Outcomes and mutational analysis of patients with lower-risk non-del5q myelodysplastic syndrome treated with antithymocyte globulin with or without ciclosporine A.

Immunosuppressive treatment is a disease-modifying therapy for lower-risk myelodysplastic syndromes (MDS). However, IST is relatively rarely used and long-term outcomes of patients are seldom reported. We retrospectively studied outcomes of 20 patients with lower-risk non del 5q MDS with transfusion dependency, with horse or rabbit antithymocyte globulin ±â€¯ciclosporine A, and frontline eltrombopag in two of them. IPSS-R was low, intermediate and high in 30%, 55% and 10% of the patients, respectively. Fifty-five percent of the patients had hypocellular bone marrow (BM). Baseline mutations were detected in 31.5% of the patients and were more frequent in patients with normo/hypercellular MDS than in patients with hypocellular MDS. Transfusion independence rate for both red blood cells (RBC) and platelets was achieved in 45% of patients. RBC transfusion duration ≤6 months, B-cell counts >0.2 G/L and, marginally, BM blasts ≤2% were associated with higher transfusion independence rate. Age and cellularity did not influence the response rate. Median transfusion independence duration was 53 months. Cumulative incidence of progression to a more aggressive myeloid disease was 0 in patients without baseline mutations and 33% in patients with baseline mutations (P = .008). Median progression-free and overall survival after treatment onset and median overall survival after loss of transfusion independence were 45.5 months, 68 months and not reached, respectively. In conclusion, antithymocyte globulin ±â€¯ciclosporine A results in durable responses in MDS, irrespective of age, in patients with lower-risk disease without B-cell lymphopenia and treated early in the course of the disease.

A randomized controlled trial comparing the efficacy and acceptability of phospo-soda buffered saline (Fleet) with sodium picosulphate/magnesium citrate (Picoprep) in the preparation of patients for colonoscopy.

OBJECTIVE: Small-volume bowel preparations for colonoscopy has become increasingly popular due to improved tolerance by patients and equivalent efficacy compared with the larger volume preparations. Comparative studies, however, between small volume preparations are lacking. This randomized controlled trial aimed at comparing the efficacy and acceptability of phospo-soda buffered saline (Fleet) with sodium picosulphate/magnesium citrate (Picoprep) in the preparation of patients for colonoscopy. METHOD: A randomized prospective trial designed to compare the efficacy and acceptability of Fleet with Picoprep in patients undergoing colonoscopy. RESULTS: Seventy-three patients undergoing colonoscopy were randomized to receive either Fleet or Picoprep as bowel preparation. Patients were asked to score the acceptability and to comment specifically on adverse events, namely headache, nausea and vomiting. The efficacy of the preparation was also assessed. The results showed no difference in efficacy (P = 0.06, chi(2) test), but there was a significant difference in acceptability (P = 0.01, chi(2) test). and side effects of patients suffering nausea (P = 0.003, chi(2) test), in favour of Picoprep. CONCLUSION: Whilst there was no difference in efficacy, there was a significant difference in acceptability and side effects in favour of Picoprep.

Relationship between entomological inoculation rate, Plasmodium falciparum prevalence rate, and incidence of malaria attack in rural Gabon.

To assess the relationships between variations of Plasmodium falciparum transmission and those of peripheral parasitaemia prevalence or malaria attack incidence rates in regions with limited fluctuations of transmission, we conducted a follow-up in two Gabonese populations. Entomological surveys were carried out from May 1995 to April 1996 in Dienga, and from May 1998 to April 1999 in Benguia. In Dienga, malaria transmission was seasonal, being not detected during two 3-month periods. Mean entomological inoculation rate (EIR) was 0.28 infective bite/person/night. In Benguia, malaria transmission was perennial with seasonal fluctuations, mean EIR being 0.76 infective bite/person/night. In Dienga, 301 schoolchildren were followed from October 1995 to March 1996. Clinical malaria attack was defined as fever associated with >5000 parasites/microl of blood. P. falciparum prevalence varied from 28 to 42%, and monthly malaria attack incidence from 30 to 169 per thousand. In Benguia, the entire population (122 persons) was followed from November 1998 to April 1999. Prevalence varied from 22 to 50%, and monthly malaria attack incidence from 52 to 179 per thousand. In each area, entomological variations were not related to parasite prevalence, but preceded malaria attack incidence with 1- or 2-month time lag, corresponding to the pre-patency period that differs in the two populations, possibly according to differences in immunity related to parasite transmission.

