Severe severe psychological repulsion reaction in patient with PAD resulted in natural lower extremity mummification.

This case report describes the very uncommon event of mummification of the lower limb occurring naturally in a patient with peripheral arterial occlusive disease aggravated by severe reactive aversion and serves as a warning that this can happen in cases of untreated advanced critical limb ischemia even in well developed countries.

Elevating tensor rank increases anisotropy in brain areas associated with intra-voxel orientational heterogeneity (IVOH): a generalised DTI (GDTI) study.

Rank-2 tensors are unable to represent multi-modal diffusion associated with intra-voxel orientational heterogeneity (IVOH), which occurs where axons are incoherently oriented, such as where bundles intersect or diverge. Under this condition, they are oblate or spheroidally shaped, resulting in artefactually low anisotropy, potentially masking reduced axonal density, myelinisation and integrity. Higher rank tensors can represent multi-modal diffusion, and suitable metrics such as generalised anisotropy (GA) and scaled entropy (SE) have been introduced. The effect of tensor rank was studied through simulations, and analysing high angular resolution diffusion imaging (HARDI) data from two volunteers, fit with rank-2, rank-4 and rank-6 tensors. The variation of GA and SE as a function of rank was investigated through difference maps and region of interest (ROI)-based comparisons. Results were correlated with orientation distribution functions (ODF) reconstructed with q-ball, and with colour-maps of the principal and second eigenvectors. Simulations revealed that rank-4 tensors are able to represent multi-modal diffusion, and that increasing rank further has a minor effect on measurements. IVOH was detected in subcortical regions of the corona radiata, along the superior longitudinal fasciculus, in the radiations of the genu of the corpus callosum, in peritrigonal white matter and along the inferior fronto-occipital and longitudinal fascicula. In these regions, elevating tensor rank increased anisotropy. This was also true for the corpus callosum, cingulum and anterior limb of the internal capsule, where increasing tensor rank resulted in patterns that, although mono-modal, were more anisotropic. In these regions the second eigenvector was coherently oriented. As rank-4 tensors have only 15 distinct elements, they can be determined without acquiring a large number of directions. By removing artefactual underestimation of anisotropy, their use may increase the sensitivity to pathological change.

Dielectric relaxation of a protein-water system in atherosclerotic artery wall.

Measurements of the dielectric properties of healthy and atherosclerotic human artery tissues were made in the frequency range of 100 Hz-100 kHz and temperatures from 22 to 260 degrees C. The temperature dependencies of the dielectric parameters for healthy tissues reveal distinctively the temperature ranges corresponding to the release of water up to 200 degrees C and the decomposition processes of elastin and collagen, above this temperature. The influence of atherosclerosis on the dielectric properties of artery tissues is significant in the whole temperature range. The relative permittivity for atherosclerotic tissues at the same temperature is much lower than for the healthy tissues. This suggests, that the polarization in atherosclerotic tissues due to protons hopping between a smaller number of sites than in healthy tissues, as a results of the thermal degradation of collagen-water. The data obtained above 200 degrees C indicate that the atherosclerosis induces the higher physico-chemical changes in the collagen when compared to elastin.

Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populations.

The polymorphic T-cell receptor Vbeta (TRBV) genes encode much of the variable region of the T-cell receptor beta chain. Analysis of allele frequencies of three closely linked polymorphic TRBV genes, TRBV7-3, TRBV9 and TRBV6-4, was undertaken in several populations. The frequencies of these alleles are not significantly different in populations of Caucasians, African Americans and Western Africans. However, Chinese population is extremely homogenous at all three loci. The current study identifies the existence of haplotypic relationships between alleles of these genes in the Caucasian population. The ORF allele TRBV7-3*A3 is found exclusively on chromosomes bearing TRBV9*A2 and TRBV6-4*A2 in this cohort. In contrast, TRBV7-3*A1 and the null allele TRBV7-3*A2 are associated only with TRBV9*A1 and TRBV6-4*A1. This pattern of linkage disequilibrium (LD) is altered in the African American and Western African populations. In these cohorts, there is a marked reduction in LD between alleles of TRBV7-3 and TRBV9. This study is consistent with previous population genetic studies wherein African-derived samples have a greater level of genetic diversity compared to Caucasians. These data also demonstrate that patterns of LD are not consistent across the entire TRBV locus.

