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Biomedical subjects

S Hofmann

Publications and source records attributed to S Hofmann.

At least 91 records · Page 5Linked to original sources
PubMed1997

Imaging of avascular necrosis of bone.

The etiology of avascular necrosis (AVN) is multifactorial. Independent of its etiology and localization it shows typical pathologies and radiological images. In the early stages localized subchondral edema is characteristic. In 50 % of all cases accompanying joint effusion may be found. Due to necrosis of the cells of bone marrow and bone fibrovascular, reactions with hyperemia can be delineated. These reactions allow us to visualize necrosis indirectly. The best imaging methods are MRI and, to a lesser extent, bone scintigraphy. In later stages calcification as well as new bone formation and microfractures are typically demonstrated and visualized best with plain X-rays and CT. Why reparations in many cases, particularly in the hip, are incomplete and may stop in any stage is unknown. Over years clinically complete silent AVNs are not an uncommon finding. Prognosis depends on the localization and size of the AVN. The number of repair mechanisms is best outlined with contrast-enhanced MRI and return of fatty marrow.

Bone and Bones↗
PubMed1997

[Melanoma-associated retinopathy with night blindness. Case report].

BACKGROUND: Night blindness is usually symptomatic of retinal dysfunction. However, apart from congenital forms of night blindness such as congenital stationary night blindness (CSNB) and pigmentary retinopathy without clumping of pigment, the acquired forms of night blindness present a particular diagnostic challenge to the ophthalmologist. CASE REPORT: A 51-year-old patient with formerly healthy eyes presented with malignant skin melanoma and sudden night blindness. Along with reduced acuity, concentric visual field limitation, and a marked decrease in sensitivity of the retinal rods and cones in adaptometrical tests, significantly reduced b waves and intact a waves were registered in the flash-ERG of both eyes with otherwise inconspicuous morphologic findings. Furthermore, serum levels of antibodies (IgG) against retinal bipolar cells were found to be increased. CONCLUSION: Results indicate the presence of melanoma-associated retinopathy (MAR), which-like carcinoma-associated retinopathy (CAR)-ranks among the tumor-associated diseases of the retina. CAR, MAR, and CSNB can be differentiated immunohistochemically by serum autoantibody determination and electrophysiologically by flash-ERG. As opposed to CAR, the immune response in the case of MAR is not to antigens of photoreceptors and ganglion cells, but to retinal so-called ON-depolarizing bipolar cells mainly connected in series to the rods. In addition, a waves are intact and b waves extinct, resembling the situation of CSNB.

Autoantibodies↗
PubMed1997

Population genetics and disease susceptibility: characterization of central European haplogroups by mtDNA gene mutations, correlation with D loop variants and association with disease.

Mitochondrial (mt)DNA haplogroups in a German control group (n = 67) were characterized by screening mitochondrial coding regions encompassing most of the ND, tRNA and cyt b genes. We used a PCR-SSCP screening approach followed by direct sequencing of polymorphic mtDNA fragments. Five major mtDNA lineages, diverging in at least nine different haplogroups, could be defined by characteristic polymorphic sites in mitochondrial genes. Additional sequencing of two hypervariable segments (HVS-I and II) of the non-coding displacement (D) loop in all control subjects revealed that certain D loop variants were strongly correlated with lineages and haplogroups, while others represented hotspots occurring frequently in different haplogroups. The existence of identified lineages and haplogroups received support from data in the literature, obtained by use of different approaches. Subsequently, we investigated four disease groups for association with these haplogroups: (i) LHON patients (n = 55) carrying at least one of the primary/intermediate LHON mutations at nt 3460, 11778, 14484 and/or 15257; (ii) patients suffering from Wolfram or DIDMOAD syndrome (n = 8); (iii) MELAS patients (n = 9); (iv) a group of children, who died from 'sudden infant death syndrome' (SIDS) (n = 9). The distribution patterns among the haplogroups of the disease groups (LHON, DIDMOAD and SIDS) differed considerably from the control population. LHON and DIDMOAD were significantly under-represented in the most frequent German haplogroup DC, but were concentrated in a mtDNA lineage defined by polymorphisms at nt 4216 + 11251 + 16126. As this lineage diverged into two precisely defined haplogroups, LHON and DIDMOAD could be assigned to the two haplogroups separately. Strikingly, SIDS was often found in association with two rare German haplogroups. MELAS patients were equally distributed among German haplogroups and, moreover, did not reveal any accumulation of specific D loop variants. We conclude that certain European mtDNA haplogroups define a genetic susceptibility basis for various disorders.

