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An efficient method for the preparation of beta,gamma-unsaturated delta-lactones has been developed. The starting materials for the synthesis of these compounds are allene-substituted malonates which undergo gold-catalyzed cyclization by means of nucleophilic attack of the ester moiety on the allene. It is worth mentioning that this is the first example where an ester group attacks as a nucleophile in a gold-catalyzed transformation of allenes.

Aza-Michael additions of alpha-amino esters to fluorinated acceptors take place in a highly stereoselective manner, to give partially modified Psi[NHCH2]retropeptides incorporating a hydrolytically stable trifluoroalanine mimic. The reaction mechanism has been investigated experimentally and theoretically, in order to explain the effect of the trifluoromethyl group on the reactivity and the origins of the experimentally observed stereocontrol. The reaction is a two-step process, involving a tandem aza-Michael addition followed by a stereoselective hydrogen transfer. Both steps are base-catalyzed. The high level of stereocontrol is the result of a combination of electrostatic interactions and steric effects.

Purpose: Hemiparetic gait has been previously evaluated by several biomechanical methods, but plantar pressure distribution has been much less studied. Our purpose was to analyze the changes in the path of the center of pressure (COP) following the occurrence of hemiparesis using an F-Scan in-shoe transducer., Materials and Methods: Twenty patients, mean age 50 years [26-67] with hemiparesis due to vascular causes underwent gait analysis (by the F-Scan system). All patients had steady neurological status and were self-sufficient for gait. Podo-orthoses were removed during the test. Five to six cycles of gait, about 8 m, were recorded. Comparison of the COP path was performed between hemiparetic and healthy foot. The group control consisted of 9 healthy volunteer subjects., Results: Differences in the COP path were found in the hemiparetic foot of patients: a significant decrease for the anteroposterior displacement (P=0.002) and the lateral displacement (P=0.04) and a significant anterior displacement of the more posterior contact COP (P=0.005). The "gait line" was irregular, with slowing down going forward and, for some, going back. These results are likely consistent with the equine of the foot. No change was observed in the control group., Conclusion: The use of an F-Scan in the shoe transducer allows for revealing the importance of the COP path in analyzing hemiparetic gait; this noninvasive investigation would be helpful for evaluating the best therapy to propose to and to follow-up patients with hemiparesis.

Two families of bicyclic fluorinated uracils have been prepared starting from a gem-difluorinated unsaturated nitrile, by means of a ring-closing metathesis reaction to form the new ring, which is fused at the C-5/C-6 or N-1/C-6 positions of the uracil moiety. The selective formation of olefin regioisomers in the metathesis process can be controlled according to the reaction conditions (catalyst, solvent, and temperature). The acaricidal activities of the resulting compounds have also been investigated.

For about 15 years, technical advances in prosthetic treatment have been the main factor in the increased performance of athletes with lower-limb amputation. For trans-tibial amputation, the prosthesis for sprinting is composed of a gel liner and a socket joined by a locking or virtual vacuum liner. Because of these dynamic properties, the carbon prosthetic foot equipped with tacks ensures outstanding performance. For trans-femoral amputation, a hydraulic swing and a stance control unit are added to the same prosthesis. In comparison with the able-bodied runner, athletes with amputation have smaller loading times in the prosthetic limb and larger ones in the sound limb. The length of the energy-storing prosthetic foot is determined by the "up-on-the-toes" running gait. The sprinting gait with trans-tibial amputation is almost symmetrical. The hip extensor effort is the main compensation of propulsion reduction with lower-limb amputation. With trans-femoral amputation, the lack of knee increases the asymmetry. The total prosthetic knee extension (early in late-swing phase and lasting during total stance phase) compensates with extension of both hips, especially the opposite one. The amputation and sound limb load transfer with lumbar hyperlordosis concern the pelvis, trunk and shoulders. Because of athletes with amputation, research in prosthetic treatment has progressed. The development of orthotics and prostheses for such athletes has benefited non-athletes with amputation.

A series of potentially biologically active fluorinated uracil derivatives has been prepared in three steps from oxazolines and fluorinated nitriles with good chemical yields.