Hyperplastic polyposis of the colon and rectum.

The significance of multiple hyperplastic polyps in relation to the risk of colon cancer is unknown although recent investigation suggests a causative link. We have prospectively identified a small but distinct group of patients that also suggests an association. These patients have either numerous (usually more than twenty, in sites other than the rectosigmoid alone) or large (greater than 1 cm) hyperplastic polyps, in association with either adenomatous polyps, polyps of mixed pathology or carcinoma of the colon and rectum. Additionally, there is frequently a first or second degree family history of colorectal carcinoma.

HLA alleles in relation to specific immunity to liver stage antigen-1 from plasmodium falciparum in Gabon.

Cellular responses to synthetic peptides from the Liver Stage Antigen-1 (LSA-1) from Plasmodium falciparum were determined in 229 Gabonese children. HLA class I and II typing (by PCR-SSP and -RFLP, respectively) revealed that HLA-A*19, -B*17 (and -B*70), -DRB1*05, -DQA1*0102, -DQB1*0602 and -DPB1*0402 were the most frequent types or alleles at each locus. The DQB1*0201 and DQB1*0301 alleles were present at a higher frequency among IL-6 and IFN-gamma responders to the LSA-Rep and LSA-CTL peptides, respectively, and a higher proportion of these responders carried A*19 or B*53. The DRB1*06 type was positively related to the IL-10 production in response to the LSA-CTL peptide, and responders presented mainly A*2. The specificity A*10 was negatively associated with the cellular response to the LSA-J peptide. These results suggest a degree of genetic regulation of specific immune responses by HLA-A, operating at the pre-erythrocytic stage of development of P. falciparum in this Central African population.

Neo-adjuvant therapy improves resectability rates for colorectal liver metastases.

PURPOSE: Liver resection improves survival in selected patients with colorectal liver metastases. However, the majority of patients with colorectal liver metastases have inoperable disease at presentation. Neo-adjuvant therapy (systemic or regional chemotherapy and interstitial laser therapy) used singly or in combination may convert a selected group of patients with irresectable liver metastases into an operable state. PATIENTS AND METHODS: We report a series of patients with initially inoperable multiple colorectal liver metastases who became operable after neo-adjuvant therapy. Operability was defined as unilateral disease limited to the liver. Twelve patients (7 female, 5 male, median age 57 years, range 38-69 years) with multiple inoperable colorectal liver metastases (8 synchronous, 4 metachronous) were initially treated with systemic chemotherapy (n = 7), hepatic arterial chemotherapy (n = 2) and chemotherapy plus interstitial laser therapy (n = 3). RESULTS: In all cases, a significant response was achieved which enabled subsequent liver resection to be undertaken. There was only one postoperative complication (8%) and no peri-operative deaths. 3 patients were operated on within the last 12 months and are still alive. Of the remainder, 1 died within 1 year with recurrent disease. The remaining patients have a median survival of 2.5 years, range 1.39-4 years. CONCLUSIONS: These results are similar to those reported for patients undergoing resection for operable metastases without neo-adjuvant therapy. Aggressive multimodality treatment of colorectal liver metastases in specialised centres may improve the resectability rates and survival in a selected group of patients.

Immune responses against Plasmodium falciparum asexual blood-stage antigens and disease susceptibility in Gabonese and Cameroonian children.

The frequency and level of cellular and humoral responses to seven synthetic peptides from asexual blood stages of Plasmodium falciparum were measured in two cohorts of children living in areas highly endemic for malaria in Gabon and Cameroon. A prospective longitudinal study was conducted for one year in these sites to examine the relationship between specific in vitro immune responses and susceptibility to clinical malaria. Clinical protection was related to high proliferative responses (merozoite surface antigen-1 [MSA-1] and MSA-2 peptides) as well as to elevated antibody levels (schizont extract, MSA-2, and rhoptry-associated protein-1 [RAP-1] peptides) in the village of Dienga, Gabon. Higher response rates of interferon-gamma but lower response rates of tumor necrosis factor-alpha to four and six peptides, respectively, were observed in Dienga than in Pouma that were independent of the older age of the Gabonese children. Age accounted only for the higher prevalence rate in Dienga of the antibody responders to the peptide from Pf155/ring-infected erythrocyte surface antigen (RESA). Our results support the inclusion of epitopes from MSA-1, MSA-2, RAP-1, and Pf155/RESA antigens in a subunit vaccine against malaria, but show that a longitudinal clinical, parasitologic, and immunologic study conducted according to identical criteria in two separate areas may lead to contrasting observations, demonstrating the geographic limitation of the interpretation of such results.

