The relationship between quality of infant-mother attachment and infant competence in initial encounters with peers.

18-month-old infants and their mothers were observed in the Ainsworth strange situation (SS) in order that security of attachment might be assessed. Infant dyads were created for observation in unstructured peer interaction according to their SS classification (security of attachment). Focus was on the subgroups within the securely attached (B) category. Results indicated a relationship between quality of infant-mother attachment and infant peer competence. The B1 and B2 infants engaged in more frequent and more sophisticated interaction with peers than did the B3 and B4 infants, who intensely sought proximity and contact with their mothers in the peer session just as in the SS. The B1 and B2 infants engaged in more distal interaction with their mothers and were more sociable with the peers' mothers and with the stranger in the SS. Implications of individual differences in quality of attachment for the development of social competence and social relationships are discussed.


Peer interaction in a structured communication task: comparisons of normal and hyperactive boys and of methylphenidate (Ritalin) and placebo effects.

Peer communication patterns were assessed as school-aged boys participated in a dyadic referential communication task. The responses of comparison boys were compared to those of hyperactive boys on methylphenidate (Ritalin) and on placebo in a double-blind crossover design. 2 separate systems for assessing communication were developed, a qualitative system designed to capture the "flavor" of interaction and a quantitative system focused on specific types of communicative content. Task products and completion times were also scored. The results suggest that hyperactive children, regardless of medication status, are less likely than comparison peers to (a) modulate ongoing or habitual behavior patterns in response to externally imposed shifts in role-appropriate behaviors; (b) maintain consistent, uninterrupted goal orientation; and (c) respond to subtle social learning opportunities. In this situation, methylphenidate appeared to have a greater impact on behavioral style than on competence, decreasing perceived intensity without influencing efficiency. A mild medication-induced dysphoria was also documented. Directions for future research and the need for caution in clinical interpretation are discussed.


Concept acquisition in the human infant.

The ability of 18-, 24-, and 30-week-old infants to learn conceptual categories regarding adult female faces was examined using a habituation paradigm. Little evidence for conceptual categorization occurred at 18 or 24 weeks, but at 30 weeks infants learned to respond to "a specific female face regardless of orientation" and to "female faces in general."


Matching behavior in the young infant.

Infants as young as 2--6 weeks have been reported to exhibit matching behavior in response to seeing an adult model tongue protrusion and certain other acts. Matching behavior to the tongue model declines by 12 weeks. The present study was designed to investigate whether (1) this matching behavior represents selective imitation or a released response that can be elicited by a broad but delimited class of incentive stimuli and (2) stimulation of tongue protrusion enhances the response and delays its decline. 24 infants were observed at 6, 10, and 14 weeks. A moving pen and ball were as effective as the tongue model in eliciting tongue protrusion at 6 weeks, while a dangling ring elicited as much hand opening and closing as the hand model at 14 weeks. After the 6-week visit, 12 of the infants were exposed to the tongue model daily. This intervention delayed the decline of matching behavior to the tongue model at 14 weeks. Also, experimental infants responded selectively to the tongue model, while the pen continued to be an effective releaser of tongue protrusions among controls.


Newborn infants orient to sounds.

In 2 experiments, the majority of 21 newborn infants who were maintained in an alert state consistently turned their heads toward a continuous sound source presented 90 degrees from midline. For most infants this orientation response was rather slow, taking median latencies of 2.5 sec to begin and 5.5 sec to end. The most important factors in producing this impressive response seem to be the method of holding the infants during testing and the nature of the auditory stimulus.


Crossing the midline: limits of early eye-hand behavior.

The development of the ability to extend the hand across the body midline to contact a visually presented object was examined in 48 normal, full-term, 9--20-week infants. One of the infant's arms was restrained while the behavior of the contralateral, unrestrained arm was observed. Results indicate that infants can first contact objects placed in front of the ipsilateral shoulder, then at the body midline, and later in front of the contralateral shoulder. Between 9 and 17 weeks, success at contacting objects at the midline progressed from 33% to 93%. During this interval, the success in contacting objects presented in front of the contralateral shoulder increased from 0% to 71%. By 18--20 weeks, all infants contacted objects in all three positions. These findings indicate that visually directed hand extension and reaching skills progress from the ipsilateral to include the bilateral and later the contralateral domains. The results are considered in regard to the development of bilateral coordination and complementarity.


Smooth-pursuit eye movements in the newborn infant.

The capacity of newborn infants to smooth-pursuit eye movements in single-target tracking and in optokinetic nystagmus to a moving striped field was examined utilizing DC electrooculography. Smooth-pursuit movements were observed in all infants who were alert during testing, but they occupied less than 15% of viewing time during single-target tracking. The velocity of smooth-pursuit segments in single-target tracking increased linearly to a target velocity of 19 degrees/sec and deteriorated rapidly at faster speeds. No smooth pursuit occurred above 32 degrees/sec in single-target tracking. By contrast, optokinetic nystagmus was observed at all field velocities to 40 degrees/sec, but the speed of the mean slow component increased linearly to 25 degrees/sec and diminished above that field velocity. Infant optokinetic nystagmus differed strikingly from that of adults in that tonic ocular deviation was in the direction of field movement rather than away from it. This feature of neonatal optokinetic nystagmus is consistent with deficient foveal function and suggests that the relatively poor smooth-pursuit performance of newborns may be related to foveal immaturity.


Interference of time-related and unrelated cues with duration comparisons of young children: analysis of Piaget's formulation of the relation of time and speed.

The analysis of the relation of time and speed led Piaget to conclude that the time-speed confusion characterizing the intuitive stage undergoes development. He claimed that in the first stage, a child comparing the duration of two moving bodies attributes longer duration to the faster body, whereas in the second stage, he attributes longer duration to the slower body. It is proposed here that time-speed confusion is mediated simply by "more is more," and hence, as long as the child continues to confuse time with speed, he believes "faster" implies longer duration. Moreover, this confusion should not differ either in form or extent from the confusion of time and many other arbitrary quantitative dimensions (e.g., intensity of light). 72 children, 4-7 years old, compared duration differing either on speed or on intensity of light. As predicted, the tasks did not differ on performance level or on error types. Moreover, the performance on both tasks was consistent with the predictions of a facet model pertaining to analysis of time problems. Confusion dissipated with age and was similar for boys and girls.


The role of frames of reference in the development of responsiveness to shading information.

The use of frames of reference in interpreting shading information in pictures was studied with children from 3 to 8 years of age. After learning to discriminate tactually between a convexity and a concavity, the subjects were presented a photograph of the convexity and the concavity in which the only information for differential shape was provided by the relationship between the orientation of the shading on the shapes and the frames of reference. By changing the position of the subject's head, rotating the display, and changing the location of the source of illumination, the relevance of egocentric, environmental, and lighting-specified frames of reference was manipulated. Children in this age range were found to be sensitive to shading information for depth, both when that information was specified by only a single frame of reference and when all three frames of reference were relevant. Differences in the responsiveness to individual frames of reference were found: the egocentric (head-retina) frame of reference was most effective, followed by the environmental reference frame, and finally by the frame of reference based on the location of the light source in the space surrounding the photograph. Responsiveness to the environmental and lighting-based frames of reference increased with age, while responsiveness to the egocentric frame of reference was high for all age groups and did not increase with age.


Configuration and position encoding in children.

2 experiments were carried out to clarify the process by which children encode briefly presented spatial positions. The task in both experiments was judging whether a test dot occupied the same position on a card as any 1 of a number of dots which had been presented tachistoscopically. Subjects were first, third, and fifth graders. In the first experiment, performance improved with grade level for stimulus arrays composed of more than 1 dot. The finding contrasts with an earlier report of only minimal developmental change in position encoding, but the procedures of the earlier study appear to have permitted a confounding of position and configural encoding. In the second experiment, position encoding was found to improve with increasing pattern goodness at all age levels. The finding attests to a powerful influence of pattern information on the perceptual system and further suggests that position information is encoded within configural information.


Neonatal respiratory instability and infant development.

This study examines the relationships between neonatal sleep respiratory instability and infant development. A group of 122 full-term healthy infants was observed during a nap within the first and fourth weeks of life. During each nap, a continuous polygraphic recording was obtained of respiratory activity and extraocular movements. The relative frequency and average duration of apneic pauses (greater than or equal to 2 sec) in each testing session for an infant were employed to calculate a measure of respiratory instability (PSA4) previously found to be related to the occurrence of prolonged sleep apnea. 28 of the infants in this study were maintained at home on apnea monitors. The Bayley Scales of Infant Development were administered to each infant at approximately 9 months of age. Comparisons of infants with high versus low PSA4 values and of monitored versus unmonitored infants were not strongly distorted by imbalances in birth weight, sex, race, birth order, method of feeding, Sudden Infant Death Syndrome (SIDS) sibship, parental education, age at developmental assessment, and developmental tester. Those with increased respiratory instability (PSA4 greater than or equal to -0.04) within the first week of life averaged significantly lower in mental and psychomotor development. Utilization of home apnea monitors was not significantly associated with developmental scores.


The temporal relationship between infant heart rate acceleration and crying in an aversive situation.

The temporal relationship between heart rate (HR) acceleration and crying was examined in 16 8-16-month-old infants. Consistently, the HR acceleration began well before the onset of crying, suggesting that such acceleration is not merely a by-product of crying. The accelerations observed were above and beyond a return to baseline following orienting. The crying itself validates the association between these instances of HR acceleration and negative effect.


Serial habituation or regression to the mean?

The serial habituation hypothesis states that the order that infants fixate and habituate to component features of a complex form is determined by the salience of those features. Infants' fixation of the most salient feature of a complex form is reduced after exposure to that complex form, supporting the serial habituation hypothesis. Regression to the mean can also explain this result. In the present study, 4-month-olds were either presented with a complex form containing the relevant feature, or they were presented with another complex form lacking that feature. If the reduction in fixation to the most salient feature is due to the presentation of the complex form, then a reduction in fixation should only be observed in the condition in which the complex form containing that feature was presented. A reduction was observed in both conditions supporting a regression to the mean interpretation of the data.


Matching of auditory-visual and temporal-spatial information by seven- and nine-year-old children.