Analysis of the Ser786Pro interleukin-4 receptor alpha allelic variant in allergic and nonallergic asthma and its functional consequences.

Asthma and other atopic disorders affect a large percentage of the population. While many factors contribute to the phenotype of asthma, there is a strong genetic predisposition. IL-4 is a central mediator of allergic inflammation. Along with IL-13, it is the major cytokine responsible for the induction of IgE synthesis. Furthermore, IL-4 acts on Th0 cells and promotes their differentiation into Th2 cells resulting in the production of more IL-4 and IL-13, thereby propagating the allergic cascade. Both IL-4 and IL-13 utilize IL-4Ralpha as a component of their cognate receptor complexes. Eight polymorphisms of the IL-4Ralpha gene resulting in amino acid changes in the coding sequence have been described, and several have been associated with asthma. The central objective of this study was to elucidate the role of the Ser786Pro polymorphism in asthma and its impact on IL-4R function. One-hundred ninety-six individuals with asthma and 53 controls were genotyped for Pro786. Pro786 occurred infrequently in the general population with an allele frequency of 1.8% and, thus, is unlikely to play a major role in atopy or asthma. The Pro786 allele frequency was 1.5% in the asthma group and 2.8% in the control group. The asthma group was subdivided into allergic and nonallergic asthma, and the Pro786 allele frequencies were 1.7 and 1.0%, respectively. The data suggested linkage disequilibrium between Ser786Pro and the Gln576Arg allele, which is associated with atopy. In order to study the impact of the polymorphism on receptor signaling function, we transfected a mouse B lymphoma cell line with the wild-type and Pro786 variants of human IL-4Ralpha. The Ser786Pro polymorphism in isolation did not affect IL-4R function.

A novel polymorphism in the pseudogene TCRBV5S5 combines with TCRBV6S1 to define three haplotypes.

In the current study, we report a G to A single nucleotide polymorphism at base pair 396 of the TCRBV5S5P gene. This polymorphism has a frequency of 0.20 in a cohort of Caucasian controls. In addition, we provide evidence for linkage disequilibrium between TCRBV5S5P and the TCRBV6S1 gene.

Math5 is required for retinal ganglion cell and optic nerve formation.

The vertebrate retina contains seven major neuronal and glial cell types in an interconnected network that collects, processes and sends visual signals through the optic nerve to the brain. Retinal neuron differentiation is thought to require both intrinsic and extrinsic factors, yet few intrinsic gene products have been identified that direct this process. Math5 (Atoh7) encodes a basic helix-loop-helix (bHLH) transcription factor that is specifically expressed by mouse retinal progenitors. Math5 is highly homologous to atonal, which is critically required for R8 neuron formation during Drosophila eye development. Like R8 cells in the fly eye, retinal ganglion cells (RGCs) are the first neurons in the vertebrate eye. Here we show that Math5 mutant mice are fully viable, yet lack RGCs and optic nerves. Thus, two evolutionarily diverse eye types require atonal gene family function for the earliest stages of retinal neuron formation. At the same time, the abundance of cone photoreceptors is significantly increased in Math5(-/-) retinae, suggesting a binary change in cell fate from RGCs to cones. A small number of nascent RGCs are detected during embryogenesis, but these fail to develop further, suggesting that committed RGCs may also require Math5 function.

p53, MDM2, bcl-2 staining in follicular neoplasms of the thyroid gland.