Child↗
PubMed1997

Diagnostic patterns for bone marrow oedema syndrome and avascular necrosis of the femoral head in dynamic bone scintigraphy.

This study used logistic regression analysis to assess qualitative patterns of tracer accumulation in an attempt to improve the diagnostic utility of bone scintigraphy for the detection of the bone marrow oedema syndrome (BMOS) and avascular necrosis (AVN) of the femoral head. Forty-eight symptomatic patients aged 44 +/- 9 years (mean +/- S.D.) with a final diagnosis of AVN (n = 29 hips), BMOS (n = 22), nine other hip disorders or a normal hip were examined with dynamic bone scintigraphy and qualitatively assessed for 11 scintigraphic signs in four phases by three blinded investigators. The accuracy for a correct diagnosis based on individual experience was 60-61% for the three observers, even if different signs were emphasized. A cold spot in the femoral head in both blood pool phases and the bone phase was seen only in 24% of AVN hips. Diffuse tracer accumulation in the femoral head, neck and the intertrochanteric region in the blood pool phases was seen only in 36% of BMOS hips. The arterial phase and the finding of a normal acetabulum in the bone phase had no diagnostic utility in this study. The presence of uptake increased the accuracy of differentiating AVN and BMOS from other disorders or normal hips to 88%. AVN could be differentiated from BMOS with an accuracy of 86% if the signs of the femoral head and inter-trochanteric uptake were combined into a diagnostic pattern. The scintigraphic pattern described increases the diagnostic accuracy of planar dynamic bone scintigraphy for BMOS and AVN.

Adult↗
PubMed1997

A controlled study of 2 doses of idebenone in the treatment of Alzheimer's disease.

Two doses of idebenone were studied in a prospective, randomized, double-blind, placebo-controlled multicentre study in patients suffering from dementia of the Alzheimer type (DAT) of mild to moderate degree. Diagnosis was based on DSM-III-R (primary degenerative dementia) and NINCDS-ADRDA criteria (probable Alzheimer's disease). A total of 300 patients were randomized to either placebo, idebenone 30 mg t.i.d. or 90 mg t.i.d. (n = 100, each) and treated for 6 months. The primary outcome measure was the total score of the Alzheimer's Disease Assessment Scale (ADAS-Total) at month 6. Secondary outcome measures were the ADAS cognitive (ADAS-Cog) and noncognitive scores (ADAS-Noncog), the clinical global response (CGI-Improvement), the MMSE, the Digit Symbol Substitution test (DSS) and several scales for the assessment of daily activities (the self- and observer-rating scales NAA and NAB of the Nuremberg Age Inventory NAI and Greene's Assessment). Safety parameters were adverse events, vital signs, ECG and clinical laboratory parameters. Clinical and psychometric evaluations were performed at baseline, and after 1, 3 and 6 months of treatment. After month 6 idebenone 90 mg t.i.d. showed statistically significant improvement in the primary efficacy variable ADAS-Total and in ADAS-Cog. An analysis of therapy responders performed for 3 outcome measures (CGI-global improvement, ADAS-Cog, ADAS-Noncog), selected to represent different domains of assessment, revealed significant superiority of idebenone 90 mg t.i.d. with respect to placebo in each of the 3 variables and in the concordance of responses across the 3 measures. Exploratory results for a subgroup of patients (ADAS-Total > or = 20) showed dose-related superiority of idebenone additionally on ADAS-Noncog and the CGI-Improvement scale. Safety results were inconspicuous for all assessments. The study results demonstrate the efficacy and safety of idebenone in the treatment of DAT patients.

