Distribution of iatrogenic retinal breaks in macular hole surgery

BACKGROUND: Intraoperative peripheral iatrogenic retinal breaks can be a serious complication of vitreous surgery. This study was undertaken to determine whether vitreous surgical techniques used for macular hole surgery were associated with a different incidence or distribution of retinal breaks. METHODS: The authors prospectively evaluated a series of 181 consecutive eyes undergoing macular hole surgery. Contemporaneous reporting of intraoperative and postoperative retinal breaks and postoperative retinal detachments was performed. Comparison was made to historic controls of two case series of patients undergoing vitreous surgery for other indications. RESULTS: Of 181 eyes, 10 (5.5%) had 15 intraoperative retinal breaks. Of the 15 breaks, 3 (20%) were in the quadrant near the surgeon's right-hand sclerotomy, 9 (60%) were in the two inferior quadrants, and 11 (73%) were in the two temporal quadrants. By comparison to previously reported case series, tears in our series were less likely to be near the right-hand sclerotomy (P = 0.00055) and more likely to occur in the two inferior retinal quadrants (P = 0.00015) and two temporal retinal quadrants (P = 0.0042). Two patients (1.1%) of 181 had postoperative retinal detachments. CONCLUSIONS: Patients undergoing vitreous surgery for macular hole have a similar incidence but different location of iatrogenic retinal breaks when compared with patients undergoing pars plana vitrectomy for other indications. These breaks are not distributed near sclerotomy sites and tend to be in the inferior and temporal retina. This establishes the need for greater intraoperative surveillance in these areas.     

Survival after relapse in childhood acute lymphoblastic leukemia: impact of site and time to first relapse--the Children''s Cancer Group Experience

After cardioversion from atrial fibrillation (AF) many patients develop early recurrence of the arrhythmia. While these patients may be appropriate for immediate prophylaxis against AF recurrence their identification at the time of cardioversion is not possible. Since the signal-averaged P wave (SAPW) is abnormal in individuals with atrial arrhythmia, we assessed its utility for predicting early AF recurrence after cardioversion. Seventy-five cardioversions in 31 patients were evaluated. The mean age was 59 (range 28-79) years; 26 were male. Fifty-eight cardioversions were internal using low energy biphasic DC shocks delivered via electrodes placed in the right atrial appendage and coronary sinus. P wave specific signal averaging was performed at 3 and 24 hours after each cardioversion to estimate filtered P wave duration and energy from 20, 40, and 60 to 150 Hz. Follow-up was by regular clinic visits and transtelephonic ECG monitoring. Early recurrence of AF (prospectively defined as sinus rhythm duration < 1 week) occurred after 30 cardioversions. No differences were found in any P wave variable measured at 3 hours between these cardioversions and those that resulted in a longer duration of sinus rhythm. Paired 3- and 24-hour signal-averaged data were available in 47 cardioversions. There were significant falls in P wave energy from 3 to 24 hours after 31 cardioversions that resulted in sinus rhythm for > 1 week, (P40: 3 hours 11.2 [+/- 1.5] micro V2.s, 24 hours 8.6 [+/- 1.2] micro V2.s, P < 0.001), but not following the 16 after which AF returned within 1 week (P40: 3 hours 9.0 [+/- 1.2] micro V2.s, 24 hours 8.5 [+/- 1.2 micro V2.s, P = NS). A fall in P40 of > 25% had a positive predictive accuracy for maintenance of sinus rhythm of 87%; negative predictive accuracy was only 37%. Similar falls in P wave energy occurred after cardioversions that resulted in longer term (> 4 weeks) sinus rhythm, but not in those that did not. However, the predictive accuracy of a fall in P40 was less (positive predictive accuracy 38%, negative predictive accuracy 62%). Patients with relapsing permanent AF who remain in sinus rhythm for at least 1 week after cardioversion show a fall in P wave energy within the first 24 hours. However, in these patients the technique does not predict recurrent AF within 1 week nor sinus rhythm > 4 weeks. These observations suggest persistent disordered atrial activation as a mechanism for early recurrence of AF after cardioversion.     

17 alpha-alkyl- or 17 alpha-substituted benzyl-17 beta-estradiols: a new family of estrone-sulfatase inhibitors

A series of 17 alpha-derivatives of 17 beta-estradiol was synthesized and tested for their ability to inhibit the estrone-sulfatase activity transforming estrone sulfate to estrone. A strong inhibitory activity was obtained when an alkyl side chain or a substituted benzyl was introduced at position 17 alpha of estradiol. The 17 alpha-(3'-bromobenzyl)-estradiol (26) and 17 alpha-(4'-t-butylbenzyl)-estradiol (30) were the most potent estrone-sulfatase inhibitors obtained in our study with IC50 values of 24 and 28 nM, respectively. They also represent a new family of estrone-sulfatase inhibitors. These compounds are about 300-fold more effective in interacting with the enzyme than the substrate estrone sulfate itself.     

Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience

BACKGROUND: The Quebec Neuroblastoma Screening (QNS) Project completed a 5-year program for measuring urinary vanillylmandelic acid (VMA)/homovanillic acid (HVA) levels at age 3 weeks and/or 6 months in 89% of 476,603 Quebec-born infants from 1989-1994; 45 screening positive preclinical cases (S-positive cases) and 20 congenital/neonatal (C/N) cases were identified. As of April 1997, an additional 59 cases in the same birth cohort were diagnosed clinically; these neuroblastomas developed after screening verified normal VMA/HVA levels (S-negative cases). METHODS: Pathology specimens from 45 of 59 S-negative cases were reviewed centrally and classified according to the Shimada system. Results were compared with clinical data and also with S-positive and C/N cases. RESULTS: Of 45 S-negative cases, 27 tumors had favorable histology (FH) and 18 had unfavorable histology (UH). Approximately 52% of FH tumors were diagnosed before age 1 year, whereas UH tumors were nearly exclusively (94%) diagnosed after age 1 year (P < 0.01). Approximately 89% of FH tumors were Stage I, II, or IV-S, whereas 72% UH tumors were Stage III or IV (P < 0.001). All children with FH tumors were alive at last follow-up (range of follow-up period: 9-79 months; median, 35 months), whereas 8 children with UH tumors died of disease even after limited follow-up (range of follow-up period: 0-60 months; median, 20 months). By contrast, S-positive and C/N cases were predominantly (97%) FH tumors, often (76%) Stage I, II, or IV-S, with excellent clinical outcome (survival rate of 98%). CONCLUSIONS: The majority of the UH neuroblastomas that developed in the birth cohort of the QNS Project were included in the group of S-negative cases and could not be detected by the screening at age 3 weeks and/or 6 months.     

Retinoid-X receptor signalling in the developing spinal cord

Retinoids regulate gene expression through the action of retinoic acid receptors (RARs) and retinoid-X receptors (RXRs), which both belong to the family of nuclear hormone receptors. Retinoids are of fundamental importance during development, but it has been difficult to assess the distribution of ligand-activated receptors in vivo. This is particularly the case for RXR, which is a critical unliganded auxiliary protein for several nuclear receptors, including RAR, but its ligand-activated role in vivo remains uncertain. Here we describe an assay in transgenic mice, based on the expression of an effector fusion protein linking the ligand-binding domain of either RXR or RAR to the yeast Gal4 DNA-binding domain, and the in situ detection of ligand-activated effector proteins by using an inducible transgenic lacZ reporter gene. We detect receptor activation in the spinal cord in a pattern that indicates that the receptor functions in the maturation of limb-innervating motor neurons. Our results reveal a specific activation pattern of Gal4-RXR which indicates that RXR is a critical bona fide receptor in the developing spinal cord.     

Initial cervical exploration for parathyroidectomy is not benefited by preoperative localization studies

Published data is controversial as to the ability of preoperative localization studies (PLS) to enhance the outcome of initial cervical exploration in patients with primary hyperparathyroidism (PHPT). One surgeon's experience was reviewed to compare surgical success, operative time, and morbidity of initial cervical exploration for PHPT in patients who had undergone PLS versus those who had not. From August 1991 to September 1997, 95 patients who had not undergone prior central cervical exploration presented for surgical management of PHPT. Sixty-seven patients underwent initial cervical exploration without any PLS having been performed (Group A). Twenty-eight patients underwent PLS, either alone or in combination, before surgical intervention (Group B). Analysis of intergroup variability was conducted upon the data available using a two-tailed t test for independent samples. In addition, the sensitivities and positive predictive values of the PLS were calculated using study reports and operative and histologic findings. There was no statistically significant difference in surgical success between those patients who had PLS and those that did not undergo PLS. Sixty-four of 67 patients (95.5%) not having PLS were cured with initial surgery, while 27 of 28 patients (96.4%) who had PLS were surgically cured. Mean postoperative calcium and intact parathormone levels were similar between the two groups, and the mean operative time did not differ. Permanent hypocalcemia occurred in one patient, and five patients had transient hoarseness. Thirty-six total PLS were obtained at an average cost of $752.68/patient, and seven patients underwent multiple tests. Overall, sestamibi scan had the highest positive predictive value (81%). For adenomatous disease alone, sestamibi scan was the most sensitive (83%). Our study shows that for matched groups limited to age, sex, and clinical diagnosis, the use of PLS did not shorten operative time, decrease complication frequency, nor alter the success of the operation as measured by postoperative calcium and parathormone levels. Therefore, routine use of preoperative localization studies before initial cervical exploration for PHPT cannot be recommended.     

