Ill Health or Illness: A Reply to Hofmann

In this article I respond to Björn Hofmann’s criticism of some elements in my theory of health. Hofmann’s main objective is to question “Nordenfelt’s basic premise that you can be ill without having negative first-person experiences, and to investigate the consequences of abandoning the premise.” One of Hofmann’s critical points is that my theory of health does not lend voice to the individual. My response is essentially conducted in four steps: (1) I question the aim of conceptual analysis that Hofmann proposes for the analysis of the notion of health. (2) I maintain that my analysis, in spite of Hofmann’s contention, lends voice to the individual. It does so via my notion of subjective illness but also via my notion of vital goal. (3) I argue that conditions, such as coma, paralysis and mania are salient instances of ill health and that these may become neglected if the use of the terms “ill” and “illness” is restricted to instances where negative subjective experiences are present. (4) I rehearse my main arguments for selecting disability as the core element of ill health and respond to Hofmann’s contention that persons who are in great pain can sometimes nevertheless perform perfectly.     

Vigabatrin and retinal changes

Purpose: Vigabatrin is an effective antiepileptic drug but visual field constriction (VFC) is found to be a severe side-effect. The aims have been to investigate whether visual field constriction (VFC) is related to changes in the electroretinography (ERG). Methods: Twenty patients with localisations related epilepsy of whom one half had received vigabatrin were subjected to examination without informing about the treatment given. The eye examination included Goldmann perimetry and ERG. Results: All the patients had normal visual acuity. A total of three patients (30%) in the vigabatrin group and none in the control group were found to have VFC. In the vigabatrin group ERG examination were normal in one case, in five cases there were changes scotopic, photopic and in the oscillatory potentials (OP), while the remaining four had changes in two of these parameters. OPs were abnormal in eight of 10 patients. Of the three patients with VFC all had changes in ERG. The four patients with the most severe abnormalities in ERG had received high daily doses of vigabatrin (4 – 6 mg) in a period. In the control group no abnormality was observed in five cases, and in the remaining five changes were present in one or two of the potentials. Conclusion: It is found that 30% of patients treated with vigabatrin, develop VFC, and none in the control group. Similarly more patients in the vigabatrin group had changes in the ERG as compared to the control group, and the number of abnormal potentials are significantly higher among patients with VFC compared to those without. But the finding of abnormal ERG results is not synonymous with VFC, and this is important to bear in mind when examining patients that cannot cooperate to a VF examination. An individual sensitivity to vigabatrin is supposed, but severe ERG changes occurred in all patients having had high daily doses slant4 g.     

Scanner-assisted carbon dioxide laser surgery: a retrospective follow-up study of patients with hidradenitis suppurativa

BACKGROUND: The chronic fistulating lesions of hidradenitis suppurativa spread by contiguous growth, and all affected tissue needs to be surgically removed. OBJECTIVE: The aim of our study was to evaluate a surgical method for treatment of Hurley stage II hidradenitis suppurativa (HS), the carbon dioxide laser rapid-beam optomechanical scanner system in continuous mode. METHODS: Thirty-four patients were evaluated after treatment; 31 patients were women, and the mean age was 33.9 years (range, 15-55 years). All patients had had HS for a mean of 13.4 years (range 1-35 years) and more than 3 recurrences of suppurating lesions in the year before inclusion in the study. All lesions had been classified as Hurley stage II. The mean follow-up time after carbon dioxide laser surgery was 34.5 months (range, 7-87 months), and patients were later contacted by telephone about recurrences and the end results. RESULTS: The mean healing time was about 4 weeks (range, 3-5 weeks). During follow-up, 4 of the 34 patients had recurrences at the surgical site, that is, locoregional HS. Thirty had no recurrences in the treated area, but in 12 cases de novo suppurating lesions, separated from the initial surgical site by >5 cm, developed. Twenty-five patients had flares of HS lesion(s) in an area other than the treated site. Eight had no recurrences. CONCLUSION: Macroscopically controlled tissue-selective carbon dioxide laser treatment of HS is a fast, efficient treatment and well accepted by the patients.     

Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer’s disease patients and controls

The apolipoprotein E (ApoE) ε4 allele is the strongest risk factor of sporadic Alzheimer’s disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE ε2, ε3, ε4) remain controversial. Using a novel mass spectrometry-based method, we quantified total ApoE and specific ApoE isoform concentrations and potential associations with age, cognitive status, cholesterol levels and established AD biomarkers in cerebrospinal fluid (CSF) from AD patients versus non-AD individuals with different APOE genotypes. We also investigated plasma total ApoE and ApoE isoform composition in a subset of these individuals. In total n = 43 AD and n = 43 non-AD subjects were included. We found that CSF and plasma total ApoE levels did not correlate with age or cognitive status and did not differ between AD and non-AD subjects deeming ApoE as an unfit diagnostic marker for AD. Also, whereas CSF ApoE levels did not vary between APOE genotypes APOE ε4 carriers exhibited significantly decreased plasma ApoE levels attributed to a specific decrease in the ApoE4 isoform concentrations. CSF total ApoE concentrations were positively associated with CSF, total tau, tau phosphorylated at Thr181 and Aβ1-42 of which the latter association was weaker and only present in APOE ε4 carriers indicating a differential involvement of ApoE in tau versus Aβ-linked neuropathological processes. Future studies need to elucidate whether the observed plasma ApoE4 deficiency is a life-long condition in APOE ?4 carriers and whether this decrease in plasma ApoE predisposes APOE ?4 carriers to AD.     

Craniopagus parasiticus Everard Home's Two-Headed Boy of Bengal and some other cases

Craniopagus parasiticus, or épicome, is a rare teratological type, of which only six cases have been recorded in the medical literature. It differs from craniopagus conjoined twins in that the body and limbs of the parasitic twin are underdeveloped, leaving in some cases only a parasitic head, inserted on the crown of the autositic twin. The first case of this malformation was Everard Home's famous Two-Headed Boy of Bengal, whose skull is preserved at the Hunterian Museum. In this historical review, Home's case is presented in some detail, and the later cases are used to explain further some of its particulars.     

Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid

The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, we present the discovery of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid (1) based on a rational design process. Target compound 1 was synthesized by a stereoselective strategy in 10 steps from commercially available starting materials. Binding affinities of 1 at native ionotropic Glu receptors were determined to be in the micromolar range (AMPA, 51 μM; KA, 22 μM; NMDA 6 μM), with the highest affinity for cloned homomeric KA receptor subtypes GluK1,3 (3.0 and 8.1 μM, respectively). Functional characterization of 1 by two electrode voltage clamp (TEVC) electrophysiology at a nondesensitizing mutant of GluK1 showed full competitive antagonistic behavior with a K(b) of 11.4 μM.     

Evidence for a bimodal relation between serum lysozyme and prognosis in 232 patients with acute myeloid leukaemia

Lysozyme values are sometimes used as an aid for diagnostic subtyping of acute myeloid leukaemia (AML), since monocytic forms often show high levels. We wanted to study if pretreatment serum lysozyme has any relation to prognosis in AML. For this purpose, 232 adult AML patients who had received remission induction therapy at two hospitals were reviewed retrospectively. Their median age was 65.5 yr. Sixty-three patients were FAB classified as "monocytic" AML (M4, M5) and 169 as "non-monocytic" AML (M0, M1, M2, M3, M6). A linear relation was rejected, and a bimodal relation was found between lysozyme and prognosis where values below 20 or above 80 mg L-1 were indicative of better outcome than values in the range 20-80 mg L-1. Analysed in three categories with cut-off levels at 20 and 80 mg L-1, lysozyme showed an independent effect on complete remission (CR) frequency (P = 0.0003), overall survival (P < 0.0001), and CR duration (P = 0.0005) in multivariate analysis. The hazard ratios (HR) for lysozyme <20, 20-80, and >80 mg L-1 regarding overall survival were 1.0, 3.3, and 0.7. Influence of lysozyme on survival was bimodal both in "non-monocytic" AML (HR 1.0, 3.0, and 0.1) and M4-M5 (HR 1.0, 10.1, and 1.2). Our finding of a bimodal relation between serum lysozyme and prognosis in AML should be regarded as a new hypothesis and controlled in other studies.     

