Infantile hemiplegia: clinical,electroencephalographic and computerised tomography study

Thirty-one patients with post-neonatally acquired infantile hemiplegia were assessed clinically, electroencephalographically and by CT scan. The mean age of onset of illness and when first seen in the neurology clinic were 20·2±20·1 months and 16·8±8·4 yr, respectively. Epilepsy was seen in 74 per cent of cases and mental retardation in 70 percent. Among patients with epilepsy, the EEG and CT scan were abnormal in 83 per cent and 87 per cent respectively. There was a positive correlation between an abnormal EEG and CT scan in 84 per cent of cases. The cause of hemiplegia could be clinically determined in only eight cases (26%). However, the CT scan showed abnormalities like cortical atrophy and porencephalic cyst, suggestive of a vascular or inflammatory aetiology in 68 per cent. The usefulness of CT in determining the aetiology in acquired infantile hemiplegia, especially when seen many years after the onset of illness is, emphasized.     

Comparative efficacy between the glycoprotein IIb/IIIa antagonists roxifiban and orbofiban in inhibiting platelet responses in flow models of thrombosis

This study was undertaken to compare the platelet binding characteristics and anti-platelet efficacy of a nonpeptide glycoprotein IIb/IIIa antagonist roxifiban with orbofiban in static and dynamic adhesion and aggregation assays. The results indicate that roxifiban binds with higher affinity to glycoprotein IIb/IIIa receptors and exhibits slower dissociation rates than orbofiban. Furthermore, the platelet inhibitory effects of roxifiban, but not orbofiban, were unaffected by changes in plasma calcium concentrations. Both agents reduced, in a concentration-dependent manner, the size of platelet thrombi deposited onto collagen I upon perfusion of heparinized blood at a shear rate of 1,500/s. At a clinically achievable concentration of 60 nM, roxifiban abrogated the formation of thrombi containing > 20 platelets per thrombus, thereby displaying comparable in vitro efficacy to that achieved by the theoretical maximal abciximab blood concentration (3.5 microg/ml) produced after standard treatment. In contrast, orbofiban, even at 500 nM, was only effective in inhibiting the formation of larger platelet thrombi (> or =150 platelets per thrombus). Pretreatment of surface-anchored platelets with roxifiban (100 nM), but not orbofiban (500 nM), inhibited monocytic THP-1 cell attachment under flow. However, this heterotypic adhesion process was also suppressed when orbofiban (500 nM) was maintained in the perfusion buffer during the entire course of flow experiment. These findings demonstrate roxifiban (unlike orbofiban) is a potent glycoprotein IIb/IIIa antagonist with a long receptor-bound lifetime and prolonged anti-platelet efficacy and may thus be beneficial for the treatment and prevention of acute ischemic syndromes.     

Long-term outcome of congenital intestinal pseudoobstruction

We evaluated 85 children with congenital chronic intestinal pseudoobstruction (CIP) over the past 10 years. Twelve (14%) were born prematurely. One had a family history of CIP. Six had systemic diseases. Thirty-five (41%) had urinary bladder involvement. Manometric features were consistent with myopathy in 32, neuropathy in 48, and mixed disease in 5. Of 48 patients with neuropathy, 6 had urinary bladder involvement (12.5%) (P < 0.0001 vs myopathy), and 10 had malrotation (21%) (P = NS vs myopathy). Upon referral, 53 (62%) were dependent on partial or total parenteral nutrition (PN). At the time of chart review (median 25 months after evaluation), 22 patients had died, 14 of whom were on total PN, 13 of them died because of PN-related complications and 1 died of sepsis. Three others died of sepsis while on partial PN (P = 0.007 vs mortality in patients fed enterally) and five died after small bowel transplantation. In conclusion, in children with congenital CIP, the risk for prematurity is increased twofold, the majority of cases are sporadic, abnormal bladder function is more common in myopathic CIP, and complications related to parenteral nutrition are the main cause of death in children with CIP.     

Total plasma clearance of 51Cr-EDTA: variation with age and sex in normal adults

Although inulin clearance measured during constant infusion is still considered the reference method, single-injection of 51Cr-EDTA with subsequent plasma sampling has become the most popular technique for the routine assessment of glomerular filtration rate. Despite the fact that the technique has been in use for 30 years, there are only a few reports of normal values calculated directly from 51Cr-EDTA data and normal ranges have generally been produced by conversions of inulin data. The aim of this study was to measure the variation in total plasma clearance, calculated directly from 51Cr-EDTA measurements, in normal males and females, of Saudi Arabian origin, over a wide range. Altogether, 201 potential kidney donors aged 16-60 years were studied. No statistically significant association of total plasma clearance with age or sex could be demonstrated; however, predictive equations suggesting a small decline in total plasma clearance with age were developed. The figures presented suggest that the reduction in total plasma clearance of 51Cr-EDTA with age is relatively shallow up to the age of at least 60 years and that normal ranges produced by conversion of inulin data may overestimate the decline with age.     

