Association between prostate-specific antigen and leptin, adiponectin, HbA1c or C-peptide among African-American and Caucasian men.

Prior studies report slightly lower prostate-specific antigen (PSA) levels among obese men. To understand this effect, we investigated the association between PSA and blood HbA1c, C-peptide, leptin and adiponectin levels in African-American (AA) (n=121) and Caucasian (CA) (n=121) men. Among AA men, PSA levels decreased with increasing C-peptide levels (PSA=0.99, 0.93, 0.75 and 0.53 ng ml(-1) across quartiles of C-peptide, respectively; P(trend)=0.005). Among CA men, PSA levels decreased with increasing HbA1c (PSA=0.84, 0.73, 0.77 and 0.45 ng ml(-1) across quartiles of HbA1c, respectively; P(trend)=0.005). This may suggest that metabolic disturbances related to metabolic syndrome or diabetes affect the ability to detect early-stage prostate cancer.

Implications of industrial loads for ammonia pollution in an urban lake.

The recent history of loading of total ammonia (T-NH3) and organic nitrogen (N) from a pharmaceutical manufacturing facility to a municipal treatment plant (Metro) in Syracuse, New York, and the discharge of these constituents from Metro to N-polluted Onondaga Lake is documented. Further, the benefit of the implementation of pretreatment at the pharmaceutical plant, and the effect of an upset event at this treatment facility on loading to Metro and the lake and inlake concentrations are also documented. Models are used as analytical tools to couple loading and in-lake concentrations, to delineate the role that this pharmaceutical facility has played in the lake's ammonia pollution problem, and to evaluate the potential implications of future pretreatment upset events for the success of a rehabilitation program that is underway for the lake. The responsiveness of the lake to reductions in external loading is established by the lower T-NH3 concentration observed in the upper waters of the lake in the spring of 1999. Model analysis demonstrates this reduction was primarily (approximately 75%) because of the decrease in loading from the pharmaceutical facility achieved by pretreatment. An abrupt increase in loading in May 1999 associated with an upset event at the pretreatment facility caused a corresponding increase in the T-NH3 concentration of the lake of approximately 0.5 mg N/L. Model projections demonstrate that the load from the pharmaceutical plant before construction of the pretreatment facility exacerbated the lake's ammonia problems by increasing the occurrence and margin of violations of the toxicity standard. Continued upset events at the pretreatment plant could compromise the lake rehabilitation program.

Multimeric hemoglobin of the Australian brine shrimp Parartemia.

The hemoglobin molecule of the commercially important brine shrimp Artemia sp. has been used extensively as a model for the study of molecular evolution. It consists of nine globin domains joined by short linker sequences, and these domains are believed to have originated through a series of duplications from an original globin gene. In addition, in Artemia, two different polymers of hemoglobin, called C and T, are found which differ by 11.7% at the amino acid level and are believed to have diverged about 60 MYA. This provides a set of data of 18 globin domain sequences that have evolved in the same organism. The pattern of amino acid substitution between these two polymers is unusual, with pairs of equivalent domains displaying differences of up to 2.7-fold in total amino acid substitution. Such differences would reflect a similar range of molecular-clock rates in what appear to be duplicate, structurally equivalent domains. In order to provide a reference outgroup, we sequenced the cDNA for a nine-domain hemoglobin (P) from another genus of brine shrimp, Parartemia zietziana, which differs morphologically and ecologically from Artemia and is endemic to Australia. Parartemia produces only one hundredth the amount of hemoglobin that Artemia produces and does not upregulate production in response to low oxygen partial pressure. Comparison of the globin domains at the amino acid and DNA levels suggests that the Artemia globin T gene has accumulated substitutions differently from the Parartemia P and Artemia C globin genes. We discuss the questions of accelerated evolution after duplication and possible functions for the Parartemia globin.

Responses of Onondaga Lake, New York, to early stages of rehabilitation: unanticipated ecosystem feedbacks.

Responses of polluted Onondaga Lake, New York, to early stages of a phased program to rehabilitate the lake from the effects of domestic waste inputs are documented. The analysis is based on more than 10 years of paired monitoring of the effluent (total ammonia and total phosphorus) of a wastewater treatment plant (WWTP) that discharges to the lake as well as the lake itself (including total ammonia, nitrite, total and dissolved forms of phosphorus, plankton biomass and composition, Secchi disc transparency, and zebra mussel density). Major reductions in total ammonia and total phosphorus loading relative to the preceding decade are reported for the WWTP for the November 1998 through October 1999 interval. Dramatic and, in some cases, unanticipated changes in the lake's water quality and biota in response to the reductions in loading are documented for the April to October interval of 1999 including: (1) major decreases in total ammonia concentrations and improved status with respect to ammonia toxicity standards, (2) development of dense populations of zebra mussels, (3) decreases in fall concentrations of nitrite and improved status with respect to the related toxicity standard, (4) decreases in total phosphorus and total dissolved phosphorus concentrations, and (5) a severe Microcystis (phytoplankton) bloom that caused nuisance conditions and poor clarity. The zebra mussel invasion is attributed to the reductions in total ammonia concentrations to below toxic levels. The Microcystis bloom was probably related to the abrupt increase in the zebra mussel population. Additional reductions in phosphorus loading from the WWTP will be required to limit phytoplankton production and avoid the potential for continued nuisance conditions. Potential complications in resolving lake responses to future reductions in loading associated with the zebra mussel invasion are considered.

