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Biomedical subjects

S Lang

Publications and source records attributed to S Lang.

At least 181 records · Page 10Linked to original sources

CD4-imitating human antibodies in HIV infection and anti-idiotypic vaccination.

Anti-idiotypic vaccination against HIV infection aims at inducing an anti-gp120 immune response through anti-CD4 Abs mimicking epitopes of the gp120 molecule. The mAb IOT4a induces anti-gp120 Abs in rabbits. This study investigates the presence of human serum Abs cross-reacting with anti-CD4 mAbs and gp120 during HIV infection and after parenteral vaccination with IOT4a. Ten HIV-infected volunteers without immunodeficiency were inoculated s.c. with 0.6, 1.2, or 2.4 mg IOT4a. Six booster injections followed until day 35. Sera from study patients, 80 HIV-positive, and 43 seronegative controls were examined by a panel of assays, including an ELISA using competition against biotinylated recombinant CD4, flow cytometry assaying inhibition of anti-CD4 mAbs and biotinylated gp120 binding to CD4-positive lymphocytes, and an IOT4a immunoblot. After vaccination, an increase in competitive binding activity, which was quantitative in ELISA and flow cytometry, was observed. In the ELISA, competition against biotin-CD4 was quantitatively quenched by preincubating sera with r-gp120 or anti-CD4 mAbs such as IOT4a and Leu3a. Naive sera or sera from blood donors had no such effect in the assays employed, while 5/80 HIV sera showed binding qualities similar to vaccinees. These results suggest that 1) CD4 internal-image Abs emerge in a small proportion of HIV-positive individuals, and 2) parenteral vaccination with mAb IOT4a can induce a gp120 cross-reacting immune response that inhibits gp120 binding to CD4.

Adult↗

[Osteomyelitis. A pathomorphologic overview].

Osteomyelitis is an infection of the bone marrow caused by both non-specific and specific agents. Non-specific endogenic osteomyelitis represents the most frequent form, followed by the specific form caused by Mycobacterium tuberculosis infection. Typically, the non-specific form occurs in children and young adults, and the sites most frequently affected are the distal and the proximal ends of the tibia and femur. In tuberculosis, osteomyelitis is predominantly located in the vertebral bodies. In rare cases osteomyelitis can be caused by viruses, fungi or echinococcus. It may also occur as so-called acute endogenic osteomyelitis, such as plasmocellular osteomyelitis and Brodie's abscess. Histologically, dense infiltration of leucocytes, granulation tissue and bone sequesters can be seen. In tuberculosis granulomas with central necrosis, epithelioid cells and giant cells of Langhans type are characteristically found. Most forms of acute osteomyelitis can be successfully treated with antibiotics, leading to complete healing without complications. Only a few reported cases develop into a secondary, chronic form.

Adolescent↗

Intraoperative autologous blood donation preserves red cell mass but does not decrease postoperative bleeding.

BACKGROUND: Postoperative bleeding and transfusion remain a source of morbidity and cost after open heart operations. The benefit of the acute removal and reinfusion of fresh autologous blood around the time of cardiopulmonary bypass-a technique known as intraoperative autologous donation (IAD)-has not been universally accepted. We sought to more clearly evaluate the effects of IAD on allogeneic transfusion and postoperative bleeding by removing, preserving, and reinfusing a calculated maximum volume of fresh autologous whole blood. METHODS: Ninety patients undergoing coronary artery bypass grafting or valvular operations were prospectively randomized to either have (IAD group) or not have (control group) calculated maximum volume IAD performed. Treatment was otherwise identical. Transfusion guidelines were uniformly applied to all patients. RESULTS: An average volume of 1,540 +/- 302 mL of fresh autologous blood was removed and reinfused in the IAD group. Postoperative hematocrits were significantly greater at 12 and 24 hours postoperatively in the IAD group versus the control group despite a significant decrease in both the percentage of patients in whom allogeneic red blood cells were transfused (17% versus 52%; p < 0.01) and the number of red blood cell units transfused per patient per group (0.28 +/- 0.66 and 1.14 +/- 1.19 units; p < 0.01). Conversely, chest tube output, incidence of excessive postoperative bleeding, postoperative prothrombin time, and platelet and coagulation factor transfusion requirement did not differ between groups. CONCLUSIONS: These results indicate that intraoperative autologous donation serves to preserve red blood cell mass. Its routine use in eligible patients is therefore justified. However, the removal and reinfusion of an individually calculated maximum volume of fresh autologous blood had no effect on postoperative bleeding or platelet and coagulation factor transfusion requirement. This lack of hemostatic effect belies the beliefs of many about the primary action of IAD, helps to delineate the optimal way in which to perform IAD, and carries implications regarding the use of allogeneic platelet and coagulation factors for the treatment of early postoperative bleeding.

