitoring and medical surveillance. They were divided into subgroups, one in which Cd-B and Cd-U exceeded 10 micrograms/l and 10 micrograms/g creatinine respectively and the other in which they were below these proposed biological exposure indices. Urinary beta 2-microglobulin was used as an indicator of tubular damage. Over the past 3 years 12 workers had raised urinary beta 2-microglobulin values (above 250 micrograms/l). Among workers with Cd-B and Cd-U levels always below the above limits, less than 3% had increased urinary excretion of beta 2-microglobulin, a percentage comparable with that of the reference population. When Cd-B exceeds 10 micrograms/l and Cd-U 10 micrograms/g creatinine on one or more occasions (although the median value still remains below this level), the frequency of tubular damage seems to be considerably higher (8.4 and 7.5% respectively). Thus the Cd-B and Cd-U limits proposed appear to be quite safe if strictly respected. However, median values appear too high to rule out the possibility of an increased incidence of tubular alterations.


Integrated personal monitoring of cadmium exposure in Sweden. Methods for the personal monitoring of human exposure to cadmium from air, food and beverages were studied in a group of 15 non-smoking women in Stockholm. Particles in the breathing zone air and duplicates of all food and beverages ingested were collected during seven consecutive days, as were faeces corresponding to the food ingested. Spot samples of blood and urine were also taken. The main sampling problems were caused by the noise of the personal air monitors and the short operation time of the batteries. On average, dietary cadmium (8.5 micrograms per day) contributed 99% of the total cadmium absorbed. There were large day-to-day variations in intake, most peaks corresponding to the consumption of seafood. Faecal cadmium was shown to reflect the total amount of cadmium ingested. There was a significant (p < 0.05) correlation between cadmium concentrations in blood (median 0.3 microgram/l) and average daily dietary intake of cadmium, but the blood cadmium levels could vary by a factor of four at one and the same average daily intake. The median urinary cadmium level was 0.2 microgram/l.


Cadmium as an environmental hazard.

Cadmium as an environmental hazard. Cadmium occurs in nature at low concentrations, but human activities have caused cadmium contamination in all continents with the exception of Antarctica. In some areas, environmentally exposed humans have suffered kidney damage which has sometimes progressed to severe kidney failure and skeletal disease. In mammals and birds, cadmium accumulates in livers and kidneys at concentrations of 0.1-2 mg/kg and 1-10 mg/kg wet weight, respectively. Animals with a long life span such as horses have very high concentrations of cadmium in their organs: in renal cortex samples obtained from old horses, concentrations of nearly 200 mg/kg have been found. Histopathological examination of kidneys from environmentally exposed horses and certain species of sea birds have revealed morphological changes indicative of chronic interstitial nephritis. Remarkably high concentrations of cadmium (5-160 mg/kg) have recently been found in kidneys obtained from penguins living in Antarctica. The cadmium accumulation observed in animals living in Antarctica is unlikely to be the result of anthropogenic pollution. It shows how little we know and understand about the natural flow and behaviour of this elusive element in the ecosystems of the planet.


Sources of cadmium, its distribution and turnover in the freshwater environment. Cadmium enters the aquatic environment from numerous sources, e.g., via the atmosphere, from which the cadmium released by combustion, mainly of fossil fuels, is deposited. Since some fertilizers contain up to 40 mg/kg cadmium, wash-out from agricultural land is another source. Zinc ores contain up to several percent of cadmium, and there may be high concentrations in raw zinc, zinc alloys and zinc compounds, so that cadmium may enter the aquatic environment from mining residues, solid wastes and wastewater discharges. Once in the aquatic environment, cadmium is highly mobile. Its dissolved species are extremely labile, and are the first to be released, e.g., when salinity increases in estuaries. Sediments reflect the metal loading in the past, and their analysis can be the key to an understanding of the fate of anthropogenic discharges into the hydrosphere. The internal cadmium loading of aquatic systems can be estimated from the remobilization rates of cadmium from sediments.


Sources and pathways of cadmium in the environment. Cadmium occurs naturally in rocks and soils, usually in concentrations of less than 1 microgram/g, but soils derived from some marine black shales and from rocks containing lead-zinc minerals frequently contain much larger amounts. These may lead to increased cadmium uptake by crops and vegetables grown for human consumption. Anthropogenic sources, including smelter emissions and the application of fertilizers and sewage sludge to land, may lead to contamination of both soils and crops. Regional cadmium enrichment or contamination of the surface environment can be delineated by geochemical surveys and by the compilation of soil inventories. The factors influencing the uptake of cadmium into food crops and the role of the atmosphere and soil as sources of cadmium in the diet and water supplies are discussed. No adverse health effects related to cadmium were found in an area where the cadmium intake of the local population was double the estimated United Kingdom average.


