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The recent results of Protocol T have illustrated the efficacy of aflibercept in the treatment of diabetic macular edema. It also demonstrated that in patients with poor vision (<6/12), aflibercept offers anatomical and visual advantages over ranibizumab and bevacizumab in the first 12 months of treament. At 2 years, the difference between the three drugs decreased with patients with a better baseline VA (69–78) showing a statistically insignificant advantage for ranibizumab compared with aflibercept.These results were achieved using a pro-re nata (PRN) protocol, which was not previously studied in large phase 3 trials, VIVID and VISTA, that chose to compare the 2.0 mg dose in a monthly and bimonthly regimen. In this review article, we analyzed earlier studies such as DAVINCI and VIVID and VISTA to determine which treatment strategy offers the best results; monthly, bimonthly, or PRN. We also studied the different doses for aflibercept used in DAVINCI to determine which is more effective the 0.5 mg dose or the 2.0 mg dose. In addition, we analyzed the recent data from protocol T with regards to visual and anatomic outcomes to try to determine whether these results concur with previous studies. Finally, we discuss the role of aflibercept as a potential alternative to any diabetic macular edema regimen regardless what the primary drug used is.

This study assessed the behavioural and psychological profiles of children conceived by in-vitro fertilization (IVF) who are now at school age. A total of 743 IVF children born at one institution and now of school age, over 4 years old, were surveyed with Achenbach questionnaires. Follow-up telephone interviews were conducted with non-responders. The results from the study group were compared to the questionnaire control group using one-tailed t-test with statistical significance set less than 0.05. There was an 84% overall response rate. Sixty-seven per cent returned questionnaires. An additional 17% completed a telephone interview. The study group had no statistically significant increase in the rate of behavioural or psychological problems compared with the control group. There were no statistically significant differences within the study group related to sex or to multiple gestation IVF births. This large group of school-age IVF children has normal psychological development with no identified adverse effect of their status as IVF children. Determining the role, if any, of IVF in the very small number of children with behavioural and psychological problems will require additional study.

Sequential percutaneous renal biopsies in six dogs given gentamicin at 10 mg/kg every 8 hours (intramuscular) were examined before treatment and 5, 9 and 12 days after treatment. Renal function tests (blood urea nitrogen and serum creatinine) and urinary enzyme excretion (β glucuronidase, N acetyl-glucosaminidase, galactosidase and muramidase) were measured daily. Periodic acid Schiff (PAS)-stained, 3-μm sections of renal biopsies taken before drug treatment showed pale and swollen proximal tubular epithelium that occluded the tubular lumen. The apical surface of all proximal tubules (brush border) stained intensely. On day 5, brush border staining was decreased or absent and many proximal tubules had open lumina and hyaline globules in the cytoplasm. Ultrastructurally, the numbers of cytoplasmic lysosomes were increased and most contained large lamellar inclusions (myelin figures). Biopsies on day 9 were characterized by an increase in the size and number of cytoplasmic hyaline globules and an absence of brush border staining. Scattered proximal tubule cells were necrotic. Intact proximal tubules and other parts of the nephron frequently contained amorphous granular casts or necrotic debris. Ultrastructurally, proximal tubules had intact brush borders and showed a remarkable increase in the number and size of lysosomes of all types. On day 12 the severity of these changes progressed, and cytosegrosomes became numerous. Urinary enzyme levels (β glucuronidase and N acetyl-glucosaminidase) were elevated by day 2, galactosidase elevated by day 4 and muramidase elevated by day 5. Clinically significant elevations in serum creatinine (day 6) and blood urea nitrogen (day 12) were preceded by elevations in urinary enzyme excretion and by severe alterations in renal tubular morphology.

Abstract: DNA typing of nine short tandem repeat (STR) loci was carried out on unrelated Israeli Jewish and Arab individuals. All loci were highly polymorphic and the distribution of the obtained genotypes did not deviate from Hardy-Weinberg equilibrium. A comparison between Jewish and Arab population data revealed statistically significant differences in allele frequency distributions for some of the loci. The results presented in this study enable the use of these nine STR loci for forensic, identification and paternity cases in the Jewish and the Arab populations of Israel.

Oxidative damage to DNA is caused by reactive by-products of normal metabolism, as well as by radiation. Oxidized DNA bases excised by DNA repair enzymes and excreted in urine were measured in four different species to determine the relation between specific metabolic rate (ml of O2 consumed per gram of body weight per hr) and oxidative DNA damage. An average of 6.04 nmol of thymine glycol per kg/day and 2.58 nmol of thymidine glycol per kg/day were found in mouse urine and 1.12 nmol of thymine glycol per kg/day and 0.95 nmol of thymidine glycol per kg/day were found in monkey urine. On a body weight basis, mice excrete 18 times more thymine glycol plus thymidine glycol than do humans, and monkeys excrete 4 times more thymine glycol plus thymidine glycol than do humans. When results among mice, rats, monkeys, and humans are compared, specific metabolic rate correlates highly with oxidative DNA damage. These findings are consistent with the theory that free radical-induced DNA damage may play a central role in the aging process.

