Post-phototherapy neonatal bilirubin rebound: a potential cause of significant hyperbilirubinaemia.

AIM: To determine the incidence of post-phototherapy neonatal plasma total bilirubin (PTB) rebound. METHODS: A prospective clinical survey was performed on 226 term and near-term neonates treated with phototherapy in the well baby nursery of the Shaare Zedek Medical Center from January 2001 to September 2002. Neonates were tested for PTB 24 hours (between 12 and 36 hours) after discontinuation of phototherapy, with additional testing as clinically indicated. The main outcome measure, significant bilirubin rebound, was defined as a post-phototherapy PTB > or =256 micromol/l. Phototherapy was not reinstituted in all cases of rebound, but rather according to clinical indications. RESULTS: A total of 30 (13.3%) neonates developed significant rebound (mean (SD) PTB 287 (27) micromol/l, upper range 351 micromol/l). Twenty two of these (73%) were retreated with phototherapy at mean PTB 296 (29) micromol/l. Multiple logistic regression analysis showed significant risk for aetiological risk factors including positive direct Coombs test (odds ratio 2.44, 95% CI 1.25 to 4.74) and gestational age <37 weeks (odds ratio 3.21, 95% CI 1.29 to 7.96). A greater number of neonates rebounded among those in whom phototherapy was commenced < or =72 hours (26/152, 17%) compared with >72 hours (4/74, 5.4%) (odds ratio 3.61, 95% CI 1.21 to 10.77). CONCLUSION: Post-phototherapy neonatal bilirubin rebound to clinically significant levels may occur, especially in cases of prematurity, direct Coombs test positivity, and those treated < or =72 hours. These risk factors should be taken into account when planning post-phototherapy follow up.

Maternal and umbilical cord serum leptin concentrations in small-for-gestational-age and in appropriate-for-gestational-age neonates: a maternal, fetal, or placental contribution?

Leptin is secreted during pregnancy by the placenta and by the maternal and fetal adipose tissues. The leptin levels mainly reflect the amount of fat stored and thus are indicative of the energy balance, i.e., small-for-gestational-age (SGA) neonates represent the negative metabolic balance of in utero starved babies. We chose to compare maternal and umbilical cord leptin levels in pregnancies complicated by asymmetrical SGA versus those with appropriate-for-gestational-age (AGA) neonates as well as a model of multifetal growth concordant gestations in order to establish through the 'leptin link' the relative contributions of mother, fetus, and placenta to fetal weight. We found that the maternal leptin levels at delivery correlated poorly with the maternal weight gain/body mass index and with neonatal birth weight. Furthermore, the umbilical cord leptin levels correlated well with neonatal and placental weights in the AGA group but not in the SGA group. As in AGA singleton pregnancies, in multifetal uncomplicated pregnancies, the umbilical cord leptin levels correlated well with the birth weight of individuals, regardless of the status of the twin or triplet in the set. Thus, we speculated that in SGA neonates the birth weight represents the lean body weight and the low adipose tissue content (as opposed to the AGA neonates who have a substantial adipose tissue content) and, therefore, reflects mainly the basic placental contribution.

High prevalence of low serum vitamin B12 in a multi-ethnic Israeli population.

This study ascertained serum vitamin B12 levels among patients with Gaucher disease and among healthy Israelis. Serum B12 and metabolites' levels were studied in consecutive adult patients with Gaucher disease not treated with enzyme plus Ashkenazi Jewish neighbour-controls, together with healthy blood-donor volunteers of various ethnicities. Each group showed a high incidence of low serum B12 concentrations, with a 22.3% incidence among Ashkenazi Jews and 40% among patients with Gaucher disease. These findings raise questions on the individual and community levels of serum B12. We recommend evaluation of B12 levels among geographically contingent peoples.

Onset of jaundice in glucose-6-phosphate dehydrogenase-deficient neonates.

