Albrecht Von Graefe's Ophthalmic Educational Visit to William Wilde in Dublin in 1851.

Aim There were little information in literature about Albrecht von Graefe's ophthalmological education in Ireland, which was in summer 1851. The aim of this work is to illustrate his stay with Sir William Wilde in Dublin. A brief review of the two giants of ophthalmology also was given. Methods Historical search of the data, and the biography of the corresponding ophthalmologists were recorded and analysed. Institutes for history of medicine as well as medicohistorians also were contacted. Results Graefe visited Sir William Wilde at the end of his 3-years European ophthalmic educational travels. He learned from him about treatment and examinations of the eye and the skills of various ophthalmic operations, and organization of work in his eye hospital. After that he founded the famous private Eye Clinic in Berlin, and became one of the greatest ophthalmologists of the 19th century. Conclusion Graefe's talent, hard work, high quality of education and later continuous contacts with his teachers contributed to modernization and internationalization of ophthalmology.

Microsatellite variation of ESR1, ESR2, and AR in Serbian women with primary ovarian insufficiency.

OBJECTIVE: This study aimed to investigate the potential role of microsatellite polymorphisms of the estrogen receptor alpha gene (ESR1) TA repeat, estrogen receptor beta gene (ESR2) CA repeat, and androgen receptor gene (AR) CAG and GGN repeats among Serbian women with primary ovarian insufficiency (POI). These microsatellites have been reported to be associated with POI in different racial/ethnic populations. METHODS: A cohort of 196 POI cases matched with 544 fertile controls was recruited by the Institute for Endocrinology, Diabetes and Metabolic Disorders of Serbia between 2007 and 2010. DNA was extracted from saliva. The four microsatellites were genotyped using a PCR-based assay to determine the repeat lengths. RESULTS: POI patients carried shorter repeat lengths of ESR2 (CA)n than controls (P = 0.034), but the difference was small. ESR1 (TA)n was on the borderline of statistical differences between groups (P = 0.059). AR (CAG)n and (GGN)n showed no association with POI. CONCLUSIONS: We cautiously conclude that microsatellite polymorphisms of gonadal steroid receptor genes might contribute to the genetic basis of POI in Serbian women, but a larger-scale study and family-based studies are warranted to validate our findings even though the sample size in this study is larger than any previously published in this field.

Acute responses to structured aerobic and resistance exercise in women with gestational diabetes mellitus.

Research on the acute responses to exercise in pregnancy is scarce, especially for women affected by gestational diabetes mellitus (GDM). The aim of this study was to investigate responses to a single bout of exercise performed multiple times throughout the pregnancy in women diagnosed with GDM. Data from 18 pregnant women (aged: 32.8 ± 3.8) diagnosed with GDM, treated with diet only, were analyzed. Participants' pre-pregnancy body mass index was 24.4 ± 4.9 kg/m2 , 50% of them were nulliparous, and 50% of the sample regularly exercised before the pregnancy. The exercise intervention consisted of an individual structured aerobic and resistance exercise program performed twice per week from the time of diagnosis until at least the 36th week of pregnancy. The exercise program included 20 minutes of aerobic exercise, 20-25 minutes of resistance exercise, and 10 minutes of cool down. Maternal heart rate, systolic and diastolic blood pressure, temperature and fetal heart rate were measured at every exercise session, along with blood glucose on 3 occasions. In total, 365 exercise sessions were analyzed (85 in the second trimester and 280 in the third trimester), on average 20.3 ± 7.7 per participant. Heart rate and fetal heart rate were elevated during both the aerobic and resistance parts of the exercise session (P < .01) in comparison with the baseline while systolic and diastolic blood pressure did not change in the total sample. There was a slight elevation in tympanic membrane temperature during the aerobic part of the session (P < .01). All parameters returned to baseline levels by the end of the session. Glucose levels dropped from the baseline, from 4.7 ± 0.6 to 3.9 ± 0.4 mmol/L (P < .01). There were no differences in responses to exercise between the second and third trimesters, nor between pre-pregnancy exercisers and non-exercisers. The combination of aerobic and resistance exercise for women diagnosed with GDM does not have harmful short-term effects if performed according to guidelines. Likewise, exercise can be considered useful for controlling hyperglycemia in pregnancy for women affected by GDM.

[OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS OF DIABETIC MACULAR OEDEMA].