Evidence of a critical period of airway instability during central apneas in preterm infants

The timing and magnitude of airway narrowing in central apneas is unknown. We have developed a method of apnea classification that relies on the transmission of cardiac airflow oscillation to indicate airway patency. Using a theoretical model, we showed that the amplitude of the cardiac airflow oscillation is proportional to airway diameter for small lumens. While in the majority of central apneas the amplitude of the cardiac airflow oscillation remains nearly constant, in a subset of events the waveform decreases with time, suggesting airway narrowing. We hypothesized that this is not a random occurrence but reflects a critical period of airway instability during central apnea. To test this hypothesis we studied 41 preterm infants. Of 4,456 central apneas, 585 had a decrease in the amplitude of the cardiac oscillation. The amplitude of the cardiac airflow oscillation during an apnea was recorded to provide a dynamic measure of changes in airway diameter with time. To allow for comparisons between patients the amplitude of each cardiac airflow oscillation was expressed as a proportion of the maximum amplitude observed in each infant. We then compared the amplitude at multiple successive 0.5 s intervals with the amplitude of the cardiac airflow oscillation observed at the apnea outset using ANOVA. We found a significant decrease in cardiac airflow oscillation after only 1 s irrespective of the apnea duration (3 to 16 s). We conclude that airway narrowing during central apnea is not a random occurrence but appears shortly after the onset of the apnea. We speculate that the phenomenon is secondary to passive airway relaxation.     

Pharmacokinetics of a single dose of teicoplanin in burn patients

Patients with severe burns are susceptible to infection with Gram-positive organisms including methicillin-resistant Staphylococcus aureus, and often require higher antibiotic dosages compared with other patients. This study examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15 adults and five children with severe burns. Adults were aged 21-82 years with a median total body surface area (TBSA) burn of 30% (range 15-60%). Children were aged 10 months-l0 years with median TBSA burn of 15% (10-30%). At 12 h, the median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and 7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L). Using a three-compartment model, the median terminal half life in adults was 114 h (47-278 h). Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41 h). The median concentration of teicoplanin in fluid from the burn wound was 60% of the serum antibiotic concentration. A single iv dose of 12 mg/kg of teicoplanin was sufficient to produce therapeutic serum concentrations in burn patients for 24 h, but monitoring of antibiotic levels in serum may be advisable in those with high total clearance, especially children.     

Near-infrared heavy-atom-modified fluorescent dyes for base-calling in DNA-sequencing applications using temporal discrimination

A series of near-IR fluorescent dyes were prepared which contained an intramolecular heavy atom for altering the fluorescence lifetimes to produce a set of probes appropriate for base-calling in a single-lane DNA sequencing format. The heavy-atom modification consisted of an intramolecular halogen situated on a remote section of the chromophore in order to minimize the perturbation on the lifetimes and fluorescence quantum yields. In addition, the dye series possessed an isothiocyanate functional group to allow facile attachment to sequencing primers. The unconjugated dyes showed similar absorption and emission maxima (lambda abs = 765-768 nm; lambda em = 794-798 nm) as well as fluorescence quantum yields that were invariant, within experimental error, with the heavy atom. However, the lifetimes of these dyes were found to vary with the identity of the halogen substitution (I, tau f = 947 ps; F, tau f = 843 ps, measured in methanol), with an average variation within the dye series of 35 ps. The spectroscopic properties of the free dyes and the dyes conjugated to sequencing primers on the 5'-end of the oligonucleotide were determined in a DNA-sequencing matrix (denaturing gels containing formamide). The results indicated slight differences in the fluorescence properties of the free dyes compared to those of the dye/ primer conjugates in this particular matrix. Inspection of the ground-state absorption spectra showed significant aggregation for the free dyes in this solution, but the conjugated dyes exhibited no sign of aggregation due to the highly anionic nature of the oligonucleotide. The fluorescence lifetimes of the dye/primer conjugates demonstrated lifetimes which ranged from 735 to 889 ps, with an average variation of 51 ps, an adequate difference to allow facile discrimination of these dyes in DNA-sequencing conditions. In addition, the free solution electrophoretic mobilities of the native heavy-atom-modified dyes were found to be very similar. When the dye/primer conjugates were electrophoresed in a cross-linked polyacrylamide gel electrophoresis capillary column, they comigrated, indicating that, in single-lane sequencing applications, when utilizing these dyes, no postrun corrections would be required to correct for dye-dependent mobility shifts.