Molecular basis of reduced or absent expression of decay-accelerating factor in Cromer blood group phenotypes

The human erythrocyte blood group system Cromer consists of high- incidence and low-incidence antigens that reside on decay-accelerating factor (DAF; CD55), a glycosyl-phosphatidylinositol-anchored membrane protein that regulates complement activation on cell surfaces. In the Cromer phenotypes Dr(a-) and Inab there is reduced or absent expression of DAF, respectively. This study investigated the molecular basis of the reduced DAF expression by polymerase chain reaction amplification of genomic DNA and RNA/cDNA obtained from Epstein-Barr virus- transformed lymphoblastoid cell lines. Sequence analysis of the Inab propositus showed a single nucleotide substitution in exon 2 of the DAF gene and at the corresponding position in the cDNA, G314-->A resulting in Trp53-->Stop. This truncation near the amino terminus explains the complete absence of surface DAF in the Inab phenotype. A similar analysis was performed for two Dr(a-) individuals, including KZ, who was previously reported to be Inab phenotype but is now shown by immunochemical and serologic methods to be Dr(a-) phenotype. A single nucleotide change was found in exon 5 of the DAF gene, C649-->T resulting in Ser165-->Leu, which we had previously shown to lead to loss of the Dra epitope. However, two species of cDNA were found, one encoding full-length DAF with the single amino acid change and the more abundant species having a 44-nucleotide deletion. The 44 nucleotide deletion includes the single polymorphic site, which creates a cryptic branch point in the Dr(a-) allele that leads to use of a downstream cryptic acceptor splice site. This shifts the reading frame and leads to a premature stop codon that precludes membrane anchoring. Thus, the single point mutation in the Dr(a-) phenotype results in a novel use of alternative splicing and provides a molecular explanation for both the antigenicity and the reduced DAF expression seen in this phenotype.     

Naproxen sodium in the treatment of migraine

Seventy patients with classical or common migraine were treated during their attacks with either naproxen sodium or placebo in a randomised, double-blind parallel group study. The initial dose of naproxen sodium was 825 mg followed one hour later by a further 550 mg, if symptoms were the same or had improved. If the migraine symptoms had worsened, patients were offered an escape analgesic combination of 1000 mg paracetamol and 10 mg metoclopramide. Patients were assessed at monthly intervals for changes in the severity and duration of headache, premonitory symptoms (mainly visual disturbances) and photophobia, nausea and vomiting associated with migraine attacks that had occurred since the previous visit. Patients were studied for a maximum of ten attacks and significant improvement was observed in the severity and duration of headache when the patients were on naproxen sodium. Also the premonitory symptoms and photophobia improved significantly on naproxen sodium and significantly less rescue analgesics were required. Patients suffering from common migraine had less severe headaches and photophobia when taking naproxen sodium than when taking placebo and the headaches were shorter in duration and patients took less rescue analgesic. No significant difference was observed between the treatment groups in patients with classical migraine. Ten patients in the placebo group and six in the naproxen sodium group reported side-effects but these were possibly related to the use of rescue medication. Naproxen sodium proved safe and effective in common migraine attacks, but in this study efficacy was not established for classical migraine.     

Epidemiology of paediatric trauma admissions at Queen Elizabeth Central Hospital,Blantyre

We conducted an audit of paediatric trauma admissions to QECH, Blantyre, in September 2003. There were 107 trauma cases representing 8.8% of all paediatric admissions and mean age was 6 years. The commonest cause of trauma was falls (42.9%) followed by burns (31.8%) and road traffic accidents (14.9%). Of the road traffic accidents, only one case was a passenger, the rest were pedestrians hit by moving vehicles. Fracture of limbs was the commonest injury sustained (44.9%) and burns the second commonest injury (31.8%). Most (52.6%) children were brought into hospital within 24 hours of injury while 26.3% came in between 24 hours and 48 hours and 21.1% after 48 hours or more. Death occurred in 7.5% of cases. The mean number of days in hospital was 8.9 days.     