Techniques of presenting information temporally in the auditory and visual modalities and spatially in the visual modality were used to assess information processing in 7- and 9-year-old children. The results of the study were interpreted as contradictory to the view that modalities are specialized for the processing of distinct forms of information. Viewed developmentally with related literature, however, the study also suggests that some specialization of modalities may be found in the preschool years, with a school-age shift to nonspecialization.


The development of cognitive maps of large- and small-scale spaces.

Kindergartners, second, and fifth graders made repeated trips through a large- or small-scale model town, and then constructed from memory the layout of buildings in either a large- or small-scale space. Accuracy of construction increased as a function of developmental level and repeated trips through the town. Children's constructions were most accurate when they were tested in the same-scale environment as that in which they developed their spatial knowledge; accuracy was impaired significantly only when children were exposed to a small space and then reconstructed in a large space. Results were interpreted in terms of a "competence-load trade-off."


Doctor or nurse: children's perception of sex typed occupations.

128 children between ages of 5 and 6 years were shown 4 films depicting all possible combinations of female and male physicians and nurses. Results showed that when confronted with counter-stereotypical occupational portrayals, children were likely to relabel them into the typical instance of the male physician and the female nurse. There was a stronger tendency for the subjects to relabel the male nurse than to relabel the female physician. The children's relabeling of the roles presented was not due to inattention to the stimulus materials (videotapes). Neither sex, nor age, nor the number of physician visits in the last year were related to the frequency of relabeling. Maternal employment and exposure to real male nurses were related to correct identification of the male nurse and the female physician. The results suggest that the relabeling and its asymmetric character may be due to the differential exposure of children to female physicians and male nurses.


Genetic microsurgery by laser: establishment of a clonal population of rat kangaroo cells (PTK2) with a directed deficiency in a chromosomal nucleolar organizer.

An ultraviolet laser beam was focused to a submicron spot on one of the nucleolar organizer regions of mitotic chromosomes of rat kangaroo cells in tissue culture. The daughter cells were isolated and cloned into a viable population that maintained the directed nucleolar deficiency. It is concluded that the laser can be used to delete preselected genetic regions and the genetic deletion is maintained as a heritable deficiency in subsequent daughter cells.


Difference between diploid and aneuploid Chinese hamster cells in replication at mid-S-phase.

Following partial synchronization of the heteroploid Chinese hamster cell line V-79 and of normal diploid lung fibroblasts of the Chinese hamster in culture, their DNA replication during S-phase aws compared by means of a BrdU-incorporation/thymidine pulse technique and Hoechst-Giemsa differential staining of metaphase chromosomes. This comparison indirectly shows the S-phase of the heteroploid cells of V-79 to be 2 h shorter than the diploid cell S-phase. When the thymidine pulse is applied to diploid lung fibroblasts at mid-S-phase, differential staining colours metaphase chromosomes a pale blue. Performing the corresponding experiment with V-79 cells, neither a pale blue nor dark red staining is obtained, but rather an intermediate shade, showing prominently dark staining regions in parts. The pause in DNA synthesis observed at mid-S-phase of the diploid Chinese hamster lung fibroblasts seems to be omitted at mid-S-phase of the V-79 cells.


Internuclear control of DNA synthesis in exconjugant cells of Paramecium caudatum.

An exconjugant cell of Paramecium caudatum has two kinds of macronuclei, fragmented prezygotic macronuclei and postzygotic new macronuclei (anlagen). Although the DNA synthesis in the fragmented prezygotic macronucleus continues until the third cell cycle after conjugation, selective suppression of the DNA synthesis in the prezygotic macronucleus takes place at the fourth cell cycle. The inhibition of DNA synthesis in prezygotic fragmented macronuclei is due to the presence of a postzygotic macronucleus (anlage) in the same cytoplasm because the inhibition does not occur when the postzygotic macronucleus (anlage) is removed by micromanipulation during the third or fourth cell cycle. Well-developed postzygotic macronuclei (anlagen) with full ability to divide have the ability to depress the DNA synthesis of prezygotic macronuclear fragments. The suppression of DNA synthesis in prezygotic macronuclear fragments seems to be irreversible. Competition for the limited amount of DNA precursors also plays an important role in the onset of the selective suppression of the DNA synthesis.


Quantitative determination of amplified rDNA and its distribution during oogenesis in Xenopus laevis.

The number of extra-chromosomal nucleoli and their rDNA content were determined during oogenesis in Xenopus laevis. The highly variable number of nucleoli (500 to 2,500) in oocytes of the same stage and from the same female or of different stages or from different females is not a measure of the extent of amplification. In all oocytes examined, a inversely proportional relation was found between the number of nucleoli in an oocyte and their mean rDNA content. These results indicate that there is no variation of the rDNA content of oocytes during oogenesis nor between oocytes of different females. The varying nucleolar numbers found in oocytes result thus from fusion and fission of pre-existing nucleoli. The determination of the rDNA content, in absolute units (35 pg), after amplification which occurs at the beginning of oogenesis, makes it possible to calculate the rDNA content of one nucleolus. This ranged from 0.7.10(-2) pg to 15.10(-2) pg, corresponding to about 500--11,000 cistrons of rDNA. No distinct size classes between these two extremes were observed.


Visualization of Transcription in early mouse embryos.

Transcriptional activity during early mammalian embryogenesis was examined in 2 cell, 4--8 cell and late morula/early blastocyst mouse embryos. Zona pellucida-free embryos were obtained after pronase digestion followed by a PMSF wash to inhibit proteolytic activity. The embryos were then lysed with NP40 detergent and spread for electron microscopy according to Miller and Bakken (1972). pre-mRNA transcription was observed at all stages. Comparison of growing RNP chain lengths revealed statistically significant differences in the distribution of shorter fibrils between the successive developmental stages examined. The number of shorter fibrils was lower in the 4--8 cell stage than in either of the two other stages. Transcription complexes of ribosomal type were detected only in 4--8 cell and morula/blastocyst embryos. Structures resembling replication loops were observed within chromatin from all stages. Similar loop-like structures as well as individually transcribed RNP fibrils were also occasionally found on fibres emerging from mitotic chromosomes. The results are discussed in the context of recent findings concerning genetic expression in early mouse embryos.


Expermental hybridization within the genus Triturus (Urodela: Salamandridae). III. Evidence for crossing-over, true chiasmata and chomosomal homologies in the spermatogenesis of F1 species hybrids, T. cristatus carnifex female X T. marmoratus male.

Spermatogenesis in the F1 hybrid (2n=24=12 female + 12 male) between the closely related newt species T. cristatus carnifex and T. marmoratus was apparently normal up to pachytene. Many unpaired chromosomes were present at diplotene and a typical diakinesis was lacking. Primary spermatocytes at meta- and meta-anaphase contained up to 12 regular intergenomal bivalents and a corresponding number of univalents when less then 12 II. Most chiasmata were terminal or subterminal, some intercalary. Chiasmata between corresponding heterospecific chromosomes can be reported as true: real crossing over has taken place, proving the presence of primary chromosomal homologies between the 2 sets of the parental species. Evidence for recombination is based on the segregation of particular markers (i.e., subterminal C-bands and NORs) observed in certain chromosomes at metaphase II. One chromatid of single chromosomes can show the T. cristatus "pheno-type" and the other the T. marmoratus phenotype". A few primary spermatocytes contain a certain number of irregular associations (intragenomal or intrahaploid bivalents, irregular intergenomal bivalents, chromosome multivalents) joined by chiasmata which can be defined as anomalous. Other abnormalities concern the occurrence of interlocked bivalents which occasionally show an anomalous exchange between heterologous chromatids. Cytogenetic criteria useful to evaluate the taxonomic relationships between different species have been discussed as well as some possible trends in chromosome evolution and speciation within the genus Triturus.


Prognosis of Crohn's disease with onset in childhood or adolescence.

A long-term follow-up study of 522 patients (1955-1974) with onset of Crohn's disease under age 21 was conducted. Follow-up information was obtained for 513 (98.4%) of the patients. The mean follow-up for the entire series was 7.7 years with a greater than five-year follow-up for 67% of patients. Nearly 60% of the patients were ages 16--20 at onset of disease. Operation had been performed for 69% of the patients and 13 (2.4%) had died. Among the survivors 67% considered themselves to be in suboptimal health. Although clinical features and complications varied considerably with anatomic disease location, colonic disease generally caused more disability than small intestine location of disease. Age at onset did not correlate with clinical severity except for presence of growth retardation. Thus, this long-term follow-up study demonstrated the chronic nature of Crohn's disease with onset under age 21. It also emphasized that the disease more commonly affected adolescents than children, that operation was required in about two thirds of the patients, and that, while mortality was low, morbidity from the disease continued for many years.


A controlled study comparing cimetidine treatment to an intensive antacid regimen in the therapy of uncomplicated duodenal ulcer.

The authors report the results of a randomized study in which comparison was made between two different kinds of treatment in patients affected by uncomplicated duodenal ulcer endoscopically diagnosed. The first group was treated with 1 g of cimetidine per day, during a period of four weeks (200 mg three times a day and 400 mg at bedtime); the second with a liquid Al-Mg antacid compound, 210 ml/day 30 ml, 1 and 3 hr after meals and 30 ml before bedtime) for four weeks. Fity-one patients were studied, 27 treated with cimetidine, 24 with antacids. At the end of the four-week period, 21 patients (77.7%) in the cimetidine group and 18 patients (75%) in the antacid group were completely healed. Benign side effects were remarked in both types of treatment, none of which made it necessary to suspend treatment. No significant variation of the basal and peak acid output before and after each kind of treatment was observed, while a slight but significant increase in fasting serum gastrin concentration was noted after treatment in the antacid group.


Depressed jejunal secretion of water and ions in response to prostaglandin E1 in adult celiac disease.

In order to test in man the concept that intestinal fluid secretion originates from the crypts of Lieberkühn, we assessed the jejunal secretory effect of intraluminal prostaglandin E1 (PGE1) (0.9 microgram/kg/min) in untreated adult celiac disease (ACD, N = 7), treated ACD (N = 4) and normal subjects using the intestinal perfusion technique. In untreated ACD (1) water and solutes were malabsorbed (or secreted) in the basal period; (2) fluid and ion secretion seen during PGE1 infusion and net secretory effect of PGE1 (difference in transport between basal and PGE1 periods) were reduced (P less than 0.01); (3) the effects of PGE1 inhibition of sodium insorption, and stimulation of sodium exsorption, were decreased and abolished, respectively. In treated patients PGE1-induced secretion returned towards normal values. Our finding of a depressed secretory response to PGE1 in the face of marked crypt hypertrophy do not support the concept that crypt cells are the major site of intestinal fluid secretion.


