[Current and future effects of climate change on ophthalmology]. / Aktuelle und zukünftige Auswirkungen des Klimawandels auf die Augenheilkunde.

BACKGROUND AND OBJECTIVES: Climate change is also an increasingly important issue in the healthcare system. Due to its anatomical and physiological nature, the eye is directly exposed to environmental influences and changes in a special way. METHODS: The current literature is used to illustrate the effects of climate-induced changes and the respective influences on the eye. A PubMed search (cut-off date 3 October 2021) using the search terms "climate change" or "planetary health" or "global health" and in each case "ophthalmology" or "eye" or "ocular" was used to determine the development of the number of publications between 2011 and 2021. RESULTS: Measurable effects of climate change are already evident in a wide variety of ophthalmological fields. The significance of this topic, for instance, is reflected in a relatively constant increase in the number of publications and an almost tenfold increase in the number of publications per year from 2011 to 2021. CONCLUSION: The impact of climate change on eye diseases and on the field of ophthalmology is multifaceted and could be expected to intensify in the coming years. Therefore, the interrelationships need to be further investigated in future studies, preferably on a large scale.

Type 1 diabetes mellitus and exercise in competitive athletes.

AIMS: The number of patients with type 1 diabetes mellitus who are actively participating in competitive sports is increasing. Here, we aimed to assess individual experiences of competitive athletes with type 1 diabetes and to compare these experiences with current recommendations. METHODS: A survey of 20 competitive athletes with type 1 diabetes, categorized as endurance (n=10) and non-endurance (n=10) athletes, was performed. RESULTS: Endurance and non-endurance athletes did not differ in gender distribution, age, body mass index, and known diabetes duration. Self-reported target blood glucose values prior to exercise were lower in non-endurance than in endurance athletes (195±34 vs. 137±28 mg/dl, P=0.001). The majority of all athletes experienced activity-induced hypo- and hyperglycemic events, independently of exercise type. However, endurance athletes used additional carbohydrate units to prevent activity-induced hypoglycemic events more frequently without monitoring their blood glucose levels than non-endurance athletes (50% vs. 0%, P=0.01). The reduction of the insulin dose on training and competition days compared to days without exercise was similar for endurance and non-endurance athletes. CONCLUSION: These results point to a very individual adaption of the athlete's therapy during training and competition. However, there are distinct differences in diabetes management between endurance and non-endurance athletes.

Sudden death in an 8-week-old infant with Beckwith-Wiedemann syndrome.

The authors report a case of a 2-month-old girl diagnosed with Beckwith-Wiedemann syndrome (BWS) who was born prematurely and died suddenly in the hospital just before being discharged. BWS is a malformation syndrome associated with an increased risk of childhood tumors. The major features of BWS are macroglossia, abdominal wall defects, and visceromegaly, frequently leading to premature birth. Due to complex inheritance patterns, a predominance of nonfamilial cases, and the variability in expression of the features (termed incomplete penetrance), the risk of delayed diagnosis is evident. Secondary to hyperplastic pancreatic islands, hypoglycemia occurs frequently, and if not anticipated, adequate measures for prevention of hypoglycemic episodes may be delayed, resulting in possible intellectual deficits. The infant presented here died of natural causes: immaturity of the lungs resulting in marginal respiratory function and compounded by increased risk for asphyxia secondary to the enlarged tongue. The clinical history and findings in this infant are discussed in respect to the genetic syndrome with their relevance to medicolegal examination and the causes and manner of death.

Primary nodal gastrinomas.