The aim of this study was to measure macular thickness of diabetes mellitus type 2 patients with nonproliferative diabetic retinopathy and clinically significant macular edema based on optical coherence tomography (OCT) findings and to show morphological characteristics of diabetic macular edema. A prospective study was carried out at the Department of Ophthalmology, Split University Hospital Center. It included 40 patients aged 40-83, all with type 2 diabetes mellitus. Macular area was assessed by OCT, with measurement of central subfield thickness, cube volume and cube average thickness. The mean central subfield thickness was 509.1 µm, mean cube volume 13.1 mm(3) and mean cube thickness 365.1 µm. Diabetic macular edema is classified as diffuse, focal, cystoid, and associated with serous macular detachment and macular traction. Diffuse diabetic macular edema was most common, present in 22 (55%) patients, followed by focal macular edema in 8 (20%), cystoid in 4 (10%), associated with macular traction in 4 (10%) and morphological serous macular detachment as the least common in 2 (5%) patients. OCT is the gold standard for the diagnosis of diabetic macular edema. It is an important diagnostic method for high resolution imaging of anatomical structures of the macula and vitreoretinal surface.

PROF. DR CARL FERDINAND RITTER VON ARLT (1812-1887): HIS LIFE AND WORK DURING HIS OPHTHALMOLOGICAL CAREER IN PRAGUE.

The aim of this paper is to provide an overview of the life and work in Prague of the famous ophthalmologist Carl Ferdinand Ritter von Arlt (1812‒1887). The paper presents data on his stay in Prague while studying Medicine and working as a private physician and ophthalmologist. Professor von Arlt was Head of the Chair of Ophthalmology at Charles University. He was Director of the Eye Clinic at Prague General Hospital from 1849 to 1856. A detailed description is given of his residences and their appearance today. Very little has been written about this aspect, so the paper will be a supplement to his impressive biography. A brief, chronological, systematic and concise biography is also provided, including details of his family and his contributions to Ophthalmology. During his 25-year stay in Prague (1831-1856), he commuted between the city centre and the General Hospital where he worked. He changed the location of his residence five times. It is important to note and not to forget where one of the greatest ophthalmologists of the 19th century worked and resided in Prague.

Essential role for Stat5 in the neurotrophic but not in the neuroprotective effect of erythropoietin.

The transcription factors signal transducer and activator of transcription 5a and 5b (Stat5) are activated by the neuroprotective and neurotrophic cytokines, erythropoietin (EPO) and growth hormone (GH). Here, we show a dissociation of the intracellular pathway mediating the protective effect of EPO against glutamate toxicity from that needed for its neurotrophic activity using hippocampal neuronal cultures from Stat5a/b-knockout (Stat5(-/-)) mouse fetuses. Both pretreatment and post-treatment with EPO counteracted glutamate-induced cell death in Stat5(+/+) and Stat5(-/-) neurons. Acute pharmacological inhibition of Janus kinase 2 (JAK2)/Stat signalling had no effect on EPO neuroprotection, whereas inhibition of phosphatidylinositol-3' kinase (PI3K)/Akt pathway abolished the protective effect of EPO in both Stat5(+/+) and Stat5(-/-) neurons. GH effectively protected Stat5(+/+) cells against glutamate toxicity but had no effect in Stat5(-/-) neurons or in Stat5(+/+) neurons treated with JAK2/Stat or PI3K inhibitor. EPO and GH stimulated neurite outgrowth and branching of Stat5(+/+) neurons by activating PI3K/Akt signalling but had no trophic effect in Stat5(-/-) cells. We conclude that in hippocampal neurons, Stat5 is not required for neuroprotection by EPO but is together with Akt essential for its neurotrophic activity. Both Stat5 and Akt are needed for neuroprotective and neurotrophic signalling of GH in neurons.

Platelet-rich plasma (PRP) for the treatment of vulvar lichen sclerosus in a premenopausal woman: A case report.

The use of platelet-rich plasma (PRP) for the treatment of lichen sclerosus (LS) in a 38-year-old premenopausal woman is reported. The diagnosis was confirmed histologically and the symptoms documented using the ICIQ Vaginal Symptoms Questionnaire (ICIQ-VS) and the Female Sexual Function Index (FSFI) questionnaire. PRP was prepared from autologous blood using the Regen Cellular Matrix Kit. PRP was administered twice over two months. Histology at follow-up one month after the second administration showed the epidermis was nearly normal and upper dermal cellularity had been restored. The patient was symptom-free and both her ICIQ-VS and her FSFI scores had improved significantly. PRP is a potential new treatment option for LS which needs further assessment in randomized controlled trials.

Effect of eicosapentaenoic acid and docosahexaenoic acid supplementation on C-peptide preservation in pregnant women with type-1 diabetes: randomized placebo controlled clinical trial.