Analgesic and antiinflammatory effects of two novel kappa-opioid peptides

BACKGROUND: This study investigates two new kappa-agonist tetrapeptides, FE 200665 and FE 200666, with high peripheral selectivity as a result of poor central nervous system penetration. METHODS: Four days after administration of Freund adjuvant into the hind paw of male Wistar rats, antinociceptive effects of intraplantar and subcutaneous injection of FE 200665 and FE 200666 were measured by paw pressure algesiometry and compared with the kappa-agonist U-69,593. Peripheral and kappa-receptor selectivity was assessed by the antagonists naloxone methiodide (NLXM) and nor-binaltorphimine, respectively. Antiinflammatory effects were evaluated by paw volume plethysmometry and histologic score. RESULTS: Similar to intraplantar U-69,593, intraplantar FE 200665 (3-100 microg) and FE 200666 (1-30 microg) resulted in significant and dose-related increases of paw pressure thresholds. Higher doses of FE 200665 (0.2-20 mg) and FE 200666 (0.06-6 mg) were required by subcutaneous route to produce similar antinociceptive responses, supporting a peripheral site of action. nor-Binaltorphimine dose-dependently antagonized this effect, implying kappa-opioid selectivity. Analgesic effects of subcutaneous FE 200665 and FE 200666 were abolished by intraplantar nor-binaltorphimine, and both subcutaneous and intraplantar effects were dose-dependently antagonized by subcutaneous NLXM, further demonstrating a peripheral site of action. One to 6 days after Freund adjuvant inoculation, single and repeated intraplantar injections of FE 200665, FE 200666, and U-69,593 significantly reduced paw volume and histologic scores. Both changes were reversed by intraplantar nor-binaltorphimine and subcutaneous NLXM. CONCLUSION: FE 200665 is a peripherally selective kappa-agonist with potent analgesic and antiinflammatory properties that may lead to improved analgesic-antiinflammatory therapy compared with centrally acting opioids or standard nonsteroidal antiinflammatory drugs.     

Do practice guidelines guide practice? A prospective audit of induction of labor three years experience

BACKGROUND: To examine the effect of implementation of guidelines for induction of labor on the process of care and outcome measures. METHOD: Guidelines for induction of labor were implemented in January 1996 following an audit report identifying inconsistency in clinical practice. A prospective audit was carried out following the implementation of a new strategy directed towards pre-induction cervical ripening in nulliparae with unfavorable cervices and the use of low dosages of vaginal prostaglandin E2 for induction of labor. Level of compliance and outcome measures were compared before and after implementation of guidelines. RESULTS: In the period of January 1995 to November 1997, 1,230 women were induced with a singleton viable pregnancy in a cephalic presentation with a gestational age > or = 37 weeks with no history of rupture of membranes or cesarean section. Completed forms were available for 1,147 women (370, 421 and 356 in 1995, 1996 and 1997, respectively). Among nulliparous women, there was a reduction in the number of women who were admitted with cervical score of < or = 4 (24%, 40%, and 54% in 1997, 1996, and 1995, respectively; p=0.0001), an increase in the number of women who had amniotomy on admission (32%, 25% and 12% in 1997, 1996, and 1995, respectively; p=0.0001) and a shorter induction-delivery interval. No change in outcome measures was noted among multiparous women despite reduced dose of prostaglandin E2 used for induction of labor. A marginal reduction of both Cesarean section and failed induction rates were noted in both nulliparae and multiparae. Level of compliance improved with successive rounds of audit. CONCLUSION: Explicit guidelines do improve clinical practice, when introduced and monitored in the context of rigorous evaluations. However, the size of improvement could vary.     

Copper levels in women using intrauterine devices or oral contraceptives

A study was undertaken to explore the role of the copper IUD (Cu-200) in contraception and to lower its side effects. Endometrial and plasma concentrations of copper were determined spectrographically in the late proliferative and late secretory phases in 15 women wearing the copper IUD, in 6 short-term Lippes loop users, in 23 long-term Lippes loop users, in 17 patients on oral contraception, and in 32 women who were not using contraception,y The last group of women served as controls. The findings showed a decrease in the endometrial copper level in the secretory phase but no change in the plasma concentration of copper in the control group. Both Cu-200 and Lippes loops produced a rise in endometrial copper which was significant during the secretory phase. The possibility of a local foreign body reaction is noted. Combined steroid pills caused variable degrees of increase of endometrial and plasma copper in both phases. Endometrial copper levels were elevated in both phases of the cycle, while plasma copper showed a probably significant rise in the proliferative phase only. The change in plasma copper may be explained by changes occurring in hormonal pattern during pill therapy.     

Human alphavbeta3 integrin potency and specificity of TA138 and its DOTA conjugated form (89)Y-TA138

The present study was undertaken to define the alphavbeta3-binding potency and specificity of TA138, a nonpeptide integrin antagonist, and its conjugated form, 89Y-TA138. Various integrin-specific binding and functional assays as well as cell-adhesion assays were used to determine the potency and integrin specificity for TA138 and 89Y-TA138. Both TA138 and 89Y-TA138 inhibited alphavbeta3-mediated [125I]echistatin binding to 293-beta3-transfected cells, with IC50 values of 0.046 and 0.059 microM, respectively, and IC50 values of 0.012 and 0.018 microM, respectively, in inhibiting an alphavbeta3 integrin-mediated 293-beta3-transfected cell adhesion to fibrinogen. TA138 inhibited human umbilical vein endothelial cell adhesion to fibrinogen, with an IC50 value of 0.052 +/- 0.006 microM. Both TA138 and 89Y-TA138 demonstrated a relatively high degree of specificity for human alphavbeta3 integrin as compared with other human integrins, including alphavbeta5, alphaIIbbeta3, and alpha5beta1 (IC50 > 10 microM). Both 89Y-TA138 and TA138 demonstrated comparable alphavbeta3 affinity and specificity as compared with other closely related human integrins such as alphavbeta5, alphaIIbbeta3, or alpha5beta1.