BACKGROUND: The term primary lymph node gastrinoma was first used to describe a group of patients with gastrin-producing tumors present in lymph nodes located in a well-defined anatomic region. The patients had no known primary tumors in the pancreas or gastrointestinal tract and had disease-free survival for up to 18 years. The anatomic region in question has a triangular shape that extends from the cystic and common bile ducts to the second and third portion of the duodenum and the neck and body of the pancreas. The term gastrinoma triangle was coined to identify the area; in addition, it was postulated that lymph nodes located in the gastrinoma triangle normally contained neuroendocrine cells capable of secreting gastrin and other neuropeptides. From its inception, the postulate became the subject of controversy. DESIGN: To extend previous observations, we examined the lymph nodes located in the gastrinoma triangle of 20 autopsy cases for the presence of neuroendocrine cells, as determined by immunohistochemistry, using antibodies to a panneuroendocrine substance (eg, synaptophysin) and a specific neuropeptide (eg, gastrin). Scanning for positive cells was performed by 2 observers (M.E.H. and M.C.C.). We compared the findings in these lymph nodes with lymph nodes obtained from axillary and inguinal dissections during surgical procedures. RESULTS: In all, 417 lymph nodes were studied. Five of the 20 gastrinoma triangle cases contained synaptophysin reactive cells, whereas 3 had gastrin reactive cells. None of the axillary and inguinal lymph nodes contained neuroendocrine cells. CONCLUSION: Our findings support the hypothesis of entrapment of neuroendocrine cells during development and the presence of primary nodal gastrinomas.

Congenital sacrococcygeal teratomas: effect of gestational age on size, morphologic pattern, ploidy, p53, and ret expression.

Prognosis of infants born with sacrococcygeal teratomas (SCTs) correlates with gestational age (GA). The survival rate after 30 weeks of gestation is 75%, compared to 7% before 30 weeks of gestation. Studies correlating GA with size, morphologic composition of teratomas, ploidy or expression of cell cycle control proteins such as p53, and ret [a tyrosine kinase receptor of the GDNF (glial cell line-derived neurotrophic factors)] receptor family may provide information explaining differences in survival. Seven SCTs (GA 21 to 41 weeks), ranging in size from 5 to 15 cm, were evaluated for morphologic composition. DNA ploidy was assessed in mature and immature neural elements. Immunohistochemical reactivity with monoclonal antibodies recognizing p53, and ret was quantitated and correlated with morphological pattern and GA. Relative size of teratomas to infants' weight and content of immature neural tissues correlated inversely with advancement of GA. Yolk sac tumor (YST) and immature tissues showed aneuploid cell populations. Nuclear p53 reactivity was apparent in the teratoma with YST in the microcystic patterns, the neuroectodermal rosettes, and the glandular patterns. Ret reactivity was seen in osteoclasts adjacent to bone formation surrounding developing teeth in an immature teratoma, and in rare mature neural cells of one SCT of 35 weeks GA. The rapid growth of SCT (GA <30 weeks) correlates with increase in immature neural tissues. Our study confirms aneuploidy in YST and suggests aneuploid populations within immature tissues. p53 accumulates in a variety of patterns of YST and may be seen in immature components of SCTs. To understand the possible role of ret, further studies comparing ret expression in immature human tissues are needed.

Invasive cystic hypersecretory ductal carcinoma of breast: a case report and review of the literature.

Few individual cases of invasive cystic hypersecretory ductal carcinoma of the breast have been described. Review of 33 cases of cystic hypersecretory carcinoma, including the current case, indicate that only 6 cases presented with invasive disease. Two of these cases had positive nodes and 2 had distal metastases. The case presented here is unique in an additional aspect: the contralateral breast harbored lobular breast carcinoma 10 years after mastectomy of the first malignancy. Bilateral breast disease resulting in bilateral mastectomies over long-term follow-up, as in the case presented here, was reported in 3 of 33 cases.

Prospective study of the atopy preventive effect of maternal avoidance of milk and eggs during pregnancy and lactation.

