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Biomedical subjects

C Huber

Publications and source records attributed to C Huber.

At least 55 records · Page 3Linked to original sources

Secondary evaluation of hydrogel lens implants.

OBJECTIVE: To review patients currently forming part of a study of poly 2 hydroxyethylmethacrylate (P-HEMA) 'Hydrogel' intraocular lenses. DESIGN: Patients were taking part in the Hydrogel arm of a prospective trial at Scarborough Hospital. Recruitment was by letter. SETTING: District General Hospital. PATIENTS: One hundred and eight from the Scarborough trial in whom a Hydrogel lens had been implanted. INTERVENTIONS: An independent assessment was carried out at a median interval of 20 months following surgery. Visual acuities were assessed with best possible refraction and the eyes examined both before and after pupil dilation. MAIN OUTCOME MEASURES: Visual acuity and major complications. RESULTS: 91% had visual acuities of 6/9 or better and 30% achieved 6/5. In 61% the central area (3 mm diameter) of posterior capsule was clear but 39% had significant fibrosis or pearl formation in this area and 8% had undergone posterior capsulotomy. Five major decentrations had taken place, one of which occurred following a spontaneous rupture of the posterior capsule 17.6% of patients showed significant pigment dispersion behind the IOL either on the posterior capsule or in the anterior vitreous that could not be accounted for purely by surgical trauma. An atonic iris sphincter was noted in 17% of eyes. CONCLUSIONS: This lens gives good visual results but its stability and tendency to cause pigment shedding need to be closely monitored.

Aged

Zinc deficiency and zinc repletion: effect on the response of rats to infection with Trichinella spiralis.

The expulsion of a primary infection of Trichinella spiralis was studied in rats fed diets containing (per kg diet) either 3 mg Zn [zinc deficient (Zn-)] or 40 mg Zn [zinc adequate (Zn+)]. A dose of 2000 muscle larvae (ML) impaired weight gain (mg/g body wt) in all groups compared with uninfected controls [eg, 0-7 d postinfection (dpi): infected Zn-, -105 +/- 10 (means +/- SEM); uninfected Zn-, 54 +/- 19 (p less than 0.001)]. In a study with 20.5 ML/g body wt, some Zn- rats were transferred at the time of infection to the zinc-adequate diet. [This was the zinc-repleted group (ZnR).] Both groups retained a group of pair-fed controls (Zn-PF and ZnRPF). The percentage dose established at 7 dpi was similar in all groups (32.5-39.3%) but at 13 dpi recoveries were 19.4 +/- 2.2% for Zn-, 0.1 +/- 0.1% for Zn-PF, 1.6 +/- 0.9% for ZnR, 0.6 +/- 0.2% for ZnRPF, and 4.1 +/- 2.2% for Zn+ (p less than 0.001). Up to 13 dpi, all groups except ZnR lost weight. These results show that zinc deficiency impairs the expulsion of T spiralis in rats.

Animals

Zinc deprivation and zinc repletion: effect on the response of rats to infection with Strongyloides ratti.

The course of a subcutaneous weight-related infection with Strongyloides ratti was followed in rats fed diets containing either 3 mg Zn/kg diet [zinc deficient (Zn-)] or 40 mg Zn/kg diet [zinc adequate (Zn+)]. At 19 d postinfection (dpi) the proportions of larvae persisting in the intestines as adult worms were 52 +/- 2% (means +/- SEM) for Zn-, 39.5 +/- 2.5% for pair-fed Zn- (Zn-PF), and 31.6 +/- 3.2% for Zn+ (p less than 0.001, analysis of variance); some Zn- rats were then transferred to the zinc-adequate diet [This was the zinc-repleted group (ZnR).] Both groups retained a group of pair-fed controls (Zn-PF and ZnRPF). Between 19 and 28 dpi ZnR animals gained weight faster than did Zn- animals and had heavier thymuses relative to body weight. Zinc deficiency enhances the establishment of S ratti larvae in the intestine of rats and alters the characteristics of intestinal expulsion of the nematodes; however, spontaneous cure was achieved by 38 dpi in both Zn- and control groups.

Animals

Evaluation of cytokines and cytokine-induced secondary messages in sera of patients after liver transplantation.

