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Biomedical subjects

P Winter

Publications and source records attributed to P Winter.

At least 55 records · Page 3Linked to original sources
PubMed1997

Screening and biochemical characterization of transthyretin variants in the Portuguese population.

The study of pathogenic and nonpathogenic transthyretin (TTR) variants is very important for the understanding of such TTR-related diseases as hereditary amyloidosis and also to establish a relationship between the structure and function of the molecule. Variants with clinical manifestations can be easily detected, but clinically silent variants can be detected only by population screening programs using specialized techniques. Hybrid isoelectric focusing (HIEF) in extremely flattened immobilized pH gradients (IPG) allows the detection of even neutral amino acid substitutions and has been used to analyze approximately 5,000 samples from the Portuguese population. Comparison with samples from carriers of three known TTR mutations (Met 30 associated with hereditary amyloidosis, Met 119, and Asn 90) was also made. In this study we detected: (1) 8 individuals carriers of TTR Met 30, (2) 35 carriers of TTR Met 119, (3) 12 carriers of TTR Asn 90, (4) 1 compound heterozygote for TTR Met 30/Met 119, and (5) 5 variants that presented a different pattern from the controls used. We also performed DNA sequencing analyses of two of the variants with the different band pattern in HIEF. The individuals were found to be carriers of TTR Ile 122 and TTR Thr 190, respectively. All the mutations detected, except for Asn 90, result from substitutions in CpG hot spots and thus can be rather frequent in the populations. Studies on the clinical evolution of the compound heterozygotes and on the physical-chemical properties of these hybrid TTRs will help to understand the pathogenicity associated with TTR.

Amyloidosis↗
PubMed1997

Tumour induction as a consequence of immunosuppression after renal transplantation.

Immunosuppressed recipients of organ transplants have a higher incidence of carcinoma than the general population. A retrospective analysis was made at the Department of Urology of Bonn University, investigating 236 renal allograft recipients as to the incidence of neoplasms before and after transplantation. Eleven patients developed malignant tumours after transplantation. In 4 out of these 11 patients, case history showed pre-existing malignancies. Two of the 4 patients developed a second tumour, while the other two had tumour progression (latency period 21-77 months). Three of the 4 patients died of their tumours 21, 42 and 77 months after transplantation, whereas one female patient is still alive and free of neoplasms 32 months after transplantation. In 7 out of these 11 patients de novo tumours were diagnosed (latency period 3-88 months). All of them are still alive (NED between 15 and 85 months), six of them with good transplant function. There was no difference to be seen in the incidence of malignancies between kidneys supplied by Eurotransplant (n = 40) and ABO compatible kidneys from our own donors (n = 196). The higher incidence rate of neoplasms in transplant recipients requires high standards in preventive measures. Any suspicious change that may occur in the course of a thorough follow-up of transplant recipients must be removed and examined histologically. Patients with previous malignant diseases must be payed special attention, since they frequently tend to develop another malignant tumour and progression of existing tumours, respectively. As far as immunosuppression is concerned, therapeutic guidelines for the treatment of transplant recipients do not differ from those set up for patients on haemodialysis. Since immunosuppression with increased rates of tumour incidence can also be observed in dialysis patients, the mere fact of increased incidence of neoplasms cannot be taken as an argument against transplantation. With a more or less equal risk of tumour incidence the crucial factor should be the higher quality of life for transplant recipients.

Adenocarcinoma↗
PubMed1997

Dissolution of artificial (natural) stones in a standard model: first results.

In studying the dissolution of stones in vitro, the advantage of artificial stones in comparison to natural stones is that one can get substance-specific standardized and reproducible results. Our investigations were performed with artificial stones composed of natural material (calcium apatite). These stones were of spherical form and consisted of layers built up around a core. They were comparable to natural stones in their physical properties. Litholysis was performed in a special apparatus with continuous exposure to Suby G solution under standard conditions. Natural stones of the same chemical composition served as a reference. Statistical measurements were performed. By hardening of the artificial stones, it was possible to reach a dissolution comparable to natural stones composed of calcium apatite depending on the Suby G concentration (artificial 2.5 resp. 4.75 mg/h; natural 2.18 resp. 4.2 mg/h). For the first time, an artificial stone model has been created with reproducible behaviour in response to chemolitholysis and with properties of dissolution comparable to those of natural stones of identical chemical composition.