Aged↗
PubMed1997

Phenotypic analysis of T lymphocytes isolated from non-small-cell lung cancer.

BACKGROUND: The study of the nature of tumor-infiltrating lymphocytes (TIL) may provide insight into the complex issue of tumor-host interactions. METHODS: Cytofluorometric analysis was performed to characterize the phenotypic profiles of TIL from non-small-cell lung cancers (NSCLC) and pulmonal metastases of different primary locations. An extensive panel of antibodies was used specific to different activation-associated molecules on T cells. In 10 patients, findings on the T cell phenotype of TIL were compared with the findings in peripheral blood lymphocytes (PBL) from the same patients. Furthermore, we investigated whether the measurement of the TIL phenotype might serve as a prognostic parameter correlating with survival of patients with NSCLC. RESULTS: In contrast to PBL, T cells infiltrating lung tumors expressed significantly higher amounts of various activation antigens. However, the immunophenotype of TIL hardly differed among different histological subtypes and pulmonal metastases. Addressing the prognostic value of the lymphocytic composition of TIL, we found no significant difference in the survival of NSCLC with high or low percentages of T and natural killer cells, whereas high percentages of B cells were associated with increased survival (p = 0.05). Patients with high percentages of CD13+ tumor-infiltrating T cells had significantly poorer prognosis according to Cox's multivariate analysis. CONCLUSION: Our results indicate that different tumor histologies within the lung are characterized by a 'similar' T cell phenotype, at least with respect to the surface molecules studied by us. The measurement of the expression of activation-associated markers on T cells may have prognostic value in the pathological evaluation of NSCLC.

Adult↗
PubMed1997

Endothelin-1 stimulates steroid secretion of human adrenocortical cells ex vivo via both ETA and ETB receptor subtypes.

The role played by endothelins (ETs) and their receptor subtypes (ETA and ETB) in the regulation of steroid hormone secretion in human adrenal gland remains unclear. Therefore, we investigated the gene expression of ET-1 and its receptors in highly pure preparations of human adrenocortical cells and the effect of ET-1 on their secretory activity. Reverse transcription-PCR with primers specific for prepro-ET-1, ET-converting enzyme-1, ETA, and ETB complementary DNAs demonstrated the expression of all of these genes in human adrenocortical cells. ET-1 increased the secretion of aldosterone and cortisol by enhancing both earlier and late steps of their synthesis. The secretory response to ET-1 was partially (60%) inhibited by BQ-123 and BQ-788, which are selective antagonists of the ETA and ETB receptors, respectively. When added together, the two antagonists suppressed the secretagogue effect of ET-1. Collectively, these findings suggest that ET-1, acting via both ETA and ETB receptors, may exert an autocrine/paracrine regulation of the function of the human adrenal cortex.

Adrenal Cortex↗
PubMed1997

Histomorphology and bone morphometry of the bone marrow edema syndrome of the hip.

From a prospective study of patients with MR imaging proven bone marrow edema syndrome of the hip, bone biopsies that were retrieved at core decompression treatment of 32 femoral heads (from 28 men and 3 women; age range, 25-63 years) were evaluated microscopically. The undecalcified microtome sections showed diffuse or spotty areas of interstitial and intrasinusoidal fluid in the marrow cavities, together with fat cell destruction or fibrovascular regeneration or both in exactly the regions exhibiting the magnetic resonance signals for bone marrow edema. The vital bone trabeculae in these edematous regions showed more or less continuous, partly osteoblast covered osteoid seams, and often, formation of irregular woven bone (microcallus), pointing to increased bone formation activity. Preceding or active osteoclastic resorption was rarely seen. Computer assisted bone morphometry revealed age related normal to elevated bone volume densities (above 20% bone volume of tissue volume); thus, no evidence for osteoporosis was present. In addition to increased osteoid volumes, a decreased maximal hydroxyapatite content and a shift to undermineralized bone was found by mineral densitometry of corresponding microradiographs, when compared with age matched femoral heads without bone pathology. These bone mineral changes, but not transient bone loss, could be the explanation for the more or less subtle and transient radiolucency in hips affected by bone marrow edema syndrome. Live trabeculae and active bone formation, however, point to increased repair capacity, which seems the key for the spontaneously reversible course of this syndrome. There is still controversy whether the bone marrow edema syndrome represents a distinct transient disease or an early reversible phase of avascular necrosis, but because of the similarities in histopathology reported for early classic avascular necrosis and bone marrow edema in the literature and in the authors' own material, a common pathophysiology is discussed for these seemingly different diseases.

