Intraocular silicone lenses in silicone oil: an experimental study

Background: To evaluate a potential effect of silicone oil on flexible silicone intraocular lenses, four lenses (STAAR AA-4203) were stored in silicone oil under sterile conditions for periods between 1 month and 3 years. Method: The edge and surface of the lenses were examined by scanning electron micrography and the findings compared with a lens of the same model which had been stored in Ringer's solution for 2 years. Results: After 1 year of silicone oil exposure, droplets of different sizes adherent to the surface of the lens were found. These changes proceeded to a wave-like appearance of the surface after 2 and 3 years of storage, so that a continuous layer of silicone oil polymers is probably covering the intraocular lens. Conclusion: Optical interference has to be considered a possibility if it turns out that the droplets cannot be removed during silicone oil evacuation. Consequently silicone intraocular lenses without hydrophilic preparation of the surface should not be implanted in eyes undergoing combined anterior and posterior segment surgery with silicone oil tamponade or in eyes with high risk for vitreoretinal complications.The authors state that they have no proprietary interest in the marketing of the products mentioned herein or competing products     

In Vitro and In Vivo Activity of 16,17-dehydro-epipregnanolones: 17,20-Bond Torsional Energy Analysis and D-ring Conformation

Purpose. Certain neuroactive pregnane steroids (also known as “epalons”) are allosteric modulators of the GABA_A receptor and have been shown to be potent anticonvulsants, anxiolytics, sedative/hypnotics, and anesthetic agents. The purpose of this study was to calculate the structural consequences of introduction of a double bond in the 16,17-position and to determine if this modification would selectively reduce sedative activity, but maintain the potent anticonvulsant activity of neuroactive steroids. Methods. We have studied the biochemical and behavioral effects of introducing a 16,17 double bond into the naturally occurring neuroactive steroids, 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) and 3α-hydroxy-5β-pregnan-20-one (3α,5β-P) and three synthetic neuroactive steroid derivatives, 3α-hydroxy-3β-methyl-5α-pregnan-20-one (3α,3βMe,5α-P), 3α-hydroxy-5α-androstane (3α,5α-A), and alphaxalone (3α,5α-11-one-P). Results. The 16-ene analogs of most of these neuroactive steroids were found to be 7- and 16-fold less potent in inhibiting [³⁵S]TBPS binding to GABA_A receptors and in a similar fashion, had reduced anticonvulsant and sedative potency in proportional amounts. The exception was the androstane (3α,5α-A) without a 17-acetyl group, that had virtually identical IC₅₀ and ED₅₀ values for the saturated and unsaturated derivatives. Calculation of the torsional energy profile for each of the 17-acetyl side chain conformations showed that the conformational energy minima found in the α,β-unsaturated keto systems, produce an orientation of the 20-keto group that is rotated by 165 degrees when compared to the non-conjugated acetyl group (determined by X-ray crystallography and its minimum energy conformation). Conclusions. The modified orientation of the 20-keto group of neuroactive steroids containing a 16-ene, provides an explanation for their decreased biological activity overall, but did not lead to an enhanced protective index.     

Radiation doses of yttrium-90 citrate and yttrium-90 EDTMP as determined via analogous yttrium-86 complexes and positron emission tomography