Adult↗

Cartilaginous exostoses of the mandible.

Although cartilaginous exostosis is considered to be the most common tumor of the skeleton, it is relatively uncommon in the jaws. The pathogenesis of the lesion is unclear. Three cases are presented and the development of the tumors from embryonic cartilage is discussed.

Adolescent↗

An imbalance in T-helper cell subsets alters immune response after cardiac surgery.

Growing evidence indicates that cell-mediated immunity is altered after cardiac surgery with cardiopulmonary bypass (CPB). The objective of this prospective randomized study was to investigate (1) if an imbalance in T-helper cell (TH) subsets, i.e. TH1/TH2, may be responsible for these alterations and (2) if they can be counteracted. Twenty patients formed control group A. Twenty group B patients received indomethacin and thymopentin for immunomodulation. In vitro tests included measurements of TH, interleukin (IL)-2 as a cytokine primarily produced by TH1 cells, and IL-6 as a cytokine primarily produced by TH2. Delayed-type hypersensitivity (DTH) skin response and specific antibody (AB) production were used as in vivo tests for TH1- and TH2-induced immune response, respectively. Postoperatively, group A patients showed a persistent, significant reduction of TH, IL-2 synthesis and DTH skin response as compared to baseline values, while IL-6 synthesis remained unaltered and AB production increased (P < 0.05). In group B patients no change in TH, IL-2 and IL-6 synthesis, or DTH skin response was observed (P < 0.05 vs A). Postoperative AB production increased significantly in group B. These results indicate a significant suppression of TH1-induced cell-mediated immune response following CPB, while TH2-induced response remains normal. A normal TH2 response may be helpful for recovery following cardiac surgery by cleaning the body of the byproducts of CPB. A suppression of TH1 response may gain clinical significance whenever a postoperative infection requires this response, but can be effectively counteracted by immunomodulatory intervention with indomethacin and thymopentin.

Aged↗

First-pass uptake of methotrexate after intra-arterial bolus injection in human head and neck cancers.

The aim of this study was to quantify first-pass uptake of methotrexate into tumour and healthy tissue after intra-arterial (i.a.) injection in patients with head and neck cancers. Twenty-one patients were studied; during surgery, a bolus injection of 10 mg of 3H-labelled methotrexate was administered into the tumour-supplying artery. At 15-20 s after injection, and again 2-3 h later, a biopsy of the tumour and of surrounding healthy tissue was taken and radioactivity was measured. In 8 of 17 pretreated patients the biopsy specimens contained no tumour cells. In tumour-bearing patients, radioactivity in tumour was three times higher than in healthy tissue (P = 0.006). In tumour-negative patients there was no difference in activity between the two biopsy sites (P = 0.889). However, after 2-3 h the concentration of methotrexate in all surgical specimens returned to near background level and the initial difference between tumour-positive and tumour-negative samples was lost. Our results show that i.a. injection of methotrexate does not necessarily lead to high tumour cell exposure.

Antimetabolites, Antineoplastic↗

[Soft tissue sarcomas of the ENT area. A report of experiences of the Vienna University ENT Clinic].

BACKGROUND: Soft-tissue sarcomas of the head and neck are rare. Local recurrence is common, and wide excision is thought to be the mainstay of treatment. Surgical radicality is limited by the vicinity of vital organs. Improvement of cure rates therefore is expected mainly from combined treatment modalities. METHOD: Retrospective analysis of 32 cases of soft-tissue sarcoma on file at the Department of Otorhinolaryngology of the University of Vienna between 1954 and 1994. RESULTS: The most frequent descriptive histological diagnosis was polymorphic cell sarcoma in 11 cases. An immunohistological verification was possible in seven cases. The larynx and the pharynx (16 percent each) were the most common sites of affection. Incidence peaks were noted in the third and seventh decade of age. Treatment during the 1950s consisted of surgery and/or irradiation and was supplemented from the 1960s on by polychemotherapy. The median survival was 29 months. Three patients are alive, two patients died free of disease and six patients were lost to follow-up. CONCLUSION: Permanent cure was rare but each therapeutic regimen seemed to provide prolongation of life. The most important prognostic factors were tumor size, histologic grade, and surgical margins.

Adolescent↗

Production and characterization of anti-human interferon gamma receptor antibody fragments that inhibit cytokine binding to the receptor.

