Endothelin-like immunoreactivity in aqueous humor of patients with primary open-angle glaucoma and cataract

Background: Experimental evidence suggests a role of endothelin-1 (ET) in the regulation of intraocular pressure (IOP). Method: Therefore, inpatients undergoing cataract surgery, ET-like immunoreactivity (STIR) was measured by radioimmunoassay in pooled samples of aqueous humor of eyes with primary open-angle glaucoma (POAG) and normotensive eyes with cataract only. Results: ETIR was significantly (P < 0.05) higher in patients with cataract and POAG (20.5 ± 1.8 pg/ml,n = 12; preoperative IOP 21.4 ± I.1 mmHg,n = 33) than in patients with cataract only (15.8 ± 1.6 pg/m1,n = 15; preoperative IOP 16.0 ± 0.6 mmHg,n = 77). Conclusion: This finding may indicate a role of ET in POAG or ocular antihypertensive treatment, and its relevance should be further investigated.     

Hippocampal loss of the GABAA receptor α1 subunit in patients with chronic pharmacoresistant epilepsies

Alterations of gamma aminobutyric acid (GABA)-mediated neurotransmission have been implicated in the pathogenesis of epilepsies. Here we examine the distribution of the GABA_A receptor in the hippocampus of 78 surgical specimens from patients with chronic pharmacoresistant focal epilepsies. The receptor was localized immunohistochemically with the monoclonal antibody bd-24 which selectively recognizes the ₁ subunit of the GABA_A receptor. The results were compared with the receptor distribution of 28 normal hippocampal specimens obtained at autopsy. In the great majority of the surgical specimens a loss of GABA_A receptor immunoreactivity was present in CA1 (92.3%), CA4 (78.2%), the dentate granular cell layer (70.5%) and the molecular layer of the dentate gyrus (65.4%). The subiculum revealed a normal staining pattern in all but 4 cases. In no instance did we observe an increase of immunoreactivity in any region or cell population. The decrease of GABA_A receptor immunoreactivity was closely related to neuronal loss in the respective specimen and to Ammon's horn sclerosis. There was no correlation between GABA_A receptor loss and the patient's age at surgery, duration of seizures, age at onset of seizures and to the presence or absence of secondary generalized tonic clonic seizures. The data suggest that the observed loss of GABA_A receptor immunoreactivity is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.     

The life and work of Dr. George Byron Hayes, pioneer maxillofacial surgeon

When the First World War broke out in April of 1914, an American dentist practicing in Paris offered his services to the French government. He was Dr. George Byron Hayes, a native of a small upstate New York village and a graduate of the dental school of the University of Michigan. The new type of trench warfare led to facial wounds on a scale never before experienced in any conflict. But the military medical services had no experience or skill in dealing with these new and devastating wounds. Dr. Hayes stepped into the breach and performed such exceptional and often miraculous surgery that he was hailed by the entire Western world. The French government made him a Chevalier of the Legion of Honor and the U.S. government awarded him the Distinguished Service Medal, seldom awarded to a civilian. The most prominent surgeon of the day, Dr. Harvey Cushing, brought a team of physicians from Harvard to observe the treatment rendered wounded soldiers in the American Hospital in Neuilly, France, and, in lauding Dr. Hayes' work, stated that his contributions were the most remarkable of all, and that dental surgery should now be recognized as a specialty, the equal of any in medicine.     

Salvage of contaminated fractures of the distal humerus with thin wire external fixation

Fractures and osteotomies of the distal humerus that are contaminated or infected represent a difficult management problem. Stable anatomic fixation with plates and screws, the acknowledged key to a good result in the treatment of bicondylar fractures, may be unwise. A thin wire circular (Ilizarov) external fixator was used as salvage treatment in such complex situations in five patients. The fixator allowed functional mobilization of the elbow while allowing achievement of the primary goal of eradicating the infection or colonization. Two patients required a second operation for fixation of a fibrous union of the lateral condyle. One patient with a vascularized fibular graft later required triple plate fixation for malalignment at the distal host and graft junction. Four of five patients ultimately achieved complete union. The fracture remained ununited in one patient who has declined additional intervention. All five patients achieved at least 85 degrees ulnohumeral motion, two after a secondary elbow capsulectomy performed after healing was achieved. This experience suggested that the Ilizarov construct, although not a panacea, represents a reliable method of skeletal stabilization that allows functional mobilization while elimination of infection or colonization is ensured. If necessary, stiffness and incomplete healing can be addressed with an increased margin of safety at subsequent operations.     

