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Biomedical subjects

J T Manning

Publications and source records attributed to J T Manning.

At least 19 recordsLinked to original sources

The 2nd to 4th digit ratio and autism.

It has been suggested that autism may arise as the result of exposure to high concentrations of prenatal testosterone. There is evidence that the ratio of the lengths of the 2nd and 4th digit (2D:4D) may be negatively correlated with prenatal testosterone. We measured 2D:4D in 95 families recruited via the National Autistic Society, UK. The sample comprised a total 72 children with autism (62 males, 10 females; age range 2 to 14 years), including 23 children (20 males, three females) with Asperger syndrome (AS), 34 siblings, 88 fathers, 88 mothers and sex- and age-matched control participants. We found that the 2D:4D ratios of children with autism, their siblings, fathers and mothers were lower than population normative values. Children with AS, who share the social and communicative symptoms of autism but have normal or even high IQ, had higher 2D:4D ratios than children with autism but lower ratios than population normative values. There were positive associations between 2D:4D ratios of children with autism and the ratios of their relatives. Children with autism had lower than expected 2D:4D ratios and children with AS higher ratios than expected in relation to their fathers' 2D:4D ratio. It was concluded that 2D:4D ratio may be a possible marker for autism which could implicate prenatal testosterone in its aetiology.

Adolescent↗

Mucosa-associated lymphoid tissue lymphoma with initial supradiaphragmatic presentation: natural history and patterns of disease progression.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma commonly presents in the gastrointestinal (GI) tract. Supradiaphragmatic MALT lymphoma is less common and its natural history is not well defined. This study was conducted to understand the natural history, to determine the frequency of synchronous disease in the GI tract, and to understand the patterns of disease progression after treatment for supradiaphragmatic MALT lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 39 patients who presented with supradiaphragmatic MALT lymphoma between 1991 and 1997. RESULTS: The median age of patients was 58 years (range, 25-90 years) with 16 male and 23 female patients. The most common primary site was salivary gland followed by ocular adnexa, lung, oral cavity, and others. Sixteen patients underwent esophagogastroduodenoscopy and biopsy (EGD + Bx) and 4 were found to have gastric involvement. Ann Arbor stages were the following: IEA, 17; IIEA, 5, IIEB, 1; and IVA, 16. The initial treatments were: involved field radiation therapy (n = 10), chemotherapy (n = 14), combination of radiation therapy and chemotherapy (n = 9), observation after biopsy (n = 4), antibiotics only (n = 1), and patient refusal of further intervention (n = 1). Seven patients received antibiotics as a part of the initial treatment. Every patient except for 1 was alive at a median follow-up of 39.5 months (range, 3-83 months). Thirty-six patients achieved complete response (CR) to the initial treatment. The actuarial 5-year progression-free survival rate was 83%. Progression of the disease occurred in 4 patients, with 2 in the stomach. Salvage attempts were made to 4 and were successful in 3. Of the 2 patients who relapsed in the stomach, 1 had negative EGD + Bx at the time of initial diagnosis. An EGD + Bx was not done in the second patient. CONCLUSION: Supradiaphragmatic MALT lymphoma appears to have a favorable prognosis. However, routine evaluation of the stomach is recommended for patients who present with supradiaphragmatic MALT lymphoma at the time of initial evaluation and at the time of relapse. Patients who failed initial therapy can be successfully salvaged with further treatment.

Adult↗

The outcome of combined-modality treatments for stage I and II primary large B-cell lymphoma of the mediastinum.

