Risk factors associated with BMSCC greater than 200 000 cells/ml in dairy herds in southern Chile.

A cross-sectional survey of 523 dairy farms in the south of Chile was carried out to quantify risk factors associated with bulk-milk somatic-cell count (BMSCC) >200 x 10(3)cells/ml. Questionnaires followed by one reminder were sent to 3710 dairy farms via the 11 milk-processing plants that they supplied in October 1998. The response proportion was 14.1%. The median BMSCC was 289 x 10(3) cells/ml (range: 74 x 10(3) to 1800 x 10(3)cells/ml). The median herd size was 70 cows (range: 7-616); herd size was not associated with BMSCC. The annual milk yield of 33.2% of the herds was <4000 l and 53.4% had an annual milk yield of 4 x 10(3) to 6 x 10(3) l. Clinical-mastitis records were kept by 55.3% of the farmers. Seventy-six percent of the farmers (377/499) reported <10 clinical cases of mastitis in the year prior to the questionnaire. Logistic multiple regression indicated that BMSCC >200 x 10(3)cells/ml was more likely when foremilking was practised, and when cows were collected in a yard before milking. BMSCC was less likely to be >200 x 10(3)cells/ml when teats were washed with water containing disinfectant compared with plain water; when the udder and teats were always checked before milking compared with, sometimes or never; when cows with mastitis were milked first compared with any other ordering, and when farmers recorded individual-cow somatic-cell count (ICSCC) compared with when ICSCC was not recorded.

[Human fascioliasis symptoms. A case report with review of the literature]. / Das Krankheitsbild der humanen Fasciolose. Ein Fallbericht mit Literaturübersicht.

We present the case of a 17 years old man with fasciola hepatica infection. After initial therapy with Praziquantel and Metronidazole abdominal pain as well as eosinophilia persisted. The diagnosis was made by ERC and examination of the bile, where typical ovulas were found. An analysis of faeces and the serology (ELISA, IFAT) were not diagnosticated. After papillotomy, extraction of the parasites and therapy with Triclabendazole the patient became asymptomatic, the serology turned to negative and the haematology was normalised.

Does smoking protect from Alzheimer's disease? Alzheimer-type changes in 301 unselected brains from patients with known smoking history.

The objective of this report is to investigate whether smoking exerts any influence on the number of senile plaques and Alzheimer neurofibrillary tangles. A retrospective study was based on unselected consecutive autopsy findings on the brains of 301 patients aged 65 years or older examined at the Institute of Pathology, Basel. Brains were investigated according to a fixed protocol. Histological examination was performed on 15 paraffin-embedded tissue blocks per brain using staining with silver impregnation specific for Alzheimer neurofibrillary tangles and for senile plaques, and Alzheimer-type changes were quantified. Retrospective assessment of smoking history was also based on a fixed protocol. Statistical analysis of the relationship between the smoking habits and the amount of Alzheimer-type changes was performed and included analysis of 72 age- and sex-matched smoker-nonsmoker pairs from within the total of 301 cases to compensate for variations in these changes due to age/sex alone. The influence of smoking on the total of 301 cases cannot be proven statistically. But a protective action against senile plaque formation could be demonstrated in 28 age matched pairs of smoking-nonsmoking women. Furthermore a positive correlation between the amount of smoking and the neurofibrillary changes as expressed in Braak stages in smokers of both sexes was present. Thus, there seems to be an influence of nicotine on the structural alterations of Alzheimer's disease which can exert itself in opposite directions.

Fermentation database mining by pattern recognition.

