Primary vitrectomy without scleral buckling for rhegmatogenous retinal detachment

Background: Pars planta vitrectomy has evolved as an alternative method in the treatment of more complicated rhegmatogenous retinal detachments. We report a series of patients who underwent primary vitrectomy with gas tamponade without the use of additional scleral buckling. Methods: A retrospective study of 53 patients with a follow-up of 6–45 months (mean 17.8 months) was carried out. Preoperative findings included unusual, multiple or large breaks, vitreous haemorrhage, proliferative vitreoretinopathy and bullous retinal detachment. Preoperative visual acuity was between light perception and 1.0, with 30% (16/53) of patients with 0.4 or better. Results: Retinal reattachment was achieved in 64% of cases (34/53) with one and in 92% (49/53) with one or more operations. Final visual acuity was between light perception and 1.0, with 41% (22/53) of patients with 0.4 or better. Cataract formation occurred in 86% (37/43) of all patients with a clear lens preoperatively. Macular pucker was noted in 11 % (6/53) and postoperative proliferative vitreoretinopathy causing redetachment in 6% (3/53). Conclusion: With primary vitrectomy, a high final anatomical success rate with few intraoperative complications can be achieved in more complicated forms of rhegmatogenous retinal detachment. The major drawback of the procedure is the high incidence of post-operative cataract formation.     

Effects of the enantiomers of disopyramide and its major metabolite on the electrophysiological characteristics of the guinea-pig papillary muscle

Summary Disopyramide, a Class la antiarrhythmic drug, is clinically used as a racemic mixture; R(–)disopyramide and S(+)disopyramide. The major metabolite in man is desisopropyldisopyramide: R(–)desisopropyl-disopyramide and S(+)desisopropyldisopyramide. The effects of the four compounds were compared on the electrophysiological characteristics of the guinea-pig papillary muscle using the standard microelectrode technique. At an external K⁺ concentration of 5.4 mmol/l and a stimulation frequency of 1 Hz, S(+)disopyramide (20 mol/l) increased action potential duration (APD) by more than 18%, while it was diminished by 6% in the presence of R(–)disopyramide. Resting membrane potential amounted to –87.1 ± 0.5 mV (n = 14) and –85.6 ± 1.2 mV (n = 10), respectively. Also a small but significant difference in effect on the maximal rate of depolarization was observed, R(–)disopyramide being more potent, related with a slower recovery of the maximal rate of depolarization.The enantiomers of the metabolite appeared to be three times less potent than those of the parent drug in their effect on the maximal rate of depolarization. The characteristics of the enantiomers of the metabolite correlated with those of the parent drug: also the R(–)-enantiomer was more potent in decreasing the maximal rate of depolarization and caused more shortening of the action potential than the S(+)enantiomer.Time constants for onset and recovery of/from rate dependent block of the maximal rate of depolarization were dependent upon the external K⁺ concentration, both for the enantiomers of the parent drug and those of the metabolite. Onset slowed down while recovery accelerated when external K⁺ was increased. Time constants were lower for the metabolite.When stimulation interval was shortened, the effect on the maximal rate of depolarisation increased. Only for the metabolite statistical significant stereoselective differences were observed at all stimulation intervals. The effects on the action potential duration were dependent upon stimulation interval; for all enantiomers the action potential duration tended to be relatively (% of control) higher at short stimulation intervals than at large stimulation intervals. The effect on the maximal rate of depolarization was also voltage dependent, but no significant differences were observed between the enantiomers, for the parent drug as well as for the metabolite. Send offprint requests to N. Verbeke at the above address     

“Real time” measurement of endogenous dopamine release during short trains of pulses in slices of rat neostriatum and nucleus accumbens : role of autoinhibition

