Biomedical subjects

B Hanchard

Publications and source records attributed to B Hanchard.

At least 55 records · Page 3Linked to original sources

PubMed1996

Zidovudine and interferon therapy for adult T-cell leukaemia/lymphoma. Results of a preliminary study at UHWI-Mona.

Seven patients with adult T-cell leukaemia/lymphoma (ATL) were treated with a combination of zidovudine (AZT) and interferon after failed chemotherapy. One patient showed a major response for nine months. The remainder showed progressive disease further complicated by drug toxicity. The poor responses could be explained by patient selection, since most patients had advanced disease refractory to chemotherapy. A larger more protracted study is required for further evaluation of this treatment option.

Acute Disease↗

PubMed1995

Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac.

Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months; no chemotherapy regimen appears successful in inducing long-term disease-free survival. The scientific basis of the present study is that ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference, we administered anti-Tac armed with Yttrium-90 (90Y) to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of 90Y-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5- to 15-mCi doses used, 9 of 16 evaluable patients responded to 90Y anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (> or = grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with 90Y anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy.

Adult↗

PubMed1995

Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma incidence.

BACKGROUND: We previously reported from a case-control analysis that T-cell non-Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphotropic virus type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for HTLV-I infection was very high in younger patients. PURPOSE: The objective of this study was to estimate the age-specific incidence rates of NHL among HTLV-I-infected and HTLV-I-uninfected adults in Jamaica and Trinidad. METHODS: Population rates of HTLV-I infection were calculated from available census reports and serosurvey data. Incidence rates for NHL were calculated from all incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined whether the immunophenotype of the tumor cells was T cell, B cell, or other. NHL incidence rates were computed according to HTLV-I status, age, sex, and tumor phenotype for each country separately and for both countries combined by weighting to the relative population size of each country. RESULTS: The age-standardized NHL incidence rate (mean +/- SE) in Jamaica was 1.9 +/- 0.2 per 100,000 person-years (PY). In Trinidad, the rate was 2.9 +/- 0.4 per 100,000 PY. Overall, the incidence of NHL increased with age and was higher in males than in females. In the HTLV-I-infected population, the incidence of NHL was inversely related to age, and age-specific rates were higher in males than in females. The NHL incidence in those estimated to have acquired HTLV-I infection in childhood, however, showed no sex difference, and one in 1300 such carriers (95% confidence interval: one in 1100 to one in 1600) per annum were estimated to be at such risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was highest in those patients infected with HTLV-I early in life (perinatally or via breast milk), with high, sustained risk from early adulthood in both sexes. CONCLUSIONS: While overall NHL incidence rates reveal that HTLV-I endemicity does not impose an exaggerated lymphoma burden on these populations, the risk for lymphoma among carriers who acquire infection early in life is dramatic and is consistent with the hypothesis that virus exposure early in life is most important for lymphoma-genesis. IMPLICATIONS: Studies of HTLV-I carriers known to be infected in childhood may provide insight into markers intermediate in the lympho-magnetic process. Strategies to disrupt early-life transmission of HTLV-I, notably mother-infant transmission, may be critical in reducing the burden of lymphoreticular disease in these populations.

Adolescent↗

PubMed1995

Human T-cell lymphotropic virus type I and severe neoplasia of the cervix in Jamaica.

Human T-cell lymphotropic virus type I (HTLV-I) was associated with carcinoma of the cervix in Japan in a recent study that compared hospital cases with healthy population-based controls. To test this relationship in women more alike for cervical neoplasia risk factors (including sexual behavior and human papilloma virus; HPV), we enrolled consecutive patients from a colposcopy clinic in Kingston, Jamaica (an HTLV-I endemic area). Patients underwent Pap smear, colposcopy, biopsy and cervical swab for detection of HPV by polymerase chain reaction. Cases were defined as women with CIN-3 or invasive cancer (CIN-3/CA). Controls included all patients with either CIN-I or koilocytotic atypia, atypical squamous cells of undetermined significance or benign cervical pathology (all but one had at least inflammatory changes). Patients with CIN-2 were excluded to minimize risk of case-control misclassification. Cases were much more likely to be HTLV-I seropositive than controls. Although mean age differed significantly between cases (mean age = 39 years) and controls (mean age = 33 years), control for age did not explain the relation of CIN-3/CA with HTLV-I. Among HPV DNA positive subjects the age-adjusted association was not diminished but lost statistical significance. HTLV-I seroprevalence may be independently associated with progression to severe neoplasia of the cervix.

