A new instrument for drainage or injection of fluid within subretinal space

PURPOSE: To describe a new instrument, the subretinal aspiration and injection device (SR-AID), designed to facilitate the controlled external drainage or injection of fluid in the subretinal space. METHODS: The SR-AID is formed by an assembly of a probe, handle body, and a driving unit. The curved conduit within the probe segment forms a curved tunnel and acts as a guide along which a needle moves back and forth. The feasibility of fluid injection beneath the attached retina was tested in animal eyes. The efficacy of subretinal fluid drainage with the SR-AID were assessed in six cases of clinical retinal detachment. RESULTS: External approach to the subretinal space under ophthalmoscopic monitoring can be achieved by oblique angle penetration of the scleral wall with a needle from the SR-AID. Fluid was injected successfully into the subretinal space in three of six rabbit eyes and in two of two pig eyes. The mean duration required for the drainage of subretinal fluid with the SR-AID was 127 seconds. There was no incidence of significant subretinal hemorrhage or retinal perforation in the animal experiments and in human cases. CONCLUSION: Our case series suggests that the SR-AID provides an efficient and safe means of access to the subretinal space.     

Plasma stability of two glycosyl indolocarbazole antitumor agents

In recent years, several glycosyl indolocarbazole derivatives have been developed as antitumor agents targeting the topoisomerase I-DNA complex and a few of them were evaluated in clinical trials. The lead drug in the series is compound A which bears a formylamino substituent on the N-imide F-ring. This compound has shown promising antitumor activities in vivo and was tested clinically but it has been recently replaced with a more active analogue, J-107088, bearing a (hydroxymethyl-2-hydroxy) ethylamino substituent on the N-imide F-ring. We have compared the plasma stability of two molecules in this series, compounds A and D, which only differ by the nature of the group on the imide ring. The conversion of the compounds into the anhydride species B was studied by HPLC and the resulting metabolite, formed both in human plasma ultrafiltrate and in water, was characterized by NMR and mass spectrometry. Absorption measurements provided a facile method to follow the conversion of compounds A and D into their metabolite product B. Altogether, the experimental data demonstrate that the replacement of the NHCHO substituent of compound A with a hydrophilic NHCH(CH(2)OH)(2) chain preserves the intact imide function that is known to be essential for topoisomerase I inhibition and cytotoxicity. The transformation of compound A into the anhydride metabolite B (or its diacid open form) occurs much more slowly compared to compound D. Half-life parameter t(1/2) of 67 and 245 min(-1) were calculated for compounds A and D, respectively. A molecular modeling analysis, performed to compare the conformation and electronic properties of compounds A and D, offers a rational explanation for the gain of chemical stability of the indolocarbazole derivative D. The data provide important information for the rational design of antitumor indolocarbazole derivatives.     

Polymorphism of the insulin gene is associated with increased prostate cancer risk

High insulin levels are linked with increased cancer risk, including prostate cancer. We examined the associations between prostate cancer with polymorphisms of the insulin gene (INS) and its neighbouring genes, tyrosine-hydroxylase and IGF-II (TH and IGF2). In this study, 126 case-control pairs matched on age, race, and countries of origin were genotyped for +1127 INS-PstI in INS, -4217 TH-PstI in TH, and +3580 IGF2-MspI in IGF2. The homozygous CC genotype of +1127 INS-PstI occurred in over 60% of the population. It was associated with an increased risk of prostate cancer in nondiabetic Blacks and Caucasians (OR=3.14, P=0.008). The CC genotype was also associated with a low Gleason score <7 (OR=2.60, P=0.022) and a late age of diagnosis (OR=2.10, P=0.046). Markers in the neighbouring genes of INS showed only null to modest associations with prostate cancer. The polymorphism of INS may play a role in the aetiology of prostate cancer. Given the high prevalence of the CC genotype and its association with late age of onset of low-grade tumours, this polymorphism may contribute to the unique characteristics of prostate cancer, namely a high prevalence of indolent cancers and the dramatic increase in incidence with age.     