The functional outcome of operative treatment of ununited fractures of the humeral diaphysis in older patients

Twenty-two elderly patients (average age, seventy-two years) who had an atrophic, unstable, ununited fracture of the humeral diaphysis were managed with plate-and-screw fixation and application of an autogenous bone graft from the iliac crest. Fifteen of the patients had had at least one previous operation in an attempt to obtain union of the fracture. One patient had an active infection and two had a quiescent infection, all with Staphylococcus epidermidis. The average duration of nonunion before the patients were first seen by us was two years and four months (range, five months to sixteen years). Fifteen of the nonunions were synovial. In each patient, at least one modification of the standard technique of plate-and-screw fixation was needed as a result of osteopenia. In order to enhance fixation, the standard protocol incorporated the use of a long plate (with an average of eleven holes and an average length that was 76 percent of that of the bone), a plate with a blade (used in thirteen patients), and replacement of loose, 4.5-millimeter cortical-bone screws with 6.5-millimeter cancellous-bone screws (twelve patients). Spiked nuts (Schuhli nut; Synthes, Paoli, Pennsylvania) that lock the screws to the plate, creating a solid point of fixation analogous to a blade, were incorporated into the protocol when they became available (used in six patients). In five limbs, the nonunion was associated with an osseous defect that could not be addressed by shortening of the bone alone. Three of these limbs were stabilized with a bridge plate that had been contoured to stand away from the bone at the site of nonunion (so-called wave-plate osteosynthesis), and the remaining two limbs were stabilized with a combination of intramedullary and extramedullary plates. In one of these two limbs, the extramedullary plate was contoured (that is, a wave plate). The fracture united in twenty (91 percent) of the patients. There was no progressive loosening or breakage of a fixation device, even in two patients who had radiographs that were suggestive of an incomplete union. Five of the patients were followed for a limited duration (average, one year and six months) as a result of death or illness. They had two excellent results, two good results, and one poor result according to a modification of the rating system of Constant and Murley. The remaining seventeen patients, including the two who had a persistent nonunion, were followed for an average of three years and one month (range, two years to five years and ten months). They had significant improvements in all of the functional scores at the most recent follow-up evaluation: the average score according to the modified system of Constant and Murley increased from 9 to 72 points (p < 0.001), the average score according to the Enforced Social Dependency Scale decreased from 39 to 9 points (p < 0.001), and the average score based on the Disabilities of the Arm, Shoulder, and Hand Questionnaire decreased from 77 to 24 points (p < 0.001). According to the scores based on the Disabilities of the Arm, Shoulder, and Hand Questionnaire, nine of the seventeen patients who had been followed for more than two years had an excellent result, four had a good result, two had a fair result, and the two who had a persistent nonunion had a poor result. Complications included postoperative delirium, a stitch abscess, transient radial nerve palsy, a fracture distal to the plate, and the need for a blood transfusion, in one patient each. Two patients had a fibrous union. There were no major medical complications. An unstable, united fracture of the humeral diaphysis can be extremely disabling and may threaten the ability of an elderly patient to function independently. Operative treatment can be very successful when the techniques of plate-and-screw fixation are modified to address osteopenia and relative or absolute loss of bone. Healing of the fracture substantially improves function and the degree of independence     

