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John T Manning

Publications and source records attributed to John T Manning.

29 records · Page 2Linked to original sources
PubMed2003

A pilot study of rituximab in patients with recurrent, classic Hodgkin disease.

BACKGROUND: To explore the potential role of infiltrating benign B cells in classic Hodgkin disease (HD) lesions in supporting the survival of malignant Hodgkin and Reed-Sternberg (H/RS) cells, the authors initiated a pilot study of rituximab. Rituximab is used to primarily deplete normal B cells from HD lesions. METHODS: Patients with recurrent, classic HD who had received a minimum of two prior treatment regimens, regardless of whether H/RS cells expressed CD20, were treated with 6 weekly doses of 375 mg/m2 rituximab to selectively deplete infiltrating benign B cells. Objective tumor response was determined 3 weeks after completion of the last dose of rituximab and every 3 months thereafter. Serum samples were collected from patients before they started rituximab therapy and 3 weeks after the final course of rituximab. Serum cytokine levels of interleukin 6 (IL-6), IL-10, IL-12, IL-13, and interferon gamma were determined using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Twenty-two patients with nodular sclerosis histology were evaluable for treatment response. Five patients (22%) achieved partial or complete remission that lasted for a median of 7.8 months (range, 3.3-14.9 months). Remissions were observed in patients only at lymph node and splenic sites, but not at extranodal sites, and were irrespective of CD20 expression by H/RS cells. Furthermore, systemic (B) symptoms resolved in six of seven patients after therapy. In two patients, partial remissions were associated with a decline in serum IL-6 levels. CONCLUSIONS: The current data suggest that rituximab therapy in patients with recurrent, classic HD can alter serum IL-6 cytokine levels, can improve B symptoms, and may result in clinical remissions.

Adolescent↗
PubMed2003

Melanin and HIV in sub-Saharan Africa.

HIV is common in sub-Saharan Africa. Sexually transmitted bacterial and fungal infections increase the chance of HIV infection. Melanin can prevent the penetration of skin and mucus membranes by microorganisms, and soluble melanin can inhibit HIV replication. We suggest that melanin may reduce the incidence of HIV infection through venereally acquired skin lesions, thus reducing the risk of sero-conversion and slow the progress to AIDS. Indigenous sub-Saharan peoples are highly melanized, but there is pigment variation between populations. We show that skin reflectance, a negative correlate of melanin, is positively associated with adult rate of HIV in sub-Saharan countries. There is no such relationship in populations outside sub-Saharan Africa. We suggest that melanin concentration in black people may correlate with resistance to HIV infection.

Africa South of the Sahara↗
PubMed2003

Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma.

PURPOSE: Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients. PATIENTS AND METHODS: A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT. RESULTS: The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields. CONCLUSION: With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.

Adult↗
PubMed2003

Dissolution of the lymphoid follicle is a feature of the HHV8+ variant of plasma cell Castleman's disease.

The plasma cell variant of Castleman's disease (PCD) may occur in a variety of clinical settings. One recently delineated type of PCD is caused by human herpesvirus 8 (HHV8) infection. Lymph nodes from 25 patients with PCD, including six HHV8+ and 19 HHV8- cases, were studied. Three patients with HHV8+ PCD were also infected with human immunodeficiency virus-1. Features common to all cases were interfollicular plasmacytosis and variably hyperplastic and regressed follicle germinal centers. Features associated only with HHV8+ PCD included follicle dissolution resulting from blurring of the mantle zone boundary (p = 0.0001), presence of atypical plasma cells and immunoblasts within these areas (p = 0.0006), and more prominent interfollicular vascular proliferation than in HHV8- PCD. HHV8+ cells were predominantly immunoblasts and small lymphocytes that were highly enriched in the mantle zones of altered follicles. These areas showed a predominance of plasmacytoid forms expressing lambda light chain in four of six cases. The extrafollicular fibroblastic network surrounding altered germinal centers demonstrated marked upregulation of low-affinity nerve growth factor receptor in five of five HHV8+ cases but in only two of 10 HHV8- cases. We conclude that HHV8+ PCD is distinctive histologically because of the accumulation of infected lymphocytes in the mantle zone leading to progressive dissolution of the germinal center and altered regulation of the surrounding stroma.

AIDS-Related Opportunistic Infections↗
PubMed2002

CD56(+) TdT(+) blastic natural killer cell tumor of the skin: a primitive systemic malignancy related to myelomonocytic leukemia.

