[A 52-week oral chronic toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) in rats with a recovery period of 5 weeks. The chronic toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 0.4, 2, 10, 50 and 250 mg/kg/day for 52 weeks. The drug was then withdrawn for 5 weeks. The results are summarized as follows: There were no deaths or toxic signs caused by the drug throughout the experimental period. There were no drug-related changes in food consumption, ophthalmological examination, hematology or blood chemistry. Slight suppression of growth was observed in males in the 250 mg/kg group. This change was reversed on withdrawal of the drug. Drug crystals were observed in the urinary sediments of both sexes in the 250 mg/kg group, but this change disappeared on withdrawal of the drug. Gross pathological examination revealed the following changes: enlargement and nodule formation in the pancreas in both sexes given more than 10 mg/kg of the drug; dark red spots in the glandular stomach in males in the 250 mg/kg group; thickening of the small intestinal walls in both sexes given more than 50 mg/kg. Of these organs, no changes were observed in the stomach and small intestine at the end of the recovery period. Increased pancreas weight was observed in both sexes given more than 50 mg/kg of the drug. Examination at the end of the recovery period suggested reversibility, showing a lesser degree of change. Histopathological examination revealed the following changes in the pancreatic acinar cells: acidophilic foci and nodules in both sexes given more than 10 mg/kg of the drug; adenoma in one male in the 250 mg/kg group; increased zymogen granules in both sexes given more than 50 mg/kg of drug; fine vacuolization in females in the 250 mg/kg group. At the end of the recovery period, increased zymogen granules and fine vacuolization of the acinar cells were not found. Furthermore, erosion or healed erosion in the glandular stomach, duodenum and jejunum was observed in a few males or females in the 250 mg/kg group, but those changes disappeared after the recovery period. In the liver, altered cell foci was observed more frequently in males in the 250 mg/kg group than the other groups, but this change also disappeared after the recovery period. In addition, brown pigmentation in the proximal renal tubules of the kidney was observed in both sexes in the 250 mg/kg group, but lesions observed in the examination after the recovery period were less noticeable than in the examination at the end of the administration period.


[A 52-week chronic oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) in dogs]. A chronic oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187), a new protease-inhibiting agent, was carried out using male and female beagle dogs. FUT-187 was orally administered to the dogs at dose levels of 7.5, 15, 30 and 60 mg/kg/day for 52 weeks, followed by 5 weeks' recovery period. Results are summarized as follows: 1. In general conditions, vomiting, salivation and the passage of mucousy stools were observed in dogs given 15 mg/kg/day or more, and diarrhea was observed at 30 mg/kg/day or more. One male given 15 mg/kg/day showed transient pallidity of the oral mucosa, and another male in the same group showed apnea and abdominal breathing. In addition, one male given 30 mg/kg/day was euthanatized due to extreme weakness, as weight loss and pallid oral mucosa, and another male in the same group died after showing acute toxic symptoms such as hyperpnea, tonic convulsion and ataxic gait. 2. Weight gain was slightly suppressed in females given 60 mg/kg/day. No significant changes in food consumption were observed. 3. Hematological examination revealed no statistically significant changes. Decreases in RBC counts, Ht values and Hb concentrations, and increased reticulocyte counts were observed in one male of 15 mg/kg/day group, which also showed pallid oral mucosa, and in one male of the 30 mg/kg/day group, which was euthanatized in a moribund state. 4. Blood biochemistry revealed increased GPT activity in males given 15 and 30 mg/kg/day and females given 60 mg/kg/day, which was accompanied by sporadic increases in GOT, A1P and/or gamma-GTP activities. Males given 30 mg/kg/day or more showed decreased total protein. 5. Hepatic function testing (ICG test) showed no statistically significant changes. One female given 60 mg/kg/day showed increased accumulating concentration of ICG. 6. There were no toxicological changes in urinalysis, fecal occult blood, renal function (PSP clearance), ophthalmological and electro-cardiographic examinations. 7. In pathological examination, inflammatory cell infiltration and microgranuloma formation in liver were noted periportally or perivenularly in both sexes given 15 mg/kg/day or more (except for 30 mg/kg/day males). In the some cases, atrophy, degeneration and necrosis of hepatocytes and/or fibrosis around inflammatory cells and microgranuloma were observed. In the spleen, one male given 15 mg/kg/day and one female given 60 mg/kg/day showed increased plasma cells in the red pulp. In the case sacrificed in a moribund condition, findings in the liver and spleen similar to those in surviving cases were detected, but were more severe, and the liver showed diffuse fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)


[A 13-week subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in rats]. The toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 2, 10, 50, 250 and 1250 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks for recovery. The results are summarized as follows: In the 1250 mg/kg/day group, 9 out of 20 males died with decreased body weight and exhaustion. Histopathological examination revealed renal papillary necrosis, ulcer in the urinary bladder, hemostatic lesions in the lungs and liver, ulcer or erosion in the stomach, duodenum and jejunum. The surviving animals in this group showed swelling of the limbs due to synovitis, transient salivation immediately after administration, suppression of growth with decreased food consumption. Urinalysis revealed a low pH, increased ketones and bilirubin excretion, dark yellowish change in color, the appearance of "leaflet-shaped" crystals and increased red blood cells and epithelial cells in the urinary sediment, increased water intake, decreased specific gravity and decreased sodium, potassium and chloride in the urine. Hematologically, there was an increase in the white blood cell count. A biochemical analysis of the blood revealed decreased amylase activity, glucose and total protein levels and increased GOT activity and inorganic phosphorus levels. Pathological changes were observed in the pancreas, kidney, digestive tract, urinary bladder and liver. The pancreas showed macroscopical enlargement and increased organ weight. Histopathologically, there were several alterations in the acinar cells, such as vacuolization due to increased fat droplets, nuclear irregularity, prominent nucleoli, irregular arrangement and vesiculation of rough endoplasmic reticulum (rER), dilatation of developed Golgi apparatus and increased free ribosomes. In the kidney, increased weight and pigmentation in the proximal tubular epithelium were noted. Electron microscopically, these pigments were recognized as secondary lysosomes containing filamentous material and electron dense granules within a lucent matrix. In the digestive tract, ulcer or erosion in the stomach and duodenum, and villous proliferation in the small intestine were observed. Furthermore, hyperplasia and vacuolization were noted in the mucosal epithelium of the urinary bladder. In addition, loss of perilobular fat droplets in the liver and increased adrenal weight without histological change were observed. After a 5-week recovery period, these changes disappeared almost completely. In the 250 mg/kg/day group, slight suppression of growth the appearance of "leaflet-shaped" crystals in the urinary , sediment, increased water intake and decreased sodium in the urine were observed. The pancreas showed enlargement, increased weight, acinar cell hypertrophy with increased zymogen granules, fine vacuolization, slight derangement and vesicular of rER, and dilatation of Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS)


[Reproductive and developmental toxicity studies of FUT-187. (I)--Fertility study in rats with oral administration of FUT-187]. FUT-187 was given orally at 20, 120 and 720 mg/kg during the pre-pairing period (63 days prior to pairing in males and 14 days prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (days 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. One male of the 720 mg/kg group died due to treatment. Temporary salivation was observed in males and females in the 20 mg/kg or more groups. In males, increases in the weight of the pancreas in the 120 mg/kg or more groups and the adrenals in the 720 mg/kg group, a depression of body weight gain and decreases in food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In females, an increase in the weight of the pancreas in the 120 mg/kg or more groups, a slight depression of body weight gain during the early stage of pregnancy and a decrease in the food intake, and a decrease in the weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. No dose-related changes were found in the estrus, copulation, insemination and fertility indices. In fetuses, decreased numbers of corpora lutea, implantation and live fetuses were observed in the 720 mg/kg group. There were no treatment-related abnormalities in fetal mortality, sex ratio, weights of fetuses and placenta, and external and visceral examinations. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for the parents, 720 mg/kg for reproductive performance and 120 mg/kg for fetal development.


[Reproductive and developmental toxicity studies of FUT-187. (III)--Postnatal study in rat F1 offspring from dams treated orally with FUT-187 during the period of fetal organogenesis]. A postnatal study of F1 offspring exposed to FUT-187 during fetal organogenesis was carried out using Crj : CD rat. FUT-187 was dosed by gavage at 0, 50, 200 and 800 mg/kg/day from day 7 to 17 of gestation. All pregnant rats were allowed to deliver newborns, and F1 offspring were examined for development indices and reproduction and learning ability. Effects at 800 mg/kg included temporary salivation, body weight depression and decreased food intake. There were no adverse effects on delivery and lactation and no significant changes on neonatal development, growth, reproduction and learning ability in the F1 offspring. These results indicate that the no effect dose level of FUT-187 is 200 mg/kg/day in dams, and 800 mg/kg/day in offspring.


[Reproductive and developmental toxicity studies of FUT-187. (V)--Perinatal and postnatal study in rats with oral administration of FUT-187]. FUT-187 was given orally at 20, 120 and 720 mg/kg to female rats during the perinatal and postnatal periods and the effect on dams and offspring were evaluated. One dam during the terminal period of gestation and 3 dams after delivery in the 720 mg/kg group died due to FUT-187. In dams, an increased pancreas weight in the 20 mg/kg or more groups, temporary salivation after dosing in the 120 mg/kg or more groups, and a depression of body weight gain and decreased food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In offspring, postnatal death rate in the 720 mg/kg group tended to increased. Decreased body weight gain and delayed appearance of abdominal hair and descent of testis in the 720 mg/kg group were statistically significant in comparison with controls. There were no treatment-related abnormalities in visceral examination, organ weight, skeletal examination, sensory function, behavioral function, learning ability or reproductive function. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for dams, and 120 mg/kg for reproductive performance of dams and offspring development.