Adult↗

PubMed1995

Distribution of HLA and haplotypes of Colombian and Jamaican black populations.

To investigate the genetic background of the black populations of Colombia and Jamaica, we determined HLA types of 78 Colombian and 98 Jamaican blacks from 2 different socioeconomic groups (Jamaican #1 and Jamaican #2) and estimated the frequencies of HLA genes and haplotypes. A phylogenetic tree based on the HLA gene frequencies revealed that Jamaican #1 and Jamaican #2 were distinct from each other, Jamaican #1 being closely related to the Colombian blacks and the Jamaican #2 being closely related to Senegalese and Zairean populations. Three-locus HLA haplotypes of Colombian and Jamaican #1 blacks were an admixture between Africans and Caucasians or South American Indians, while Jamaican #2 blacks were relatively homogeneous and appeared to conserve African lineages. The major five-locus HLA haplotypes were not shared among Colombian, Jamaican #1 and Jamaican #2 blacks. These results indicated that the black populations of Colombia and Jamaican were originated from African blacks and admixed variably with Caucasians and South American Indians to make genetic subpopulations in Colombia and Jamaica.

Black People↗

PubMed1995

IgA antiphospholipid antibodies in HTLV-1-associated tropical spastic paraparesis.

A retrovirus, human T cell lymphotropic virus type 1 (HTLV-1), is an essential but not a sufficient aetiologic factor for tropical spastic paraparesis (TSP). Because some TSP patients have biological false positive tests for treponemal infections (BFP-STS), we used ELISA to study BFP-STS and anticardiolipin antibodies in 42 Jamaican TSP patients. The data indicate that in TSP anticardiolipin antibodies occur in about 26% of patients, are associated with biological false positive treponemal serology, are relatively restricted to the IgA isotype and may be induced by HTLV-1 or other nontreponemal infections.

Adult↗

PubMed1995

Tropical spastic paraparesis occurring in HTLV-1 associated infective dermatitis. Report of two cases.

An association between HTLV-1 infection and infective dermatitis (ID) a relapsing eczematous condition of Jamaican children, was reported in 1990. These patients are at risk of developing other known HTLV-1 related diseases. We have observed the development of HTLV-1 associated myelopathy/tropical spastic paraparesis in two patients, ages 14 and 35 years, who were diagnosed with ID at ages 2 and 10 years, respectively. Infective dermatitis of children serves as an early marker of HTLV-I infection and may predict later development of either the malignant outcome, adult T-cell leukaemia/lymphoma or the neurologic manifestation HAM/TSP among adult carriers of HTLV-1 infection.

Adolescent↗

PubMed1995

Age-specific incidence of cancer in Kingston and St. Andrew, Jamaica, 1988-1992.

During the period 1988-1992, a total of 4,030 malignant neoplasms were recorded in Kingston and St. Andrew, Jamaica. These comprised 1,829 in males and 2,201 in females. Histological confirmation was obtained in 83.4%. The crude incidence rate for males was 128.5, and 136.2 for females. The age-standardized rates (ASR) were 179.9 for males and 166.1 for females. Age-specific rates by site, sex and age are tabulated. Attention is drawn to increased incidence for cancers of prostate, larynx, bronchus and non-Hodgkin's lymphoma in males. There was also an increase in female breast cancer (crude rate 36.0; ASR 47.1). Invasive cervix cancer has shown no significant change in incidence. Neoplasms of the body of the uterus have increased (crude rate 7.6; ASR 9.5). The rise in cancer of breast and body of uterus suggests that the influence of exogenous oestrogens should be considered.

