Lymphohematopoietic progenitors of normal mice

We have identified and characterized the lymphohematopoietic progenitors in the bone marrow of normal mice using a single-step methylcellulose culture assay. Lineage-negative Ly-6A/E (Sca-1)+ progenitors isolated from normal mice were plated in methylcellulose culture containing steel factor (SF), interleukin-7 (IL-7), erythropoietin (Ep), and IL-11. After 16 to 17 days of culture, pre-B- cell-containing multilineage myeloid colonies can be microscopically identified; however, flow-cytometric analysis of individual colonies for B220-positive cells proved superior to in situ microscopic identification of lymphomyeloid colonies. Approximately 10% (6/66) of the mixed colonies without a conspicuous B-cell component had B220- positive cells. The single cell origin of the lymphomyeloid colonies was confirmed by micromanipulation. Although the combination of SF, IL- 7, and Ep was sufficient to support formation of lymphomyeloid colonies, addition of IL-11, granulocyte colony-stimulating factor or IL-12 to the combination of SF, IL-7, and Ep increased the number of lymphomyeloid colonies. IL-1 alpha and IL-3 independently inhibited the expression of the B-lymphoid lineage when added to the combination of SF, IL-7, Ep, and IL-11. Approximately four times more lymphohematopoietic progenitors are present in normal mice than in mice treated with 5-fluorouracil.     

Intraobserver and interobserver variation of ultrasound diagnosis of Oesophagostomum bifurcum colon lesions

Infection by the nematode Oesophagostomum bifurcum is focally distributed in Africa and causes a syndrome of abdominal pain, obstruction, or abdominal mass because of its predilection for invasion of colonic mucosa. To determine the reliability of ultrasound for the detection of colon pathology induced by this parasite, three studies to assess the intraobserver and interobserver variation of the technique were performed. In an area of northern Ghana endemic for O. bifurcum, 181 people from a low-prevalence village and 62 people from a high-prevalence village were examined twice by the same observer, and 111 people were independently examined by two observers in a moderately endemic village. The kappa statistics for the prevalence observations in the three studies were 0.82, 0.87, and 0.81, respectively, and kappa values for the intensity observations were 0.66, 0.63, and 0.71, respectively. The upper 95% confidence intervals of the average absolute difference in nodule size measurements in Study 1 and Study 3 were 3.6 and 4.5 mm, respectively. Therefore, ultrasound is useful in the diagnosis and management of O. bifurcum colon infection.     

Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation

The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone.     

International validation of the Chinese University Prognostic Index for staging of hepatocellular carcinoma:a joint United Kingdom and Hong Kong study

The outcome of hepatocellular carcinoma （HCC） patients significantly differs between western and eastern population centers. Our group previously developed and validated the Chinese University Prognostic Index （CUPI） for the prognostication of HCC among the Asian HCC patient population. In the current study, we aimed to validate the CUPI using an international cohort of patients with HCC and to compare the CUPI to two widely used staging systems, the Barcelona Clinic Liver Cancer （BCLC） classification and the Cancer of the Liver Italian Program （CLIP）. To accomplish this goal, two cohorts of patients were enrolled in the United Kingdom （UK; n = 567; 2006-2011） and Hong Kong （HK; n = 517; 2007-2012）. The baseline clinical data were recorded. The performances of the CUPI, BCLC, and CLIP were compared in terms of a concordance index （C-index） and were evaluated in subgroups of patients according to treatment intent. The results revealed that the median follow-up durations of the UK and HK cohorts were 27.9 and 29.8 months, respectively. The median overall survival of the UK and HK cohorts were 22.9 and 8.6 months, respectively. The CUPI stratified the patients in both cohorts into three risk subgroups corresponding to distinct outcomes. The median overall survival of the CUPI low-, intermediate-, and high-risk subgroups were 3.15, 1.24, and 0.29 years, respectively, in the UK cohort and were 2.07, 0.32, and 0.10 years, respectively, in the HK cohort. For the patients who underwent curative treatment, the prognostic performance did not differ between the three staging systems, and all were suboptimal. For those who underwent palliative treatment, the CUPI displayed the highest C-index, indicating that this staging system was the most informative for both cohorts. In conclusion, the CUPI is applicable to both western and eastern HCC patient populations. The performances of the three staging systems differed according to treatment intent, and the CUPI was demonstrated to be optimal for those     

Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.      

The Heartsink Patient: A Preliminary Study

Eight GPs identified 78 heartsink patients; in an open-endedinterview they were asked to explain why they regarded themin this way. A GP's definition of a heartsink patient was influencedby GP sex, practice location, and time of surgery, althoughthe number of participating GPs was too low to make any definiteassertions. Practitioners' anticipations of heartsink consultationswere generally over-exaggerated, with most of the encountersgoing better than expected. GPs expressed the view that thesepatients raised serious professional issues for them, whilstthere was also a dislike for these patients' personalities andbehaviour. Two levels of the heartsink state are hypothesized:one, a state of inertia, is when the heartsink patient has beena chronic high user of the primary health care system, and aGP has exhausted all avenues. The other is an acute situationwith those heartsink patients who have been low users of thesystem in the past. Recent, new events in these patients' liveshave raised an issue that is just as much to do with patientand doctor reaction to these events, as it is about findinga diagnosis or solution to the problem. We present the results and hypotheses to provoke further discussionand research.     

Proteinuria, hematuria, and leukocyturia in children with mixed urinary and intestinal schistosomiasis

Quantitative parasitological assessment and quantitative analysis of proteinuria, hematuria, and leukocyturia were carried out in 182 Sudanese schoolboys with mixed urinary and intestinal schistosomiasis. Pathological proteinuria was found in 73% of patients (median = 380, 95% confidence limits = 200 to 500 mg/liter). The median protein/creatinine ratio was 0.54. SDS polyacrylamide gel electrophoresis showed an excretion of albumin, transferrin, and IgG consistent with a postrenal pattern of proteinuria. Pathological erythrocyturia occurred in 84% of patients (median = 255, 95% CL = 95 to 629 cells/microliter) and leukocyturia in 77% of patients (median = 148, 95% CL = 93 to 246 cells/microliter). Phase contrast microscopy revealed intact erythrocytes, suggestive of postrenal hemorrhage. Proteinuria, erythrocyturia, and leukocyturia correlated significantly with the ova excretion in the urine, but not with egg excretion in the stool. Oxamniquine reduced ova excretion in the stool but did not influence pathological urine findings. In patients treated effectively with Praziquantel or Metrifonate, pathological PU, EU, and LU decreased markedly 1 month post treatment. PU in severely proteinuric patients reached physiological values 5 months post therapy. We suggest that the proteinuria, erythrocyturia, and leukocyturia in mixed schistosomiasis were of postrenal origin.