Changes in aqueous outflow after in vitro neodymium: yttrium aluminum garnet laser cyclophotocoagulation

To examine the possible role of transscleral outflow routes, enucleated human and porcine eyes underwent noncontact neodymium:yttrium aluminum garnet (Nd:YAG) laser cyclophotocoagulation 3 mm posterior to the limbus. Pars plana lesions were verified histologically. The eyes were perfused with saline solution at 50 mm Hg perfusion pressure, placing the tip of the needle into the hyaloid orbicular space. The outflow facility was 0.072 microliter/min/mm Hg in paired controls and 0.105 microliter/min/mm Hg in human lasered eyes, a difference of 31%. In porcine eyes the difference was 43%. Since concepts of aqueous production, impaired circulation, and inflammation do not apply to enucleated eyes, the increase may be related to pars plana transscleral flow facilitated by disruption of the neuroepithelial barrier.     

Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling.

Although Hedgehog (HH) signaling plays a critical role in patterning the ventral midbrain, its role in early midbrain specification is not known. We examined the midbrains of sonic hedgehog (Shh) and smoothened (Smo) mutant mice where HH signaling is respectively attenuated and eliminated. We show that some ventral (Evx1+) cell fates are specified in the Shh-/- mouse in a Ptc1- and Gli1-independent manner. HH-independent ventral midbrain induction was further confirmed by the presence of a Pax7-negative ventral midbrain territory in both Shh-/- and Smo-/- mice at and before embryonic day (E) 8.5. Midbrain signaling centers are severely disrupted in the Shh-/- mutant. Interestingly, dorsal markers are up-regulated (Wnt1, Gdf7, Pax7), down-regulated (Lfng), or otherwise altered (Zic1) in the Shh-/- midbrain. Together with the increased cell death seen specifically in Shh-/- dorsal midbrains (E8.5-E9), our results suggest specific regulation of dorsal patterning by SHH, rather than a simple deregulation due to its absence.     

Melanoma

The incidence of melanoma in the US is rising at a rate second only to that of lung cancer in women. Early stage melanoma is curable, but once metastatic, it is almost uniformly fatal. The immunotherapy of melanoma is a new and exciting therapeutic modality that is being extensively investigated worldwide. Interferon-alpha has an approximately 16% response rate in metastatic melanoma. In the randomised trials to date, no combination of chemotherapeutic or hormonal agent with interferon-alpha has proven to be superior to dacarbazine, the reference agent for the treatment of metastatic melanoma. The role of interferon-alpha-2b in the adjuvant therapy of localised melanoma at high risk for relapse has recently been established, with the results of 2 large randomised trials conducted by the US Intergroup, one showing improvement in both relapse-free survival and overall survival, and the other in relapse-free survival only. Interferon-gamma has not been effective in the adjuvant setting or in metastatic disease, but is part of combination protocols used for regional therapy for extremity melanomas. Interleukin-2 has an overall response rate of 15 to 20% in metastatic melanoma and produces some complete and durable remissions. The US Food and Drug Administration has recently approved the use of high-dose bolus administration of recombinant interleukin-2 for the therapy of metastatic melanoma. Results of combination chemotherapy and immunotherapy regimens containing interleukin-2 (biochemotherapy) are promising, and ongoing research will determine whether a survival impact will be confirmed in randomised studies. Vaccine therapy is another exciting area of research, and clinical trials are ongoing in both metastatic melanoma and as adjuvant therapy. A bewildering array of vaccines (whole cell, carbohydrate and peptide) is available, and it remains to be seen which of these numerous preparations will be most effective. Adjuvant therapy trials with a ganglioside GM2 vaccine and others are ongoing. Numerous peptide vaccines are also being investigated for metastatic melanoma, singly and in combination with other immunotherapeutic agents.     

Towards a complete North American Anabaptist genealogy: A systematic approach to merging partially overlapping genealogy resources.

Genetic studies on closed populations benefit from comprehensive, searchable genealogy resources. To support studies of Anabaptists, a computerized database has been developed that merges two large genealogy books, the "Fisher Family History" and the "Amish and Amish Mennonite Genealogies." The former is more current but the latter is more comprehensive for the 18th and 19th centuries. Therefore, the merger of the two books is significantly more useful than either book alone. We demonstrate the utility of the merged database with two results: an increase in inbreeding coefficients and the identification of parent-child relationships that do not exist in either book. Am. J. Med. Genet. 86:156-161, 1999. Published 1999 Wiley-Liss, Inc.     

Timing of surgery for common pediatric surgical conditions

Depending upon various factors the surgical procedures in childhood are divided into three groups—immediate, intermediate and elective. The timing of surgery is probably the most important factor governing the outcome of surgical correction in pediatric surgery. With continuing research and clinical experience our understanding of the various conditions have improved and with that has come a change in the optimum timing of many surgical procedures. This paper highlights the best timing of surgery for some of the commoner pediatric surgical procedures and the reasons behind these so that the children may be referred to pediatric surgeons in time.     

Percutaneous transluminal myocardial revascularisation: current status and future perspectives

Percutaneous transluminal myocardial revascularisation presently appears to be a potential palliative treatment for coronary artery disease, neither controlled with drugs nor amenable to available coronary revascularisation techniques. Ongoing trials will provide answer to short and long term efficacy. Recent developments using angiogenic growth factors appear very promising, and the role of growth factors as an adjunct to percutaneous transmyocardial revascularisation with laser remains to be seen.     

Somatic growth and renal function after unilateral nephrectomy for Wilms' tumor

Solitary kidneys in renal donors and patients who have undergone unilateral nephrectomy for malignant disease have been reported to undergo hyperfiltration injury. This study was undertaken to evaluate the somatic growth and development of followed-up patient after Wilms' tumor to evaluate their renal function and identify any evidence of injury in the remaining kidney. The growth and development of all the children was found to be normal, as was DTPA clearance. Microalbuminuria in 24-h urinary collections was detected in 84% of the patients, indicating evidence of hyperfiltration injury. This study highlights the need for close monitoring of the renal function of long-term follow-up patients after Wilms' tumor in addition to the routine monitoring for tumor recurrence. Accepted: 26 May 1998