Flaw strength distributions and statistical parameters for ceramic fibers: the normal distribution.

The present paper investigates large sets of ceramic fibre failure strengths (500 to 1000 data) produced using tensile tests on tows that contained either 500 or 1000 filaments. The probability density function was determined through acoustic emission monitoring which allowed detection and counting of filament fractures. The statistical distribution of filament strengths was described using the normal distribution. The Weibull equation was then fitted to this normal distribution for estimation of statistical parameters. A perfect agreement between both distributions was obtained, and a quite negligible scatter in statistical parameters was observed, as opposed to the wide variability that is reported in the literature. Thus it was concluded that flaw strengths are distributed normally and that the statistical parameters that were derived are the true ones. In a second step, the conventional method of estimation of Weibull parameters was applied to these sets of data and, then, to subsets selected randomly. The influence of other factors involved in the conventional method of determination of statistical parameters is discussed. It is demonstrated that selection of specimens, sample size, and method of construction of so-called Weibull plots are responsible for statistical parameters variability.

Leadership 99. Interview by Terese Hudson.

Cost control, customer service and collaboration among health care sectors rank as top concerns with panelists in H&HN's annual Leadership Report. Efforts to improve community health are a priority, too, but are often frustrated by financial and other constraints. The 16 panelists represent managed care, physicians, and hospitals and health systems.

Life-threatening, antiglobulin test-negative, acute autoimmune hemolytic anemia due to a non-complement-activating IgG1 kappa cold antibody with Pra specificity.

A 21-year-old man with fulminant cold autoantibody hemolytic anemia (CAHA) was hospitalized with hemoglobinemia, hemoglobinuria, hemoglobin concentration of 3.3 gm per dL, a negative direct antiglobulin test (DAT) with polyspecific and anti-C3d reagents, a negative Donath-Landsteiner test, and a cold agglutinin titer of 80. He failed to respond to corticosteroids, multiple plasma exchanges, and cyclophosphamide; he required 54 transfusions in 10 days to maintain a hemoglobin concentration of 6.0 to 10.0 g per dL. He improved dramatically after a splenectomy was performed. The wide-thermal-amplitude cold agglutinin proved to be an IgG1 kappa antibody with Pra specificity. The patient's serum exhibited normal complement activation. When the DAT was carried out at 0 to 4 degrees C, the result was strongly positive for IgG; the indirect antiglobulin test at 0 to 4 degrees C was positive with the patient's serum diluted 1 in 640. Within 6 months, he was in complete remission and receiving no therapy. As compared with eight patients with CAHA that was exclusively IgG-mediated, this patient is remarkable for his requirement for many transfusions and for DATs that were consistently negative for C3d.

Cancer surveillance. Who stands to benefit?

Currently, surveillance or risk-oriented follow-up of patients in the individual practice setting may be the most efficacious means of reducing the morbidity and mortality associated with selected types of cancer. Intervention into carcinogenesis or alteration of the natural history of cancer requires a clear understanding of the pathogenesis of the disease and patient acceptance of interval surveillance. Because etiologic information and patient compliance are frequently limited, careful scrutiny of recommendations for cancer screening or prevention is essential. It is through taking detailed family, occupational, and carcinogen-exposure histories and doing a thorough physical examination that the primary care physician can best utilize information regarding the risk of cancer and the benefits of available methods of prevention and treatment.

Effects of altered porphyrin synthesis on brain neurochemistry.

Lead is one of several environmentally significant substances which alter porphyrin synthesis in several organs. Biochemically, the consequences of both acute and chronic lead exposure, at relatively low dose, are increases in tissue and plasma levels of the porphyrin precursor aminolevulinic acid (ALA) and inhibition of the enzyme ALA dehydrase. These effects are considered for their possible role in the neurotoxicity associated with lead exposure. The effects of lead, on porphyrin metabolism and on neurochemistry and behavior, are compared to those associated with exposure to the "suicide" inhibitor of ALA dehydrase, succinylacetone. Similarities in both porphyrinopathy and in associated neurotoxicity suggest an etiologic role for altered porphyrin synthesis in lead neurotoxicity.

Clinical trial of desferrioxamine entrapped in red cell ghosts.

Ten patients with excess body iron stores of different levels and with different diagnoses were given desferrioxamine inside osmotically lysed and resealed red blood cells (red cell ghosts). Red cell ghost entrapped desferrioxamine was given intravenously and, ten days later, an equal dose of desferrioxamine was administered via slow subcutaneous infusion over 10 h. Differences were apparent for these single dose challenges with respect to the pattern of urine iron excretion and the efficiency of iron chelation. The red cell ghost method consistently improved the efficiency of chelation, especially in patients with modestly increased body iron stores. This method of treatment may therefore prove to be of particular value in the patient with early siderosis who is embarking on a programme of regular transfusion for refractory anaemia.

Hepatic protoporphyrin production in human protoporphyria. Effects of intravenous hematin and analysis of erythrocyte protoporphyrin distribution.