BACKGROUND/OBJECTIVES: Type-1 diabetes mellitus (T1DM) is caused by autoimmune insulitis. There are evidences that pregnancy and n-3 fatty acids exhibit suppressive effect on human inflammatory system. SUBJECTS/METHODS: Ninety pregnant women with T1DM were included in the prospective randomized placebo controlled clinical trial. Forty-seven of them were put on standard diabetic diet enriched with EPA and DHA twice a day (EPA 120 mg and DHA 616 mg; Study group) and 43 pregnant diabetic women were on standard diabetic diet with placebo (Control group). Duration of T1DM in all participants was between 5 to 30 years. Blood samples were analyzed from all pregnant women for fasting C-peptide (FC-peptide), fasting plasma glucose (FPG) and HbA1c in each trimester throughout pregnancy and after delivery. Umbilical vein blood was analyzed for fetal C-peptide level, glucose concentration and insulin resistance. RESULTS: In the Study group FC-peptide concentration raised from 59.6±103.9 pmol/l in first trimester, to 67.7±101.3 pmol/l in the second trimester and to 95.1±152.7 pmol/l in the third trimester. Comparing the FC-peptide values during first and third trimester a statistically significant increase in third trimester was found (P<0.001). In the Control group FC-peptide concentration ranged from 41.7±91.6 pmol/l in the first trimester to 41.2±70.9 mmol/l in the second trimester while in the third trimester it reached 52.4±95.3 pmol/l. Comparing the FC-peptide values during first and third trimester the statistical difference was not significant. CONCLUSION: Combining of LC n-3 PUFAs and pregnancy yields immunological tolerance and stimulates the production of endogenous insulin in women with T1DM.

Epidural anesthesia from an obstetrics point of view.

With the acceptance of new ideas in medicine and modernization of life styles, it is necessary to conduct delivery as a beautiful act of giving life with the least amount of pain possible using epidural anesthesia. Thus, not only is the physical aspect of delivery improved but also benefits from anesthesia are seen in obstetrics. To conduct epidural anesthesia successfully during delivery, certain conditions are necessary regarding the fetus and mother. Such conditions include an adequate Bishop score, fetal head presentation, the presence of amnion, adequate term of delivery and Doppler flows that do not compromise vaginal delivery. Primiparas in term pregnancies without pathological conditions related to mother or fetus were examined. The duration of delivery was observed in a group of primiparas that did not receive epidural anesthesia (group A) and a group of primiparas that received epidural anesthesia (group B). The study lasted one year.

Molecular detection of human papillomavirus in women with minor-grade cervical cytology abnormalities.

BACKGROUND: Human papillomavirus (HPV) has been shown to be the major risk factor for the development of cervical carcinoma, the second most common cancer among women worldwide. Cervical cytology has been the main screening tool for detection of premalignant lesions in last 50 years. OBJECTIVE: The utility of a molecular assay for detection of HPV in cervical smears was evaluated. STUDY DESIGN: A total of 466 women with minor-grade cervical cytology abnormality supposed to be produced by HPV were included. Patients were classified into three groups: Patients with reactive changes, patients with cervical intraepithelial neoplasia grade 1 (CIN 1), and patients with cervical intraepithelial neoplasia grade 2 (CIN 2). In all patients, another cervical swab was obtained and tested for the HPV genome using the Digene Hybrid Capture II. This assay is able to distinguish between high-risk and low-risk HPV types. RESULTS: Based on cytology results, 44 patients showed reactive changes, 250 patients displayed CIN 1, and 172 patients displayed CIN 2. With the molecular assay, HPV was detected in 289/466 (62%) patients. The high-risk HPV type was present in 263 (56.4%) patients and the low-risk type in 26 (5,5%) patients. In 25% of patients with reactive changes, the HPV genome was detected. Corresponding rates for patients with CIN 1 and CIN 2 were 55 and 81%, respectively. CONCLUSION: Molecular detection of HPV should additionally be used to cytology in patients whose cervical smears display reactive changes, CIN 1, or CIN 2. The employed assay allows identification of patients who are at risk for development of high-grade cervical lesions.

Sudden death from trophoblastic embolism in pregnancy.

A case of a 24-year-old multigravida, with dry cough, dyspnea, fatigue, and weight loss with normal foetal growth rate is reviewed. Upon admission the patient suddenly became tachycardic, tachypnoic, cyanotic, followed by a non-palpable peripheral pulse, and asystole unresponsive to resuscitation. The autopsy revealed massive pulmonary trophoblastic embolism, bilateral pregnancy luteoma, and accelerated placental maturation. Trophoblastic embolism should be taken into consideration whenever cardiorespiratory emergency develops during pregnancy.