Presentation,management,and outcome of newly diagnosed glioblastoma in elderly patients

OBJECT: Optimum management for elderly patients with newly diagnosed glioblastoma(GBM) in the temozolomide(TMZ) era is not well defined.The object of this study was to clarify outcomes in this population.METHODS: The authors retrospectively reviewed 105 consecutive cases involving elderly patients(age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008.RESULTS: The patients’ median age was 74 years(range 66-87 years),and the median Karnofsky Performance Status(KPS) score was 80(range 40-90).Half of the patients underwent biopsy and half underwent resection.Patients with deep-seated lesions(19 patients [18%]) or multifocal lesions(34 patients [32%]) were more likely to have biopsy than resection(p = 0.0001 and 0.0009,respectively).New persistent neurological deficits developed in 7 patients(6.7%).Postoperative hemorrhage occurred in 6 patients(5.7%),all of whom underwent biopsy.Complete follow-up data regarding adjuvant treatment was available in 84 patients.Forty-one(49%) were treated with chemotherapy(mostly TMZ) and radiation therapy(RT),and 23(27%) with RT alone.Nineteen(23%) received only palliative care after surgery(more common with biopsy,p = 0.03).Chemotherapy complications occurred in 28.6%(Grade 3 or 4 hematological complications in 11.9%).The median values for progression-free survival(PFS) and overall survival(OS) were 3.5 and 5.5 months.In a multivariate analysis,younger age(p = 0.03,risk ratio [RR] 0.34,95% CI 0.13-0.89),single lesion(p = 0.02,RR 0.51,95% CI 0.30-0.89),resection(p = 0.04,RR 0.54,95% CI 0.31-0.94),and adjuvant treatment(p = 0.0001,RR 0.24,95% CI 0.11-0.49) were associated with better OS.Only adjuvant treatment was significantly associated with prolonged PFS(p = 0.0007,RR 0.27,95% CI 0.13-0.57).With combined therapy with resection,RT,and chemotherapy,the median PFS and OS were 8 and 12.5 months,respectively.CONCLUSIONS: The prognosis for GBM worsens with increasing age in elderly patients.With important risks,resection and adjuvant treatment are associated with prolonged survival.Although selection bias cannot be excluded in this retrospective study,advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.     

Eradication of minimal disease in severe combined immunodeficient mice with disseminated Daudi lymphoma using chemotherapy and an immunotoxin cocktail

Severe combined immunodeficient (SCID) mice injected intravenously with a human Burkitt's lymphoma cell line (Daudi) develop disseminated lymphoma (SCID/Daudi), which is fatal in 100% of the mice. Early treatment of these mice with either an immunotoxin (IT) cocktail (consisting of anti-CD19-ricin A chain plus anti-CD22-ricin A chain) or chemotherapy significantly prolonged survival but was not curative. Combination therapy with the IT cocktail and any one of three chemotherapeutic drugs (doxorubicin, cytoxan, or camptothecin) cured the mice. Cure was demonstrated by both histopathologic examination of treated mice and, more importantly, by adoptive transfer of cells from organs of the cured mice to naive SCID mice where 100 tumor cells would have caused disease in the recipients. These results provide a strong rationale for combining IT therapy with conventional chemotherapy in the treatment of B-cell neoplasia.     

Serum potassium values in relation to the use of diuretics in patients with unstable angina pectoris

