Evidence for quantum sticking of slow positronium.
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Biomedical subjects
Publications and source records attributed to T Martin.
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A 7-year-old girl had a 4 X 3 X 3 cm nodule on the left wrist with axillary lymphadenopathy. Acid-fast bacilli were seen on a smear from a biopsy specimen of this granulomatous skin lesion. A Rhodococcus species grew on culture. Skin infections caused by Rhodococcus may be more common than the few prior case reports suggest.
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Current models of the virus-like agents of scrapie and bovine spongiform encephalopathy (BSE) have to take into account that structural changes in a host-encoded protein (PrP protein) exhibit an effect on the time course of these diseases and the survival time of any man or animal exposed to these pathogens. We report here the sequence of different forms of the bovine PrP gene which contain either five or six copies of a short, G-C-rich element which encodes the octapeptide Pro-His-Gly-Gly-Gly-Trp-Gly-Gln or its longer variants Pro-Gln/His-Gly-Gly-Gly-Gly-Trp-Gly-Gln. Out of 12 cattle, we found eight animals homozygous for genes with six copies of the Gly-rich peptide (6:6), while four were heterozygous (6:5). Two confirmed cases of BSE occurred in (6:6) homozygous animals.
Cases from the files of Action for Victims of Medical Accidents which had resulted in stillbirth, perinatal or neonatal death and long term mental or physical handicap were reviewed. In 41 cases there was both a detailed letter from the parents and an independent review by a senior obstetrician. The reviewer's main criticisms were of inadequate fetal heart monitoring, lack of involvement of senior staff and inadequate records. The fetal heart trace was missing in 7 cases and over half of the remaining 34 traces available were misinterpreted or not acted on. In 17 cases junior doctors failed to recognize fetal distress and managed a delivery that they did not have the experience to deal with. In a further 6 cases, senior staff were called but did not come. Records were criticized for being incomplete, illegible or missing. In a few cases unjustified alterations appeared to have been made. Women reported that on some occasions staff ignored their worries, were unsympathetic and gave too little information. Some parents also experienced considerable difficulty in obtaining a clear explanation of the nature and cause of their child's condition.
From the beginning of the century to this day 57 cases of male genital self-mutilation have been reported in the English literature. In German publications we found 5 case descriptions. Although no precise data are available on the prevalence of male genital self-mutilation, such acts are presumably much more frequent than the small number of published cases would suggest. In the literature several features are regarded as risk factors for self-mutilation, such as e.g. homosexual or transsexual tendencies, repudiation of the male genitals, absence of a competent male for identification during childhood, feeling of guilt for sexual offences, and self-injury in the anamnesis. The most frequent diagnoses are schizophrenia and affective psychosis; alcohol intoxication was diagnosed in about one-fourth of the cases published. In the present paper we summarize data from the literature on epidemiology, psychopathology, psychodynamic and sociocultural factors in male genital automutilation and we describe 2 new cases of self-castration in which several of the risk factors described above were observed. We conclude that although it is difficult to estimate the risk of self-castration in view of the heterogeneity of the respective patient groups, the danger of such deeds should be kept in mind if the above factors are present.
Cisplatin is one of the most active chemotherapeutic agents for the treatment of squamous carcinoma of the head and neck; however, neurotoxicity and nephrotoxicity are dose-limiting. The analog, carboplatin, is a promising new agent with similar activity but a different spectrum of toxicity. To evaluate if a therapeutic advantage could be achieved with acceptable toxicity, a combination of carboplatin 350 mg/m2 and cisplatin 50 mg/m2 were administered every 28 days to patients with recurrent or metastatic disease who had received no prior chemotherapy. Of 24 patients enrolled in this study, 21 were assessable for response and toxicity. Five partial responses were observed (24%; 95% confidence interval [Cl], 4.9% to 38.6%). No complete response occurred. Two of these patients received definitive radiotherapy and achieved complete responses. The median survival of all patients was 24 weeks. Hematologic toxicity was dose-limiting necessitating a decrease in the starting dose of carboplatin to 300 mg/m2. Nonhematologic toxicity was infrequent and mild. Significant renal impairment occurred in only two patients. Although treatment with the combination of carboplatin and cisplatin is feasible, we found no therapeutic advantage in terms of an increased response or survival.