PURPOSE: Primary mediastinal large B-cell lymphoma (PML) has clinicopathologic features distinct from those of other diffuse large-cell lymphomas. However, the optimal treatment for this tumor is evolving, and in particular, the role of radiation therapy remains undefined. We conducted a retrospective review to evaluate the role of radiation therapy in this disease. METHODS AND MATERIALS: The medical records of 40 consecutive patients with Ann Arbor Stage I or II PML treated at our institution from January 1980 to December 1995 were reviewed. There were 18 patients with Stage I disease and 22 patients with Stage II disease; 62.5% were women and 37.5% were men. The median age was 32.4 years (range, 17-74 years). The tumor scores were 0 in 1 patient, I in 5 patients, II in 13 patients, III in 7 patients, IV in 4 patients, and unknown in 10 patients. The International Prognostic Index (IPI) was 0 in 10 patients, I in 26 patients, II in 2 patients, and unknown in 2 patients. All patients were treated with doxorubicin-based chemotherapy, and 35 patients received radiation therapy. For most patients who received radiation therapy, an involved field or a modified-mantle field was used, and a dose of 40 Gy in 20 fractions or 39.6 Gy in 22 fractions was administered. Univariate analysis was performed to identify prognostic factors. RESULTS: The median follow-up in surviving patients was 56 months (range, 19-194 months). The actuarial 5-year relapse-free survival (RFS) rate and overall survival (OS) rate for all patients were 67% and 72%, respectively. Thirty-five patients achieved a complete response; 32 of these patients received radiation therapy. The patterns of failure for the complete responders were as follows: locoregional failure alone for 1 patient (at the margin of the radiation field); distant failure alone for 5 patients; and both locoregional (in-field) and distant failure for 1 patient. There were no failures after 2.5 years. None of the 5 patients who never achieved a complete response had local control, and all died with disease. Only 2 of the 5 completed the planned course of radiation therapy; both had massive mediastinal disease. There was no treatment-related death from the initial chemotherapy or radiation therapy. One patient developed a second malignancy (sarcoma) within the radiation field after 13 years. The tumor score was a significant predictor of RFS (p = 0.016) and OS (p = 0.006), but the IPI did not prove to be a significant predictor. CONCLUSION: We recommend consolidative radiation therapy in view of the excellent local control and the lack of significant toxicity. Modified mantle or involved field appears to be an adequate volume, and 39.6-40 Gy appears to be an adequate dose. The tumor score is a significant prognostic factor.

Adolescent↗

Sinus histiocytosis with massive lymphadenopathy and malignant lymphoma involving the same lymph node: a report of four cases and review of the literature.

Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, is a disorder of unknown cause. Rarely, patients with SHML also have malignant lymphoma, usually involving anatomic sites different from those involved by SHML We report four patients in whom SHML and malignant lymphoma were identified in the same lymph node biopsy specimen. The SHML in each case was present as a small focus, less than 1 cm. Immunohistochemical studies showed that the abnormal histiocytes were positive for S-100 and negative for CD1a. The malignant lymphomas included two cases of follicular lymphoma and two cases of Hodgkin's disease, nodular lymphocyte predominant type. The presence of SHML in these patients did not impact clinical decisions, and there was no evidence of SHML elsewhere. Thus, the presence of focal SHML associated with malignant lymphoma in these cases was an incidental histologic finding that seems not to have had any clinical significance.

Adolescent↗

5'-->3' exonuclease-based real-time PCR assays for detecting the t(14;18)(q32;21): a survey of 162 malignant lymphomas and reactive specimens.

We describe our experience using two real-time polymerase chain reaction (PCR) assays for detecting the t(14;18)(q32;q21) in a large series of non-Hodgkin's lymphomas (NHLs). These assays utilize the 5'-->3' exonuclease activity of Taq polymerase, which cleaves a probe labeled with a fluorescent reporter dye at its 5' end and a quencher dye at its 3' end during the extension phase of PCR. In a previous study, Luthra and colleagues developed these real-time PCR assays for detecting the t(14;18) involving the major and minor breakpoint cluster regions of the bcl-2 gene and assessed a small number of NHLs. In this larger study, we analyzed 135 NHLs, 6 Hodgkin's disease, 10 reactive biopsy specimens, and 11 peripheral blood specimens. The NHL group included 46 of 70 (65.7%) follicular NHLs, 1 of 2 (50%) diffuse small cleaved cell NHLs, and 13 of 24 (54.2%) diffuse large B-cell NHLs with the t(14;18) detected by conventional PCR methods. There was excellent agreement between the real-time and conventional PCR assays with overall concordance in 160 of 162 (98.8%) specimens. For the NHLs, concordance was found in 134 of 135 (99.3%) specimens. Disagreement was observed in one case of follicular NHL in which the real-time PCR assay detected bcl-2 minor breakpoint cluster region/JH DNA fusion sequences and the conventional method was negative. The overall concordance for 10 benign biopsy specimens and 11 normal peripheral blood samples was 20 of 21 (95.2%). One lymph node biopsy specimen that showed reactive follicular hyperplasia was positive for the bcl-2 minor breakpoint cluster region/JH DNA fusion sequences detected by the real-time PCR assay but was negative by conventional PCR methods. This patient had no clinical evidence of NHL. We conclude that real-time PCR assays for detecting the t(14;18) are sensitive, specific, and more convenient than conventional PCR methods.