Relationships between malaria prevalence and malaria-related morbidity in school children from two villages in central Africa.

To investigate the relationship between parasite prevalence and malaria-related morbidity, we carried out a comparative study among cohorts of school children from two villages, Dienga, Gabon, and Pouma, Cameroon, both located in malaria-endemic areas. Seven to 17 year-old children attending primary schools were similarly followed-up at each site to evaluate the frequency of malaria attacks. Follow-up involved daily temperature recording (and blood smears in the case of fever) and preparation of blood smears every two weeks. In Pouma, 186 children were followed-up for six months. In Dienga, 228 children were followed-up for nine months. The mean prevalence rate of Plasmodium falciparum infections (as assessed by the blood smears) was twice as high in Pouma compared with Dienga (45.2% versus 26.8%; P < 0.0001), whereas the monthly malaria attack rate (as assessed by the daily surveillance) was twice as high in Dienga compared with Pouma (21.5% versus 41.4%; P = 0.003). The possible implication of several parameters that may differ between the two areas, such as the malaria transmission level, the economical and social status of the inhabitants, the characteristics of infecting parasite strains, and the genetic background of the population, is discussed.

HLA class II polymorphism in a Gabonese Banzabi population.

The HLA class II typing of 167 unrelated Gabonese individuals from the Banzabi ethnic group was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The most frequent alleles at each locus were DRB1*1501-3 (0.31), DQA1*0102 (0.50), DQB1*0602 (0.42) and DPB1*0402 (0.29). The estimation of the haplotype frequencies as well as the observation of the segregation of several haplotypes using additional HLA typing of relatives, revealed that the three-locus haplotype DRB1*1501-3-DQA1*0102-DQB1*0602 was found at the highest frequency (0.31) among these individuals. This haplotype is not typically African and has already been described in Caucasians, but its presence at high frequency is exclusive to populations originating from Central Africa, and can thus be designated as a particular genetic marker of these populations.

Colorectal cancer in adolescents.

Colorectal cancer, one of the most common malignancies among adults, is rare in adolescence. This low incidence coupled with non-specific symptoms and aggressive natural history leads to a poorer prognosis than in reported adult series. This article describes two cases of colorectal cancer in adolescents and reviews the literature regarding this rare condition. Earlier diagnosis and a greater understanding of the natural history may lead to improved treatment with concomitant improvements in survival.

Leptospirosis and Ebola virus infection in five gold-panning villages in northeastern Gabon.

An exhaustive epidemiologic and serologic survey was carried out in five gold-panning villages situated in northeastern Gabon to estimate the degree of exposure of to leptospirosis and Ebola virus. The seroprevalence was 15.7% for leptospirosis and 10.2% for Ebola virus. Sixty years after the last seroepidemiologic survey of leptospirosis in Gabon, this study demonstrates the persistence of this infection among the endemic population and the need to consider it as a potential cause of hemorrhagic fever in Gabon. There was no significant statistical correlation between the serologic status of populations exposed to both infectious agents, indicating the lack of common risk factors for these diseases.

Ebola hemorrhagic fever outbreaks in Gabon, 1994-1997: epidemiologic and health control issues.

From the end of 1994 to the beginning of 1995, 49 patients with hemorrhagic symptoms were hospitalized in the Makokou General Hospital in northeastern Gabon. Yellow fever (YF) virus was first diagnosed in serum by use of polymerase chain reaction followed by blotting, and a vaccination campaign was immediately instituted. The epidemic, known as the fall 1994 epidemic, ended 6 weeks later. However, some aspects of this epidemic were atypical of YF infection, so a retrospective check for other etiologic agents was undertaken. Ebola (EBO) virus was found to be present concomitantly with YF virus in the epidemic. Two other epidemics (spring and fall 1996) occurred in the same province. GP and L genes of EBO virus isolates from all three epidemics were partially sequenced, which showed a difference of <0.1% in the base pairs. Sequencing also showed that all isolates were very similar to subtype Zaire EBO virus isolates from the Democratic Republic of the Congo.

Seroprevalence of four sexually transmitted diseases in a semi-urban population of Gabon.