[Antigenicity study of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) in guinea pigs and mice. Antigenicity study of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187), a new protease inhibitor, was investigated in guinea pigs and mice and the following results were obtained. 1. In guinea pigs immunized with FUT-187 plus adjuvant by intramuscular/subcutaneous routes, ASA, ACA and PCA reactions challenged intravenously or intradermally were positive. 2. In guinea pigs immunized with FUT-187 plus adjuvant by intramuscular/subcutaneous routes, ASA and PCA reactions challenged orally were negative. 3. In guinea pigs immunized with FUT-187 by the oral route, ASA, ACA and PCA reactions were negative. 4. In guinea pigs immunized with IABA and AN plus adjuvant by intramuscular/subcutaneous routes, ASA and PCA reactions were negative. 5. 48-hr PCA reactions were elicited with sera obtained from BALB/c and C3H/He mice immunized with FUT-187 plus adjuvant by the intraperitoneal route, responses were negative. 6. From the results of hapten inhibition tests using anti-FUT-187 guinea pig serum, it is suggested that the antigenicity of FUT-187 is attributable to the its benzoic acid.


[A 13-week subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in dogs. A subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187), a new protease-inhibiting agent, was carried out in beagle dogs of both sexes. FUT-187 was administered to dogs at daily oral doses of 15, 50 and 150 mg/kg. Dogs in 150 mg/kg group were given twice a day in a.m. and p.m.. The results were as follows: 1. Changes of physical sign attributed to FUT-187, consisted of vomiting, diarrhea, salivation, decrease of locomotor activity, sedation and hyperemia of eye mucosa. These changes expect vomiting vanished within about 2 hours after treatment. One male given 150 mg/kg died on day 19 and two females given 150 mg/kg were sacrificed on day 55 and 67 due to deterioration of systemic conditions. 2. Body weight gain was suppressed in males given 150 mg/kg and females given 50 mg/kg or more. 3. In hematological examinations, some changes suggesting anemia or inflammation were observed in a few animals received 50 mg/kg or more 4. In serum biochemical examinations, dogs given 50 mg/kg or more had decrease of albumin, total protein, A/G ratio and total cholesterol, increase of GPT activity. In liver function test, decrease of function was observed in a few animals in 150 mg/kg group. These changes diminished by the end of recovery period. 5. In autopsy findings, ulcer formation and desquamation of mucosa in the digestive tract were observed in dead or sacrificed animals and survived animals given more than 50 mg/kg. In sacrificed animals, liver was yellow in color and intussusception was seen. 6. Plasma levels of intact FUT-187 and metabolites on the day 37 or 83 were higher than that on the first day of administration. 7. In histopathological examinations, ulcer formation, desquamation, degeneration and/or atrophy of mucosa in the digestive tract were observed in the animals from 50 mg/kg and 150 mg/kg groups. In addition, fatty deposition in hepatocytes was observed in one dead animal and two sacrificed animals.(ABSTRACT TRUNCATED AT 400 WORDS)


A simple animal model for inducing and releasing surgical jaundice in rats. Surgical jaundice can be easily induced by ligation of bile duct, but it is not easy to reverse the ligation in rats. Therefore, a simple method was designed in our laboratory to address the problem. Obstruction of bile duct can be achieved by the compression by two arms of a fine silicon tube enveloped in an outer bigger silicon tube. Both silicon tubes are then fixed and sutured to the abdominal peritoneum. Therefore, if the releasing of the obstruction is required, removal of the inner fine silicon tube by removing off the previous suture tire of silicon tube which had settled under the skin. Thus, the reversing of obstruction could be achieved without extensive exploration into the abdominal cavity. One week after obstruction the bile duct of rats were dialated 6.10 +/- 1.26 mm (Mean +/- SD) in rats. The serum bilirubin and alkaline phosphatase were 6.29 +/- 1.26 mg% and 229.30 +/- 82.22 IU respectively. The dilated bile duct decreased into 3.00 +/- 0.98 mm one week after decompress with this method. Serum bilirubin and alkaline phosphatase were 1.80 +/- 0.79 mg% and 90.50 +/- 19.60 IU respectively. It proved that this animal model was simple and had the benefit of being able to sample the bile without contamination with intestinal contents after decompression.


Ultrasonography of chest diseases: analysis of 154 cases. Sonographic characteristics of various chest diseases in 154 cases were analysed according to margin of the lesion, internal echogenecity, posterior echo enhancement, air bronchogram etc. We intended to present the basic sonographic patterns of common chest diseases. The study included 10 normal cases, 10 cases with lung abscesses, 31 cases of pneumonia, 24 cases of tumors, 11 cases of obstructive atelectasis, 8 cases of pleuropericarcadial effusions, 10 cases of minimal effusions, 6 cases with pleural thickening, 32 cases of massive pleural effusion with simple compression atelectasis and 12 cases of pneumonia with parapneumonic effusion. Sonographically, normal lung showed hyperechoic zone beneath the chest wall. Identification of arc or ring-shaped wall favored lung abscess. Air bronchogram could only be found in pneumonia. Mass showed various internal echogenecity. The internal echogenecity in obstructive atelectasis was very homogeneous which could not be found in tumor. Pleural thickening showed linear hyperechogenecity beneath the chest wall. In minimal effusion, the line of the diaphragm could be easily identified. Pleuropericardial effusion could be easily diagnosed by chest sonography. The line of the pericarcadium could be clearly identified. The internal echogenecity of massive effusion were various. The internal echogenecity of simple compression atelectasis showed very homogeneous hyperdense internal echogenecity. The internal echogenecity of lung parenchyma in pneumonia with parapneumonic effusion was similar to that of pneumonia. Obstructive atelectasis, mass, consolidation and encapsulated effusion could be differentiated by chest sonography without much difficulty. Sonography could aid chest radiography by giving more morphologic information and was cheaper than computed tomography.


Maximum inspiratory pressure: a neonatal criterion for weaning from mechanical ventilation. Thirty-three newborn infants admitted to the neonatal intensive care unit of our hospital were studied. Mechanical ventilation was used for more than 24 hours for each patient. Maximum inspiratory pressure (MIP) was measured by means of a manometer at the oral end of the endotracheal tube just prior to extubation. Of the 33 studied neonates, 28 were successfully weaned at the first attempt of extubation (group I). Five neonates failed at the first attempt of extubation and required tracheal reintubation (group II). The mean birth weight was 1.78 +/- 0.86 kg, the mean gestational age was 32.6 +/- 4.3 weeks and the mean duration of intubation was 4.2 +/- 2.1 days in group I. The mean birth weight was 1.74 +/- 0.61 kg, the mean gestational age was 32.8 +/- 3.5 weeks and the mean duration of intubation was 7.0 +/- 2.6 days in group II. The mean MIP value in group I was -42.57 +/- 7.18 cm H2O and the mean MIP value in group II before the first attempt of extubation was -21.2 +/- 1.79 cm H2O. The patients in group I had a significantly lower MIP (P < 0.01) than group II, of the 28 patients in group I, 27 had MIP equal to or exceeding -35 cm H2O and only one case had MIP of -30 cm H2O. We conclude that measurement of MIP is a simple, useful and safe method for neonates to predict successful extubation from prolonged mechanical ventilation. A neonate with a MIP exceeding -35 cm H2O can be safely weaned from mechanical ventilation.


[Flow cytometric analysis of DNA in esophageal cancer]. Malignancy is the first of the ten leading causes of death in Taiwan area, however, since 1978, esophageal cancer is on the first ten causes of malignancy. Esophageal cancer is an aggressive neoplasm with a generally poor prognosis. This is usually related to the advanced stages of the neoplasm at presentation and at diagnosis. In this study, the DNA content in tumor was analyzed by flow cytometry, and compared it with clinical- pathological data, especially the survival time. All thirty seven cases (36 male, 1 female, mean age: 56.5 +/- 10.3 y/o) received operation at Kaohsiung Medical College Hospital in the past 11 years and 29 cases (27 male, 2 female, mean age: 62.2 +/- 9.6 y/o) proved to be esophageal cancer by endoscopic biopsy were assayed in this study. The formalin fixed-paraffin embedded block is used to analyze DNA content by flow cytometry. After comparing these results with clinical-pathological data, there were no significant difference in sex, age, duration, tumor location and length. However, there is a significant correlation between ploidy and tumor cell differentiation, that is, most of the diploid cells were well differentiated while most of the aneuploid cells were poorly differentiated. The median survival time of diploid cases was 325 days which was longer than the 277 days in aneuploid group, but there was no significant difference between these two groups. The same result was noticed in DNA index. Multiple variables analysis of prognostic factors disclosed that there were significant difference in correation with age tumor location tumor length, and whether there was combined radiotherapy and operation. But there were no significant relationship between survival and DNA ploidy DNA index distant metastasis surrounding tissue invasion sex duration and tumor cell differentiation. These data suggest that DNA folw cytometry analysis alone, may not provide a sueful biologic basis for the variable prognosis seen with esophageal tumors.


[The functional assessment of chronic pain patients activity of daily living and psychosocial disability]. The purpose of this study was to investigate the impact of activity of daily living and psychosocial function in patients with chronic nonmalignant pain. From Jun. 1989 to Nov. 1989, one hundred and eleven cases were assessed by Sickness Impact Profile (SIP) and Taita Symptom Check List (TSCL) to evaluate the disabilities associated with chronic pain. Patients showed significant impairment in the functions of physical psychosocial work and recreational activities. It was also apparent that the psychosocial disabilities were more severe than physical disabilities. Specifically, they showed anxiety depression and significant somatization. Analysis by stepwise multiple regression indicates that sex age educational level employment status diagnosis and pain intensity were the significant influencing factors related to the disabilities of activity of daily living and psychosocial function. The results supported the validity of the SIP as a measurement of functional status with chronic pain patients. Specifically, the psychosocial dimension was significantly correlated with the psychological and psychosocial distress categories of the TSCL. Based upon its reliability validity breadth of assessment and ease of administration, the SIP appeared to be well suited for the assessment of patients with chronic pain and for evaluating the efficacy of multidisciplinary pain treatment.


Congenital absence of the pulmonary valve: report of two cases with review of the literature. Congenital absence of the pulmonary valve is an uncommon combination of anomalies. Recently, we encountered two such cases, one associated with tetralogy of Fallot (case 1), the other with ventricular septal defect (case 2). Clinically, our cases had minimum symptoms. The congenital cardiac anomalies were diagnosed with physical examination, chest x-ray film, echocardiography, and confirmed with cineangiography. These procedures disclosed a rudimentary pulmonary valve, pulmonary regurgitation and aneurysmal dilatation of the main and right pulmonary artery. In case 2, the right lower pulmonary artery occlusion and left hydronephrosis were also demonstrated by magnetic resonance imaging. The two cases underwent surgical repair to correct the tetralogy of Fallot and the ventricular septal defect respectively. Our experience in diagnosing these cardiac anomalies is reported.


[Clinical and scanning electron microscopic studies on Norwegian scabies infection]. Two typical cases of Norwegian scabies were studied clinically, scanning electron microscopically and histopathologically. Case 1 was a boy with Down's syndrome and case 2 was a man with adult T cell leukemia/lymphoma. Their clinical pictures showed hyperkeratotic plaques and warty crusts on hands, feet, ears, elbows and buttocks. Direct examination of the KOH preparation revealed many embryonated sarcoptic eggs, postpartum egg-shells, fecal pellets, larvae and male and female adult mites. Histopathologic examination showed several burrows inside the thick horny layer. Many sarcoptic egg-shells, mites and fecal pellets were found in the burrows. Psoriasiform hyperplasia and parakeratosis were noted, too. The size and shape of the sarcoptic eggs and the detailed structure of mites and molt were observed by using a scanning electron microscope. Besides, hook-like structures were noted at the tarsi of both forelegs and hindlegs. We suggest that the larvae crawl out from longitudinal openings in the egg-shell by the use of hook-like structures. The mites also used these hook-like structures to make the burrows. Scanning electron microscopy provides a good method to understand the dynamics of these burrowing parasites. It is helpful in illustrating the behavior of the scabies mites in their burrows in Norwegian scabies patients.


[Ileal inflammatory fibroid polyp: case report]. The inflammatory fibroid polyp is a rare, polypoid lesion in the gastrointestinal tract. It occurs in the stomach, small intestine, and large intestine in descending order of frequency. This case report shows an ileal inflammatory fibroid polyp that causes ileoileal intussusception. So far, the histogenesis and pathogenesis of these kinds of polyps are still uncertain. Under the microscopic examination, the lesion appears to be made up of spindle-shaped or stellate cells that are morphologically identical to proliferating fibroblasts. Immunostaining results are strongly positive for vimentin and focally positive for S100 protein. However, epithelial membrane antigen, factor VIII R Ag, smooth muscle actin, and lysozyme test are all negative. This favors the view that the inflammatory fibroid polyp is fibroblastic in origin.


The serum ferrokinetics in Parkinson's disease. Ferrous ion is an essential cofactor in dopamine synthesis and its decrease may reduce the dopamine production in the nigrostriatal system, the basis of pathogenetic mechanism in Parkinson's disease (PD). Therefore, parkinsonians may have an abnormal systemic ferrokinetics. The serum iron, ferritin, total-iron-binding-capacity (TIBC) levels and transferrin saturation were analysed in 15 patients with Parkinson's disease and 30 controls. The serum iron was lower in PD (95.53 +/- 33.5 micrograms/dl) than in controls (102.5 +/- 32.5 micrograms/dl), but the difference was statistically nonsignificant. The ferritin, TIBC and transferrin saturation were also similar in both groups. The systemic ferrokinetics in our PD was normal, but the ferrokinetics between the central and systemic compartments was different in PD. Therefore, reduction of central dopamine in PD is unlikely due to hypoferruginemia.


A comparative study with intracavernous injection of prostaglandin E1 versus papaverine for the diagnostic assessment of erectile impotence. The intracavernous injection of vasoactive drugs is a valuable diagnostic aid and an important tool for the treatment of erectile failure. A comparative study with intracavernous injection of prostaglandin E1 (PGE1) and papaverine was performed in 60 patients with impotence. We evaluated the efficiency and side effects of both agents. The overall positive response rate was 85.0% in the PGE1 group and 65.0% in the papaverine group which suggests PGE1 has a stronger vascular effect. The mean onset of maximal erection was after 9.6 minutes in the PGE1 group and after 6.5 minutes in the papaverine group. The mean maintenance of erection was for 53.2 minutes in the PGE1 group and for 38.6 minutes in the papaverine group. There were no systemic side effects of either agent. Three instances of injection pain and 2 of burning sensation in the penis were noted in the PGE1 group, while in the papaverine group, there were 21 reports of injection pain, 4 of prolonged erection and 2 of burning sensation in the penis. These results suggest that PGE1 is a more desirable vasoactive alternative for the diagnosis of impotence.


Cystic intracranial meningioma.

Cystic intracranial meningioma. Between April 1983 and April 1991, we studied nine cases of intracranial meningioma with cystic change out of 100 intracranial meningioma patients. The incidence was 9%. The patient's ages ranged from 40 years to 75 years old. There were five men and four women, of them, three had intratumoral cysts, and six had peritumoral cysts. Histologically, 7 cases were diagnosed as meningothelimatous type, one as psammomatous and the other one as angioblastic type. All the tumors with cystic change in this series were greater than two centimeters in diameter. Because the morphology was indistinct, Nauta's type II cystic meningioma was easily misdiagnosed as glioma or metastatic tumors preoperatively. Microsurgery is the best way for complete removal of the cyst wall to prevent recurrence.


[The strength and functional performance of patients with Duchenne muscular dystrophy based on natural history]. Duchenne muscular dystrophy (DMD) is a disease of progressive muscular weakness and wasting. This study is designed to evaluate the muscle strength and functional performance of patients with DMD during the natural progression of this disease. This study comprises a sample of 35 subjects who were confirmed to have DMD. Manual muscle testing (MMT) was used to evaluate muscle strength, the Brooke functional scale to rate the motor function of the upper extremity, and the Vignos functional scale to rate the motor function of the lower limbs. The results showed a significant positive correlation between age and the decrement in strength, i.e. a one year increment in age led to a 3.9% decrease in the average muscle strength. The strength loss always occurred in a typical pattern proceeding from the lower extremities to the upper extremities, and from the proximal to the distal parts. There was a significant negative correlation between muscle strength and both the Brooke and Vignos functional scales. These findings may suggest that decreased muscle strength results in a progressive worsening of the functional performance of the extremities. In addition, the Brooke scale is significantly correlated with the Vignos scale through the natural course of DMD. The high percentage (90.5%) of subjects without the long leg braces needed for ambulation indicates an inadequate rehabilitation care for DMD patients in this country.


[Dipyridamole Tc-99m MIBI myocardial perfusion scintigraphy in patients with post-infarction chest pain symptom]. To evaluate the efficacy of stress Tc-99m MIBI myocardial perfusion imaging using intravenous dipyridamole in detecting coronary artery disease (CAD) and to determine if chest pain symptom is a proper index for detection of myocardial ischemia in post-infarction patients, we observed 73 cases (65 men, 8 women, 38-79 years old) between Sept. 1990 and May 1992. All patients were suffered from old myocardial infarction (MI) evidenced by history and ECG and were divided into two groups: group I involving 41 patients with post-infarction chest pain symptom and group II including 32 patients without post-infarction chest pain symptom. Among them, 19 (group IA) of group I and 11 (group IIA) of group II received coronary arteriography (CAG) for comparison. Of the 41 group I post-infarction chest pain patients, 17 suffered from old anterior or antero-septal wall (AW) MI, 21 from old inferior wall (IW) MI, 1 from old lateral wall (LW) MI and 2 from combined old AW and IW (AIW) MI by ECG. All 17 patients with AWMI suffered from AW perfusion defect (7 were MI, 10 were MI with ischemia) but 7 of them from multivessel disease (MVD) by Tc-99m MIBI. All 21 patients with IWMI suffered from IW perfusion defect (9 were MI, 12 were MI with ischemia) but 13 of them from MVD by Tc-99m MIBI. Of the patient with LWMI and 2 patients with AIWMI suffered from MVD by Tc-99m MIBI. Of the 32 group II post-infarction patients without chest pain symptom, 12 suffered from old AWMI, 14 from old IWMI, 2 from old LWMI, 3 from AIWMI and 1 from ALWMI by ECG. Of the 12 patients with AWMI, 11 suffered from AW perfusion defect (6 were MI, 5 were MI with ischemia) but 1 of them from MVD by TC-99m MIBI. All 14 patients with IWMI suffered from IW perfusion defect (12 were MI, 2 were MI with ischemia) but 4 of them from MVD by Tc-99m MIBI. Of the 2 patients with LWMI suffered from LW infarction by Tc-99m MIBI. Of the 3 patients with AIWMI and 1 with ALWMI suffered from MVD by Tc-99m MIBI. Of the 11 patients in group IA and 5 patients in group IIA with AWMI, CAG revealed the incidence of infarct-related recanalization of LAD was 9/11(82%) and 4/5(80%) respectively and the respective incidence of MVD was 6/11(55%) and 0/5(0%).(ABSTRACT TRUNCATED AT 400 WORDS)


[Muscle histochemical changes in rats swimming under high temperature]. The aim of this study was to investigate the effects on muscle tissues of increasing amounts of exercise under normal and high temperatures. An experimental swimming test was applied to completely exercised rats. There were 42 adult male rats divided into 4 groups, including normal control rats, rats which swam to death under room or high temperature conditions, and rats swimming under high temperatures. Immediately after the exercise, the soleus (SOL) and extensor digitorum longus (EDL) muscles were removed by surgical excision. All specimens were frozen in isopentane cooled to -70 degrees C in liquid nitrogen. Cryostat cross sections were cut and stained using histologic and histochemical staining methods to observe pathological changes. The major changes included interstitial edema, muscle fiber atrophy, muscle fiber necrosis, hypercontracted fibers, and ragged red fibers. The rats exercised to death under high temperatures had more apparent changes than those not exercised to death. These results indicate that pathological changes in muscle will be brought about by increasing the amount of exercise and environmental temperature. Since there are more fast twitch fibers in the EDL than in the soleus, pathological changes in muscle tissues are more severe in the EDL.


A simultaneous bilateral attack of infectious corneal ulcers in an extended-wear soft contact lens wearer: a case report. A case study was made of a 23-year-old female with simultaneous bilateral infectious corneal ulcers related to extended-wear soft contact lenses. Cultures revealed Pseudomonas aeruginosa and Acinetobacter calcoaceticus. Multiple high risk factors were combined, including extended-wear, poor lens care, bilateral alternate wearing, and smoking. Amphetamine addiction may also have played a role. After treatment, a visual acuity of 20/20 was achieved in both eyes by the use of rigid gas-permeable contact lenses.


