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Biomedical subjects

M J Goodman

Publications and source records attributed to M J Goodman.

At least 19 recordsLinked to original sources

Breast cancer in multi-ethnic populations: the Hawaii perspective.

The five major ethnic groups in Hawaii's population of 1.1 million are the Japanese, comprising 23%; Caucasians, 23%; ethnic Hawaiians, 19.9%; Filipinos, 11.3%; and Chinese, 4.8%. Only 14% of the population is foreign born. Breast cancer incidences are 29.2 per 100,000 among Filipinos, 51.3 for Japanese, 64.1 for Chinese, 104.3 for Hawaiian, and 105.6 for Caucasian women. The Caucasian incidence is similar to mainland US rates, but the incidence among Hawaii's Japanese is more than twice the rate in Japan. Japanese in Hawaii have less postmenopausal breast cancer than Caucasians, fewer axillary lymph node metastases, and a greater proportion of non-invasive tumors. Late stage at diagnosis is common among Filipino and ethnic Hawaiian woman, and their risk of death is 1.5-1.7 times that of Caucasian, Chinese, and Japanese women with the disease, even after adjustment for age, extent of disease, and socio-economic status. In the BCDDP screening study, only 20% of breast cancers detected in ethnic Hawaiians were not yet palpable and were found by mammography alone. Comparative studies of diet and estrogen levels in the ethnic groups of Hawaii and the parental populations in Japan and the West do not account for the degree of variation observed in breast cancer incidence and tumor pathology. Future research directions are suggested with a view to accounting for these differences.

Breast Neoplasms

Estimating the sensitivity of breast cancer screening--experience with the Honolulu BCDDP data.

The 'capture-recapture' models for estimating breast cancer screening sensitivity can be generalized to include factors that affect sensitivity such as cancer size. Including such factors can help reduce the covariance between mammographic and physical exam sensitivity, which will improve the estimates. One model relating sensitivity to cancer length is presented and tested using data from the Honolulu Breast Cancer Detection Demonstration Project (BCDDP). The model predicts sensitivity fairly well for large breast cancers, but underestimates sensitivity for small cancers. Using both mammography and physical examination, the total screening sensitivity is estimated as 0.91 +/- 0.03 for cancers longer than 12 mm (for the second through fifth screenings for Honolulu and Tucson screening data combined). Limited data suggest similar screening sensitivities for Orientals and Caucasians in Hawaii. Shortcomings of the BCDDP data include inaccurate measurements of cancer length. Suggestions to improve data for future work are given.

Breast Neoplasms

Microscopic activity in ulcerative colitis: what does it mean?

To determine the prognostic importance of microscopic rectal inflammation we followed up 82 patients (aged 21 to 78 years, 44 men) with chronic quiescent ulcerative colitis over 12 months. At trial entry each patient underwent a rectal biopsy and sections were graded independently by two histopathologists. A chronic inflammatory cell infiltrate of varying severity was present in all biopsy specimens, and 58% had crypt architectural irregularities. In addition, 32% had evidence of acute inflammatory activity: 28% acute inflammatory cell infiltrate, 11% crypt abscesses, and 22% mucin depletion. Agreement between the two histopathologists for the presence of each of these features was 94% (90-98%). During the 12 month follow up 27 patients (33%) relapsed after a mean interval of 18 weeks (range 3-44 weeks). Relapse rates were unrelated to duration or extent of disease or to the type of maintenance drug treatment. In patients with an acute inflammatory cell infiltrate 52% relapsed, whereas in the absence of such an infiltrate only 25% relapsed (p = 0.02). Similarly, relapse rates were higher in the presence of crypt abscesses (78% v 27%, p less than 0.005), mucin depletion (56% v p less than 0.02), and breaches in the surface epithelium (75% v 31%, p = 0.1). The presence of a chronic inflammatory cell infiltrate or crypt architectural irregularities, however, bore no relation to the frequency of colitis relapse.

Adult

Why do patients with ulcerative colitis relapse?

To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis.

Adolescent

Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis.

To assess the safety and efficacy of delayed-release mesalazine (5-aminosalicylic acid) as maintenance treatment for patients with ulcerative colitis, 100 patients with quiescent colitis were randomly grouped to receive either delayed-release mesalazine or an equivalent dose of enteric-coated sulfasalazine in a 48-wk trial. Groups were comparable for age, sex, and duration and extent of disease. Relapse rates at 48 wk were as follows: sulfasalazine 38.6% (95% confidence limits, 24%-54%) and mesalazine 37.5% (95% confidence limits, 24%-53%), chi 2 = 0.01, p greater than 0.90. Mean time to relapse, cumulative relapse rate, and relapse severity were similar in the two groups. Headaches and upper gastrointestinal symptoms--common at trial entry--improved to a greater extent in patients receiving mesalazine. Delayed-release mesalazine is an effective treatment for maintaining ulcerative colitis remission and is associated with fewer side effects than equivalent doses of enteric-coated sulfasalazine.