A chylous mesenteric cyst and a study of its contents.

A case of a patient with a large chylous cyst in the mesentery of the small intestine is presented. After excision of the cyst, the chyle was analyzed with special reference to its protein and lipid content. The composition of the chyle compared with that of intestinal lymph of experimental animals suggests that the fluid in the cyst has undergone concentration in terms of protein.


An association between primary biliary cirrhosis and jejunal villous atrophy resembling celiac disease.

A 76-year-old female presented with malabsorption and was subsequently shown to have jejunal villous atrophy. There was only partial clinical and histologic recovery with gluten withdrawal, but this was thought to be due to poor adherence to the diet. The findings were considered to be consistent with adult celiac disease. During the course of investigations, she was also found to have primary biliary cirrhosis. This is the fifth recorded instance of this association and the first from North America. Because these are uncommon conditions, it is postulated that this is unlikely to be a chance association. The recognition of this coexistence is of practical importance in the investigation and treatment of patients with primary biliary cirrhosis and celiac disease.


Drug effects on the liver: a tabular compilation of drugs and drug-related hepatic diseases.

Geneic and chemical names of drugs and the possible adverse effects of these drugs on the human liver were tabulated. All drugs compiled in these tables have been approved by the Federal Drug Administration. They are currently available in the United States, and they are listed in the 1979 Physicians' Desk Reference. The tables include: (1) names of drugs that have caused a characteristic morphologic change, such as cholestatic lobular hepatitis; (2) morphologic diagnoses that have been documented after administration of each drug; and (3) references that can be matched to each drug and to its effects on the liver.


Measurement of glycoprotein content and cell kinetics in preulcerous gastric mucosa.

In an attempt to evaluate the role of gastric mucosal defense factors in ulcerogenesis, we measured the levels of glycoproteins in the mucosa as well as mucosal cell turnover in the preulcerous phase and compared these parameters to the normal mucosa in the same animal. Ovalbumin-presensitized Praomys (Mastomys) natalensis were challenged in the gastric wall with ovalbumin and a gastric ulcer developed at the challenge site 3 days later as a result of a mucosal anaphylactic reaction. This model enabled us to study the events occurring at the site of a future ulceration. Gas-liquid chromatographic determination of mucosal glycoproteins showed that the normal and preulcerous mucosae had similar levels. Cell turnover, determined by [3H]thymidine incorporation, was stimulated as a result of the preulcerous anaphylactic reaction at 24 hours postchallenge whereas at 48 hours the values were not different from those obtained in controls. These results suggest that the pathogenesis of anaphylactic gastric ulcer involves a change in cell turnover but no changes in the production of gastric mucus.


Malignancy in a 19-year experience of adult celiac disease.

Malignancy has developed in 10 of 93 patients with celiac disease who attended this hospital from 1959 to 1978. Four patients developed lymphoma, 5 a squamous carcinoma of the esophagus, and 1 an adenocarcinoma of the ileum. Because the majority of patients were ingesting varying amounts of gluten at the time of their follow-up no conclusion can be drawn about the possible role of a gluten-free diet in the prevention of malignancy.


Differential diagnosis of pancreatic mass lesion with percutaneous fine-needle aspiration biopsy under ultrasonic guidance.

Ultrasonically guided percutaneous fine-needle aspiration biopsy for cytological diagnosis was performed on 28 patients with ultrasonically scanned solid mass lesions of the pancreas in an attempt to make a differential diagnosis between pancreatic cancer and chronic pancreatitis. In 25 of the 28 patients, enough cells were aspirated to enable a cytological diagnosis to be made. In 19 of these 25 patients, malignant cells were obtained, while the aspirates from 6 patients contained only normal pancreatic cells. In 3 of the 28 patients, insufficient numbers of cells were obtained to allow the establishment of a cytological diagnosis. Pancreatic cancers were present in 22 of the 28 patients, and among these a positive diagnosis of cancer was made by aspiration biopsy in 86.4% (19/22). The technique resulted in no false positive diagnoses of cancer among 6 patients with chronic pancreatitis. No complications, such as bleeding, fistula formation, and elevation of the serum amylase, followed the procedure. This new method appears to be extremely useful in the diagnosis of pancreatic mass lesions.


Studies on nicotinic acid interaction with bilirubin metabolism.

The mechanism by which intravenous administration of nicotinic acid (NA) increases serum unconjugated bilirubin in patients with the Gilbert's syndrome has been investigated. Studies using the technique of percutaneous transhepatic catheterization of the splenic vein and coil planet centrifuge suggested that following intravenous injection of NA some of the circulating erythrocytes were rendered osmotically fragile and trapped by the spleen and that unconjugated bilirubin increased in the splenic vein blood. In patients with liver cirrhosis, the increments of unconjugated bilirubin were closely correlated with the weights of the spleens removed for the management of varices. In rats, intravenous NA injection enhanced heme oxygenase activities in the spleen, but not uridine-5'-diphosphate (UDP)-glucuronyltransferase activity in the liver. These results are consistent with the hypothesis that NA-induced unconjugated hyperbilirubinemia is a result of complex reactions which include increased erythrocyte fragility, increased splenic heme oxygenase activity, and increased formation of bilirubin in the spleen.


Effect of hydrophobic detergent on lipid absorption in the rat and on lipid and sterol balance in the swine.

The effects of hydrophobic detergent on fat absorption in the rat were determined under two conditions. In the first, a high dose of detergent was given in a test lipid meal to rats not previously exposed to this agent. A marked delay in digestion of triglyceride in association with malabsorption was observed. In the second, a relatively small dose of detergent was given to rats pretreated with dietary supplement of detergent. No delay of digestion or uptake was observed but absorbed, reesterified lipid was noted to accumulate in the mucosa. Morphologic studies showed abnormal collections of fat droplets in the enterocytes. Sterol and fat balance studies were done on swine on chronic dietary detergent supplement. Mild steatorrhea with excess fecal excretion of neutral sterols was observed. It is concluded that hydrophobic detergents can have an inhibitory effect on both intraluminal and intracellular events of fat absorption.


Association of cimetidine and bone-marrow suppression in man.

A 29-year old woman who was on steroids for Behcet's disease received intravenous cimetidine for severe gastrointestinal bleeding. A bone-marrow examination performed a few days prior to cimetidine treatment showed a normally active marrow. On the fifth day of cimetidine therapy, agranulocytosis (800/ml) and a very low platelet count (40,000/ml) were observed; bone-marrow failure was documented both by biopsy and aspiration. No other drug known to be myelotoxic was given. This severe hematologic side effect of cimetidine resolved within 10 days after discontinuation of the drug.


Permanent disability from skin diseases. A study of 564 patients registered over a six year period.

An analysis of causes of permanent disability indicates which diseases most frequently result in chronicity and inability to work. A nation-wide study comprising all applications for permanent disability pension due to skin diseases in the period 1970--1976 was carried out. A total of 564 persons applied. The most common diagnosis was contact dermatitis followed by psoriasis and connective-tissue diseases. Allergic contact dermatitis alone accounted for 222 cases. 70% of these were due to nickel and chromium allergy. In all the diagnostic groups there was a preponderance of women except for hyperkeratotic hand eczema and genodermatoses. The frequency of the individual disorders in the present study is discussed in relation to their prevalence and prognosis in the literature.


[Acute axillary eczema caused by mercury compounds].

Not every axillary dermatitis is caused by an allergy against corresponding cosmetics (deodorants or anti-perspirants). This is shown in a 24-year-old man with an acute contact dermatitis in the left axilla. Sensitization probably developed against mercury salts due to the regular use of thermometers which were kept in a disinfecting solution containing phenylmercuric borate. The patient was in two hospitals for a check up before heart surgery and temperature was regularly measured in the left axilla. In both clincis phenylmercuric borate was used for desinfection of the thermometers. The sensitivity was proofed by positive patch tests.


[Cold-induced skin damage].

Two cases of cold-induced skin-damage are reported. In one case cold-induced panniculitis (Adiponecrosis e frigore) in a small child was found. In the other case a Dermo-Hypodermitis in an elderly lady was found, where cold was possibly just one, even if certainly the most important factor of realisation for the disease. In both cases neither the parents, respectively the patient, thought of cold-inducement of the disease, neither were anamnestic circumstances sufficiently explorated by the prior treating doctors, so that it seems justified to demonstrate such events in relation to this subject.


[Efficacy and tolerability of cefazedone in infectious skin diseases; determination of serum and tissue concentrations (author's transl)].

The efficacy and tolerance of Cefazedone, a new Cephalosporin derivate, were investigated in an open clinical trial on 40 patients with bacteriological skin infections. Patients with Erysipelas, impetiginized dermatoses and Pyodermia were treated during an average period of 9 days mainly with a dosage of 2X1 g i.v., in some cases with 2X2 g i.v. daily. The success of the treatment was good--very good in 92% of the cases. All pathogens isolated before treatment (Streptococci, St. aureus, E. coli) were eliminated after treatment. 2 patients showed transitory incompatibility reactions due to too rapid injections. The local and systemic tolerance were excellent in all other cases. 1 hour after i.v. injection of 1 g Cefazedone to 20 patients the mean concentration in the serum was 51 micrograms per ml and in the skin-tissue 10.6 micrograms/g.


[Iodine-induced hyperthyroidism due to contrast media (author's transl)].

A prospective study in an area with endemic goitre showed 18 patients (15.1%) out of 119 investigated with iodine containing contrast media to be hyperthyroid after 28 days. Oral cholecystography led to the highest (27.9%) and infusion urography to the lowest (5.3%) rate of hyperthyroidism. Determination of the serum concentration of thyroxine, triiodothyronine, basal and stimulated thyrotropine is not a suitable method to detect the risk for hormonally euthyroid patients before a contrast media investigation.


[Possibilities of assessing cerebrovascular disease by audiometry: Comparison with Doppler ultrasound in the assessment of extracranial vascular occlusion (author's transl)].