Structure modification and biological activity of some griseofulvin derivatives. Griseofulvin is an orally acting anti-fungal antibiotic with very limited water solubility. Five chemical modifications were made on the griseofulvin structure in order to evaluate these changes on the antifungal and water solubility properties. Antifungal activity was measured against Tricophyton mentagrophytes, T. rubrum, T. terrestre, and Microsporum canis. The oxime of griseofulvin was the most potent of the five compounds tested, but it was only of equal or less potency than griseofulvin. The somewhat increased water solubility of some of these compounds was offset by the lower anti-fungal potency of the structural modification.


Flow cytometric DNA analysis of pleural effusions. A total of 71 cases of pleural effusion in patients with and without cancer were analyzed by conventional cytology and flow cytometry (FCM) in order to detect cells with an abnormal DNA content (aneuploidy). For cytologic examination, the samples were prepared using standard techniques. Sample for FCM analysis were centrifuged and exposed to hypotonic solution containing detergent and propidium iodide. Thirty-eight patients had pleural effusion due to benign disease, whilst 33 patients had primary lung cancer. All 38 patients with benign pleural effusions showed FCM diploidy. There were 17 aneuploidy (52%) and 16 diploidy (48%) in the 33 patients with lung cancer by FCM analysis. Four of these 33 effusions were cytologically negative, however, FCM showed aneuploidy in 2 of these 4 patients. Based on these results, FCM analysis combined with conventional cytopathology yielded 100% specificity, 94% sensitivity and 100% predictive value of positive result. There were no false-positive results but 2 false-negative results. These findings suggest that FCM is a rapid and useful technique in the analysis of pleural effusion and can be a very useful adjunct to conventional cytopathology.


Influence of central obesity and obesity level on the prevalence of NIDDM and impaired glucose tolerance. The purpose of this study was to determine the association of the prevalence of non-insulin-dependent diabetes (NIDDM) with central obesity, obesity, and family history of diabetes. This survey consisted of 1590 subjects (646 men, 944 women) aged 30 years or more from the Sun-Ming district of Kaoshiung city. Glucose tolerance status was ascertained by both medical history and a 75-g oral glucose tolerance test according to World Health Organization criteria. In men and women with central obesity (WHR > or = 0.92 in men and > or = 0.85 in women) or obesity (BMI > or = 27.6 kg/m2 in men and > or = 28.3 kg/m2 in women) (WHR: waist-hip ratio; BMI: body mass index), the prevalence of impaired glucose tolerance (IGT) and diabetes was significantly higher, except the prevalence of diabetes in both sexes with obesity and the prevalence of IGT in women with central obesity were not statistically different, as compared with nonobese subjects. The prevalence of diabetes in men significantly increased from the first quartile to the fourth quartile of BMI and the waist-hip ratio (WHR) (4.48% to 9.21% in BMI, 3.67% to 13.61% in WHR), while the prevalence in women also significantly increased from the first to fourth quartile (2.45% to 11.76% in BMI, 2.04% to 13.49% in WHR). Multiple logistic regression analyses revealed similar increase in the prevalence of diabetes among both men and women for every 1 kg/m2 increase in BMI and every 0.05 increase in WHR (1.07-fold and 1.09-fold in BMI, 1.34-fold and 1.32-fold in WHR, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


An analysis of brain tumors in south Taiwan. A series of 544 pathologically verified brain tumors were analyzed for the relative incidence and location of tumors as well as the distribution of age and sex. These data were compared to series from north Taiwan, mainland China, America, Germany, and Japan. The incidence of gliomas among brain tumors in south Taiwan (25.4%) was lower than other reports (31-44%). It is interesting to note that the incidence of gliomas in Asian reports is lower than those in America and Germany. A much higher percentage of meningiomas and pituitary adenomas were seen in Taiwan's reports than in those from other countries. Aggressive surgical decompression of brain metastases in selected cases is advised and they comprised 15.1% of total brain tumors operated on. The incidence of brain tumors in the older age group in south Taiwan (22.1%) was much higher than those reported from mainland China (1.65%). Our series revealed a preponderance of tumors in females over males, which may be affected by the greater number of female-predominate meningiomas and pituitary adenomas.


[A dental anthropological study of Chinese in Taiwan (3). Dental trait]. Models of the upper and lower dental arches of 125 Chinese children in Taiwan with acceptable normal permanent dentition were surveyed in order to understand the developmental grades of dental traits from the viewpoint of dental anthropology. Developmental grades of dental traits were classified, calculated, statistically analysed by x2 test and results were summarized. Upper anterior teeth showed high frequency of shovel form; upper lateral incisors showed less tendency of regression. Interstitial cusp, lingual cusp, paracusp, central prominence and occlusal groove of lower premolars developed prominently. Upper molars showed low frequency of Carabelli cusps. Hypocone of upper second molars showed strong tendency of regression, but metacone had low regression tendency and a strong degree of compression. Compared to Japanese, Central American and South American Indians and Caucasians, the development of dental traits of Chinese in Taiwan was more similar to that of Japanese than to others. The characteristics of dental trait of Chinese in Taiwan and Japanese also showed greater similarity to Central and South American Indians than to Caucasians.


[A survey of the relationships between children and their parents in chronic disease risk factors, health knowledge and lifestyles]. The purpose of this study is to understand the relationships for risk factors, health knowledge and lifestyles between children and their parents. 2806 primary schoolchildren in Kaohsiung City were measured for selected risk factors: serum cholesterol (CHOL), triglyceride (TG), systolic and diastolic blood pressure and height and weight for obese index (Rohrer's index). Children whose Rohrer's index > or = 150, or blood pressure, or CHOL, or TG level were above the 95th percentile distribution in the same age group were categorized as the risk group, the other children fell into the non-risk group. Using random sampling, 180 children were chosen from risk group and non-risk group respectively. A structured questionnaire about health knowledge and lifestyles were filled out by these children and their parents. In the risk group, the questionnaire was completed by 157 children, 103 fathers and 112 mothers. In the non-risk group, 102 children, 83 fathers and 82 mothers completed the questionnaire. The same risk factors examination of children was given to parents; 86 fathers and 144 mothers completed the examination from the risk group, while 56 fathers and 98 mothers completed the examination in the non-risk group. The results showed that: (1) there were significant positive correlations between children and their parents in CHOL, TG and obese index in risk group; children of mothers with higher CHOL and TG levels also showed higher CHOL and TG levels, (2) childrens' health knowledge was not correlated with parents' health knowledge, (3) childrens' lifestyles showed a significant positive correlation with mothers' lifestyles, (4) health knowledge has a significant positive correlation with childrens' and parents' lifestyles, (5) healthy lifestyles have a negative correlation with Rohrer's index in children and a negative correlation with TG level in fathers. The results suggest the presence of certain relationships for risk factors and lifestyles between children and their parents.


[Aicardi syndrome: a case report].

[Aicardi syndrome: a case report]. A 5-year-old girl had suffered from infantile spasms since 3 months of age. Cranial computerized tomography revealed agenesis of the corpus callosum. Abnormal ocular fundus features consisted of bilateral disc colobomas and lacunar pigment change in her right eye. The clinical presentations were consistent with Aicardi syndrome. The ophthalmologic manifestations of Aicardi syndrome will be discussed in this paper.


[Surgical treatment of biliary cyst].

[Surgical treatment of biliary cyst]. The experience with surgical treatment of 21 patients with a biliary cyst who underwent 25 operations has been analysed. The authors came to a conclusion about unexpediency to use the walls of a cyst in creation of the cystodigestive anastomosis. The operations with complete removal of the cystic wall are recommended.


[Differential treatment of focal traumatic brain injury]. On the basis of observation of 65 patients with focal traumatic injury to the brain (hematoma of mater encephali was noted in 24, intracerebral--in 27, a focus of type III brain contusion--in 24, type IV--in 11, multiple hematomas and foci on contusion-crush--in 21), the criteria for their non-surgical treatment have been substantiated. Choice of a method for the treatment depends on the sizes of a hematoma, focus of contusion-crush, location of an injury, degree of its influence on the brain structures (deformation, shift), value of intracerebral pressure, dynamics of the clinico-roentgenologic symptoms.


[Staged treatment of patients with lymphedema of the lower extremities]. At examination of 120 patients with lymphedema of the lower extremities, in 70% of them, structure and function of lymphangion were preserved. State of lymphangion is of great importance in substantiation of the tactics of treatment. In preserved morphofunctional properties of lymphangion, the operation of lymphovenous shunting is effective in 83% of the patients. Stimulation of contractile activity of the lymphatic vessels at the stages of in-patient, out-patient treatment and that in sanatoria and health resorts contributes to improvement of a result of treatment of the patients.


[Venous occlusive plethysmography in assessment of hemodynamics in arterial thrombosis of the lower extremities]. With the use of a method of venous occlusive plethysmography changes, in regional arterial and venous hemodynamics in 75 patients with arterial thrombosis as well as in 47 after reconstructive intervention at the immediate period, and in 25--at the late period were studied. It was established that in ischemia progression, the volume blood flow rate at rest and maximum rate decreased, indicating severe impairement in reserve possibilities of blood flow, maximum venous outflow reduced, venous filling of the vessels increased. In thrombosis, rough disorders in reserve possibilities of blood flow in the aorto-iliac segment were noted. After operation, dynamics of the indices didn't depend on type of reconstructive intervention and was determined only by adequacy of blood flow restoration in the extremity.


[Methods for surgical prophylaxis of the development of acute gastroduodenal ulcers]. The results of the use of prolonged novocaine blockade with the aim of prevention of the development of acute gastroduodenal ulcers in 57 patients are presented. In 21 case, the prolonged blockade of the vagus nerves was used, in 36--that of the ligamentum teres hepatis. After the operation, the proteolytic activity and acidity of gastric juice were studied. All the patients underwent gastroduodenofibroscopy with biopsy and target pH-metry. Under the influence of novocaine blockade, the proteolytic activity decreased, pH increased. At endoscopy, no acute erosive-ulcerous lesion of mucosa was revealed. Thus, a high effectiveness of the use of prolonged novocaine blockade has been proved.


