[Anatomy and physiology of the nasolacrimal ducts]. / Anatomie und Physiologie der ableitenden Tränenwege.

Ophthalmologists and interventional radiologists are not the only professionals for whom diseases of the efferent tear duct system occupy centre stage; this applies also to ENT specialists involving endonasal conservative or surgical treatment. On the basis of current knowledge and taking account of results yielded by own research in recent years and of clinical aspects, we here give an overview of basic knowledge on the anatomy and physiology of the nasolacrimal system. In doing so functional aspects regarding tear transport as well as embryological and pathophysiological issues are integrated.

[Avulsion of the Globe after Bicycle Accident--Clinical and Histopathological Evaluation]. / Avulsio bulbi nach Fahrradsturz - klinische und histopathologische Begutachtung.

BACKGROUND: Potential pathological mechanisms and complications of traumatic avulsio bulbi will be discussed based on the history, clinical, and histopathological findings of two patients. HISTORY AND SIGNS: Both patients were heavily affected by alcohol and had a bicycle accident with subsequent perforation of the upper eyelid by the handlebar-mounted hand brake levers. The accident resulted in disruption of the optic nerve and anterior displacement of the globe. THERAPY AND OUTCOME: In one patient, it was possible to reposition the globe into the orbit; however, the second patient's eye had to be enucleated. Functional testing demonstrated permanent loss of vision of the primary involved eyes, visual field defects, and visual impairment of one fellow eye. CONCLUSION: Avulsio bulbi describes a severe trauma to the eye often induced by sport and traffic accidents. Special attention should be addressed to the primary non-affected fellow eye with regard to potential functional defects.

Report of a new case with pentasomy X and novel clinical findings.

Pentasomy X is an extremely rare sex chromosome abnormality, a condition that only affects females, in which three more X chromosomes are added to the normally present two chromosomes in females. We investigated the novel clinical findings in a 1-year-old female baby with pentasomy X, and determined the parental origins of the X chromosomes. Our case had thenar atrophy, postnatal growth deficiency, developmental delay, mongoloid slant, microcephaly, ear anomalies, micrognathia and congenital heart disease. A conventional cytogenetic technique was applied for the diagnosis of the polysomy X, and quantitative fluorescent polymerase chain reaction (QF-PCR) using 11 inherited short tandem repeat (STR) alleles specific to the chromosome X for the determination of parental origin of X chromosomes. A cytogenetic evaluation revealed that the karyotype of the infant was 49,XXXXX. Comparison of the infant's features with previously reported cases indicated a clinically recognizable specific pattern of malformations referred to as the pentasomy X syndrome. However, to the best of our know-ledge, this is the first report of thenar atrophy in a patient with 49,XXXXX. The molecular analysis suggested that four X chromosomes of the infant originated from the mother as a result of the non disjunction events in meiosis I and meiosis II. We here state that the clinical manifestations seen in our case were consistent with those described previously in patients with pentasomy X. The degree of early hypotonia constitutes an important early prognostic feature in this syndrome. The pathogenesis of pentasomy X is not clear at present, but it is thought to be caused by successive maternal non disjunctions.

[Updated incidence of dry eye syndrome in Germany]. / Aktuelle Inzidenz des Trockenen Auges in Deutschland.

BACKGROUND: Dry eye is one of the most common eye surface disorders. Patients suffer in particular from annoying subjective symptoms that compromise quality of life. The aim of the study was to find out when patients consult ophthalmologists in Germany and what symptoms they present. PATIENTS/MATERIAL AND METHODS: 170 patients treated at ophthalmological practices in Bavaria, Saxony and Saxony-Anhalt with dry eye were surveyed regarding their symptoms. RESULTS: The majority of those questioned were 40 years of age or older (88 %) (average: 60), female (59 %) and described a variety of subjective symptoms (65 %). More than five different concurrent symptoms were named. There is a recognisable increase in cases - by more than 3.5 times - at the age of forty (in women) and fifty (in men). CONCLUSIONS: We hope to contribute with the data obtained to a more complete understanding of this highly complex pathological process. A further aim is to facilitate recognition of this mostly chronic condition in its early stages when the symptoms are still poorly defined. The data on the German population obtained here should become part of a comparative analysis within the international context. Despite considerable scientific effort, dry eye remains a difficult challenge for both patients and attending physicians.

RAGE influences obesity in mice. Effects of the presence of RAGE on weight gain, AGE accumulation, and insulin levels in mice on a high fat diet.