Constipation is a major problem for institutionalized patients. This prospective study was performed on a population of 152 in-patients of a stroke rehabilitation center. Constipation was defined as less than three stools weekly or the use of laxative medication. Constipation occurred in sixty percent of the patients. The incidence of constipation was not related to age or sex but was strongly related to functional status of patients assessed by Barthel Index (p<0.003). The influence of both brain lesion or reduce activity is evaluated.

The association of ifosfamide with cisplatin and 5-fluorouracil for the management of advanced squamous cell carcinoma of the head and neck was assessed in this trial. Ifosfamide was given initially to 12 patients in combination with standard fixed doses of cisplatin and 5-fluorouracil, at 1,000 mg/m2 daily on days 2, 3, and 4. Two patients died of neutropenia and severe infection, and the authors recruited seven more patients who were treated with a lower dose of ifosfamide, 800 mg/m2 daily on days 2, 3, and 4. One of the seven patients died of neutropenia and severe infection. Three complete remission were observed in 18 patients evaluable for efficacy. The study was closed early because of the severe toxicity profile demonstrated by this scheme and because of no clear advantage in efficacy versus cisplatin plus 5-fluorouracil combinations.

Objectives: The purpose of this study was to test the therapeutic effect of human recombinant erythropoietin (rH-EPO) on anemia of prematurity., Material and Methods: Fifty-eight preterm infants less than 34 weeks of gestational age from three different hospitals were studied. Transfusional policies were similar in all three centers. Infants with ABO or Rh incompatibility were excluded. At 28 days after birth, 28 infants (48.3%) had hemoglobin levels under 10.5 g/dL and were randomized to receive rH-EPO or standard care. Those infants ascribed to the treatment group received 200 U/kg of body weight of rH-EPO subcutaneously once a day, three days a week for 4 weeks together with oral supplements of ferrous sulfate at a dosage of 4 mg/kg/day. Both groups received daily doses of 50 micrograms of folic acid and 5U of vitamin E per os. Erythropoietin and ferritin were determined at randomization and at 60 days of age. Hemoglobin, reticulocytes, leucocytes, granulocytes and platelets were measured once a week, from the beginning of the treatment until 60 days of age., Results: At randomization into treatments, there were no significant differences between the groups with respect to weight, gestational age, hemoglobin (9.42 +/- 0.73 vs 9.26 +/- 0.68 g/dL), reticulocytes (61.7 +/- 32.2 vs 68.0 +/- 61.0 x 10(9)/L), ferritin, EPO1 leucocytes or platelets. At 60 days of age, the treatment group showed higher hemoglobin values (10.5 +/- 1.73 vs 9.1 +/- 1.0 g/dL, p < 0.05). There were no significant differences between reticulocyte counts (176.4 +/- 91.1 vs 112.6 +/- 85.0 x 10(9)/L), granulocytes (2,351 +/- 868 vs 2,075 +/- 856 x 10(9)/L), platelets (400 +/- 138 vs 316 +/- 164 x 10(9)/L) or ferritin (209 +/- 177 vs 393 +/- 328 micrograms/mL). Of the infants in the nontreated group, 13.3% received blood transfusions between 30 and 60 days of age, while only 6.7% of the treatment group did (p = 0.31)., Discussion: We have been able to find 11 controlled studies in the medical literature which deal with the clinical usage of rH-EPO in newborns. Six use the hormone in an early phase and 5 in a posterior one. Our study should be included in the later and, as happens in most of them, demonstrates the efficacy of rH-EPO in the treatment of late anemia of the preterm newborn as shown by an increment in the hemoglobin levels and a trend towards the diminution in the use of blood transfusions. We have not observed substantial adverse effects.