BACKGROUND: An unusual cutaneous tumor that has blastic morphology and coexpresses CD56 and terminal deoxynucleotidyl transferase (TdT) has been recently recognized and termed blastic natural killer cell lymphoma. METHODS: The authors identified seven cases of such CD56(+)TdT(+) blastic tumors presenting in skin at their institution. The authors correlated clinical course with histomorphology and immunophenotype. RESULTS: All 7 patients (6 men, 1 woman, 52-85 years) presented with rapidly growing, frequently multiple cutaneous nodules. All patients had low level bone marrow involvement at diagnosis and frequently had lymph node involvement. Tumor cells were of intermediate size with irregular nuclear contours, fine chromatin, and indistinct small nucleoli. The expression of TdT varied between 5% and over 90% of the neoplastic cell population. Tumor cells were negative for surface CD3, CD5, and CD20 in all cases, but some patients showed expression of CD2 (three out of five), cytoplasmic CD3 (two out of seven), CD4 (six out of seven), and CD16 (three out of seven). Molecular studies showed absence of T-cell receptor gene rearrangements in all cases. All seven patients had rapid progression of disease, and six patients have died of their disease or complications. Three patients developed progressively increasing numbers of bone marrow blasts that had a myeloid immunophenotype and were negative for TdT and CD56. Two patients met criteria for acute myeloid leukemia at 11 and 22 months after presentation, respectively. CONCLUSIONS: CD56(+) TdT(+) blastic tumor presenting in skin is a systemic malignancy likely of primitive/undifferentiated hematopoietic origin. Patients might subsequently develop tumors of myeloid or myelomonocytic phenotype, indistinguishable from acute myelogenous leukemia.

Aged↗
PubMed2002

Epstein-Barr virus-positive B-cell lymphoproliferative disorders arising in immunodeficient patients previously treated with fludarabine for low-grade B-cell neoplasms.

We describe five patients with treated low-grade B-cell neoplasms who subsequently developed Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorders (BLPDs). The low-grade B-cell neoplasms were B-cell chronic lymphocytic leukemia in four patients and splenic marginal zone lymphoma in one patient. All patients had received treatment with fludarabine for the low-grade B-cell neoplasm, and three had also received Campath-1H. The EBV-BLPDs arose 2-12 months after completion of fludarabine therapy and morphologically resembled the EBV-BLPDs that occur in the setting of iatrogenic immunodeficiency. Molecular genetic studies showed that these lesions were clonally distinct from the low-grade B-cell neoplasm in three of four cases assessed. Two patients did not receive therapy for the EBV-BLPD. The lesions regressed spontaneously in both patients but recurred in one. One patient underwent surgical excision and remains without evidence of the EBV-BLPD. One patient received aggressive multiagent chemotherapy with a complete response initially, but the EBV-BLPD recurred after 12 months. One patient received antiviral therapy and responded completely but died 2 months later of an opportunistic infection. We conclude that patients with low-grade B-cell neoplasms treated with fludarabine, possibly in combination with other immune suppressive agents, may subsequently develop EBV-BLPDs that morphologically resemble other iatrogenic immunodeficiency-associated BLPDs. Most are clonally distinct from the underlying low-grade B-cell neoplasm. A subset of these lesions may regress without systemic therapy.

Antineoplastic Agents↗
PubMedDate not supplied

Digit ratio and hand-grip strength in German and Mizos men: cross-cultural evidence for an organizing effect of prenatal testosterone on strength.

The ratio of the length of the second and fourth digits (2D:4D), a putative proxy of prenatal testosterone (PT), is correlated with measures of physical fitness. The relationship between the organizing effect of PT on physical fitness is likely to arise as a response to intrasexual male competition for females. Physical strength is also likely to be important in intrasexual conflict, but nothing is known concerning the relationship between 2D:4D and strength. The strength of an individual is strongly influenced by body size, and 2D:4D is strongly dependent on ethnicity. We present evidence that strength, as measured from hand-grip strength, is related to 2D:4D in samples from two ethnic groups (52 Caucasian men from Germany, and 88 Oriental Mizos men from northeast India) which differed markedly in size. We found that 1) the German men were heavier and stronger, but had higher 2D:4D (lower PT) than the Mizos men; 2) a median split for grip strength into low (LGS) and high (HGS) groups showed that for right-hand 2D:4D (but not left-hand 2D:4D), the LGS men had higher 2D:4D than the HGS men; and 3) the relationships between right 2D:4D and grip strength were independent of ethnicity, age, height, and weight. Measures of grip strength correlate strongly with strength in other muscle groups, so we conclude that PT may have an early organizing effect on strength in men, and this is likely to be widespread in human groups.