Sixty-two follicular adenomas of the thyroid were investigated by immunohistochemistry for the expression of p53, MDM2 and bcl-2 proteins. The wild type of 393 aminoacid nuclear p53 phosphoprotein is the product of a gene located on the short arm of chromosome 17. The p53 protein controls the growth of transformed cells in a culture and thus termed a suppressor gene product. Mouse double minute 2 (MDM2) gene product has been described to occur in malignant epithelial tissue, the protein product of this gene binds to and presumably inactivates the growth suppressive effect of wild type p53 protein. Bcl-2 is an oncogene whose product inhibits apoptosis in many cells types. Some scattered nuclei in two adenomas (3.2%) stained positively for p53. The adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found, both patients are alive and well. In 12 adenomas (19%) there was positive reaction for MDM2 protein, whereas none of them where p53 positive. All cases were strongly positive for bcl-2 staining. We conclude that p53 protein expression is not confined to follicular adenomas, while MDM2 and bcl-2 genes products are.

Expression of proteins: D1 cyclin and Ki-67 in papillary thyroid carcinomas.

The aim of the study was an evaluation of expression of D1 cyclin and Ki-67 proteins in tissue of human papillary thyroid carcinoma (PTC) in a group of papillary microcarcinomas and in a group of PTC with a degree of staging higher than pT1a in TNM classification. We performed immunohistochemical staining and found no statistical differences between groups. These results suggest that changes of expression of D1 cyclin are an early event in tumorigenesis.

[The usefulness of the method of planar diffusion echo imaging (EPI DWI) in the diagnosis of cerebral ischemia]. / Przydatnosc metody echa planarnego obrazowania dyfuzyjnego (EPI DWI) w diagnostyce udarów niedokrwiennych mózgowia.

The preliminary results of MR echoplanar diffusion-weighted imaging (EPI DWI) in patients with stroke are presented. Twelve patients (5 females, 7 males) aged 36-78 years (mean 63.8) were examined by 2T system. No focal lesions were found in the acute phase of stroke on T1-weighted images. Narrowing of sulci in the region of stroke was the only abnormal finding. Focal hyperintense lesions were shown on PD and T2-weighted images in 50% of patients in the acute phase, 7 hours after the onset of clinical symptoms. On EPI diffusion-weighted images focal decrease of apparent diffusion coefficient (ADC) was observed in all cases of the acute phase of stroke after 3 hours. EPI DWI allows for earliest detection of ischaemic lesions in brain tissue. The method is especially useful in characterisation of the acute phase of stroke and shows its evolution thanks to the use of ADC.

Role of short TE 1H-MR spectroscopy in monitoring of post-operation irradiated patients.

Post-surgical radiation therapy is a routine procedure in the treatment of primary malignant brain tumors. Along with modest therapeutic effects conventional fractionated radiotherapy, in spite of any modifications, produces damage to non-malignant brain tissues lying within the treatment volume, the extent of which depends on radiation dose. Serial 1H-MRS allows non-invasive investigation of tissue metabolic profiles. In the present study the ratios of resonance signals assigned to the major 1H-MRS-visible metabolites (N-acetylaspartate, choline, creatine, inositol, lactate and lipid methylene group) were evaluated before, during and after post-surgical fractionated radiotherapy in brain regions close to and more distant from the tumor bed, receiving different radiation exposures (60 and < 40 Gy, respectively). The study group consisted of ten patients (aged 28-51). A MRI/MRS system (Elscint 2T Prestige) operating at the field strength of 2 T and the proton resonance frequency of 81.3 MHz has been used and the 1H-MR spectra were acquired using single voxel double-spin-echo PRESS sequence with a short TE. The spectra were post-processed with automatic fitting in the frequency domain. It was found that although the metabolite profiles depend on the dose obtained, but other stress factors (like surgery) seem to contribute to the overall picture of the metabolic status of the brain as well. In studies of early irradiation injuries, an increase of choline related ratios may serve rather as cell proliferation indictors than as cell injury ones, whereas the mI/Cr ratio appears as one of the first indicators of local irradiation injury. In order to establish the prognostic marker for early radiation damage, however, it seems necessary to analyze all visible metabolites as well. None of the metabolites separately may serve as such an indicator due to the complexity of tissue metabolism. Interestingly, MRI reveals no changes during the therapy process, whereas the metabolite ratios are being affected in the course of time, thus supporting the presumption that the 1H-MRS is a valuable method of radiation therapy monitoring.

