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Biomedical subjects

W N Gibbs

Publications and source records attributed to W N Gibbs.

At least 37 records · Page 2Linked to original sources

2'-Deoxycoformycin therapy in adult T-cell leukemia/lymphoma.

Six Caribbean patients with histologically and immunologically characterized adult T-cell leukemia/lymphoma (ATL) were treated intravenously (IV) with 2'-deoxycoformycin (DCF) at a dose of 5 mg/m2 on days 1, 2, 8, 15, and 22 with four additional weekly doses to convert any partial responses (PR) to complete responses (CR). Patients were considered eligible for this study if refractory to or relapsed from combination chemotherapy, had a life expectancy of 4 weeks or more, a performance status greater than or equal to 50%, normal renal and hepatic function, and no chemotherapy within 4 weeks. Clinical characteristics of the patients in this study included lymphadenopathy in five patients, skin involvement in four patients, bone marrow infiltration in five patients, and central nervous system involvement in two patients. Circulating ATL cells were present in four patients, and three were hypercalcemic. Of five patients evaluable for response, there was one PR of 1 month, and two minor responses lasting 2 and 3 weeks. The median duration of survival for all treated patients was 3 weeks or more. The DCF was associated with moderate side effects, including conjunctivitis in three patients, nausea and vomiting in two patients, progressive hepatic insufficiency in one patient, and moderate myelotoxicity in three patients. Infections occurred in four patients, including two cases of oral candidiasis and two cases of fatal neutropenic sepsis in patients receiving concurrent intrathecal methotrexate. As a single agent, DCF appears to have limited activity in advanced refractory/relapsed ATL. Studies in the future should explore DCF in combination with other cytotoxic agents as initial therapy in better-risk patients.

Adult↗

Non-Hodgkin lymphoma in Jamaica and its relation to adult T-cell leukemia-lymphoma.

Of 95 patients consecutively diagnosed with non-Hodgkin lymphoma, 52 (55%) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positivity was strongly associated with skin involvement, leukemia, and hypercalcemia (p less than 0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 9 patients had indolent courses and a median survival of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinant of adult T-cell leukemia-lymphoma.

Adolescent↗

Molecular and immunologic analysis of a chronic lymphocytic leukemia case with antibodies against human T-cell leukemia virus.

The human T-cell leukemia virus type-I (HTLV-I) is a unique, exogenous, horizontally transmitted retrovirus which is T-cell tropic, and has been associated with a specific type of aggressive leukemia/lymphoma of mature T-cell origin. In a survey of lymphoid malignancies in Jamaica, antibodies to HTLV-I were also found in 6 of 17 patients with chronic lymphocytic leukemia (CLL), raising the possibility of an etiologic relationship. Further studies were undertaken on one of these patients to clarify the nature of the disease and possible virus relationship. Cell surface marker analysis of her peripheral blood cells documented that the majority of circulating lymphocytes were B-cells. DNA-cloned probe analysis with a complete HTLV-I proviral genome of these peripheral malignant B-cells, was negative for integrated virus. A T-cell line was established in culture from her peripheral blood. The presence of HTLV-I in the cultured T-cell line was established by the detection of expressed viral specific gag protein p-19 and proviral DNA. Thus, a B-cell lymphoid malignancy can occur in the presence of HTLV-I infected T-cells, suggesting the possibility of an indirect leukemogenic mechanism.

Aged↗

Seroepidemiologic studies of human T-cell leukemia/lymphoma virus type I in Jamaica.