Discrimination loss in the speech-audiogram (one-syllable test) was tested on 61 patients with cerebrovascular disease due to extracranial vessel stenosis in the area of the carotid artery distribution. In 44 of the patients (extracranial vessel stenosis or occlusion) the results were compared with the carotid angiogram and Doppler ultrasonography. There was agreement between loss of discrimination, localisation by angiography, ultrasound results and the relevant clinical findings in 32 of 36 patients. In 17 patients audiometry was performed before and after surgical reconstruction of the internal carotid artery. Among 13 patients in whom the results could be assessed, discrimination improved postoperatively in 11 (at least 20% in six, at least 10% in five). The combination of ultrasound and audiometry can be used as a screening method in unclear cases to evaluate suspected cerebrovascular disease, simplify indications for carotid angiography, and used serially, follow any further development of the vascular disease.


[Acute renal failure due to diffuse cholesterol crystal embolisation during streptokinase treatment (author's transl)].

In a 65-year-old man livedo reticularis occurred in the lower half of the body two days after beginning lysis with streptokinase. This was followed by skin and toe necrosis as well as acute renal failure. Autopsy showed a severe ulcerative atherosclerosis of the aorta with cholesterol crystal embolisation in numerous organs, particularly in both kidneys. The coincidence in time leads one to assume that the streptokinase treatment encouraged acute diffuse embolisation by dissolving the protective thrombi over the ulcerative atheromatous plaques.


Role of antiplatelet agents in cerebrovascular disease.

It is now generally accepted by neurologists that most transient ischaemic attacks, particularly in the carotid artery territory, have a thromboembolic basis. These emboli are, for the most part, fibrin-platelet aggregates. Others which contain atheromatous debris are more likely to produce longer lasting neurological deficits. If one assumes this hypothesis then it is reasonable to employ drugs which interfere with platelet aggregation in order to prevent cerebrovascular symptoms and signs. Acetylsalicylic acid (aspirin) prevents aggregation by inhibiting the 'release reaction' initiated by thromboxane A2. This inhibition lasts for the life of the affected platelets. Recent trials in the United States and Canada have demonstrated a positive clinical benefit from the employment of aspirin in patients suffering from transient cerebral ischaemic attacks and amaurosis fugax. There was a reduction or cessation of the attacks in both males and females and a 50% reduction of stroke morbidity and mortality in males.


[Value of pharmacokinetic data during the treatment of psychoses with haloperidol].

Pharmacokinetic data of psychotropic drugs should allow a better understanding of therapeutic results and side effects. The different factors influencing liberation, absorption, protein binding, distribution, metabolism and excretion are reviewed. Then, the principal pharmacokinetic data of haloperidol are exposed with a special emphasis on the lack of information about the correlations between plasma levels and clinical effects. The role of pharmacokinetic informations in the interpretation of responses to treatment is detailed, wishing that the monitoring of haloperidol plasma levels will be more developped in a next future.


[Psychoses with painful manifestations].

Apart from pain related to nociception and pain due to sensory deafferentation, some patients complain repeatedly of some visceral, abdominal or peripheric type of pain, urging surgeons to perform iterative operations in spite of the lack of anatomical background: these patients often labelled as cenestopaths, can be included in the group of severe obsessional neurosis, pain being the main or unique obsessional symptom. Alike other compulsive symptoms of obsessional neurosis, prefrontal lobotomy, topectomy and best of all, prefrontal cryocorticectomy provide an excellent control of pain with little or no side effects.


[Evaluation of the effects of psychomotor reeducation in aged patients with dementia].

Psychomotor re-education has been attempted experimentally with a population of demented patients in a geriatric ward. It draws on the methods employed at the Bel Air Psychiatric Clinic, in particular the principle of transfer of training. To assess the effect, if any, of the therapy, two psychological rating scales devised specially for demented patients, were established by the team of psychologists at the Grenoble Teaching Hospital. These rating scales are based on the theoretical notions of J. de AJURIAGUERRA and colleagues, that is, the concepts of structural analysis, of involution and homogeneity or inhomogeneity. The psychological test rating scale proposed explores four aspects of mental activity : memory, operating mechanisms, visual defects, space perception and orientation. The rating scale is described in detail, with its references, instructions and scoring.


Parathyroid hormone release is not associated with acute sympathetic arousal in goats.

Physiological activation of the sympathetic adrenomedullary (SAM) axis following both thermal and non thermal stress was assessed by changes in serum norepinephrine, glucose and/or protein as well as indices of peripheral blood flow. The occurrence of elevated serum parathyroid hormone (PTH) did not reliably reflect SAM activation as might be predicted from pharmacological studies that document a beta adrenergic receptor mechanism in the parathyroid gland that mediates catecholamine stimulated release of PTH into the circulation. The beta agonist isoproterenol at 1 microgram/min for 60 min did produce a transient increase in serum PTH at 20 min. Overall, the data raise doubts about the physiological significance of the adrenergic receptor in the parathyroid gland. Significant increases in serum PTH of 67% and 109% above basal respectively were seen following ruminal loading with cold and thermoneutral water. Associated with the PTH change were increased serum phosphorus and elevated or constant serum protein and serum total calcium.


Chromatographic and biological properties of immunoreactive somatostatin in hypothalamic and extrahypothalamic brain regions of the rat.

A sheep antiserum to somatostatin was used to develop RIA and immunoaffinity chromatography methods for the study of immunoreactive somatostatin (IRS) in brain tissue. IRS extracted from rat median eminence, anterior hypothalamic-preoptic area, amygdala, and parietal cortex bound reversibly to immunoaffinity columns, providing a technique for concentration and partial purification. Immunoaffinity purified IRS from each of the four brain regions eluted as four peaks on gel filtration chromatography. Each peak possessed biological activity, as determined by inhibitory effects on the release of GH from cultured rat anterior pituitary cells. No differences were detected by the methods employed between IRS from the anterior hypothalamic-preoptic area, which is rich in IRS-containing neuronal cell bodies, and that from the median eminence, where IRS is localized predominantly in nerve terminals.


Dopamine levels in hypophysial stalk plasma of the rat during surges of prolactin secretion induced by cervical stimulation.

Tonic hypothalamic inhibition of PRL release is partially explainable by dopamine secretion into hypophysial portal blood. However, the probable existence of other PRL-inhibiting factors as well as PRL-releasing factors opens to question the role of dopamine in the dynamic regulation of PRL secretion. We investigated this question in the present study by measuring dopamine concentrations in hypophysial stalk blood of the rat during the surgess of PRL secretion induced by cervical stimulation. Urethane anesthesia, necessary for the surgery attendant to stalk blood collection, did not suppress the surge of PRL secretion induced by cervical stimulation 16-24 h previously. Increases in plasma PRL levels during such surges were 4- to 5-fold above baseline. Dopamine concentrations in hypophysial stalk plasma were 36% lower in cervically stimulated than in control rats during the diurnal and nocturnal PRL surges. However, dopamine levels were not different during the interval between the surges, a time at which PRL levels are similar in stimulated and control rats. To determine if the observed 36% decrease in dopamine levels might account for the associated 4- to 5-fold rise in PRL levels during surges, we treated rats with alpha-methyl-p-tyrosine to block endogenous dopamine secretion and then infused dopamine at various rates to achieve plasma dopamine concentrations throughout the physiological range. These dopamine levels significantly but incompletely suppressed PRL levels, and a 36% decrease in administered dopamine was associated with only an approximate 1.5-fold increase in plasma PRL levels. Thus, it is unlikely that changes in dopamine secretion alone can account for the increased release of PRL engendered by cervical stimulation.


The presence of a cytoplasmic estrogen receptor in sexually mature rabbit epididymides: comparison with the estrogen receptor in immature rabbit epididymal cytosol.

Cytosol prepared from epididymides of castrated adult rabbits contains an estrogen-specific binding component that sediments in the 4--5S region on 0.01 M KCl sucrose gradients. The estrogen-specific binding component is not detectable on sucrose gradients unless the cytosol-[3H]estradiol mixture is first extracted with charcoal to remove uncomplexed and rapidly exchangeable ligand from the sample. The macromolecular bound [3H]estradiol that remains after charcoal extraction dissociates from the receptor with a dissociation half-time of greater than 24 h and is of high affinity (Kd = 6.5 +/- 0.9 X 10(-9) M). The estrogen receptor in the adult rabbit epididymis can also be demonstrated when charcoal-extracted samples are chromatographed on Sephadex G-200. Using this system, the major estrogen-specific binder has an apparent molecular weight of less than 200,000. In contrast, the epididymal estrogen receptor in sexually immature rabbits sediments as an 8S species on low salt gradients and has an apparent molecular weight of 200,000 or greater when assessed by chromatography on Sephadex G-200. The estrogen receptor in both age groups is distributed along the length of the epididymal duct. The highest concentration of the cytoplasmic receptor in both mature and immature rabbits is in the cauda epididymidis. The age-dependent changes in the amount of the receptor suggest that it may be involved in maturational changes in the epididymis. The alterations in the physicochemical properties may reflect physiological changes in the epididymis or in the endocrine status of the animal.


Testosterone secretion by rat, rabbit, guinea pig, dog, and hamster testes perfused in vitro: correlation with Leydig cell mass.

Testes from guinea pigs, rabbits, dogs, rats, and hamsters perfused in vitro with maximally stimulating concentrations of ovine LH released 9.76 +/- 2.05, 12.80 +/- 3.15, 28.94 +/- 3.01, 3.18 +/- 0.41, and 0.70 +/- 0.12 microgram testosterone (T)/h, respectively. Adjusting for differences in testicular weight did not eliminate significant (P less than 0.01) species variation in testicular capacity for T secretion in response to ovine LH. Similarly, correction for Leydig cell mass, as determined by morphometric analysis, still left significant (P less than 0.01) differences in the testosterone secretion rates in response to ovine LH for guinea pigs (262.5 +/- 38.6 micrograms T/g Leydig cell), rabbits (205.5 +/- 50.7 micrograms T/g Leydig cell), dogs (116.4 +/- 14.8 micrograms T/g Leydig cell), rats (83.55 +/- 21.80 micrograms T/g Leydig cell), and hamsters (18.24 +/- 3.55 micrograms T/g Leydig cell). The data suggest that significant between-species variation of T production in response to ovine LH is not due to quantitative differences in the mass of Leydig cells.