Increased plasma concentration of epidermal growth factor in female patients with non-toxic nodular goitre.

OBJECTIVE: Epidermal growth factor (EGF) is believed to be one of the most potent growth factors for the thyroid gland. DESIGN AND METHODS: We tested plasma EGF concentrations (radioreceptor method) in patients with non-toxic nodular goitre (NNG). Blood samples from patients with NNG were collected on the day before the surgery, during subtotal thyroidectomy (sTx)--from peripheral and thyroid veins, on the 3rd day after sTx, 3 months after sTx, and 9 months after the surgery. RESULTS: Before the operation, the mean plasma EGF concentration in 50 women with NNG was significantly higher (1.16 +/- 0.69 ng/ml; mean +/- S.E.) than that in 32 control female patients subjected subsequently to other (non-thyroid) operations (0.41 +/- 0.27 ng/ml; P < 0.001), and that in 20 healthy women (0.35 +/- 0.11 ng/ml; P < 0.001), both of which groups were without goitre or had a small non-toxic diffuse goitre. The surgical treatment of NNG resulted in a significant reduction in plasma EGF 3 months after sTx (0.56 +/- 0.22 ng/ml). A further slight decrease was observed 9 months after sTx (0.44 +/- 0.14 ng/ml). CONCLUSIONS: Our observations confirm the assumption that EGF may participate in the process of goitre formation in human subjects. However, the source of EGF involved in this process remains unclear. Some findings could suggest that plasma EGF, which was increased in patients with NNG, may be of non-thyroid origin; however, the majority of our observations strongly stress the significance of an intact thyroid in the preservation of an unchanged EGF value, suggesting a role of locally produced EGF in the pathogenesis of NNG.

Thymidine Kinase (EC 2.7.1.21) Activity in Homogenates of Human Thyroid Tissue, Following the Exposure to Epidermal Growth Factor (EGF) in vitro.

The activity of thymidine kinase (TK - EC 2.7.1.21) was measured in human thyroid tissue homogenates incubated in vitro. This enzyme functions as a part of the pyrimidine salvage pathway involved in DNA synthesis. The thyroid tissue was obtained from the thyroids of patients thyroidectomized at the Department of Endocrine Surgery, Medical University of lodz because of: 1. non-toxic nodular goiter (NTNG): tissue macroscopically unchanged, woman 46 yrs; 2. non-toxic adenoma (NTA), woman 37 yrs; 3. toxic adenoma (TA), woman 45 yrs. The tissue was incubated for 4 hours in RPMI 1640 medium (Gibco), containing Hepes buffer, 15 % FCS and the examined substance - epidermal growth factor (EGF) - used in five different concentrations (0.1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml). The TK activity was measured according to Cheng and Prusoff (1974) as modified by Greger and Draminski (1989). The reaction products were separated by ascending chromatography. It was found that: 1. TK activity in thyroid tissue from NTNG and NTA did not significantly differ from control incubations without EGF, while it was significantly higher in the thyroid tissue from TA; 2. in the range of concentrations from 1 ng/ml to 1000 ng/ml, EGF increased TK activity in the macroscopically unchanged tissue from NTNG; 3. the incubation of the tissue from NTA with EGF resulted in the increase of TK activity in a concentration-dependent manner; 4. EGF stimulated TK activity in the tissue from TA, but the difference was significant only after the lowest EGF concentration. The obtained results suggest a possible role of EGF in the pathogenesis of NTNG, as well as of NTA and TA in humans.

Secondary adrenal insufficiency associated with autoimmune disorders: a report of twenty-five cases.