UNLABELLED: The preventive effect of maternal avoidance of cow's milk and eggs on the development of atopic dermatitis and sensitization to food allergens was studied in a prospective trial with families at high risk for atopy, intervention included encouraging exclusive breast feeding for at least 3 months and delaying the controlled introduction of solid foods. In addition, one group received a maternal diet with the complete avoidance of milk and eggs in the last trimester of pregnancy and during the period of exclusive breast feeding, another group had the same diet starting after delivery, and mothers of the third group had no dietary restrictions. The period prevalences of atopic dermatitis as well as the rates of specific sensitization to eggs and milk at 6 and 12 months were not significantly different between groups. We were unable to demonstrate a significant preventive effect of maternal diet. CONCLUSION: While breast feeding should be promoted for children at risk for atopy, mothers can be encouraged to stay on normal diet during pregnancy and the breast feeding period.

Double minutes in the papillary thyroid cancer cell line PTC-1113A.

The cell line PTC-1113A was established from a metastasizing recurrent papillary thyroid cancer. The cell line was growing as monolayer and showed a complex karyotype with chromosome numbers ranging from 30 to 140/metaphase. A proportion of metaphases contained double minutes and/or pulverized chromosomes. Extrachromosomal DNA seemed to originate from a B-group chromosome. A chromosome 4 painting probe hybridized to extrachromosomal material, representing double minutes (dmin) and possibly minutes. In addition, fluorescence in situ hybridization (FISH) with the chromosome 4 library detected a translocation chromosome and a pulverized chromosome originating from chromosome 4. PTC-1113A is, to our knowledge, the single papillary thyroid cancer cell line demonstrating evidence of gene amplification.

Utilisation of amino acid mixtures in adolescents with phenylketonuria.

The nutritional regimen of patients with phenylketonuria (PKU) comprises a diet of natural proteins and phenylalanine (Phe)-free amino acid (AA) mixture. The main daily protein requirement is covered by a Phe-free AA mixture. In an adult with PKU, the consumption of the daily AA requirement in one single dose at breakfast caused nausea and vomiting. Therefore, four studies were designed to investigate the adverse and metabolic effects resulting from large intakes of AA mixtures used in the treatment of PKU patients with respect to the following: (1) biochemical effects following consumption of one single dose of Phe-free AA mixture in healthy persons; (2) transient metabolic changes caused by different individual regimens of AA intake in healthy persons and in one PKU patient; (3) nitrogen excretion in PKU patients taking the AA mixture in two or three portions; and (4) catabolic metabolism of AA in a PKU patient. In healthy subjects following the ingestion of the AA mixture in one bolus there was an increase in the blood levels of the given AA and also an increase in blood insulin concentration and a decrease in blood glucose concentration. These changes were less marked when the AA mixture was divided into three portions per day. In contrast, in a PKU patient following the ingestion of AA there was an increase in blood glucose. The urinary nitrogen excretion was greater in PKU patients when one compared to three portions of AA mixture was taken. The consumption of the daily requirement of AA mixture in one single does produced increased catabolism in a PKU patient. In conclusion it is recommended that the total daily amount of AA mixture should be divided into a minimum of three portions.

Proto-RET is rearranged in the new human papillary thyroid cancer cell line PTC-1113A.

The receptor tyrosine kinase proto-RET is believed to contribute to thyroid oncogenesis by activation of its tyrosine kinase either by point mutation or rearrangement. The papillary thyroid cancer cell lines PTC-1113A, L, and R were established from a recurrent thyroid cancer and its metastases. The rearrangement of the proto-ret oncogene in the cell line PTC-1113A is demonstrated by Southern analysis utilizing the probe for rearranged ret that encodes the fusion protein H4/tyrosine kinase. In contrast, rearranged ret alleles were not found in the cell lines that developed from metastases, nor in DNA isolated from the recurrent tumor. The cell line PTC-1113A may represent a population of tumor cells that gained a growth advantage due to rearranged ret. This is the second human thyroid cancer cell line harboring rearranged ret, and may serve to study the function of ret activation in thyroid cancers.

Cytogenetic analysis of thyroid tumors after cryopreservation.