Effects of the calcium antagonist verapamil on in vitro synthesis of skeletal collagen and noncollagen protein.

Effects of the calcium antagonist verapamil on the synthesis of fetal rat bone collagen and noncollagen protein were investigated in tissue culture. Protein synthesis was quantitated by measuring the incorporation of [3H]proline into collagenase-digestible (CDP) and noncollagen protein (NCP) using bacterial collagenase; [3H]proline was added for the last 2 h of culture. Verapamil (10(-5)--10(-4) M) decreased the incorporation of label into CDP and NCP after 24 h of culture; CDP formation was inhibited to a greater extent than NCP. The inhibitory response was observed in the presence and absence of unlabeled medium proline and was not associated with changes in trichloroacetic acid-extractable radioactivity. Increasing medium calcium from 1.0 to 5.0 mM did not affect the response to 10(-4) M verapamil, whereas 3.0 mM calcium abolished the response to 10(-5) M verapamil. The inhibitory effect was reversed by 48 h of control treatment subsequent to 24-h treatment with the antagonist. Verapamil did not decrease the incorporation of [3H]thymidine into DNA or [3H]uridine into RNA, nor was there any effect of the antagonist on the DNA content of cultured bones. The prostaglandin synthetase inhibitor indomethacin did not affect the response to verapamil. We conclude that a critical concentration of intracellular calcium is necessary for normal synthesis of skeletal protein in tissue culture, and that collagen may be more sensitive to changes in intracellular calcium than NCP. In addition, other ions (e.g. sodium and potassium) may also be involved in the control of skeletal protein synthesis.


Milk ejection reflex linked to slow wave sleep in nursing rats.

Correlations between cerebral activity of nursing rats and the milk ejection reflex were studied in Sprague-Dawley rats with 15- to 17-day-old litters. The stretch reaction of the pups, which expresses the onset of milk ejection, was closely correlated with the slow sleep epochs of the mother. Once the litter started suckling, milk ejection only took place when the mother fell asleep and electroencephalographic features of slow wave sleep appeared. Milk ejection was never found during paradoxical sleep nor when the mother was awake. Sleep deprivation for 30 min impaired milk ejection in spite of continuous suckling of the nipples by the pups. If the mother was allowed to sleep immediately afterwards, ejection of milk occurred. A 24-h sleep-wakefulness pattern did not show differences between nursing and controls. Our results show that suckling, although necessary, is not enough to set off milk ejection. This reflex only appears when the mother falls asleep, suggesting that oxytocin release is linked to suckling and slow wave sleep.


Glucose infusion potentiates the acute insulin response to nonglucose stimuli during the infusion of somatostatin.

These studies assessed the ability of glucose infusions to potentiate the acute insulin response (AIR) to iv isoproterenol (12 micrograms), arginine (750 mg), or glucose (5 g) that was previously inhibited by an infusion of somatostatin (SRIF). SRIF (1.7 micrograms/min) markedly inhibited the AIR to isoproterenol (AIR before SRIF, 28 +/- 1 microU/ml; AIR during SRIF, 8 +/- microU/ml; P less than 0.025), arginine (AIR before SRIF, 6 +/- 2 microU/ml; AIR during SRIF, 1 +/- 1 microU/ml; P less than 0.01), and glucose (AIR before SRIF, 19 +/- 7 microU/ml; AIR during SRIF, 1 +/- microU/ml; P less than 0.05). The administration of a glucose infusion of 105 mg/min partially restored the AIR to isoproterenol and arginine. Glucose infused at 440 mg/min fully restored the AIR to both isoproterenol (AIR during SRIF plus glucose, 31 +/- 4 microU/ml) and arginine (AIR during SRIF plus glucose, 9 +/- 2 microU/ml). In contrast, the AIR to glucose was not affected by infusion of glucose (AIR during SRIF plus glucose, 0 +/- 1 microU/ml). In the absence of SRIF, glucose infusion potentiates the AIR to isoproterenol and arginine but not to glucose. Therefore, during SRIF infusion, glucose retains the ability to potentiate the AIR to nonglucose stimuli despite the loss of the ability to stimulate insulin release directly. These data suggest that the potentiating effects of glucose and the inhibiting effects of SRIF may be mediated by a common mechanism affecting insulin release.


Radiochromium distribution in hypophysectomized and adrenalectomized rats.

The effects of hypophyseal and adrenal ablation (HYPOX, ADX) on trivalent radiochromium (51Cr) distribution and of GH and T4 replacement in HYPOX rats were determined. Hypophysectomy increased body retention of 51Cr by 20--35%, and hormonal replacement restored body retention to normal. Serum 51Cr was increased 300--800%, resulting in depressed tissue to serum 51Cr ratios. GH replacement partially restored the 51Cr distribution abnormalities in HYPOX rats to normal. The combination of T4 with GH enhanced the restoration of normal 51Cr distribution, and tissue to serum 51Cr ratios returned to baseline levels. ADX had no effect on body retention of 51Cr but had a small effect on increases in serum and tissue 51Cr levels. As a result, tissue to serum 51Cr ratios did not change. These data indicate that in the HYPOX state there is a marked disturbance in Cr metabolism which is due to deficiencies of both GH and T4. Whether or not adrenal hormones are envolved in 51Cr distribution will require further study.


Comparison between the action of estradiol and that of the antiestrogen U 11-100 A on the induction in the rat uterus of a specific protein (the induced protein).

When measured by an in vitro approach, involving incubation in the presence of labeled leucine, the rate of synthesis of the specific estrogen-induced protein (IP) after in vivo stimulation of the rat uterus by the antiestrogens U 11-100 A (UA; 1-(2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphtyl)-phenoxy]ethyl)pyrrolidine hydrochloride) or CI-628 (alpha-[4-pyrrolidinoethyoxy]phenyl-4-methoxy-d-nitrostilbene) was very low compared to the response measured under the same conditions after in vivo stimulation with 17 beta-estradiol (E2). In the course of investigations aimed at clarifying the role of IP in estrogen action, we have conducted similar experiments, but the labeling step aimed at detecting and measuring IP  synthesis was carried out in vivo. We have observed that UA promoted a full IP response which is lost or missed in incubated uteri. Similar results were obtained with CI-628 and tamoxifen. A comparison between IP responses obtained and measured in vivo after E2 and those after UA action revealed that the responses paralleled the number of receptors that are translocated to the nucleus by each compound. Thus, while transient after E2 treatment, the IP (or IP-like) response was maintained for as long as 12 h (as is the nuclear receptor occupancy) when UA was used as inducer. Several explanations for the disappearance of the UA-induced IP response under in vitro conditions are considered.


Endoscopic appearance of irradiated gastric mucosa.

Irradiation of the epigastric area for gastric cancer may induce actinic lesions of the stomach characterized on endoscopic examination by ulcerations, haemorrhagic gastritis, fragility of the mucosa, thickening and congestion of the gastric folds.


Relation of intestinal metaplasia to the acid-secreting area.

The distribution of intestinal metaplasia in relation to the acid-secreting are was investigated in 66 patients not suffering from gastroduodenal diseases. Studies were made via the endoscopic Congo Red test in combination with the methylene blue staining method. In this test, the acid-secreting area is identified as a "discolored" area in which Congo Red turns from red to blue-black, and areas of intestinal metaplasia were observed as areas staining blue with methylen blue. A close relationship was found between the acid-secreting area and the distribution of intestinal metaplasia; in general, intestinal metaplasia tended to be more extensive and more frequent when the acid-secreting area was small. It was also found that intestinal metaplasia increased with age. However, even in patients who were over 40 years of age, intestinal metaplasia was seen in 12.5% only, if the acid-secreting area was large. Hence, it appears likely that development of intestinal metaplasia is more closely related to the acid-secreting function than to aging.


Diagnosis of resectable pancreatic carcinomas by means of ERCP and intraoperative fine-needle biopsy.

In 27 out of 30 resectable carcinomas of the pancreas or the periampullary region we succeeded in recognizing microscopically the malignant nature of the lesion before removing the neoplasm. This was possible 3 times preoperatively during ERCP by means of forceps biopsy taken from the tumorinfiltrated duodenal wall and with 24 patients intraoperatively by means of fine needle biopsy and cytological rapid diagnosis.


Lymphangioma of the oesophagus. Diagnosis and treatment by endoscopic polypectomy.

Finding a lymphangioma in the upper digestive tract is a rather infrequent event. A case of a 64-year-old man is reported. Diagnosis was made in the course of an endoscopic oesophagogastroduodenal examination and tumor excision with a diathermy snare at the same time. Two years after resection there was no sign of recidivation of the tumor.


Obstruction of the duodenal bulb caused by gallstone perforation.

Because of acute symptoms in the upper abdomen, upper gastrointestinal endoscopy was performed in a 75-year-old female patient. A large (5 cm x 10 cm) perforated gallstone was embedded in the duodenum, causing complete obstruction of the duodenal bulb. The stone was removed via pylorotomy. A fistula remained between the gallbladder and the duodenum. Cholecystectomy was not carried out because of the unfavourable cardiac condition of the patients. There was no complications.


The diagnosis of post-cholecystectomy cystic duct fistula utilizing endoscopic retrograde cholangiopancreatography.

A patient developed persistent right upper quadrant pain and tenderness following cholecystectomy. An endoscopic retrograde cholangiopancreatogram showed leakage of bile through the cystic duct remnant into the subhepatic space. The endoscopic retrograde cholangiopancreatographic findings (ERCP) are described.


Selective endoscopic contrastography (S.E.C.): an original association of radiology and endoscopy of the small and large intestine.

A more complete diagnostic information can be obtained by "carrying" the contrast medium through the fibercoloscope to those sites of the bowel where neither radiology alone nor endoscopy alone succeed in solving the diagnostic problem. The indications for a selective perendoscopic contrast study during coloscopy are few, but well defined and certainly not negligible:--demonstration and assessment of stenoses (unclarified by radiology and endoscopy);--accurate evaluation of the last ileal loop;--diagnostic study of ileo-colic surgical anastomoses;--fistulous tracts. Seventy-six patients were examined, without complications. The method proved useful in 42% of cases, conclusive in 33%, useless or inconclusive in 17%, unsuccessful in 8% (technical difficulties). On this basis, selective endoscopic contrastography is considered of use whenever its specific indications apply.