Chromosomes, Human, Pair 14↗

The ratio of 2nd to 4th digit length: a new predictor of disease predisposition?

The ratio between the length of the 2nd and 4th digits is: (a) fixed in utero; (b) lower in men than in women; (c) negatively related to testosterone and sperm counts; and (d) positively related to oestrogen concentrations. Prenatal levels of testosterone and oestrogen have been implicated in infertility, autism, dyslexia, migraine, stammering, immune dysfunction, myocardial infarction and breast cancer. We suggest that 2D:4D ratio is predictive of these diseases and may be used in diagnosis, prognosis and in early life-style interventions which may delay the onset of disease or facilitate its early detection.

Disease↗

Follicle center lymphoma and Warthin tumor involving the same anatomic site. Report of two cases and review of the literature.

We report 2 cases of follicle center non-Hodgkin lymphoma (NHL) and Warthin tumor involving the same site. Case 1 is a 68-year-old woman with Warthin tumor and grade 1 follicular NHL involving a periparotid lymph node. She had localized NHL and was treated with radiation therapy; dissemination developed 54 months later. Case 2 is a 55-year-old man with a 17-year history of a parotid mass with gradual enlargement during the last 5 years. Surgical excision revealed Warthin tumor and grade 1 follicular NHL involving the right parotid gland and surrounding lymph nodes. Immunohistochemical studies supported the diagnosis of NHL in both cases; the neoplasms were positive for CD20 and BCL-2 and negative for CD3. Polymerase chain reaction analysis done on paraffinembedded tissue of case 1 revealed monoclonal immunoglobulin heavy chain gene rearrangement and bcl-2/JH fusion DNA sequences diagnostic of the t(14;18)(q32;q21). The small size of the Warthin tumor in case 1, clearly arising in lymph node, supports the hypothesis that Warthin tumor arises from heterotopic salivary gland ducts within lymph nodes. The localized NHL in both patients suggests that the NHL initially arose in the lymph node involved by Warthin tumor, and, thus, the Warthin tumor may have provided a source of long-term antigenic stimulation from which a monoclonal B-cell population subsequently arose.

Adenolymphoma↗

Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. An uncontrolled trial.

BACKGROUND: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is related to Helicobacter pylori infection and may depend on this infection for growth. OBJECTIVE: To determine the response of gastric MALT lymphoma to antibiotic treatment. DESIGN: Prospective, uncontrolled treatment trial. SETTING: University hospital referral center and three collaborating university and community hospitals. PATIENTS: 34 patients with stage I or stage II N1 gastric MALT lymphoma. INTERVENTION: Two of three oral antibiotic regimens--1) amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2)tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily--were administered sequentially (usually in the order written) for 21 days at baseline and at 8 weeks, along with a proton-pump inhibitor (lansoprazole or omeprazole) and bismuth subsalicylate. MEASUREMENTS: Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsy. Partial remission was defined as a reduction in endoscopic tumor stage or 50% reduction in the size of large tumors. RESULTS: 34 patients were followed for a mean (+/-SD) of 41 +/- 16 months (range, 18 to 70 months) after antibiotic treatment. Of 28 H. pylori-positive patients, 14 (50% [95% CI, 31% to 69%]) achieved complete remission, 8 (29%) achieved partial remission (treatment eventually failed in 4 of the 8), and 10 (36% [CI, 19% to 56%]) did not respond to treatment. Treatment failed in all 6 (100% [CI, 54% to 100%]) H. pylori-negative patients. Patients with endoscopic appearance of gastritis (stage I T1 disease) were most likely to achieve complete remission within 18 months. Tumors in the distal stomach were associated with more favorable response than tumors in the proximal stomach. CONCLUSIONS: A subset of H. pylori-positive gastric MALT lymphomas, including infiltrative tumors, may respond to antibiotics. The likelihood of early complete remission seems to be greatest for superficial and distal tumors.