Adolescent↗

PubMed1994

Adult T-cell leukemia/lymphoma: a working point-score classification for epidemiological studies.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy that occurs most frequently in south-western Japan and the Caribbean basin. The primary etiologic agent for this disease, human T-lymphotropic virus type I (HTLV-I), is endemic in these areas. Only a small percentage of individuals infected with HTLV-I develop ATL. The factors that determine the development of malignant disease as an outcome of HTLV-I infection in an individual are unknown. ATL is histopathologically heterogeneous and firm diagnosis is made on the contribution of clinical, laboratory and histopathologic features. The wide variety of laboratory assays available to geographically diverse populations has led to a need to standardize the criteria for determining the diagnosis of this disease for epidemiologic studies. This report summarizes current information regarding ATL and proposes a classification facilitating comparison of case series in geographically and ethnically different populations.

Adult↗

PubMed1994

Viral-specific humoral immune responses following transfusion-related transmission of human T cell lymphotropic virus type-I infection.

The immunoglobulin (Ig) isotypes of antibodies to specific proteins of the human T cell lymphotropic virus type I (HTLV-I) were determined by Western blot analysis of serial specimens from six individuals who experienced HTLV-I seroconversion following blood transfusion; five remained asymptomatic carriers, while one developed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) 32 weeks posttransfusion. Analysis of Ig isotypes demonstrated that while IgM was the most frequent early response to gag (p19, p24) and env (r21e) proteins within the first 3 months following transfusion, IgG and IgA responses could also be detected within this period. HTLV-I-specific antibody responses plateaued in all Ig isotypes, including IgM, within the next 4- to 6-month period following transfusion and persisted through the entire study period (> 4 years). Comparison of antibody profiles in Ig isotypes and IgG1 and IgG3 subclass among asymptomatic carriers and one individual who developed HAM/TSP demonstrated no evidence of isotypic prominence or IgG subclass restriction in either group. These results indicate the appearance of HTLV-I-specific IgM that persists even after the primary infection and suggest that such response does not appear to provide an early marker of seroconversion. Further, we found no evidence of isotypic prominence or restriction of the antibody response in recipients who remained asymptomatic compared to one who developed HAM/TSP.

Blotting, Western↗

PubMed1994

Helicobacter pylori in patients undergoing upper endoscopy in Jamaica.

One hundred and two consecutive patients undergoing upper gastrointestinal endoscopy were tested for H. pylori by a rapid urease test, using antral biopsy specimens. There were 60 men (mean age 54 yrs) and 42 women (mean age 49 yrs). Fifty-six patients (55%) were positive for H. pylori. Of male patients, 36 (60%) and of female patients, 20 (48%) tested positive. Sixty-eight per cent of patients with antral gastritis, 65% with duodenal ulcer and 60% with gastric ulcer had H. pylori. Thirty-nine patients (70%) positive for H. pylori were from major urban areas, and 17 (30%) were from rural areas of Jamaica. In patients without H. pylori, 61% and 39% were from urban and rural areas, respectively. Forty-four patients (79%) with H. pylori and 40 (87%) without H. pylori had piped water in their homes. Ninety-three per cent of all patients had electricity and 88% had refrigeration. There was no difference between patients positive or negative for H. pylori with regard to the use of alcohol, marijuana or tobacco. There was also no difference between both groups in exposure to domestic animals in the home environment. H. pylori is associated with antral gastritis and peptic ulcer disease in Jamaican patients. There are no specific environmental or social factors that seem to predispose to infection.

Duodenitis↗

PubMed1993

Role of HTLV-I in development of non-Hodgkin lymphoma in Jamaica and Trinidad and Tobago. The HTLV Lymphoma Study Group.

Human T-cell lymphotropic virus type I (HTLV-I) has been implicated in the aetiology of adult T-cell leukaemia/lymphoma in Japan and elsewhere, particularly the Caribbean. We have carried out parallel case-control studies in Jamaica and in Trinidad and Tobago to quantify the role of HTLV-I in the development of non-Hodgkin lymphoma (NHL). 135 cases of NHL were enrolled in Jamaica and 104 in Trinidad and Tobago. Controls were selected from patients treated in the same wards or clinics at the same time as the cases. Overall, patients with NHL were 10 times more likely than were controls to be seropositive for HTLV-I (Jamaica odds ratio 10.3 [95% CI 6.0-18.0], Trinidad and Tobago 14.4 [7.6-27.2]). In both countries the association between NHL and HTLV-I was greatest for T-cell lymphomas (18.3 [9.5-35.6] and 63.3 [25-167]). Among T-cell lymphomas especially, there was no significant difference between men and women in the association between NHL and HTLV-I, but there was a significant inverse relation between age and likelihood of HTLV-I seropositivity. B-cell lymphomas were predominant in the older age groups and were not associated with HTLV-I seropositivity. These findings are consistent with the hypothesis that early life exposure to HTLV-I is important for risk of subsequent ATL. Prevention of vertical transmission of HTLV-I could reduce by 70-80% cases of NHL in people under 60 years in this region.

Adult↗

PubMed1993

Sibling adult T-cell leukemia/lymphoma and clustering of human T-cell lymphotropic virus type I infection in a Jamaican family.

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) infection is endemic in Jamaica, with an estimated crude seroprevalence of 5%. Adult T-cell lymphoma/leukemia (ATL), a disease caused by HTLV-I, has an incidence of 1-2/100,000 in the Jamaican population. Familial ATL has not previously been reported from Jamaica. METHODS: Hospital records and histologic specimens of the two cases were reviewed. HTLV-I infection was confirmed by antibody testing and by polymerase chain reaction on paraffin-embedded tissue, where serum was unavailable. Family members were identified by the patients' parents. After giving informed consent, family members were asked to complete an interviewer-administered questionnaire and to agree to phlebotomy. RESULTS: ATL developed 10 years apart in two siblings from a Jamaican family at age 16 and 24 years. A study of 19 members of their extended family, including both parents, 2 grandparents, and 3 siblings, revealed an overall HTLV-I seroprevalence of 17%. This compared with 75% among parents and siblings living in the same household as the patients. HTLV-I antibody-positive (HTLV-I-positive) and negative family members had similar mean age. Three of 3 HTLV-I-positive subjects were breast-fed, compared with 10 of 15 HTLV-I-negative subjects. Intravenous drug abuse, sex with prostitutes, homosexuality, and blood transfusion were not reported. The mean number of sexual partners were similar. Both parents, who were antibody-positive, had polylobated atypical lymphocytes in their peripheral blood. CONCLUSION: The HTLV-I antibody seroprevalence is greater in the family than in the general population, consistent with the modes of transmission. The antibody seronegativity of both grandmothers suggests sexual transmission between parents. The development of ATL at age 16 and 24 years is consistent with maternal-infant transmission and a long latent period, as reported by other authors.

Adolescent↗

PubMed1993

Mother-to-child transmission of human T-cell lymphotropic virus type I (HTLV-I) in Jamaica: association with antibodies to envelope glycoprotein (gp46) epitopes.

To study mother-to-child transmission of HTLV-I in Jamaica, we screened antenatal patients in Kingston, Jamaica, from 1983 to 1985. Of 2,329 women, 81 (3.5%) were HTLV-I seropositive. Two to three years later, 36 seropositive mothers were recontacted, and blood was drawn from them and their children. All sera were tested for HTLV-I antibodies, and mother's sera were additionally tested for HTLV-I whole-virus antibody titer, syncytium-inhibition neutralizing antibody titer, and titers to six synthetic peptides from the HTLV-I envelope glycoprotein gp46. Seventeen of 74 (23%) [95% confidence interval (CI) 15-34%] children were seropositive. HTLV-I transmission was associated with breast-feeding duration > 6 months [relative risk (RR) 3.2; CI 0.4-22.1], maternal age > 30 years (RR 2.8; CI 1.0-7.8), and higher maternal whole-virus antibody titer (RR 3.3; CI 1.3-8.5). After controlling for higher whole-virus antibody titer, transmission remained associated with higher titer of neutralizing antibody and higher titer of antibody to the peptide sp4a1, corresponding to amino acids 196-209 of the gp46 envelope glycoprotein. We conclude that mother-to-child transmission of HTLV-I in Jamaica is associated with longer duration of breast-feeding, older age, and higher HTLV-I antibody titer, in particular to a certain immunogenic portion of the gp46 envelope glycoprotein.

Adolescent↗

PubMed1993

Cytotoxic activities of recombinant immunotoxins composed of Pseudomonas toxin or diphtheria toxin toward lymphocytes from patients with adult T-cell leukemia.