OBJECTIVE: We asked whether neonatal jaundice associated with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency commences either in utero or in the immediate postnatal period and whether this perinatal bilirubinemia is the precursor of the subsequent neonatal jaundice and hyperbilirubinemia. METHODS: Mandatory serum total bilirubin (STB) determinations were performed within 3 hours of birth, to reflect the in utero state (first STB), and on the third day of life (second STB), with additional determinations as clinically necessary, on healthy, term male neonates at high risk for G-6-PD deficiency. G-6-PD Mediterranean mutation was determined by molecular means. G-6-PD-deficient neonates were compared with control participants. The relationship of first STB values to second STB and subsequent hyperbilirubinemia (defined as STB >/=256 micromol/L [15.0 mg/dL]) was determined. RESULTS: Both first and second STB values were significantly higher in the G-6-PD-deficient neonates (n = 52) than in control participants (n = 166; 50 +/- 12 micromol/L vs 44 +/- 10 micromol/L [2.9 +/- 0.7 mg/dL vs 2.6 +/- 0.6 mg/dL] and 174 +/- 52 micromol/L vs 152 +/- 52 micromol/L [10.2 +/- 3.1 mg/dL vs 8.9 +/- 3.0 mg/dL] for the first and second STB values, respectively). The rate of rise between these 2 points was greater in the G-6-PD-deficient neonates (2.6 +/- 0.9 micromol/L/h vs 2.2 +/- 0.9 micromol/L/h [0.15 +/- 0.05 mg/dL/h vs 0.13 +/- 0.05 mg/dL/h). Sixteen (30.8%) of the G-6-PD-deficient neonates developed hyperbilirubinemia compared with 10 (6%) of control participants (relative risk: 5.11; 95% confidence interval: 2.47-10.56). In both G-6-PD-deficient and normal populations, first STB values correlated significantly with both second STB values and with those who subsequently developed hyperbilirubinemia. Significantly more G-6-PD-deficient neonates with a first STB value greater than or equal to the mean developed hyperbilirubinemia compared with those with first STB less than the mean: 13 of 28 neonates versus 3 of 24 (relative risk: 3.7; 95% confidence interval: 1.20-11.51). This difference did not reach statistical significance in the control group. CONCLUSIONS: Higher first STB values, an increased risk of hyperbilirubinemia in G-6-PD-deficient neonates with first STB value greater than or equal to the mean, and significant correlation between first STB values and second STB values and hyperbilirubinemia suggest that jaundice in G-6-PD-deficient neonates commences in the immediate perinatal period, most likely in utero.

The questionable use of albumin for the prevention of ovarian hyperstimulation syndrome in an IVF programme: a randomized placebo-controlled trial.

BACKGROUND: The role of intravenous (IV) albumin administration in the prevention of ovarian hyperstimulation syndrome (OHSS) and in the improvement of IVF conception outcomes was evaluated in a prospective, randomized, placebo-controlled double blind study. METHODS: Ninety-eight women were enrolled in the study and were consecutively assigned to either a treatment group or a control group. Eleven patients were lost to follow-up after assignment. Of the remaining 87 women, 46 received albumin on the day of oocyte retrieval, and 41 received 0.9% sodium chloride solution as a placebo control. Outcome measures included OHSS incidence rates and pregnancy rates in the two trial groups. RESULTS: Four of the 46 patients in the study group developed severe OHSS and six developed moderate OHSS. In the control group, one of the 41 developed severe OHSS and five developed moderate OHSS. The difference in OHSS incidence rates between the two groups was not statistically significant [relative risk (RR) = 1.49, 95% CI = 0.59-3.73]. Fourteen patients (30%) in the intervention group conceived, compared with 16 patients (39%) in the control group. The difference in conception rates between the two groups was not statistically significant (RR = 0.78, 95% CI = 0.44-1.39). CONCLUSIONS: Albumin appears to have no positive effect on OHSS or conception rates, while its use carries the risk of undesirable side effects, including exacerbation of ascites in OHSS, nausea, vomiting, febrile reaction, allergic reaction, anaphylactic shock and risk of virus and prion transmission. We suggest that this form of treatment should not be included in the prevention of OHSS.

Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function.