Background: Until now, preoperative parathyroid imaging has been considered unnecessary because currently available techniques do not provide any better results than an expert surgeon. We conducted a multicenter prospective study evaluating the capability of technetium 99m sestamibi scintigraphy in the preoperative identification of pathologic glands., Methods: Ninety-three patients with hyperparathyroidism, seven of them reoperative cases, were studied. In addition, 20 age-matched normocalcemic control subjects were also studied., Results: Surgical confirmation of scintigraphic images was obtained in 91 of 93 cases (sensitivity, 97.8%). In all reoperative cases (n = 7), in all cases of ectopic glands (whether operated or not; n = 6), and in all patients with a single-gland disease (n = 70), topographic identification of the pathologic gland was correct in 100%. In multiple-gland disease (n = 23), involvement of more than one gland was visualized in only 61% of the patients; however, in 91% of patients, at least one gland was localized. Surgical success-defined as postoperative normocalcemia-with this approach was 100%. All scans of normocalcemic control subjects were negative. Of 31 patients in whom a multinodular goiter coexisted, seven presented a significant radionuclide background at 120 minutes' scan. False-positive images were found together with those corresponding to the pathologic glands in only three cases., Conclusions: 99mTc-sestamibi is a highly reliable, sensitive, and specific technique for imaging of pathologic glands in hyperparathyroidism, especially in single-gland disease. It may be considered as a first line single-procedure when a preoperative topographic diagnosis is required.

Preoperative localization of ectopic parathyroid lesions is crucial for the correct treatment of patients with primary hyperparathyroidism. Invasive and noninvasive procedures, including selective venography, ultrasound, CT and MRI provide limited sensitivity in the detection of ectopic lesions. We report three patients in whom 99mTc-MIBI scintigraphy accurately detected ectopic parathyroid adenomas and was instrumental in the cure for these patients. Technetium-99m-MIBI scintigraphy provides a simple and accurate noninvasive test for the detection of ectopic parathyroid adenomas.

Objective: The use of preoperative imaging in patients with hyperparathyroidism remains controversial. Many of the available techniques are insufficiently sensitive and specific to justify their routine use. We have evaluated the sensitivity and specificity of 99mTc-sestamibi scintigraphy in the management of patients with different forms of hyperparathyroidism., Design: Preoperative imaging evaluation was carried out by scintigraphic detection of pathological parathyroid glands using 99mTc-sestamibi as a radiotracer; confirmation of scan findings was obtained surgically., Patients: A group of 25 patients with primary (n = 21) or secondary (n = 4) hyperparathyroidism were studied. All were considered for surgical treatment., Measurements: In all cases parathyroid imaging was carried out by 99mTc-sestamibi scintigraphy together with at least one other imaging technique which included CT-scan, ultrasonography, MRI or 201TI/99mTc subtraction scintigraphy. Blood tests included measurements of total calcium and PTH., Results: 99mTc-sestamibi scintigraphy correctly localized 20 out of 21 adenomas, giving a sensitivity of 95.2%, markedly higher than that obtained with the other imaging techniques (ultrasonography 75%, 201TI/99mTc subtraction scintigraphy 57.1%, CT-scan 41.7% and MRI 33%). Of a total of 17 glands identified surgically as hyperplastic and confirmed by pathological examination, 99mTc-sestamibi scintigraphy showed a positive image in 10, corresponding always to the larger abnormal glands (sensitivity 58.8%, higher than that observed with the other techniques). No false positive images were obtained with 99mTc-sestamibi. All the ectopic adenomas (n = 3) were identified preoperatively, which contributed significantly to the surgical approach., Conclusion: In patients with hyperparathyroidism, 99mTc-sestamibi scintigraphy may be used as the single imaging technique as it shows a very high sensitivity and specificity in the preoperative localization of pathological parathyroid glands; the benefit of localizing parathyroid tissue prior to surgery in cases of ectopic adenomas clearly indicates that when an imaging procedure is required, this technique may be of great help in the management of hyperparathyroidism.