Anti-Bacterial Agents↗

Jamaican Symmetry Project: long-term study of fluctuating asymmetry in rural Jamaican children.

Fluctuating asymmetry, small deviations from perfect bilateral symmetry, is negatively correlated with health and positively correlated with sexual selection in human adults, but the accumulation, persistence, and fitness implications of asymmetries during childhood are largely unknown. Here, we introduce the Jamaican Symmetry Project, a long-term study of fluctuating asymmetry and its physical and behavioral correlates in rural Jamaican children. The project is based on an initial sample of 285 children (156 boys and 129 girls), aged 5 to 11 years. We describe the design of the project and the methodology of measuring 10 paired morphometric traits. All traits except hand width showed fluctuating asymmetry. Fluctuating asymmetries of the legs tended to be related and were less than half as great as fluctuating asymmetries of the arms and ears. Therefore the legs may show high developmental stability resulting from selection for mechanical efficiency. A fluctuating asymmetry composite score revealed that boys have significantly lower fluctuating asymmetry than girls and that this effect resides mainly in the elbows. There were significant positive relationships between composite fluctuating asymmetry and age, height, and weight, but multiple regression analyses showed that age was negatively related to fluctuating asymmetry, whereas body size was positively correlated. These findings are compared with results from recent English studies.

Analysis of Variance↗

Unusual presentation of mycosis fungoides as pigmented purpura with malignant thymoma.

Thymoma is known to be associated with many lymphoreticular and nonlymphoreticular tumors. A woman who presented with patch stage mycosis fungoides with skin lesions resembling a pigmented purpura was found to have an anterior mediastinal mass on routine staging evaluation. A core needle biopsy of the mass revealed a lymphocyte predominant malignant thymoma. Review of the literature reveals many diseases with dermatologic manifestations associated with thymoma; however, malignant thymoma coexisting with mycosis fungoides has not previously been reported.

Adult↗

Symmetry and performance in middle distance runners.

Deviations from perfect symmetry in paired traits such as ear size and nostril width may indicate developmental instability and/or short-term fluctuations in hormones. In both cases symmetry is thought to be optimal and to indicate high phenotypic quality. The purpose of this work was to determine the relationship between symmetry and performance in middle-distance runners. Fifty male subjects participated in this study. Deviations from perfect bilateral symmetry were measured in seven traits; ear size, nostril width, 2nd to 5th digit length and wrist width. After measurements were made the subjects were ranked for athletic ability and they reported their best 800 metre and 1500 metre times. Symmetric subjects had higher rankings for athletic ability (nostrils, p<0.001 and ears, p< 0.001), lower best 800 metre times (nostrils, p<0.05 and ears, p<0.01) and lower best 1500 metre times (3rd digit, p<0.01 and ears, p<0.05) than asymmetric subjects. This conclusion remained essentially the same after Bonferroni adjustment for multiple tests and when experience and age were controlled for in multiple regression tests. We conclude that symmetry in traits such as nostrils and ears indicates good running ability. It may therefore be useful in predicting the future potential of young athletes.

Adult↗

The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen.