Anemia in persistent nephrotic syndrome (NS) has been described in a few case reports but has not been studied systematically. We present a group of 19 children with NS who developed anemia before the deterioration of kidney function. The aim of our study is to determine whether erythropoietin (EPO) and/or iron deficiency are causative factors and to evaluate the effect of EPO replacement therapy. Serum EPO levels, iron status, and vitamin B(12) concentrations were measured in nephrotic patients with anemia (NS-A) and compared with those of nephrotic children with normal hemoglobin (Hb) levels (NS-NHb; n = 13). Two control groups consisted of age-matched patients without kidney disease or hypoxemia with either iron deficiency anemia (IDA; n = 19) or normal Hb concentrations (NHb; n = 16). Most NS-A patients experienced persistent steroid-resistant NS, whereas most NS-NHb children had steroid-responsive NS. Although serum iron, ferritin, and B(12) levels were significantly lower in NS-A children, appropriate replacement therapy that resulted in normalization of ferritin and/or cobalamin levels did not lead to correction of the anemia. NS-A patients had greater EPO levels than those without anemia (21.6 +/- 3.3 versus 5.5 +/- 0.8 IU/L; P: < 0.001), but their response to anemia was inappropriately low compared with IDA children (EPO, 94.6 +/- 15.1 IU/L) despite similar Hb concentrations. EPO therapy for 4 to 9 months in 6 NS-A children with Hb levels less than 9 g/dL led to resolution of the anemia. In conclusion, anemia is a common feature of persistent NS that develops before the deterioration of kidney function. Depletion of iron stores may contribute to the development of anemia, but iron replacement therapy is ineffective. Nephrotic patients have EPO deficiency with a blunted response to anemia. The EPO deficiency is amenable to EPO therapy, which is recommended for this group of patients.

An implant releasing the gonadotropin hormone-releasing hormone agonist histrelin maintains medical castration for up to 30 months in metastatic prostate cancer.

PURPOSE: The administration of gonadotropin hormone-releasing hormone agonists is well established for treating metastatic prostate cancer. In an ongoing study we evaluated the effect of a long acting implant that releases the gonadotropin hormone-releasing hormone agonist histrelin ([ImBzl]D-His6,Pro9-Net) in 15 patients with disseminated prostate cancer. MATERIALS AND METHODS: The 2.6 cm. implant releasing 60 microg. histrelin daily is inserted subcutaneously into the upper arm using local anesthesia. Of the patients 8 received 1 and the remainder received 2 implants. Treatment with the antiandrogen flutamide or cyproterone acetate began 2 weeks before implant insertion and continued for up to 12 weeks. Testosterone, luteinizing hormone (LH) and prostate specific antigen were determined monthly, and a metastatic evaluation was performed every 6 months. RESULTS: LH and testosterone increased after flutamide administration and decreased after implant insertion. By day 28 LH and testosterone were completely suppressed. LH and testosterone decreased immediately after cyproterone acetate administration. Prostate specific antigen began to decrease during antiandrogen therapy and decreased further after implant insertion. One patient requested implant removal after 1 year for personal reasons and 1 died of an unrelated cause 18 months after insertion. Escape was demonstrated in 4 cases at 5, 10, 12 and 19 months, although LH and testosterone remained suppressed. Duration of treatment in the remaining 9 patients was between 21 and 30 months. LH and testosterone remained completely suppressed and prostate specific antigen levels were in the normal range. The clinical and biochemical response was identical in those who received 1 or 2 implants. At 12 months 8 patients were challenged at intermittent intervals for up to 24 months with a bolus of 100 microg. gonadotropin hormone-releasing hormone followed by 2 weeks of flutamide. The response was compared with that in untreated controls recently diagnosed with prostate cancer. Unlike controls there was complete LH suppression in the 8 challenged patients. CONCLUSIONS: A histrelin implant suppresses LH and testosterone in prostate cancer for up to 30 months. This finding represents a significant improvement over existing preparations, which must be administered at 1 to 3-month intervals.

The origin of serum progesterone during the follicular phase of menotropin-stimulated cycles.