Summary Release of endogenous dopamine elicited in slices of rat neostriatum or nucleus accumbens by a single electric pulse or by trains of 4 or 10 pulses was examined using fast cyclic voltammetry.Single electric pulses gave rise to a marked and transient increase in the extracellular concentration of dopamine in the neostriatum (by 0.43 mol/l) and nucleus accumbens (by 0.39 mol/l). The overflow elicited by subsequent pulses delivered at a frequency of 0.2 Hz caused separate but much smaller peaks of dopamine concentration, whereas the overflow elicited by subsequent pulses delivered at 1 Hz caused only a shoulder in the descending limb of the peak due to pulse 1. Four pulses at 5 Hz produced a monophasic response that was higher than the single pulse-evoked peak. Nomifensine 1 mol/l greatly increased and prolonged the evoked overflow of dopamine. In the absence of nomifensine, metoclopramide 0.3 mol/l did not change the response to a single pulse or 4 pulses delivered at 0.2 Hz but increased the response to 4 or 10 pulses at 1 Hz and to 4 pulses at 5 Hz. In the presence of nomifensine, metoclopramide increased the response to a single pulse as well as, to a greater extent, the response to 4 pulses at 0.2 Hz and 4 pulses at 1 Hz. Sulpiride 1 mol/l produced effects similar to those of metoclopramide in the neostriatum in the presence of nomifensine. During trains of pulses at 0.2 or 1 Hz, metoclopramide and sulpiride did not increase (or increased only slightly in the presence of nomifensine) the initial peak that reflected dopamine overflow elicited by pulse 1, but increased greatly the subsequent peaks (0.2 Hz) or the sholder (1 Hz) that reflected the overflow due to the subsequent pulses.The study demonstrates the release of dopamine in the neostriatum and nucleus accumbens with high temporal resolution so that, at least at low frequency, the release elicited by each pulse in a train can be recognized. As previously concluded from experiments with ³H-dopamine, single pulses elicit a large release whereas subsequent pulses delivered at 0.2 to 5 Hz elicit much smaller release. Presynaptic autoinhibition develops immediately after pulse 1 in trains of appropriately spaced pulses. However, it is only partly responsible for the marked fall in release after pulse 1; other, unknown factors contribute to the decline.The experiments were carried out at the Department of Pharmacology, Queen Mary and Westfield College, London, UK, while N.L. was a visiting scientist Send offprint requests to N. Limberger at the above address     

Measurement of cardiac output-transtracheal Doppler versus thermodilution

The ABCOM 1 transtracheal Doppler (TTD) has been developed as a non-invasive cardiac output monitor. With this device, cardiac output is continuously calculated from ascending aortic blood flow velocity and aortic diameter obtained via an ultrasound transducer incorporated into the tip of an endotracheal tube. We evaluated the clinical use of the ABCOM 1 monitor and compared cardiac outputs obtained using the TTD system with simultaneous thermodilution (TD) measurements. We found the operation of the ABCOM 1 monitor to be difficult and time-consuming. In our operating rooms, acceptable Doppler signal quality was difficult to obtain. There was no correlation between 36 simultaneously obtained TTD and TD cardiac output measurements. The average difference between measurement techniques and the limits of agreement were unacceptably large (mean difference = 3.04 L.min-1, mean +/- 2 SD = -6.04 to 12.48 L.min-1). Separately analyzing only those measurements during which Doppler signal quality was adequate did not improve agreement between TTD and TD measurements. On the basis of these findings, TTD cannot be recommended as a clinical cardiac output measurement technique.     

Changes in Intestinal Transit Time after Proctocolectomy Assessed by the Lactulose Breath Test

After proctocolectomy with ileal pouch-anal anastomosis (IPAA) patients have increased stool frequency and intermittently use antidiarrheal medication. In addition to other factors, gastrointestinal transit time (MTT) could influence stool frequency. The aim of this study was to investigate how MTT changes after IPAA and to study whether MTT has an influence on daily stool frequency. In a prospective trial MTT was investigated with the lactulose breath test in 12 patients undergoing surgery for chronic ulcerative colitis (CUC) or familial adenomatous polyposis coli (FAPC) at different stages: before proctocolectomy, after IPAA with loop ileostomy, and 3 months and 1 year after ileostomy closure. MTT was also measured in 12 patients with IPAA, 12 patients with subtotal colectomy and ileorectal anastomosis (IRA), and 8 patients with conventional proctocolectomy and Brooke ileostomy (CPC) several years after surgery. Twelve healthy volunteers served as controls. Before IPAA, MTT was prolonged in CUC versus FAPC and controls. After restoration of gut continuity MTT was markedly accelerated. After 1 year MTT was slowed again, though values before proctocolectomy and those in controls were not reached. Several years after surgery MTT was significantly prolonged in IPAA and IRA versus controls. In CPC, MTT could not be determined by lactulose breath test. Stool frequency showed an inverse correlation to MTT in IPAA. In conclusion, this study shows that orocecal and oropouch transit are accelerated in the early postoperative period after (procto)colectomy but prolonged in the long-term course. Adaptation of the small bowel takes longer than 1 year. Impairment of stool frequency may be partly due to this adaptation.     