Adult↗
PubMed1997

Analysis of the mitochondrial DNA from patients with Wolfram (DIDMOAD) syndrome.

Wolfram or DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness) syndrome, which has long been known as an autosomal-recessive disorder, has recently been proposed to be a mitochondrial-mediated disease with either a nuclear or a mitochondrial genetic background. The phenotypic characteristics of the syndrome resemble those found in other mitochondrial (mt)DNA mediated disorders such as Leber's hereditary optic neuropathy (LHON) or maternally inherited diabetes and deafness (MIDD). Therefore, we looked for respective mtDNA alterations in blood samples from 7 patients with DIDMOAD syndrome using SSCP-analysis of PCR-amplified fragments, encompassing all mitochondrial ND and tRNA genes, followed by direct sequencing. Subsequently, we compared mtDNA variants identified in this disease group with those detected in a group of LHON patients (n = 17) and in a group of 69 healthy controls. We found that 4/7 (57%) DIDMOAD patients harbored a specific set of point mutations in tRNA and ND genes including the so-called class II or secondary LHON mutations at nucleotide positions (nps) 4216 and 4917 (haplogroup B). In contrast, LHON-patients were frequently (10/17, 59%) found in association with another cluster of mtDNA variants including the secondary LHON mutations at nps 4216 and 13708 and further mtDNA polymorphisms in ND genes (haplogroup A), overlapping with haplogroup B only by variants at nps 4216 and 11251. The frequencies of both haplogroups were significantly lower in the control group versus the respective disease groups. We propose that haplogroup B represents a susceptibility factor for DIDMOAD which, by interaction with further exogeneous or genetic factors, might increase the risk for disease.

DNA, Mitochondrial↗
PubMed1997

Melanoma-associated paraneoplastic retinopathy: case report and review of the literature.

A 51-year-old white male suffering from metastatic malignant melanoma of the skin presented with lymph node metastases and paraneoplastic retinopathy 4 years after resection of the primary tumour. There were no cerebral metastases. Ocular symptoms consisting of night blindness and sensations of 'shimmering lights' persisted after total resection of the inguinal lymph node metastases and administration of dacarbazine and prednisone. Perimetry of both eyes was abnormal with concentric restriction. Electroretinography showed significantly reduced amplitudes in both eyes. Only 11 patients with melanoma-associated retinopathy (MAR) have been described. High titres of autoantibodies against whole retina extract were detected by enzyme-linked immunosorbent assay (ELISA) reactions. Indirect immunohistochemistry showed strong autoantibody activity against retinal bipolar cells.

Autoantibodies↗
PubMed1996

Clinical and radiological results after Austin bunionectomy for treatment of hallux valgus.

The results of the Austin osteotomies for hallux valgus deformity performed at the Orthopedic Hospital Gersthof were reviewed at least 1 year after surgery. Of the 53 consecutive patients (66 operations) with an average follow-up of 24.3 months, 49 patients (62 feet) were interviewed. Of the reviewed patients 86.6% achieved good or excellent clinical results. The complication rate was 8%, including hallux varus n (3), superficial n (1) and deep n (1) wound infections, hypoaesthesia n (2), and reflex sympathetic dystrophy n (1). There was one case of avascular necrosis of the first metatarsal head and none of non-union. The Austin osteotomy is a safe and effective treatment of mild and moderate hallux valgus deformity.