Human protoporphyria with atypical features suggesting increased hepatic protoporphyrin synthesis was investigated in 2 patients. Analysis of the distribution of protoporphyrin among circulating erythrocytes of increasing age indicated that the erythrocyte porphyrin burden derived predominantly from erythroid sources in case 1, and from hepatic sources in case 2. Intravenous hematin was administered to both patients to assess any negative feedback effect on protoporphyrin synthesis. Erythrocyte, fecal and plasma porphyrin levels were measured serially during basal, treatment, and follow-up periods. In case 1, a significant (P less than 0.001) drop in both fecal and plasma levels accompanied hematin, while erythrocyte levels remained unchanged. Hematin produced no appreciable changes in porphyrin concentrations in case 2. Allergic vasculitis followed hematin use in both cases. Based on data of this study and on previous data, a model for protoporphyrin transport and clearance was developed in which the variable clinical and biochemical manifestations of human protoporphyria are related to the relative contributions of erythroid and hepatic sources to the abnormal protoporphyrin pools.

Hematin therapy for acute porphyria.

1. A therapeutic trial of intravenous hematin is presented. Eleven cases of AIP and one of VP who did not improve with conventional treatment (high carbohydrate intake) received this new agent. 2. Urinary ALA, PBG and, when possible, uroporphyrin and coproporphyrin were used to monitor the chemical response to the treatment. Objective clinical parameters of hypertension and tachycardia were followed when present in addition to subjective estimates of acute porphyric symptomatology (abdominal pain, backache, extremity pain and paresthesias, weakness, depression, etc.). 3. At a dosage of approximately 3 mg/kg, diminution of urinary ALA and PBG excretion was achieved in every patients. Hypertension and tachycardia improved in those instances where they were observed in association with the attack. Also, subjective improvements in the clinical status of the patients were observed frequently. 4. Hematin appears to be a promising therapeutic agent for the treatment of acute attack forms of porphyria.

Hematin administration to an adult with lead intoxication.

Lead poisoning and acute intermittent porphyria (AIP) may exhibit similar neurologic manifestations, and they have in common elevated excretion of urinary aminolevulinic acid (ALA). Despite their similarities, the possible pathophysiologic connection between AIP and lead poisoning in not known. Because intravenous hematin administration has produced biochemical improvement in AIP, a hematin trial in lead intoxication was of interest with respect to some of the heme metabolism abnormalities observed in the condition. Significant diminution of urinary ALA and coproporphyrin excretion occurred in association with intravenous hematin administration.

Family evaluations in acute intermittent porphyria using red cell uroporphyrinogen I synthetase.

Acute intermittent porphyria (AIP) is a primary disorder of haem biosynthesis that is chemically characterised by raised urinary porphobilinogen (PBG). A defect in the biochemical pathway at the step of PBG conversion to uroporphyrinogen has been shown to be a result of a partial deficiency of the enzyme uroporphyrinogen I synthetase (uro I syn). The ascertainment rate of latent AIP (that is, chemically manifest but clinically asymptomatic) was examined in 185 individuals from 12 AIP kindreds using three parameters: red cell uro I syn, quantitative urinary PBG, and pedigree analysis with respect to uro I syn. Approximately 80% of individuals could be assigned as normal or latent AIP on the basis of the uro I syn assay alone. The remaining 20% could not be assigned because of an intermediate range of activity for the red cell assay in which the diagnosis cannot be certain. When the pedigree was used in the evaluation of the uro I syn data, the number of uncertain individuals, with respect to AIP, decreased to 10%. The enzyme method detected latent AIP in 37.5% of blood relatives, whereas quantitative urinary PBG alone detected only 15.2%. The pattern of inheritance for the uro I syn deficiency is consistent with Mendelian dominant inheritance, and it is likely that it is the basic inherited defect in AIP.

Idiopathic hemochromatosis in a young female. A case study and review of the syndrome in young people.

Idiopathic hemochromatosis (iH) is typically a disease of older males. The case presented here describes a 26-yr-old woman with problems presenting heart failure, insulin-dependent diabetes, hepatomegaly, and secondary amenorrhea. The diagnosis was established by serum iron and transferrin saturation measurements, liver biopsy, and bone marrow examination for iron. Twenty grams of iron were removed by phlebotomy over 30 mo, and the patient's symptoms improved. A review of the literature pertinent to people with symptomatic onset of IH before age 30 yr revealed 52 young people in addition to this case. In contrast to IH patients older than 30, there was an almost equal ratio between the sexes, a greater frequency of cardiomyopathy and hypogonadism, and a lower frequency of diabetes mellitus and hepatic involvement. An autosomal recessive mode of inheritance appears to be most likely in this young group.

Danazol administration to females with menses-associated exacerbations of acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a disorder of porphyrin metabolism in which the basic defect is a partial deficiency of uroporphyrinogen I synthase. The clinical disorder is more common in women, and some experience acute attacks before menstrual periods. Oral contraceptives have prevented menstrual-associated attacks in some cases, but exogenous estrogens and progestins are otherwise contraindicated in this disease. Danazol, a new synthetic steroid with weak androgenic activity, was thought to be of potential therapeutic benefit in AIP because of its effect of decreasing gonadotropin secretion without exposure to estrogen or progesterone. The drug was administered at a dosage of 200 mg t.i.d. to two adult females with AIP who were experiencing frequent exacerbations of their disease in association with their menstrual periods. Symptomatic and chemical evidence for exacerbation of porphyria occurred within 10 days of commencing danazol treatment in both patients.