Striatal dopamine transporter density in major depression

Rationale: There are no previous data available regarding [¹²³I]β-CIT binding to the dopamine transporter sites in the basal ganglia in depressed patients. Objective: The present study tested the hypothesis that the brain DAT density in depressed patients is lower than that in matched healthy controls. Methods: Fifteen drug-naive outpatients with major depression and 18 healthy controls were investigated using single photon emission computerized tomography (SPECT) with a high-affinity dopamine transporter specific radioligand, ¹²³I-labeled β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)-tropane). Results: We found a significantly higher [¹²³I]β-CIT uptake in both sides of the basal ganglia in patients with major depression than in the controls (Mann-Whitney U-test, P = 0.002 on the right and P = 0.003 on the left). Conclusions: The radioligand uptake reflecting the DAT density was significantly higher among the patients than in the controls. This finding is unexpected, since it is generally believed that monoaminergic neurotransmission is lower in depression, and therefore it could be assumed that a reduction in dopamine transmission would lead to secondary down-regulation of DAT density. However, it is possible that up-regulation of the DAT may be the primary alteration, which leads to lower intrasynaptic dopamine concentration and to lower dopamine neural transmission. Received: 20 October 1998/Final version: 25 January 1999     

Differences in the response of Sprague-Dawley and Lewis rats to bezafibrate: The hypolipidemic effect and the induction of peroxisomal enzymes

The effects of bezafibrate administered at 10 and 50 mg/kg/day for 7 days to male Sprague-Dawley (SD) and Lewis rats were investigated in order to determine the interrelation between the changes in serum and hepatic lipid contents and activities of selected peroxisomal, microsomal and mitochondrial enzymes in the two rat strains. In both strains, bezafibrate effectively reduced serum and hepatic lipids, increased the liver weight, induced a proliferation of peroxisomes, and selectively elevated the activities of carnitine acetyltransferase and of the enzymes of the peroxisomal -oxidation system. Moreover, immunoblotting revealed that the drug specifically enhanced the concentration of only those peroxisomal enzymes involved in fatty acid -oxidation. The data obtained demonstrate that although the responses initiated by bezafibrate are qualitatively similar in both strains, they differ in their magnitude in a dose-dependent manner, with the Lewis strain exhibiting a more pronounced response than the SD rats. These results show that dose-dependent strain differences as well as the generally known species differences should be taken into account in pharmacological and toxicological evaluations of fibrates in rodents. Furthermore, generalization and extrapolation from rodent studies should be treated with great caution.     

Nd-YAG laser ablation of arteriosclerotic obstructions: Clinical long-term results in femoropopliteal artery occlusions

Laser recanalization of peripheral artery occlusions was performed in 338 patients. A continuous wave Nd-YAG laser was used in combination with sapphire-probe laser catheters. The initial recanalization rate was 85%. Complications such as dissections, perforations, emboli and spasm were observed in 14%. The cumulative patency rate after 3 years was 48%.     

The pericapsular osteotomy of the Os ilium in the treatment of flat acetabula

Summary The operative correction of the pathological flat acetabulum in congenital dislocation of the hip, myelodysplasia and cerebral palsy can be performed with pelvic osteotomies and acetabuloplasties. In the light of our own experiences gained with different methods we prefer the pericapsular osteotomy of the ilium according to Pemberton since 1971. After the evaluation of the results the advantages of the method compared with other procedures are presented in the light of the improvements of correction and the rate of complication.

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Zusammenfassung Die operative Korrektur der Flachpfannen bei Luxationshüfte, Myelodysplasie und Zerebralparese kann mittels Beckenosteotomie oder Azetabuloplastik erzielt werden. Anhand eigener Erfahrungen mit verschiedenen Methoden wird seit 1971 die perikapsuläre Iliumosteotomie nach Pemberton bevorzugt. Nach Auswertung der Ergebnisse werden die Vorteile der Methode gegenüber den anderen Verfahren anhand des Korrekturgewinnes und der Komplikationsrate dargelegt.

     

The pharmacokinetics of high-dose medroxyprogesterone acetate (MPA) in the therapy of advanced breast cancer

Summary Oral MPA 1.5 g/day leads to plasma concentrations between 1 and 12 g/ml, with a broad intra-and interindividual variance. The plateau state is reached in between 4 and 16 days. Plasma concentrations in the plateau state are very sensitive to dose modifications. After cessation of administration, the decline in plasma levels seems to proceed in two phases, with half-times of about 20 h and 4 days. Extraction procedures reveal no benefit in discriminating between MPA and its metabolites.