BACKGROUND: The metabolic syndrome is defined by the presence of obesity, insulin resistance, dyslipidemia, and hypertension. Advanced glycation end products (AGEs) are stable end products of the Maillard reaction, whereby AGE accumulation is considered not only a biomarker of aging but is also associated with several degenerative diseases. AGEs are recognized by several receptor molecules of which the receptor of AGEs (RAGE) is currently the most intensively studied receptor. Activation of RAGE causes an unfavorable proinflammatory state and deletion of RAGE in diabetic animals has been reported to protect against atherosclerosis. AGEs and a high fat diet are associated with cardiovascular diseases, whereas is still not clear whether a direct link between high fat nutrition and AGEs exists in vivo. MATERIALS AND METHODS: C57BL/6 and C57BL/6 RAGE -/- mice were fed a high fat diet to induce obesity. Weight, insulin, lipid levels, AGE modifications, and cardiac gene expression were analyzed. RESULTS: The absence of RAGE resulted in accelerated weight gain, increased plasma cholesterol, and higher insulin levels in obese mice. The hearts of normal and obese RAGE -/- mice contained lower levels of the AGE arginine-pyrimidine and 3DG-imidazolone than RAGE + / + animals. RAGE -/- mice also exhibited lower expression of the genes encoding the antioxidative enzymes MnSOD, Cu/ZnSOD, and ceruloplasmin in cardiac tissue, whereas the AGE receptors AGER-1, -2, and -3 were equally expressed in both genotypes. Obese mice of both strains expressed increased amounts of AGER-2. Only obese RAGE + / + mice exhibited a reduced mRNA accumulation of Cu/Zn SOD. CONCLUSION: These data suggest that RAGE is involved in the development of obesity and insulin resistance.

Rapid detection of fetal aneuploidies by quantitative fluorescent-polymerase chain reaction for prenatal diagnosis in the Turkish population.

Prenatal diagnosis is testing for diseases or conditions in a fetus or embryo before it is born. It employs a variety of techniques to determine the health and condition of an unborn fetus. The main goal of this process is to perform prenatal diagnosis at the earliest possible stage of gestation. In this regard, quantitative fluorescent-polymerase chain reaction (QF-PCR), a novel technique that is fast and reliable, was employed to detect aneuploidies (13, 18, 21, X and Y) without the need of the time-consuming culturing process. The QF-PCR method can detect five different chromosome aneuploidies with 98.6% accuracy. In this study, 1874 amniotic fluid samples of pregnant subjects, who were referred to the Department of Medical Biology and Genetics, Adana, Turkey (molecular biology section), were analyzed with the QF-PCR technique by employing 27 short tandem repeat (STR) markers to detect chromosomes 13, 18, 21, X and Y aneuploidies. We detected 31 subjects (1.7%) with aneuploidies or euploidies out of the 1874 subjects. The average age of the pregnant subjects was 32 (range: 14-49). Abnormal karyotypes detected were as follows: 47,XX,+21 (19.4%, 6/31), 47,XY,+21 (48.4%, 15/31), 48,XXX,+21 (3.2%, 1/31), 69,XXX (3.2%, 1/31), 47,XY,+13 (3.2%, 1/31), 47,XXY (9.6%, 3/31), 47,XXX (9.6%, 3/31) and 45,X (3.2%, 1/31). Moreover, some STR markers were found to be more specific to the Turkish population. In conclusion, QF-PCR can be regarded as an alternative method of conventional cytogenetic analysis as it is a rapid and reliable method; however, in most cases it is required to be supported or validated with conventional cytogenetic karyotyping and some STR markers employed for QF-PCR can be more informative for a given population.

Association of serum sex steroid levels and bone mineral density with CYP17 and CYP19 gene polymorphisms in postmenopausal women in Turkey.

Many clinical conditions, including osteoporosis, are associated with serum levels of sex steroids. Enzymes that regulate rate-limiting steps of steroidogenic pathways, such as CYP17 and CYP19, are also regarded as significant factors that may cause the development of these conditions. We investigated the association of two common polymorphisms, in the promoter region (T→C substitution) of CYP17 and exon 3 (G→A) of CYP19, with bone mineral density (BMD) in the lumbar spine and femoral neck and serum androgen/estradiol, in a case-control study of 172 postmenopausal women aged 62.3 ± 9.6 years (mean ± SD). The CYP17 TC genotype was significantly overrepresented in patients compared to controls, and TC genotype neck T-score and lumbar T-score values were significantly higher in patients compared to controls. CYP17 TC and TT genotype testosterone and DHEA-SO(4) levels were lower in patients compared to controls. All three genotypes of CYP19 had almost the same distribution among patients. The CYP19 AG genotype, however, was most frequent among controls. CYP19 lumbar BMD levels were close to each other among the different genotypes; however, AA and AG genotypes were significantly lower in patients. Testosterone and DHEA-SO(4) levels in the CYP19 GG genotype were higher compared to those of the other genotypes in patients but not in controls. CYP19 GA individuals had lower E(2) levels and lower BMD in controls and patients. Femoral neck BMD and lumbar T-score were also diminished with GA transition. In conclusion, CYP17 and CYP19 gene polymorphisms were found to be associated with osteoporosis in postmenopausal women in Turkey.