We have previously shown that the recombinant single-chain immunotoxin anti-Tac(Fv)-PE40, composed of the variable domains of the anti-Tac monoclonal antibody in a single-chain form joined to a derivative of Pseudomonas exotoxin (PE), is cytotoxic toward malignant cells from adult T-cell leukemia (ATL) patients. Using this assay, we have now compared the activity of anti-Tac(Fv)-PE40 with that of an improved version, anti-Tac(Fv)-PE40KDEL which contains an altered carboxyl terminus, and also with two chimeric toxins made with diphtheria toxin (DT). One of these is a fusion of amino acids 1-388 of DT with anti-Tac(Fv) and is termed DT388-anti-Tac(Fv). The other, DT388-IL2, contains interleukin 2 (IL2) at the carboxyl terminus of the same DT derivative. We incubated these toxins with malignant ATL peripheral blood mononuclear cells (PBMCs) for 1-3 days and then measured [3H]leucine incorporation. We found that anti-Tac(Fv)-PE40KDEL was the most cytotoxic agent and was followed in decreasing order of activity by anti-Tac(Fv)-PE40, DT388-anti-Tac(Fv), and finally DT388-IL2. Trypan blue staining showed that inhibition of protein synthesis correlated with cell death. Time course studies showed that the recombinant toxins containing anti-Tac(Fv) were cytotoxic even if exposed to the cells for only one hour. After intravenous injection into mice, the half-life of anti-Tac(Fv)-PE40 or anti-Tac(Fv)-PE40KDEL was 30 minutes. Normal PBMCs were resistant to all four toxins. Recombinant immunotoxins made with anti-Tac merit further study as potential reagents in the treatment of ATL.

Adult↗

PubMed1992

A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion.

To evaluate the risk of transfusion-related transmission of HTLV-I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV-I serological screening assay. This information would prove useful in formulating strategies for blood-donor screening. We followed 118 pre-transfusion HTLV-I-negative transfusion recipients at monthly intervals post-transfusion for 1 year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV-I seroconversion was estimated and risk-factor data associated with seroconversion among 66 HTLV-I-exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44%) of recipients of HTLV-I-positive cellular blood components, 0/12 recipients of positive non-cellular donor units and 0/52 recipients of HTLV-I-negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week [odds ratio (OR) = 6.34, 95% confidence interval (CI) = 1.83 to 21.92], male sex (OR = 4.79, 95% CI = 1.15 to 20.0) or use of immuno-suppressive therapy at time of transfusion (OR = 12.20, 95% CI = 0.95 to 156). Risk of blood-borne infection per person per year in Jamaica was estimated to be 0.009%. Our results confirm that blood transfusion carries a significant risk of HTLV-I transmission and that screening of donor blood effectively prevents HTLV-I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood-donor screening for HTLV-I is not possible.

Blood Donors↗

PubMed1992

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the progression to and maintenance of the leukemic state in vivo is unclear because of the inability of most previous studies to readily detect HTLV-I RNA in infected individuals. By using the reverse transcriptase-polymerase chain reaction, we detected spliced messages for the HTLV-I pX regulatory genes in primary uncultured cells from ATL patients and healthy asymptomatic carriers. In addition to the expected doubly spliced pX message, three alternatively spliced mRNAs were demonstrated (pX delta 17, pX-p21rex, and pX-orfII mRNAs, where orf = open reading frame). The same splice sites were shown in the messages from uncultured ATL cells and from the HTLV-I-producing C10/MJ cell line. Alternatively spliced pX mRNAs have the potential to code for known and putative pX gene products. Among the transcripts is a monocistronic mRNA likely to code for p21rex (pX-p21rex mRNA). Since alternative splicing of HTLV-I pX mRNA can be found in primary uncultured cells, it is likely to have a functional significance in vivo. This suggests possible roles for HTLV-I gene expression in the progression to and maintenance of ATL, as well as in the phase preceding it.

Base Sequence↗

PubMed1992

Solitary rectal ulcer syndrome.

Solitary Rectal Ulcer Syndrome (Rectal Prolapse Syndrome) is an uncommon and imperfectly understood entity which, however, should be included in the differential diagnosis of ano-rectal symptoms. This article reports on the nine cases so far diagnosed at the University Hospital of the West Indies (UHWI), and offers a brief review of the condition.

Adult↗