Adolescent↗
PubMed1996

[Detection of tyrosinase mRNA using reverse transcription/polymerase chain reaction with fine needle punctures of melanoma metastases].

Tyrosinase mRNA produced by melanoma cells can be detected by reverse transcriptase-polymerase chain reaction (rt-pcr) with fine-needle tissue punctures. Fine-needle punctures from six suspected skin and lymph node metastases in three patients with malignant melanoma were analysed via rt-pcr for tyrosinase mRNA. All the suspected metastases were surgically removed and histologically examined separately. In each case the rt-pcr results and the histological diagnosis corresponded. This less invasive and highly sensitive method could prove to be a useful alternative in the diagnosis of melanoma metastasis.

Aged↗
PubMed1996

Activation in novice and expert parachutists while jumping.

Heart and respiration rates were measured ambulatorily in 16 novice and 25 expert (> 380 delayed free-fall jumps) sports parachutists while making a static-line jump. Self-reported anxiety and heart rate peaked near the point of jumping in both groups rather than earlier in experts, as reported by Fenz and Epstein (1967, Psychosomatic Medicine, 29, 33-51). While sitting in the airplane 1 min before exit, mean heart rate was 124 bpm in novices and 102 in experts and increased during jumping to 170 and 145, respectively. The almost identical rise in the two groups could be accounted for largely by physical exertion, replicated with jumps from a training model on the ground. Exercise testing at a different location showed that experts were more fit. Respiration rate was higher in the airplane than at baselines, especially for novices. In conclusion, our results are more compatible theoretically with extinction of anticipatory anxiety than with learned anxiety inhibition.

Adult↗
PubMed1996

Lesions of the acetabular labrum: accuracy of MR imaging and MR arthrography in detection and staging.

PURPOSE: To determine the accuracy of magnetic resonance (MR) imaging and MR arthrography in the detection and staging of lesions of the acetabular labrum. MATERIALS AND METHODS: Fifty-seven hips of 56 patients with chronic hip pain and a strong clinical suspicion of labral lesions were examined with a three-dimensional gradient-echo sequence in the coronal oblique and sagittal oblique projections before and after the intraarticular injection of gadopentetate dimeglumine. The labra were evaluated on the basis of morphology, signal intensity, the presence or absence of a tear, and their attachment to the acetabulum. Twenty-two of the hips underwent surgical intervention, and 35 hips were treated conservatively. RESULTS: Twenty of the 22 labra with surgical proof were staged accurately with MR arthrography. On the conventional MR images, only eight of the 22 labra were staged correctly. Whereas the sensitivity of MR arthrography was 90% and its accuracy was 91%, the sensitivity of MR imaging was 30% and its accuracy was 36%, compared with surgical findings. CONCLUSION: MR arthrography enables accurate detection and staging of lesions of the acetabular labrum and appears to be indicated in the assessment of chronic hip pain in patients with a strong suspicion of labral lesions.

Acetabulum↗
PubMed1996

[The effectiveness and tolerance of ramipril in comparison to captopril for heart failure in dogs].

In this study 43 animals suffering from a decompensated heart failure were treated with one of two different ACE-inhibitors. 16 animals received Captopril, 27 were treated with Ramipril. A clinical examination was performed prior to the onset of therapy. Controls were performed two weeks, six weeks and seven months after the beginning of treatment. In the captopril-group 12 animals improved by at least one degree, four dogs died within the examination period. In the ramipril-group 16 of 27 dogs treated with a dosage of 0.125 mg/kg bw once a day showed an improvement of one or more degree and 6 animals died. In 8 animals the dose of 0.125 mg/kg bw once a day was increased to 0.125 mg/kg bw twice a day which consequently led to an improvement in 4 dogs. Ramipril and captopril were considered equal in tolerance. The study will be continued with a ramipril dosage of 0.25 mg/kg bw once a day in all further patients.

Angiotensin-Converting Enzyme Inhibitors↗