Significance of endoscopy for evaluation of vesico-ureteral reflux.

The role of urethrocystoscopy in the evaluation of vesico-ureteral reflux is discussed. In addition to voiding cystourethrograms and excretory urography endoscopic examination of patients with vesico-ureteral reflux permits the determination of the extent of the uretero-vesical junction malformation. The length of the submucosal ureter, the orifice configuration and its location as well as the trigonal muscular development are parameters which lend themselves to endoscopic evaluation. Their importance in the decision of whether vesico-ureteral reflux is treated conservatively or surgically is discussed. In addition, urethrocystoscopy may give valuable information on the causes of secondary vesico-ureteral reflux.


Present status of endoscopic laser techniques in urology.

Following a brief description of the physical and biomedical characteristics of laser light, a report is given on the development and present status of laser endoscopy in urology. Presently there appear to be two principal indications: i. e. certain bladder tumors and urethral strictures. Neodymium: YAG and argon ion lasers are used for both disorders. The special laser features of these instruments are described.


Endoscopic procedures in the treatment of urologic disorders in children.

Cystoscopy has been a well established procedure in adult urology for years and more recently for the endoscopic evaluation of the lower urinary tract of infants and children. Utilizing small caliber cold light endoscopes and resectoscopes, therapeutic manipulations are readily possible. Among these are extraction of ureteral stones, lithotripsy of bladder calculi, transurethral resection of bladder tumors, as well as transurethral incision and resection of bladder-neck obstructions, urethral valves and urethral stenoses. The excellent results obtained in the treatment of infravesical urinary obstruction have contributed to the importance of transurethral surgery in pediatric urology.


Fiberendoscopic evaluation of ureterosigmoidostomies.

Sixteen patients having undergone ureterosigmoidostomy have been examined using fiberoptic coloscopes. Morphology and function of both the colonic mucosa and the ureteral stumps have been evaluated by direct observation, biopsy brush cytology and i.v. injection of methylen blue. The obtained encouraging results point to this fiberendoscopic diagnostic approach as an easy and useful follow-up examination of patients with intestinal urinary diversions.


Gastric involvement in Sjögren's syndrome simulating early gastric carcinoma.

The case of a 42-year-old woman with Sjögren's syndrome accompanied by severe gastric infiltration and interstitial nephritis is reported. Presentation was with finger stiffness, Raynaud's phenomenon and abdominal discomfort. There were endoscopic and radiological features of early cancer, type IIc (depressed type). Resected stomach showed atrophic gastritis with erosion. Histology showed focal to relatively diffuse destruction of the gastric glands with minimal intestinal metaplasia and dense collections of lymphoid cells with occasional germinal centers in the interstitium of the gastric mucosa. Renal biopsy revealed similar severe diffuse interstitial infiltration of lymphoid cells. Distal renal tubular acidosis was confirmed by sodium bicarbonate and ammonium chloride loading test. Satisfactory improvement in xerostomia, keratoconjunctivitis sicca and other laboratory data occurred on prolonged administration of adrenal steroids and cyclophosphamide.


Cadmium analysis by radiochemical neutron activation analysis.

Radiochemical neutron activation analysis (RNAA) has been routinely used at the National Bureau of Standards to analyze Cd in a variety of environmentally important matrices. The method used to separate Cd from other neutron-activated products is solvent extraction. Zinc diethyldithiocarbamate [Zn(DDC)2] in chloroform will quantitatively extract Cd from an aqueous solution over a pH range from 1 to 12. In addition to the extraction of Cd, Zn(DDC)2 will also extract Cu, which can interfere with the Cd analysis by producing a high background level of radiation. This can be avoided by first extracting with Bi(DDC)3 in chloroform which removes Cu, but not Cd. Copper concentrations can, therefore, be determined in addition to Cd. This two extraction radiochemical separation procedure is very versatile and is often used as part of a larger multi-element analysis scheme. One such scheme involves the use of an inorganic-ion exchanger, Hydrated Manganese Dioxide (HMD), to retain As, Sb, Se, and Cr prior to extraction. The eluted fraction is then extracted with Bi(DDC)3 to remove Cu, and then with Zn(DDC)2 to remove Cd.


Effects of nutritional factors on metabolism of dietary cadmium at levels similar to those of man.

Several nutrients are known to affect cadmium toxicity, but little is known about the effect of dietary nutrient levels on absorption and tissue retention of cadmium at low dietary levels, similar to those of man. Feeding gradedlevels of zinc in a casein-gelatin diet to young Japanese quail with 109Cd (as the chloride) and 0.062 ppm added cadmium decreased the cadmium concentrations in the proventriculus-ventriculus, duodenum, jejunum-ileum, and the liver, but not in the kidney. Zinc also affected some zinc, iron, manganese, and copper tissue levels. Different tissue concentration patterns of cadmium and essential minerals were obtained with two purified control diets, one based on casein-gelatin and the other on soy isolate as the principal protein sources. The data show that relatively small dietary changes can markedly affect tissue levels of cadmium and that a low intake of zinc may increase the risk to dietary cadmium exposure. The complexity of the nutrient interrelationships and their effects on cadmium require further study to define mechanisms, which may be similar to those produced by low cadmium intakes in man.


Cadmium effects in rats on tissue iron, selenium, and blood pressure; blood and hair cadmium in some oregon residents.

Exposure of rats to cadmium causes a marked depletion of iron in liver and kidney. Selenium neither counteracts or intensifies the influence of cadmium on tissue iron levels. Selenium injections protect against cadmium-induced testicular damage but cause this element to accumulate in the testes at higher concentration than in animals exposed to cadmium without selenium. Selenium injection diverts the binding of cadmium from low molecular weight proteins to high molecular weight ones. Dosing rats with selenium and cadmium or inclusion of Se or Cd in the diet did not result in altered cadmium binding in tissues, raising some questions concerning the environmental significance of these injection experiments. Addition of selenium to a diet containing cadmium decreased the accumulation of cadmium in liver and kidney, but increased its deposition in testes. The metabolism of cadmium bound to metallothionein was markedly different as compared to the inorganic salt of this element. Dietary ascorbate, but not citrate or cysteine, decreased the deposition of cadmium in rat tissues. In some low-level exposure experiments with cadmium (1 to 1000 ppb), no differences were found in the percentage of dose absorbed or rate of cadmium accumulation when provided in food versus water. Female rats tended to absorb more cadmium than males. The binding of cadmium to cytosolic proteins was found to be different between rats fed low levels of cadmium (up to 1 ppm) as compared to those fed high levels of this element (100 ppm). Cadmium was not found to contribute to hypertension in rats, and a summary of results by various investigators is presented. Blood and hair cadmium levels in Oregon residents were found to be highest in employees of a mine, and hair cadmium was found to be respectively higher in smokers than nonsmokers and in metal workers than office workers. No relationships were observed in humans between blood or hair cadmium levels and blood pressure.


Biliary excretion of cadmium.

Biliary excretion of cadmium was studied in two groups of five rats which were given repeated injections of 109Cd. The first group was given a total amount of 6 mg Cd/kg which was 6 times as much as the second group. The elimination of cadmium in bile, urine, and feces was measured 4 to 5 weeks after the last injection. The relative biliary excretion of cadmium was the same in both groupetion, which was 0.001% but, less than the total fecal elimination of cadmium, which averaged 0.034% during the same time.


Metabolism of orally administered cadmium-metallothionein in mice.

The main source of cadmium in the diet is cereal or meat, especially in liver and kidney. Since the cadmium in both liver and kidney is bound to metallothionein, a heat-stable protein, the gastrointestinal absorption and metabolism of cadmium metallothionein (CdMt) was studied in detail. The selective renal cadmium deposition after oral CdMt was analogous to the studies on injected CdMt. Metallothionein with 109Cd or 35S-cysteine radioactive label was isolated from rat liver and administered orally (60 microgram Cd) through a gastric tube to mice (C57 BL/6J). After 4 hr, a major portion of the ingested CdMt was isolated intact from intestinal mucosal cells. However, only a small amount of cadmium bound metallothionein was present in the kidney supernatant. The protein moeity was also degraded completely in kidney. The absorption and tissue distribution of cadmium from oral-cysteine and cadmium-glutathione complexes were similar to that after oral CdCl2 in mice. These results that oral CdMt may be absorbed intact from the gastrointestinal tract and the protein is degraded during renal deposition.


Renal tubular dysfunction and abnormalities of calcium metabolism in cadmium workers.

Tubular proteinuria is generally accepted as the critical effect following long-term, low-level exposure to cadmium as seen in an industrial environment. This effect may not be of immediate importance to the health of the individual, but the significance, in terms of long-term morbidity and mortality, of the renal tubular defect of which it is an indicator is not fully understood, and certain sequelae may have remained unrecognized due to inadequate follow-up.Follow-up studies have been performed in nine of 12 workers who were initially investigated in 1962. In six of the men exposures ranged from 28 to 45 years to cadmium sulfide dust and for shorter periods in the earlier years to cadmium oxide fume and dust. These six men had tubular proteinuria when first seen, and this has persisted in the five survivors. All six men had hypercalciuria, and two of them became recurrent stone formers. One man whose urinary calcium excretion later fell to a low level more recently developed vitamin D resistant osteomalacia. In addition, each of the six men had exhibited some, but not all, of a variety of biochemical abnormalities related to other proximal renal tubular defects, and the worker who developed osteomalacia had additional evidence of a distal tubular defect. The five survivors also have evidence of slowly progressive deterioration in glomerular function.Follow-up of this small group has shown that renal tubular dysfunction in cadmium workers may continue symptom-free for long intervals, but in a proportion of cases serious clinical effects may develop after a number of years.


Metallothionein synthesis and degradation: relationship to cadmium metabolism.