Amniotic fluid and maternal plasma prostaglandins in hypertonic saline-induced abortion.

Intraamniotic instillation of 20% sodium chloride solution was carried out in 12 women within the 16th to 18th weeks of pregnancy. PgE2 and PgF2 alpha levels were monitored both in amniotic fluid 5 and 11 h following NaCl instillation as well as in the maternal plasma within the 5-h interval up to 36 h after instillation had been performed. A significant increase was observed of both PGE2 and PGF2 alpha concentrations in the amniotic fluid of all women who underwent induction of abortion. PgF2 alpha in amniotic fluid was increasing abruptly during the time of abortion, reaching the value of 249.7 +/- 19.6 ng/l (n = 12; P less than 0.001). Maternal plasma PgF2 alpha showed a continuous mild increase from 20.4 +/- 5.5 ng/l before to the maximum level, recorded 36 h after instillation, ranging within 205 +/- 1.0 ng/l (n = 4; P less than 0.001). A statistically significant increase in the levels of PgE2 and PgF2 alpha in both amniotic fluid and maternal plasma suggests that the release of primary PGs is a pathognomonic event for initiating labor pains, maturation of the cervix in abortions induced via intra-amniotic instillation of hypertonic NaCl solution.

Hyperbaric oxygen therapy in two patients with non-arteritic anterior optic neuropathy who did not respond to prednisone.

Recent advances in understanding the effects of hyperbaric oxygen (HBO) on retinal anoxia gave rise to new interest in the possibility of using it as therapeutic treatment for ischemic conditions of the retina and optic nerve. Two patients with non-arteritic anterior ischemic optic neuropathy due to a high-grade ophthalmic artery stenosis were treated with HBO at 2 atm abs in an effort to increase oxygen delivery for the eye. Both patients showed marked improvements of visual acuity and visual field 3-5 months following the event. Our results are intriguing although the achieved improvement could be coincidental.

Review on prostaglandin and oxytocin activity in preterm labor.

The principal difference between term and preterm labor is how they are activated. It has been proposed that term labor results from physiological activation of the common terminal pathway, whereas preterm labor is a pathological condition caused by multiple etiologies that activate one or more of the components of this pathway. Increased uterine contractility at preterm labor results from activation and stimulation of the myometrium. Myometrium is stimulated by increased concentrations ofprostaglandins and oxytocin. Increased production of stimulatory prostaglandins by intrauterine tissues is generally considered a central component of the cascade of events leading to preterm parturition. Prostaglandins act to mediate cervical ripening and to stimulate uterine contractions and indirectly to increase fundally dominant myometrial contractility by up regulation of gap junctions, oxytocin and arginine vasopressin receptors and synchronizations of contractions. The authors tried to explain the role and influence of oxytocin in human parturition, as well as the novel therapy in inhibiting the contractions in preterm labor. The selective oxytocin inhibitor was tested in vitro on human myometrium and decidua by the author of this article among the first in the world.

The incidence and seasonal variations of acute primary angle-closure glaucoma.

The incidence and seasonal variations of acute primary angle-closure glaucoma (APACG) was studied. It was based on a retrospective chart review of 121 hospital patients in Split, Croatia for the fifteen-year period from 1985 through 1999. The average incidence was 4.1 cases per 100,000 per year in the total population and 7.1 per 100,000 in those aged 30 years and older. APACG affects women almost twice more often than men. The incidence rate increased with age. No seasonal variations in the occurrence of APACG and no correlation with the mean duration of light exposure per season were found.

Ponderal index and disproportionate fetal growth in IDDM pregnancies.