The prevalence of HTLV-I antibodies was evaluated in Jamaica among persons with various malignant, infectious, autoimmune and hematologic disorders and in clinically normal persons. Results document that: (1) the prevalence of HTLV-I antibodies in this population increases with age; (2) overall, there is no significant difference in the antibody prevalence between males and females; (3) antibody-positive individuals are born in all major regions of the island and geographical variance in antibody prevalence by place of birth was not prominent; (4) there is further confirmation of the high prevalence of HTLV-I antibody-positive lymphomas in Jamaica; and (5) the prevalence of HTLV-I antibodies in hemophiliacs, patients with chronic lymphocytic leukemia (CLL), myelogenous leukemias, and patients with breast cancer is higher than in the age-matched population without malignancies, although none of these differences were statistically significant. The increased prevalence in hemophiliacs is most likely related to their frequent transfusion with blood products, but it has not yet been determined whether the prevalence in patients with other diseases is related to their diseases or other as yet undefined factors in common.

Adolescent↗

Adult T-cell leukemia/lymphoma in Jamaica and its relationship to human T-cell leukemia/lymphoma virus type I-associated lymphoproliferative disease.

We had shown previously that the prevalence of human T-cell leukemia/lymphoma virus type I (HTLV-I)-antibody positivity is high in Jamaican non-Hodgkin's lymphoma (NHL) patients and that virus-positive patients have the clinical features and poor prognosis of adult T-cell leukemia/lymphoma (ATL). Sixty-two % of 45 NHL patients diagnosed consecutively between 2/1/82 and 1/31/84 and studied prospectively were HTLV-I-antibody positive. Skin involvement (38%), hypercalcemia (44%), and leukemia (40%) were unusually prevalent and there was a strong association (p less than 0.05) with HTLV-I-antibody positivity. Fifty-two % of the patients had bone marrow infiltration, and 74% of these patients were HTLV-I-antibody positive (p = 0.06). Lymphadenopathy (96%), hepatomegaly (60%), and splenomegaly (25%) were detected with about the same frequency as in other series of NHL patients with advanced disease, and 61-88% of these patients were HTLV-I-antibody positive. Patients were classified into those with "typical ATL" (NHL associated with 2 of the 4 features i) hypercalcemia; ii) histologically proven skin infiltration; iii) leukemia; and iv) bone marrow infiltration, providing that the morphology of infiltrating or leukemic cells was characteristic of ATL; those "consistent with ATL" (NHL associated with 1 of these 4 features); and "non-ATL" (NHL without any of these 4 additional features). Thirty-two (71%) of the NHL patients were ATL patients, i.e., had features typical of or consistent with ATL, and 78% of these were HTLV-I-antibody positive. HTLV-I provirus was detected in tumour cells of all HTLV-I-antibody positive patients tested. Three (23%) of the non-ATL patients were HTLV-I-antibody positive. There was no correlation between histopathological features and the clinical classification or HTLV-I-antibody positivity. Median survival of ATL and non-ATL patients was 16 and 53 weeks. Although the disease was usually fulminant, 34% of the ATL patients had a subacute or chronic course. Skin involvement and leukemia were prominent in these patients. Hypercalcemia was the chief prognostic determinant. Median survival of hypercalcemic and normocalcemic ATL patients was 13 and 86 weeks (p less than 0.05). Hypercalcemia caused 10 deaths, infections 12, and death was due to tumour progression in 4 patients. Infections were usually due to pyogenic organisms and only 2 patients had systemic opportunistic infections. Six (27%) of 22 chronic lymphocytic leukemic (CLL) patients were HTLV-I-antibody positive.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

HTLV: epidemiology and relationship to disease.