Three single-chain antibody fragments that recognize the extracellular human interferon gamma receptor alpha-chain (IFN gamma R), and inhibit the binding of human IFN gamma, have been produced in Escherichia coli. These fragments are derived from murine anti-receptor monoclonal antibodies, and comprise the variable heavy (VH) domain linked to the variable light (VL) chain through a 15 amino acid linker [(GGGGS)3]. Using surface plasmon resonance technology (BIAcore), the soluble proteins were shown to retain a high affinity for recombinant IFN gamma R, and by radioimmunoassay to possess a high inhibitory activity towards IFN gamma-binding to human Raji cells. The antibody fragments most likely recognize epitopes that overlap the cytokine binding site on the receptor surface. Attempts to dissect further the antibodies to isolated VH- and VL-chains and to synthetic linear and cyclic peptides derived from the individual complementarity determining regions failed to afford fragments with significant IFN gamma R binding affinity. Nevertheless, these native-like variable region fragments and petidomimetics derived from them are of interest in the design of novel IFN gamma R antagonists.

Amino Acid Sequence↗

Transport and metabolic pathway of thymocartin (TP4) in excised bovine nasal mucosa.

Thymocartin (TP4, Arg-Lys-Asp-Val) is the 32-35 fragment of the naturally occurring thymic factor (thymopoietin). Here studies on the nasal transport and metabolism of TP4 were performed. Freshly excised bovine nasal mucosa was taken as a model membrane. For permeation studies typical donor-receiver experiments (side-by-side) and finite-dose experiments with small volumes of highly concentrated solutions were carried out. The metabolic pathway of TP4 in nasal mucosa was found to occur according to a typical aminopeptidase cleavage pattern, stepwise forming Lys-Asp-Val and Asp-Val. TP4 metabolism experiments under reflection kinetics showed a saturation profile above 0.5 mumol mL-1. A non-linear kinetic model consisting of three steps in sequence was sufficient to describe the kinetics: for the first step saturable Michaelis-Meat kinetics, and for the second and the third step first-order kinetics were assured. The model was capable of simultaneously fitting the data for the full range of initial concentrations from 0.1 up to 1.0 mumol mL-1. Saturation kinetics was also found to be the prominent feature of the permeation experiments performed. In the lower concentration range (< 0.4 mumol mL-1), transport of TP4 across nasal mucosa was controlled by metabolism, in the higher concentration range (> 0.85 mumol mL-1) diffusion control became more important. We conclude that enhancement of absorption can be achieved when nasal aminopeptidases are saturated, e.g. at high TP4 concentrations.

Absorption↗

Observer variability in histopathological reporting of non-small cell lung carcinoma on bronchial biopsy specimens.

AIMS: To evaluate the ability of histopathologists to sub-classify non-small cell lung carcinomas on bronchial biopsy material using the current World Health Organisation (WHO) classification. METHODS: Twelve histopathologists each reviewed 100 randomly selected bronchial biopsy specimens which had originally been reported as showing non-small cell lung carcinoma. For each case, two sections were circulated, one stained by haematoxylin and eosin and the other by a standard method for mucin (alcian blue/periodic acid Schiff). The participants were allowed to indicate their degree of confidence in their classification of each case. A standard proforma was completed and the results were analysed using kappa statistics. RESULTS: Where the participants were confident in their classification, they were actually quite good at sub-classifying the non-small cell carcinoma sections (kappa = 0.71, standard error = 0.058). Overall, however, the results were only fair (kappa = 0.39, standard error = 0.034). CONCLUSIONS: The majority of non-small cell lung carcinomas can be correctly categorised on adequate bronchial biopsy material. Where a confident diagnosis was made, both squamous carcinoma (kappa = 0.73) and adenocarcinoma (kappa = 0.83) were well recognised.

Adenocarcinoma↗

Overexpression of tenascin in cholesteatoma and external auditory meatal skin compared to retroauricular epidermis.

In the present study the distribution of tenascin in cholesteatoma was immunohistochemically investigated. The results were compared with those in external auditory meatal skin and in retroauricular skin of healthy controls. The staining pattern was additionally correlated to the degree of cell proliferation as detected by the monoclonal antibody MIB-1 (Ki-67 antigen). Retroauricular skin showed a limited distribution of tenascin in the papillary dermis and a sparse reactivity of MIB-1 in only a few epithelial cells. External auditory meatal skin revealed a more pronounced reaction for tenascin and MIB-1. In contrast, cholesteatoma tissue exhibited an abundant and continuous expression of tenascin covering the whole stroma compartment. This coincided with a significant increase of MIB-1-positive cells in the basal and suprabasal epithelial layers. Doublestaining experiments revealed most prominent stromal tenascin-expression in areas with marked signs for epithelial proliferation. This suggests that tenascin is selectively increased in response to epidermal hyperproliferation. This matrix protein thus shows a quantitatively and qualitatively enhanced expression under pathological conditions. Moreover, the abundant reactivity for tenascin in the cholesteatoma provides evidence of a deregulated cell-matrix interaction involved in the hyperproliferative process of cholesteatoma formation.

