Enhancement of spontaneous fibrinolytic activity in diabetic retinopathy.

The fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.     

Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2

Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. USH is clinically and genetically heterogeneous with at least 11 chromosomal loci assigned to the three USH types (USH1A-G, USH2A-C, USH3A). Although the different USH types exhibit almost the same phenotype in human, the identified USH genes encode for proteins which belong to very different protein classes and families. We and others recently reported that the scaffold protein harmonin (USH1C-gene product) integrates all identified USH1 molecules in a USH1-protein network. Here, we investigated the relationship between the USH2 molecules and this USH1-protein network. We show a molecular interaction between the scaffold protein harmonin (USH1C) and the USH2A protein, VLGR1 (USH2C) and the candidate for USH2B, NBC3. We pinpoint these interactions to interactions between the PDZ1 domain of harmonin and the PDZ-binding motifs at the C-termini of the USH2 proteins and NBC3. We demonstrate that USH2A, VLGR1 and NBC3 are co-expressed with the USH1-protein harmonin in the synaptic terminals of both retinal photoreceptors and inner ear hair cells. In hair cells, these USH proteins are also localized in the signal uptaking stereocilia. Our data indicate that the USH2 proteins and NBC3 are further partners in the supramolecular USH-protein network in the retina and inner ear which shed new light on the function of USH2 proteins and the entire USH-protein network. These findings provide first evidence for a molecular linkage between the pathophysiology in USH1 and USH2. The organization of USH molecules in a mutual 'interactome' related to the disease can explain the common phenotype in USH.     

Problems of priority change in kidney allocation and beyond

Standardized and transparent priority setting in medicine, desirable as it is, will generally exacerbate inter-temporal equity problems arising from changes in treatment priorities: when can it be fair that the treatment of already waiting patients who would have had priority under an established system should be postponed (withheld) for an extended period of time to advance the treatment of others under a reformed system? The reform of the Eurotransplant system of priority setting in kidney allocation (ETKAS), which is in many respects ideal, is a case in point. To give due weight to new medical knowledge, waiting time after the onset of end state renal failure should change from a priority-enhancing to a priority-reducing factor. Since those who have gained in priority by waiting under the present system would be set back under the new, severe problems of transitional justice must be overcome when responding to advances in medical knowledge. The paper explores conceptually some possible ways of rule change and indicates their general relevance from an ethical and a practical point of view for future problems of medical resource allocation under transparent, standardized priority-setting rules.     

Are patient-reported outcome measures biased by method of follow-up? Evaluating paper-based and digital follow-up after lumbar fusion surgery

Background Context

Long-term follow-up of patient-reported outcome measures (PROM) is essential in both modern spinal care and research. Lack of time and staff are commonly reported barriers to implementing long-term follow-up of PROM. Automated and digital follow-up systems for PROM collection are seeing widespread use, yet their validity and comparative effectiveness have never been evaluated.

Radio-frequency tumor ablation: internally cooled electrode versus saline-enhanced technique in an aggressive rabbit tumor model

PURPOSE: To compare two methods of radio-frequency (RF) ablation, saline enhancement technique and internally cooled electrodes, for the treatment of small breast cancers in an animal model--highly aggressive VX2 rabbit tumors surrounded by adipose tissue. MATERIALS AND METHODS: Twenty-seven tumors were implanted into retroperitoneal fat of 14 New Zealand White rabbits. RF ablation was performed with ultrasonographic (US) guidance after tumors had grown to 15 mm. Fourteen tumors in seven animals were treated with internally cooled electrodes (30-mm-tip single electrode, 60 W, 10 min); 13 tumors in seven animals, with saline enhancement (0.5 mL/min of saline, 25-mm tip, 30 W, 10 min). Autopsy and histopathologic assessment were performed 3 weeks after therapy. RESULTS: Real-time US of RF ablation was not possible with either method because of obscuration by the increasing hyperechogenicity of the tumor and the surrounding adipose tissue. Equivalent efficacy was demonstrated with the two methods. Significantly greater complications were observed with the saline technique: Free retroperitoneal fluid was detected in one of seven animals with internally cooled electrodes and in all seven animals with saline enhancement (P <.01). Damage to remote structures such as the kidney, spine muscle, and skin was observed at autopsy in one of seven animals with internally cooled technique versus five of seven with saline enhancement (P <.01). CONCLUSION: Given a lower complication rate and similar treatment efficacy in an animal tumor model, internally cooled RF electrode may be advantageous to adjuvant saline infusion for the minimally invasive treatment of breast tumors.     

Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia for Elective Cesarean Delivery

Background: Hypotension due to vasodilation during subarachnoid block (SAB) for elective cesarean delivery may be harmful. Heart rate variability (HRV), reflecting autonomic control, may identify patients at risk of hypotension.