Yttrium-90 is used for palliative therapy for the treatment of skeletal metastases, but because it is a pure - emitter, data on the pharmacokinetics and radiation doses to metastases and unaffected organs are lacking. To obtain such data, the present study employed yttrium-86 as a substitute for⁹⁰Y, with detection by positron emission tomography (PET). The study compared the properties of two different⁸⁶Y complexes —⁸⁶y-citrate and⁸⁶Y -ethylene diamine tetramethylene phosphonate (EDTMP) — in ten patients with prostatic cancer who had developed multiple bone metastases (the ten patients being divided into two groups of five). Early dynamics were measured up to 1 h post injection (p.i.) over the liver region, followed by subsequent whole-body PET scans up to 3 days p.i. Absolute uptake data were determined for normal bone, bone metastases, liver and kidney. Radiation doses were calculated according to the MIRD recommendations. Based on the pharmacokinetic measurements of the distribution of the⁸⁶Y complexes, it was possible to calculate radiation doses for the bone metastases and the red bone marrow delivered by complexes containing⁹⁰Y. In 1 cm³ of bone metastasis, doses of 26±11 mGy/MBq and 18±2 mGy/MBq were determined per MBq of injected⁹⁰Y- citrate and⁹⁰Y- EDTMP, respectively. The doses to the bone marrow were 2.5±0.4 mGy/MBq for⁹⁰Y- citrate and 1.8±0.6 mGy/MBq for⁹⁰Y-EDTMP.⁸⁶Y and PET provide quantitative information applicable to the clinical use of⁹⁰Y. This method may also be useful for the design of other⁹⁰Y radiopharmaceuticals and for planning radiotherapy dosages.     

Die lokalisierte Form einer sympathischen Reflexdystrophie

Introduction

The reflex sympathetic dystrophy (RSD) syndrome usually shows a distally generalized distribution pattern of symptoms. Here we report a case with a distally localized form of RSD.

Patient and methods

In a 53-year-old woman, following a local lesion in the nail bed of the left thumb, a neuroma developed at the side of the lesion during the next half year. She was finally operated upon. Following that intervention, a complex and painful clinical syndrome occurred that for the most part affected only the thumb. A clinical neurological examination was carried out, including distal suprasystolic compression of the affected extremity after bandaging it (the so-called ischemia test). For diagnostic and therapeutic reasons, afterwards a conventional blockade of the ipsilateral stellate ganglion was applied.

Results

The clinical investigation showed a triad of autonomic (swelling, side difference of skin temperature, hyperhydrosis), motor (reduced movement ability, tremor) and sensory disturbances (spontaneous pain, allodynia), which nearly exclusively affected the entire left thumb. The spontaneous pain showed an orthostatic component (the pain being diminished or exaggerated when the extremity was elevated or lowered, respectively) and was suppressed by the ischemia test. Following the sympathetic block, all symptoms disappeared within one day (follow-up period: 5 months).

Conclusion

In contrast to the common clinical picture of RSD, with a distally generalized distribution of symptoms, the present case showed a so-called localized form of RSD, its triad affecting only the thumb with the lesion. Typically, the pain showed an orthostatic component and was suppressed by the ischemia test. The sympathetic block was immediately successful, proving the occurrence of this form of RSD for the first time. In similar clinical cases, this form of RSD should be considered as a differential diagnosis.     

Fish oil treatment and apolipoprotein(a).

Two recent reports showed a lowering of elevated lipoprotein(a) levels upon treatment with fish oil. The aim of this paper was to confirm this finding and to establish a dose-effect relationship. A double blind, placebo controlled cross-over study was carried out in 48 subjects with apolipoprotein(a) ("Apo(a)") values between 34 and 1062 U/l (median 387 U/l). The subjects were divided into 3 groups receiving 3.5, 7.1 and 10.6 g omega-3 fatty acids/day during 28 days. Parameters measured were blood levels of eicosapentaenoic acid ("EPA"), Apo(a) and fasting blood lipids. EPA levels rose in the three dosage groups by factors 7, 9 and 14, respectively, if compared to values upon placebo. Triglycerides were significantly lowered in a dose depending manner. Apo(a), however, was not changed. This held true for different baseline Apo(a) values and different fish oil dosages. It is concluded that fish oil treatment during 4 weeks cannot lower elevated Apo(a) levels.     