Between July 1984 and March 1986, we conducted a prospective randomized trial comparing propranolol and endoscopic sclerotherapy in the prevention of recurrent variceal hemorrhage in a group of non selected alcoholic cirrhotics. Seventy-six patients with variceal hemorrhage were randomized to receive propranolol (P) (34 patients), or sclerotherapy (S) (42 patients) approximately 12 days after initial bleeding. The 2 groups were similar as concern age, sex, etiology of cirrhosis, severity of liver failure, the number of previous hemorrhages, and the severity of initial hemorrhage. No side effects were observed in the P group; 20 patients (48 percent) in the group S had at least one side effect although minor. After an average follow-up of 36 months, 18 patients in group P (53 percent) and 23 in group S (55 percent) had hemorrhagic recurrence. Rebleeding occurred from other sources than esophageal varices in 5 patients, in the group S only. Five patients in group P and 8 patients in group S died of rebleeding. During the follow-up period, 8 patients in group P (23 percent) and 13 patients in group S (31 percent) died. No significant difference could be demonstrated between the 2 groups as regards the percentages of patients without variceal rebleeding or survival, calculated according to the Kaplan Meier method. In conclusion, in this trial, no significant difference could be demonstrated between propranolol and endoscopic sclerosis in the prevention of recurrent variceal hemorrhage in alcoholic cirrhotic patients.
Ten of 100 mature ewes were afflicted with acute oxalate toxicosis within 40 hours after being temporarily penned in a lot that contained considerable growing Rumex crispus (curly dock). Clinical signs of toxicosis included excess salivation, tremors, ataxia, and recumbency. Affected ewes were markedly hypocalcemic and azotemic. Oxalate crystals were not observed in urine. Gross postmortem lesions were minimal and nondiagnostic in 2 ewes that died peracutely, but perirenal edema and renal tubular degeneration were clearly observable in ewes euthanatized on the third day of toxicosis. Diagnosis of oxalate toxicosis was confirmed by histopathologic findings. Samples of Rumex spp contained 6.6 to 11.1% oxalic acid on a dry-weight basis, a concentration comparable with that in other oxalate-containing plants that have caused acute oxalate toxicosis.
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U. maydis is a fungal pathogen of corn with two forms: one is yeast-like and nonpathogenic; the other is filamentous and pathogenic. The b locus, with 25 different alleles, regulates this dimorphism: any combination of two different alleles triggers pathogenic development, whereas the presence of identical alleles results in the yeast-like form. We have cloned four b alleles (b1, b2, b3, and b4) and show that the b locus contains a single open reading frame (ORF) of 410 amino acids with a variable N-terminal region and a highly conserved C-terminal region (60% and 93% identity, respectively). Mutational analysis confirms that this ORF is responsible for b activity. The b polypeptides appear to be DNA binding proteins because they contain a motif related to the homeodomain in their constant region. We propose that combinatorial interactions between b polypeptides generate regulatory proteins that determine the developmental program of the fungus.
The development of highly sensitive immunoassays has made the detection of the multireactivity of antibodies a relatively common phenomenon. Polyreactivity is frequent in human auto antibodies, especially in rheumatoid factors (RFs), but the structural basis and the significance of this phenomenon remain substantially unknown. Recently, we showed that the double reactivity of a human monoclonal RF with histones was probably due to two distinct binding sites. However, cross-reactivity seems more frequent among polyclonal RFs occurring during autoimmune diseases than with monoclonal RFs. We studied double-reactive (IgG and histone H3) polyclonal RFs in a patient suffering from primary Sjögren's syndrome. We showed by means of affinity chromatographies that H3 cross-reactive RFs were only a small subset of the total patient's RFs and that this subset was enriched in IgA class. Competitive inhibition experiments suggested the existence of two distinct binding sites for IgG and H3. These results were confirmed by showing the selective sensitivity to acid treatment of the histone binding site and by producing a murine antiidiotope monoclonal antibody BII 2.1 defining an idiotope on bireactive RF apparently linked to the H3 binding site. This idiotope was absent in a panel of monoclonal RF, one of them cross-reacting with histone H3. This report extends previous results concerning a monoclonal RF to the polyclonal RFs which occur during autoimmune diseases.
