Environmental covariates: effects on the power of sib-pair linkage methods

The effect of inclusion of environmental risk factors on the power of sib-pair linkage methods was tested for a qualitative trait. It was found that inclusion of an environmental variable did not increase the power of the Haseman-Elston (H-E) sib-pair nonparametric linkage analysis test. However, a significant increase in power was observed for both the H-E and affected-sib-pair tests, even in small samples, when persons unexposed to the environmental risk factor were coded as unknown.     

Sham radiation in clinical trials assessing radiotherapy for exudative age-related macular degeneration

BACKGROUND: To evaluate the effectiveness of sham radiation treatments in masking patients to their randomization group in the Radiation of Age-Related Macular Degeneration (ROARMD) Study. METHODS: Patients with choroidal neovascularization complicating age-related macular degeneration were randomized to a treatment (RAD) group that received external beam irradiation (seven treatment sessions) or to a control (SHAM) group that received sham radiation (one sham treatment session). During a telephone survey, 62 of 73 randomized patients responded to the following questions: Do you think you received radiation? Why do you feel that way? Did the vision in your study eye worsen after enrollment? RESULTS: Eighty-one percent of the RAD group and 59% of the SHAM group thought that they had received radiation. In patients who thought that their vision had stabilized or improved, 82% thought that they had received radiation. In patients who thought that their vision was worse, only 39% thought that they had received radiation. In 54% of patients, subjective perception of vision influenced their guess as to whether they received radiation. CONCLUSIONS: Subjective patient perception of visual outcome was the most influential variable for masking. Variation between radiation treatment and sham session techniques, such as equipment used and duration of treatments, played a lesser role in the masking of patients. Seven treatment days correlated with a higher number of patients who thought that they had received radiation. Although our procedures do not strictly mask the two groups, one sham radiation session was effective in keeping patients guessing their randomization group.     

Thallium-201 myocardial perfusion scintigrams in the evaluation of aorto-coronary saphenous bypass surgery.

The effect of aorto-coronary bypass graft surgery (CBG) upon regional myocardial perfusion (RMP) was studied in 23 patients using thallium-201 myocardial perfusing imaging after exercise. We compared the changes in RMP with the clinical status and ECG's during graded treadmill exercise (GTX) before and after CBG. After CBG, the New York Heart Association's "functional class" improved from 3.2 +/- 0.1 (mean +/- SE) to 1.2 +/- 0.2, p less than 0.005. The GTX performance of the patients was also significantly improved postoperatively as judged by the total exercise time (11.7 +/- 0.6 min postop, compared with 7.2 +/- 0.5 min preop; p less than 0.005). Postoperative improved Tl-201 scintigrams were observed in 19 patients, but in only nine patients did the perfusion distribution return to normal. Thus, Tl-201 exercise scintigrams following CBG demonstrate improved RMP in most patients. Failure of regional myocardial perfusion to improve postoperatively, however, does not preclude marked alleviation of angina and improved exercise tolerance.     

Functional anatomy of the gastroesophageal junction

The study of the functional anatomy of the gastroesophageal junction allows for the demonstration of a double mechanism that combats the conflict of pressures that tends to lead to gastroesophageal reflux. On one hand, the LES, an intrinsic structure, is directly related to the muscle fibers of the organ and responds to a neurohormonal physiologic command. On the other hand is an anatomic entity, centered by the crura of the diaphragm, closely related to the movements of respiration. These structures constitute a second, extrinsic sphincter that gives rise to the zone of high pressure in the terminal esophagus. This role is difficult to assess, and its importance is underestimated. The proper functioning of these two mechanisms implies that the gastroesophageal junction remains in place within the diaphragmatic channel of the esophagus. Also important are the postural phenomena associated with the sloping position of the fundus. In patients with gastroesophageal reflux, the decrease of the pressure measured in the terminal esophagus accounts for the occurrence of reflux. Investigators concede that, under the influence of abdominal straining, the gastroesophageal junction tends to ascend into the diaphragmatic channel. The results are twofold: (1) the muscle fibers of the lower esophagus relax, explaining the incompetence of the intrinsic sphincter, and (2) the sphincteric zone is withdrawn from its muscular diaphragmatic environment. Physicians should consider these structures as a whole in approaching the surgical treatment of reflux. The construction of a periesophageal valve has no anatomophysiologic basis. A gastropexy procedure must be added to replace the gastroesophageal junction in its anatomic setting and keep it there. This procedure also allows retightening of the muscle fibers of the esophageal wall, which is essential in long-term surgical correction.     