Cadmium and health: the Belgian experience. Studies in the 1970s on chronic cadmium poisoning in man in Belgium showed that the earliest effect was renal dysfunction with proteinuria. Subsequent studies were focused on the characterization of cadmium proteinuria, the diagnosis and prognosis of cadmium nephropathy and the assessment of the concentrations in urine and renal cortex leading to its occurrence. Chronic exposure to cadmium in industry gives rise to a proteinuria which may be tubular, glomerular or mixed in character. This proteinuria may be accompanied or preceded by a variety of other renal effects. In active male workers, three main groups of thresholds for urinary cadmium have been identified for the induction of these effects with corresponding thresholds in the renal cortex. However, these estimates probably cannot be extrapolated to the general population exposed to cadmium mainly by the oral route. The results of a large-scale cross-sectional study (Cadmibel) suggest that subclinical changes in tubular function may occur in the general population above a threshold of urinary cadmium as low as 2 micrograms/24h.


Estimation of dietary intake of cadmium: reliability of methods. The reliability of intake studies depends on representative sampling of foods, quality assurance of analytical methods, selection of adequate food consumption data and combining concentrations of heavy metals in foods with food consumption figures. The food balance sheet is usually unsuitable for intake estimations of cadmium, since it covers mainly unprocessed food and does not include individual food consumption data. The reliability of household surveys could be improved by taking food wastage into account, more detailed description of meals eaten outside the home, and calculating per capita consumption figures. The duplicate portions method seems to be the most reliable of the available techniques, but does not provide realistic information on variations in long-term intake, for which dietary surveys, food recall studies or food frequency questionnaires should be used. The duplicate portions technique is suitable for studies of risk groups. The average intake of cadmium in Finland is about 10 micrograms per day, but 5-10% of the population ingests more than 20 micrograms of cadmium per day. Additional exposure from smoking, ambient air and drinking-water considerably increases the variation in exposure.


Factors affecting the intestinal uptake of cadmium from the diet. Human data on the effects of diet composition on intestinal cadmium uptake are almost completely lacking but animal experiments indicate that it may profoundly influence the intestinal uptake of ionic cadmium. Thus, rats and mice fed human dietary items absorbed 5-8 times more cadmium than animals fed ordinary rodent pellets. All the data currently available indicates that, both in humans and in experimental animals, the bioavailability of dietary cadmium is not very different from that of ionic cadmium. However, diet composition may markedly affect the uptake of the latter. Accordingly, a valid assessment of the bioavailability of cadmium can be made in experiments where ionic cadmium is administered mixed with the diet. It is important, however, to discriminate between diet composition at the time of administration and dietary status. A better understanding of the factors affecting intestinal cadmium uptake is necessary in assessing the risk associated with dietary cadmium exposure and further studies are therefore urgently needed.


Pulmonary deposition, clearance and effects of inhaled soluble and insoluble cadmium compounds. The factors affecting the deposition of inhaled cadmium particles in different regions of the respiratory tract are discussed. The retention kinetics of inhaled cadmium compounds is determined by the various clearance processes. It is necessary to differentiate clearly between in vitro (water) solubility and in vivo (lung) solubility. Thus both cadmium oxide and cadmium sulfide particles are rather insoluble in water but the former are readily solubilized in the lung while the latter are cleared mainly by mechanical transport via alveolar macrophages. The pulmonary retention half-times of inhaled cadmium compounds are longer by approximately a factor of ten in primates than in rats. Acute pulmonary inflammatory effects of inhaled cadmium compounds are related to their in vivo solubility, and an approximately 10-fold higher dose of cadmium sulfide as compared with the chloride or oxide must be administered to the lung to elicit the same inflammatory response. Differences in biological effects may also exist with respect to the chronic effects of inhaled cadmium compounds, e.g., the pulmonary carcinogenic potency of inhaled cadmium sulfide may be less than that of other cadmium compounds.


