Clinical characteristics of prostate cancer in African Americans, American whites, and Senegalese men.

OBJECTIVES: To describe the clinical features of prostate cancer in Senegalese men and compare these features with those found in African-American and white American men. METHODS: We identified an unselected series of 121 patients with prostate cancer diagnosed at two hospitals in Dakar, Senegal between 1997 and 2002. Medical record abstractions were undertaken to evaluate the prostate tumor characteristics, patient age at diagnosis, prostate-specific antigen (PSA) levels, and reason for referral. In addition, these characteristics were compared with a sample of 455 U.S. white men and 60 African-American men with prostate cancer who were studied as part of a prostate cancer case-control study. RESULTS: Senegalese men had a significantly worse tumor stage than Americans (41.3% versus 18.8%, P <0.001), a significantly worse mean PSA level at diagnosis (mean PSA 72.7 ng/mL versus 9.0 ng/mL in Americans; P <0.001), and were diagnosed at a significantly later age than U.S. men (69 years versus 61 years, P <0.001). U.S. men were most likely to be diagnosed with prostate cancer after an elevated PSA test, and Senegalese men were most often diagnosed after presenting for prostate-related symptoms. CONCLUSIONS: These observations are not unexpected given the differences in the patterns of prostate cancer screening and health care in the United States compared with Senegal. However, our data provide descriptive information about the characteristics of prostate cancer diagnosed in Senegal and highlight differences in the characteristics and detection of these tumors across populations with very different healthcare systems.

Association of SRD5A2 genotype and pathological characteristics of prostate tumors.

The enzyme product of SRD5A2, 5alpha-reductase type II, is responsible for converting testosterone to the more metabolically active dihydrotestosterone. Therefore, SRDSA2 may be involved in the development or growth of prostate tumors. To examine the effects of allelic variants in the gene SRDSA2 on the presentation of prostate tumors, we studied a sample, primarily Caucasian, of 265 men with incident prostate cancer who were treated by radical prostatectomy. We assessed the relationship of the A49T and V89L polymorphisms at SRD5A2 with clinical and pathological tumor characteristics of these patients. We found no association of V89L genotypes with any of the characteristics studied. The presence of the A49T variant was associated with a greater frequency of extracapsular disease [odds ratio (OR), 3.16; 95% confidence interval (CI), 1.03-9.68] and a higher pathological tumor-lymph node-metastasis (pTNM) stage (OR, 3.11; 95% CI, 1.01-9.65). In addition, the A49T variant was overrepresented in two poor prognostic groups, which have been correlated with reduced rates of biochemical disease-free survival. One group included men with at least two of the following poor prognostic variables: (a) stage T3 tumor; (b) PSA level >10; and/or (c) Gleason score, 7-10 (OR, 3.46; 95% CI, 1.04-11.49). The second group included men with positive margins and high Gleason score (OR, 6.28; 95% CI, 1.05-37.73). Our results suggest that the A49T mutation may influence the pathological characteristics of prostate cancers and, thus, may affect the prognosis of these patients.

Attendance at cancer follow-up clinic: does it increase anxiety or provide reassurance for men successfully treated for testicular cancer?

This cross-sectional descriptive study examined the meaning of the cancer follow-up clinic for men who have been successfully treated for testicular cancer. The sample of 62 men were selected using a nonprobability quota sampling method before attendance at a routine testicular cancer follow-up clinic within the Directorate of Clinical Oncology, Western General Hospitals NHS Trust, Edinburgh, Scotland. Subjects were given four instruments to complete immediately before seeing the doctor in the clinic, and two instruments to complete on day 8 after the clinic appointment. Instruments included the State-Trait Anxiety Inventory (STAI), a demographic questionnaire, and two Likert scales adapted for use in the study: the Common Concerns about Testicular Cancer questionnaire and the Psychological Consequences of Screening questionnaire (PCQ). Results demonstrated that men attending the clinic exhibit low levels of anxiety at the points measured, but gain a great deal of reassurance from the clinic visit. Results also demonstrated the areas of concern about testicular cancer and its management that influence anxiety in the follow-up clinic.

Survivorship and the cancer follow-up clinic.