A phase I/II dose escalation study of carboplatin in the treatment of newly diagnosed patients with advanced ovarian cancer receiving paclitaxel.

The objective of this study was to determine the maximum tolerated dose of carboplatin when administered with paclitaxel in previously untreated patients with ovarian cancer. Patients were treated with paclitaxel at 225 mg/m2 for 3 hours followed by carboplatin at an area under the curve (AUC) of 6, 7, 8, or 9 every 3 weeks. Granulocyte colony-stimulating factor was added if needed to maintain dose intensity before dose reductions were used for grade 4 hematologic toxicity or febrile neutropenia. Twenty-two patients were enrolled in the study. At the AUC 6 level, five of six patients finished all six cycles. At the AUC 7 level, four of five patients completed six cycles, although three required dose reductions for toxicity. At the AUC 8 level, all four patients completed six cycles and two required dose reductions. The AUC 9 level was not well tolerated. Only four of seven patients completed six cycles. Neutropenia was common, and transient thrombocytopenia was more severe and required dose reduction, especially in later cycles. An AUC of 8 is the maximum tolerated dose of carboplatin in combination with paclitaxel at 225 mg/m2 for 3 hours.

Ancient and recent intron stability in the Artemia hemoglobin gene.

Artemia has evolved three distinct hemoglobins formed by the association of two nine-domain globin polymers. Sequence analysis of cDNA clones corresponding to two polymers, named T and C, indicates that their genes are the products of a duplication event some 60 million years ago. The present study indicates the presence of 22 introns in each of the T and C polymer genes. The 22 introns are classified into two groups: 17 correspond to positions within globin domains, and 5 correspond to interdomain linkers (or N- and C-terminal extensions). Intron position and reading frame phase are precisely conserved between T and C polymers for all 22 introns, but within each gene the position and phase are not always consistent from domain to domain or from linker to linker. The discordance of Artemia hemoglobin introns is discussed in terms of different model mechanisms and constraints: intron sliding, intron loss or gain, and the exon definition model of primary transcript RNA splicing. The results suggest that constraints of pre-mRNA processing should be considered when considering intron positional changes in homologous genes.

Variable substitution rates of the 18 domain sequences in Artemia hemoglobin.

The Artemia hemoglobin is a dimer comprising two nine-domain covalent polymers in quaternary association. Each polymer is encoded by a gene representing nine successive globin domains which have different sequences and are presumed to have been copied originally from a single-domain gene. Two different polymers exist as the result of a complete duplication of the nine-domain gene, allowing the formation of either homodimers or the heterodimer. The total population size of 18 domains comprising nine corresponding pairs, coupled with the probability that they reflect several hundred million years of evolution in the same lineage, provides a unique model in which the process of gene multiplication can be analyzed. The outcome has important implications for the reliability of local molecular clocks. The two polymers differ from each other at 11.7% of amino acid sites; however when corresponding individual domains are compared between polymers, amino acid substitution fluctuates by a factor of 2.7-fold from lowest to highest. This variation is not obvious at the DNA level: Domain pair identity values fluctuate by 1. 3-fold. Identity values are, however, uncorrected for multiple substitutions, and both silent and nonsilent changes are pooled. Therefore, to determine the variability in relative substitution rates at the DNA level, we have used the method of Li (1993, J Mol Evol 36:96-99) to determine estimates of nonsynonymous (KA) and synonymous (KS) substitutions per site for the nine pairs of domains. As expected, the overall level of silent substitutions (KS of 56. 9%) far exceeded nonsilent substitutions (KA of 6.7%); however, for corresponding domain pairs, KA fluctuates by 2.3-fold and KS by 1. 7-fold. The large discrepancies reflected in the expressed protein have accrued within a single lineage and the implication is that divergence dates of different genera based on amino acid sequences, even with well-studied proteins of reasonable size, can be wrong by a factor well in excess of 2.

Phase I dose escalation of paclitaxel in patients with advanced ovarian cancer receiving cisplatin: rapid development of neurotoxicity is dose-limiting.