Dogs were given gentamICIn (10 mg/kg) intramuscularly every 8 hr for 10 days. Levels of serum creatinine rose by day 6 (0.91 ± 0.08 vs. 0.75 ± 0.02 mg/dl for controls, P < 0.05) and of blood urea nitrogen by day 8 (24.3 ± 4.80 vs. 16.1 ± 0.90 mg/dl for controls, P < 0.05). Gentamicin nephrotoxicity occurred earlier and was more marked when furosemide (2 mg/kg) was added: the level of serum creatinine by day 6 was 1.62 ± 0.25 mg/dl (P < 0.05), and the level of blood urea nitrogen by day 8 was 181 ± 23.5 mg/dl (P < 0.01). Elevations in the activities of the urinary enzymes, β-glucuronidase, N-acetyl-β-glucosaminidase, and muramidase preceded rises in levels of serum creatinine and blood urea nitrogen. Examination of serial percutaneous renal biopsy specimens showed that gentamicin administration was associated with hyaline droplet degeneration, lysosomal changes, and, later, cell necrosis (primarily of the proximal tubules). Changes in renal morphology were more severe and occurred earlier when furosemide was administered concomitantly. In summary, furosemide enhanced gentamicin nephrotoxicity. Enzymuria was an early sign of gentamicin nephrotoxicity.

Described is an effort to dispel ageist attitudes in medical students. Supervised by faculty members, the medical students participated in weekly health seminars and provided health counseling for older people living in the community. Preliminary assessment revealed that providing the opportunity to physicians-in-training to become acquainted with active, healthy elderly individuals begins to dispel the stereotypical views engendered by their previous exposure to only the frail, acutely ill, elderly patients typically encountered in the hospital setting.

The effect of furosemide (F) on gentamicin (GN) nephrotoxicity was examined in a dog model.GN 10 mg/kg and F 2 mg/kg were given IM every 8 hours for 9 days. Elevation of BUN and serum creatinine values was earlier and more marked than in dogs given only GN. Serial percutaneous renal biopsies showed earlier and more severe renal injury in GN+F dogs. Increased activities of the urinary enzymes muramidase (MUR), B-glucuronidase (BG) and N-acetyl-glucosaminidase (NAG) were early signs of biopsy confirmed renal injury.Furosemide appears to potentiate gentamicin nephrotoxicity, perhaps in relation to volume depletion. Elevated urinary enzyme activities provide an early clue to the onset of renal injury.§Mean enzyme activity ± SEM expressed as U/mg of urinary creatinine. *p<.05, **p<.01 [compared to control or control (F) values].

Proximal renal tubular damage is reflected by increased urinary enzyme activity. The urinary enzymes muramidase (MUR), Beta glucuronidase (BG) and N-acetyl-glucosaminidase (NAG) were determined in infants and children receiving gentamicin, and compared to age matched controls.No significant decline in GFR as reflected by serum creatinine and BUN was observed in the gentamicin treated group. However, urinary enzyme activity in both infants and older children receiving gentamicin therapy was significantly higher than in controls, indicating proximal tubular injury. Urinary enzyme activities in neonates were significantly higher than in older children.Urinary enzyme activities are a sensitive means of detecting gentamicin tubular toxicity.*Mean activity ± SEM expressed as U/mg of urinary creatinine.

Four infants, two with omphaloceles and two with gastroschisis, developed sustained systemic hypertension following closure of their abdominal wall defects. Mean systolic blood pressure rose from a preoperative level of 70 mmHg to a peak postoperative level of 131 mmHg. Lower extremity blood pressures were not reduced. However, three infants had edema of the lower extremities. In all infants, blood urea nitrogen, serum creatinine, intravenous pyelograms, and urinalyses were normal. Catecholamine levels in two infants were normal. Three infants had normal peripheral plasma renin activity (PRA) and iodohippurate renal scans. One infant had an elevated PRA associated with evidence of utero pelvic junction obstruction by renal scan. The duration of hypertension ranged from 12 days to 180 days (mean 89.5 days). Two infants were treated with hydrochlorothiazide and hydralazine, while in two, hypertension resolved spontaneously. The etiology of the hypertension remains unclear. Possible mechanisms include: 1) compression of the renal parenchyma and/or vasculature; and 2) pressure or traction on the splanchnic and/or pelvic nerve supply. Since the incidence of abdominal wall defects is roughly 1 per 2300 live births, hypertension secondary to surgical correction of this condition may not be uncommon.

Furosemide (F) enhances the nephrotoxicity of gentamicin and a related aminoglycoside, netilmicin (NET) (Kid Int 12:538, 1977; Ped Res 13:366, 1979). To determine whether enhancement is primarily due to volume depletion, dogs were given im injections q8h for 10 days of the following: (F) alone 2 mg/kg, Grp 1; (NET) alone 15 mg/kg, Grp 2; (NET) 15 mg/kg + (F) 2 mg/kg, Grp 3. Group 4 received (NET) 15 mg/kg + (F) 2 mg/kg + gavage (75 mEq NaCl+40 mEq KC1/1 in a daily volume equal to 5% of body weight). Serum creatinine (Scr) values in Group 3 exceeded values of all other groups. Scr values did not differ between Groups 2 and 4. Necropsied renal tissue revealed moderate to severe diffuse acute tubular necrosis in Group 3; Groups 2 and 4 had only mild areas of tubular necrosis.The studies suggest that (F) enhancement of (NET) nephrotoxicity is primarily due to volume depletion.