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A patient with primary biliary cirrhosis who had high hepatic, serum, and urine copper levels was found by slit-lamp biomicroscopy to have pigmented corneal rings similar to Kayser-Fleischer rings. Wilson's disease was excluded on the basis of the elevated serum ceruloplasmin and copper levels, the lack of neurological disease despite advanced liver disease, a negative family history, and the typical clinical features of primary biliary cirrhosis. Although the exact chemical nature of the corneal rings is unknown, the cornea may be another tissue associated with elevated tissue copper levels in primary biliary cirrhosis.

Self-powered detectors are being used in an increasing number of heavy and light water reactors in both safety and flux mapping systems. The types available can be divided into neutron and gamma sensitive devices, with the neutron detectors further subdivided into those with a delayed response (the most common examples are Rh and V devices) and those with an instantaneous response (for example Co). The gamma sensitive devices, of which Pt is the most common example, all have instantaneous response. The properties of these detectors are related to their operating mechanisms and the relationship between them will be reviewed in the paper. These differences result in a series of detectors each with their own favorable and unfavorable characteristics. For example, Rh detectors produce the highest current of those considered but suffer from a delayed response (95% response in about 150 sec), and rapid burnup. Co detectors produce an instantaneous response, and burn up more slowly, but their current is about 1/60 that of Rh and they suffer from the buildup of a long lived background from neutron activation. Finally Pt detectors also produce an instantaneous response and have almost no burnup but their current is approximately 1/10 that of Rh and their response involves a mixture of neutron and gamma induced currents. At Westinghouse, we have been studying these detector characteristics by means of a Monte Carlo program written for that purpose and some of the insight gained from these calculations will be described in the paper.

There have been a number of experimental attemptsl,2 to determine the gamma and neutron responses of Pt self-powered (s-p) detectors in a reactor. The results of these measurements are subject to large uncertainties because a separation of the two components requires measurements in fields of differing neutron to gamma ratios. The problems arise from the difficulty of interrelating the results obtained under these different conditions. In this paper, we present a calculated result for the thermal neutron sensitivity of a Pt s-p detector using a model and computer program described elsewhere3. The accuracy of the computational method has been verified by a comparison between the calculated and measured neutron sensitivities of other s-p detectors. The calculated Pt result of 6.2 ± 10-24 A n-1 cm sec-1 turns out to be a factor of 1.5 lower than one of the experimental results and about 8 times lower than the other. Although the calculated and lower experimental results are quite similar, it is still felt that the former is the more accurate, based on 1) the difficulty and thus possible inaccuracy of the experiments, 2) burnup data, and 3) the established accuracy of calculations for other s-p detectors of similar type.

In-core gamma sensitive self-powered detectors have desirable characteristics such as instantaneous response and low burnup, but they do not directly measure the thermal neutron flux. Their usefulness thus depends on how well the in-core gamma flux distribution follows that of the thermal neutton flux, or more precisely how the distribution in the detector current follows that of the thermal neutron flux. To determine the behavior of these detectors we have computed the response of Pt and Pt-clad Inconel self-powered detectors to gammas from .1 to 8 MeV including the effect of recoil electrons produced in the surrounding material. Using these results and gamma spectra obtained from reactor design calculations the distributions over a PWR core of the current from each detector was determined and compared with that of the thermal neutron flux. The comparison showed that the distributions from either detector and the thermal neutron flux remained consistent within about 5% over most of the core but deviations of 10-15% occurred near the radial boundary of the core and 20-30% occurred at the very top and bottom. Thus a single calibration constant can be used to relate detector current to neutron flux for all the self-powered detectors in the core except those located very near the core boundaries.

The response of self-powered detectors are characterized by a sensitivity indicating the induced current per unit flux per unit length. However, a reactor neutron spectrum consists of a thermal and epithermal component and we show that the current produced by epithermal neutrons in Pt, Co and Rh detectors is a significant fraction of the total response. Since the ratio of the two spectral components varies with position within the core and with the age of the fuel a single sensitivity is not satisfactory for accurate flux measurements. A proper flux determination requires a knowledge of separate thermal and epithermal sensitivities as well as a means of measuring or calculating the ratio of the two neutron spectral components. In the paper we further discuss why the two sensitivities are required, provide values for Pt, Co and Rh detectors, describe how they were obtained and finally provide an interpretation of data in the literature in the light of the two sensitivities.