Apatites↗
PubMed1997

Management of complete ureteral replacement. Experiences and review of the literature.

The common treatment for patients with extensive damage to the ureter is complete ureteral replacement, combining Boari flap-psoas bladder hitch and downward mobilization of the involved kidney, with complete ideal replacement of the ureter, renal autotransplantation, of elective nephrectomy. Three case reports serve to describe two options of reconstructive treatment for complete ureteral replacement. The operative techniques, their limits, their postoperative results, and the treatment alternatives are discussed with due regard to recent literature. In the case of ileal replacement we have used a very short ileal segment to reduce the absorption surface of the ileal mucosa. Reflux prevention of the ileal segment was performed by creating an invaginated distal ileum nipple which was additionally fixed at the Boari flap by a third stapler row (auto suture TASS) to prevent potential nipple-gliding.

Adult↗
PubMed1997

Production of artificial urinary stones from natural materials and their physical properties. First results.

Considered from a clinical point of view, all artificial stones known so far are inappropriate for experimental investigations, because they do not correspond to natural urinary stones in shape, physical properties and chemical composition. A special technique has now been developed for the production of biometric artificial stone models. Standard artificial carbonate apatite stones were produced by a coating technique where several layers of a suspension consisting of pure substance were applied around a core. Density and crushing strength of these ball-shaped artificial stones corresponded to natural apatite stones. Experimental chemolitholysis investigations showed comparable results in respect to the dissolution of artificial apatite stones and of natural stones of the same chemical composition. The disintegration behaviour was studied in ESWL tests which revealed a correlation between generator voltage and number of shock waves necessary for complete disintegration. For the first time, an artificial urinary stone has now been produced which is comparable to a natural stone of the same chemical composition not only in shape but also in its physical properties and lysis behaviour. These stones are suitable for use in systemic scientific investigations on disintegration and chemolitholysis.

Apatites↗
PubMed1996

A new isoleucine substitution of Val-20 in transthyretin tetramers selectively impairs dimer-dimer contacts and causes systemic amyloidosis.

The most frequent form of inherited amyloidoses is associated with mutations in the transthyretin (TTR) gene coding for 127-amino acid residues of four identical, noncovalently linked subunits that form a pair of dimers in the plasma protein complex. Amyloid fibrils containing the variant and to a lesser extent the wild-type form of the TTR molecule are deposited in various organs, including peripheral nerves and the myocardium, with polyneuropathy and cardiomyopathy as major clinical manifestations. So far, more than 40 distinct amino acid substitutions distributed throughout the TTR sequence over 30 positions have been found to be correlated with an increased amyloidogenicity of TTR. Most of these amyloidogenic amino acid substitutions are suspected to alter the conformation and stability of the monomer. Here we identify and characterize by protein and DNA analysis a novel amyloidogenic Val-20 to Ile mutation in a German three-generation family. The index patient suffered from severe amyloid cardiomyopathy at the age of 60. Conformational stability and unfolding behavior of the Ile-20 monomer in urea gradients was found to be almost indistinguishable from that of wild-type TTR. In contrast, tetramer stability was significantly reduced in agreement with the expected change in the interactions between the two opposing dimers via the side chain of Ile-20. Our observations provide strong evidence for the view that amyloidogenic amino acid substitutions in TTR facilitate the conversion of tetrameric TTR complexes into those conformational intermediates of the TTR folding pathway that have an intrinsic amyloidogenic potential.

Amino Acid Sequence↗
PubMed1996

Wilms' tumour in adults. Review of 10 cases.

Nephroblastoma (Wilms' tumour) is very rarely found in adult patients. We report on 10 cases to demonstrate the diagnostic and therapeutic problems. In case of flank pain, large tumour mass, fast tumour growth and young age, the possibility of Wilms' tumour should be taken into consideration even in adult patients. The chances for a successful treatment by primary surgery with adjuvant therapy are favourable for the lower stages I and II. All our patients presenting with tumour stages I and II have survived and have been free of disease for 68 months now. One of the patients with stage III Wilms' tumour died 8 months postoperatively while the other one has been free of disease for 120 months now. In the advanced stage IV no patient survived. In cases of inoperable large tumours in adults, the possibility of primary chemotherapy should be considered under certain circumstances. Rapid tumour regression may confirm the diagnosis and will make feasible a salvage operation in some cases.

