Biomedical subjects
Publications and source records attributed to C Neumann.
The authors present the case-history of a patient operated on account of a pulmonary aspergilloma, incl. analysis of postoperative infectious complications. The course is confronted with data in the literature. Based on the professional literature on the subject the authors discuss the contemporary approach to surgical treatment of this disease.
The outcome of pregnancy was studied in 148 women over a two year period in a rural area of Kenya as part of a prospective longitudinal study whose main objective was to study the functional effects of mild to moderate malnutrition. Data were collected on maternal anthropometric variables monthly, haemoglobin levels were determined by blood samples taken every six months, food intake was based on two days each month of actual weight and recall. Each woman's past reproductive history was established at the beginning of the study. Birth weight was taken and recorded within seventy two hours of delivery. Discriminant analysis was used to identify predictors of low birthweight. The analysis was based on 123 cases who had complete data on all the variables used in the equation. Of those included in the analysis, 14 women (11%) delivered low birthweight babies and 109 had normal birthweight babies. Results of the discriminant analysis showed that mid upper arm circumference (MUAC), body mass index (BMI), Blood haemoglobin levels (HB) and socioeconomic status (SES), are the best predictors of low birthweight. Ranked in order of relative contribution to birthweight they are BMI, HB, MUAC and SES. Low birthweight prevalence was determined as being 11.2 per cent. Eighty per cent of all known cases were correctly classified using the four variables. As a screening tool for low birthweight this model with four variables has 93% sensitivity, 78.4% specificity, 35.13% positive predictive value and 98.98% negative predictive value. The results suggest that it is possible to identify women at high risk for delivering low birthweight babies at the community level.
Between August 30 and September 8, 1995, 38,000 women and several hundred men met in Huairou, China, to discuss the global status of women and to lobby for specific wording in the Agenda for Women that was being finalized in Beijing as part of the United Nations Fourth World Conference on Women. This article has two main objectives. The first objective is to summarize the priority concerns identified in Huairou that are related to international environmental health, especially concerns related to women. The second objective is to provide the rationale and documentation that support including these topics as part of professional education and practice in environmental health in the United States. It is hoped that this discussion will aid environmental health professionals in better appreciating the connection between global environmental health problems and local problems and the applicability of gender-relevant environmental health concerns to local programming, policies, and infrastructure.
The authors present an account on the use of an intraluminal intestinal stent to treat early postoperative ileus. They demonstrate on a case-history the possibility to combine the tube inserted via jejunostomy and with laparostomy. In the discussion they deal also with the historical development of intubation of the small intestine and support of controlled adhesion formation.
In eight patients with delayed union or nonunion after 3 degrees open fracture of the tibia, a minimally invasive technique of autologous bone grafting was performed. Bone harvesting from the iliac crest and debridement of the fracture side were done percutaneous by using a 5.5 mm acromionizer without complications. In seven of eight patients complete fracture healing could be achieved (88%). Percutaneous autologous bone grafting can be recommended on limited bone defects in patients with nonunion or delayed union of the tibia and severe soft tissue damage in the lower leg.
Assay methods based on the Griess reaction are frequently used to measure nitrite and nitrate in urine, plasma, and other biological fluids. With minor exceptions, careful attention has not been paid in extending the Griess assay from aqueous solutions to biological fluids, In the present study, parallel measurements of nitrite and nitrate were performed in urine, plasma, and aqueous solutions with a published batch assay based on the Griess reaction and with gas chromatography-mass spectrometry (GC-MS). We report here further interferences by free reduced thiols, proteins, and other plasma constituents in the Griess assay but not in GC-MS. The best correlation (r2 = 0.985) between the Griess assay and GC-MS was observed for aqueous solutions in the absence of thiols. Unlike GC-MS, the Griess assay was not applicable to whole human plasma and urine samples. For the measurement of nitrate in diluted human urine samples, reduction by cadmium was performed both under acidic (pH 2 or 5) and alkaline (pH 8.8) conditions. The mean recovery rate of nitrate from urine samples was quantitative in the GC-MS but amounted to only 30-80% in the Griess assay. Measurement of nitrate in human urine samples (n = 33) resulted in an excellent correlation between two GC-MS techniques (r2 = 0.979) but only in a poor correlation (r2 < 0.64) between the Griess assay and GC-MS. Unlike GC-MS, the batch Griess assay is associated with many problems in measuring nitrate in biological fluids.
Morphogen gradient theories have enjoyed considerable popularity since the beginning of this century, but conclusive evidence for a role of morphogens in controlling multicellular development have been elusive. Recently, work on three secreted signalling proteins. Activin in Xenopus, and Wingless and Dpp in Drosophila, has strongly suggested that these proteins function as morphogens. In order to define a factor as a morphogen, it is necessary to show firstly, that it has a direct effect on target cells and secondly, that it affects the development of target cells in a concentration-dependent manner. With these criteria in mind, the evidence available for a variety of proposed morphogens is discussed. While the evidence is not conclusive in most of the cases considered, there is a strong case in favour of the three proteins mentioned above, which suggests that morphogens are potentially of general importance in controlling the development of multicellular organisms.
Allograft rejection is associated with complement activation. Yet inconsistent results were obtained in evaluating plasma levels of complement factors or activation products as rejection markers. Therefore the human anaphylatoxin C5a and the soluble terminal complement complex (TCC) were measured by daily enzyme immunoassays on plasma (P) and urine (U) samples from 28 patients undergoing renal transplantation over a mean postoperative period of 25.8 days. The complement levels were evaluated longitudinally (cutoff of 100% increase on the previous day's level) during periods of rejection, stable graft function, acute tubular necrosis, and cytomegalovirus disease. Regarding the detection of 13 acute rejection episodes, U-C5a showed a diagnostic accuracy of 81% (sensitivity of 85%, specificity of 77%), P-C5a one of 62%, and P-TCC one of only 30%. The U-C5a increment (mean rise of 379%) preceded the clinical diagnosis of rejection by an average of 1.6 days. Cytomegalovirus diseases (n = 4) were associated with high P-C5a levels (mean increase of 251% by the time of the first detection of viral DNA). In contrast, resumption of kidney function after acute tubular necrosis (n = 10 periods) was heralded by marked peaks of U-C5a (x = 43.7 microg/l). U-TCC was not detected in any clinical setting. In conclusion, as opposed to P-TCC, U-TCC, and P-C5a, the anaphylatoxin C5a, measured daily in urine, might have potential as an early and reliable marker for acute renal allograft rejection.
BACKGROUND: Specific T-cell responses to food antigens have been described in children with atopic dermatitis (AD). However, a subgroup of adolescent and adult patients still experiences food-responsive AD. OBJECTIVE: This study was designed to evaluate lymphocyte responses to bovine casein in adult patients with AD. METHODS: The stimulatory capacity of lipopolysaccharide-depleted bovine casein was tested in proliferation assays and in limiting dilution assays. Casein-specific T-cell clones (TCCs) were generated and characterized. RESULTS: Higher proliferative responses to casein and modulation of cytokine receptors were observed in patients with milk-responsive AD compared with individuals without clinical reactions on milk ingestion. The results did not correlate with the amount of casein-specific IgE in the serum. The frequencies of T cells that grew in the presence of casein or house dust mite antigens were similar. Only 27% of CD4+ casein-specific TCCs from these patients, but the majority of house dust mite-specific TCCs, produced IL-4 on mitogen stimulation. Interferon-gamma, on the other hand, was produced by the majority of TCCs with both specificities. CONCLUSION: A specific T-cell-mediated immune response to casein can be found in the blood of adolescent and adult patients with milk-related exacerbation of AD. In contrast to house dust mite-specific T cells, casein-specific T cells of adult patients who respond to cow's milk with worsening of AD produce little or no IL-4.
Mechanisms regulating the balance of T-helper 1 (Th1) and T-helper 2 (Th2) immune responses are of great interest as they may determine the outcome of allergic and infectious diseases. Recently, in mice, nitric oxide (NO), a powerful modulator of inflammation, has been reported to preferentially down-regulate Th1-mediated immune responses. In the present study, we investigated the effect of NO on the production of Th1- and Th2-associated cytokines by activated human T cells and human T-cell clones. Cytokine secretion was measured in the presence of the NO-donating agents 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). Both NO-donors markedly inhibited the release of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-5, IL-10 and IL-4 by anti-CD3 activated T cells. A preferential inhibition of Th1-associated cytokines was not observed. Neither was nitrite found in the supernatants of activated T cells, nor was specific mRNA for inducible and constitutive NO synthase detectable, indicating that T cells themselves did not contribute to the observed effect of the NO donors. Costimulation with anti-CD28 monoclonal antibodies (mAb) prevented SIN-1/SNAP-mediated down-regulation of cytokine production only in part. In contrast, when T cells were stimulated by phorbol-ester and ionomycin, they were refractory to SIN-1-induced inhibition of cytokine production. When SIN-1 was added after the onset of anti-CD3 stimulation, the inhibitory effect was found to be less pronounced, indicating that SIN-1 may interfere with early signal transduction events. The addition of superoxide dismutase (SOD) and catalase did not restore the effects of SIN-1, demonstrating that the inhibition of cytokines was due to NO and not to oxygen intermediates. Furthermore, 8-Br-cGMP-mediated increase of intracellular cGMP caused the same pattern of cytokine inhibition as observed with SIN-1 and SNAP. Using a single cell assay, these agents were shown to reduce the frequency of IFN-gamma-producing T cells, suggesting that not all T cells are susceptible to SIN-1/SNAP. However, cytokine production by purified T-cell subpopulations (CD4+, CD8+, CD45RA+, and CD45RO+) was equally impaired by NO donors. In conclusion, in contrast to the murine system, our results do not provide evidence that NO preferentially inhibits Th1-cytokine secretion of activated human T cells in vitro.
Different T-helper subsets, which are characterized by the secretion of distinct cytokines (Th1, Th2), have been found in house dust mite-exposed skin of sensitized individuals and in nickel-specific T lymphocytes from nickel contact allergic and non-allergic individuals. In order to evaluate the role which adhesion molecules may play in the homing of different T-cell subsets into allergen-exposed skin of atopic and normal individuals, we compared the expression pattern of adhesion molecules in patch test reactions to house dust mite antigen (D.pt.), nickel sulfate (Ni) and the irritant anthralin. Biopsies were taken at various time points after application of these agents and studied by immuncytochemistry. To exclude an endogenous difference in adhesion molecule expression in atopic and non-atopic skin, sequential biopsies from Ni patch tests of 2 normal individuals were also included in this study. The expression of E-selectin, P-selectin, CD31, VCAM-1 and ICAM-1 on endothelial cells and other cells in the skin was quantified by microscopic evaluation. Skin homing T cells were also quantified using antibodies to CD3, CD4, CD8, UCHL-1, L-selectin and the cutaneous lymphocyte antigen (CLA). Independent of the eliciting substance, all lesions showed an upregulation of all adhesion molecules tested, with the exception of CD62. The appearance of E-selectin and an increase in ICAM-1 and VCAM-1 expression were first observed at 12 h after application of the various agents. In parallel, the number of CLA+ and L-selectin+ lymphocytes increased steadily. No principle differences could be established between the various types of skin reactions in atopic individuals, nor did the skin of patients with AD differ from normal controls. Our results provide evidence that differential expression of adhesion molecules does not play a major part in observed differential homing of Th1 and Th2-cell subsets into patch test sites provoked by house dust mite and nickel sulfate in atopic and non-atopic individuals.
Atopic dermatitis is a lymphocyte-mediated skin disease. We studied the expression of the adhesion molecule alpha6 integrin by immunohistochemistry in spontaneous atopic inflammation as well as during the eliciting phase of atopen (Dermatophagoides pteronyssinus), antigen (nickel sulfate) and irritative (anthralin) induced patch test reactions in atopic skin. Results were compared with nickel sulfate patch test reactions in normal skin. A role of the alpha6 integrin, expressed at the luminal side of blood vessels, for T cell migration in lesional atopic skin was supposed. In normal human skin the alpha6 integrin was weakly expressed by blood vessels and by basal epithelial cells of the epidermis. In acute and chronic lesional skin of patients with atopic dermatitis dramatic upregulation of alpha6 integrin expression was observed on endothelial cells and in the epidermis. The similar pattern of upregulated suprabasal alpha6 integrin expression was established in the patch test reactions 48 h after atopen and antigen application or irritation of the skin without differences in dependence on the eliciting substance. No difference of alpha6 integrin expression was seen between atopic and normal skin. Tumor necrosis factor alpha, interleukin-1, interleukin-4 and interferon gamma play a role in atopic inflammation. Tumor growth factor beta and interleukin-6 are mitogenic/growth factors for keratinocytes. For this reason the effect of these cytokines and of phorbol-12-myristate-13-acetate on the expression level of alpha6 integrin was tested in short-term skin organ culture of normal and atopic skin as well as in keratinocyte cultures. In these assays no cytokines had an effect on alpha6 integrin expression suggesting another mechanism which regulates this integrin. However, the increased expression of alpha6 integrin in the suprabasal epidermis is associated with a T cell influx into the epidermis. We speculate that the alpha6 integrin expression may lead to an epidermotropism of T cells during inflammation.
The objectives of the present study were 1) to compare results obtained by the traditional manual method of measuring heart rate (HR) and heart rate response (HRR) to the Valsalva maneuver, standing and deep breathing, with those obtained using a computerized data analysis system attached to a standard electrocardiograph machine; 2) to standardize the responses of healthy subjects to cardiovascular tests, and 3) to evaluate the response to these tests in a group of patients with diabetes mellitus (DM). In all subjects (97 healthy and 143 with DM) we evaluated HRR to deep breathing. HRR to standing, HRR to the Valsalva maneuver, and blood pressure response (BPR) to standing up and to a sustained handgrip. Since there was a strong positive correlation between the results obtained with the computerized method and the traditional method, we conclude that the new method can replace the traditional manual method for evaluating cardiovascular responses with the advantages of speed and objectivity. HRR and BPR of men and women did not differ. A correlation between age and HRR was observed for standing (r = -0.48, P < 0.001) and deep breathing (r = -0.41; P < 0.002). Abnormal BPR to standing was usually observed only in diabetic patients with definite and severe degrees of autonomic neuropathy.
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Binding of interleukin-6 to its receptor (IL-6R) induces the association of the IL-6R alpha chain (IL-6Ralpha) with a 130-kDa transmembrane glycoprotein, gp130. This event activates tyrosine kinases of the Janus kinase (JAK) family and transduces signals to the cytosol or nucleus. To further characterize the biochemical mechanisms by which IL-6 promotes cell proliferation, we investigated the effects of IL-6 on the growth and transmembrane signaling of several lymphoid cell lines. In the IL-6-dependent cell line B-9, IL-6 induced a rapid, transient, and concentration-dependent tyrosine phosphorylation of several cytosolic proteins as detected by antiphosphotyrosine immunoblots. The molecular weight of major bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 44, 65, 70, 80, 137, 148, 184, and 190 kDa, respectively. Similar effects of IL-6 on tyrosine phosphorylation were observed in the human multiple myeloma cell line LP-1. Because JAKs were unlikely to mediate all the biological effects of IL-6, we investigated whether members of the Src family of tyrosine kinases were also activated in B-9 or LP-1 cells. IL-6 induced the activation and tyrosine phosphorylation of p59Fyn, p56/59Hck, and p56Lyn. Coprecipitation experiments with anti-Hck, anti-Lyn, anti-Fyn, and anti-gp130 antibodies revealed a physical association with gp130 of p56/59Hck and p56Lyn, but not p59Fyn, in LP-1 cells. Together, these results show for the first time that several Src kinases may become activated by IL-6 (p59Fyn, p56/59Hck, and p56Lyn) and associate with gp130 (p56/59Hck and p56Lyn).
It is well established that many schizophrenia patients manifest behavioral dysfunction long before the onset of clinical symptoms of illness. Some show signs of motor and socioemotional deficit as early as infancy. The present study examines the relations among childhood neuromotor, affective and behavior characteristics, and the association of these factors with adult brain morphology (MRI) in schizophrenia patients. Data on neuromotor functions and negative affect were obtained from coding of childhood films. Parents of patients provided information about six dimensions of childhood behavior problems. Analyses of data from patients and healthy siblings revealed that childhood neuromotor abnormalities and negative affect were associated with some of the behavioral dimensions. Among the patients, early childhood neuromotor deficits and negative affect were linked with greater ventricular enlargement in adulthood. The ratings of the behavior problem dimensions showed a complex relation with adult brain morphology, suggesting that externalized problems are linked with more abnormalities (smaller brain volume and larger ventricles), whereas internalized problems are associated with less abnormality. The findings are discussed in light of their implications for the developmental origins of brain abnormalities in schizophrenia.