The differentiation of the urinogenital system and the appendicular skeleton in vertebrates is under the control of Hox genes. The common control of digit and gonad differentiation raises the possibility that patterns of digit formation may relate to spermatogenesis and hormonal concentrations. This work was concerned with the ratio between the length of the 2nd and 4th digit (2D:4D) in humans. We showed that (i) 2D:4D in right and left hands has a sexually dimorphic pattern; in males mean 2D:4D = 0.98, i.e. the 4th digit tended to be longer than the 2nd and in females mean 2D:4D = 1.00, i.e. the 2nd and 4th digits tended to be of equal length. The dimorphism is present from at least age 2 years and 2D:4D is probably established in utero; (ii) high 2D:4D ratio in right hands was associated with germ cell failure in men (P = 0.04); (iii) sperm number was negatively related to 2D:4D in the right hand (P = 0.004); (iv) in men testosterone concentrations were negatively related to right hand 2D:4D and in women and men LH (right hand), oestrogen (right and left hands) and prolactin (right hand) concentrations were positively correlated with 2D:4D ratio and (v) 2D:4D ratio in right hands remained positively related to luteinizing hormone and oestrogen after controlling for sex, age, height and weight.

Adolescent↗

The relationship between breast asymmetry, breast size and the occurrence of breast cancer.

Breast cancer is the second most common cancer among women in the world and in developed countries it is the most common. The early identification of women at risk is therefore of great importance and any additional measures which may aid diagnosis, particularly in high risk groups, would be of benefit. Breast volume and breast asymmetry were calculated from mammograms of 250 women with breast cancer and compared with those of 250 age-matched controls. There was evidence that breast cancer patients had more breast asymmetry and larger breasts than age-matched healthy women. The former observation is the first evidence that high breast asymmetry may be a risk factor for breast cancer. Breast asymmetry is likely to be a predictor of, rather than the effect of breast cancer.

Aged↗

Symmetry and ovulation in women.

Women have cryptic ovulation, and self-observation methods of determining the timing of ovulation, such as monitoring cervical mucus symptoms or recording basal body temperature, are not reliable. It has recently become apparent that the symmetry of paired soft tissue traits, such as breast size and digit length, changes across the menstrual cycle. This paper presents evidence that symmetry in four paired soft tissue traits showed a marked increase on the day of ovulation. The difference (i.e. the asymmetry) between the size of the left and right trait in ears, 3rd, 4th and 5th digits was measured. The timing of ovulation was confirmed by real-time pelvic ultrasonography and trait measurements were made without knowledge of scan results. Asymmetry was lowest on the day of ovulation (day 0), decreasing by about 30% from day -1, and significant within-subjects changes occurred from days -2 to day -1, and day -1 to day 0. The practical and evolutionary implications of these findings are discussed.

Adult↗

Hodgkin's disease variant of Richter's syndrome: experience at a single institution.

Patients developing Hodgkin's disease (HD) after a diagnosis of chronic lymphocytic leukemia (CLL), are frequently included in a series of patients with Richter's syndrome (RS). We sought to determine the natural history of the association of CLL and HD. Over a 21 year period, 1374 patients with CLL have been registered in our computer data base. Seven cases of CLL and HD have been documented and confirmed. The median age of these patients was 71 years (range 44-77) and clinical features included male gender (86%), B symptomatology (86%), rapidly progressive lymphadenopathy (71%), prior CLL therapy (71%), advanced Ann Arbor stage (86%), marrow involvement with HD (43%), and autoimmune hemolytic anemia (29%). HD was documented by excisional lymph node biopsy in six cases and splenectomy in one. Mixed cellularity HD was shown in six and nodular sclerosis in one. Five of the biopsies revealed intervening areas consistent with small lymphocytic lymphoma. The Sternberg-Reed (SR) cells were CD15+ in 6/7 cases, and Ki-1+ in the 6 patients tested. CD45 and CD20 staining of the SR cells was nonreactive. The median time to development of HD was 45 months (range 0 to 96). The overall responses to different chemotherapy regimens was approximately 25% with only one CR. Six patients have died at 3, 9, 10, 13, 15 and 36 months and one patient is alive with progressive disease at 11 months. Our data suggests that CLL patients have a heightened risk for HD, features of advanced HD on presentation, and a poor response rate with short survival.

Adult↗