Adult

The distribution of estradiol in the sera of normal Caucasian, Chinese, Filipina, Hawaiian and Japanese women living in Hawaii.

Mean concentrations of sex-hormone-binding-globulin (SHBG) and the percentage distribution of estradiol between the non-protein-bound, albumin-bound and SHBG-bound fractions were not different in Caucasian, Hawaiian, Chinese, Japanese and Filipinas living in Hawaii. The widely varying incidence rates for breast cancer are therefore not explained by variations in the availability of estradiol.

Adult

Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse.

Oral formulations of 5-aminosalicylic acid (mesalazine) appear less toxic than sulphasalazine. We have therefore compared sulphasalazine, low dose mesalazine and high dose mesalazine in the treatment of mild to moderate relapse of ulcerative colitis. Sixty one patients (32 men, aged 20-78 years) were randomly allocated to sulphasalazine 2 g daily, mesalazine 800 mg daily, or mesalazine 2.4 g daily in a double blind, double dummy, four week trial. Groups were comparable for age, sex, extent of disease, and pretrial sulphasalazine intake. Four patients were unable to complete the study because of treatment failure (two taking sulphasalazine and two high dose mesalazine). A further two patients taking sulphasalazine developed side effects necessitating withdrawal. Within treatment comparisons revealed significant improvement of: sigmoidoscopic grade in the sulphasalazine group; rectal bleeding, sigmoidoscopic and histological grade in the low dose mesalazine group; stool frequency, rectal bleeding and sigmoidoscopic grade in the high dose mesalazine group. Greater improvement in rectal bleeding (p less than 0.05) and sigmoidoscopic appearances (p less than 0.05) occurred in patients taking high dose mesalazine than in those taking sulphasalazine. In two patients taking high dose mesalazine minor rises of plasma creatinine concentrations occurred, suggesting the need to monitor renal function.

Adult

Medicalization and its discontents.

This paper raises the question of the ethically proper balance in health care policy between the medical-clinical-high technology model of health service and the grass-roots, community based or traditional models of care. Paradoxical imbalances between the two approaches are traced to political, economic or prestige factors. Case studies examined include the hospitalization of non-contagious leprosy patients while protecting the anonymity of AIDS-infected prostitutes, medical resistance to the adoption of a clinical role by Community Cancer Centers, and the continued preference in some quarters for elaborate (and often delayed) hospital treatment for such problems as infant diarrhea, despite the availability of much simpler solutions, as in the case of the widely successful oral rehydration therapy. A balanced approach to world health problems, we argue, rests not on inflationary lowering of health care standards to achieve nominal victories, nor on stainless steel high technology panaceas but on mobilizing resources around human needs.

Acquired Immunodeficiency Syndrome

Sulphasalazine induced seminal abnormalities in ulcerative colitis: results of mesalazine substitution.

Seminal abnormalities are commonly found during sulphasalazine treatment. Although these changes appear reversible after drug withdrawal this may result in colitis relapse. Animal studies suggest that 5-aminosalicylic acid, the active component of sulphasalazine, does not impair fertility. Sixteen patients with quiescent ulcerative colitis were studied. Each patient produced three samples of semen at weekly intervals. Of the 48 samples analysed 39.6% showed oligospermia, 41.7% showed an increased number of abnormal forms and 91.7% showed impaired motility. Nine patients substituted enteric coated mesalazine (5-aminosalicylic acid) for sulphasalazine for a minimum period of three months. During this time one patient developed a salmonella associated colitis relapse; the others remained well. Improvement in sperm count (p less than 0.02), motility (p less than 0.001) and morphology (p less than 0.02) occurred in all cases. To date, four successful pregnancies have resulted, three in couples complaining of long term infertility. Treatment with enteric-coated mesalazine allows the recovery of seminal abnormalities induced by sulphasalazine in patients with colitis.

Adult

Thyroid function and the incidence of breast cancer in Hawaiian, British and Japanese women.