Adolescent↗
PubMed1996

Mortality from scrotal cancer in metal machinists in England and Wales, 1979-80 and 1982-90.

The hazard of scrotal cancer from cutting oils was first recognized in the 1950s, and led to various control measures including the introduction of solvent refined oils, use of splash guards, provision of protective clothing and washing facilities and education of workers to encourage early detection and treatment of tumours. To assess how effective these controls have been, we have analyzed occupational mortality from scrotal cancer in England and Wales during 1979-80 and 1982-90. Over this 11-year period 85 deaths were attributed to the disease in man aged 20-74. This represents a reduction in mortality from the 1960s. Significantly elevated proportional mortality ratios (PMRs) were found in press and machine tool setters (PMR 1,678, five deaths), centre lathe turners (PMR 1,099, three deaths) and machine tool operators (PMR 303, eight deaths), but all of the metal machinists who died of scrotal cancer had been born before 1930, and could have worked with cutting oils before controls were introduced. These findings are reassuring, but continued monitoring of scrotal cancer incidence and mortality is required.

Adult↗
PubMed1996

Homozygosity and heterozygosity for the transthyretin Leu64 mutation: clinical, biochemical and molecular findings.

Transthyretin gene point mutations cause hereditary amyloidosis with an autosomal dominant pattern of inheritance. The disease usually manifests itself in heterozygous patients, although a few homozygotes have been reported. We describe two unrelated patients carrying the Leu64 mutation, one of whom presents a homozygous genotype (Family B). Homozygosity was confirmed by sequence analysis, RG-PCR and double one-dimensional electrophoresis of the plasma protein. Although the clinical picture of the homozygous patient of Family B was more severe than that shown by the heterozygous members of Family A, the variability often displayed by FAP patients does not allow any firm conclusion about the role of homozygosity in the seriousness of the disease.

Aged↗
PubMed1996

Mortality of farmers and farmers' wives in England and Wales 1979-80, 1982-90.

OBJECTIVES: To examine the mortality patterns of male and female farmers and farmers' wives in England and Wales. METHODS: Information on all deaths in England and Wales at ages 20-74 during the periods 1979-80 and 1982-90 was obtained from the Office of Population Censuses and Surveys. Proportional mortality ratios (PMRs) and proportional cancer mortality ratios (PCMRs) were used to compare the mortality of farmers with that of the general working population, and of farmers' wives with wives of all working men. RESULTS: Farmers and farmers' wives had high mortality from accidents and suicide and from certain respiratory diseases. Mortality from hernia was also raised. Deaths from cancer were generally below expectations, but the PMR for prostatic cancer was 112 (95%CI 106-118). The PMRs and PCMRs for oesophageal cancer were significantly increased in male farmers from two counties where cider is produced. CONCLUSIONS: The occupational hazards of farming continue to be associated with excess mortality, and most of the risks extend also to farmers' wives. Action is needed to reduce deaths, particularly from accidents and suicide.

Accidents, Occupational↗
PubMed1996

Cancer mortality among shoe manufacturing workers: an analysis of two cohorts.

OBJECTIVES: To examine the cancer risk of shoe manufacturing workers and evaluate whether the risk was associated with exposure to leather dust and solvents. METHODS: Data from two historical cohort studies of shoe workers were expanded and analysed in parallel. A total of 4215 shoemakers from England contributing 103 726 person-years at risk and 2008 shoemakers from Florence, Italy, contributing 54,395 person-years at risk were included in the analysis. Exposure to leather dusts and solvents from glues was evaluated on the basis of job title information. Standardised mortality ratios (SMR) were calculated as ratios of observed deaths (Obs) over expected derived from national mortalities. RESULTS: Overall mortality was lower than expected in both cohorts (English cohort: Obs 3314, SMR 81, 95% confidence interval (95% CI) 78-84; Florence cohort: Obs 333, SMR 87, 95% CI 78-97). An increased risk of nasal cancer was found (English cohort: Obs 12, SMR 741; Florence cohort: Obs 1, SMR 909). 10 of the 13 cases occurred among English workers employed in the manufacture of welted boots (SMR 926, 95% CI 444-1703), a sector of the industry thought to have had the highest exposure to leather dust. Mortality from leukaemia was not increased in the English cohort (Obs 16, SMR 89), but was increased in the Florence cohort (Obs 8, SMR 214, 95% CI 92-421); and the highest risk was found among shoe workers in Florence who were first exposed between 1950 and 1959 when exposure to benzene was substantial (Obs 3, SMR 536, 95% CI 111-1566). Some evidence for an excess risk of stomach, bladder, and kidney cancer, as well as multiple myeloma and non-Hodgkin's lymphoma was also found in the Florence cohort only among workers employed in jobs with the highest exposure to solvents. CONCLUSIONS: These findings confirm the associations between exposure to leather dust and nasal cancer and between exposure to benzene and leukaemia in the shoe manufacturing industry and suggest that the risk of other cancers may be increased among workers exposed to solvents or glues.