[Lipid peroxidation and impairement in erythrocytic properties in patients with ulcer disease before and after surgery]. The state of peroxide oxidation of lipids (POL) in the erythrocytes before and after the operation was studied. In patients with ulcer disease, the correlation between POL activity and changes in erythrocytic properties was noted. At the period of disease exacerbation, activation of POL processes in erythrocytes, suppression of the antioxidation protection (AOP), impairement in hemorheologic indices (increase in aggregation of erythrocytes, their resistance to acid hemolysis, reduction in their capacity for deformation) were revealed. Pronouncement of the pathologic changes after the operation depended on a background state of POL and AOP. In ulcer disease, the impairment in POL/AOP balance caused the development of postoperative complications. To prevent the development of complications, the administration of antioxidants is expedient.


[The effect of smoking on the long-term outcome of closure of perforated gastric and duodenal ulcer]. Examined were 164 patients at the long-term period after closure of a perforative ulcer of the stomach and duodenum. The negative effect of smoking on acid production and protective barrier of gastroduodenal mucosa leading to worsened healing of an ulcer closed and its recurrence in 50% of the patients operated on has been established. It was noted that in smokers, irrespective of a number of the cigarettes being smoked, an excellent and good long-term result was observed 2.5 times less often, and a poor one--3 times more often than in non-smokers.


[Method of intraoperative hemostasis in parenchymatous hemorrhage]. The authors have developed a new method for intraoperative hemostasis in parenchymatous hemorrhage. Hemostasis is achieved by means of electrophoresis of fibrinogen and some other factors of blood coagulation into the organ parenchyma. Approbation of the method on dogs has demonstrated its atraumaticity and safety.


[Cystic duct obstruction in the pathogenesis of acute experimental cholecystitis]. The experimental model of acute cholecystitis with a regulated cuff, which permits to reproduce the state of bile outflow in patients with acute inflammation of the gallbladder, when the cystic duct is partially, or completely obturated, has been developed. The results of investigation can contribute to choice of surgical tactics in acute cholecystitis.


[Treatment of external pancreatic fistula]. In the clinic, 56 patients with an external pancreatic fistula was treated. After conservative treatment, a fistula closed in 43 patients, and was functioning in 13. Fistuloenterostomy was performed in 6 patients, resection of the left lobe of the pancreas--in 7. There were no complications and lethal outcomes. The method for return of the pancreatic juice into the duodenum has been suggested.


[Diagnostic accuracy in acute pancreatitis in the prehospital and early hospital stages]. The results of the analysis of diagnosis of acute pancreatitis on the basis of studying 3634 case records are presented. Errors in the diagnosis of acute pancreatitis at the prehospital stage were established in 61.9%, at the early hospital stage--in 32.35% of cases, usually in the form of hyperdiagnosis of the disease.


[Repeated surgeries of the bile ducts].

[Repeated surgeries of the bile ducts]. The results of examination and operative treatment, of 74 patients with the postcholecystectomic syndrome, who underwent 81 restorative and reconstructive operation 1 month to 21 year after cholecystectomy, have been summarized. The postoperative lethality was 8%. Peritonitis and hepatic failure were the main causes of death. Necessity of early performance of a reoperation has been substantiated.


[Choice of operative intervention in the treatment of echinococcosis of the left hepatic lobe]. The results of treatment of echinococcosis of the left hepatic lobe in 15 patients have been analysed. Resection of the left hepatic lobe is considered an operation of choice in presence of a large cyst.


[Informative value of amino acid reserve in the blood plasma in cholestatic and septic syndrome]. Syndrome of cholestasis is characterized by pronounced increase in concentration of the sulphur containing, ketogenic amino acids and intermediates of a cycle of urea formation in the blood plasma; sepsis--by decrease in pool of glycogenic amino acids, increase in concentration of free ammonium and reduction in correlation of amino acid concentration with branched hydrocarbon chain of aromatic amino acids. In cholestasis, the levels of ammonium alpha-amino butyrate and aromatic amino acids were the most informative indices, in sepsis--content of lysin, glutamate, cystein and cysteate.


[Use of absorbable antimicrobial suture material at the gastroenteric anastomosis in patients with gastric and duodenal disease]. The authors in creation of the internal layer of sutures of gastroenteric anastomoses in 80 patients have used the synthetic antimicrobial absorbable material. No complications related to use of the suture material were revealed. The results obtained permit to recommend the new suture material for more wide use in the gastrointestinal surgery.


[Computerized tomographic semiotics of acute pancreatitis]. In the article, the expediency of the use of computerized tomography in the diagnosis of the different forms of acute pancreatitis in 49 patients is substantiated and results are analysed.


[New approaches in diagnosis and therapy of the thoracic outlet syndrome]. The results of diagnosis and treatment of the thoracic outlet syndrome (TOS) in 35 patients have been analysed. Compression of the subclavicular neurovascular bundle at the site of its outlet from the thoracic cavity was most frequent cause of TOS development. A degree of compression was assessed quantitatively by the data of a modified functional dynamic test. The modified operation, including resection of the I rib (and of a cervical one in its presence), scalene muscle, musculus pectoralis minor, periarterial sympathectomy of the subclavicular artery, was performed. In narrow (less than 1.5 cm) costoclavicular space, the II rib was additionally resected. An excellent long-term result is indicative of the effectiveness of the method.


[Radiodiagnosis of the thoracic outlet syndrome]. The results of roentgenological investigations in thoracic outlet syndrome are summarized. The method for defining the width of a costoclavicular cleft and its diagnostic importance in 72 patients operated on is described. A role of anomalies of the osteofibrous formations in the development of neurovascular compression is noted.


[Surgical treatment of non-specific aortoarteritis of the aorto-femoral segment]. For 15 years, the authors observed 158 patients with non-specific aortoarteritis. Of them in 37 (23.4%), isolated lesion of the terminal aorta, iliac and femoral arteries was revealed; in 81.1%--severe degree of ischemia of the lower extremities, 39.4% of men had impotency. Associated lesions of the aorta and arteries of the lower extremities was revealed in patients with acute inflammatory process. The extent of vascular occlusion depended on its presence. Surgical treatment was performed in 35 patients; in 30, the reconstructive operations were performed, in 3--lumbar sympathectomy, in 2--amputation of an extremity. At the early postoperative period, a good result has been noted in 82.9%, 5.7% of patients died. Twenty six patients were followed up for 5 years, 60.1% of them have shown a good result.


[Level of circulating immune complexes in patients with complicated cholelithiasis]. In 165 patients with the different forms of cholelithiasis, a level of the circulating immune complexes (CIC) was measured in the blood serum and bile from the common bile duct at the postoperative period. In associated purulent-resorptive and cholemic intoxication, the CIC level in the blood serum and bile increases. This, in turns, enhances the likelihood of the development of purulent-septic complications at the postoperative period, and requires performance of target immunocorrection.


[Value of exhaled air acetone level in assessing the impairement of secretory pancreatic function in acute destructive pancreatitis]. For the first time, a semiconductor gas sensor of original construction was employed to measure acetone level in the biologic liquids and gases in patients with acute destructive pancreatitis. A statistically significant difference in acetone level in the exhaled air of the healthy subjects, patients with edematous and destructive forms of acute pancreatitis and diabetes mellitus has been established.


The effect of auxiliary conditions on intestinal unstirred layer diffusion modelled by numerical simulation. Estimation of intestinal unstirred layer thickness usually involves inducing transmural potential difference changes by altering the content of the solution used to perfuse the small intestine. Osmotically active solutes, such as mannitol, when added to the luminal solution diffuse across the unstirred water layer (UWL) and induce osmotically dependent changes in potential difference. As an alternative procedure, the sodium ion in the luminal fluid can be replaced by another ion. As the sodium ion diffuses out of the UWL, the change in concentration next to the intestinal membrane alters the transmural potential difference. In both cases, UWL thickness is calculated from the time course of the potential difference changes, using a solution to the diffusion equation. The diffusion equation solution which allows the calculation of intestinal unstirred layer thickness was examined by simulation, using the method of numerical solutions. This process readily allows examination of the time course of diffusion under various imposed circumstances. The existing model for diffusion across the unstirred layer is based on auxiliary conditions which are unlikely to be fulfilled in the same intestine. The present simulation additionally incorporated the effects of membrane permeability, fluid absorption and less than instantaneous bulk phase concentration change. Simulation indicated that changes within the physiologically relevant range in the chosen auxiliary conditions (with the real unstirred layer length kept constant) can alter estimates of the apparent half-time. Consequently, changes in parameters unassociated with the unstirred layer would be misconstrued as alterations in unstirred layer thickness.


Synonymous codon preferences in bacteriophage T4: a distinctive use of transfer RNAs from T4 and from its host Escherichia coli. Codon usage data of bacteriophage T4 genes were compiled and synonymous codon preferences were investigated in comparison with tRNA availabilities in an infected cell. Since the genome of T4 is highly AT rich and its codon usage pattern is significantly different from that of its host Escherichia coli, certain codons of T4 genes need to be translated by appropriate host transfer RNAs present in minor amounts. To avoid this predicament, T4 phage seems to direct the synthesis of its own tRNA molecules and these phage tRNAs are suggested to supplement the host tRNA population with isoacceptors that are normally present in minor amounts. A positive correlation was found in that the frequency of E. coli optimal codons in T4 genes increases as the number of protein monomers per phage particle increases. A negative correlation was also found between the number of protein monomers per phage and the frequency of "T4 optimal codons", which are defined as those codons that are efficiently recognized by T4 tRNAs. From these observations it was proposed that tRNAs from the host are predominantly used for translation of highly expressed T4 genes while tRNAs from T4 tend to be used for translation of weakly expressed T4 genes. This distinctive tRNA-usage in T4 may be an optimization of translational efficiency, and an adjustment of T4-encoded tRNAs to the synonymous codon preferences, which are largely influenced by the high genomic AT-content, would have occurred during evolution.


Probability of occurrence of specific oligomers. We improved an already existing formula for calculating the probability of occurrence of specific oligomers (Grob & Stüber, 1987) by taking into account unequal base distribution. This method identifies specific oligomers in a given sequence as candidates for biological signals.