Retinal astrocytomas: long-term follow-up.

BACKGROUND: Retinal astrocytomas are exceedingly rare benign tumours of the retina. Their occurrence can be solitary or multiple, uni- or bilateral, isolated or in association with a phakomatosis such as tuberous sclerosis or neurofibromatosis type 1. PATIENTS AND METHODS: We report the long-term follow-up in three patients with retinal astrocytomas. RESULTS: Over many years of follow-up all astrocytomas showed very little progression and no deterioration of visual function. Subtle changes occurred inside the lesions. CONCLUSIONS: Even after long-term follow-up the natural course of retinal astrocytic hamartomas seems to be favourable, with visual loss and significant growth being unlikely to occur. A thorough ophthalmological and general evaluation, in order to rule out an underlying systemic disease and to document the ocular status, are needed initially. Thereafter eye examinations can be scheduled in long intervals.

Trefoil factor family peptide 3 at the ocular surface. A promising therapeutic candidate for patients with dry eye syndrome?

Dry eye syndrome is a widespread disease accompanied by discomfort and potential visual impairments. Basic causes are tear film instability, hyperosmolarity of the tear film, increased apoptosis as well as chronic inflammatory processes. During the last decades, our understanding of dry eye syndrome has considerably increased. However, the molecular mechanisms of the disease remain largely elusive. In this context, our group focuses on trefoil factor 3 (TFF3). Among other factors, TFF3 performs a broad variety of protective functions on surface epithelium. Its main function seems to be in enhancing wound healing by promoting a process called 'restitution'. Studies evaluating TFF3 properties and effects at the ocular surface using in vivo as well as in vitro models have revealed a pivotal role of TFF3 in corneal wound healing. Subsequent studies in osteoarthritic cartilage seem to draw a different picture of TFF3, which still needs further elucidation. This manuscript summarizes the findings concerning TFF3 in general and its role in the cornea as well as articular cartilage - two tissues which have some things in common. It also discusses the potential of TFF3 as a candidate therapeutic agent for the treatment of, for example, ocular surface disorders.

Loss of classical transient receptor potential 6 channel reduces allergic airway response.

BACKGROUND: Non-selective cation influx through canonical transient receptor potential channels (TRPCs) is thought to be an important event leading to airway inflammation. TRPC6 is highly expressed in the lung, but its role in allergic processes is still poorly understood. OBJECTIVE: The purpose of this study was to evaluate the role of TRPC6 in airway hyperresponsiveness (AHR) and allergic inflammation of the lung. METHODS: Methacholine-induced AHR was assessed by head-out body plethysmography of wild type (WT) and TRPC6(-/-) mice. Experimental airway inflammation was induced by intraperitoneal ovalbumin (OVA) sensitization, followed by OVA aerosol challenges. Allergic inflammation and mucus production were analysed 24 h after the last allergen challenge. RESULTS: Methacholine-induced AHR and agonist-induced contractility of tracheal rings were increased in TRPC6(-/-) mice compared with WT mice, most probably due to compensatory up-regulation of TRPC3 in airway smooth muscle cells. Most interestingly, when compared with WT mice, TRPC6(-/-) mice exhibited reduced allergic responses after allergen challenge as evidenced by a decrease in airway eosinophilia and blood IgE levels, as well as decreased levels of T-helper type 2 (Th2) cytokines (IL-5, IL-13) in the bronchoalveolar lavage. However, lung mucus production after allergen challenge was not altered by TRPC6 deficiency. CONCLUSIONS: TRPC6 deficiency inhibits specific allergic immune responses, pointing to an important immunological function of this cation channel in Th2 cells, eosinophils, mast cells and B cells.

Distribution of sex chromosomes in dysgenetic gonads of mixed type.