Self-powered (s-p) detectors are useful for incore neutron measurements in nuclear reactors because of their small size, ruggedness and simplicity. In one type of detector, a delayed current results from the beta activity induced in the device by the neutron flux while a second type gives an instantaneous response due to the compton electrons produced by the gammas released following the capture of neutrons in the device. To test these physical models and more importantly, to point the way to improvements in design without having to resort to excessive experimentation, a Monte-Carlo model was constructed to allow computations to be made of the response of both types of detector. The calculations were performed for Rh and V delayed and Co instantaneous detectors with emitter diameters of .051 cm and insulator thickness of .025 cm in all cases. The agreement with experiment was fairly good and the small discrepancies which occur are discussed in the paper.

For optimum operation of fast breeder reactors, knowledge of the incore power and breeding distributions is desirable. Because of the high temperature liquid sodium environment in the breeders, an activation method rather than a technique involving ion chambers seems to be the most appropriate experimental technique at present. An activation system has been worked out in which 1/16" BeO balls containing oxides of 235U and 238U are inserted into the reactor for activation and withdrawn to be counted in a Ge(Li) counter. Measurements of the activated fission and 239Np gamma-rays yield the desired information. Parameters and procedures are obtained based on a specific fast Demonstration Breeder design. However, only slight modification would be required for the application to other breeders.

Elastic scattering of 100 MeV protons by 3He and 4He has been measured over a wide range of angles. Analysis of the small-angle results was carried out using a superposition of nucleon-nucleon amplitudes computed with both modern and old phase shifts. No significant differences were found in the accuracy of the predictions resulting from the two sets, but in both cases the 3He results were better than those of 4He. The peaking evident in the backward p–4He scattering but not seen in heavy nuclei has been interpreted in terms of an exchange interaction using an optical model analysis.

Sixteen patients with Wilson disease (hepatolenticular degeneration) were studied from the hemostatic point of view, particularly with regard to platelet function. Five of the patients had a mild bleeding tendency that was characterized by easy bruising. Moderate thrombocytopenia was observed in three of the five bleeders and in two of the others. One bleeder was thrombocytotic and hyperfibrinogenemic. Bleeding times, platelet retention and prothrombin consumption were abnormal rarely. However, 15 of the 16 patients had some abnormality of platelet aggregation: one when adenosine diphosphate was added to platelet rich plasma, three when epinephrine was added, and the remainder when collagen was added. The collagen abnormalities were delayed or absent aggregation (five patients, four of whom were bleeders) and absence of a change of shape (12 of the 16 patients). Platelet aggregation was completely normal in only one patient.

Biliary bile acid composition and pattern of bile acid conjugation with glycine or taurine were found to be within normal limits in six patients with documented Wilson's disease. Four patients had previous biopsy evidence of cirrhosis (three with active hepatitis), but most conventional liver function tests gave normal results at the time of the study. Serum levels of conjugates of cholic acid, measured by radioimmunoassay, were not increased. However, plasma disappearance if intravenously injected glycine conjugate of cholic acid was significantly delayed in all subjects, suggesting that this is a more sensitive test of hepatic excretory function and may be of value for assessing hepatic function in patients with this rare genetic disorder. No evidence of a primary disturbance in bile acid metabolism was found in these patients.

The records of 54 consecutive patients with Wilson's disease seen at the Mayo Clinic from 1952 through early 1977 were reviewed to determine the frequency fo hematologic abnormalaties in their evaluation. Leukopenia and thrombocytopenia sometimes have been ascribed to treatment with D-penicillamine and its toxicity; however, we have found cytopenia to be a frequent finding in the presenting laboratory data of patients with Wilson's disease. Twenty-eight patients (52%) had thrombocytopenia and 16 of these patients (30% of the total) also had leukopenia. Severe, acute, intermittent hemolytic episodes were the initial and only presenting complaint of one patient. Six of the patients with significant cytopenias had splenectomy, and in all cases the peripheral blood counts returned to normal values. Long-term treatment with D-penicillamine improved the hepatic and neurologic dysfunction in most patients; however, the cytopenias remained unchanged except in three patients (treated 2, 5, and 10 years).