Disproportionate macrosomia refers to excessive weight characterized by a high weight/length ratio. Disproportionate macrosomia is associated with an increased likelihood of neonatal complications. The aim of the study was to investigate incidence of ponderal indexes and disproportionate fetal growth rate in newborns originating from IDDM and healthy pregnancies. 144 IDDM pregnancies and 432 uneventful pregnancies with normal findings of oral glucose tolerance test were studied, and matched 1:3 for gestational age, sex of newborn, mothers's parity and year of delivery. The pregnancies selected terminated between 30-40th gestational week and resulted with live birth. Mean birth weight (+/- SD) in IDDM group was 3558 +/- 817.6 compared to 3132.4 +/- 534.4 grams of control group (F = 51.49; p < 0.001), mean birth length was 49.8 +/- 3.5 vrs 49.1 +/- 2.5 (F = 8.55; p < 0.005), mean gestation age by examination for both study groups 37.9 +/- 1.9, mean ponderal index of IDDM group was 2.82 +/- 0.28 vrs. 2.63 +/- 0.24 (F = 64.52; p < 0.001) of control group, rate of Apgar score < 7 was 21.14% vrs. 5.08% (chi 2 = 30.30; p < 0.001). 53.4% of IDDMs had macrosomia compared with 8.33% of control infants (chi 2 = 140.25; p < 0.001), and 35.24% of IDDMs had disproportionate macrosomia compared with 5.79% of control infants. Significantly higher rate of both proportionally and disproportionally grown infants with macrosomia was found among IDDMs than among control infants. The rate of disproportionate macrosomic infants significantly differ among study group.

The effect of coagulation parameters on the placental respiratory and nutritive function in women having chronic hypertension with superimposed preeclampsia.

The aim of this study was to explore the relationship between coagulation and fibrinolytic system parameters with nutritive and respiratory placental function. We have analysed 79 pregnant women, of which 39 with severe preeclampsia (index group) and 41 healthy pregnant women. When comparing the study groups in third trimester, significantly lower platelet counts, fibrinogen values and antithrombin III values have been found in the index group compared to the control group. Factor VII levels were not found to be significantly different. The control group revealed significantly higher levels of coagulation factors II, V and VIII, compared to the index group. The increase of FDP, reduction of fibrinogen and increase of fibrinolysis in index group, when compared to the control group of healthy pregnant women, are the reflection of the intravascular fibrin deposition that leads to the described coagulation changes and consecutively to the foetal growth retardation. Indirect evidence are the correlation between newborns' weight and fibrinogen levels/fibrinolytic activity.

Holistic approach to analysis of medical data: vulvar cancer.

This paper continues the series of studies introducing holistic approach to analysis of clinical data. Namely, besides the information regarding his/her disease, each hospitalized cancer patient also provides the variety of data regarding his/her psychological, cultural, social, economical, genetic, constitutional and medical background. The aim of this study was to introduce a holistic approach to analysis of medical data, in this case clinical data regarding cancer of the vulva. Such approach requires the collection of data regarding different aspects of the cancer patients, and after the satisfactory sample size is obtained (which should be at least five times greater than the number of examined patient characteristics), the performance of factor analysis. In this study, the authors have processed the data regarding 25 characteristics of all 755 vulvar cancer patients treated between 1938 and 1990 at the Department for Gynecological Oncology of the University Hospital for Gynecology and Obstetrics, Zagreb, Croatia. In factor analysis, the principal components were rotated after the initial extraction (the authors recommended the use of oblimin rotation) in order to obtain better ground for interpretation of the obtained results. The next step in this approach was the stepwise exclusion of characteristics with smallest commonality according to Kaiser-Meyer-Olkin criteria, and retaining the characteristics and components with the most significant impact on the explained system variance. When the number of principal components and initial analyzed characteristics was reduced to 3-4 and 7-10, respectively, the ultimate interpretations and conclusions were made. This approach outlined some clusters of correlations between medical data which are difficult to identify using other statistical procedures, primarily the impacts of various socioeconomic and hereditary-constitutional variables on overall survival.

Influence of hyperglycemia on early embryonal growth in IDDM pregnant women.

The association between maternal diabetes mellitus and congenital anomalies is well established. Congenital malformations in the offspring of diabetic mothers account for approximately forty percent of perinatal deaths. The aim of the study was to identify incidence of early embryonal delay in diabetic and normal pregnancies, and to examine relationship between the HbA1c values and early embryonal growth delay. One hundred twenty IDDM and fifty and four healthy women enrolled into the study. Pregnancy duration was confirmed by beta-HCG measurements within a fortnight from the missed menstrual period. No statistical difference was detected between the studied groups for gestational age, prepregnancy weight, newborns' birthweight and sex. The risk of spontaneous abortion in IDDM pregnancy with delayed embryonal growth was eight times higher than in IDDM pregnancies with normal growth pattern. No fetal malformations were determined in fetuses or newborns of either groups. The mean value and standard deviation of HbA1c in the IDDM patients with normal embryonic growth was 7.3 +/- 1.5%, and in the group of early embryonic growth, delay 9.39 +/- 2.37% respectively (F = 7.79; p = 0.006). This study confirmed the relationship between embryonal growth, spontaneous abortions and abnormal metabolic control of IDDM pregnancies.