In a four-week-old child with female external and internal genitalia but with clitoris hypertrophy chromosome analysis from blood lymphocytes revealed a 46,XY karyotype. No deletion of Y chromosomal sequences was detected by PCR analysis of genomic DNA isolated from peripheral blood leucocytes. Because of the increased risk for gonadal tumours, gonadectomy was performed. Conventional cytogenetic analysis of the left dysgenetic gonad revealed a gonosomal mosaicism with a 45,X cell line in 27 of 50 metaphases. The dysgenetic left gonad demonstrated a significantly higher proportion (P = 0.005) of cells carrying a Y chromosome (46.3%) than the streak gonad from the right side (33.9%). Histomorphological examination of the left gonad revealed immature testicular tissue and rete-like structures as well as irregular ovarian type areas with cystic follicular structures. Interphase FISH analysis of the different tissues of this dysgenetic gonad demonstrated variable proportions of cells with an X and a Y chromosome. Whereas Sertoli cells and rete-like structures revealed a significantly higher proportion of XY cells in relation to the whole section of the dysgenetic gonad (P < 0.0001), almost all granulose-like cells carried no Y chromosome. The proportion of XY/X cells in theca-like cells and Leydig cells was similar to that of the whole dysgenetic gonad. In contrast to these findings, spermatogonia exclusively contained an XY constellation.

Carcinoembryonic antigen-related cell-cell adhesion molecule C-CAM is greatly increased in serum and urine of rats with liver diseases.

C-CAM (rat cell CAM/human CD66a) is ubiquitous and multifunctional. It is involved in intercellular adhesion, signal transduction and cell growth inhibition. Structurally, it is related to the carcinoembryonic antigen. In the present study serum, bile and urine of rats with liver diseases were analyzed for the presence of cell CAM. After bile duct ligation and during galactosamine (GalN) hepatitis we found that large amounts of liver membrane-bound C-CAM are secreted or shed into blood. The serum level of another liver membrane-bound protein, LI-cadherin, is not increased. It was shown that C-CAM is also present in bile fluid, and for the first time that C-CAM is present in the urine of rats with liver diseases. A particularly high concentration was measured in the urine of rats suffering from GalN hepatitis.

Human renal cell carcinogenesis is accompanied by a coordinate loss of the tissue specific transcription factors HNF4 alpha and HNF1 alpha.

Human renal cell carcinogenesis is usually accompanied by dedifferentiation processes including the loss of expression of tissue specifically expressed genes. Based on the hypothesis that these dedifferentiation processes might be attributed to a functional change in tissue specific transcription factors, we have analyzed the expression and function of the tissue specific transcription factor HNF4 alpha in human renal cell carcinomas. By Western blot analysis and gel retardation assay using HNF4 alpha specific antibodies, we observed that in most cases the amount as well as the binding activity of HNF4 is reduced in the tumor samples compared to the corresponding normal tissues. Furthermore, we found a clear correlation between the HNF4 alpha binding activity and the amount of another transcription factor (HNF1 alpha), which is thought to be transcriptionally activated by HNF4 alpha. We therefore speculate that disruption of the HNF4 alpha/HNF1 alpha pathway of kidney specific gene expression might be an important molecular mechanism in renal cell carcinogenesis.

The adjunctive value of routine biochemistry in nutritional assessment of hospitalized patients.

Nutritional screening and assessment of patients are not part of the routine procedures at hospital admission, although a large percentage of patients is malnourished. Similarly, nutritional status of patients and dietary intake is usually not monitored during hospitalization. In contrast a great number of laboratory investigations for screening purposes accompanies most, if not all, hospital admissions. Several of those routine markers carry important nutritional information and could convey several aspects of patients' nutritional requirements. This review proposes that laboratories in particular could provide a service for the nutritional interpretation of available routine data which would help clinicians to focus on nutrition related problems. The nutritional meaning of basic physical characteristics (age, sex, height, and weight), urinary excretion of ketone bodies, urea and creatinine, and serum concentrations of urea, phosphate, iron and albumin are discussed in detail and the assessment of protein malnutrition, metabolism, and requirements is emphasized. Finally, a proposed sample layout for the nutritional interpretation of routinely available biochemical and basic physical data is presented.

Tumour microdissemination and survival in metastatic melanoma.