Serum-free thyroxine (FT4) concentrations are lower in Hawaiian and Hawaiian Caucasian women than in Hawaiian Japanese, Hawaiian Filipino, Hawaiian Chinese, and English and Japanese mainland women. There is a high inverse correlation between FT4 and risk of breast cancer in these ethnic groups. Thyroid-stimulating hormone (TSH) concentrations, which are inversely correlated with FT4, generally show the same relationship.

Adult

Ammonium inhibits processing and cytotoxicity of reovirus, a nonenveloped virus.

Successful viral infection involves a series of interactions between the virus and the host cell. The outcome of viral infection is, in fact, dependent on intact cellular function; it is required for viral binding, internalization, and uncoating. To determine the potential importance of lysosomal processing on the outcome of infection with a nonenveloped virus, we have studied the effects of NH4Cl on the course of reovirus infection on a beta-cell tumor in culture. Addition of 10 mM NH4C1 to the medium inhibited viral growth by greater than 80% and reduced toxic effects of the virus on cell viability, protein, and DNA synthesis by 30-45%. In addition, synthesis of viral proteins was markedly decreased. Uptake of virus prelabeled with [35S]methionine was not affected by the ammonium; however, cleavage of mu1C, an outer capsid protein of the virus whose cleavage appears to be required for viral replication, was delayed. These results suggest that intracellular processing of reovirus is dependent on a lysosomal pathway and that disruption of this pathway can alter the course of viral infection.

Ammonia

Prevention--how misuse of a concept undercuts its worth.

Some health leaders and researchers have launched mass prevention programs without sound biomedical groundwork. They have oversold the benefits of prevention and underestimated the secondary effects. Some have forced nonmedical concerns into the medical model. Others have blurred the distinctions between prevention and other measures such as screening or therapy. Some have transferred responsibility for disease to the victim. A few have imputed magical powers to certain symbols of prevention, in order to create an illusion of control.

Attitude

Differential effects of viral infection on islet and pituitary cell lines.

Although reovirus infection may lead to changes in endocrine function in vivo, little is known about the precise interaction of reovirus with endocrine cells. In this study we have examined the effects of reovirus infection on two types of endocrine cells, GH4C1 cells and RINm5F cells. Both type 1 reovirus and type 3 reovirus infect the two cells lines and appear to grow equally well. Viral replication occurred within the first 24 h following infection after which viral titers remained stable for 3 days. By 48-72 h after viral infection, substantial cytopathic effects were noted in RINm5F cells infected with both type 1 and type 3 reovirus. In GH4C1 cells, type 3 reovirus was most effective in producing cell death, and type 1 reovirus was significantly less cytotoxic despite a similar viral titer. Only type 1 reovirus caused a specific inhibition of overall protein and DNA synthesis, and this occurred only in the RINm5F cells. Over the time course studied, GH4C1 cells successfully infected with type 1 reovirus demonstrated no cytopathic effects, and only minimal alterations in cellular function were noted. Intracellular insulin content and insulin secretion, a "luxury function" of the RINm5F cells, were also surprisingly well maintained in the first 48 h after viral infection. In addition, virally infected cells were able to respond to glyceraldehyde, an insulin secretagogue, although the response appeared to be somewhat blunted compared to that of control cells. These results suggest that viral infection of endocrine cells results in specific alterations that depend on the nature of the infecting virus. In addition, the cellular environment of the host cell may be an important determinant in the outcome of viral infection.

Animals

Factors associated with breast structure in breast cancer patients.

The breast duct patterns and radiographic density, or dysplasia, of 104 breast cancer patients in Hawaii were examined by mammography. The proportions of the four types of breast structure were analyzed for possible relation with age, menopausal state, height, weight, and race. Multiple regression analysis indicated that menopausal state appears to be more important than age per se for the general change in breast structure. Low body weight, but not race, is associated with prominent duct patterns and dysplasia.

Adult

Age at menopause in relation to reproductive history in Japanese, Caucasian, Chinese and Hawaiian women living in Hawaii.

A multiple regression analysis was undertaken to examine the relationship between age at menopause and selected biological and sociological variables in the reproductive history of Caucasian, Japanese, Chinese and part-Hawaiian post-menopausal women living in Hawaii. The analysis was conducted using the medical history records of 196 Caucasian, 181 Japanese, 72 Chinese and 60 Hawaiian women. Age at menarche, parity and months spent breast-feeding were found to have no significant effect on age at menopause. Regression models were not found to be heterogeneous among ethnic groups and no substantial interaction of ethnic group was found with age at menarche, parity or months spent breast-feeding.

Asian People