The study was designed to investigate the source of progesterone secretion during pituitary suppression and ovarian stimulation. It involved 416 women undergoing in-vitro fertilization (IVF) who were treated with gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) (group I), 139 women undergoing ovulation induction with HMG only (group II) and nine women who were diagnosed previously as late-onset adrenal hyperplasia and treated continuously with dexamethasone, in addition to ovulation induction (group III). During HMG treatment, serum oestradiol and progesterone were measured every 1-2 days. If progesterone concentration exceeded 3.0 nmol/l, at least 36 h before human chorionic gonadotrophin (HCG) administration, the patients were prospectively randomized to treatment with dexamethasone or not and the hormones concentrations were measured again 12 h later. Mean age and pretreatment serum concentrations of dehydroepiandrosterone sulphate, androstenedione, testosterone and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, were not significantly different in the patients with and without progesterone elevation. Pituitary down-regulation did not reduce the incidence of progesterone elevation (13.9 and 12.2% in groups I and II respectively), while in group III, progesterone concentrations did not increase. After dexamethasone administration a significant decrease in serum progesterone concentration was demonstrated (mean +/- SD, -2.1 +/- 1.4 and -1.6 +/- 1.2 in groups I and II respectively, while in the untreated patients it increased (+1.9 +/- 1.9 and +4.2 +/- 4.8). The increase in serum progesterone concentrations was not accompanied by an increase in cortisol and 11-deoxycortisol but by an increase in LH. After dexamethasone administration the concentrations of cortisol, 11-deoxycortisol and LH significantly decreased. Progesterone concentration was positively correlated with both oestradiol concentration (r = 0.290; P < 0.05) and the number of oocytes retrieved (r = 0.207; P < 0.05). We conclude that at least a part of serum follicular-phase progesterone appears to be of adrenal origin. High oestrogen concentrations (or other ovarian factors) may cause changes in the hypothalamic-pituitary-adrenal axis and in adrenal enzyme activity as a part of the complex 'cross-talk' between the hypothalamic-pituitary-ovarian and the hypothalamic-pituitary-adrenal axes.

Elevated serum progesterone levels during pituitary suppression may signify adrenal hyperandrogenism.

OBJECTIVE: To investigate whether elevated serum P levels after pituitary down-regulation signify adrenal enzyme defects or hyperandrogenism. DESIGN: Prospective study. SETTING: Assisted reproduction unit in a university medical center. PATIENT(S): Two hundred twenty-seven IVF patients treated by the long down-regulation protocol. INTERVENTION(S): Oral dexamethasone (DEX) administration if P level exceeded 0.8 ng/mL (conversion factor to SI unit, 3.180) after pituitary suppression. MAIN OUTCOME MEASURE(S): Serum concentrations of P, E2, LH, DHEAS, and 17 alpha-hydroxyprogesterone and ACTH stimulation tests. RESULT(S): In eight patients (3.5%), serum P levels exceeded 0.8 ng/mL and E2 and LH levels confirmed pituitary down-regulation. Mean DHEAS levels in the patients in this group were significantly higher than in the other patients. All eight patients demonstrated a significant decrease in serum P level after DEX administration. In five patients the ACTH stimulation test suggested an adrenal defect. Five pregnancies were achieved after the addition of DEX to the treatment protocol. CONCLUSION(S): High serum P levels after pituitary down-regulation appear to be of adrenal origin and may be the first indication of an adrenal enzyme defect. Further investigation such as an ACTH stimulation test is recommended, followed by treatment with DEX if indicated.

Ultrasonographic "endometrial three-layer" pattern: a unique finding in ectopic pregnancy.

Although diagnostic ultrasonography is playing an increasing role in the investigation of the patient with suspected ectopic pregnancy (EP), it has significant limitations in the very early stages of pregnancy. By sonographically exploring the intrauterine echoes in 45 cases of documented EP, we demonstrated a unique pattern in 28 cases (62.2%). A well-defined spheric structure forming an endometrial three-layer (ETL) pattern was seen, probably formed by a midline echo between the two adjacent edematous proliferative layers of the endometrium, the latter resembling the late proliferative endometrium. In 17 patients with a proved EP (37.8%), the ETL pattern was not demonstrated. However, the ETL was not demonstrated in all 40 cases of early intrauterine pregnancy and all 50 cases of miscarriage. These findings suggest a 100% specificity and a sensitivity of 62.2% for the ETL pattern in the diagnosis of EP.

Adrenal suppression among asthmatic children receiving chronic therapy with inhaled corticosteroid with and without spacer device.

