Prenatal methyl mercury exposure in relation to neurodevelopment and behavior at 19 years of age in the Seychelles Child Development Study.

BACKGROUND: Fish are important sources of protein and contain a variety of nutrients, such as n-3 long-chain polyunsaturated fatty acids (PUFA), essential for normal brain development. Nevertheless, all fish also contain methyl mercury (MeHg), a known neurotoxicant in adequate dosage. Our studies of the Seychelles Child Development Study (SCDS) Main Cohort enrolled in 1989-1990 (n=779) have found no consistent pattern of adverse MeHg effects at exposures achieved by daily fish consumption. Rather, we have observed evidence of improved performance on some cognitive endpoints as prenatal MeHg exposure increases in the range studied. These observations cannot be related to MeHg and may reflect the role of unmeasured covariates such as essential nutrients present in fish. To determine if these associations persist into young adulthood, we examined the relationship between prenatal MeHg exposure, recent PUFA exposure and subjects' neurodevelopment and behavior at 19 years of age. METHODS: We examined 533 participants using the following test battery: the Profile of Mood States-Bipolar (POMS-Bi); Finger Tapping; Kaufman Brief Intelligence Test (K-BIT); measures of Fine Motor Control and Complex Perceptual Motor Control; and Visual Spatial Contrast Sensitivity. We collected the following covariates: maternal IQ, family life course stressors, socioeconomic status, and subjects' recent postnatal MeHg, sex, and computer use. Primary analyses (based on N=392-475) examined covariate-adjusted associations in multiple linear regression models with prenatal MeHg as the primary exposure measure. Secondary analyses additionally adjusted for total n-6 and fish-related n-3 PUFA measured in the subjects' serum at the 19-year examination. RESULTS: Study participants had a mean prenatal MeHg exposure of 6.9 ppm, and a mean recent postnatal exposure of 10.3 ppm. There were no adverse associations between prenatal MeHg and any of the measured endpoints. For recent postnatal MeHg exposure, however, adverse associations were observed for Finger Tapping (non-dominant hand) among women and for the K-BIT Matrices for both sexes, with or without adjustment for PUFA. CONCLUSION: Our findings continue to provide no evidence for an adverse effect of prenatal MeHg exposure on development in a cohort that consumes fish daily. Observations for postnatal MeHg exposure will need to be confirmed using more comprehensive exposure measures.

Help-seeking from clergy and spiritual counselors among veterans with depression and PTSD in primary care.

Little is known about the prevalence or predictors of seeking help for depression and PTSD from spiritual counselors and clergy. We describe openness to and actual help-seeking from spiritual counselors among primary care patients with depression. We screened consecutive VA primary care patients for depression; 761 Veterans with probable major depression participated in telephone surveys (at baseline, 7 months, and 18 months). Participants were asked about (1) openness to seeking help for emotional problems from spiritual counselors/clergy and (2) actual contact with spiritual counselors/clergy in the past 6 months. At baseline, almost half of the participants, 359 (47.2%), endorsed being "very" or "somewhat likely" to seek help for emotional problems from spiritual counselors; 498 (65.4%) were open to a primary care provider, 486 (63.9%) to a psychiatrist, and 409 (66.5%) to another type of mental health provider. Ninety-one participants (12%) reported actual spiritual counselor/clergy consultation. Ninety-five (10.3%) participants reported that their VA providers had recently asked them about spiritual support; the majority of these found this discussion helpful. Participants with current PTSD symptoms, and those with a mental health visit in the past 6 months, were more likely to report openness to and actual help-seeking from clergy. Veterans with depression and PTSD are amenable to receiving help from spiritual counselors/clergy and other providers. Integration of spiritual counselors/clergy into care teams may be helpful to Veterans with PTSD. Training of such providers to address PTSD specifically may also be desirable.

Influence of cranberry proanthocyanidins on formation of biofilms by Streptococcus mutans on saliva-coated apatitic surface and on dental caries development in vivo.