PURPOSE: To determine the maximum-tolerable dose (MTD) of paclitaxel in a phase I dose-escalation study when combined with cisplatin in patients with advanced ovarian cancer receiving filgrastim for prophylaxis of myelosuppression. PATIENTS AND METHODS: A total of 23 patients with stage II (bulky residual), III, or IV epithelial ovarian cancer were treated (following debulking surgery) with paclitaxel as a 3-hour infusion followed by cisplatin (75 mg/m2) administered over 4 hours on day 1, repeated every 21 days for six cycles. Filgrastim (5 micrograms/kg/d) was administered subcutaneously (SC) beginning on day 2 of each cycle through neutrophil recovery (absolute neutrophil count [ANC] > 10,000/microL). Patients were assigned to one of six escalating dose levels of paclitaxel: 150 (n = 3), 175 (n = 3), 200 (n = 3), 225 (n = 4), 250 (n = 4), and 275 mg/m2 (n = 6). RESULTS: At each paclitaxel dose level (150, 175, 200, 225, 250, and 275 mg/m2), the numbers of patients who completed six cycles without dose reduction were three (100%), three (100%), two (66%), two (50%), three (75%), and zero (0%), respectively. The numbers of patients who experienced a grade III/IV adverse event (hematologic or nonhematologic) were zero (0%), two (66%), two (66%), one (25%), four (100%), and five (80%), respectively. Reasons for dose reduction included neurotoxicity (225 mg/m2, n = 1; 275 mg/m2, n = 2), neutropenia (225 mg/m2, n = 2), diarrhea (275 mg/m2, n = 2), and nephrotoxicity (225 mg/m2, n = 1). Reasons for not completing six cycles at full or reduced dose included neuropathy (200, 225, and 275 mg/m2, n = 1 each) physician request (275 mg/m2, n = 1), and death (275 mg/m2, n = 1). Hematopoietic toxicity was minimal. Six patients developed grade III/IV neutropenia. No patient developed thrombocytopenia below a level of 50,000/microL. CONCLUSION: The MTD of paclitaxel was determined to be 225 mg/m2 when administered as a 3-hour infusion and combined with cisplatin (75 mg/m2). Nonhematologic dose-limiting toxicities were neuropathy and diarrhea. The neuropathy often had a rapid onset, especially at the higher dose levels.

Treatment of poor-prognosis sex cord-stromal tumors of the ovary with the combination of bleomycin, etoposide, and cisplatin.

OBJECTIVE: To investigate the clinical activity of the combination of bleomycin, etoposide, and cisplatin for metastatic ovarian sex cord-stromal tumors of all types and poorly differentiated Sertoli-Leydig cell tumors confined to the ovary. METHODS: The regimen was administered as follows: bleomycin 10-15 mg/day by continuous intravenous (IV) infusion on days 1-3; etoposide 100 mg/m2 IV per day on days 1-3; cisplatin 100 mg/m2 IV on day 1. End points for analysis included response, progression-free survival, and survival. RESULTS: Nine patients were entered in this trial. The median age was 37 years (range 12-69). Histologic types included adult granulosa cell tumor in five patients, juvenile granulosa cell tumor in one, poorly differentiated Sertoli-Leydig cell tumor in two, and mixed tumor in one. Stage distribution was as follows: stage Ia, two; stage IIc, one; stage IIIc, one; recurrent, five. Of the six patients with measurable disease, two (33%) had a complete response (one surgical and one clinical), and three (50%) had a partial response, for an overall response rate of 83%; one patient had no response. Toxicity was acceptable; two patients had mild bleomycin pulmonary toxicity. Of the three patients with nonmeasurable disease, one relapsed, one developed progressive disease, and one remains in remission. Of the seven patients with metastatic disease, only one (14%) had a durable remission. Median progression-free survival was 14 months. Median survival time was 28 months. At the time of analysis, two patients were alive disease-free, three were alive with disease, and four were dead of disease. CONCLUSION: Although the overall response rate to the combination of bleomycin, etoposide, and cisplatin was high, the regimen apparently lacks durable activity in this group of tumors. More active drugs and modalities should continue to be investigated.

Midgut volvulus associated with pregnancy.

These two cases of pregnancy-associated volvulus show that the symptomatology and physical findings of volvulus can be confusing, leading to failure of diagnosis. CT and upper gastrointestinal studies may be of help in making this diagnosis.

Stage I cervical adenocarcinoma: prognostic evaluation of surgically treated patients.