In recent years there has been growing interest in the needs of those individuals who have survived cancer. It is now possible to describe the adjustments that these individuals will make, predict when such difficulties will arise, and identify those most vulnerable to adjustment difficulty. The value of the cancer follow-up clinic has also received scrutiny, drawing on work previously undertaken in the cancer screening clinic setting. Issues discussed in the literature include the purpose of follow-up, the most appropriate health care professional to undertake the follow-up clinic, and the financial cost of cancer follow-up. There exists an opportunity for cancer nurses at present to develop roles in the clinic setting, offering patient-centred and cost-effective alternatives to physician-led follow-up.

Relative transcriptional inducibility of the human interferon-alpha subtypes conferred by the virus-responsive enhancer sequence.

This paper addresses the role of transcriptional regulation in the determination of the levels of expression of different interferon-alpha subtypes secreted from Namalwa cells following infection with Sendai virus. Using RT-PCR to determine the relative abundance of mRNA species coding for the various subtypes, we found a general correlation with corresponding protein levels, indicative of a role for transcriptional control in the determination of levels of individual subtypes. We have used reporter gene constructs to compare the inducibility of the virus-response elements from the IFNA1, A2, A4, and A14 subtype genes cloned upstream of a secreted alkaline phosphatase gene. The inducibility of these reporter gene constructs broadly correlated with the relative mRNA abundances in both transiently and stably transfected Namalwa cells. During work with stable cell lines, we found that G418, the drug used for the selection of transfected cells, inhibited the induction of interferon by both Sendai virus and double-stranded RNA. This inhibition was reversible when G418 was removed from the medium 24 h before the addition of virus.

Analysis of interferon-alpha 2 sequences in human genomic DNA.

We have analyzed the genomic DNA sequence corresponding to the human interferon-alpha 2 (IFN-alpha 2) gene locus. In human lymphoblastoid Namalwa cells, we have detected sequences corresponding to IFN-alpha 2b and -2c, while in human KG-1 cells both IFN-alpha 2a and -2b were present. However, in 100 independent IFN-alpha 2 clones derived from 20 unrelated Caucasian volunteers, we found only sequences corresponding to IFN-alpha 2b. Statistical analysis of this result suggests that the sequences corresponding to IFN-alpha 2a and -2c are either rare allelic variants of this gene, occurring in only a minority of the Caucasian population, or are restricted to transformed cell lines.

Regulation of pineal rhythms in chickens: effects of blinding, constant light, constant dark, and superior cervical ganglionectomy.

Pineal serotonin N-acetyltransferase activity and melatonin content exhibit marked daily changes in chickens; peak values occur during the period of low locomotor activity which coincides with dark in a 24-hour light-dark cycle. The photic and neural regulation of these daily changes were studied by measuring pineal serotonin N-acetyl-transferase activity, hydroxyindole-O-methyltransferase (HIOMT) activity, and melatonin content in experiments in which chickens were subjected to light-dark cycles, constant light, and constant dark and were surgically blinded or superior cervical ganglionectomized. It was found that: 1) The daily changes in N-acetyltransferase activity and melatonin content appear to persist in constant dark, and they disappear in constant light. 2) The eyes are not necessary for photic control of the daily changes, and the effect of constant light on N-acetyltransferase activity and melatonin content may be non-visual, that is, the eyes not being necessary. 3) The occurrence of the daily change in N-acetyltransferase activity and melatonin content does not require the superior cervical ganglia; the persistence of the changes in constant dark, however, may require the ganglia. 4) HIOMT activity was lower in constant light than in light-dark cycles and lower still in constant dark than in constant light. Neither the presence of the eyes nor the superior cervical ganglia affected HIOMT activity, as previously reported.

Regulation of pineal rhythms in chickens: refractory period and nonvisual light perception.

Pineal serotonin N-acetyltransferase activity and melatonin content exhibit marked daily rhythms in chickens; peak values occur during the period of low locomotor activity which coincides with dark in a 24-h light-dark regime. We studied the regulation of these daily rhythms by measuring pineal serotonin N-acetyltransferase activity, hydroxyindole-O-methyltransferase (HIOMT) activity, and melatonin content in experiments in which birds were exposed to light-to-dark and dark-to-light transitions at atypical times. We observed that there is a refractory period for dark-initiation of the increase in pineal N-acetyltransferase activity and melatonin content. We also learned that a dark-to-light transition causes a rapid decrease in dark-elevated pineal N-acetyltransferase activity and melatonin content. The rapid decrease occurs in blinded chickens as well as sighted ones. HIOMT activity did not change consistently in any of the experimental treatments.