The value of tyrosinase messenger RNA (mRNA) detection by reverse-transcriptase polymerase chain reaction (RT-PCR) as a marker for circulating melanoma cells remains controversial. However, it has been suggested that detection of melanoma cell mRNA may be used to evaluate prognosis and disease progression in patients with advanced malignant melanoma. We used a highly sensitive tyrosinase RT-PCR detection assay to test peripheral blood specimens of 80 patients with metastatic malignant melanoma. Moreover, we developed a multiple marker RT-PCR assay detecting a variety of additional melanocyte/tumour specific markers addressing the potential heterogeneity of gene expression of circulating melanoma cells. Thus subgroups of 32 and 12 out of all the 80 patients were also analysed for multimarker gene expression in their peripheral blood and bone marrow specimens, respectively. Altogether, 15 out of 80 patients tested positive for one or more molecular markers with heterogeneous melanocyte/tumour gene expression patterns. All RT-PCR positive patients presented with progressive and widely disseminated disease. We concluded that the detection of melanoma cell mRNA occurs in a stage of massive tumour progression and may predict poor clinical outcome in advanced malignant melanoma patients (p < 0.001). In addition, the multiple marker RT-PCR analysis was more reliable and sensitive than a single molecular marker assay for the detection of melanoma cells.

[Chemoimmunotherapy in the systemic treatment of advanced renal carcinoma]. / Chemoimmuntherapie des fortgeschrittenen Nierenzellkarzinoms.

Polychemotherapy and immunomodulating treatment using IL-2 and/or IFN-alpha produce objective responses in a proportion of advanced renal cell carcinoma patients. The goals of an improved cost effectiveness and therapeutic index of interleukin-2 and/or Interferon-alpha in combination with chemotherapeutic agents require the design of risk factor adapted individual therapeutic strategies for the outpatient setting. High dose i. v. IL-2 therapy in metastatic renal cell carcinoma has been proven effective [11]. Other modalities of applying IL-2 have been described [12-14] (Table 1). A cumulative risk-score identified three risk-groups with significant differences in median survival [16]. The SC use of IL-2 and INF-alpha has been established in the treatment of RCC [16, 23]. It appears that combination chemoimmunotherapy including p. o. retinoic acid is far more effective than single agent treatment. Further studies will have to be designed to improve therapeutic index and cost effectiveness in systemic combination therapy in metastatic RCC.

[In vitro and in vivo investigations of a modified textile keratoprosthesis. ACTO TexKPRO]. / In-vitro- und In-vivo-Untersuchung einer modifizierten textilen Keratoprothese. ACTO TexKPRO.

BACKGROUND: Clinical application of a keratoprosthesis (KPRO) is still a challenging task. Recent developments reflect the concepts of nut and bolt, intrastromal implantation or an osteoodontokeratoprosthesis (OOKP). A new concept of a textile KPRO has been evaluated in a limited human study with considerable difficulties which after termination of the study and considerable improvements was restarted using animal experiments. MATERIALS: The ACTO TexKPRO is made from polyvinylidene difluoride (PVDF) fibers and transparent silicone. The first and second developmental stages differed in density and size of fibers and furthermore in surface modifications of the fibers and optics which were improved for the second prototype. METHODS: Implantation of the prosthesis was performed in four patients with corneal blindness and in two cases retinal disease which required surgery. In the later animal experiments surgery was performed on three rabbits. Surgery was performed by redressing the conjunctiva, opening of the eyeball with a central 6.5 mm trephination, removal of the lens and iris and implantation and suturing of the TexKPRO. If required a silicone oil endotamponade was placed. RESULTS: All eyes were stable with the keratoprosthesis. The first prototype showed conjunctival recession on the textile haptics with highly susceptible endopthalmitis risk due to infection of the PVDF so that we decided to remove the prosthesis from all eyes after one case of severe endophthalmitis occurred. The longest time of placement was 40 months and the shortest time 6 months. All eyes were restored by keratoplasty. In animals with the new haptic we found better conjunctivalization and stable implantation of the KPRO. DISCUSSION: The textile KPRO provides a stable implantation procedure and safe connection of fibers to the scleral wound bed. The optical and mechanical implantation is safe and stable. Surface epithelialization is improved with the new surface modifications and different PVDF fiber density but beforel new implantations are planned further conceptual changes will be introduced.

[Trauma of periorbital soft tissue. Reconstruction with regard to functional and aesthetic aspects]. / Trauma der periorbitalen Weichteile. Rekonstruktion unter funktionellen und ästhetischen Gesichtspunkten.

Complex midfacial trauma requires interdisciplinary management. A wide range of reconstructive procedures are needed and if necessary secondary and even tertiary interventions should be performed at the appropriate time. We present the case of a 45-year-old man who was involved in a car accident and presented with severe injuries to the periorbital soft tissue. The focus was on the reconstruction of this sensitive region with regard to functional and aesthetic aspects. In view of the severity of the injuries the final clinical status is considered to be very important. Special issues and pitfalls in the reconstruction of trauma cases and potential management are discussed.