BACKGROUND: Inhaled corticosteroids have become a first-line treatment for chronic asthma. It has been shown that inhaled corticosteroids can have a measurable effect on the hypothalamic-pituitary-adrenal axis in asthmatic children. OBJECTIVE: To investigate the prevalence of adrenal suppression among asthmatic children receiving chronic therapy with low to moderate doses (up to 1000 micrograms) of inhaled beclomethasone dipropionate via a metered dose inhaler (MDI) and via MDI attached to a spacer device (MDI-spacer). METHODS: The study included 39 asthmatic children currently undergoing therapy; 24 received beclomethasone dipropionate by MDI attached to a spacer, and 15 directly by MDI. All the patients had been treated for at least 4 months. Another 21 children were normal controls. The 24-hour urinary free cortisol excretion was measured to evaluate hypothalamic-pituitary-adrenal axis function. RESULTS: Seven of 15 (47%) patients from the MDI group had reduced 24 hour-urinary free cortisol excretion and 2 of 24 (8%) in the MDI-spacer group (P = .006). The mean 24-hour urinary free cortisol excretion of the MDI group was 0.0185 +/- 0.0089 microgram/gram creatinine, and the MDI-spacer and the control groups were, 0.0290 +/- 0.0138 microgram/gram creatinine and 0.0270 +/- 0.0118 microgram/gram creatinine, respectively, (P = 0.37, f = 3.51 ANOVA). CONCLUSION: Chronic inhalation of low to moderate doses of corticosteroids is associated with adrenal suppression in some asthmatic children. This side effect is more common among patients inhaling directly from the MDI and is less frequent when a large volume spacer is attached to the MDI.

Oral pulse therapy with vitamin D3 for control of secondary hyperparathyroidism.

Twelve dialysis patients received oral pulse therapy with 1-alpha-hydroxyvitamin D3 in a dose of 0.1 microgram/kg body weight twice weekly and daily calcium carbonate (1.5-3.5 g) for a period of 8-12 months. This treatment was very effective in suppressing secondary hyperparathyroidism without causing hypercalcaemia and/or hyperphosphataemia.

Low dose ketoconazole attenuates serum androgen levels in patients with polycystic ovary syndrome and inhibits ovarian steroidogenesis in vitro.

OBJECTIVE: To investigate the effects of a low-dose ketoconazole on ovarian steroidogenesis and on serum androgen levels in polycystic ovary syndrome (PCOS). DESIGN: In vitro, human granulosa-luteal cells were incubated with ketoconazole and radiolabeled steroid substrates, to follow their metabolic fate by thin-layer chromatography analysis. In vivo, normally cycling women (n = 7) in their luteal phase were administered one tablet of 200 mg ketoconazole at 8 A.M. Serum steroid levels, sampled basally and at 12 P.M., 4 P.M., and 8 A.M. the next morning, were compared with untreated control group (n = 7) values. Polycystic ovary syndrome women (n = 11) were similarly administered ketoconazole 6 to 10 days after occurrence of spontaneous menses. Adrenal origin of hyperandrogenemia was excluded by stimulation with ACTH and a normal basal DHEAS. The steroid diurnal variation was determined in the same patients a day before treatment. RESULTS: In vitro, ketoconazole selectively inhibited the key steroidogenic cytochromes, namely P450scc, P45017 alpha, and P450arom (IC50 = 0.5 to 1.0 microgram/mL). In vivo, in the luteal phase, ketoconazole transiently decreased serum values (mean +/- SE) of E2 (19.2% +/- 2.1%) and P (38.3% +/- 8.5%) within 4 to 8 hours. The same low-dose ketoconazole, administered to PCOS women, decreased serum values of androstenedione (17.6% +/- 4.7%), T (24.6% +/- 7.6%), and free T (30.7% +/- 7.7%). In contrast, 17 alpha-hydroxyprogesterone increased concomitantly (78.5% +/- 10.8%), suggesting a greater suppressibility of the P45017 alpha lyase activity. The E2 levels in PCOS patients were slightly elevated (29.1% +/- 5.6%), resulting in a 1.7- to 2.3-fold increase of the E2:T ratio. CONCLUSIONS: These findings suggest that a low-dose ketoconazole may facilitate a decreased intraovarian T:E2 ratio, which may prove favorable for follicular maturation in PCOS.

Hypernatremia in the acutely ill elderly patients: role of impaired arginine-vasopressin secretion.