Use of erythropoietin in patients with multiple myeloma

The prevalence of tumour anaemia in patients with multiple myeloma is greater than 80%. At the time of diagnosis 20% of these patients are already anaemic. In about 70% of patients with multiple myeloma, recombinant human erythropoietin (r-HuEPO) leads to a reduction in transfusion frequency, resulting in a drop in transfusion- related side-effects like infections and immune reactions, iron overload and hyperviscosity which often negatively influence the course of disease. A further reason for the use of erythropoietin is to achieve and maintain high haemoglobin levels (11-12 g/dl), which are of considerable prognostic significance in patients with multiple myeloma. Increasing Hb levels with r-HuEPO also improve the quality of life of patients, thus leading to better therapy compliance. The trade-off between high costs of an erythropoietin treatment and lower indirect costs (infusion material, personal equipment, patient transport costs, etc.) should be evaluated. Nevertheless, an exact definition of patients for whom the use of erythropoietin is beneficial is warranted. The pathogenesis of anaemia and the clinical experiences of erythropoietin in patients with multiple myeloma are discussed.     

Moscatilin from the orchid Dendrobrium loddigesii is a potential anticancer agent

The Dendrobrium species have been commonly used in traditional Chinese medicine as a tonic to nourish the stomach, replenish body fluid, and reduce fever. However, their application as possible therapeutic agents for the treatment of cancers has not been examined. In this study, we want to examine the efficacy of using moscatilin, a natural antiplatelet agent extracted from the stems of Dendrobrium loddigesii, as an anticancer agent. Our results have shown that moscatilin exerts potent cytotoxic effect against cancer cell lines derived from different tissue origins, including those from the placenta, stomach, and lung, but not those from the liver. In addition, we have found that the mechanism of action of moscatilin may be related to its ability to induce a G2 phase arrest in responsive cells. However, unlike some G2 arresting agents, moscatilin has no detectable inhibitory effect on cyclin B-cdc-2 kinase activity. Thus, the precise nature of its cytotoxic mechanism remains to be determined. Our results in this study imply that moscatilin is potentially efficacious for chemoprevention and/or chemotherapy against some types of cancer.     

Detection of recurrent or residual nasopharyngeal carcinomas after radiotherapy with technetium-99m tetrofosmin single photon emission computed tomography and comparison with computed tomography--a preliminary study

The effectiveness of technetium-99m tetrofosmin (Tc-TF) single photon emission computed tomography (SPECT) of the head and neck for detecting recurrence of nasopharyngeal carcinomas (NPC) was evaluated and compared with computed tomography (CT). Both Tc-TF SPECT and CT of the head and neck were performed in 36 NPC patients 4 months after radiotherapy. All 36 then underwent histopathological examinations of nasopharyngeal biopsies. Based on the histopathological results, the sensitivity, specificity, and accuracy of visually interpreted Tc-TF SPECT images, to differentiation of recurrent NPC from benign lesions, were 64%, 96%, and 86%, respectively. The sensitivity, specificity, and accuracy of CT for detecting recurrent NPC were 73%, 88%, and 83%, respectively. The Tc-TF SPECT has a better specificity but a lower sensitivity to differentiate benign lesions and recurrent/residual NPC when compared with CT. Combined Tc-TF SPECT and CT sensitivity and specificity were 100% and 88%, respectively. There are much better either test alone. However, further studies, including a larger NPC patient population, are warranted to determine the exact role and clinical usefulness of Tc-TF SPECT to differentiate benign lesions and recurrent/residual NPC.     

Role of metastasectomy in the management of thyroid carcinoma: the NIH experience

BACKGROUND AND OBJECTIVES: We studied the impact of metatasectomy on disease outcome in 29 advanced nonmedullary thyroid carcinoma (ThyrCa) patients who were operated on between 1969 and 2001 at NIH to further define its role in the management of this malignancy. METHODS: Data were extracted by retrospective chart review. A Kaplan-Meyer survival curve was constructed, and comparative stratification for various parameters was performed. RESULTS: During 47 surgeries, the following lesions were resected from mid-mediastinum/hila, 17; lung parenchyma, 12; skeleton, 14; kidneys, 2; and brain, 2. All patients received multiple radioiodine (RAI) treatments. External-beam radiotherapy, chemotherapy and other palliative measures were used in selected patients. Six patients (21%) died within 74.7 +/- 54.7 months after the first distant metastasectomy. The outcome of the remaining patients was as follows: complete remission, 3; partial remission, 10; and 10: progressive disease, 10, with a follow-up of 175 patient-years. Metastasectomy led to a decrease of 38% in thyroglobulin levels in 23 patients. Cumulative survival rates were 78.5 +/- 8.4% at 5 years and 50.2 +/- 12.5% at 10 years (mean +/-SEM) after initial distant metastasectomy. CONCLUSIONS: Our data show that extensive targeted metastasectomy in the setting of a tertiary center can be beneficial to patients with disseminated ThyrCa with persistent or recurrent distant disease, when used in conjunction with nonsurgical treatment modalities.