The predicted primary structure of the measles virus hemagglutinin

The complete nucleotide sequence of cloned cDNAs corresponding to the full length of the mRNA encoding the measles virus hemagglutinin (H) protein has been determined. the mRNA contains a single large open reading frame which is capable of encoding a protein of 617 amino acids with a molecular mass of 69,250 Da. The deduced amino acid structure of the protein indicates that the only major hydrophobic region of sufficient length to anchor the molecule in membranes is located near the amino terminus. Comparison of the amino acid structure of the measles virus H protein with that of the hemagglutinin-neuraminidase (HN) molecules of Sendai virus and simian virus 5 (SV5) reveals little homology. However, 11 of the 13 cysteine residues found in the measles H protein can be aligned with cysteines in the Sendai virus HN protein in similar positions relative to one another. Five potential N-linked glycosylation sites are present in the measles H protein sequence. These are relatively closely grouped between amino acids residues 168 and 240 in the amino terminal half of the molecule. No obvious structural features are present in the measles H protein amino acid sequence which might explain the reported absence of neuraminidase activity associated with the molecule.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Cell-mediated immune responses to Plasmodium falciparum purified soluble antigens in sickle-cell trait subjects

To determine the possible differences in the immune response to Plasmodium falciparum between sickle-cell trait (Hb AS) and normal haemoglobin (Hb AA) individuals, we examined 35 Hb AS and 24 Hb AA subjects matched for age and microenvironment. Their age was 2-55 years and all lived in a malaria endemic area 300 km south of Khartoum. Antibodies to ring-infected erythrocyte surface antigen (Pf155/RESA) and to circumsporozoite (CS) protein (anti-NANP40) indicated equal exposure to falciparum malaria. Peripheral blood mononuclear cells (BMNCs) from 20/35 (57%) Hb AS subjects compared with 10/24 (42%) Hb AA subjects, responded to affinity-purified P. falciparum soluble antigens (SPAg). Of those responding to SPAg, 9 (26%) Hb AS subjects and only two (8%) Hb AA subjects had high responses. The mean proliferative response to SPAg of BMNCs from Hb AS individuals was significantly higher than in Hb AA individuals (P less than 0.025). Responses of BMNCs to PPD and PHA were also higher among Hb AS individuals and correlated positively with responses to SPAg. These findings support the hypotheses that the sickle-cell trait protects individuals from P. falciparum infections, at least in part, by modulating the immune response.     

Perinatal outcomes in inflammatory bowel disease

Objective: To determine whether inflammatory bowel disease (IBD) is associated with increased risk for adverse perinatal outcome.

Methods: A case–control study of 116 singleton pregnancies with IBD compared to 56?398 singleton controls delivered between 1986 and 2001.

Results: Patients with IBD were slightly older (32.8 vs. 30.6 years, p <?0.001), more likely to be Caucasian or Asian than Black or Latino (92% vs. 57%, p <?0.001) and have private health insurance (33% vs. 3%, p <?0.001). IBD was associated with an increased risk for labor induction (32% vs. 24%, p?=?0.002), chorioamnionitis (7% vs. 3%, p?=?0.04) and Cesarean section (32% vs. 22%, p?=?0.007), but there were no differences in neonatal outcomes. Subgroup analysis demonstrated an increased risk for low birth weight (LBW) in the ulcerative colitis group vs. the Crohn's disease group (19% vs. 0%, p?=?0.002). Patients with prior surgery for IBD had a lower incidence of LBW (0% vs. 12%, p?=?0.03). Flares during pregnancy were associated with an increased risk for preterm delivery (27% vs. 8%, p?=?0.02) and LBW (32% vs. 3%, p?=?0.003).

Conclusion: IBD was an independent risk factor for Cesarean section but there was no increase in adverse perinatal outcome. Crohn's disease, prior IBD surgery and quiescent disease were associated with a lower risk for LBW.     

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease. Atherosclerotic renovascular disease is an important cause of end-stage renal disease (ESRD). The exact incidence of ESRD and the rate of decline in glomerular filtration rate (GFR) in patients with this condition is unknown. We report the mortality, the rate of decline in renal function, and incidence of ESRD in 51 patients with bilateral atherosclerotic renovascular disease followed-up for a median period of 52 months. None of these patients had undergone any surgical or radiological intervention. Renal function was determined by serial measurements of serum creatinine. Bilateral atherosclerotic renovascular disease was associated with a high mortality rate; the crude mortality rate at 60 months was 45%. Assessment of renal function showed impaired renal function at time of angiography and a nonuniform and variable decline in renal function during the period of observation. The median GFR decreased from 39 mL/min (range, 15 to 80 mL/min) at time of angiography to 31 mL/min (range, 10 to 70 mL/min) and 24 mL/min (range, 10 to 40 mL/min) at 24 and 60 months, respectively (P < 0.05). The calculated mean rate of decline in GFR for all patients was 4 mL/min/yr (range, 1 to 16 mL/min/yr). Over the 5 years, there was a progressive increase in the incidence of ESRD. Of the original 51 patients who underwent angiography, six patients reached ESRD. The crude incidence of ESRD was, therefore, 12%. Patients who reached ESRD were characterized by advanced azotemia at the time of angiography (median GFR, 25 mL/min) and a rapid decline in GFR (8 mL/min) compared with patients who did not reach ESRD during the observation period (median GFR, 43 mL/min and an average rate of decline GFR of 3 mL/min).     

Radiotherapy for melanotic freckles

Five patients who received radiotherapy (RT) for 7 melanotic freckles (MF, also known as Hutchinson's freckles, lentigo maligna) were reviewed 8 to 37 months after their treatment by RT. Local control and a favourable cosmetic result occurred in all patients. Treatment toxicity was minimal. Few reports about the use of RT for MF exist. Many other treatments including observation alone have been associated with high rates of recurrence, and in some cases conversion to invasive melanoma has occurred. RT appears to be a safe and effective treatment for this condition, providing that doses equivalent to 44 Gy in 11 fractions or more are given.     

Tarsal navicular stress fractures: radiographic evaluation

Tarsal navicular stress fractures are a potential source of disabling foot pain in physically active individuals. The diagnosis of tarsal navicular stress fracture requires a high index of clinical and radiographic suspicion because the fracture is only rarely evident on routine radiographs or standard tomograms. The radiographic diagnosis of a tarsal navicular stress fracture may require anatomic anteroposterior tomograms or a radionuclide bone scan with plantar views. Radiographic examinations of 23 fractures in 21 patients are evaluated.