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Biomedical subjects

M Spycher

Publications and source records attributed to M Spycher.

At least 19 recordsLinked to original sources
PubMed2000

Product equivalence study comparing the tolerability, pharmacokinetics, and pharmacodynamics of various human immunoglobulin-G formulations.

In this randomized, double-blind, parallel-group study, a commercially available human immunoglobulin-G product, IVIG, was compared with two test formulations: (1) IVIG-N, which is a nanofiltered formulation of IVIG, and (2) IVIG-L, which is a nanofiltered, liquid, ready-for-use IgG formulation containing nicotinamide, L-proline, and L-isoleucine as stabilizers. Three groups of 10 healthy subjects each received a single 0.6 g/kg dose of one of the formulations infused over 3.5 to 6.8 hours, depending on the total volume to be infused. Blood samples were obtained over a 6-week period to assess pharmacokinetics, immunogenicity, and the pharmacodynamic effects on leukocytes and TNF-alpha. A blood sample was taken at 6 months for a viral safety check. Administrations were generally well tolerated with only one reference IVIG infusion stopped prematurely due to headache. The IgG Cmax and AUC over the 6-week blood sampling period from both test formulations satisfied equivalence criteria compared with the reference formulation. In subjects receiving IVIG-L, peak concentrations of the stabilizer nicotinamide ranged from 0.34 to 0.47 mmol/L and of nicotinamide-N-oxide from 0.03 to 0.04 mmol/L, which are below those reported to cause adverse events. During the infusion of IVIG, leukocyte counts initially declined from a baseline of 5.7 +/- 1.1 x 10(9)/L to 3.7 +/- 0.8 x 10(9)/L at 2 to 4 hours and returned to baseline by 24 hours. TNF-alpha levels, reflecting activation of the monocyte-macrophage system by the infused IVIG, rose from a baseline of 13 +/- 4 pg/mL to a peak of 272 +/- 324 pg/mL at 2 to 4 hours and returned to baseline by 24 hours. These patterns were generally similar for the test formulations, with the exception that the increase in TNF-alpha levels was dampened for IVIG-N, although this was not statistically significant. There was no evidence of immunogenicity or viral transmission from any of the formulations. Hence, these three formulations were generally well tolerated, yielded similar systemic exposure to IgG over a 6-week period after administration, and did not give rise to immunogenicity or viral safety concerns.

Adolescent↗
PubMed1999

Reduction of selenite and detoxification of elemental selenium by the phototrophic bacterium Rhodospirillum rubrum.

The effect of selenite on growth kinetics, the ability of cultures to reduce selenite, and the mechanism of detoxification of selenium were investigated by using Rhodospirillum rubrum. Anoxic photosynthetic cultures were able to completely reduce as much as 1. 5 mM selenite, whereas in aerobic cultures a 0.5 mM selenite concentration was only reduced to about 0.375 mM. The presence of selenite in the culture medium strongly affected cell division. In the presence of a selenite concentration of 1.5 mM cultures reached final cell densities that were only about 15% of the control final cell density. The cell density remained nearly constant during the stationary phase for all of the selenite concentrations tested, showing that the cells were not severely damaged by the presence of selenite or elemental selenium. Particles containing elemental selenium were observed in the cytoplasm, which led to an increase in the buoyant density of the cells. Interestingly, the change in the buoyant density was reversed after selenite reduction was complete; the buoyant density of the cells returned to the buoyant density of the control cells. This demonstrated that R. rubrum expels elemental selenium across the plasma membrane and the cell wall. Accordingly, electron-dense particles were more numerous in the cells during the reduction phase than after the reduction phase.

Inactivation, Metabolic↗
PubMed1998

Metaplastic lipid-rich carcinoma of the breast.

A case of lipid-rich mammary carcinoma identified in a lumpectomy specimen from a 56-year-old female is presented. The tumor showed features of poorly differentiated invasive ductal carcinoma of clear-cell phenotype. Cytoplasmic lucency was mainly accounted for by the accumulation of neutral fat and, to a lesser degree, glycogen. Tinctorial properties included positivity of tumor cells with Sudan III dye and diastase-sensitive periodic acid-Schiff staining. Ultrastructural examination confirmed the presence of abundant cytoplasmic lipid droplets and some glycogen rosettes. On immunohistochemistry, most tumor cells reacted for cytokeratin, vimentin and S-100 protein, and there was focal expression of carcinoembryogenic antigen. A minority of tumor cell nuclei expressed progesterone receptors. As an additional feature, part of the lesion exhibited chondroid metaplasia. Lipid-rich carcinoma of the breast is exceedingly rare and, to our knowledge, no such example harboring metaplastic elements has been described previously.

Biopsy, Needle↗
PubMed1996

[Multiple sclerosis: therapy with recombinant beta-1b interferon: initial results with 30 multiple sclerosis patients in northwest Switzerland].