Estimates of mean alveolar PCO2 during steady-state exercise in man: a theoretical study. The partial pressure of carbon dioxide in arterial blood is an important operator in the control of breathing, by actions on peripheral and central chemoreceptors. In experiments on man we must often assume that lung alveolar PCO2 equals arterial PCO2 and obtain estimates of the former derived from measurements in expired gas sampled at the mouth. This paper explores the potential errors of such estimates, which are magnified during exercise. We used a published model of the cardiopulmonary system to simulate various levels of exercise up to 300 W. We tested three methods of estimating mean alveolar PCO2 (PACO2) against the true value derived from a time average of the within-breath oscillation in steady-state exercise. We used both sinusoidal and square-wave ventilatory flow wave forms. Over the range 33-133 W end-tidal PCO2 (P(et)CO2) overestimated PACO2 progressively with increasing workload, by about 4 mmHg at 133 W with normal respiratory rate for that load. PCO2 by a graphical approximation technique (PgCO2; "graphical method") underestimated PACO2 by 1-2 mmHg. PCO2 from an experimentally obtained empirical equation (PnjCO2; "empirical method") overestimated PACO2 by 0.5-1.0 mmHg. Graphical and empirical methods were insensitive to alterations in cardiac output or respiratory rate. End-tidal PCO2 was markedly affected by respiratory rate during exercise, the overestimate of PACO2 increasing if respiratory rate was slowed. An increase in anatomical dead space with exercise tends to decrease the error in P(et)CO2 and increase the error in the graphical method. Changes in the proportion of each breath taken up by inspiration make no important difference, and changes in functional residual capacity, while important in principle, are too small to have any major effect on the estimates. Changes in overall alveolar ventilation which alter steady-state PACO2 over a range of 30-50 mmHg have no important effect. At heavy work loads (200-300 W), P(et)CO2 grossly overestimates by 6-9 mmHg. The graphical method progressively underestimates, by about 5 mmHg at 300 W. A simulated CO2 response (the relation between ventilation and increasing PCO2) performed at 100 W suggests that a response slope close to the true one can be obtained by using any of the three methods. The graphical method gave results closest to the true absolute values. Either graphical or empirical methods should be satisfactory for detecting experimentally produced changes in PACO2 during steady-state exercise, to make comparisons between different steady-state exercise loads, and to assess CO2 response in exercise.(ABSTRACT TRUNCATED AT 400 WORDS)


Coexistence and competition in HIV infections. In this paper we extend our explanation of a model for the dynamics of the interaction between HIV and the cells of the immune system (Nowak et al., 1990). We show that the Simpson index of viral diversity is a Lyapunov function for a simplified version of this model. We also present a more general mathematical characterization of the nature of the diversity threshold exhibited by the model, including for the first time heterogeneity in parameters like virus replication rate, cytopathicity and antigenicity. The more general diversity threshold condition includes the different contributions of strains with higher replication rates and cytopathicities or strains that are only weakly recognized by the immune system. This leads to some new insights and a more detailed understanding of why the viral diversity falls once the diversity threshold is exceeded.


Spatial patterns of cells in dividing epithelia. The spatial patterns of cell boundaries in a view of the apical surface of a dividing epithelium are explored by constructing a hypothetical cell pattern of an epithelium of dividing cells. The two elements specified in the hypothetical pattern are the orientation of division planes and the separation between the division planes in neighbouring cells. The orientations of division planes in one generation are all the same but are orthogonal to those in the preceding generation. The division-plane orientations follow in an orthogonal succession, as happens in early embryos. The division planes in neighbouring cells are offset. The contractions of division planes that would occur during cytokinesis distort existing boundaries creating various types of cell shapes. The patterns generated resemble cell patterns found in life. The hypothetical pattern is regenerative and shows how epithelial cell patterns where cells divide might arise. It has enabled the putative identification of sister cells and first cousins in the embryonic chick chorion.


Sensitivity analysis of a new model of carcinogenesis. A new simulation model of carcinogenesis is described which, in addition to the features of a standard clonal two-stage model (loss of both copies of a tumor suppressor gene by point mutations, cell division and cell death), includes a quantitative description of mitotic recombination, DNA repair, and cell to cell interactions in all stages. The model is implemented as a discrete event process. The results of a sensitivity analysis of the model are presented. The most sensitive parameters were found to be: the number of normal cells at risk, and the division rate, death rate and DNA repair efficiency for the intermediate stage cells. Accurate information about these parameters is important for a quantitative understanding of carcinogenesis. The sensitivity of the model to the number of normal cells indicates the importance of understanding the nature of the cells at risk, for example, stem cells vs. differentiated cells. The model can be used to assess the importance of chromosomal damage such as mitotic recombination and epigenetic mechanisms such as hyperplasia and cytotoxicity in the onset of malignant tumors.


Does frequency-dependent selection optimize fitness? In evolutionary biology, the axiom that natural selection tends ideally to maximize inclusive fitness of the individual or some other suitable quantity is often advanced (Cody, 1974; Maynard Smith, 1978; Krebs & McCleery, 1984; Houston et al., 1988). Moreover, the evolutionists generally distinguish two situations (Dawkins, 1980; Maynard Smith, 1982): one in which fitness is independent of the frequency of the phenotypes present in the population (frequency-independent selection), and one in which it does depend on this frequency (frequency-dependent selection). This led some authors such as Parker (1984), and more recently Parker & Maynard Smith (1990), to consider "a 2-speed optimization": frequency-independent selection should lead to a "simple optimum" at the end of the selective process, since all the individuals should have the same strategy and the mean fitness of the population should be maximized; frequency-dependent selection, formulated in terms of the theory of games, should lead to a "competitive optimum" even though the "evolutionary stable strategy" (or "ESS"; Maynard Smith & Price, 1973) characterizing the equilibrium "is not the strategy that maximizes fitness in a population sense" (Parker & Maynard Smith, 1990: 30). Our aim in this short communication is to criticize the concept of "competitive optimum" by Parker & Maynard Smith, as well as the general ability of natural selection to "maximize fitness", even in "phenotypic models" (Lloyd, 1977). These models, devoid of genetic constraints since each strategist is assumed to reproduce its own kind, are especially suitable for examining the ideal effect of natural selection.


Resource-dependent selection.

Resource-dependent selection. This paper presents a resource-dependent viability selection differential equation model of continuously reproducing diploid population with two alleles at one locus for a single limiting resource. This model assumes that the genotypic fitness is only a function of the limiting resource. The conditions that the interior equilibrium point of the system exists are that the heterozygote fitness is positive and the homozygote fitness is negative, or the heterozygote fitness is negative and the homozygote fitness is positive at the point. The sufficient and necessary conditions of locally asymptotical stability of the interior equilibrium point are that the heterozygote fitness is positive at the point, or the locally asymptotically stable equilibrium corresponds to the point at which the level of the limiting resource is locally minimized on the zero mean fitness curve, f = 0.


Threshold consensus methods for molecular sequences. We introduce a parameterized threshold consensus method (th chi) for molecular sequences which is based on a majority-rule voting principle. In contrast to other frequency-based methods, the th chi method uses a single criterion to return ambiguity codes of different lengths. We derive basic features of the method and establish that it returns at most two ambiguity codes at any position of the consensus sequence. We bound from below the size of the frequency gap that exists when the th chi method returns an ambiguity code. Using such properties, we compare the th chi method to other consensus methods for molecular sequences which are defined in terms of threshold or gap criteria.


Phase resetting and fixed-delay stimulation of a simple model of respiratory rhythm generation. In a previous study (Lewis et al., 1990), the response of the respiratory rhythm to a perturbing stimulus was investigated using two different stimulus protocols: phase resetting and fixed-delay stimulation. The first protocol consists of measuring the effects of perturbing an oscillator at different phases of the cycle on the duration of the perturbed cycle. The resulting phase response curves (PRCs) can be used to characterize the properties of the oscillator (Winfree, 1980). A second protocol, fixed-delay stimulation, involves perturbing an oscillator at a fixed latency from the onset of the cycle, repeated every n-th cycle. If a single stimulus produces an effect that lasts longer than a single cycle, complicated responses can be expected from fixed-delay stimulation (Lewis et al., 1987). A simple three-phase model for respiratory rhythm generation based on a hypothesis by Richter and coworkers (1982, 1983, 1986) was investigated in the context of these experimental studies. Phase resetting and fixed-delay stimulation protocols were simulated in the model. PRCs of the model resemble those obtained experimentally: a phase-dependent prolongation or shortening of the inspiratory phase depending on the stimulus magnitude, and a slight prolongation of the expiratory phase. Stimuli delivered to the model repetitively during successive inspiratory periods at a fixed-delay produced various combinations of shortened and prolonged cycles, similar to those observed in the experiments. However, the marked increases in cycle duration observed in the experiments during, as well as after, stimulation were not evident in the model. These comparisons suggest that (1) PRCs may not be an adequate way to evaluate certain models of rhythmogenesis, and (2) to improve the present simplified formulation of the three-phase model of the respiratory oscillator, time-varying stimulus dependent effects should be incorporated.


Analysis of vagally induced sinus arrhythmias. Vagal stimulation at precise times in successive cardiac cycles can elicit sinus arrhythmias. Two mechanisms have been identified that can, but do not necessarily, cause these vagally induced sinus arrhythmias. First, changes in cycle length elicited by a given concentration of acetylcholine (ACh) depend on the phase of the pacemaker cell action potential when the ACh binds to muscarinic receptors. Second, acetylcholinesterase degrades ACh rapidly enough for the mean concentration of ACh per cardiac cycle to vary from cycle to cycle. We used a mathematical model of the underlying cellular physiology, to examine whether these mechanisms are responsible for arrhythmogenesis. Computer simulation showed that both mechanisms contribute to the vagally induced sinus arrhythmias.