Preoperative Evaluation of Pancreatic Masses with Positron Emission Tomography Using 18F-fluorodeoxyglucose: Diagnostic Limitations

Identification of pancreatic cancer in patients presenting with an enlarged pancreatic mass is a major diagnostic problem. Positron emission tomography (PET) using the radiolabeled glucose analogue ¹⁸F-fluorodeoxyglucose (FDG) has been suggested to provide excellent accuracy for noninvasive determination of suspicious pancreatic masses. We conducted a prospective study to verify these results. Forty-two patients admitted for pancreatic surgery underwent PET scanning. Image analysis was based on visual film evaluation and quantification of regional tracer uptake. PET imaging was visually analyzed by three observers blinded for the results of other diagnostic tests; they qualitatively graded the scans using a five-point scale (I = low to V = high) for the presence and intensity of focal FDG uptake. Diagnosis was proven by histology (n= 38) or follow-up (n= 4). Furthermore, the results of PET were compared with helical computed tomography (CT) and conventional ultrasonography (US), done during the routine diagnostic workup before pancreatic cancer surgery. Regarding only the results with scores of IV and V as positive for representing definite malignancy yielded a sensitivity of 71% and a specificity of 64% for film reading. Quantification of regional tracer uptake contributed no significant diagnostic advantage for differentiation between benign and malignant tumors. Helical CT revealed a sensitivity of 74% and a specificity of 45.5% and abdominal US 56% and 50%, respectively. We concluded that PET imaging provides only fair diagnostic accuracy (69%) for characterizing enlarged pancreatic masses. PET does not allow exclusion of malignant tumors. In doubtful cases, the method must be combined with other imaging modalities, such as helical CT. The results indicate that the number of invasive procedures is not significantly reduced by PET imaging.     

Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor.

PURPOSE: To investigate the safety and tolerability and to explore the pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with solid tumors that express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR-positive, solid malignancies that were not amenable to any established chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without routine premedication until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated with EMD72000 at five different dose levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria grade 3 headache and fever occurring after the first infusion were dose limiting at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe side effects, especially no allergic reactions or diarrhea, were observed. Acneiform skin reaction was the most common toxicity, but it was mild, with grade 1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic analyses demonstrated a predictable pharmacokinetic profile for EMD72000. Pharmacodynamic studies on serial skin biopsies revealed that EMD72000 effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding patients received treatment for up to 18 months without cumulative toxicity. CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at the investigated doses significantly inhibited downstream EGFR-dependent processes.     

Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial.

PURPOSE: We analyzed the benefits of a risk-adapted postremission strategy in adult lymphoblastic leukemia (ALL), and re-evaluated stem-cell transplantation (SCT) for high-risk ALL. PATIENTS AND METHODS: A total of 922 adult patients entered onto the trial according to risk groups: standard-risk ALL (group 1), high-risk ALL (group 2), Philadelphia chromosome-positive ALL (group 3), and CNS-positive ALL (group 4). All received a standard four-drug/4-week induction course. Patients from group 1 who achieved a complete remission (CR) after one course of induction therapy were randomly assigned between intensive and less intensive postremission chemotherapy, whereas those who achieved CR after salvage therapy were then included in group 2. Patients in groups 2, 3, and 4 with an HLA-identical sibling were assigned to allogeneic SCT. In groups 3 and 4, autologous SCT was offered to all other patients, whereas in group 2 they were randomly assigned between chemotherapy and autologous SCT. RESULTS: Overall, 771 patients achieved CR (84%). Median disease-free survival (DFS) was 17.5 months, with 3-year DFS at 37%. In group 1, the 3-year DFS rate was 41%, with no difference between arms of postremission randomization. In groups 2 and 4, the 3-year DFS rates were 38% and 44%, respectively. In group 2, autologous SCT and chemotherapy resulted in comparable median DFS. Patients with an HLA-matched sibling (groups 2 and 4) had improved DFS. Three-year DFS was 24% in group 3. CONCLUSION: Allogeneic SCT improved DFS in high-risk ALL in the first CR. Autologous SCT did not confer a significant benefit over chemotherapy for high-risk ALL.     

Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group.

PURPOSE: To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. PATIENTS AND METHODS: Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. RESULTS: Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. CONCLUSION: An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis.