Bone marrow mononuclear cell count does not predict neutrophil and platelet recovery following autologous bone marrow transplant: value of the colony-forming unit granulocyte-macrophage (CFU-GM) assay

The common use of the marrow autograft mononuclear cell (MNC) count derives from positive correlative studies following allogeneic transplantation and from earlier conflicting data regarding the value of the bone marrow autograft colony-forming unit granulocyte-macrophage (CFU-GM) assay for prediction hematologic recovery after ABMT. We conducted a retrospective analysis at our institution to determine whether autograft CFU-GM levels predict engraftment of neutrophils and platelets after ABMT in heavily pretreated patients with hematologic malignancies. Between 1 January 1993 and 1 March 1995, 58 heavily pretreated patients received only marrow cells as the autograft product. Patients with Hodgkin's disease (n = 25), acute myeloid leukemia (n = 19), and non-Hodgkin's lymphoma (n = 14) underwent intensive therapy with etoposide and melphalan. Unpurged marrow containing a minimum of 1.5 x 10(8)/kg (range: 1.5-4.8) was infused. Median time to an absolute neutrophil count > or = 0.5 x 10(9)/L was 21 days (range 10-270) and median time to a platelet count > or = 20 x 10(9)/L independent of transfusions was 44 days (range 13-317). There was no correlation between autograft MNC count and neutrophil or platelet engraftment. However, a correlation between autograft CFU-GM and both platelet and neutrophil recovery was demonstrated with a threshold CFU-GM of 3 x 10(4)/kg; delayed neutrophil recovery was observed in 79% of patients below this threshold compared to only 9% in those with an autograft CFU-GM level of more than 3 x 10(4)/kg (p = 0.0001). Similarly, platelet recovery was delayed in 76% of patients below, and 20% of those above this threshold (p = 0.003). We conclude that marrow autograft CFU-GM is predictive of engraftment of both platelets and neutrophils in heavily pretreated patients after ABMT for hematological malignancies.     

Traumatic dental injuries in a cohort of 16-year-olds in northern Sweden

The prevalence and yearly incidence of traumatic tooth injury between 1 and 16 years of age were studied in a cohort of 16-year-olds, born in 1975, and residing in the County of V?sterbotten, northern Sweden. The study comprised 3007 dental records from the public dental health service. The general distribution was 50.3% girls and 49.7% boys. The records showed that 35% of the children on one or more occasions had sustained injury to their primary or permanent dentition. The frequency was nearly twice as high for boys (64%) as for girls (36%). Twenty-five percent of the 16-year-olds had met with tooth injury more than once and this group consisted predominantly of boys. The incidence of injury episodes to primary and permanent teeth was 28 per 1000 per year. The boys had sustained trauma to their teeth most frequently when they were 4 years of age and between the ages of 8 and 11. This was also true for girls at 4 and at 9 years of age, although less evidently so. In the primary dentition, the majority of dental injuries had affected the supporting tissue of the maxillary incisors. In the permanent dentition, 75% of the traumatised teeth were upper incisors. Fractures of varying severity constituted 60% of all registered diagnoses in this dentition, followed by subluxation (19%) and concussion (11%).     

Evaluation of biologic gastrin activity of compound CI-988 in the isolated, vascularly perfused rat stomach

BACKGROUND: The peptoid CI-988 has previously been shown to have high affinity for the cholecystokinin (CCK)-B/gastrin receptor and has been reported to be a powerful CCK antagonist in many systems, although it has agonist activity on histidine decarboxylase in the rat. METHODS: In the present study the effect of CI-988 on acid secretion and histamine release in the totally isolated, vascularly perfused rat stomach was assessed. RESULTS: CI-988 was found to be a gastrin agonist with regard to the stimulation of both histamine release and acid secretion. CONCLUSION: Thus, in this stomach model CI-988 behaved as a CCKB/gastrin agonist. The present study underlines the importance of testing the biologic activity of ligands in models with sufficient sensitivity.     

Oncogenic RAS genes impair erythroid differentiation of erythroleukaemia cells

RAS mutations occur frequently in acute myeloid leukaemia and myelodysplasia, suggesting a functional role for this oncogene in leukaemogenesis. We show here, for the first time, that both N-RAS and H-RAS can impair erythroid differentiation of erythroleukaemia cells induced with hexamethylene bisacetamide. Transformation by RAS allowed extended proliferation in the presence of inducer and also inhibited maturation as measured by impaired haemoglobinization and reduction in cell size. These data provide an interesting counterpoint to the effect of mutant RAS on monocytic cells, where it has a potentiating effect on differentiation and may indicate a causal link between the activation of RAS and erythroid lineage dysplasia in preleukaemia.     