Fifty-eight patients with Wilson's disease are reviewed, of whom 25 symptomatic patients experienced liver disease first and 28, brain disease. Ten of these patients presented with liver disease alone, 19 with brain disease alone, and 24 with evidence of both liver and brain disease. The remaining five were discovered as asymptomatic siblings of known patients. Three of the patients with hepatic presentation and one with neurologic presentation later experienced the other type of symptomatology, bringing the total number of patients with mixed disease to 28. Of the 44 patients with brain disease, 12 presented primarily with extrapyramidal findings, 6 with cerebellar findings, and 17 with both; pseudobulbar findings were noted in 9 patients, all of whom had other symptoms of severe nervous system disease. In addition to these presentations, in an appreciable number of patients the first symptoms were of a mental or emotional disorder. Disease of other organ systems, such as the joints and kidneys, also occurred but infrequently. Where adequate family information was available, 13 of 65 siblings (20%) were known to have had or were suspected of having had Wilson's disease. This is consistent with the autosomal-recessive pattern of inheritance.

Fifty-three patients with Wilson's disease were studied with regard to ophthalmologic abnormalities. Of the 35 symptomatic patients initially seen and treated at the Mayo Clinic, 34 (97%) had Kayser-Fleischer rings and 6 (17%) had sunflower cataracts at the time of diagnosis. In patients followed for a year or more, penicillamine therapy resulted in improvement of the Kayser-Fleischer rings in 18 of 20 (90%) patients and total clearing of the sunflower cataracts in 4 of 5 patients. The specific pattern of copper deposition in Kayser-Fleischer rings and the improvement with treatment occurred along four reproducible stages. None of five asymptomatic siblings of patients with known Wilson's disease had Kayer-Fleischer rings at the time of initial study. In one (untreated) of the five, Kayser-Fleischer rings developed 20 months after the initial normal slit-lamp examination. The presence of Kayser-Fleischer rings, and the absence of other ophthalmologic signs (such as nystagmus, cranial nerve palsies, and other movement disorders), can be of great assistance in the diagnosis of Wilson's disease. Once the condition has been diagnosed, specific medical therapy with penicillamine and low-copper diet dramatically improves what would otherwise be an inevitably fatal course.

To the Editor.— Since the presence of Kayser-Fleischer rings has been deemed pathognomic of Wilson disease (hepatolenticular degeneration), I would like to call your attention to an exception to that rule. 1 A patient with primary biliary cirrhosis (PBC) was found by slit-lamp examination to have pigmented corneal rings that were similar to Kayser-Fleischer rings. Although the exact nature of these corneal rings is unknown, this patient with PBC had increased hepatic, serum, and urine copper levels. Wilson disease was excluded, despite the presence of these pigmented corneal rings, by the serum ceruloplasmin and copper concentrations, in conjunction with the lack of neurologic disease (despite the advanced hepatic dysfunction) and the typical clinical picture of PBC. Apparently, not all patients with pigmented corneal rings have Wilson disease.

Wilson's disease usually has its onset in childhood, adolescence, or early adulthood. The clinical picture of hepatic dysfunction without dysfunction of the central nervous system is more typical of the disease in the child or the adolescent than in the adult. We are presenting the case of a man whose age at onset of the disease was 55 years and who had the hepatic complications of Wilson's disease without clinical evidence of disease of the central nervous system. All patients with chronic hepatitis (chronic active liver disease) or cirrhosis of unknown etiology should be screened for the possibility of Wilson's disease. This screening should include slit-lamp biomicroscopy for Kayser-Fleischer rings, determination of serum ceruloplasmin concentration, and measurement of 24-hour urinary excretion of copper. If doubt exists concerning the diagnosis, either a radiocopper kinetic study, using 64Cu or 67Cu, or, if the patient's condition permits, a liver biopsy with measurement of hepatic copper concentration should be done. The rubeanic stain of hepatic tissue for copper is unreliable in making or excluding the diagnosis of Wilson's disease.

A patient with primary biliary cirrhosis who had high hepatic, serum, and urine copper levels was found by slit-lamp biomicroscopy to have pigmented corneal rings similar to Kayser-Fleischer rings. Wilson's disease was excluded on the basis of the elevated serum ceruloplasmin and copper levels, the lack of neurological disease despite advanced liver disease, a negative family history, and the typical clinical features of primary biliary cirrhosis. Although the exact chemical nature of the corneal rings is unknown, the cornea may be another tissue associated with elevated tissue copper levels in primary biliary cirrhosis.