[Project for amending regulations regarding jobs prohibited to women]. Considering that the current legal regulations on jobs prohibited to women lack consistency, especially in relation to the criteria for including specific jobs into the prohibited category, and because the regulations fail to protect women satisfactorily from the harmful effects of occupational and environmental loads and exposures, preparation of new legal regulations on those matters has been attempted. Special stress has been put on specifying parameters which, when measured and compared with the suggested allowable values, should provide a basis for deciding whether a woman can be employed at a specified post. Separate criteria have been specified to determine jobs prohibited to women: a) irrespective of age, b) at reproductive age, c) during pregnancy and lactation. The irrespective-of-age restrictions result from lower average physical efficiency of women in relation to men, lower muscular strength and different psychical or biological characteristics. Lower allowable physical loads and lower maximum allowable weights of objects to be carried or moved by women have been specified. In specifying the restrictions for women at the reproductive age it has been assumed that, when determining the maximum allowable concentrations of chemicals at workplaces, effects of those chemicals on the reproducibility and health state of the off spring were taken into consideration. However, for chemicals which, according to the present knowledge, show genotoxic, teratogenic, or reproduction-disturbing effects, employers will be obliged to inform the reproductive-age female employees about the risk involved, as well as to take steps to reduce, as far as possible, below MAC the concentrations of those chemicals in the ambient air at workplaces. The restrictions in the employment of the pregnant and lactating women are intended to ensure conditions enabling correct development of pregnancy and safe growth of the fetus and, subsequently, of the neonate. The restrictions relate to: physical effort--as this has been proved to affect the course and the outcome of pregnancy (increased abortion risk, reduced duration of pregnancy, reduced neonate weight); exposure to carcinogens--as there is evidence that carcinogens display genotoxic properties and are capable of permeating the placenta: exposure to agents which can disturb the course of pregnancy and damage the fetus or unfavourably affect health condition of the offspring even if the MAC and MAI values are not exceeded; exposure to biologic agents, evidently harmful to the fetus and to the condition of health of the progeny.(ABSTRACT TRUNCATED AT 400 WORDS)


[Identification of potential carcinogenic dyes and intermediates on the basis of their genotoxicity]. 41 dyes, pigments and surface-active compounds were tested for mutagenic and genotoxic properties. It was found that 43% of the studied dyes of Polish make which belonged to the azo, triarylmethane and anthraquinone compounds were mutagenic or genotoxic. All the studied pigments and surface active compounds did not reveal potential carcinogenic activity except for NNO Dyspergator whose possible genotoxic activity needs confirmation in further study.


[Biological evaluation of Indian and Chinese talc aggressiveness]. In order to evaluate biologically the action of two different kinds of talc pulmonary and hemolytic tests were applied and pathomorphological examination carried out on animals. The study was performed on 120 rats within the 6th and 9th months periods. The talcs used in the experiment did not indicate any fibrogenic properties. Morphologic examination did not show any differences in the pathogenetic activity between the Indian and Chinese talcs Inflammatory changes within the lungs and bronchi, pulmonary emphysema and increased levels of fibrosis indices in biochemical examinations have drawn our attention to problems connected with longterm exposure to talc dust.


[Effect of carbon disulphide on platelet aggregation in women]. This study was performed in 50 female subjects aged 20-50 years. The women in group II were exposed to 10-14 mg/m3 carbon disulphide. Platelet aggregation was determined according to Born, the concentration of cholesterol and triglycerides with the enzymic method and LDL-cholesterol and HDL-cholesterol by precipitation. It was found that women exposed to CS2 had a significantly higher (p < 0.01) concentration of LDL-Ch. Furthermore, these women demonstrated very active platelet aggregation, reflected mainly by decreased aggregation threshold due to ADP influence.


[application of electromyography (EMG) in recognition of lumbo-sacral back pain]. Power spectra of electromyograms (EMG) of back muscles in the lumbo-sacral area were compared in two groups of subjects. In the first one EMGs were registered in 49 young, healthy, males working in standing posture. The recordings were carried out at rest, after application of a 20 kg load and at the onset of pain. In the second group 31 subjects of both sexes and different age, suffering from intense back pain of various etiology, were investigated and compared with a group of 15 healthy persons. In the first group the power level increased after the loading, and in 42 subjects it showed further rise when the pain appeared. In the second group the power level at the range of 25 to 400 Hz, at rest, was significantly higher in the back pain patients than in healthy subjects. The results are discussed from the point of view of their applicability for the diagnosis of back pain.


[Activity of selected enzymes in urine of workers from the repair brigades in chemical plants "Organika-Azot" in Jaworz]. In 45 repair service workers of a chemical plant producing pesticides the serum concentration of creatinine and uric acid as well as the concentration of proteins and the activity of alkaline phosphatase, a alanine and aspartate aminotransferases, lactic dehydrogenase, and N-acetyl-beta- glucosaminidase in urine were determined. As compared to 31 healthy controls, the serum creatinine concentration was significantly higher (in any case the creatinine and uric acid concentration did not exceed the upper normal limit), the urine lactic dehydrogenase and N-acetyl-beta- glucosaminidase activity, factored by creatinine, was significantly elevated. The results of the examinations point to a discrete lesion of the kidneys.


[Assessment of the degree of air pollution at the work place in coke batteries of polycyclic aromatic hydrocarbons]. The paper discusses the method and results of the assessment of PAHs in airborne particular matter collected at high-level exposure sites in the coke plant. Qualitative analysis of PAHs fraction was made and the content of the most prevalent PAHs was determined.


[Musculo-skeletal system diseases in dentists--an analysis of consultation cases referred to the outpatient department of occupational diseases]. During 1984-1991, 188 dentists referred for consultation to the Outpatient Department of Occupational Diseases, Institute of Occupational Medicine in connection with suspected occupational disease of musculo-skeletal system were examined. In total, 122 (64.9%) cases of the occupational diseases were diagnosed, among which chronic inflammation of humeral bone epicondyles (61.5%) and periarticular shoulder inflammation (25.4%) dominated. Claims associated with spondylosis and discopathies were decided to be rejected, as those changes are frequent in the general population and according to the legal regulations currently in force, are not included among occupational diseases resulting from the occupational work.


[Prospective examinations concerning the effect of exposure to aromatic hydrocarbons on health status]. The purpose of the study was to evaluate the general and toxicological status of footwear factory workers exposed to toluene, benzene and trace amounts of chromium. The subjects were 80 persons who worked with the glue, and were professionally exposed to aromatic hydrocarbons such as toluene and benzene AT amounts not exceeding the TLVs. The mean age of the subjects was 46.89 years and the mean period of work 20.26 years. Complete internal and neurological examinations were carried out. The following parameters were determined: hematocrit, hemoglobin, erythrocytes, leukocytes, platelets, reticulocytes, chromium, copper, zinc in serum and hippuric acid in urine (in 30 persons). In the examined group no changes in the leukocyte system were found. Two women had a lower hemoglobin level and erythrocyte count. In three persons thrombocytopenia was observed (3.75%). The mean metal levels in serum were within normal values. Only in 4 persons (5.0%) elevated levels of phenol in urine were found which indicated exposure to benzene. In 30 subjects (18 women and 12 men) (most exposed to toluene) the hippuric acid level in urine was examined. It was found to range from 130 mg/l to 2080 mg/l. In the control group not exposed to either of the solvents the level of hippuric acid in urine varied from 190 to 330 mg/l. There was little effect of aromatic hydrocarbons on hematopoiesis. The increased absorption of benzene or toluene found in the examined persons would indicate a necessity for biological monitoring of this group.


[Opinions on health status and ability to work of persons with a history of subarachnoid hemorrhage]. This paper is based on the author's own experience obtained during her activities at the Outpatient Department of Occupational Diseases, Institute of Occupational Medicine, Lódź, Poland, as well as on the literature data relating to the methods of evaluating health condition in people with subarachnoid hemorrhage history. Factors affecting prognosis and their effect on the possibility of taking up occupational job have discussed. Jobs contraindicated for people with subarachnoid hemorrhage history have been specified.


[Current state of studies on the effect of organic solvents on the nervous system]. Current problems of clinical neurotoxicology, particularly the effect of organic solvents on the nervous system functions have been discussed. A review of the literature on the neurophysiological methods for use in toxicology been presented. Special attention has been paid the usefulness of evoked potential testing for detecting early changes in the nervous system caused by action of neurotoxic chemicals.


[Lead in the 90's: "new" rules for the "oldest" of environmental toxins?]. Present lead (Pb) exposures in working and general environments are undoubtedly lower than several decades ago so that mean blood lead levels (PbB) in the main industrial sectors using lead, such as ceramics and accumulator manufacturing, are now about 30 micrograms/100 ml and in the general population between 10 and 15 micrograms/100 ml and in some situations decidedly below 10 micrograms/100 ml. At the same time increasingly more accurate and sometimes original knowledge has been acquired on the effects of low-level Pb exposure, especially the effects on the nervous system, the cardiovascular system, the endocrine and immune systems, on heme-containing enzymes, and on the reproductive system. The question of a possible mutagenic and carcinogenic action of Pb is, however, still open. It is also clear that many of the above effects were observed for PbB levels considerably below the current limit levels. For certain effects, like those on heme, the central nervous system, and blood pressure, it has not been possible to establish a threshold below which they will not occur. With effects that are so different in nature and degree and with changed exposure conditions, a critical re-examination of the assumptions on which current knowledge and prevention models are based appeared appropriate. In particular, action models are proposed for discussion which, besides the priority aim of restricting use of Pb to those situations where there is no alternative and to those working environments which guarantee compliance with modern regulations and prevention procedures, have two differentiated objectives: the first is to eliminate the dose-dependent effects occurring at exposures higher than those in the general population; the second is to reduce to the lowest possible level the effects with no threshold or with as yet unestablished threshold, by means of actions in favour not only of occupationally exposed groups but also the general population.


[Metabolic polymorphisms and the cancer risk: the evaluation of epidemiological studies]. Genetic modulation of environmental exposures associated with common malignancies is an attractive mechanism to explain differential susceptibility to tobacco or occupation-related carcinogens in the population. The paper reviews the evidence for an association between three genetically based metabolic polymorphisms (N-acetyltransferase, Debrisoquine, hydroxylase, aryl hydrocarbon hydroxylase), which have been implicated in the modulation of lung or bladder cancer risks. Fair to good support emerged for both an association of the acetylation phenotype with occupationally related bladder cancer and for an association of the debrisoquine metabolic phenotype with lung cancer, although in neither case was the evidence completely convincing. Epidemiologic evidence for an association between aryl hydrocarbon hydroxylase and lung cancer is presently problematic because of the difficulties in the assay and subsequent confounding factors.