A large volume of data is routinely collected during the course of typical fermentation and other processes. Such data provide the required basis for process documentation and occasionally are also used for process analysis and improvement. The information density of these data is often low, and automatic condensing, analysis, and interpretation ("database mining") are highly desirable. In this article we present a methodology whereby process variables are processed to create a database of derivative process quantities representative of the global patterns, intermediate trends, and local characteristics of the process. A powerful search algorithm subsequently attempts to extract the specific process variables and their particular attributes that uniquely characterize a class of process outcomes such as high- or low-yield fermentations.The basic components of our pattern recognition methodology are described along with applications to the analysis of two sets of data from industrial fermentations. Results indicate that truly discriminating variables do exist in typical fermentation data and they can be useful in identifying the causes or symptoms of different process outcomes. The methodology has been implemented in a user-friendly software, named db-miner, which facilitates the application of the methodology for efficient and speedy analysis of fermentation process data. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 443-452, 1997.

Automatic bioprocess control. 4. A prototype batch of Saccharomyces cerevisiae.

The recent investigations in our high performance bioreactors have shown that living cells can be extremely sensitive to physical-chemical environmental conditions and their changes. Consequently, the relationship bioreactor-living cell must thoroughly be investigated in order to discuss both: whether bioreactor characteristics are limiting/dominating during cultivation and to what extent controlled changes of the cellular environment can lead the cells to a desired physiological state. For these investigations, a generally accepted biological test organism would be helpful, of which the requirements and reactions under certain conditions are well known. Saccharomyces cerevisiae is a well known, very robust but nevertheless sensitive organism, eligible for this purpose. In this article a typical batch cultivation on glucose is presented, collected from approx. 300 experiments. Regarding metabolite production and consumption, seven different phases are distinguished on the basis of approx. 20 sensor signals and their metabolic background is discussed. Prerequisite, however, was an exhaustive knowledge upon extracellular conditions, a task which could successfully be fulfilled with the highly automated equipment introduced in the preceding articles of this series.

Automatic bioprocess control. 5. Biologically and technically caused effects during cultivation.

Experimental programs are the basis for the development of new processes as well as for basic biological research. Hence, an unbiased approach is essential, otherwise the interpretation of results will be misleading. The complex chemical composition of cultivation media in combination with the impedded measuring under monoseptic conditions are ideal circumstances for misinterpretations and unsuited experimental approaches. In this article, practical examples for such pitfalls are given. They are undervalued in mass transfer and mixing effects, error propagation during RQ determination and possible influence of the medium preparation on the time evolution of the growth process. Further, the difficulty of sound interpretation is demonstrated by a batch cultivation carried out under sinusoidal changes of the stirrer speed. Summary conclusions close this series about equipment, methodology and benefits of bioprocess automation.

Biomass determination.

The reasons for and historical backgrounds of biomass determination are discussed under the aspects of theoretical and practical importance, usefulness and representativity. Off-line methods are evaluated and compared with on-line methods; constraints of applications and conclusiveness of results are rated. Special emphasis is given to the fact that mere knowledge of a bio-mass concentration is not sufficiently valuable to learn more about physiology nor to determine the effectiveness of a biotechnological process. A combination of several different alternative measuring principles in parallel as well as the exploitation of software sensors is proposed as a promising future solution.

On-line measurement in biotechnology: techniques.

Bioprocesses are generally ill controlled. This is due to the fact that the measurement of relevant variables is difficult. Therefore, fundamental knowledge of metabolic interrelations is, at least in vivo, limited. In this article, some of the most important measurement techniques are reviewed in order to provide an evaluation of their current state. Emphasis is given to the underlying principles and on-line capability which allow to judge their importance and potential for exploitation resulting in well (maybe entirely) controlled bioprocesses in the future.

On-line measurement in biotechnology: exploitation, objectives and benefits.

Sound data biologically relevant are prerequisites when developing high-performance bioprocesses. Understanding of physiological regulation as well as sophisticated control strategies are highly dependent on the observability of the culture, i.e. the generation and exploitation of suited signals even under complex environmental measurement conditions. Against this background, the increasing number of analytical systems is very supportive and, accordingly, an appropriate handling of sensors and measured data is of decisive importance. This article reports on practical experience with routines for maintenance, service and calibration of hardware sensors which improve the quality of measurements significantly. Verification and validation of signals is outlined in order to make the value of data exploitation tools obvious. A method for the characterization of information is introduced by practical examples of Saccharomyces cerevisiae cultures when explaining the specific properties of extracting biological information from raw data. Finally, examples for advantageous exploitation of on-line data are given.