Transient hypokalaemia may occur in acutely ill patients andis associated with an increased incidence of life-threateningarrhythmias. Therefore, we performed a retrospective analysisof the serum potassium values of 538 patients with unstableangina included in the Holland Interuniversity Nifedipine/metoprololTrial in relation to the use of diuretics. On admission, 113of these patients used diuretics. Potassium sparing diureticshad been used in 65 Patients (group A) and non-potassium sparingdiuretics in 48 patients (group B). From the 425 patients noton diuretics a random sample of 56 (group C) was drawn. Bloodsamples were taken routinely on admission to the coronary careunit. The serum potassium values found for groups A, B and Cwere 3.77±0.55, 3.44±0.69 and 4.14±0.48,respectively, and the prevalence of hypokalaemia (<3.6 mmol)40, 65 and 14% respectively. Rate ratio [95% confidence interval(C1)] for hypokalaemia when compared to groups C was 2.6 (1.2–5.6)group A and 4.9 (2.4–10.1) for group B. The prevalenceof hypokalaemia was higher for women than for men (rate ratio,95% C1: 1.4, 0.9–2.2). Patients already on beta-blockertherapy showed a 10% lower prevalence of hypokalaemia (rateratio, 95% C1: 0.7, 0.5–1.1). These data were compared with serum potassium values of 104patients with stable angina, who reported to the outpatientclinic. These patients were also divided into three groups accordingto the use of diuretics. Only in 15% of the patients using non-potassiumsparing diuretics was hypokalaemia observed. These findings indicate that patients with unstable angina havelow serum potassium levels and a high prevalence of hypokalaemiaon admission to the coronary care unit. Potassium levels areinfluenced positively by pre-existing beta-blockade and stronglynegatively by diuretics, especially non-potassium sparing diuretics.The effect of beta-blockers suggest a transient catecholaminedependent mechanism.     

Jejunal Biopsies in Protein-calorie Malnutrition and Intestinal Parasitic Infestation in Brazil

Jejunal biopsies were performed in 71 subjects, who were classified into three groups as follows: Forty-one patients, on a poor diet, without clinical signs of malnutrition, with and without parasitic infestation; nineteen patients with severe protein-calorie malnutrition, with and without parasitic infestation; control group, ten medical students and one of the authors on a normal diet and without parasitic infestation.
The dissecting microscope appearance showed mild alteration of the intestinal villi of Group A patients with parasitic infestation and severe alteration on Group B patients, especially those with parasitism.
On histological examination, only the total mucosal thickness showed statistically significant differences between the Group B (severe protein malnutrition) and the other groups.     

A device to measure in vivo forces in human flexor tendons during carpal tunnel operations

An apparatus has been designed to measure the in vivo forces transmitted along human hand flexor tendons during carpal tunnel release procedures. The tendon will be run through three hooks, the central one of which is attached to a load cell. The rationale is that once these forces are known this will aid in the design of repair techniques and rehabilitation regimens. As a first stage, an in vitro validation study is presented using cord subjected to varying forces to mimic an in vivo flexor tendon under varying conditions of use. Our results show that we can accurately and reproducibly measure the force in the cord.     

Long-term degradation of resin-based cements in substances present in the oral environment: influence of activation mode

Indirect restorations in contact with free gingival margins or principally within the gingival sulcus, where the presence of organic acids produced by oral biofilm is higher, may present faster degradation of the resin-based cement pellicle.

Objectives:

To investigate the degradation of four resin-based cements: Rely X ARC (R), Variolink II (V), enforce (E) and All Cem (A), after immersion in distilled water (DW), lactic acid (LA) and artificial saliva (AS) and to analyze the influence of the activation mode on this response.

Material and Methods:

Two activation modes were evaluated: chemical (Ch) and dual (D). In the dual activation, a two-millimeter thick ceramic disk (IPS empress System) was interposed between the specimen and light-curing unit tip. Specimens were desiccated, immersed in distilled water, artificial saliva and lactic acid 0.1 M at 37ºC for 180 days, weighed daily for the first 7 days, and after 14, 21, 28, 90 and 180 days and were desiccated again. Sorption and solubility (µg/mm³) were calculated based on ISO 4049. The data were submitted to multifactor analysis of variance (MANOVA) and Tukey''s HSD test for media comparisons (α=0.05).

Results:

Sorption was higher after immersion in LA (p<0.05) and increased significantly with time (p<0.05). Sorption was influenced by the activation mode: Ch>D (p<0.05). The lowest solubility was presented by R (p<0.05).

Conclusions:

Lactic acid increased the degradation of resin-based cements. Moreover, the physical component of activation, i.e., light-activation, contributed to a low degradation of resin-based cements.