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.     

Efficacy of ornithine-alpha-ketoglutarate (OKGA) as a dietary supplement in growing rats

New substrates of potential benefit to critically ill patients receiving traditional nutritional support have been suggested to meet organ or tissue specific needs. The addition of an anabolic stimulus during nutritional support therefore appears to be a reasonable adjunct to augment protein synthesis. The purpose of this investigation was to evaluate the efficacy of the neutral salt ornithine alphaketoglutarate (OKGA) as a dietary supplement to promote growth in young rats by enhancing protein metabolism. A group of 16 male Sprague-Dawley rats (150-170g) were housed in individual metabolic cages and after dark-light cycle adaptation were fed ad libitum an oral liquid diet for 7 days. Half of the animals were given the control diet and the other half was fed a test diet. This isonitrogenous test diet contained the control diet with 2.3% of nitrogen (N) replaced by N from OKGA. Daily weight, food intake and urinary excretions of N, creatinine, urea, orotic acid, polyamines and amino-acids were determined. At the end of 7 days of free-feeding, the rats were sacrificed and blood was collected for free amino-acids. Rats fed the OKGA supplemented diet consumed 16% more diet, retained 11% more nitrogen and gained 15% more weight. The accelerated protein metabolism is reflected in the changes in plasma and urinary free amino-acid levels. Enhanced protein anabolism is evident from the increased urinary excretion of polyamines in the OKGA fed rats. The increased ratio of urinary urea N to total N and the decreased orotic acid excretion in OKGA fed rats suggests thata NH(4)(+) was efficiently diverted through urea cycle. It is concluded that in growing rats, supplementing isonitrogenous diet with OKGA significantly stimulates food intake compared to controls. This results in better weight gain and improvement in protein metabolism.     

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.     

Stimulation of bone formation in vivo by phosphate supplementation

The effect of phosphate supplementation on bone remodeling was assessed in six mature, healthy beagle dogs. The phosphate supplement was given in divided doses orally, daily for 12 weeks in the form of a neutral potassium phosphate preparation. The dose averaged 108 mg P/kg per day, which is double the normal canine phosphorus intake. Bone remodeling was assessed by measurement, at sacrifice, of areas of cortical bone containing different colorcoded tetracyclines which had been continuously administered during 12-week control and treatment periods; remodeling was assessed kinetically during the control and treatment periods by replicate studies employing⁴⁷Ca intravenously.Both techniques demonstrated that the principal effect of phosphate supplementation was a significant stimulation of bone formation. Within cortical bone, formation was doubled, from an average of 2.7% to 5.3% per year. The major location of new bone deposits was endosteal. Whole skeletal mineral accretion, measured kinetically, increased 45% above an average control value of 0.154 g/day. These studies suggest that, in the adult dog, normal plasma phosphate levels are suboptimal for new bone formation.Even with this short duration of administration, phosphate produced microscopic calcification of the renal parenchyma. However, there was no biochemical evidence of renal functional impairment.     

Patterns of substance use among patients in an urban psychiatric emergency service

Data from patients visiting an urban psychiatric emergency service in California were examined to document incidence and patterns of substance use and ethnic differences among users. A total of 392 patients were randomly assigned to receive a drug screen (N = 198) or to receive usual care (N = 194). Forty-four percent of the mandatorily screened patients had positive screens for any substances: 37 percent were positive for any drugs, and 7 percent were positive for alcohol only. Cocaine was present in 62 percent of the drug-positive screens. Blacks were two and a half times more likely than whites to have positive screens for drugs and five times more likely to have positive screens for cocaine.     

A chimeric opioid peptide with mixed μ agonist/δ antagonist properties

Abstract: There is evidence to indicate that opioid compounds with mixed μ agonist/δ antagonist properties are analgesics with low propensity to produce tolerance and physical dependence. A chimeric peptide containing the potent and selective μ agonist H‐Dmt‐D‐Arg‐Phe‐Lys‐NH₂ ([Dmt¹]DALDA) (Dmt = 2′,6′‐dimethyltyrosine) and the potent and selective δ antagonist H‐Tyr‐TicΨ[CH₂‐NH]Cha‐Phe‐OH (TICP[Ψ]) (Cha = cyclohexylalanine), connected ‘tail‐to‐tail’ via a short linker, was synthesized using a combination of solid‐phase and solution techniques. The resulting peptide, H‐Dmt→D‐Arg→Phe→Lys‐NH‐CH₂‐CH₂‐NH‐Phe←Cha[NH‐CH₂]ΨTic←Tyr‐H, showed the expected μ agonist/δ antagonist profile in the guinea‐pig ileum and mouse vas deferens assays. Its μ and δ receptor binding affinities were in the low nanomolar range, as determined in rat brain membrane binding assays.     

Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2.

PURPOSE: Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P =.64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received > or = 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect. CONCLUSION: Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials.     

Solid tumors in patients treated for Hodgkin's disease: a report from the German Hodgkin Lymphoma Study Group.

BACKGROUND: Long-term survivors of successfully treated Hodgkin's disease (HD) are at risk for late complications. Among these, secondary solid tumors are most serious because they are often fatal. The aim of this retrospective analysis was to assess the incidence, relative risk and risk factors of secondary solid tumors in HD patients registered in the database of the German Hodgkin Lymphoma Study Group (GHSG). PATIENTS AND METHODS: From 1983 to 1998, the GHSG conducted three generations of clinical trials for early, intermediate and advanced stage HD (HD1-HD9) involving a total of 5367 patients. Data on incidence, risk factors and relative risk were updated in March 2003. RESULTS: A total of 127 patients with secondary solid tumors were identified. Among these, lung cancer (23.6%), colorectal cancer (20.5%) and breast cancer (10.2%) were the most frequent. After a median follow-up of 72 months the cumulative risk of developing a solid tumor was 2%, with an overall relative risk (RR) of 2.4 (lung cancer, 3.8; colorectal cancer, 3.2; breast cancer, 1.9). For most patients (n=67; 52.8%) developing a secondary solid tumor, treatment modality consisted of chemotherapy combined with radiotherapy in extended field technique (RR = 3.3). CONCLUSIONS: With a median follow-up of 72 months, there were 127 patients developing solid tumors out of a total of 5367 HD patients treated in the GHSG studies HD1-HD9. The cumulative risk of 2% is expected to increase over time due to the rather short median observation time and slow progression of solid malignancies.     

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.