OBJECTIVE: Addison's disease is frequently a component of autoimmune polyendocrinopathies while secondary adrenal insufficiency associated with autoimmune disorders is believed to be a rare event. We present a series of patients with secondary adrenal insufficiency coexisting with autoimmune diseases and/or antithyroid autoantibodies. DESIGN AND PATIENTS: Among a group of 102 patients with secondary adrenal failure of unknown origin diagnosed at the Department of Endocrinology of the Centre for Postgraduate Medical Education (Warsaw, Poland) we have identified a group with associated autoimmune disorders. Thyroid abnormalities occurred most frequently. Other diseases included insulin-dependent diabetes mellitus, pernicious anaemia, vitiligo, premature ovarian failure and autoimmune thrombocytopaenia. There were 23 women and one man aged 17-72 years at the time of investigation. Additionally, we included a woman with Addison's disease in whom the ACTH deficiency appeared 18 years after the onset of primary adrenal hypofunction. MEASUREMENTS: Pituitary-adrenal function tests comprised urinary excretion of 17-hydroxycorticosteroids in basal conditions and during a 2-day tetracosactrin test, plasma concentrations of ACTH and cortisol, and a 2-day metyrapone test (in eight cases). Thyroid function and immunity tests were: TSH, thyroxine, the antithyroglobulin, antimicrosomal and anti-peroxidase autoantibodies. Other endocrine studies included: serum LH, FSH and PRL. RESULTS: The 17-hydroxycorticosteroid values, both basally and during stimulation tests were consistent with a diagnosis of secondary adrenal insufficiency. Serum cortisol and plasma ACTH concentrations were low. In 14 patients primary hypothyroidism was confirmed by low T4 levels. In three patients subclinical primary hypothyroidism was revealed (elevated TSH levels). Three patients who had a past history of Graves' disease were euthyroid at the time of investigation. Twenty-three patients had antibodies against peroxidase. Most patients had gonadotrophins and PRL values within normal limits. CONCLUSIONS: The co-existence of autoimmune disorders with secondary adrenal insufficiency suggests an autoimmune aetiology for the ACTH deficiency.

MRI versus CT in the diagnosis of Nelson's syndrome.

The purpose of the study was to evaluate the utility of MRI and CT in the diagnosis of Nelson's syndrome, i. e. pituitary tumours in patients bilaterally adrenalectomized for Cushing's disease. Thirteen patients, followed up for 5-29 years after adrenalectomy, were studied. In 6 of them CT and MRI revealed no changes in the pituitary gland. In the remaining 7 patients only three CT scans were suggestive of a pituitary adenoma. MRI studies with administration of gadodiamide confirmed the CT diagnosis of Nelson's tumour in 3 patients and disclosed microadenomas in a further 4 patients. Neurosurgical treatment in 4 patients confirmed the MRI findings. Additionally CT and MRI examinations were performed in 5 patients suspected of a recurrent Nelson's tumour 3-11 years after neurosurgery. MRI visualized recurrent adenomas in 3 patients that were not well seen by CT scans. In our experience MRI was more effective than CT in the diagnosis of Nelson's syndrome.

INFLUENCE OF EGF ON THE RELATIVE VOLUMES OF COLLOID, EPITHELIUM AND STROMA AND ON THYROCYTE NUCLEI SIZE IN RAT THYROID LOBES IN VITRO.

The epidermal growth factor (EGF) is believed to be a potent growth factor for the thyroid gland. In the present study, we have examined the relative volumes of the main histological compartments (colloid, epithelium and stroma) and the size of thyrocyte nuclei (the mean volume, the mean intersection area and the mean perimeter) in the rat thyroid lobes incubated in vitro for 18 hrs with EGF, applied in 5 different concentrations: 0.1, 1.0, 10, 100 and 1000 ng/ml. Morphometric evaluation was performed, using a computer image analysis system, developed by us. We found that EGF - in concentration of 100 ng/ml - increased the relative volume of stroma when compared to controls, as well as to all the other groups incubated in exposure to that growth factor (used in different concentrations); at the same time, EGF decreased the relative volume of epithelium in the thyroid gland (statistical significance has been recorded only vs. EGF concentrations of 10 ng/ml and 1000 ng/ml). On the other hand, we observed that EGF - in concentration of 100 ng/ml - significantly increased the mean nuclear volume and the mean intersection area of thyrocyte nuclei when compared to the controls, as well as to EGF in concentrations of 1 ng/ml and 1000 ng/ml. With regards to the mean perimeter, a significant increase of its length was noted in the EGF(100 ng/ml)-exposed group vs. the group incubated with an addition of EGF (1 ng/ml).

