Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients

BACKGROUND: Campath 1H is a depleting, humanized anti-CD52 monoclonal antibody that has now been used in 31 renal allograft recipients. The results have been very encouraging and are presented herein. METHODS: Campath 1H was administered, intravenously, in a dose of 20 mg, on day 0 and day 1 after renal transplant. Low-dose cyclosporine (Neoral) was then initiated at 72 hr after transplant. These patients were maintained on low-dose monotherapy with cyclosporine. RESULTS: At present, the mean follow-up is 21 months (range: 15-28 months). All but one patient are alive and 29 have intact functioning grafts. There have been six separate episodes of steroid-responsive rejection. One patient has had a recurrence of her original disease. Two patients have suffered from opportunistic infections, which responded to therapy. One patient has died secondary to ischemic cardiac failure. CONCLUSIONS: Campath 1H has resulted in acceptable outcomes in this group of renal allograft recipients. This novel therapy is of equal efficacy compared to conventional triple therapy, but allows the patient to be steroid-free and to be maintained on very-low-dose immunosuppressive monotherapy.     

Anti-inflammatory activity of c(ILDV-NH(CH2)5CO), a novel, selective, cyclic peptide inhibitor of VLA-4-mediated cell adhesion.

1. Small, N- to C-terminal cyclized peptides containing the leucyl-aspartyl-valine (LDV) motif from fibronectin connecting segment-1 (CS-1) have been investigated for their effects on the adhesion of human T-lymphoblastic leukaemia cells (MOLT-4) to human plasma fibronectin in vitro mediated by the integrin Very Late Antigen (VLA)-4 (alpha4beta1, CD49d/CD29). 2. Cyclo(-isoleucyl-leucyl-aspartyl-valyl-aminohexanoyl-) (c(ILDV-NH(CH2)5CO)) was approximately 5 fold more potent (IC50 3.6+/-0.44 microM) than the 25-amino acid linear CS-1 peptide. Cyclic peptides containing two more or one less methylene groups had similar potency to c(ILDV-NH(CH2)5CO) while a compound containing three less methylene groups, c(ILDV-NH(CH2)2CO), was inactive at 100 microM. 3. c(ILDV-NH(CH2)5CO) had little effect on cell adhesion mediated by two other integrins, VLA-5 (alpha5,beta1, CD49e/CD29) (K562 cell adhesion to fibronectin) or Leukocyte Function Associated molecule-1 (LFA-1, alphabeta2, CD11a/CD18) (U937 cell adhesion to Chinese hamster ovary cells transfected with intercellular adhesion molecule-1) at concentrations up to 300 microM. 4. c(ILDV-NH(CH2)5CO) inhibited ovalbumin delayed-type hypersensitivity or oxazolone contact hypersensitivity in Balb/c mice when dosed continuously from subcutaneous osmotic mini-pumps (0.1-10 mg kg(-1) day(-1)). Maximum inhibition (approximately 40%) was similar to that caused by the monoclonal antibody PS/2 (7.5 mg kg(-1) i.v.) directed against the alpha4 integrin subunit. 5. c(ILDV-NH(CH2)5CO) also inhibited oxazolone contact hypersensitivity when dosed intravenously 20 h after oxazolone challenge (1-10 mg kg(-1)). Ear swelling was reduced at 3 h and 4 h but not at 1 h and 2 h post-dose (10 mg kg(-1)). 6. Small molecule VLA-4 inhibitors derived from c(ILDV-NH(CH2)5CO) may be useful as anti-inflammatory agents.     

Level of use of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in humans correlates with EEG power and coherence

Rationale: Despite animal studies implicating 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. Objective: The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. Methods: Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject’s consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. Results: MDMA use was positively correlated with absolute power in the alpha (8–12 Hz) and beta (12–20 Hz) frequency bands, but not with the delta (1–3 Hz) or theta (4–7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated. Conclusions: Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs. Received: 19 October 1998/Final version: 12 January 1999     

A comparison of the haemodynamic effects of intrathecal meperidine,meperidine-bupivacaine mixture and hyperbaric bupivacaïne

Purpose

To study the haemodynamic effects of intrathecal meperidine, administered either alone or mixed with bupivacaïne.