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Galactose is incorporated into glycogen by a different metabolic route than glucose and fructose, the other major dietary monosaccharides. Oral galactose (4 g/kg) was given to 24-h-fasted adult rats to 1) compare quantitatively the disposition of galactose with that of glucose and fructose; 2) examine the effects of galactose on hepatic utilization of other metabolic fuels; and 3) examine circulating and liver galactose concentrations to determine whether net hepatic uptake of galactose, like glucose, occurs against a concentration gradient. Galactose absorption, hepatic blood flow, portal venous, arterial, hepatic venous, and liver concentrations of galactose, glucose, lactate, and alanine, and hepatic glycogen concentrations were measured at intervals up to 240 min. Concentrations entering and exiting the liver, hepatic intracellular concentrations, and net hepatic uptake/output were calculated. Galactose concentration entering the liver increased to a peak of 18.8 +/- 0.8 mumol/ml plasma water at 60 min and then decreased but remained above the control value. Liver galactose concentration increased dramatically from 0.28 +/- 0.04 to 21.2 +/- 1.1 mumol/ml liver water and exceeded plasma concentrations, even during the 1st 120 min when concentration gradients across the liver indicated net galactose extraction. Whole blood galactose concentrations initially were lower and then exceeded plasma concentrations, indicating that erythrocytes maintained galactose concentrations exceeding those in plasma. The data suggest that the hepatic and erythrocyte transport systems for galactose represent active mechanisms. Fifty-one percent of absorbed galactose was lost in urine; 18% of the remaining galactose load could be accounted for by net glycogen accumulation. Net increases in galactose, lactate, and alanine uptake could account for the glycogen synthesized but not for the net hepatic glucose output, which changed very little (6% increase).
Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usually does not produce clinical manifestations. This report describes primary cortisol resistance in a boy with isosexual precocity. A 6 7/12-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) tests. There were no features of glucocorticoid excess. Serum androstenedione and dehydroepiandrosterone concentrations were 4.7 +/- 0.3 nmol/L (mean +/- SEM of four measurements; normal less than 1.2) and 13.5 nmol/L (single measurement; normal, 1.0-2.2), respectively. The serum testosterone concentration was 0.9 nmol/L (normal, less than 0.7), and FSH and LH were normal. Serum cortisol concentrations were 1590 +/- 110 nmol/L (normal, 190-630) and 580 +/- 60 nmol/L (normal, 50-410) at 0800 and 2000 h, respectively. Serum cortisol responded normally to insulin-induced hypoglycemia. Glucocorticoids and adrenal androgens were resistant to suppression by dexamethasone. The Kd of [3H]dexamethasone binding to the glucocorticoid receptors of mononuclear leukocytes was increased (6.4 +/- 0.8 nM; mean +/- SEM of four determinations; normal, 1.4-3.4; P less than 0.001), but the binding capacity was normal. This patient with isosexual precocity has PCR, as indicated by functionally abnormal glucocorticoid receptors and hypercortisolism without other clinical or biochemical manifestations of Cushing's syndrome. Excessive adrenal stimulation by ACTH caused increased secretion of both cortisol and adrenal androgens, and the latter caused the clinical manifestations. PCR should be considered in other male children with isosexual precocity or female children with heterosexual precocity.
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The potential therapeutic value of anti-idiotypic antibodies during B cell proliferations largely depends on the stability of the target Ig idiotopes. We investigated this stability in a clinical condition of so called nonmalignant monoclonal B cell proliferation, mixed cryoglobulinemia. The idiotypic profile of a single IgM kappa monoclonal auto-antibody with anti-IgG activity (rheumatoid factor (RF] which originated from a patient suffering from a nonmalignant mixed cryoglobulinemia was followed over a period of 3 yr. As judged from the reactivity of a panel of five different mouse monoclonal anti-idiotypic antibodies mapping the RF variable regions, there was no idiotypic change in the serum IgM RF. At a cellular level, in vitro stimulation of the patient's PBL gives rise to IgM kappa auto-antibodies that were shown to bear the same idiotypic determinants as the serum IgM kappa. We then investigated the effects of the anti-idiotypic antibodies on the in vitro IgM kappa production. When stimulated with PWM and in the presence of anti-idiotypic antibodies (10 micrograms/ml), the patient's PBL produced less IgM RF (18 to 62% inhibition). The same inhibition of IgM RF production was observed after EBV infection of the patient's PBL (from 19 to 90% inhibition). In both cases, the remaining IgM RF production was idiotypically indistinguishable from the serum IgM RF. The implications of the idiotypic stability and of the results of in vitro idiotypic manipulation could be important in view of both the understanding of nonmalignant cryoglobulinemia and of the possible therapeutic use of anti-idiotypic antibodies in diseases.