Case-Control Studies↗

Dietary salt, intracellular ion homeostasis and hypertension secondary to early-stage kidney disease.

Abnormal salt metabolism plays a central role in the pathogenesis of hypertension caused by early-stage renal disease. The mechanisms by which alterations in salt balance and the vasoconstrictor state are related are unclear. We studied the effects of three different salt diets (3, 6-9 and 12 g sodium chloride) on cellular ion homeostasis in platelets in 20 patients with renal hypertension. Compared to normal subjects, patients with renal hypertension had raised cytosolic sodium and calcium concentrations. The platelet sodium pump activity was significantly depressed and calcium ATPase activity increased. These abnormalities of cellular ion metabolism were aggravated by salt overload. On the other hand, dietary salt restriction tended to normalise these parameters. The data presented indicate that a circulating inhibitor of the sodium pump plays a central role in the pathogenesis of salt-induced renal hypertension and that the final common pathway of hypertension secondary to early-stage parenchymal renal disease is an elevation of resting cytosolic calcium followed by an elevation of peripheral vascular resistance.

Adolescent↗

Bone metastasis with superimposed osteomyelitis in prostate cancer.

The following case of a male patient with a history of prostate cancer suffering from pain and swelling in the right mandibular area illustrates the well-known diagnostic problem of a superinfected tumor. Orthopan tomography and CT showed no defects in bone structure or smooth tissue. Whole-body bone scanning showed increased tracer uptake in the mandibular bone and in several other locations in the skeletal system. Antigranulocyte immunoscintigraphy showed increased uptake over the right mandible, whereas the other metastatic sites were visualized as cold spots. A second CT scan depicted a sclerotic lesion with surrounding periostal reaction and soft-tissue swelling and was interpreted as osteomyelitis. Therefore, clinical symptoms, bone scanning, antigranulocyte immunoscintigraphy and follow-up CT resulted in a diagnosis of osteomyelitis, although open needle biopsy revealed the lesion to be prostate cancer metastasis with massive leukocytic invasion.

Antibodies, Monoclonal↗

Utility of technetium-99m-sestamibi to assess osseous tumor spread.

We report the staging results and the surgical outcome of a male patient with squamous-cell carcinoma in the floor of the mouth and a bone SPECT scan suggestive of local tumor infiltration of the mandible. Additional 99mTc-sestamibi SPECT imaging of the primary tumor and superimposing of both studies excluded osseous tumor spread and less extensive surgery was performed. Pathohistological examination confirmed the scintigraphic results and indicated a nonspecific periostal reaction as the cause of the positive bone scan. Nevertheless, a high-resolution camera and careful superimposition of both studies is mandatory if the differential diagnosis of an osseous tumor spread of a malignant tumor in the floor of the mouth and possibly less extensive surgery is at stake.

Carcinoma, Squamous Cell↗

Evaluation of the general practice program of women education for breast self-examination.

The aim of the study was to evaluate the program of education of women for breast self-examination (BSE) in general practice. A random sample of 5% of women over 18 years of age, living in Dugave (a suburb in Novi Zagreb) were chosen for the study. The study covered 251 women of whom 122 (48.6%) presented for BSE training. Women were taught about BSE by the method which included the theoretical part, group discussion, practical training on silicon breast model, individual practice of BSE, and additional individual assessment of the acquired skill of BSE. Six months after the BSE training, out of 116 women presented for retesting, BSE was performed by 91 (78.4%) women: 75 (82.4%) performed BSE regularly once a month or in two months, while 60 (65.9%) women dedicated sufficient time to BSE. Assessment of BSE performance in our subjects showed palpation with the longer parts of fingers and palpation of the whole breast to be skills best mastered by the women. Palpation of the nipple area and palpation of the armpit were sections of BSE in which the women also achieved good results. It is surprising that breast inspection, easy as the procedure may seem, is the section of BSE in which the women did not achieve expected results. On the post-course assessment, as many as 15 (12.9%) women left out breast inspection, while 10 (8.6%) women performed breast inspection in a completely wrong way. Keeping self-records on BSE was by far the most poorly assessed part. Incomplete keeping of self-records on BSE findings is an important objection to BSE as a procedure which should contribute to the systematic continuous drive for early detection of breast cancer. The most important conditions for the education of women for BSE are the knowledge, ability and willingness of the GP and members of his team to provide health education to the population under their care. BSE is not the ultimate solution, but is a significant step in the continuous struggle against breast cancer. That is why it is essential that all women be informed about BSE and as many women as possible be covered by systematic education for BSE. Authors' results indicate that it is possible to implement the proposed model of continuous education of women for BSE within the scope of work of the GP's team.

Adolescent↗