G protein-mediated receptor-receptor interaction: studies with chemotactic receptors in membranes of human leukemia (HL 60) cells

Summary Differentiated human leukemia (HL 60) cells contain high numbers of receptors for the chemotactic factors, N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) and complement component 5a (C5a), both coupled to pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins). Agonist activation of either receptor stimulated binding of the GTP analog, guanosine 5-[-thio]triphosphate (GTP[S]), to membrane G proteins and by a similar extent in a non-additive manner. The possible interaction of the two receptors was studied by measuring agonist binding to one receptor in the presence of the other receptor agonist. fMet-Leu-Phe and C5a had no effects on [¹²⁵I]C5a and fMet-Leu-[³H]Phe receptor binding, respectively, when studied in the absence of regulatory ligands. Similarly, the inhibitory effects of NaCl and GDP on agonist receptor binding were not altered in the presence of the other receptor agonist. In contrast, in the presence of the GTP analogs, GTP[S] and guanosine 5-[,-imino] triphosphate, fMet-Leu-Phe and C5a reduced the binding of [¹²⁵I]C5a and fMet-Leu-[³H]Phe, respectively, in a concentration-dependent manner. The potencies of the GTP analogs to inhibit binding of [¹²⁵I]C5a and fMet-Leu-[³H]Phe was increased about 3-fold by fMet-Leu-Phe and C5a, respectively. The data presented suggest that fMet-Leu-Phe and C5a receptors share the same G protein pool in membranes of HL 60 cells and that activation of these G proteins by one of the two receptors decreases the availability of G proteins for the other receptor. Correspondence to T. Wieland at the above address     

The combined treatment of preimplantation mouse embryos in vitro with cadmium (CdSO4, CdF2) and X-rays

The influence of cadmium (up to 10^?4 M), fluoride (up to 10^?4 M), and X-rays (up to 18.8 Gy) on different variables of preimplantation mouse embryos in vitro has been examined. The agents were applied either singly or in combination (0.94 Gy X-rays +3×10^?7 M CdSO₄ or CdF₂; 0.94 Gy X-rays +3×10^?6 M CdSO₄ or CdF₂). The following variables were determined:

1. the microscopic visible development until 144 h post conceptionem (=144 h p.c.),
2. the average cell numbers (48 h p.c., 56 h p.c., 72 h p.c., 96 h p.c., 120 h p.c., 144 h p.c.),
3. the number of micronuclei (72 h p.c.),
4. the distribution of cell nuclei within the cell cycle (72 h p.c.).

Nearly all results of the combination experiments correspond to the sum of the single effects. Only two values (out of about 40) significantly exceed the value obtained after addition of the single effects; both values lie within the envelope of additivity.     

Characterization of human lymphocyte antigen class I antigen-processing machinery defects in renal cell carcinoma lesions with special emphasis on transporter-associated with antigen-processing down-regulation.

The HLA class I antigen-processing machinery (APM) plays a crucial role in the generation of peptides from endogenously synthesized proteins and in their presentation to cytotoxic T lymphocytes. The potential role of defects of APM components in immune escape mechanisms used by malignant cells has prompted us to analyze their expression in renal cell carcinoma (RCC) lesions with special emphasis on TAP because of its critical role in the loading of HLA class I antigens with peptides. Immunohistochemical staining of 51 formalin-fixed RCC lesions and autologous normal renal epithelium detected transporter associated with antigen processing (TAP)1 and tapasin deficiencies in 63 and 80% of the tumor lesions. Impaired low molecular weight protein (LMP)2 and LMP7 expression was found in 73 and 33% of the RCC lesions analyzed, respectively. In contrast to the high frequency of APM component down-regulation, HLA class I heavy chain and beta(2)-microglobulin defects were detected in only 12 and 10% of the lesions, respectively. Concomitant TAP1 and LMP2 deficiencies were found in approximately 57% of RCC lesions, whereas a coordinated down-regulation of all APM components occurred only in 5% of the tumor specimens analyzed. The presence of APM defects was independent of tumor stage and grade but varied significantly among the RCC subtypes. TAP abnormalities do not appear to be attributable to structural alterations because no mutations in TAP1 were detected in TAP1-deficient RCC lesions. These data suggest that TAP defects in RCC lesions are caused by regulatory abnormalities. Therefore, T-cell-based immunotherapy may benefit from the administration of cytokines that up-regulate TAP expression.     

Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.