The study objective was first to investigate serum levels of tumor necrosis factor alpha, interleukin 1 beta, interferon gamma, interferon alpha, interleukin 2, beta-2-microglobulin (B2M), and urinary neopterin in patients after orthotopic liver transplantation; and second to relate their levels to clinical complications. The design used was the prospective observation study, and the setting used was the transplant unit of a university medical center. Serum samples were collected from 20 patients every alternate day from transplantation until discharge. The measurements and main results were as follows: concentrations of cytokines, B2M, and neopterin were performed using commercially available radioimmuno-assays. In seven out of nine patients with acute cellular rejections, elevated levels of TNF-alpha, IFN-gamma, IL-1, B2M, and neopterin were detected. The highest absolute levels of TNF-alpha were observed in patients with CMV disease. Increments in bacterial infections were comparable to those seen in the above-mentioned groups with the exception of IFN-gamma, which remained stable. IL-1 serum levels showed a different pattern with peak concentrations measured in sera before transplant and during rejection, while in the case of CMV disease levels gradually decreased. No detectable levels of IFN-alpha or IL-2 were observed. Our results indicate that enhanced endogenous production of TNF-alpha and IFN-gamma accompanied by elevated levels of B2M and neopterin represent a regular feature of inflammatory complications after liver transplantation. Serum cytokine levels however were not useful in distinguishing between rejection and infection. Evaluation of neopterin was more sensitive than cytokine or B2M measurement for the detection of inflammatory complications.

Adolescent

Endogenous IFN-gamma during human bone marrow transplantation. Analysis of serum levels of interferon and interferon-dependent secondary messages.

Serum levels of interferon-gamma and the IFN-dependent marker molecules neopterin and beta 2-microglobulin were assessed in BMT recipients. Concentrations of the latter two markers were corrected for creatinine levels in order to eliminate the impact of alteration of kidney function. Serum levels were assessed daily using commercially available radioimmunoassays. Twelve patients were studied during the early phase of allogeneic bone marrow transplantation and eleven additional patients during complications of BMT. Results indicated that both the conditioning regimen for BMT as well as major clinical complications such as infection and acute graft-versus-host disease strongly influence the endogenous patterns of the lymphokine and its secondary messages. During allogeneic BMT IFN-gamma and neopterin levels exhibited a biphasic pattern with a first peak during conditioning with high-dose cyclophosphamide and a second still higher peak at the time of hemopoietic regeneration. beta-2-microglobulin ratios increased during conditioning and remained elevated throughout observation. Serious infections of bacterial and viral origin as well as GvHD were accompanied by elevated levels of all three serum parameters studied. The kinetics of enhanced endogenous production, however, differed between infectious complications and GvHD. Increasing concentrations were observed during infections subsequent to clinical manifestation, whereas they preceded disease manifestation in GvHD.

Biopterins

Aniline blue staining as a marker of sperm chromatin defects associated with different semen characteristics discriminates between proven fertile and suspected infertile men.

A retrospective study of 49 men with proven fertility and 396 suspected infertile men was conducted with the primary objective of investigating the relationship between the nuclear maturity of sperm and male fertility. Acidic aniline blue staining was used to detect chromatin defects of sperm nuclei related to their nucleoprotein content as associated with DNA. The discriminant value of the percentage of unstained nuclei (= percentage of mature heads, MH) and of other semen characteristics, was analysed by a stepwise (forward) linear regression model. Semen characteristics that discriminated significantly between the two groups of subjects were, in descending order: (1) the percentage of normal sperm, (2) the percentage of amorphous heads, (3) the percentage of tapered heads, (4) semen volume, and (5) the percentage of MH. The discriminant value of each of the significant characteristics was studied by means of ROC-curves. MH had the best ROC-curve profile; its cut-off value was found to be equal to 70% (74.5 +/- 2.6% for the donor group versus 53.0 +/- 1.1% for the patient group). A simple infertility score (SIS) including MH, was built according to the cut-off values inferred from the ROC-curves. SIS allowed an overall satisfactory separation of the two groups (less than or equal to 4 = fertile, 5-6 = uncertainty zone, greater than 6 = infertile). Our results indicate that the addition of the evaluation of sperm head maturity to routine semen analysis improves the assessment of fertility in men.

Aniline Compounds

Evolution of a group of transposed human V kappa genes.

Eleven V kappa genes within a genomic region which has been transposed from the short to the long arm of chromosome 2 have been characterized by sequence analyses. Nine of the analysed genes exist within the genome in three highly homologous copies each. Sequence comparisons of the triplicated genes make it very likely that the three copies of a given gene were produced at different times during evolution. A chain of events which led to a stepwise amplification of precursor genes is discussed.

Amino Acid Sequence

C3-containing serum immune complexes in patients with systemic lupus erythematosus: correlation to disease activity and comparison with other rheumatic diseases.