Current cytogenetic evaluation of solid tumors is performed on fresh tissue specimens requiring on-call tissue culture facilities. The application of cryopreservation to tumor samples prior to cytogenetic analysis allows collection of tumors to a desired sample size. We evaluated methods of cryopreservation for their effects on growth potential from 11 benign thyroids and one papillary thyroid cancer. Mitotic indices and thyroglobulin expression applying imunocytology were analyzed. Compared to fresh tumors, the revived tumor samples showed unaltered thyroglobulin expression. A statistically significant (p < 0.004) prolongation to develop mitotic activity occurred in samples received after the freezing of dispase digested tissues, but not in samples frozen as thinly cut pieces. In addition, the data show that cytogenetic analysis at the 400-band level can be achieved in cryopreserved thyroid tissues.

Chromosomal aberrations in two adrenocortical tumors, one with a rearrangement at 11p15.

Adrenocortical tumors are detected with increasing frequency, but symptomatic cases with excessive hormone production are rare. We investigated cytogenetically one benign aldosterone-producing tumor (Conn Syndrome)(case 1) and one malignant cortisol-producing tumor (Cushing Syndrome)(case 2). Radioimmunoassay of cell culture supernatant of case 2 detected cortisol secretion during 2 months in culture. Flow cytometry of spill-out cells from case 2 showed a bimodal pattern (DNA Index 1.0, 1.4). Case 1 revealed a marker chromosome in 4/25 cells analyzed; the marker was a long acrocentric partially derived from chromosome 2,der(2q). In case 2, a cytogenetic harvest was achieved after prolonged culture time (6 weeks) and a marker chromosome, add(11)(p15), was detected in 16/22 cells. A breakpoint of 11p13, as well as loss of heterozygosity of alleles on 11p15, has been reported in the literature for other malignant adrenocortical cancers.

Dependence of the utilization of a phenylalanine-free amino acid mixture on different amounts of single dose ingested. A case report.

For patients with phenylketonuria the daily ingested phenylalanine-free amino acid mixture is the most important source of nitrogen. It is recommended to ingest one third of the total amount combined with main meals. Some patients, especially the older ones, do not follow this recommendation; they ingest the entire daily amount of amino acid mixture in one portion. This intake mode leads to an increased oxidative utilization of the amino acids. To set up an example for this metabolic phenomenon, a 13C-leucine breath test was performed in one female phenylketonuric patient. She ingested a third of her daily amount of the amino acid mixture combined with an oral tracer of 3 mg 13C-leucine/kg body weight at breakfast. The breath test was carried out by a standardized time schedule over 5 h. Three days later the breath test was repeated when she ingested the total amount of amino acid mixture in only one portion at breakfast. Total daily caloric intake and food composition were not changed. On both days a 24 h urine was collected to determine total nitrogen loss. The 13C-content of expired air was analysed by gas isotope ratio mass spectrometry, the total nitrogen content was determined using a combustion unit. The 13C-elimination rate as a percentage of the applied 13C-tracer was 9.5% on the first test day as compared to 19.6% on the 2nd day. The corresponding total nitrogen excretion was increased (4.3-6.9 g/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosomal aberrations in two sporadic gastrinomas.

Results of cell culture and cytogenetic analysis (standard and fluorescent in situ hybridization, FISH) of two sporadic gastrinomas are reported. Maintenance of hormonal activity was assessed by detection of gastrin levels during the first 3 months in culture. Case 1 showed clonal aberrations consisting of two marker chromosomes: marker 1 is a large metacentric chromosome and marker 2 is a small acrocentric chromosome. Case 2 showed a constitutional polymorphism with chromosome 15p+ and a clone in the tumor cell culture with trisomy for chromosome 3. To our knowledge, this is the first cytogenetic report of sporadic gastrinomas (Zollinger-Ellison syndrome).

Epithelial-mesenchymal transitions during cell culture of primary thyroid tumors?