The inhibition of rat hepatic mitochondrial aldehyde dehydrogenase (ALDH) isozymes was studied in apparent steady-state conditions after repeated intra-peritoneal cyanamide administration. The low-Km mitochondrial ALDH isozyme was more susceptible to cyanamide-induced inhibition (DI50 = 0.104 mg kg-1) than the high-Km isozyme (DI50 = 8.52 mg kg-1), with almost complete inhibition occurring at 0.35 mg kg-1 total cyanamide administered for the low-Km isozyme. The relationships between plasma and liver cyanamide concentrations and the inhibition of high-Km ALDH were established by means of the sigmoid Imax model. The effect of dosing rate on the plasma concentration of cyanamide at apparent steady-state showed non-linearity, indicating that clearance or first-pass metabolism of cyanamide during its absorption after intraperitoneal administration did not remain constant throughout the range of doses studied.

In order to appreciate the consequences of aging on the urethra, two prospective studies assessed its caliber in postmenopausal women. The population included aged women who came to consultation for disorders of the bladder and sphinecters. The clinical checkup, assessing the patient's age, morphology, time elapsed since menopause, local consequences of hormonal deficiency and urinary functional signs, was completed by an urodynamic examination. In the first study (76 patients), the urethra was calibrated using two Peters dilating bougies ranging from Charrière 10 to Charrière 26. In the second study (50 patients), measurements were made with OTIS-type ball dilators ranging from Charrière 9 to Charrière 30. This exploration was made in 126 patients. Urethral caliber was greater than or equal to Charrière 24 in 78% of patients. Only 2.3% of women had urethral "stenosis" with a Charrière score under 18. Contrary to what we were expecting, the urethral caliber does not seem to decrease with age. This unexpected statement and the difficulties of statistical analysis we have encountered lead us to complement our study.

Five cases of primary lymphoma of the thyroid followed at our hospital during the last decade are reviewed. The clinical and pathological characteristics are analysed and the therapeutical approach described. The age at the diagnosis ranged between 26 and 76 years, with a female versus male predominance (4 out of 5 cases). The commonest clinical feature at presentation was goiter of rapid growth accompanied by compressive symptoms. The pathologic study showed a centrocytic-centroblastic pattern in 3 cases and an immunoblastic lymphoma in the other 2 cases. Associated Hashimoto's thyroiditis was found in 4 of the patients, and extra-thyroid extension in 2 cases. An immunohistochemical study with different cell membrane markers was performed. The treatment included surgery alone in one case, chemotherapy in one case and radiotherapy in another; combined treatment (surgery plus radiotherapy) was performed in two cases. At present the average follow up period is 4.5 years with a patient having died of an unrelated cause among the five cases.

The aim of this study was to assess a technique for serum ferritin determination by means of chemoluminiscence (Magic Lite, Ciba Corning) in a series of unselected patients. A group of 100 healthy blood donors (50 men and 50 women), in whom iron deficiency had been previously excluded, was used as control. The results were validate according to the Societé Francaise de Biologie Clinique guidances. The characteristics of the method and its comparison with IRMA and ELISA techniques are described here. Its major advantages are related with simplicity and sensitivity; the main disadvantage is the necessity to repeat every step in samples with ferritin levels over 1,500 ng/dl.

The haematological parameters of 97 cases of beta thalassaemia trait and 40 cases of delta beta thalassaemia trait have been compared. No differences in haemoglobin, haematocrit, MCV, MCH, ferritin, % saturation or free erythrocyte protoporphyrin have been found. The RDW, however, is significantly increased in delta beta thalassaemia trait, its mean value (+/- SD) being 20 (2.05), even higher than that found in iron deficiency anaemia. The discrimination function described by England and Fraser may be of help in distinguishing these entities.

Contrarily to what happens in acute leukemia, the incidence of osteolytic lesions in chronic leukemia is exceedingly low. Three patients with chronic myeloid leukemia (CML) who developed such lesions during the chronic phase of their disease form the basis of this report. Osteolytic lesions appearing during the chronic phase of CML are different from those appearing during acute leukemia or during the acute terminal phase of CML, and the differences between both types of osteolysis are briefly reviewed. In the present cases the appearance of osteolytic lesions during the chronic phase of CML preceded for a variable period the terminal acute blastic phase. Therefore this complication must be considered as a sign of poor prognosis as it relates to the subsequent course of the leukemia. Even though other authors advise local radiotherapy as the treatment of choice of osteolytic lesions, only cytostatic therapy was given to the present patients, with good results as it regards the lesions per se.

