Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

TNF-alpha binding ability as a sign of peripheral blood neutrophils preactivation in the course of multiple sclerosis

Usually neglected is the role of neutrophils in causing of immunological disturbances in patients with multiple sclerosis (MS). Nevertheless, it has been indicated over the recent years that these cells possess a sufficient potential to affect both immune response and inflammation. This potential may result in MS through the process of priming of these cells by proinflammatory cytokines like TNF. We studied TNF and its soluble receptors sp55 and sp75 serum levels and binding of fluorescein isothiocyanate (FITC)-stained TNF by neutrophils. We studied three different groups of MS patients: 10 patients in relapse of the disease, 13 in its remission, and 11 in its chronic progressive form (CP-MS). The control was provided by 14 neurological patients (OND) with non-inflammatory diseases. The performed studies showed higher TNF sp55 and sp75 soluble TNF receptors serum levels in the patients with relapse, comparing with other MS patients and OND. TNF binding by neutrophils of MS patients during relapse was also higher, than other MS patients and OND. These result suggest the preactivation of neutrophils in the relapse of MS.     

Diagnostic and Perinatal Management of Fetal Extrasystole

Fifty fetuses referred to the Polish Mother's Memorial Hospital for fetal echocardiography between January 1, 1991 and June 1, 1995 were evaluated. The mean fetal gestational age at the time of diagnosis of arrhythmia was 34.1 weeks, and the mean gestational age at the time of delivery was 38.7 weeks. Checkup echocardiographic examinations were performed every 10–14 days, for a mean 2.4 studies per fetus. In most cases (48/50, 96%), premature atrial contractions were present during the first echocardiography examination. The fetal heart study was normal in 30 cases; in 7 (14%) there was tricuspid valve regurgitation, in 7 (14%) an atrial septal aneurysm, in 4 congenital heart defects, in 1 myocardial hypertrophy, and in 1 disproportion in the four-chamber view. Of the 50 fetuses, 43 underwent regular echocardiographic monitoring alone; in 7 cases, based on the presence of additional echocardiographic findings, pharmacotherapy was applied (digoxin, verapamil, or both). Three neonates died after delivery owing to malformations in two cases (one critical aortic stenosis, one spina bifida plus hygroma colli) and due to myocarditis in one case. In six of seven newborns treated in utero, myocarditis was diagnosed after birth (including the one with neonatal demise). Most of the newborns were in good condition after birth, their mean Apgar score being 8.6 and the mean birth weight 3259 g. We concluded that most extrasystoles represent an isolated anomaly, not affecting the fetal condition. Their presence should not influence the obstetric care and may require only echocardiographic monitoring. In most of our cases the premature contractions subsided after birth, although sometimes they preceded fetal supraventricular tachycardia or appeared after congenital myocarditis.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Mortality after aortic valve replacement: results from a nationally representative database

Background. Nationally representative estimates of in-hospital mortality after aortic valve replacement are needed to evaluate whether results from The Society of Thoracic Surgeons National Cardiac Surgery Database are applicable to other institutions in the United States performing these procedures.

Methods. Data from the 1994 Nationwide Inpatient Sample were used to estimate the patient characteristics and in-hospital mortality rates associated with aortic valve replacements performed in nonfederal hospitals in the United States. Procedural and hospital characteristics were examined for possible associations with in-hospital mortality.

Results. An estimated 46,397 aortic valve replacements were performed. In-hospital mortality occurred in 4.3% of first-time isolated aortic valve replacements and 6.4% overall. The highest quartile of procedure-specific hospital volume, compared with the lowest quartile, was associated with lower in-hospital mortality (adjusted odds ratio, 0.58; 95% confidence interval, 0.42 to 0.81).

Conclusions. The in-hospital mortality rates observed in this study are very similar to those reported from The Society of Thoracic Surgeons database. These data provide substantial evidence that results from The Society of Thoracic Surgeons database are representative of those achieved at other institutions. However, procedure-specific hospital volume must be considered in applying these results to individual institutions.     

Pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg

PurposeTo investigate the pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg.Material/methods.Plasma concentrations were measured in 20 critically ill patients (mean [SD]; age, 55.5 [16.5] years; weight, 80.3 [16.9] kg; and creatinine clearance, 110.0 [71.5] mL/min). Four blood samples were drawn at the following time points 0, 0.5, 6, 8 hours after infusion. Ciprofloxacin concentrations were determined by high-performance liquid chromatography. Results. In the cases where ciprofloxacin was applied in targeted antibiotic therapy the minimum inhibitory concentrations (MIC) were ≤0.5 mg/l. The maximum and minimum plasma concentrations of ciprofloxacin were 1.74 (0.58-7.90) and 0.45 (0.16-2.96) mg/l, respectively. The main pharmacokinetic parameters for ciprofloxacin in the analyzed patients were as follows: k_el, 0.21 h^?1; t_1/2kel, 3.37 h; AUC_0-inf, 10.10 mg×h/l; AUMC_0-last, 15.36 mg×h²/l; MRT, 1.71 h; V_d, 214.8 l; Cl, 39.70 l/h. Considering the maximum value of MIC (0.5 mg/l) only 30% and 25% of analyzed patients had desired values of the PK/PD indexes AUIC>125 and C_max /MIC>10, respectively.Conclusions.The target plasma concentrations after the first dose of ciprofloxacin were reached only in a few critically ill patients. Considerable inter-subject variability for PK/PD parameters in ICU patients requires systematic monitoring.     

Polymorphism of the sulfonylurea receptor gene in type 2 diabetes mellitus

Sulfonylureas are used in treatment of diabetes. Resistance to these derivatives is a therapeutical problem. Sulfonylureas act through sulfonylurea receptor 1 (SUR1) in the beta cell. SUR1 also enhances a physiological secretion of insulin induced by an increase of glucose concentration. It may be expected that polymorphism of SUR1 gene can lead to beta cell dysfunction and resistance to sulfonylureas. The aim of this study was to examine the frequency of polymorphism in exon 22 of SUR1 gene and its correlation with type 2 diabetes mellitus and sulfonylurea treatment failure. The group consisted of 42 patients with type 2 diabetes. The controls were 46 persons with proper glucose tolerance. Polymorphism was found in 5 patients and in 1 control person. Neither statistically significant difference of polymorphism frequency nor correlation between polymorphism and sulfonylurea failure was found due to a low number of cases. Polymorphism of exon 22 of SUR1 gene appeared more frequent in diabetic than in non-diabetic subjects but this was statistically not significant.     

Functionalization of α-hydroxyphosphonates as a convenient route to N-tosyl-α-aminophosphonates

Direct conversion of the α-hydroxyl group by para-toluenesulfonamide to yield α-(N-tosyl)aminophosphonates is reported. α-Aminophosphonates 23a,b–37a,b were obtained from the corresponding α-hydroxyphosphonates 6a,b–21a,b in the presence of K₂CO₃, via the retro-Abramov reaction of the appropriate aldehydes, 1–5. The subsequent formation of imines with simultaneous addition of diethyl phosphite provided access to the α-sulfonamide phosphonates 23a,b–37a,b with better diastereoselectivity than in the case of the Pudovik reaction. The mechanism for this transformation is proposed herein. When Cbz N-protected aziridine 9a,b and phenylalanine analogue 12a,b were exploited, intramolecular substitution was observed, leading to the corresponding epoxide 38 as the sole product, or oxazolidin-2-one 39 as a minor product. Analogous substitution was not observed in the case of proline 18a,b and serine 21a,b derivatives.

The reaction mechanism and diastereoselectivity of the direct transformation of α-hydroxyphosphonates 6a,b–21a,b by para-toluenesulfonamide, yielding α-(N-tosyl)aminophosphonates 23a,b–37a,b under K₂CO₃ conditions are presented.