In order to evaluate clinicopathologic determinants of recurrence in adenocarcinoma of the uterine cervix, a detailed retrospective chart review and complete pathology analysis were performed for 79 patients who had been treated by Type III radical hysterectomy between 1975 and 1988. All patients had clinical stage I disease; 77 had cervical diameters of 4 cm or less. Eleven patients (14%) developed recurrent disease with a median time to recurrence of 14 months (range, 7-51). Recurrence location was central in 5 patients, pelvic wall in 2, and distant in 4. Seven patients died of disease. Five-year actuarial survival was 89%. None of the clinical features examined as possible prognostic factors was predictive of recurrence, including patient age (P = 0.91), cervical diameter (P = 0.30), presence of pain (P = 0.53), presence of abnormal bleeding (P = 0.19), and history of oral contraceptive use (P = 0.58). However, univariate analysis showed lymph node spread (P = 0.008), lymph-vascular space invasion (P = 0.05), and increasing grade (P = 0.05) to be significant predictors of recurrence. Lymph-vascular space invasion remained significant when patients with positive nodes were excluded (P = 0.026). Depth of invasion > 3 mm was associated with greater recurrence risk than depth < or = 3 mm (P = 0.01). Number of mitoses (P = 0.10) was not significant. Multivariate analysis selected nodal positivity as the major prognostic parameter (P = 0.04). Further studies are needed to more clearly define the role of lymph-vascular space invasion, as an elevated risk ratio of 1.6 suggests an increased risk for recurrence. Patients whose pretreatment biopsies demonstrate obvious lymph-vascular space invasion might be considered for alternate treatment.

Pelvic exenteration in the elderly patient.

Advanced age is frequently considered a contraindication to radical exenterative surgery. We reviewed the outcomes of 63 patients age 65 years or older who underwent pelvic exenteration between 1960-1991 at The University of Texas M. D. Anderson Cancer Center. Sixty-three percent had preexisting medical illnesses. Major or potentially life-threatening complications were noted in 38% of the patients. An additional 38% experienced minor complications. Sixty percent experienced one or more infectious complications, including pyelonephritis, wound infection, sepsis, and flap necrosis. When both major and minor complications were considered, infectious morbidity was the single largest category. Although they are not life-threatening, nonspecific infectious morbidity and transient confusion were the most frequent individual complications, occurring in 26 and 24% of patients, respectively. Twenty-four percent of the patients experienced no complications. Thirty-four percent of the postoperative survivors suffered late major morbidity. Operative mortality was 11%; multisystem failure was the most frequent cause of death. After a mean follow-up of 4 years, 22 patients were alive with no clinical evidence of disease. Twenty-one patients died of recurrent disease, with a median time to recurrence of 9.6 months. The 5-year survival rate for the group was 46%. In comparison, 363 patients younger than age 65 who underwent exenteration during the same period experienced an operative mortality rate of 8.5% and a 5-year survival rate of 45%, neither of which were significantly different from the rates found for the older group (P = .51 and .52, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Health education evaluation and beliefs and practices in rural Tamil Nadu. 2. Family planning and antenatal care.

PIP: This paper, which reports on the effect of health services in Kanniambadi block, is a continuation of a previous paper on knowledge, attitude and practice surveys in 3 blocks in North Arcot District, Tamil Nadu. It was found that knowledge of family planning is poor, especially for temporary methods, even in the service area. However, both attitudes and practice showed a definite improvement in the service area. Knowledge of antenatal care was also poor, with only slight improvement in the service area. The influence of different factors on family planning and implications for health education are discussed. More use of group methods, and more education about temporary methods is recommended, as well as close linkage between health and development programs.^ieng

Health education evaluation and beliefs and practices in rural Tamil Nadu.

PIP: This paper reports the findings of 2 studies in North Arcot District of Tamil Nadu, one of which was an evaluation of health education programs. A wide range of information is made available on the local Tamil names for allopathic diseases, their etiology, beliefs related to preventive and curative practices, significance and medical consequences of recourse to doctors and practitioners of indigenous systems of medicine. The attitude survey covers a variety of topics about which not much is known -- immunization, sanitation, environment, antenatal care and allopathic medicine. The data suggest that allopathic treatment is preferred for most diseases, although traditional or spiritual methods continue to be used for certain diseases, many of which are believed to be the cause of infant and child mortality.^ieng

A leprosy health education project.

Results of a survey of knowledge and attitudes of the general public towards leprosy and knowledge, attitudes and practices of leprosy patients are reported. This survey is the base line for a health education project, based on social psychological theories of behavior, which is described. The results of the survey show that the general public has very little knowledge about leprosy; patients have more knowledge. Attitudes measured with a Likert scale are negative for the general public and only slightly positive for the patients. Allopathic treatment for leprosy is preferred by most, but many do not relate the "patch" to leprosy and therefore do not seek early treatment. In addition, many patients do not complete the treatment. There is much need for health education.