Response to methimazole in Graves' disease

OBJECTIVE A variety of regimens continue to be used In the treatment of Graves' disease with antithyrold drugs. We have lnvestigated the factors which determine the initial response to methimazole (time until euthyroidism Is achieved) In Graves' disease. PATIENTS Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months. MEASUREMENTS Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary Iodide excretion were measured centrally. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, Index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase. RESULTS Within 3 weeks, 40.2% of patients responded to 10mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroldism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), Index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed In patients with large goitres, iodine excretion of ≧ 100μg/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyrold within 3 weeks when urinary Iodide was <50μg/g of creatinine, and only 27% when iodide was above 100μg/g. By stepwise logistic regression, the main factors for the response to methimazole were dally dose, pretreatment T3 levels, and goitre size. CONCLUSION Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole In Graves' disease, at least In areas comprising low, subnormal and normal iodine supply.     

Gammalinolenic acid treatment of fatigue associated with primary Sjögren's syndrome

OBJECTIVE: To evaluate the efficacy of the essential omega-6 fatty acid Gammalinolenic acid (GLA) on fatigue associated with primary Sj?gren's syndrome. METHODS: Ninety patients with primary Sj?gren's syndrome (with or without signs of autoimmunity) entered a 6-month double blind placebo-controlled randomised trial with high dose GLA (extracted from Evening Primrose Oil) or corn oil. The primary outcome parameter was fatigue; secondary endpoints were eye dryness, mouth dryness, muscle and joint pain. RESULTS: No statistically significant improvement was found in fatigue assessed by Visual Analogue Scale (VAS) or in the time needed for sleeping/resting during a 24-hour period. No differences were found between the treatment and placebo group. The same applies to the secondary endpoints: no differences in VAS for eye and mouth dryness or pain, no significant changes in Schirmer-1-test, van Bijsterveld score, unstimulated whole sialometry (UWS), or use of artificial tears or analgesics. Only mild side effects were observed. CONCLUSION: According to our study results GLA (Evening Primrose oil) treatment for fatigue in primary Sj?gren's syndrome is ineffective.     

Stage-specific regulation of adhesion molecule expression segregates epithelial stem/progenitor cells in fetal and adult human livers

Purpose Regulated expression of cell adhesion molecules could be critical in the proliferation, sequestration, and maintenance of stem/progenitor cells. Therefore, we determined fetal and adult stage-specific roles of cell adhesion in liver cell compartments. Methods We performed immunostaining for the adhesion molecules, E-cadherin and Ep-CAM, associated proteins, β-catenin and α-actinin, hepatobiliary markers, albumin, α-fetoprotein, and cytokeratin-19, and the proliferation marker, Ki-67. Expression of albumin was verified by in situ mRNA hybridization. Results In the fetal liver, hepatoblasts showed extensive proliferation with wide expression of E-cadherin, β-catenin, and α-actinin, although Ep-CAM was expressed in these cells less intensely and focally in the cell membrane to indicate weak cell adhesion. Hepatoblasts in ductal plate and bile ducts showed less proliferation and Ep-CAM was intensely expressed in these cells throughout the cell membrane, indicating strong adhesion. In some ductal plate cells, β-catenin was additionally in the cytoplasm and nucleus, suggesting active cell signaling by adhesion molecules. In adult livers, cells were no longer proliferating and E-cadherin, β-catenin, and α-actinin were expressed in hepatocytes throughout, whereas Ep-CAM was expressed in only bile duct cells. Some cells in ductal structures of the adult liver with Ep-CAM coexpressed albumin and cytokeratin-19, indicating persistence of fetal-like stem/progenitor cells. Conclusions Regulated expression of Ep-CAM supported proliferation in fetal hepatoblasts through weak adhesion and helped in biliary morphogenesis by promoting stronger adhesion in hepatoblasts during this process. Restriction of Ep-CAM expression to bile ducts in the adult liver presumably facilitated sequestration of stem/progenitor cells. This stage-specific and cell compartment-related regulation of adhesion molecules should be relevant for defining how liver stem/progenitor cells enter, exit, and remain in hepatic niches during both health and disease.