Metallothionein is an integral component of the mechanism that regulates the metabolism of cadmium and zinc. The synthesis of this protein can be "induced" by oral or parenteral administration of either metal. The metallothionein mRNA content of liver polysomes is increased shortly after an influx of small amounts of either metal into hepatocytes. After sufficient amounts of this poly (A+) RNA have been synthesized, there is a concomitant increase in metallothionein biosynthesis and metal binding. Unlike synthesis, the degradation of metallothionein is markedly influenced by the species of metal bound. By using in vivo and in vitro techniques, it has been possible to demonstrate that resistance of metallothionein to degradation follows the order: thionein less than zinc metallothionein less than cadmium metallothionein. Moreover, while the polypeptide chains of cadmium metallothionein are degraded, it appears that liberated cadmium ions are quickly incorporated into nascent chains of thionein. The latter explains why the cadmium content of liver and kidney increases with age and environmental exposure. Since both zinc and cadmium bind to metallothionein, it appears that the binding sites provided by this inducible species provide a locus for interaction between zinc, a nutrient, and cadmium, an environmental contaminant.


Industrial emission of cadmium in Japan.

Direct emission of cadmium into air and water in Japan has been controlled on the basis of the Emission and Effluent Standards. Environmental quality in these media has been improved, but delayed effects of these emissions in the past are now manifest by contamination of agricultural acreage in various parts of this country. Special land improvement projects are therefore required, and cost allocation should be made on the basis of scientific assessment of natural background. An impact assessment on accidental release of potential sources of cadmium dispersed in the water system should be made on the basis of inventory surveillance. Assessment of natural background can practically be made by two means. One is to examine the vertical distribution of cadmium in a soil profile and to search for a subsurface layer in which there can be no contamination. Another is the use of the Zn/Cd ratio as an index of pollution, a value of 400 being suggested as a screening level. The transport of cadmium was found to occur principally in particulate form, and sampling and analysis of water together with suspended solid after a heavy rainfall is suggested as a useful means for assessing the character of a catchment area and for planning the improvement of land surface in mining districts.


Mortality and cancer morbidity among cadmium-exposed workers.

Preliminary data are reported from a study of 269 cadmium-nickel battery factory workers and 94 cadmium-copper alloy factory workers. The target group comprises all workers with more than 5 years exposure to cadmium at any time since the factories started production. An internal reference group of 328 alloy factory workers without cadmium exposure was also studied. The expected number of deaths and cancers was calculated with the "life-table" method by using national average incidence rates for men in different age groups and at different calendar years. It was found that among the workers in the battery factory who started work before 1948 there was an increased general mortality in the 1950's mainly due to respiratory disease. The same group had an increased renal disease mortality. There was no increase in general cancer mortality or in general cancer incidence. The risk ratio for nasopharyngeal cancer incidence was 10 (two cases), which was statistically significant. For some other sites like prostate, lung and colon-rectum the risk ratios were also greater than 1 but not statistically significant. In the alloy factory there was a tendency for an increased mortality in prostatic cancer (four cases). After correction for the "healthy worker effect" using the reference group, the risk ratio for prostatic cancer deaths was calculated as 2.4, but this was not statistically significant. The findings in this study support the earlier reports of an association between human cadmium exposure and increased risk for prostatic cancer.


Metabolic model for cadmium in man.

A metabolic model for cadmium has been formulated in terms of a flow scheme for cadmium among eight body compartments. The mathematical description of the flow of cadmium between compartments consits of a number of differential equations, and the accumulation of cadmium may thus be calculated. Coeffcients for the flow of cadmium were estimated from empirical data both from animals and man. The modelling serves two main purposes: it provides a means of using present knowledge about metabolism in order to calculate expected accumulation in critical organs and other tissues and body fluids at certain intake levels and it makes it possible to define deficiencies in our present knowledge about metabolism. Data recently collected, partly as a result of considerations related to the model, have confirmed the assumptions of a very long biological half-time in other tissues and the small excretion of cadmium via bile.


Pulmonary and gastrointestinal exposure to cadmium oxide dust in a battery factory.

The elimination of cadmium in feces was studied in a group of 15 male workers exposed to cadmium oxide dust in a nickel-cadmium battery factory. The elimination of cadmium in feces was on the average 619 and 268 microgram/day in seven smokers and eight nonsmokers, respectively. The corresponding ranges were 97-2577 and 31-1102 microgram/day. The cadmium concentrations in blood were significantly higher in smokers than in nonsmokers, both before and after one month of vacation. Among the smokers there was a significant decrease in the cadmium concentrations during the vacation period, but not among the nonsmokers. It was estimated that cadmium naturally occurring in food and cigarettes, cadmium excreted from the gastrointestinal tract, and cadmium transported from the lungs by mucocillary clearance to the gastrointestinal tract only could explain up to 100 microgram of the cadmium in the feces. Since even among some nonsmokers much higher values for fecal cadmium were recorded, this was interpreted as being the result of ingestion of cadmium from contaminated hands and other body surfaces. Among the smokers, direct oral contact with contaminated cigarettes or pipes is an additional factor; the smokers also inhale cadmium in the tobacco smoke from contaminated cigarettes. Part of that cadmium is transferred to the gastrointestinal tract by mucociliary clearance and also adds to the fecal cadmium.


Cadmium in forest ecosystems around lead smelters in Missouri.

The development of Missouri's new lead belt within the past decase has provided an excellent opportunity to study the dissemination and effects of heavy metals in a deciduous forest ecosystem. Primary lead smelters within the new lead belt have been identified as potential sources of cadmium as well as lead, zinc, and copper. Sintering and blast furnace operations tend to produce significant quantities of small particulates highly enriched in cadmium and other heavy metals. At one smelter, samples of stack particulate emissions indicate that as ms accompanied by 0.44 lb zinc, 4.66 lb lead, and 0.01 lb copper/hr. These point-source emissions, as well as a number of other sources of fugitive (wind blown) and waterborne emissions contribute to a significant deposition of cadmium in the surrounding forest and stream beds. Mobilization of vagrant heavy metals may be significantly increased by contact of baghouse dusts or scrubber slurries with acidic effluents emanating from acid plants designed to produce H2SO4 as a smelter by-product. Two separate drainage forks within the Crooked Creek watershed permit some comparisons of the relative contributions of cadmium by air-borne versus water-borne contaminants. Cadmium and other heavy metals have been found to accumulate in the forest litter and partially decomposed litter along stream beds. Greater solubility, lower levels of complexation with organic ligands in the litter, and greater overall mobility of cadmium compared with lead, zinc, and copper result in appreciable contributions of dissolved cadmium to the watershed runoff. The present paper attempts to define the principle sources and current levels of heavy metal contamination and summarizes the efforts undertaken by the industry to curtail the problem.


Acute effects of cadmium on the pregnant rat and embryo-fetal development.

In rats, of the Wistar-Porton strain, a single intravenous injection of 1.25 mg Cd2+ between days 9 and 15 of gestation results in a high incidence (80% of hydrocephalus, together with other malformations in the fetuses, examined on day 20. This dose is critical, since 1.1 mg Cd2+/kg is not teratogenic, while 1.35 mg Cd2+/kg kills all the embryos. Intravenous injection of Cd2+ to the pregnant rat on day 12 causes a dose-dependent inhibition of placental Zn2+ transport. At the teratogenic dose, Zn2+ transport is inhibited by about 75% at 4 hr. Thereafter, inhibition decreases with time but is still significant at 48 hr. At 20 hr after administration of Cd2+ the embryonic concentration of Zn2+ is depressed by 33%. In the whole embryo the activity of the Zn2+-dependent thymidine kinase is inhibited by about 60% at 4 hr and at 20 hr the DNA concentration is reduced significantly. Placental transport of 14C-leucine and 14C-uridine, as well as the embryonic incorporation of these precursors into protein and RNA is unaffected at least at short times after the administration of Cd2+. It is possible therefore, that the teratogenic effects of Cd2+ may be related to the inhibition of DNA synthesis in the embryo.


Increase in the systolic pressure of rats chronically fed cadmium.

In our laboratory, chronically feeding cadmium to groups of rats has been reproducibly associated with average increases of 15 to 20 mm Hg in systolic pressure. A total of 497 female Long-Evans rats were continuously provided with drinking water fortified with five essential elements and containing from 0.01 to 50 ppm cadmium, as the acetate, from weaning for as long as 30 months. These rats, plus 311 matched control animals which received fortified water without added cadmium, were fed a special low-cadmium diet. All 808 rats were weighed at least monthly as a screen for cadmium toxicity, and their systolic pressures were measured every 3 or 6 months. The two lowest concentrations of cadmium tested (0.01 and 0.03 ppm) were not pressor; the three highest concentrations (10, 25, and 50 ppm) ultimately proved to be toxic. All indirect systolic pressures (each measured in triplicate) of all rats which received 0.1 to 5 ppm cadmium (i.e., nontoxic pressor doses) averaged 15.0 mm Hg more than simultaneously measured pressures of control rats. This average increase over the control pressure is extremely significant statistically, even though it seems relatively small in absolute terms. Occasionally, however, some rats had much larger than average increases in pressure; thus, 10 of 60 rats receiving from 0.1 to 0.5 ppm cadmium for 18 months had systolic pressures that were more than 50 mm Hg above the average pressure of the control rats. Cadmium-induced hypertension is not limited to females or to a particular strain. Although we have usually used one strain of female Long-Evans rat from a single source, males of the same strain and female Sprague-Dawley rats have also developed comparable hypertension. All subgroup II elements can apparently induce similar increases in systolic pressure averaging 15 to 20 mm Hg, but cadmium is pressor in much smaller amounts than mercury or zinc. Thus, to induce a demonstrable increase in pressure requires more than ten times as much divalent mercuric ion as cadmium and more than 1000 times as much zinc as cadmium. Exposure to another metal along with cadmium can markedly alter the ability of cadmium to induce hypertension. Selenium protects against the hypertension induced by twice as much cadmium. Large excesses of both zinc and copper have also inhibited the induction of hypertension by cadmium. In contrast, lead, which like cadmium, can also induce hypertension, augments rather than inhibits cadmium-induced hypertension; thus, lead and cadmium together can induce an average increase in systolic pressure in excess of 40 mm Hg, at least twice as large as is usually induced by either metal alone.


Effects of cadmium ingestion in rats with opposite genetic predisposition to hypertension.