Adult↗
PubMed1996

Wilms' tumor in adults. Review of 10 cases.

A nephroblastoma (Wilms' tumor) is very rarely found in adult patients. We report on 10 cases to demonstrate the diagnostic and therapeutic problems. In case of flank pain, large tumor mass, fast tumor growth, and young age, the possibility of a Wilms' tumor should be taken into consideration even in adult patients. The chances for a successful treatment by primary surgery with adjuvant therapy are favorable for the lower stages I and II. All our patients presenting with tumor stages I and II have survived and are free of disease since 68 months at the time of the study. One of 2 patients with a Wilms' tumor stage III died 8 months postoperatively, while the other is free of disease since 120 months. In the advanced stage IV no patient survived. In cases of inoperable large tumors in adults, the possibility of primary chemotherapy should be considered under certain circumstances. Rapid tumor regression may confirm the diagnosis and will enable salvage operation in some cases.

Adolescent↗
PubMed1996

N-acetyl-beta-D-glucosaminidase excretion in calcium oxalate stone patients and its relation to the risk of stone formation.

A tubular renal damage induced by crystals in the renal tubuli can be the triggering primary but also secondary cause of stone formation. In 72 calcium oxalate stone patients (45 men, 27 women) N-acetyl-beta-D-glucosaminidase [NAG] excretion in 24h-urine was investigated. 48 healthy test persons (27 men, 21 women) served as a control group and helped to establish reference values. In order to find out a possible relation between NAG reference values and the risks of urolithiasis, lithogenous and inhibitory substances were determined in both groups. In the following, relative calcium oxalate supersaturation, representing a risk of urinary stone formation, was analyzed and compared to NAG excretion values. The threshold value of pathologic NAG excretion was determined in the group of healthy test subjects (mean value +/- 2 standard deviation) and was fixed at 4.2 U/d (women 3.06 U/d, men 4.24 U/d). In our investigations on NAG excretion significantly (p < 0.05) increased values were found in stone patients (4.43 U/d +/- 4.27) as compared to healthy test persons (2.13 U/d +/- 1.02). In the case of increased NAG excretion in stone patients there was a positive correlation between NAG excretion and increased phosphate, sulphate, uric acid, oxalate, and creatinine excretion. Only in female patients there was a relation between relative calcium oxalate supersaturation and NAG excretion values. As a result, NAG determination is considered to be an appropriate means of tracing a certain risk group within calcium oxalate stone patients.

Acetylglucosaminidase↗
PubMed1995

The potential of microsatellites for hybridization- and polymerase chain reaction-based DNA fingerprinting of chickpea (Cicer arietinum L.) and related species.