P2Y2 nucleotide receptors expressed heterologously in sympathetic neurons inhibit both N-type Ca2+ and M-type K+ currents

The P2Y2 receptor is a uridine/adenosine triphosphate (UTP/ATP)-sensitive G-protein-linked nucleotide receptor that previously has been reported to stimulate the phosphoinositide signaling pathway. Messenger RNA for this receptor has been detected in brain tissue. We have investigated the coupling of the molecularly defined rat P2Y2 receptor to neuronal N-type Ca2+ channels and to M-type K+ channels by heterologous expression in rat superior cervical sympathetic (SCG) neurons. After the injection of P2Y2 cRNA, UTP inhibited the currents carried by both types of ion channel. As previously reported [Filippov AK, Webb TE, Barnard EA, Brown DA (1997) Inhibition by heterologously expressed P2Y2 nuerones. Br J Pharmacol 121:849-851], UTP inhibited the Ca2+ current (ICa(N)) by up to 64%, with an IC50 of approximately 0.5 microM. We now find that UTP also inhibited the K+M current (IK(M)) by up to 61%, with an IC50 of approximately 1.5 microM. UTP had no effect on either current in neurons not injected with P2Y2 cRNA. Structure-activity relations for the inhibition of ICa(N) and IK(M) in P2Y2 cRNA-injected neurons were similar, with UTP >/= ATP > ITP > GTP,UDP. However, coupling to these two channels involved different G-proteins: pretreatment with Pertussis toxin (PTX) did not affect UTP-induced inhibition of IK(M) but reduced inhibition of ICa(N) by approximately 60% and abolished the voltage-dependent component of this inhibition. In unclamped neurons, UTP greatly facilitated depolarization-induced action potential discharges. Thus, the single P2Y2 receptor can couple to at least two G-proteins to inhibit both Ca2+N and K+M channels with near-equal facility. This implies that the P2Y2 receptor may induce a broad range of effector responses in the nervous system.     

Children''s dental health in Europe. Caries treatment need in 5- and 12-year-old children from eight EU countries

An analysis of how time was used in and around 60 consultations was carried out for the purpose of exploring the relationship of time use to patient satisfaction. Sixty patients across two practice settings were surveyed, immediately following their interaction with the audiologist, regarding satisfaction with the consultation. Satisfaction was measured via: (1) a four-point scale, which yielded a satisfaction rating; and (2) a check list of satisfaction with 11 aspects of the consultation, which yielded a satisfaction score. Satisfaction ratings and scores were correlated significantly (rs = 0.76 corrected for ties, P = 0.0001). The majority of patients were either 'very satisfied' (63%) or 'satisfied' (31.6%) with the consultation experience. Temporal pictures of the consultations of 'very satisfied', 'satisfied' and 'dissatisfied' patients were clearly different. For the present sample it appeared that patient satisfaction ensued when the total consultation time was equal to or exceeded 0.6 of the sum of total consultation time and the time spent waiting at the clinic immediately prior to the consultation. Regression analyses showed that of the temporal variables studied, total consultation time (TCT) and the amount of time waiting immediately pre consultation (WT) contributed most to the variation in patient satisfaction ratings and scores. Forty-two per cent of the variance in satisfaction ratings and 36% of the variance in satisfaction scores could be explained by TCT/(WT + TCT).     

Regulation of early cholesterol biosynthesis in rat liver: effects of sterols, bile acids, lovastatin, and BM 15.766 on 3-hydroxy-3-methylglutaryl coenzyme A synthase and acetoacetyl coenzyme A thiolase activities

BACKGROUND: Sclerosing peritonitis (SP) is a rare but serious complication of peritoneal dialysis (PD). Small-bowel obstruction (SBO) due to encapsulation, dense adhesions, or mural fibrous is characteristic, often associated with peritonitis. The aim of the study was to determine the incidence, clinical features, effect of duration of dialysis, and other possible aetiological factors in severe SP. METHODS: All dialysis units in Australia were surveyed for possible cases up to 1994. Patients were included if there was either surgical or radiological evidence of sclerosing encapsulating peritonitis or SBO with tanned or thickened peritoneum in the absence of other causes of SBO. RESULTS: Fifty-four patients were analysed. The duration of continuous PD was mean 52 +/- 30 months, median 48 months and range 8-127 months. Nineteen cases were diagnosed between 1980 and 1989 and 35 between 1990 and 1994, giving mean annual incidences 1.9 and 4.2 per 1000 PD periods respectively. The overall prevalence was 0.7%, which increased progressively with the duration of PD being 1.9, 6.4, 10.8, and 19.4% for patients on dialysis for > 2, 5, 6 and 8 years respectively. Sclerosing encapsulating peritonitis was diagnosed in 87% of cases, SBO in 92%, and haemoperitoneum in 8%. Peritoneal calcification was present in seven cases, all of which had been on PD > 7 years. Peritonitis was associated with 38% of cases with fungal infection in 7%. Treatment with immunosuppression in five patients appeared to result in a favourable outcome in three. The mortality rate was 56%. CONCLUSION: Severe sclerosing peritonitis is a serious complication of peritoneal dialysis and there is a time dependent increase on CAPD.