Recombinant interferon beta-1b has been registered with the Swiss health authorities since August 1995. Due to a special arrangement with health insurances it has been possible to prescribe this medication since spring 1995. We report on our experience with the first 30 consecutively treated multiple sclerosis patients. Indication, adverse event profile and clinical response to treatment are described. The most common side effects were local injection site reactions (63%), influenza-like symptoms (50%) and fatigue (33%). As compared to the prestudy period we observed a 49% reduction in the exacerbation rate. Compliance was excellent, possibly due to strict selection and extensive information about possible effects and side effects.

Adjuvants, Immunologic↗
PubMed1996

[Unusual crystalline inclusions in plasmacytoma cells of the testis in primary medullary plasmacytoma].

At the autopsy of a 68 year old man with plasmacytoma of the lambda light chain type we found polygonal interstitial cells with unusual crystalline inclusions, which were not readily identifiable and slightly resembled Leydig cells in conventional microscopy. In electron microscopy these could be identified as plasmacytoma cells, representing a testicular involvement. Comparable cells could be shown in the bone marrow. In immunochemistry we found a polyclonal reaction for lambda light chains suggesting a similar phenomenon as the so-called Russell bodies. As far as we know the literature, this finding in a testicular metastasis has not been described.

Aged↗
PubMed1996

Correlation between the development of extracolonic manifestations in FAP patients and mutations beyond codon 1403 in the APC gene.

The APC gene was investigated in 31 unrelated polyposis coli families by SSCP analysis and the protein truncation test. Twenty-three germline mutations were identified which gave rise to a variety of different phenotypes. Some of these mutations have already been described; however we report six previously unpublished mutations. Typical disease symptoms were observed in families who harboured mutations between exon 4 (codon 169) and codon 1393 of exon 15. Mutations beyond codon 1403 were associated with more varied phenotype with respect to the development of extracolonic symptoms. In this report we provide support for the notion that there appears to be a correlation between the location of an APC mutation (beyond codon 1403) and extracolonic manifestations of familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1996

BRCA1 mutations in a selected series of breast/ovarian cancer patients.

Germline mutations in the BRCA1 gene have been associated with familial breast/ ovarian cancer in large families showing high penetrance of the disease. Little is known, however, about the contribution of BRCA1 mutations to breast/ovarian cancer in small families with few affected members or in isolated early onset cases. Therefore we examined the BRCA1 gene in 63 breast/ovarian cancer patients who either came from small families with as few as one affected first degree relative, or in patients who had no family history but had developed breast cancer under 40 years of age. Using the protein truncation test, we were able to identify three unique BRCA1 germline mutations (4.8%). Two of the probands had only one affected first degree and several second degree relatives and the third had three affected first degree relatives including two sisters who, when tested, were also found to carry the mutation. There was no family history of ovarian cancer in any of the three families.

Adult↗
PubMed1995

Novel germline APC gene mutation in a large familial adenomatous polyposis kindred displaying variable phenotypes.

The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli. Many mutations have been described but the relation between their site and the phenotypic expression of the disease remains unclear. The most commonly seen mutation occurs at codon 1309. Many other mutations have been described towards the 5' end of exon 15 of the APC gene but comparatively few have been seen towards the 3' end. Recent reports have indicated the possibility of a functional boundary with respect to severity and age of onset of disease, which lies towards the 5' end of the gene. This report describes a large family whose affected members present with a very variable phenotype ranging from an early onset and severe form to a comparatively mild later onset one. The mutation that predisposes to disease in this family is at a previously undescribed site that lies towards the 3' end of exon 15 of the APC gene, which results in a stop codon. Interestingly, the stop codon is 63 codons downstream of the mutation and therefore may affect the expression of the disease. The addition of this mutation to the growing list of mutations described in the APC gene may provide some insight into the genotype/phenotype relation of the disease thus contributing to the understanding and significance of mutations at specific sites in the APC gene.

Adenomatous Polyposis Coli↗
PubMed1995

Early and severe sensory loss in three adult siblings with hexosaminidase A and B deficiency (Sandhoff disease).

Three siblings in their sixth and seventh decade with hexosaminidase A and B deficiency (adult form of GM2-gangliosidosis, variant O) developed early and severe sensory loss in addition to chronic motor neuron disease and cerebellar ataxia. Prominent mechanoallodynia was a manifesting symptom in two siblings. It is suggested that sensory deficits are due to a central-peripheral dying back axonopathy. The early and dominant sensory disturbances extend the clinical range of GM2-gangliosidosis.

Aged↗
PubMed1995

Are papillary adenomas endolymphatic sac tumors?