Occupational exposure to cadmium and lung function. A total of 69 male subjects occupationally exposed to cadmium fumes in a factory producing silver-cadmium-copper alloys for brazing, were subjected to lung function tests, including ventilation (FVC and FEV1), residual volume (RV) and alveolar-capillary diffusion capacity (TLCO and KCO). For each subject, the cumulative exposure to cadmium was calculated as the product of the number of years in the job and the average atmospheric concentration of cadmium (expressed in micrograms/m3) encountered each year. Cadmium-exposed subjects had moderately higher mean values of RV (+ 8%) as compared with the control group; the increase was greater (+ 10%) in the subgroup of workers with greater cumulative exposure to cadmium. No significant differences were observed in FVC, FEV1, TLCO and KCO.


Metallothionein: analysis in tissues and toxicological significance. The chemical forms of cadmium in tissues can be largely divided into two groups, namely metallothionein (MT)-bound and non-MT-bound. Cadmium accumulates in the body mainly as the former, while the latter, the toxic form of cadmium, can be detected typically in tissues in two cases: (i) before induction of sufficient amounts of MT to sequester cadmium; and (ii) after the accumulation of cadmium in amounts such that it is beyond the capacity of the organ concerned to synthesize enough MT. We identified alcohol dehydrogenase as the major cadmium-binding protein in the liver before induction of MT, though the enzyme activity was not affected by such binding in vivo. The capacity to synthesize MT can be determined from the relative ratio of cadmium to co-existing metals (zinc and copper) in MT, and also by the increase in cadmium in the non-MT-bound form that follows the increase in this ratio. Non-MT-bound cadmium can be detected selectively by a histochemical method using a chelating agent, thiazolylazonaphthol.


Differences in chromatographic behaviour of rat and pig metallothionein isoforms: a possible method of distinguishing between exogenous and endogenous metallothioneins. Part of the exogenous metallothionein present, e.g., in food of animal origin, can survive gastrointestinal digestion, and will be selectively taken up in the kidneys. The present paper describes a possible method of distinguishing exogenous cadmium metallothionein (CdMT) from its endogenous counterpart. Rat and pig metallothionein were purified from liver and kidneys of animals previously injected with cadmium chloride. In rats cadmium was present in two MT isoforms, RMT-1 and RMT-2. Ion-exchange chromatography of porcine liver cytosol also showed that two isoforms existed, but a major portion of the cadmium elutes with the second isoform, VMT-2. Using a reversed-phase HPLC system, the purified rat metallothionein isoforms eluted as single peaks before pig MT isoform VMT-2. The difference in chromatographic behaviour on reversed-phase HPLC between species-specific metallothioneins offers a unique possibility to study the fate of endogenous and exogenous metallothioneins simultaneously. This will be illustrated by the redistribution of 109Cd from exogenous CdMT to endogenous CdMT after intravenous injection of VMT-2 into rats.


Endogenous intestinal metallothionein possibly contributes to the renal accumulation of cadmium. At low levels of dietary cadmium chloride, cadmium accumulates directly in the kidneys and not in the liver. As dietary cadmium induces intestinal metallothionein (MT), intestinal CdMT complexes could be at least partly responsible for the renal accumulation of oral cadmium. For this to be possible, however, serosal release of mucosal CdMT would be required. To test this hypothesis, we perfused isolated rat small intestinal segments (Fisher-Parsons method) in an attempt to demonstrate the release of intestinal MT. After two weeks of feeding dietary cadmium chloride, intestinal MT was induced in amounts proportional to the dietary cadmium level. Subsequent in vitro perfusion of the small intestine revealed a concentration-dependent release of intestinal MT on the serosal side. When 109CdCl2 was present in the perfusion medium, 109Cd appeared on the serosal side mainly in the MT fraction. These results indicate that endogenous intestinal MT may deliver CdMT to the organism, thus possibly contributing to the renal accumulation of orally ingested cadmium.


Metallothionein and tissue damage.

Metallothionein and tissue damage. Metallothioneins (MTs) are a class of small cysteine-rich heavy metal binding proteins produced in response to a variety of stresses, inflammation, and as components of the acute-phase response. Although the exact role of MT in this phase is not known, a number of reports have shown that expression of hepatic MT is markedly increased in response to bacterial infection, an effect mediated by lipopolysaccharides. More recently, it has been suggested that MT may play a major role in the prevention of tissue damage. Thus MT has been shown to be an efficient free radical scavenger. Indirect activation of macrophages and neutrophils during the acute phase of inflammation result in a massive release of various species of oxygen metabolites which may be indirectly responsible for the initiation of apoptosis. In addition, expression of MT also increases cell resistance to radiation damage. Together, these results suggest that MT could be part of a generalized protective system in mammalian cells.