Adult↗
PubMedDate not supplied

Repeatability and interobserver error of digit ratio (2D:4D) measurements made by experts.

The second-to-fourth digit ratio (2D:4D) is sexually differentiated (lower in men than in women), a likely biomarker for organizational (permanent) effects of prenatal testosterone, and a correlate of many sex-dependent, hormonally influenced traits and phenotypes. The extent of 2D:4D measurement repeatability across different research groups is unknown. This study assessed the repeatability and interobserver error of 2D:4D measurements made by 17 experts (researchers who have contributed to the 2D:4D literature). Results indicate that 2D:4D, because it is a ratio variable, is notably less precisely measurable than finger length. Absolute-agreement intraclass correlation coefficients for these traits are about 0.75 vs. about 0.95, respectively. Associations of 2D:4D with target traits were usually of small size; measurement unreliability attenuates effects. This may explain some null findings and replication failures encountered in 2D:4D research. However, agreement levels are still sufficient to permit conclusions about findings from different research groups. One implication of this is that the marked geographical and population differences in typical 2D:4D levels, as reported in the literature, are veridical, and not due to divergent measurement habits across research groups. Some practical recommendations for 2D:4D measurement are offered.

Adult↗
PubMedDate not supplied

A trade-off between early growth rate and fluctuating asymmetry in Brazilian boys.

BACKGROUND: Right-left discrepancies in normally symmetrical traits are assumed to result from inability of the individual to buffer environmental and genetic stresses. Fluctuating asymmetry (FA) may therefore signal the quality of an individual to potential mates, or to parents during early life. FA could signal the heritable ability to buffer stress-the 'good genes' hypothesis. Alternatively, FA could signal the degree of within-lifetime exposure to stress, in particular during specific sensitive periods of development--the 'good development' hypothesis. AIM: We tested the hypotheses that FA at 9 years of age is positively related to (a) fetal growth rate, (b) early infant growth rate, and (c) total post-natal growth rate. METHODS: FA, weight and height were measured in a sample of 172 boys aged 9 years from Pelotas, Brazil, who had previous measurements of weight and height at birth and 6 months. RESULTS: Fetal growth was not related to FA, however FA was positively related to total weight gain after birth (p < 0.05). This association could be broadly attributed to weight gain in the first 6 months of post-natal life (p = 0.075). Those currently obese had significantly greater FA than those non-obese (p < 0.05). CONCLUSIONS: Our results support the 'good development' hypothesis, and suggest that growth rate during an early post-natal critical window, previously linked to numerous health outcomes, also has long-term effects on FA.

Anthropometry↗
PubMedDate not supplied

The second to fourth digit ratio and asymmetry.

BACKGROUND: Deviations of physical characteristics from bilateral symmetry, in otherwise symmetric individuals, are supposed to result from environmental perturbations during development. One cause of such perturbations may be sex steroids such as testosterone and oestrogen. AIM: The study examined the relationship between second to fourth digit ratio (2D:4D), a putative negative correlate with prenatal testosterone and a positive correlate with prenatal oestrogen, and asymmetry. METHODS: Eleven traits (including the second and fourth finger lengths) were measured in a sample of 680 English children aged 2-18 years, and second to fifth finger lengths in samples of 120 Austrian and English undergraduate students aged from 17 to 30 years and 213 Polish adults aged from 26 to 90 years. RESULTS: Significant U-shaped curvilinear associations between 2D:4D and all 11 traits were found in English children with the strongest associations between 2D:4D and composite asymmetry of second plus fourth digit, and second to fifth digits. Further investigation of the relation between 2D:4D and digit asymmetries in the sample of Austrian and English undergraduates and the Polish adults confirmed significant U-shaped relationships between 2D:4D and finger asymmetries. CONCLUSION: Our data show that both low 2D:4D (a marker of high prenatal testosterone) and high 2D:4D (a marker of high prenatal oestrogen) are associated with elevated levels of asymmetry and this relationship applies particularly to finger asymmetry.

Adolescent↗