Automatic bioprocess control. 2. Implementations and practical experiences.

Our improved implementation for bioprocess control allows flexible responses to many process needs. It is based on computer equipment consisting of three hierarchically ordered levels. On the lowest level, a DDC slave computer handles setpoints and simple tasks generating the chemical and physical environment for the cells. It can be designed manually by the user or automatically by the supervisory computer on the second level. This provides for raw data organization, analysis and interpretation either to support personnel on line in decision making, to select predefined control strategies, or even to search for others. In the coordinating computer on the third level, common tasks of different supervisory computers (bioprocesses) are shared, saving money for the equipment. Tasks and concepts as well as experimental experiences are described to outline the capabilities of the configuration.

Automatic bioprocess control. 1. A general concept.

Automation of bioprocesses is presented and discussed. A general concept is applied to laboratory scale reactors as well as to large scale production facilities consisting of many unit operations with a hierarchical and highly modular structure. The implementation of non-dedicated and intelligent analytical subsystems is foreseen. Hard- and software requirements are discussed in view of the functional requirements of both scientific research and production engineering. Some practical experience is reported using several different components in parallel installations.

[Health and disease in single homeless men: a secondary analysis of findings in a deaconess facility in the Federal German Republic]. / Gesundheit und Krankheit bei alleinstehenden wohnungslosen Männern: Eine Sekundäranalyse von Daten einer diakonischen Einrichtung in der Bundesrepublik Deutschland.

Only few empirical investigations on living conditions and health status of single homeless men have been conducted in Germany. The secondary analysis of a sample of 342 homeless men in a welfare hotel was conducted to describe the health status of this group and to gather informations for a possibly higher illness-risk in this group. For this purpose the medical documents and other socio-demographic data were evaluated at one point (one day in February 1985) along the ICD. A relatively high multi-morbidity for the homeless men, especially for the elder ones, could be stated. The results emphasize in etiological perspective the need to take a deeper insight into factors of workload before getting homeless and to strengthen socioepidemiological, socio-therapeutical and political efforts.

c-erbB-2 protein expression in node negative breast cancer.

We investigated the expression of c-erB-2 protein in two matched groups of breast cancer patients, one with and one without relapse. 37 patients with relapse were compared with 42 patients without recurrence for time of observation, adjuvant treatment, age, menopausal status and estrogen receptor content. Paraffin-embedded sections were stained with the polyclonal antibody 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein. The staining of c-erbB-2 was measured on a scale of 0 to 3+. C-erbB-2 staining was negative in 16 (38%) patients in the relapse-free group, and in 8 (22%) of the patients with metastases. Neither disease-free survival (DFS) nor overall survival (OS) were dependent upon the extent of c-erbB-2 expression. An analysis by estrogen receptor (ER) status (i.e. positive or negative) and by c-erbB-2 expression (i.e. positive or negative) revealed that patients with ER-positive primaries and negative c-erbB-2 have the longest disease-free survival (DFS) and overall survival (OS). We conclude that c-erbB-2 expression might be clinically useful only if other prognostic variables (e.g. estrogen receptor content in the tumor) are also considered.

Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading.