The genetic variability in agronomically important chickpea accessions (Cicer arietinum L.) as detected by single-locus restriction fragment length polymorphism (RFLP) probes, random amplified polymorphic DNA (RAPD) and isoenzyme markers, is rather low. Recently, highly polymorphic microsatellites became the markers of choice for linkage mapping and population studies. We are currently following two main strategies to exploit the variability of microsatellites and adjacent sequences for genetic studies in chickpea. (i) In an approach referred to as oligonucleotide fingerprinting, microsatellite-complementary oligonucleotides were employed as multilocus probes for in-gel hybridization. A total of 38 different probes representing di-, tri- and tetranucleotide repeats were used to analyze variability between and within four accessions of C. arietinum. Hybridization signals were obtained with 35 probes. While the abundance and level of polymorphism of different target sequences varied considerably, distinct, intraspecifically informative banding patterns were obtained with the majority of probes and all restriction enzymes tested. No obvious correlation existed between abundance, fingerprint quality, and sequence characteristics of a particular motif. (ii) In a recently developed strategy called microsatellite primed polymerase chain reaction (MP-PCR), microsatellite-complementary oligonucleotides serve as single PCR primers for genomic DNA templates. We tested the general applicability of MP-PCR by amplifying DNA samples from tomato, chickpea and two related annual Cicer species with a variety of di-, tri- and tetranucleotide repeat primers. Most but not all primers generated distinct fingerprint-like banding patterns after agarose gel electrophoresis and ethidium bromide staining of the amplification products. Since the method proved to be sensitive to reaction conditions in a way similar to RAPD analysis, we increased the PCR specificity by the introduction of a modified "touch-down" protocol. In chickpea, touch-down MP-PCR generated highly reproducible banding patterns which predominantly revealed interspecific polymorphisms. The potential of different microsatellite-based strategies for genome analysis in chickpea is discussed.

Base Sequence↗
PubMed1995

Glycosaminoglycans in urine and extracorporeal shock wave lithotripsy.

In 50 calcium oxalate stone-forming patients, the total excretion of glycosaminoglycans (GAGs) and of four subgroups [chondroitin-4-sulfate (CS-A), chondroitin-6-sulfate (CS-C), dermatan sulfate (DS) and hyaluronic acid (HY)] were investigated before extracorporeal shock wave lithotripsy (ESWL) and during the subsequent 5 days. The standard value was determined by reference to a group of healthy test subjects. The excretion of GAGs was significantly higher in healthy test persons than in stone-forming patients. Twenty-four hours after ESWL administration, GAG excretion was enhanced significantly but returned to normal values over the course of 3 days. ESWL had no influence on the proportional composition of GAG subgroups CS-A, CS-C, DS and HY. The increase in GAG excretion after ESWL indicates a transient injury of renal tissue or of the mucus layer lining the urothelium. This lesion, however, can be regarded as temporary with later restitutio ad integrum.

Adult↗
PubMed1995

Laparoscopic varicocelectomy: indication, technique and surgical results.

OBJECTIVE: To assess the efficacy of laparoscopic techniques for the operative therapy of varicocele. PATIENTS AND METHODS: Fifty-one patients who underwent laparoscopic varicocelectomy due to subfertility and/or pain between June 1992 and December 1994 were evaluated. RESULTS: In all patients, except one with a remaining slight reflux on post-operative Valsalva's manoeuvre, operative therapy was effective and no major complications occurred. The procedure was minimally invasive, effective and, because the anatomy was readily seen, multiple veins and/or collaterals were easily assessed and the surgery precise. CONCLUSION: The laparoscopic technique is an efficient, minimally invasive operation with optimal results. After a brief period of training the operation can be performed in 15-30 min and is therefore no longer than embolization techniques. Treatment of both sides in one session was not a problem.

Adult↗
PubMed1995

Differences in occupational mortality from pleural cancer, peritoneal cancer, and asbestosis.

OBJECTIVE: To assess whether the increased risk of disease related to asbestos in occupations from the construction and engineering industries applies equally to pleural cancer, peritoneal cancer, and asbestosis. METHODS: Analysis was based on deaths among men aged 20-74 in England and Wales during 1979-80 and 1982-90. (n = 1,656,096). Information about cause of death and the last full time occupation of decedents was derived from death certificates. Proportional mortality ratios (PMRs) by occupation were calculated for each of pleural cancer, peritoneal cancer, and asbestosis. RESULTS: Altogether, 2848 deaths were attributed to cancer of the pleura, 362 to cancer of the peritoneum, and 281 to asbestosis. When occupations were ranked according to PMRs from these diseases, striking differences were found. The category of construction workers which included laggers had the highest mortality from peritoneal cancer (PMR 990, 64 deaths), but a PMR of only 160 (77 deaths) for pleural cancer. In contrast, several occupations with much higher mortality from pleural tumours had no excess of peritoneal cancer. PMRs for asbestosis related more closely to those for peritoneal than pleural cancer. CONCLUSIONS: These findings suggest that the exposure-response relations for diseases related to asbestos are not all linear, and that risks of pleural mesothelioma may be underestimated by simple extrapolation from observations in cohorts with heavy exposure.

Adult↗