Hypernatremia, a common finding among the elderly, is believed to be due to water deficit. In the present study, in 12 consecutive hospitalized elderly patients (mean age 82.2 years) with moderate to severe hypernatremia (mean serum sodium 166.9 mEq/l), inappropriately low plasma levels of vasopressin were found in relation to serum osmolality (mean 1.8 pg/ml and 343 mosmol/l, respectively). All patients but 1 were hospitalized with acute febrile disease and all but 2 had underlying neurological disease. Hypernatremia persisted for at least 3 days despite the patients' rehydration. It seems, therefore, that temporary hypernatremia in elderly patients with acute febrile disease, especially in the presence of underlying neurological disorder, reflects an inadequate vasopressin response to the hyperosmolar state.

Serum and mononuclear cell potassium, magnesium, sodium and calcium in pregnancy and labour and their relation to uterine muscle contraction.

Thirty women in their third trimester of pregnancy (37-42 weeks), 40 women during and 72 h after labour and 18 non-pregnant controls were studied for changes in serum and mononuclear cell cation content, and their relationship to cervical effacement and intensity of pain as measured by plasma beta endorphin concentrations during labour. Serum magnesium fell from 0.95 +/- 0.01 (mean +/- SEM) to 0.84 +/- 0.02 mmol/litre at late pregnancy and further to 0.76 +/- 0.01 during labour (P < 0.001); serum potassium fell from 4.25 +/- 0.05 to 3.79 +/- 0.06 mmol/litre (P < 0.0001) during labour; and serum calcium fell from 2.40 +/- 0.02 to 2.28 +/- 0.01 mmol/litre at late pregnancy (P < 0.001) and further to 2.25 +/- 0.02 mmol/litre during labour (P < 0.001). Mononuclear cell magnesium content rose from 4.5 +/- 0.3 to 5.6 +/- 0.04 fmol/cell (P < 0.02); potassium content rose from 37.7 +/- 2.0 to 50.9 +/- 3.0 fmol/cell (P < 0.001); and calcium content rose from 4.4 +/- 0.4 to 7.6 +/- 1.1 fmol/cell (P < 0.105). On the other hand, mononuclear cell sodium content fell from 7.2 +/- 0.5 to 3.8 +/- 0.3 fmol/cell (P < 0.001). Plasma beta endorphin concentrations increased with increasing degrees of effacement, as did intracellular Na, whereas intracellular Mg and K showed an inverse trend. A significant correlation was found between intracellular cation and beta endorphin levels (r = -0.98, Mg; -0.99, K; 0.83, Na). These changes are probably due either to intercompartmental cation shifts or possibly to endometrial ischaemia and damage during labour.

Serum and intracellular electrolytes in patients with and without pain.

The effect of acute stress, with and without pain, on serum and mononuclear cell cation content was studied in 205 healthy women in their last trimester of pregnancy or during normal labour, in patients with acute medical conditions in which pain was or was not present, in acute surgical conditions, and immediately prior to elective surgery. In all subjects there was a fall in serum sodium, potassium, magnesium and calcium concentrations during stress, with an apparent shift into the intracellular space. An inverse correlation was present between the severity of pain and the fall in serum cations.

The relationship between beta-endorphin levels and uterine muscle contractions during labor.

Plasma beta-endorphin (BE) levels (8.6 +/- 0.8 pmol/l) (mean +/- SE) were lower in the third trimester than in non-pregnant controls (14.8 +/- 1.1 pmol/l) (P less than 0.001), increased during labor, to 29.3 +/- 4.4 pmol/l (P less than 0.005) and decreased, 72 h after delivery, to 3.5 +/- 0.4 pmol/l (P less than 0.001). BE levels were found to correlate significantly with uterine muscle contraction (r = 0.966, P less than 0.05) and with cervical effacement (r = 0.974, P less than 0.05) during labor.

A metabolic analysis of high myopia and senile macular degeneration.

Abnormal zinc and copper metabolism have been described in several retinal disorders affecting the retinal pigment epithelium. An infrequent presentation of senile macular degeneration in high myopia is well known. We examined the blood for zinc and copper and the urine for copper of three groups of patients, one consisting of high myopia, another with high myopia and primary retinal detachment and the other a group of patients with senile macular degeneration. When comparing the above groups of patients, we found statistically elevated values of serum zinc (p = less than 0.005) in the group of patients with senile macular degeneration. The significance of these findings, and a correlation with the pathogeneses of high myopia and senile macular degeneration is discussed.