Using the cluster-sampling method, the authors estimated the seroprevalence of 4 sexually transmitted diseases (STDs) among the sexually active general population in a city of 30,000 inhabitants in the east of Gabon. The seroprevalences were 2% for HIV-1, 13.8% for hepatitis B, 8.6% for Treponema pallidum and 59.6% for Chlamydia trachomatis. The seroprevalences of hepatitis B and chlamydia were stable over time and similar to those registered in other countries of central Africa. On the other hand, the seroprevalence of T. pallidum is notably low in comparison with these countries and seems to be decreasing. The seroprevalence of HIV-1 is also low but has doubled in 8 years in the city. Immigrant women from west Africa were a high-risk group for STDs but more generally, cohabiting was a risk factor for women.

PIP: Findings are presented from a seroprevalence survey of HIV, hepatitis B, syphilis, and chlamydia conducted in Franceville, Gabon, during 2 days in January 1996, in a representative sample of the sexually active general population aged 14-55 years. 456 usable sera were collected from 457 individuals recruited in 20 clusters of 25 people each. Franceville is a city of approximately 30,000 inhabitants. 2% were infected with HIV-1, 13.8% with hepatitis B, 8.6% with Treponema pallidum, and 59.6% with Chlamydia trachomatis. The seroprevalences of hepatitis B and chlamydia were stable over time and similar to those reported in other central African countries. However, the seroprevalence of T. pallidum is quite low relative to those other countries and appears to be decreasing. The seroprevalence of HIV-1 is also low, but twice the level observed in 1988.

Short-term restorative nutrition in malnourished patients: pro's and con's of intravenous and enteral alimentation using compositionally matched nutrients.

In a prospective controlled clinical study 30 patients with moderate degree of malnutrition, normal liver and kidneys, and a functioning gastrointestinal tract were randomized to receive a free amino acid and small peptide enteral diet (15 patients) or an isonitrogenous isocaloric parenteral support for at least 10 days (total energy: 2900 kcal, nitrogen: 14.5 g, carbohydrates: 380 g, fat: 112 g, N/non protein calories: 1/175). The parenteral and enteral diets had the same protein/lipid/carbohydrate composition. The data indicated that both routes led to positive nitrogen balance. Nitrogen equilibrium was achieved by day 3 in the TPN group and by day 5 in the enteral group. There were no significant changes in serum albumin within either group. Serum level of transferrin reached a significant increase in both groups (p = 0.003). Thyroxine-binding prealbumin rose significantly in both groups as well (p = 0.019 and 0.004 respectively). Statistically significant rises in lymphocyte counts (p = 0.003 and 0.001 respectively), in levels of C3 (p = 0.009 and 0.001 respectively), IgA (p = 0.002), IgG (p = 0.004 and 0.003 respectively) and IgM (p = 0.004) occurred in either treatment group. There was a high incidence of negative skin tests at the start of the study in the enteral group (73.3%) and the TPN group (60%). By the end of the study the incidence of negative results for this test was 40.0% and 26.6% respectively. Despite maintenance of similar glucose levels in both groups, TPN led to significantly (p = 0.000) higher serum insulin levels. The serum insulin increased almost linearly over the study period, and eventually prevented fat mobilization and lipolysis, so that free fatty acid levels had fallen significantly (p = 0.000). A significant elevation of the liver enzymes over the study period occurred in the TPN group, but not in the enterally fed patients. The present findings provide no evidence that semi-elemental diets are in any way inferior to isonitrogenous isocaloric regimes parenterally given for a short period of time.

Pseudoaneurysm of the radial artery complicating excision of a wrist ganglion.

A case of pseudoaneurysm of the radial artery complicating excision of a wrist ganglion is reported. Tourniquet release prior to wound closure would have allowed detection and immediate treatment of the vascular injury.

The use of thallium-201 and technetium-99m subtraction scintigraphy for the localisation of parathyroid adenomas.

Parathyroid adenomas account for approximately 85% of cases of primary hyperparathyroidism. Several preoperative localisation techniques exist to aid the surgeon during neck exploration, with varying degrees of success. We report on the results of a modification of the established technique of thallium and technetium subtraction scintigraphy. The operative findings of 60 patients undergoing neck exploration for parathyroid adenoma were correlated with preoperative thallium and technetium subtraction scintigraphy scans. The radio-isotopes were administered in the reverse order to conventional administration, resulting in enhanced imaging. The adenomatous glands were correctly localised in all cases. The 100% sensitivity of this modified scanning technique supports a strategy of unilateral scan-directed neck exploration.