Increased lead absorption in children living in an area with high concentration of ceramic workshops. Children who live in contaminated areas or whose cohabitants are occupationally exposed to lead are at a higher risk of lead absorption. The present study examined the blood lead levels of 539 nursery and primary school children living in three towns in the Umbria region (central Italy): Deruta, Corciano and Perugia. Deruta is a small town with a high number of ceramic workshops; Corciano is a mainly agricultural centre; Perugia is the largest town in Umbria. The lead concentrations of house dust, soil, air and water ducts of Deruta and Corciano were also examined. The blood lead levels were significantly increased in children in Deruta (9.7 S.D. = 3.6 micrograms/dL, p < 0.05) and Perugia (9.6 S.D. = 4.0 micrograms/dL, p < 0.05) compared to Corciano (8.3 S.D. = 1.9 micrograms/dL). In Deruta the blood lead levels were higher in children whose cohabitants worked in small ceramic factories or workshops near or in the homes (10.7 S.D. = 4.1 vs 9.0 S.D. = 3.0 micrograms/dL, p < 0.05). The mean concentration of lead in the house dust in Deruta was higher than in Corciano (2.8 S.D. = 2.5 vs 0.8 S.D. = 3.8 micrograms/m2, p < 0.01); the highest values were found in the house dust of the homes of children whose cohabitants worked in small ceramic factories either near or in the same building. There was no significant difference between the concentrations of lead in street dust or tap water of Deruta and Corciano. We conclude that the production of handworked ceramics could lead to an increased risk of lead absorption in children, particularly those who live with workers from this sector.


[The efficacy of personal prevention measures in controlling the exposure to metals of welders]. Biological monitoring of welders employed in a power plant showed urinary nickel levels largely exceeding the reference values (Ni-U welders mean = 43.2, S.D. = 22.1 micrograms/24 h; Ni-U reference values mean = 2.7, S.D. = 1.4 micrograms/24 h). Subsequently urinary excretion levels of other metals (Cr, Zn, Fe, Mn, Cu, Al, Pb) were measured for a more complete assessment of occupational exposure of these subjects; only aluminum and lead were found to slightly exceed the reference values and correlate with urinary nickel levels. As a consequence of these results, some adjustments in personal prevention measures were introduced at the workplace; the subsequent biological monitoring checks showed a progressive reduction in urinary nickel excretion levels over time in all welders.


[The exposure to tobacco smoke of the employees of a telephone company]. Smoking habits were studied in a group of employees of a telephone company. The smokers were 34% of the subjects interviewed. The non-smokers said that they were bothered by other people smoking everywhere and also to a considerable extent at the workplace. Differences between smokers and non-smokers and between exposed and non-exposed non-smokers were studied by measuring expired CO and urinary cotinine. An expired CO concentration of 10 ppm discriminated between smokers and non-smokers. A mean urinary cotinine concentration of about 16 ng/mg was found in the exposed non-smokers, corresponding to the direct smoking of 1/10 of a cigarette per day. The search for the metabolic phenotype of destromethorphane, which was taken as an indicator of susceptibility to contract lung cancer due to IPA, showed that there were no differences between smokers and non-smokers since the rapid metabolizers, and therefore subjects potentially exposed to risk of lung cancer due to tobacco smoke, prevailed in both groups.


[The blood calcium error induced by oral calcium loading: study of the homeostatic compensation mechanism]. The oral calcium load test, originally proposed for evaluating the intestinal calcium absorption and the renal calcium leak triggers some endocrine and metabolic responses addressed to correct the "calcemic error" induced by the load. Besides the increased plasma calcium there are: plasma PTH drop, increment in the urinary calcium excretion and in the threshold of tubular phosphate reabsorption. These responses have been measured and reciprocally correlated in 9 young adults at different times after the oral calcium load. The responses can be assessed with high precision in clinical practice and are in agreement with the known physiological models. The oral calcium load test is proposed as a tool for studying in the osteopenic population in the individual's capacity of correcting the calcemic error induced by the load.


[Reduction in parathormone secretion after oral calcium loading in osteoporotic adults]. The purpose of this study was to verify if a decreased inhibition of PTH secretion (abnormal suppressibility) in response to physiological increment of plasma calcium is present in patients with osteoporosis. The plasma concentration curve of intact PTH 1-84 following an oral calcium load (Pak) has been calculated in a selected population of 38 osteopenic patients (16 males and 22 females) and in a control group of 9 young healthy adults. All the patients included in this study a) had no past or present diseases and medications of potential influence on calcium homeostasis, b) showed a maximal calcemic response to the oral calcium load equal to that of the control group. PTH suppressibility was significantly smaller in the osteoporotic patients (-42% in males and -32% in females) than in the control group (-76%). This abnormal suppressibility of PTH is independent on sex and, in the females, also on postmenopausal estrogen deficiency. These results support the hypothesis that osteoporosis is associated to an altered secretory response of parathyroid glands maybe due to reduced sensitivity of the parathyroid cells to extracellular calcium.


[Microvascular complications in diabetes mellitus. Pathogenetic aspects]. Chronic microvascular complications are important causes of mortality and morbidity in people with diabetes mellitus. After 10 years of disease, nearly 70% of diabetics are affected by retinopathy and about 40% by nephropathy. Genetic factors have a great influence on the development of diabetic microvascular complications, as pointed out by their association with HLA system and Na/Li countertransport, but epidemiological and experimental studies show that the greater role is played by the metabolic milieu. Protein glycation, sorbitol pathway and lipid abnormalities can be responsible for early and fast development of the microvascular complications of diabetes mellitus.


[Osteocalcin and hyperthyroidism].

[Osteocalcin and hyperthyroidism]. Osteoporosis may be induced by hyperthyroidism through an increase of bone turnover, because bone resorption exceeds formation in this condition. Also therapy with 1-thyroxine, especially by TSH-suppressive doses, may induce a reduction in bone mineral content. Circulating osteocalcin (sBGP) significantly increases both in endogenous and exogenous hyperthyroxinemia and is considered a reliable non invasive marker of bone turnover. In this study an extra-increase of sBGP in hyperthyroid post-menopausal women towards pre-menopausal is reported, the persistence of high sBGP levels in patients affected by any type of hyperthyroidism after four months of therapy and a positive relationship with thyroid hormones (fT4). Therefore monitoring of this serum marker may be suggested also in patient chronically treated with 1-thyroxine to avoid, if possible, overzealous therapy.


[Randomized comparative study using carbocalcitonin i.m. vs carbocalcitonin nasal spray vs ipriflavone x os in the treatment of post-menopausal osteoporosis]. A comparative study of 90 post-menopausal osteoporotic women, has been carried out. The patients were divided in 3 homogeneous groups. According to 3 different schemes: Group A = 30 patients received carbocalcitonin i.m. 40 UMRC/day/1 month and 40 UMRC/alternating days/2 months followed by 1 month of wash-out for 11 months; Group B = 30 patients received carbolcitonin nasal-spray 80 UMRC/day/1 month and 80 UMRC/alternating day/2 months followed by 1 month of wash-out for 11 months; Group C = 30 patients received ipriflavone x os (600 mg/day/3 months followed by 1 month of wash-out for 3 times). BMC significantly was increased in all Groups after 7 and 11 months. In conclusion, carbocalcitonin and ipriflavone seem to show a similar improving densitometric effect in post-menopausal osteoporosis.


[The TRH test in Turner syndrome].

[The TRH test in Turner syndrome]. In order to evaluate the functionality of the hypothalamic-hypophyseal-thyroid axis in Turner's syndrome (TS), 27 subjects, aged between 5.1 and 16.1 years old, were studied, 14 of whom were karyotype 45,XO and 13 affected by mosaicism. The TRH test (200 mcg i.v.) was performed in all subjects using a single bolus. TRH titers were assayed in serum samples collected at 0, 15, 30, 60 and 90 minutes, and anti-microsome and anti-thyroglobulin, T4 and T3, were assayed in the basal sample; the latter were also assayed in the blood sample collected at 120 minutes. These results were compared with those obtained using the same test in a group of age- and sex-matched controls. Anti-thyroid antibodies and basal levels of T3 and T4 were within the norm in 26 subjects; a high basal value of TSH was only found in one patient with chromosomic mosaicism with an elevated response to TRH and a high titer of anti-microsomic antibodies. Apart from this no statistically significant differences were found in patients compared to control subjects in relation to TSH values at all stages of the test and between the two groups of TS; no significant results were found in the comparison between the areas below the curves (AUC). On the basis of these results the Authors conclude that it is not possible to reveal alterations in thyroid function attributable to hypothalamic and hypophyseal anomalies in this group of patients either with karyotype 45,XO and mosaicism.


[The role of Doppler echocardiography in assessing left ventricular diastolic function. Case histories]. The aim of this study was to provide a further contribution to evaluate the alterations induced by age on a number of simple Doppler indexes of left ventricular diastolic function. A population of 48 healthy subjects aged between 15 and 78 years old was examined using pulsed Doppler analysis of the left ventricular refilling flow. Linear regression analysis revealed a significant inverse correlation between age and peak speed during rapid refilling (r = -0.80); between age and the ratio between peak speed during rapid refilling and peak during atrial systole (r = -0.92); between age and deceleration time of peak E wave speed, although on the contrary the peak speed of diastolic refilling flow during the atrial systole (r = 0.81) increased significantly with age. Variance analysis showed that indexes of left ventricular diastolic function and age continued on the contrary to be significant n the population as a whole and in both sexes. From these findings it is clear that in the different age groups (15-29, 30-49, 50-65, and over 65) the peak speed of rapid refilling flow was significantly lower in over-65-year-olds than in elderly, middle-aged and young subjects (55 +/- 0.8, 60 +/- 0.5, 65 +/- 0.7 and 75 +/- 0.6 respectively; p < 0.001). The ratio between the peak speed of rapid refilling and that during the atrial systole was lower in over-65-year-olds compared to elderly subjects, middle-aged subjects or the youngest age group (0.94 +/- 0.09, 1.05 +/- 0.13, 1.96 +/- 0.21 and 2.68 +/- 0.50 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)