Papillary adenomas of the temporal bone have been considered as originating from the endolymphatic sac. The radiologic, surgical, and pathologic findings in a patient suffering from von Hippel-Lindau disease with bilateral papillary adenomas of the temporal bone cast some doubt on this site of origin. Radiologically, the center of tumor growth was at the top of the jugular bulb. Intraoperatively, the tumor was found to have reached the lateral wall of the endolymphatic sac, but the lumen was tumor-free. Both ciliated and nonciliated tumor cells were found in the resected tumor, resembling the ultrastructure of normal epithelial lining in the human mastoid. A strong positive immunohistochemical reaction for keratin and negative reactions for vimentin, glial fibrillary acidic protein, and S-100 protein in the tumor tissue of this patient are typical for middle ear mucosa. Therefore, the described papillary adenoma originated from the mucosa of the pneumatic spaces surrounding the jugular bulb, and the theory that the endolymphatic sac is the origin of all papillary-cystic tumors (adenocarcinomas) should be questioned.

Adenoma↗
PubMed1994

Mutational analysis of the first 14 exons of the adenomatous polyposis coli (APC) gene.

In the present study, the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) technique has been applied to the mutation analysis of the adenomatous polyposis coli (APC) gene. We examined the first 14 exons of the APC gene in 46 polyposis coli patients. Five germline mutations were observed, including a single-nucleotide substitution and small (1-4 bp) deletions leading, in 4 cases, to a stop codon. A missense mutation in exon 3 and a 1 bp deletion in exon 4 of the APC gene were observed in patients presenting with the attenuated form of FAP.

Adenomatous Polyposis Coli↗
PubMed1994

Comparative in vitro phagocytosis and F-actin polymerization of bovine neonatal neutrophils.

Analysis of neonatal neutrophil (PMN) functions should help to reveal factors which could contribute to the impaired host defense system of neonates. We analysed functional parameters of PMN from newborn calves (N-PMN) and adult bovines (A-PMN): cellular volume and F-actin content upon stimulation with complement factors, by cytofluorometry and phagocytosis of E. coli 78:80B with a colorimetric assay. Polymerization of F-actin was rapid in both N- and A-PMN, but reached higher levels in N-PMN. N-PMN are significantly smaller than A-PMN throughout the whole activation time. Percentage of phagocytosing PMN, the rate of phagocytosis, and the rate of killing are similar between A- and N-PMN after opsonization of bacteria with adult serum (AS). Opsonization with newborn serum (NS) reduced all three examined parameters: in A-PMN more (P < 0.001) than in N-PMN (P < 0.05). However, when phagocytosis was compared following age-matched opsonization (N-PMN and NS; A-PMN and AS), N-PMN phagocytosed less (P < 0.001) bacteria per PMN than A-PMN. Additionally, steroidal (dexamethasone) and non-steroidal (phenylbutazone) anti-inflammatory drugs inhibited phagocytosis by N-PMN less than by A-PMN. Higher relative F-actin content of N-PMN can be correlated with the documented functional hyperactivity of bovine N-PMN. However, the exaggerated impairment of phagocytosis in calves observed after age-matched opsonization of bacteria could potentially indicate a specific host defence defect.

Actins↗
PubMed1993

[Hereditary p53 mutation in a patient with multiple tumors: significance for genetic counseling].

We describe molecular genetic findings in a patient who initially presented with an intermediate teratoma of the testis and who many years later presented with an oligodendro-astrocytoma. In addition he developed a malignant histiocytoma over the scapula, an adenocarcinoma of the stomach and a late stage adenoma of the sigmoid colon. Due to the development of several neoplasms the possibility of either ataxia telangiectasia or Li-Fraumeni syndrome was considered in differential diagnosis. A molecular genetic investigation revealed that both he and his brother carried a germline p53 tumor suppressor gene mutation at codon 248. From this result we conclude that this family belongs to the Li-Fraumeni syndrome. Once characterized as belonging to the Li-Fraumeni syndrome, the remaining members of the family were typed to determine if they too carried the same mutation. The two children of the index patient were shown not to carry the mutation and are therefore at no increased risk of developing any of the Li-Fraumeni spectrum of malignancies. A molecular genetic investigation into similar families could help to prevent the development of additional malignancies as seen in the index patient, as radiotherapy may interfere with the normal function of the p53 protein and this may in turn help to orchestrate DNA repair after radiation.

Adult↗
PubMed1993

[Efficacy of 2 different leukocyte filters for erythrocyte concentrates].

By leukocyte reduction in red blood cell concentrates to < 5 x 10(6) leukocytes per transfused unit, febrile non-hemolytic transfusion reaction as well as alloimmunization and transmission of certain viral diseases (CMV, HTLV-1) can be prevented. Using a Nageotte hemocytometer with a large-volume chamber, the residual leukocyte number after filtration of 40 buffy-coat free red blood cell units with the filters Pall RC100 and Sepacell R500 B1 was determined in a clinical routine setting. Both tested filters underscored the limit (< 5 x 10(6) leukocytes per unit) set by the American Association of Blood Banks. Hemoglobin loss accounted for 8.9 g (Pall RC100) versus 7.7 g (Sepacell R500 B1), which is about 15-18% of the hemoglobin content of a red blood cell concentrate.

Blood Component Removal↗