Methods: Retrospectively, HRV was analyzed in 41 patients who were classified into one of three groups depending on the decrease in systolic blood pressure (SBP): mild (SBP > 100 mmHg), moderate (100 > SBP > 80 mmHg), or severe (SBP < 80 mmHg). Prospectively, HRV and hemodynamic data of 19 patients were studied. Relative low frequency (LF), relative high frequency (HF), and LF/HF ratio were analyzed.

Results: Retrospective analysis of HRV showed a significantly higher sympathetic and lower parasympathetic drive in the groups with moderate and severe compared with mild hypotension before SAB (median, 25th/75th percentiles): LF/HF: mild: 1.2 (0.9/1.8), moderate: 2.8 (1.8/4.6), P < 0.05 versus mild; severe: 2.7 (2.0/3.5), P < 0.05 versus mild. Results were confirmed by findings of LF and HF. Prospectively, patients were grouped according to LF/HF before SAB: low-LF/HF: 1.5 (1.1/2.0) versus high-LF/HF: 4.0 (2.8/4.7), P < 0.05; low-LF: 58 +/- 9% versus high-LF: 75 +/- 10%, P < 0.05; low-HF: 41 +/- 10% versus high-HF: 25 +/- 10%, P < 0.05. High-risk patients had a significantly lower SBP after SAB (76 +/- 21 vs. 111 +/- 12 mmHg; P < 0.05).     

Differential immunogenicity of HLA mismatches in clinical transplantation

Although HLA matching is beneficial in clinical transplantation, it is not feasible to select a completely HLA matched donor for every potential recipient because of the enormous polymorphism of the HLA system. As a consequence, the majority of the recipients will be transplanted with a mismatched donor organ or hematopoietic stem cell transplant. For this large group of patients it is important to take advantage of the differential immunogenicity of HLA mismatches and to select for them a donor with HLA mismatches of low immunogenicity, the so-called acceptable mismatches. The differential immunogenicity of HLA mismatches can be determined by either retrospective analysis of graft survival data or by in vitro assays measuring T-cell and B-cell alloreactivity. A recently developed computer algorithm (HLAMatchmaker) can be instrumental in selecting donors with HLA mismatches, which do not lead to alloantibody formation. The theoretical background and practical implications of this acceptable mismatch approach are discussed.     

Treatment of 2d and 3d degree complicated tibial shaft fractures with the PMMA bead pouch technic

In a consecutive series of 222 compound fractures treated at the University of Louisville Level I Trauma Center from November 1984 to January 1987, 21 severe compound tibia shaft fractures in 20 patients were managed with the antibiotic bead pouch technique. There were 5 tibia shaft fractures and 16 tib-fib fractures. There were 9 type II and 12 type III (4 III A and 8 III B) open tibias. The patients' ages ranged from 16 to 50 years; the mean age was 29 years. There were 19 men and 1 woman. The Injury Severity Score (I.S.S.) ranged from 9 to 34; the mean I.S.S. was 14.4. Porous plastic film (Opsite) is placed over the soft tissue defect to establish a "closed" bead - hematoma - fracture environment containing high local levels of antibiotic at the fracture site. All patients had external skeletal fixation, serial wound débridement, and parenteral systemic antibiotics (cefazolin, penicillin, tobramycin). An aggregate of 46 bead pouch changes were performed in the 21 tibia fractures. During these changes, 86 cultures were taken, 5 of which were positive. One patient developed a wound infection, which was caused by tobramycin-resistant Pseudomonas and Enterococcus. No cases of osteomyelitis were observed at the fracture site. Wound closure was obtained in 9 fractures with delayed primary closure, and in 12 fractures with flap coverage and/or split thickness skin grafting. All patients underwent autogenous cancellous bone grafting after wound closure was established. The mean follow-up was 26 months (range 13-43 months). At final follow-up, 4 results were rated excellent, 11 good, 3 fair and 3 poor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Real-time semantic compensation in patients with agrammatic comprehension: electrophysiological evidence for multiple-route plasticity

To understand spoken language requires that the brain provides rapid access to different kinds of knowledge, including the sounds and meanings of words, and syntax. Syntax specifies constraints on combining words in a grammatically well formed manner. Agrammatic patients are deficient in their ability to use these constraints, due to a lesion in the perisylvian area of the language-dominant hemisphere. We report a study on real-time auditory sentence processing in agrammatic comprehenders, examining their ability to accommodate damage to the language system. We recorded event-related brain potentials (ERPs) in agrammatic comprehenders, nonagrammatic aphasics, and age-matched controls. When listening to sentences with grammatical violations, the agrammatic aphasics did not show the same syntax-related ERP effect as the two other subject groups. Instead, the waveforms of the agrammatic aphasics were dominated by a meaning-related ERP effect, presumably reflecting their attempts to achieve understanding by the use of semantic constraints. These data demonstrate that although agrammatic aphasics are impaired in their ability to exploit syntactic information in real time, they can reduce the consequences of a syntactic deficit by exploiting a semantic route. They thus provide evidence for the compensation of a syntactic deficit by a stronger reliance on another route in mapping sound onto meaning. This is a form of plasticity that we refer to as multiple-route plasticity.