Although testing for circulating immune complexes (CIC) is regarded as a useful, complementary, laboratory parameter in the differential diagnosis and management of immune complex-induced vasculitis syndromes, there is still an uncertainty with regard to assay systems used for the demonstrated of soluble immune complexes. This is partly due to difficulties in the reproducibility, handling and principle limitations of available test systems for the assessment of soluble immune complexes in body fluids. In the present communication a modification of the anti-C3 test for the determination of CIC was developed using nitrocellulose as a solid phase matrix. IgG-, IgA- and IgM-containing CIC were determined and quantified using standard immune complex preparations. When 39 sera of SLE patients, 12 sera of patients with vasculitis syndromes, 10 sera of rheumatoid arthritis patients and 11 sera of patients with ankylosing spondylitis were tested, predominantly IgG-containing CIC could be demonstrated. Only in SLE patients was a significant amount of other immunoglobulin isotypes detected in CIC. In these patients a significant difference of IgG-containing CIC levels was found with regard to patients with high and low disease activity (P less than 0.0001). A significant correlation was also established between IgG-containing CIC and anti-dsDNA antibodies (P less than 0.001). In a longitudinal study the isotypes in the isolated CIC were found to be constant.

Antigen-Antibody Complex

Morphological and immunological changes of hairy cell leukemia during alpha-2-interferon therapy.

We describe a patient who presented with the clinical picture of hairy cell leukemia (HCL). Bone marrow and peripheral blood lymphoma cells showed morphological and immunological features of HCL. Under recombinant alpha-2-interferon (alpha-2-IF) therapy the characteristic morphology changed from HCL to prolymphocytic leukemia (PLL). At diagnosis the lymphoma cells expressed CD24 and FMC7 surface antigen, but stained negative for surface immunoglobulins, light chains and anti-CD5. During alpha-2-IF treatment surface antigen expression changed to CD24, CD5 and FMC7. Surface IgD and lambda light chains became strongly positive. Southern Blot analysis of peripheral blood mononuclear cells showed two rearranged immunoglobulin bands at diagnosis but only one upon alpha-2-IF therapy. These data suggest, that this patient suffered from a biclonal lymphoma, HCL and PLL. While undergoing alpha-2-IF treatment the HCL came into remission, whereas the PLL clone proved to be poorly sensitive to alpha-2-IF therapy.

Aged

Immunohistological assessment of bone marrow biopsies from patients with hairy cell leukemia: changes following treatment with alpha-2-interferon and deoxycoformycin.

Forty-six bone marrow biopsies from twelve hairy cell leukemia (HCL) patients, treated with either interferon(IFN)-alpha-2 (n = 8) or 2'deoxycoformycin(DCF) (n = 4), were examined using cryostat sections and an immunoperoxidase technique. Using this sensitive method we were able to demonstrate residual hairy cell (HC) infiltration in five cases, in which evaluation with conventional staining techniques on plastic embedded biopsies revealed complete remission. The amount of HCs in these five samples ranged from 1 to 7% (mean: 3%) of bone marrow cells. Consecutive biopsies in individual HCL patients revealed no changes of the immunological phenotype (CD19, CD22, CD25, CD10, CD11c, FMC7, HLA-DR, surface immunoglobulins) during IFN and DCF treatment. Within the infiltrated bone marrow a considerable number of "reactive" T lymphocytes was identified with prevalence of the T-helper (CD4+) subtype in untreated cases, whereas T-suppressor/cytotoxic (CD8+) cells were within the normal range. IFN treatment resulted in a reduction of CD4+ T lymphocytes (p less than 0.02). Minor alterations of CD8+ T lymphocytes and NK cells (HNK-1 + lymphoid cells) were found in bone marrow during IFN treatment. In DCF-treated patients bone marrow T lymphocytes were markedly reduced below the values of normal bone marrow. This DCF-induced T-cell depression might be related to the clinical observation of persistent cellular immune dysfunctions in HCL patients despite a DCF-induced remission.

Adult

Effectiveness of intraocular lens calculation in high ametropia.

The error in prediction of emmetropic intraocular lens power or postoperative refractive error after lens implantation was analyzed in three groups of eyes after posterior chamber lens implantation. Regression line calculation with the SRK equation or with a group-specific regression was compared with theoretical calculations in unselected, long myopic and short hyperopic eyes. The cut-off length was below 22.0 mm for the short eyes and above 25.9 mm for the long eyes. In the unselected and hyperopic group, there was only a small difference in mean error and error variance when the three calculation methods were compared. In the high myopic group, the range of error increased in all methods. The worst results were obtained with the standard SRK equation because the slope of the regression line in myopic eyes differs from the classical regression line calculated on an average population of implants. Lens calculation in high myopic eyes should therefore be performed with a specific regression line or by theoretical calculation.

Humans

Ethological studies in animals and man, their use in psychiatry.

Ethology is concerned with the observation, description and measurement of the acts and postures which make up the behavioural repertoire of animals. Man too, exhibits analogous patterns of non-verbal behaviour, many of which serve social interactions. It is shown how ethological profiles of psychiatric patients can be constructed using the same methods as are used to analyse the social behaviour of rodents. It is argued that deficits in social behaviour are a key feature of the mentally ill patient and arise when flight, i. e. escape-oriented behaviour predominates. This notion is supported by an ethological study which shows that compared to healthy subjects, depressed patients exhibit fewer facial expressions and gestures which instigate or invite social interactions. These patterns serve to isolate the depressive patients from the group. With its emphasis upon objective analysis of behaviour, the ethological approach can provide a useful adjunct to conventional but largely subjective, clinical assessment schemes. It can also help to integrate findings in man and animals since in both, the behaviour is assessed in the same kind of units according to a common conceptual framework.