This study was undertaken to explore the effects of chronic low-level cadmium ingestion in Dahl hypertension-resistant (R) and hypertension-sensitive (S) lines of rats. Groups of weanling female R and S rats were given 0 or 1 mg cadmium/1. in drinking water and fed either a low salt (0.4% NaCl) or a high salt (4% NaCl) diet for 28 weeks. Cadmium produced hypertension associated with gross cardiac hypertrophy and mild to moderate renal vascular changes in S, but not in R, rats on a low salt diet. Cadmium enhanced the rate and degree of development of salt-induced hypertension without exacerbating the hypercholesterolemia or renal vascular lesions normally observed in S rats on a high salt diet. Cadmium lowered circulating cholesterol levels in both lines on a low salt diet. Cadmium had no influence on growth, blood urea nitrogen concentration, plasma renin activity, tumor formation, or survivorship in R and S rats on either salt diet. This study indicates that the genetic composition is a critical determinant of the adverse effects of chronic low-level cadmium ingestion in rats. In addition to the experimental implications, these findings may have relevance to the problem of human "essential" hypertension.


Metallothionein in the extracellular fluids as an index of cadmium toxicity.

In rats injected with 5 micron mole CdCl2/kg, 5 days/week, metallothionein was detected in plasma by gel filtration chromatography as early as four weeks. The mean renal concentration of cadmium was 80 microgram/g. The excretion of cadmium in urine at this time was rather low and amounted to 0.01% of the total dose. The amount of metallothionein in plasma, as determined by 109Cd-binding to the 10,000 molecular weight fraction, increased markedly during week 14. Its excretion in urine, however, did not start until about 10 weeks, when the cadmium concentration in kidney approached a mean value of 212 microgram/g. Signs of renal toxicity were evident from glucosuria and proteinuria which became severe during the next four weeks. The excretion of cadmium in urine increased markedly and the majority of it was in the form of metallothionein. It is suggested that the appearance of metallothionein in plasma and urine can be used as specific indices of cadmium poisoning and that the assay of the protein in these fluids may be useful in screening for excessive cadmium exposure.


Studies on cadmium-induced inhibition of hepatic microsomal drug biotransformation in the rat.

Cadmium is a potent inhibitor of hepatic microsomal drug biotransformation in the rat. Male rats receiving a single intraperitoneal dose of cadmium exhibit significant decreases in hepatic microsomal metabolism of a variety of substrates. The threshold cadmium dose is 0.84 mg Cd/kg, and the effect lasts at least 28 days. Mechanistically, the inhibitory effect results from decreased cytochrome P-450 content since cadmium does not alter NADPH cytochrome c reductase activity. This effect is also observed following acute oral administration of cadmium in doses greater than 80 mg Cd/kg but is not observed following chronic administration of the metal via drinking water in concentrations of 5-200 ppm for periods ranging from 2 to 50 weeks. A tolerance to the inhibitory cadmium effect is observed if male rats are pretreated with subthreshold doses of the metal prior to the challenge cadmium dose. The degree of tolerance can be overcome by increasing the challenge dose of cadmium. Characterization of the tolerance phenomenon in terms of onset, duration, and intensity reveals a good correlation with the kinetics of metallothionein production, suggesting that the underlying basis for the tolerance phenomenon is likely the induction of metallothionein. A sex-related difference in the inhibitory effect of cadmium was observed. Cadmium did not inhibit the metabolism of hexobarbital or ethylmorphine in female rats but did inhibit that of aniline or zoxazolamine. Cadmium did not lower cytochrome P-450 content in female rats.


Cadmium, an effector in the synthesis of thionein.

Cadmium can elicit the synthesis of thionein in liver cells independent of tissue-organ interactions. The metal diffuses across the plasma membrane and is partitioned between subcellular components in a time dependent manner such that thionein synthesis responds to levels of nonspecifically and specifically bound cytoplasmic metal. Cadmium appears to function at the transcriptional level, and the metal may act to increase the pool of specific m-RNA's.


Early cellular effects of circulating cadmium-thionein on kidney proximal tubules.

Circulating cadmium-thionein (Cd-MT) is cleared from the mammalian circulatory system by filtration through the kidney glomerulus with subsequent reabsorption by kidney proximal tubules. Damage to the tubules results following uptake of Cd-MT, which is dependent upon time and the dose level of cadmium administered. Intravenous administration of 109Cd-MT at doses of 0.017 and 0.17 mg Cd/kg body weight with examination of total renal uptake of 109Cd at 0.5, 3, and 24 hr disclosed that the rate of clearance from the blood and uptake by the kidney was significantly more rapid at the 0.017 mg Cd/kg dose. Ultrastructural changes resulting from intravenous injection of either form A or B of Cd-MT were characterized by increased numbers of pinocytotic vesicles and small, dense lysosomal structures. There was no evidence of mitochondrial swelling or cell death at either 3 or 6 hr after injection. The subcellular distribution of cadmium in kidney tissue at various times after administration of Cd-MT was determined by using differential centrifugation techniques with 109Cd and in situ by using x-ray microanalysis. At 30 min after injection of Cd-MT, significant amounts of cadmium were present in lysosomal fractions indicating an interaction between the tubular lysosome system and Cd-MT prior to the onset of overt cellular toxicity. Results suggest that Cd-MT is reabsorbed and broken down by kidney tubule cells in a physiological manner with possible subsequent release of the toxic cadmium ion.


Some aspects of cadmium flow in the U.S.

A team of Purdue University engineers and scientists has been involved in studying sources, translocation mechanisms, and fate of cadmium in the environment. One of the principal results of this work has been the development of a cadmium flow model for the U. S. which involves simulating sources, use patterns, waste treatment and recovery techniques, waste disposal options, and environmental flow mechanisms. A series of model calculations performed specify cadmium environmental flow, fate, and human exposure for a variety of use pattern, waste treatment/recovery, and disposal scenarios over a ten-year-simulation period.


Cadmium from soil amended with sewage sludge: effects and residues in swine.

Liquid digested sewage sludge from a Chicago waste treatment plant was applied to experimental corn plots starting in 1968. The treatment plant received a high proportion of industrial effluent and the sludge averaged about 200 ppm Cd (dry weight). Corn grain harvested from the plots in 1974 was fed to growing swine for 56 days, and other swine were permitted to forage on the plots during the winters of 1975-76 and 1976-77. The sludge-fertilized corn contained higher concentrations of nutrient and toxic elements, but did not interfere with swine performance. Minor changes in hepatic microsomal oxidases and red blood cells accompanied significant increases in renal Cd and decreases in hepatic Fe. Swine foraging on these plots ingested considerable amounts of sludge soil and accumulated significantly higher concentrations of renal Cd. At lower rates of sludge application the swine outperformed those foraging both on control plots and those receiving heavy sludge applications in terms of weight gain, in-utero piglet survival, blood hemoglobin, and tissue Fe concentrations.


Cadmium uptake from feed and its distribution to food products of livestock.

Distribution of cadmium (Cd) into the edible products of three species of food-producing animals was investigated during long-term dietary administration of supplemental cadmium chloride. Cows were exposed to 0.2 (control), 2.4, and 11.3 ppm Cd on whole ration basis for a period of three months followed by a three-month period on control ration. No accumulation of Cd occurred in milk, muscle, or bone at any of the time periods. A dose-related increase of Cd was observed in liver and kidney. The Cd concentration in these organs showed a gradual rise even when the animals were given control ration for three months after an initial three-month exposure to Cd; this observation suggests a mobilization and redistribution of this metal from other tissues. Dietary Cd levels in swine rations were 0.2, 2.4, and 10.1 ppm. The highest level of Cd produced a slightly reduced growth rate in swine. No accumulation of Cd was observed in muscle, bone, or brain. Liver and kidney showed a treatment and time-related increase in cadmium values at 6 and 12 weeks on experiment. During a three-month depletion phase after an initial three months of Cd administration, no further change in liver and kidney Cd levels was observed. White Leghorn chickens were treated by administering 0.3, 1.9, and 13.1 ppm Cd in their diets for up to 6 months. No accumulation of Cd occurred in eggs or bones. A slight increase of Cd level was observed in chicken muscle after six months of exposure. Liver and kidney had the highest levels of Cd, which showed a dose and time-related increase in these organs. No depletion of liver and kidney Cd was seen during seven weeks following a six-week treatment period. In all three species, the kidney Cd levels were severalfold higher than those of liver at all dietary levels. In swine, the renal cortex and medulla had similar Cd concentration in control animals but in all animals exposed to supplemental Cd, a dramatic rise in Cd levels in renal cortex was observed. Medullary Cd did not show a proportional time and dose-related increase in Cd levels, although the levels showed some increase. In kidney and liver of all three species the Cd levels showed a positive correlation with the amount of Cd-binding protein in these tissues. Induced levels of this metal-binding protein may explain accumulation and persistence of Cd-residues in these organs. In all three species, the concentrations of renal Cd-binding protein increased at a rate greater than those in liver. Although the food-producing animals may act as an effective filter of Cd in the case of an environmental increase of this metal, consumption of visceral organs from such animals may pose a hazard. This is particularly critical since the daily intake of Cd in human diet is already estimated to exceed the tolerance limits suggested by WHO/FAO.


Deposit and mobility of cadmium in a marsh-cove ecosystem and the relation to cadmium concentration in biota.

The study reported here presents the results of an investigation of a marsh-cove ecosystem heavily contaminated by cadmium. The most contaminated aquatic sediments were dredged in 1972-73, but the resuspension of the sediments and recycle of water from the dredge spoil resulted in reestablishment of a large contaminated sediment bed with concentrations very similar to those observed before dredging. The stability of the sediment concentrations and shallow depth of the cadmium in the sediments indicate that the deposit is relatively stable in agreement with the expectations based on the water chemistry of the system. Uptake does occur in both marsh and aquatic plants and all species of animals tested. Significantly elevated concentrations are observed compared to noncontaminated areas; however, edible portions of most fish do not appear to present a hazard. Crabs appear to present the most likely source of a hazard to humans. This potential hazard is still under investigation. The dredging removed about 5.5 MT of cadmium, about one-fourth of that originally estimated to be present, but twice that amount is found to be in the cove sediments 3 to 4 years after dredging. No appreciable improvement in the ecosystem has been made, and more careful consideration should be given to the need for decontamination and the method of removal of contaminated aquatic sediments in any future case.