Fifty-one primary human breast tumors were analyzed for amplification of the c-erbB-2 protooncogene. Thirteen (25%) of the DNA samples contained multiple gene copies. Paraffin-embedded tumor sections, available from 47 of the cases, were stained with a c-erbB-2 specific antiserum. Eighty-three % (10 of 12) of the tumors containing amplified c-erbB-2 gene copies stained positively with the c-erbB-2 specific antiserum (P = 0.03). Thirteen tumors containing single copy c-erbB-2 sequences also stained positively with the antiserum. This suggests that mechanisms other than gene amplification may lead to elevated levels of c-erbB-2 protein. Finally, there was a statistically significant correlation between c-erbB-2 protein expression and parameters used in breast cancer prognosis. Positive staining was associated with positive nodal status of the patient (P = 0.02) and with tumors showing a poor nuclear grade (P = 0.02). This is the first study showing that a determination of the level of c-erbB-2 protein in paraffin-embedded tumor sections may have prognostic value for the course of human breast cancer.

Sensitive detection and typing of human papillomavirus DNA in gynecological cell scrapings by slot-blot hybridization.

A rapid and sensitive method for detecting and typing human papillomaviruses (HPVs) in cell scrapings is presented. DNA from scrapings is extracted and bound to nitrocellulose filters (Slot-Blot). By DNA-DNA hybridization with specific 32P-labelled HPV-probes (types 6/11 or 16/18) the patient's DNA is then analyzed for the presence of, and for the type of, HPV DNA sequences. A parallel hybridization with a human repetitive element (Alu sequence) allows quantitation of the different hybridization results. Experiments with HeLa cell DNA show that as little as 10(4) HPV sequences can be detected and typed specifically with this test. Evaluation of this test is completed within 6 to 7 days after cell collection. This Slot-Blot method was used to analyse 1330 specimens taken at the Bernese Dysplasia Outpatient Clinic. The results reveal a very high percentage (90%) of HPV-positive cases in the patient group examined.

[Intramural pregnancy with vague symptoms]. / Symptomarme intramurale Gravidität.

The clinical course of an intramural pregnancy in a 28-year-old nullipara is reported. Clinical and sonographic symptoms were not specific. The diagnosis was suspected on laparoscopy. At laparotomy, evidence of incipient rupture of the uterus was found, but no intraperitoneal hemorrhage. The gestational sac was removed without opening the uterine cavum, and the localization within the myometrium was confirmed histologically. Intramural pregnancy is a rare event whose pathogenesis is not clear. Surgical treatment with conservation of the uterus is possible in some cases.

[Human papillomavirus infections of the cervix uteri. I. Pathobiology, epidemiology and relation to cancer pathogenesis]. / Humane Papillomavirus-Infektionen der Cervix uteri. I. Pathobiologie, Epidemiologie und Beziehungen zur Krebspathogenese.

Infection of the uterine cervix by human papilloma viruses (HPV) is a ubiquitous yet only recently recognized lesion. The morphological findings correlate with early and late gene expression. The pathological events presumably depend upon the HPV type involved and upon environmental and host factors. The recognized risk factors are those described for epithelial dysplasias and carcinomas. The prevalence is unclear: it varies among different population groups and depends upon the investigation methods employed. The natural history of the infection is unknown, although relations between cervical HPV infection and carcinogenesis are evident. Research is handicapped by the lack of suitable animal or in vitro models.

[Human papillomavirus infections of the cervix uteri. II. Diagnosis, terminology, clinical significance of the diagnosis]. / Humane Papillomavirus-Infektionen der Cervix uteri. II. Diagnostik, Terminologie, klinische Bedeutung der Diagnose.

Cervical HPV infection may be diagnosed by colposcopy, cytology, histology and DNA hybridization. Each of these techniques alone may result in the detection of no more than 70% of the cases which are found by combining all methods. Typical cytological and histological findings are illustrated. A morphological continuum exists between HPV associated epithelial atypias (VAE), dysplasias and carcinomata in situ. The higher the grade of dysplasia, the lower the rate of cytological VAE. HPV types 16/18 are more frequently found in severe rather than in mild dysplasias. The use of hybridization techniques in mass screening programs appears premature, since the natural history of the infection is unknown. Microscopic grading of epithelial dysplasia remains the basis for patient care.