Animals

[The intraperitoneal installation of gamma interferon for the treatment of refractory ovarian carcinoma].

Patients with refractory ovarian cancer were treated intra-peritoneally with interferon-gamma. The maximum tolerated dose was achieved at 2 mg/m2. The substance was administered 3 times per week every second week. Interferon-gamma treatment activated locally the macrophages and induced a rise in neopterin urine, serum, and ascites levels. The tumor marker CA-125 showed marked fluctuations of more than 100% during interferon treatment and this was not correlated with neopterin. A flu-like syndrome and especially fatigue were the dose limiting side effects. Two of 3 evaluable patients died on tumor progression whereas one is now 18 months clinically free of disease.

Aged

Acute effects of single doses of recombinant interferon-gamma on blood cell counts and lymphocyte subsets in patients with advanced renal cell cancer.

The object of this study was to investigate the effects of different single doses of recombinant interferon-gamma (rIFN-gamma) on white blood cell counts, differential blood counts, and the relative composition of T-cell subsets in the peripheral blood of cancer patients. Sixteen patients suffering from metastasizing renal cell carcinoma received 10, 100, or 500 micrograms of rIFN-gamma three times at weekly intervals. After a therapy-free interval of 2 weeks, the next dose level was applied. The order of dose levels was assigned randomly to each patient. White blood cells, differential blood counts, and the number of Leu1, Leu3, Leu2a, Leu7, and HLA DR+ cells were measured immediately before and at 4, 24, 48, 72, 96, and 168 h after the administration of single doses of rIFN-gamma. Results indicated that white blood cells were transiently removed from the blood circulation after administration of IFN-gamma. Monocytes, HLA DR+ cells, and Leu7+ cells were reduced to below 50% of pretreatment values 4 h after application of the cytokine. CD8+ cells and granulocyte counts declined to approximately 70% of pretreatment values 24 h after IFN therapy. The preferential reduction of CD8+ lymphocytes resulted in a temporary increase of the T4/T8 ratio in these patients.

Adult

Studies of the mechanism of tolerance induced by short-term immunosuppression with cyclosporine in high-risk corneal allograft recipients. I. Analysis of CTL precursor frequencies.

Transplantation of unmatched allogeneic corneas into highly vascularized recipient eyes under the cover of short-term immunosuppression with cyclosporine enables permanent engraftment. The aim of this study was to further elucidate the mechanism(s) underlying this tolerant state. In eight "high-risk" cornea recipients the clone sizes of donor-specific and third-party reactive cytotoxic T cell precursors were assessed by limiting dilution analyses before and at three and six months after transplantation. Acquired allograft tolerance in these patients was not accompanied by clonal reduction of donor-specific CTL-p, whereas in the case of an irreversible rejection the donor-specific CTL pool size was significantly enlarged. This donor-specific CTL-p increase could already be seen two months before clinical manifestation. These patterns differed from that of tolerant renal transplant patients, in whom marked and donor-specific reduction of CTL-p was observed. During rejection identical patterns with increasing donor-specific CTL-p frequencies were seen in both groups of patients. We conclude that induction of tolerance by short-term CsA to unmatched cornea grafts is not caused by clonal reduction of the effector precursor cell pool.

Adult

Release of interleukin 2 and gamma interferon by peripheral mononuclear cells in human Schistosoma mansoni infection normalizes after chemotherapy.

Interleukin 2 (IL-2) and gamma interferon (IFN-gamma) were determined in supernatants of mitogen- and antigen-driven cell cultures from patients with hepatosplenic or intestinal schistosomiasis. Skin reactivity was tested using a panel of eight recall antigens. Results were compared with those of uninfected local controls. In both schistosomiasis groups, IL-2 activity was reduced before treatment. In less than one third of the patients, schistosomal antigens elicited detectable IL-2 activity. IFN-gamma production was reduced more severely in hepatosplenic cases, in particular after stimulation by anti-CD3 monoclonal antibodies. After anti-schistosomal therapy with praziquantel, mitogen-induced IL-2 and IFN-gamma activities became normal within 3 months in intestinal schistosomiasis, and within 6 months in the hepatosplenic patient group. Results of in vivo delayed-type hypersensitivity tests paralleled those of in vitro lymphokine production. In conclusion, evidence is presented for severe, antigen-unspecific suppression of lymphokine production and skin reactivity against recall antigens. Anti-parasitic chemotherapy is shown to reverse the impairment of cell-mediated immune responses at the cytokine level.

Adolescent