Role of metallothionein in human placenta and rats exposed to cadmium. A strong positive relationship between zinc and copper and metallothionein (MT) in placentas has been found, but a negative one between cadmium and MT. In rats given cadmium i.p. as the chloride, liver cadmium is lower and kidney cadmium higher than in cadmium-treated non-pregnant rats, suggesting that pregnancy enhances mobilization of cadmium from liver to kidney. The cadmium concentration of digested whole fetuses is not significantly increased in offspring of dams given cadmium i.p. as the chloride or CdMT, but the placental levels of cadmium and MT are increased. The placenta therefore acts as a barrier to maternal-fetal cadmium transfer. The way in which cadmium is retained in the placenta but zinc and copper are transferred to the fetus is not understood, since all are bound to MT. Focal renal tubular necrosis and placental necrosis occur at the same level of cadmium exposure, suggesting a similar threshold to cadmium toxicity for the two organs.


Teratogenicity of cadmium chloride in the South African frog, Xenopus laevis. The teratogenicity of cadmium chloride was tested by the FETAX (Frog Embryo Teratogenesis Assay: Xenopus) procedure. In five assays, groups of Xenopus embryos were grown in media containing concentrations of 0.75-56 mumol/l; controls were incubated in medium without cadmium chloride. Exposures began 5 h post-fertilization and ended 101 h post-fertilization. In control groups, > 95% of embryos survived at 101 h and the incidence of malformations was < 7%. In Cd(2+)-exposed groups, concentration-dependent mortality and numerous malformations were observed, including gut malrotation, ocular anomalies, bent notochord, misshapen fin, facial dysplasia, cardiac deformities and dermal blisters. Other abnormalities included stunted growth and hypopigmentation. The minimum concentration of cadmium chloride that inhibited growth was 18 mumol/l. The median embryolethal concentration (LC50) was 32 (SE +/- 4) mumol/l; the median teratogenic concentration (EC50) was 3.7 (SE +/- 1) mumol/l; the teratogenic index (TI = LC50/EC50) was 8.6. This study demonstrates that cadmium chloride is teratogenic for Xenopus laevis and provides a standardized experimental model for studying the molecular mechanisms of cadmium teratogenesis.


Birth weight of children and cadmium accumulation in placentas of female nickel-cadmium (long-life) battery workers. In a retrospective epidemiological study on the birth weight of 266 children of 137 female workers in a nickel-cadmium battery factory, 157 children of workers occupationally exposed to cadmium were compared with 109 born to non-occupationally exposed workers. No effect of cadmium exposure on birth weight was detected, but a statistically significant effect on birth weight of smoking during pregnancy was observed. In a prospective study on the same population of female battery workers, 27 placentas were collected and the cadmium distribution and concentration in tissue subsamples determined. Placental cadmium concentrations were positively correlated with maternal blood cadmium. The cadmium concentration in placentas ranged from < 0.002 to 0.095 microgram/g (wet weight), the mean concentration +/- SD was 0.021 +/- 0.022 microgram/g (wet weight). Morphological and ultrastructural studies of placental tissues did not reveal any effect of cadmium. This study did not provide any evidence in support of the hypothesis that the placenta may be the critical organ in exposure to cadmium.


Effects of cadmium exposure on the cardiovascular system and on calcium metabolism: results of a cross-sectional population study. This paper summarizes the findings of the Cadmibel Study, a cross-sectional population study of the health effects of cadmium, but only with respect to the cardiovascular system and calcium metabolism. The study disproved the hypothesis that exposure to cadmium would lead to an increase in blood pressure and in the prevalence of hypertension and other cardiovascular diseases. On the other hand, there was a positive relationship between urinary cadmium (Cd-U) and both serum alkaline phosphatase activity and urinary excretion of calcium. The regression coefficients obtained after adjustment for significant co-variates indicated that, when Cd-U increased two-fold, serum alkaline phosphatase and urinary calcium rose by 4% and 0.25 mmol/24 h, respectively. These findings suggest that calcium metabolism is gradually affected as cadmium accumulates in the body. The morbidity associated with the latter phenomenon is still unknown, and requires further investigation, preferably in a longitudinal prospective population study, in which the incidence of morbid events would be monitored in relation to the cadmium body burden.