Methods

We studied 42 Chinese patients, aged 59–87 yr, scheduled for transurethral bladder or prostate surgery, randomized into three equals groups, that received either meperidine 0.8 mg · kg^{?1 meperidine 0.4 mg} · kg^?1 plus 1.5 ml of 0.5% heavy bupivacaïne or 3 ml of heavy bupivacaïne 0.5%. Non-invasive systolic (SAP) and mean (MAP) arterial pressures, central venous pressure and cardiac index, stroke index and heart rate (HR) measured by the BoMed NCCOM3-R7S bioimpedance device, were recorded over the first 25 min. Systemic vascular resistance index (SVRI) was derived. Onset of sensory and motor block was also measured. Decreases in MAP of 25% were treated with colloid and metaraminol. Results: The onset of block was slower in the meperidine group (P < 0.05). Decreases in SAP, MAP and SVRI (all; P < 0.001) occurred within five minutes in all three groups. The HR was increased in the bupivacaïne group (P = 0.03), but bradycardias treated with atropine occurred in six patients receiving meperidine and four patients receiving the mixture. Six patients receiving meperidine and two patients receiving the mixture required general anaesthesia for inadequate block. The incidence of nausea and vomiting was higher in the patients receiving meperidine (P < 0.05). No other complications were encountered.

Conclusions

Intrathecal meperidine used alone or mixed with bupivacaïne has no intra-operative advantage over heavy bupivacaïne 0.5%.     

High resolution CT of the lungs in acute disseminated tuberculosis and a pediatric radiology perspective of the term “miliary”

High resolution CT (HRCT) of the lungs in six children with acute disseminated tuberculosis was evaluated. There was a wide variation in the HRCT appearances. This covered differences in size, distribution and concentration of nodular opacities. Coalescence of nodules and the presence of intestitial thickening was variable. The recognition of acute disseminated tuberculosis is important for diagnosis and has prognostic implications. The use of the term acute disseminated tuberculosis rather than miliary tuberculosis is advocated.     

Transoesophageal echocardiogram may fail to diagnose peri-operative myocardial infarction

We report a case in which a 55-yr-old man undergoing aortocoronary bypass was monitored with electrocardiogram and transoesophageal echocardiogram. Intraoperative electrocardiogram and simultaneous ECG recordings using the Holter monitor showed an ST elevation of greater than 2 mm and new Q wave formation in leads AVF and V5 during skin closure. However, the transoesophageal echocardiogram showed no wall motion abnormalities. No significant haemodynamic abnormalities were observed during the period of intraoperative ECG changes. He was treated with nitroglycerin infusion. Confirmation of a perioperative myocardial infarct was documented by postoperative 12-lead ECG and CPK-MB. A post-operative transthoracic echocardiogram showed a hypokinetic left ventricle with an anteroapical infarct. Thus transoesophageal echocardiography failed to detect an apical wall motion abnormality when the probe was placed at the midpapillary level. This limitation can be overcome by periodically obtaining apical views or by using probes with more than one imaging plane.     

Elevated serum insulin-like growth factor binding protein-2 as a prognostic marker in patients with ovarian cancer.

PURPOSE: The purpose of this research was to examine the diagnostic and prognostic significance of elevated serum insulin-like growth factor binding protein (IGFBP)-2 levels in women with ovarian cancer from diagnosis through treatment to relapse or remission. EXPERIMENTAL DESIGN: Serum collected pre- and postoperatively in women newly diagnosed with ovarian cancer, during adjuvant chemotherapy cycles, at 6 months follow-up and at relapse was analyzed for IGFBP-2. Control serum was from women undergoing pelvic or abdominal surgery for benign ovarian disease or nonovarian pathology. RESULTS: IGFBP-2 at diagnosis was significantly elevated (P < 0.0001) in women with ovarian cancer (887 +/- 62 ng/ml) compared with benign controls (337 +/- 25 ng/ml), and women undergoing nonovarian surgery (439 +/- 49 ng/ml) and correlated positively with tumor stage and cellular differentiation but not with CA125. Unexpectedly, IGFBP-2 levels increased additionally 1-week postoperatively in ovarian cancer patients (1581 +/- 90 ng/ml; P = 0.0027) as well as controls (977 +/- 95 ng/ml; P < 0.0001) and was higher in women who had suboptimal debulking compared with optimal debulking of their tumor. IGFBP-2 levels returned to normal in women without evidence of progressive disease, but remained significantly elevated in women who later relapsed. Patients with IGFBP-2 levels in the highest tertile at diagnosis had a significantly shorter progression-free interval and overall survival. CONCLUSION: In ovarian cancer IGFBP-2 is elevated at diagnosis, and corresponds to stage and histology with patients in the highest tertile of IGFBP-2 more likely to relapse and have a poorer outlook. Identification of these patients at diagnosis may allow more individualized, aggressive adjuvant treatment and follow-up, and IGFBP-2 may therefore be an important additional prognostic marker in this disease.