Fibroblast contamination of epithelial tumor cell cultures is of great concern when examining tumor cells in vitro for specific biochemical and cytogenetic changes. The observations of normal karyotypes in thyroid tumor cell cultures have raised the concern of whether residual tissue fibroblasts might obscure the cytogenetic analysis of transformed epithelial cells. We have characterized early passaged thyroid tumor cells to examine the proportions of epithelial and fibroblastic cell types. Cells were analyzed by immunocytology using antibodies recognizing the thyroid prohormone thyroglobulin, epithelial cytokeratins, and vimentin, a mesenchyme marker. Tumors consisted of one follicular adenoma and five papillary carcinomas. When examined by day 15 in culture, all cells contained filaments composed of vimentin, which most likely represents an adaptation to culture conditions. Double immunofluorescence staining for thyroglobulin and cytokeratin revealed the presence of not only epithelial but also spindle-like fibroblastoid cells possessing thyroid epithelial cell markers. The results suggest that in thyroid tumor cultures there is a unique cell type intermediate between epithelial and mesenchyme phenotypes that must be considered when performing cytogenetic analysis.

Significance of trisomy 7 in thyroid tumors.

Standard cytogenetic studies of a multifocal metastasizing papillary thyroid carcinoma revealed two clonal chromosome aberrations: rearranged 10q and trisomy 7. Trisomy 7 seemed to be restricted to tumor nodule A, whereas era (10q) was detected in tumor nodule B and in a metastatic lymph node. We applied fluorescent in situ hybridization to ask whether trisomy 7 was a feature of the original tumor nodule or an in vitro phenomenon changing quantitatively during early passages and to see whether trisomy 7 was restricted to tumor nodule A. We used the biotinylated chromosome 7 alpha-satellite probe D7Z1 on freshly dropped slides from metaphase harvests from tumor nodule A,B, and the lymph node and on touch preparations from the frozen specimen of tumor nodule A. Trisomy 7 was present in the original tumor nodule (6% of cells), as well as in early passages (P1-3) from both tumor nodules and the metastatic lymph node with a frequency of 10.7-13.2%. The detection of trisomy 7 as a stable component in short-term cell culture and its presence in the original tumor material indicates that this common numerical aberration is an in vivo phenomenon.

Genetic markers in thyroid tumors.

Tissue from nine patients with malignant tumors and two with benign tumors was cultured briefly before cytogenetic analysis. The tumors included one goiter and one Hürthle cell adenoma, one lymphoma, one medullary carcinoma, two Hürthle cell cancers, and five papillary cancers, varying widely in clinical staging and histologic differentiation. When assessed, DNA content was aneuploid in two of six malignant tumors. Various culture conditions (oxygen levels, dissociation methods, and media) were evaluated; the end points were growth, cell differentiation, and time to first harvest. Clonal aberrations were detected in one of four successfully harvested papillary cancers: they consisted of trisomy 7 and a rearrangement of chromosome 10. The rea (10) seen in 22 of 27 cells involved bands q11-21. Two other papillary tumors and a medullary cancer (a family member with multiple endocrine neoplasia type IIA) showed tetraploidy and nonclonal numerically aberrant cells. A lymphoma and two benign lesions showed no cytogenetic abnormality. The tumor with rea (10) is of special interest because abnormalities of 10q have been reported repeatedly in thyroid tumors, including two cases of papillary thyroid tumors with a structural aberration similar to that of the presented case. This rearrangement could affect the ret-proto-oncogene, localized to 10q11.2 which is activated in some papillary thyroid carcinomas.

Cytogenetic study of a papillary thyroid carcinoma with a rearranged chromosome 10.

Cytogenetic findings of a multifocal papillary thyroid cancer and a metastatic lymph node from a 29-year-old white female patient are reported. Two clonal aberrations were observed: a trisomy 7 in one nodule, and a rearranged chromosome 10 in a separate nodule and in a lymph node. The rearrangement of 10q described here is similar to other published cases and is relevant for interpreting the molecular findings associated with thyroid cancer.