The role of Ca2+ in cadmium-induced renal tubular cell injury. Changes in rat renal proximal tubule cell gene expression were studied in vitro using a cadmium metallothionein (CdMT) exposure model. Increased expression of MT together with alterations in the expression of several other stress protein products were demonstrated by 35S-two-dimensional gel electrophoresis. Stress proteins with estimated molecular masses of 32, 70 and 90 kDa were observed to be increased after 4 h of exposure. These changes preceded the onset of cell injury. Internal stores of Ca2+ were not found to be measurably altered, as measured by the changes in fluorescence of the dye FURA-2. These data suggest that the observed alterations in gene expression are directly mediated by Cd2+ and not secondary to increased availability of Ca2+ within the target cell population, perhaps mediated by the transacting factor which regulates MT synthesis. The calcuria resulting from in vivo exposure to Cd2+ in workers or CdMT exposure in animal models may be secondary to alterations in renal proximal tubule cell gene expression.


Cadmium-induced bone loss: increased susceptibility in female beagles after ovariectomy. Bone resorption, as measured by release of bone 45Ca, was significantly increased in elderly female beagles within 96 h of exposure to 15 mg/l cadmium in drinking-water. The 45Ca response was greater in ovariectomized animals than in sham-operated controls and was not mediated by changes in calciotropic hormone concentrations. Mean blood cadmium concentrations were 3-8 micrograms/l during the earliest bone resorption response and 13-15 micrograms/l at the end of the study. During seven months of cadmium exposure, bone mineral densities decreased most in the ovariectomized animals exposed to cadmium: -15.4 +/- 4.3% for the tibia distal end and -7.2 +/- 1.2% for the lumbar vertebrae (L2-L4) (mean +/- SE, n = 4). The results indicate that cadmium may act directly on bone and that postmenopausal women exposed to cadmium in industry or via cigarette smoke may be at increased risk of cadmium-induced bone loss. They also support a direct role of cadmium in the etiopathology of itai-itai disease among postmenopausal women in Japan.


Placental transfer of cadmium.

Placental transfer of cadmium. Cadmium levels in blood have been determined in mother-newborn pairs from the surroundings of a copper smelter and a control area in Northern Sweden. The smelter's cadmium emissions to the air have decreased substantially since the 1970s, and in 1989 the emission was one ton. Venous blood was sampled from the mothers during delivery and from the umbilical cords, and analysed for cadmium by flameless atomic absorption spectrophotometry. There were no significant differences in cadmium levels, as between exposed women and controls, and blood levels were low, even in an industrial area. The most important environmental exposure seemed to be smoking. There was, however, a significant increase in cadmium levels during pregnancy among non-smoking women in both groups, p < 0.01. The cadmium levels in the newborn babies were about 70% of those in the mothers. Cadmium levels in the babies of non-smoking mothers were significantly higher in the vicinity of the smelter than in the control area (p < 0.05).


Cadmium, metallothionein and renal tubular toxicity. Cadmium-induced nephrotoxicity develops at cadmium concentrations in the renal cortex of 10-300 micrograms/g wet weight. The actual concentration at which it develops depends on a number of factors, e.g., exposure route, chemical species of cadmium administered, rate of administration and simultaneous exposure to other metals. The role of these factors can be explained by a mechanism of cadmium nephrotoxicity in which both extracellular and intracellular metallothionein binding play an essential role. In reindeer used for human food, cadmium was shown to be bound to metallothionein-like proteins. If cadmium bound to such proteins enters the blood plasma via the gastrointestinal tract, this is of special toxicological significance. Metallothionein-bound cadmium in the plasma of experimental animals is efficiently transported to the kidney. Tubular dysfunction in the kidney following a normally tubulotoxic dose of cadmium bound to metallothionein was prevented by preinduction of metallothionein synthesis by small non-toxic doses of cadmium.


Application of the 'critical effect' and 'critical concentration' concept to human risk assessment for cadmium. Exposure to cadmium can give rise to a number of adverse health effects. In human risk assessment it is important to identify effects that occur at relatively low exposures, i.e., the critical effects, which are crucial for preventive action. The effect of cadmium on the kidney, namely, tubular dysfunction, has been regarded as the critical effect in long-term human exposures. Quantitative dose-response data can be derived from a risk model based on metabolic parameters and observed relationships between cadmium concentrations in the renal cortex and the occurrence of proteinuria in industrial workers. There is reasonable agreement between this model and epidemiological observations. Low-dose-low-incidence extrapolations have been made based on this model. However, experimental and epidemiological studies are providing increasing evidence that cadmium is carcinogenic and this serious effect, considered to be stochastic in character, may reasonably be considered as a critical effect. A quantitative evaluation is difficult with the available data. The preventive action usually taken for substances which are considered to be carcinogenic is to limit the use of and exposure to cadmium as much as possible, thus achieving exposure levels for cadmium lower than those giving rise to kidney damage.