Early diagnosis of Nelson's syndrome.

Nelson's syndrome is a specific form of Cushing's disease treated by bilateral adrenalectomy, presenting with a deep hyperpigmentation caused by a pituitary adenoma (corticotropinoma). These ACTH-secreting tumors are frequently aggressive, so early diagnosis is of prime importance. We have studied 33 patients with Nelson's syndrome, 28 women and 5 men, aged 14-56 yr at the time of adrenalectomy and 16-58 yr at the time of Nelson's syndrome diagnosis (observed for 5-32 yr). Methods of examination included simultaneous adrenocorticotropic hormone (ACTH) and cortisol measurements during routine hydrocortisone replacement therapy, computed tomography (CT), pituitary magnetic resonance imaging (MRI), and visual field examination. The results obtained in a group of six patients diagnosed in the last 3 yr were compared with those obtained in a group of 27 patients examined before 1992. High plasma ACTH levels accompanied by normal serum cortisol concentration were characteristic for a late stage of the disease. Absolute temporal scotomas were an early finding. MRI, especially with the gadolinium enhancement, was superior to CT in demonstrating pituitary microadenomas in Nelson's syndrome. Thus, MRI diagnosis allowed for an early neurosurgical treatment of the patients with Nelson's tumors.

[Strumectomy in children and adolescents--personal studies with 12,000 operations]. / Strumektomia u dzieci i mlodziezy--doswiadczenia wlasne obejmujace 12,000 operacji wola.

At the Surgery Clinic of the Endocrinology Institute in Lódz we operated 12 344 patients between 1974 and 1992 because of various types of goitre. Among these there were 295 children and adolescents, 2.4%- aged between 9-18 years: 268 girls (90.8%) and 27 boys (9.2%). The goitre was 9.9 times more frequent in girls than in boys. In adults the ratio was 8:1.

[Operative treatment of deep arteriovenous malformations]. / Leczenie operacyjne glebokich znieksztalcen tetniczo-zylnych mózgu.

The authors present 12 patients operated upon for arteriovenous malformations located in deep structures of brain. In terms of the location, clinical course and neurological status there were three distinct groups of patients. The results of the operative treatment lead to the conclusion that the operative treatment risk is no greater than in cases of superficial AVMs, in which it is generally accepted.

Acute subdural haematoma in adults: an analysis of outcome in comatose patients.

The authors analysed a series of 200 adult patients admitted to the Department of Neurosurgery, Medical University of Lódz with a diagnosis of acute subdural haematoma (ASDH). 63% of them were surgically treated within the first 4 hours after head injury, the others were operated on 4 to 16 hours after trauma. All patients had GCS below 10 for the whole time period from trauma to surgery. Younger patients 18-30 year old had lower mortality-25%, while patients above 50 revealed 75% mortality. Analysis of operative timing and outcome, no benefit revealed when surgery was performed within first 4 hours. However, the patients operated on later than 4 hours after trauma had smaller midline shift and less pronounced brain contusion. It must be taken into account that some patients who could benefit from early surgery-those with quickly developing haematomas and intracranial hypertension-had no chance to arrive and died in peripheral hospitals. Despite our results we advocate an urgent evacuation of haematoma, as early as possible after trauma. Significant correlation was found between midline shift, cerebral contusion on CT scans and results of surgery. Patients with bigger midline shift or presence of focal cerebral contusion revealed higher mortality and worse outcome than patients with smaller shift and no cerebral contusion visible on CT pictures.