Locally advanced and inflammatory carcinomas of the breast are two distinct entities, with widely accepted differential clinical criteria. We describe a particular type of locally advanced cancer which acquires during its evolution inflammatory characteristics, although limited to a small area of skin and thus not accomplishing the common diagnostic criteria of inflammatory carcinoma. When comparing this type of tumors, named locally advanced cancer with inflammatory component, to other locally advanced cancers, some remarkable differences are found: there is a preponderance of younger patients, premenopausal or perimenopausal, with a greater percentage of poorly differentiated tumors and negative estrogen receptors. Their evolution and survival are similar to that of inflammatory carcinomas; thus, we conclude they should be considered and treated as inflammatory carcinomas. Finally, the prognostic limitations of the TNM classification are discussed and some adjustments for future classifications are suggested.

Among giant tumours of the cauda equina, apart from ependymomas, neurinomas merit a special place. Depending on their site, they give rise to severe lumbar pain or root pain, with, almost constantly, aggravation during the night. X ray suggests the diagnosis when one finds displacement of the bone without inflammation, a regular bony defect, well-limited and asymmetric, and when the tumour is frequently prolonges in several directions across the bony orifices, sometimes giving a very large paravertebral mass which requires a double approach during surgery. The prognosis of isolated neurinomas is excellent, with disappearance of the pain immediately after operation, regression of the neurological signs or, at any rate, stabilisation when the latter are important. As far as the problem of spinal stability is concerned, this has been solved by sufficient spontaneous bony reconstruction.

Fourteen patients with malignant ovarian germ cell tumors were treated postoperatively with a short-term, sequential regimen combining cisplatin, vincristine, methotrexate, bleomycin, dactinomycin, cyclophosphamide, etoposide, Adriamycin (Adria Laboratories, Columbus, OH), and vinblastine (POMB/ACE/PAV). Two patients had Stage I disease, Five had Stage II, five had Stage III, and two had Stage IV. The histologic diagnosis was immature teratoma in five cases (two cases were Grade 2 and three cases were Grade 3) endodermal sinus tumor in two cases, dysgerminoma in three cases, and mixed germ cell tumors in four cases. The chemotherapy regimen appeared to be highly effective against all histologic types, including advanced stages, with 12 of 14 (86%) overall sustained remissions. The median duration of treatment was 5 months. The toxicity of the regimen, which contained low total doses of cisplatin and bleomycin, was only moderate. After a median follow-up of 53+ months, 13 patients were alive without evidence of disease. The results and toxicity obtained were compared with those from other currently used regimens. Also, some comments on initial surgery and second-look surgery are given.

A study was made of 72 cases of leukemia in children (the majority of which were acute lymphoblastic in type or with undiferenciated cells), in order to examine the type and frequency of pulmonary complications in leukemia, once complications of infectious etiology had been rejected. Pulmonary complications were found in 23 cases. Most often recurring image was the disseminated reticulonodular type. Nodular images and diverse pulmonary infiltrates were also discovered, these were often peribronchial and bilateral in almost every case. No significant relationship was found regarding the age of children, type of leukemia or length of time illness took to develop. Finally, present increase in the frequency of pulmonary complications in leukemia is commented and possible etiologic part antiblastic therapy might play on certain occasions is speculated.

Vascular complications are frequent in paralyzing neurologic disorders, particularly in peripheral neurologic diseases: edema of the declive, cold feet, acrocyanosis, increased sudation. An enlarged leg in a paralyzed subject presenting frequently reduced sensitivity may indicate phlebitis, but also hematoma of an undetected fracture, or osteoarthropathy. Trophic disorders, such as edema, ulcerative hyperkeratosis and subcutaneous hematoma, are sometimes indicative of an unrecognized peripheral neuropathy, notably diabetic. Sclerous complications of venous impairment, or trophic disorders in algesic dystrophy, may result in incorrect diagnosis of a neurologic disorder. In practical therapeutic terms, it is necessary to emphasize the value of elastic retention, attentive pedicure and flexible and shock-absorbing footwear.