BACKGROUND: Nonmelanoma carcinomas of the skin represent the most frequent cancers among the Caucasian population worldwide. They occur with high frequency in renal allograft recipient patients after prolonged immunosuppression. PURPOSE: We analyzed tumors obtained from both immunosuppressed and nonimmunosuppressed patients for human papillomavirus (HPV) DNA. METHODS: Twenty-nine specimens of nonmelanoma carcinomas of the skin were obtained from 19 renal allograft recipient patients; these included 20 specimens of squamous cell carcinoma (SCC) from 11 patients, five specimens of basal cell carcinoma (BCC) from four patients, and four specimens of carcinoma in situ (CIS) from four patients. Forty-one specimens of nonmelanoma carcinomas of the skin were obtained from 32 nonimmunosuppressed patients; these included 26 SCC specimens from 19 patients, 11 BCC specimens from nine patients, and four keratoacanthoma (benign epithelial tumor) specimens from four patients. A polymerase chain reaction method involving use of degenerate oligonucleotide primers, in which the conserved region of the open reading frame of the HPV L1 (major capsid protein) gene is amplified, was used to amplify total cellular DNA purified from individual tumors. The DNA of each specimen was subjected to 16 different amplification reactions; different primer combinations were used in order to increase the sensitivity and specificity of HPV detection. Resulting products were probed with a radioactively labeled, degenerate oligonucleotide. HPV-specific DNA was either sequenced directly after elution from the gel or amplified with semi-nested, degenerate primers, after which the products were cloned and sequenced. Sequences were compared with all known papillomavirus sequences. RESULTS: Thirteen (65%) of the 20 SCC specimens and three of the five BCC specimens from immunosuppressed (renal allograft recipient) patients contained identifiable HPV-related sequences, among them 13 putative novel HPV genomes. In addition, all other malignant tumor specimens from this patient group revealed faint signals upon amplification and hybridization; the origin of these signals has not been identified in the present study. In nonimmunosuppressed patients, eight (31%) of 26 SCC specimens and four (36%) of 11 BCC specimens contained sequences of HPV types. Two putative novel HPV sequences could be identified in this group. Faint signals of yet undetermined origin were observed in eight of the SCC specimens and in two of the BCC specimens. Two of four keratoacanthoma specimens contained sequences of known HPV type. (Keratoacanthoma is a nonmalignant lesion for which the natural history has not been defined.) The spectrum of HPV types in both groups of patients differed substantially. CONCLUSIONS: These data point to the frequent presence of HPV sequences in SCCs and BCCs of the skin. The etiologic relationship of these infections to the respective malignant tumors remains to be evaluated. IMPLICATIONS: The presence of HPV DNA in a large percentage of specimens of nonmelanoma carcinomas of the skin from immunosuppressed patients, as well as from nonimmmunosuppressed patients, renders a papillomavirus infection as a possible factor in the etiology of this disease.
The effect of an oral immunostimulant on adult periodontitis was evaluated in a pilot study. The preparation is successfully administered in respiratory tract infections but has not been used in oral medicine. 11 patients were treated with a bacterial lysate for three months after completing a hygiene phase preceding the study protocol. At day 0 and after 30, 60, and 90 days of medication, parameters characterizing disease activity (bleeding on probing, probing depth, clinical attachment loss and suppuration) and oral hygiene (plaqueindex) were recorded and compared to 10 controls. The treatment resulted in reduced gingival inflammatory activity and diminishing probing depths which was significant compared to the controls (p < 0.001). The exact mechanism of action induced by immunostimulant therapy remains to be clarified. The promising results of this pilot study offer a new aspect in the therapy of periodontal disease. Further investigations are necessary to define the therapeutic value of this treatment in oral medicine.