PRIMARY INTRACRANIAL GERM CELL TUMORS: Clinicopathologic Review of 32 Cases

Primary intracranial germ cell neoplasms are rare tumors and constitute a heterogeneous group. We have reviewed 32 cases, over a 21-year period, from the University of Florida. The cases include 22 germinomas, 6 mixed germ cell tumors, and 4 teratomas. The clinical presentations in these cases were more closely related to the location of the tumor, that is, pineal or suprasellar, rather than the histologic subtype. Neuroimaging evaluation was useful in distinguishing between germinomas, teratomas, and other mixed germ cell tumors (MGCTs), primarily by evaluation of cystic versus solid lesions (teratoma versus germinoma), contents of cysts (teratoma versus MGCT), and infiltrative nature of the tumors (MGCT), although cytologic-histopathologic confirmation remains necessary. Germinomas responded favorably to radiation therapy with survival periods of over 16 years; MGCTs were treated with combination chemotherapy and radiation, with a markedly poorer prognosis. This study underlines the critical significance of histopathologic evaluation of the tumor in determining therapeutic interventions as well as prognosis.     

A New Technique for Hypoglossal-Facial Nerve Repair

Hypoglossal reinnervation of the facial nerve may be required after a proximal facial nerve injury. The classic hypoglossal-facial graft procedure involves transection of the donor hypoglossal nerve, resulting in hemiglottic paralysis that, in association with paralysis of other cranial nerves, may cause speech and swallowing difficulties. Multiple lower cranial nerve palsies in conjunction with facial paralysis, as may occur after procedures such as skull base surgery, contraindicate the use of such techniques. The successful use of XII-VII “interposition jump grafts” without hemiglossal weakness has been described However, a prolonged recovery period and weaker facial reanimation have been seen. In order to attain maximum facial reinnervation while preserving hypoglossal function, we have developed a new technique of XII-VII repair. This method involves mobilization of the intratemporal portion of the facial nerve remnant, achieving a single anastomosis with the hypoglossal nerve, which has been partially incised. This technique has been used in three patients to date, with 6 to 11 months follow-up. In all cases facial tone and symmetry have been restored and voluntary facial expression accomplished. The authors conclude that by employing the techniques described highly satisfactory cosmetic and functional results may be expected, without compromising hypoglossal nerve function.     

Hair cell loss and regeneration after severe acoustic overstimulation in the adult pigeon

The extent of hair cell regeneration following acoustic overstimulation severe enough to destroy tall hair cells, was determined in adult pigeons. BrdU (5-bromo-2′-deoxyuridine) was used as a proliferation marker. Recovery of hearing thresholds in each individual animal was measured over a period of up to 16 weeks after trauma. In ears with loss of both short and tall hair cells, little or no functional recovery occurred. In ears with less damage, where significant functional recovery did occur, there were always a few rows of surviving hair cells left at the neural edge of the basilar papilla. In the region of hair cell loss, numerous BrdU labeled cells were found. However, only a small minority of these cells were regenerated hair cells, the majority being monolayer cells. Irrespective of the extent of the region of hair cell loss, regenerated hair cells were observed predominantly in a narrow strip at the transition from the abneural area of total hair cell loss and the neural area of hair cell survival. With increasing damage this strip moved progressively towards the neural edge of the papilla. No regeneration of hair cells was observed in the abneural region of total hair cell loss, even up to 16 weeks after trauma. The results indicate that there is a gradient in the destructive effect of loud sound across the width of the basilar papilla, from most detrimental at the abneural edge to least detrimental at the neural edge. Both tall and short hair cells can regenerate after sound trauma. Whether they do regenerate or not depends on the degree of damage to the area of the papilla where they normally reside. Regeneration of new hair cells occurs only in a narrow longitudinal band, which moves from abneural into the neural direction with increasing damage. In the area neural to this band, hair cells survive the overstimulation. In the area abneural to this band, sound damage is so severe, that no regeneration of hair cells occurs. As a consequence morphological and functional deficits persist.     

Functional and morphological changes in diabetic macular edema over the course of anti‐vascular endothelial growth factor treatment

Purpose:  To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti‐vascular endothelial growth factor (VEGF) treatment with Ranibizumab. Methods:  A consecutive series of 39 study eyes with centre‐involving DME were included in this study. In all subjects, best‐corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD‐OCT) cross‐sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross‐sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. Results:  Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 μm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = ?1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = ?3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = ?4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = ?1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = ?0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = ?2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. Conclusions:  ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti‐VEGF therapy with Ranibizumab in patients with DME.