With the discovery of the human retrovirus class, an important turning point in the understanding of the process by which cancer is caused and develops in humans has been achieved. As summarized here, clinical and epidemiologic studies have documented the close association of human T-cell leukemia virus (HTLV-I) to a particular form of T-cell malignancy, adult T-cell leukemia/lymphoma (ATL). Yet to be understood is the process involved in translating virus infection into malignant lymphoproliferation. Epidemiologic data suggest that this may involve a relatively long latent period between primary HTLV-I infection and subsequent malignancy risk. Presumably, identifiable co-factors will emerge to explain the trigger for malignant transformation. However, the restricted pattern of tumor phenotype suggest that this process is tightly linked to cells for which HTLV-I has a particularly strong infectious trophism. Interdisciplinary studies are currently under way in a number of laboratories to elucidate the molecular interactions in the HTLV-I associated malignant transformation process in order to correlate these with the epidemiologic data. Thus, lessons are likely to be learned from these molecular and epidemiologic studies which may provide new and important etiologic insights applicable to the prevention and therapy of cancer. Furthermore, with the recent discovery of HTLV-III, a cytopathic form of this class of human retrovirus, the likely cause of acquired immunodeficiency syndrome (AIDS) has been discovered. This has enormous public health implications for the detection, treatment, and prevention of this major medical epidemic. Epidemiologic studies are currently under way to identify what factors associated with virus exposure result in the full-blown AIDS syndrome. In addition, the malignancy potential of this new type of retrovirus is currently the subject of intensive investigation.

Acquired Immunodeficiency Syndrome↗

Human T-cell leukaemia/lymphoma virus-associated lymphoreticular neoplasia in Jamaica.

19 (34%) of 56 Jamaicans with lympho-proliferative neoplasia had antibody to the human T-cell leukaemia/lymphoma virus (HTLV) in their sera. 17 of those positive had either non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukaemia. Of 16 consecutive patients presenting with NHL, 11 (69%) were HTLV seropositive. Virus-positive patients with NHL, among whom females were over-represented, had the clinical features and poor survival typical of adult T-cell leukaemia/lymphoma. HTLV-associated leukaemia/lymphoma is a distinct clinicopathological entity, and the high incidence in this series suggests that HTLV is an important cause of lymphoreticular neoplasia in Jamaica.

Adult↗

Glucose-6-phosphate dehydrogenase deficiency and homozygous sickle cell disease in Jamaica.

The relationship between D-glucose-6-phosphate: NADP oxido-reductase (E.C.1.1.1.49; glucose-6-phosphate dehydrogenase; G6PD) deficiency and homozygous sickle cell (SS) disease was examined in 120 patients. The proportions of hemizygotes (22.6%) was slightly more than that observed, and the combined proportions of heterozygotes and homozygotes (28.3%) were slightly less than would be expected, in the general population, but the differences were not significant. However, the proportion of patients of abnormal G6PD status in the 10-19 years age group was 41.7%, significantly more than that found in the 20-29 years age group (0.02 less than P less than 0.05), or expected in the general population (P=0.05). Possible reasons for this are discussed. Difference in G6PD status did not affect the total haemoglobin concentration, reticulocyte count, unconjugated serum bilirubin or Hb F concentration, irreversibly sickled cell counts or plasma haemoglobin concentration, and there was no demonstrable correlation between clinical severity or leg ulceration and abnormal G6PD status.

Adolescent↗

Glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Jamaica.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency was detected in 16 (69.6%) of a group of 23 neonates who had unexplained moderate or severe jaundice. This proportion is significantly more than the 9.4% observed or the 22.2% expected in Jamaican neonates who are not moderately or severely jaundiced (P less than 0.003), and significantly more than the 12.6% observed or the 21.0% expected in older Jamaican children and adults (P less than 0.003). Phenobarbitone therapy and phototherapy reduced the need for exchange transfusion but this was necessary in eight patients. Two babies developed kernicterus and one died. On the other hand, only two of 21 neonates who were identified as G6PD deficient at birth subsequently became moderately or severely jaundiced, and this could be attributed to other causes in both cases. These findings indicate that apparently spontaneous neonatal jaundice is important in infants who have the G6PD A--enzyme. However, the jaundice is probably precipitated by unknown factors to which the G6PD deficient neonate is more susceptible than the infant who is not G6PD deficient. THere is also a slightly increased incidence of G6PD deficiency in neonates who develop jaundice because of ABO or Rh(D) iso-immune disease, infection or prematurity.

Adolescent↗