Cranberry crude extracts, in various vehicles, have shown inhibitory effects on the formation of oral biofilms in vitro. The presence of proanthocyanidins (PAC) in cranberry extracts has been linked to biological activities against specific virulence attributes of Streptococcus mutans, e.g. the inhibition of glucosyltransferase (Gtf) activity. The aim of the present study was to determine the influence of a highly purified and chemically defined cranberry PAC fraction on S. mutans biofilm formation on saliva-coated hydroxyapatite surface, and on dental caries development in Sprague-Dawley rats. In addition, we examined the ability of specific PAC (ranging from low-molecular-weight monomers and dimers to high-molecular-weight oligomers/polymers) to inhibit GtfB activity and glycolytic pH drop by S. mutans cells, in an attempt to identify specific bioactive compounds. Topical applications (60-second exposure, twice daily) with PAC (1.5 mg/ml) during biofilm formation resulted in less biomass and fewer insoluble polysaccharides than the biofilms treated with vehicle control had (10% ethanol, v/v; p < 0.05). The incidence of smooth-surface caries in rats was significantly reduced by PAC treatment (twice daily), and resulted in less severe carious lesions compared to the vehicle control group (p < 0.05); the animals treated with PAC also showed significantly less caries severity on sulcal surfaces (p < 0.05). Furthermore, specific A-type PAC oligomers (dimers to dodecamers; 0.1 mg/ml) effectively diminished the synthesis of insoluble glucans by GtfB adsorbed on a saliva-coated hydroxyapatite surface, and also affected bacterial glycolysis. Our data show that cranberry PAC reduced the formation of biofilms by S. mutans in vitro and dental caries development in vivo, which may be attributed to the presence of specific bioactive A-type dimers and oligomers.

Does endoscopic laser ablation of the prostate stand the test of time? Five-year results from a multicentre randomized controlled trial of endoscopic laser ablation against transurethral resection of the prostate.

OBJECTIVE: To determine the long-term objective and subjective outcome of patients with benign prostatic enlargement (BPE) treated by endoscopic laser ablation of the prostate (ELAP), as part of a multicentre randomized controlled trial of ELAP against TURP. PATIENTS AND METHODS: Initially, 151 patients with BPE were randomized to undergo either ELAP or TURP, starting in March 1992. ELAP was performed using the Urolasetrade mark fibre (Bard, Covington, GA, USA) in conjunction with a Nd:YAG laser source. All patients who had originally participated in the study were approached 5 years later to obtain a urological history, American Urological Association (AUA) symptom score and two measurements of urinary flow rate, with an ultrasonographic assessment of the postvoid residual urine volume (PVR). RESULTS: The mean duration of follow-up was 61 months; 109 patients were traced, comprising 69 who were alive and well, and had undergone no further bladder outlet surgery, 26 who had required revision surgery, 12 who were dead or terminally ill and three who had dementia. Both ELAP and TURP produced sustained improvements in mean AUA score, maximum flow rate and PVR, with respective values at 5 years of 6.3, 17.8 mL/s and 76 mL, and 6.5, 20.0 mL/s and 55 mL. Eighteen of 47 ELAP patients (38%) and eight of 51 (16%) TURP patients underwent revision surgery within the follow-up. CONCLUSION: ELAP and TURP produced similar subjective and objective outcomes at 5 years. The re-operation rate after ELAP was more than double that after TURP and suggests that ELAP should not be used routinely in the management of men with BPE.

Comparison of melanoma antigens in whole tumor vaccine to those from IIB-MEL-J cells.

Immunotherapy for melanoma shows promise. Our previous whole tumor (WT) vaccine was noted to have positive clinical effects. We have now developed a new, safer melanoma vaccine that is derived from IIB-MEL-J tissue culture (TC) cells. In this study, we compare by Western blot analyses the antigens in the WT vaccine to antigens in the TC vaccine. Sera from 12 WT vaccine recipients, 8 melanoma patients who received no immunotherapy, and 8 controls served as a source of antibodies to investigate potential antigens in the vaccines. Three major antigenic peptides with approximate molecular weighs of 46, 40, and 36 kDA were present in both vaccines, while two other antigenic peptides with approximate molecular weighs of 68 and 48 kDA were present only in the TC vaccine. The reaction was similar between the patients who received the WT vaccine and those who did not receive the vaccine. Some of the individuals who did not have melanoma showed some reaction, but not to the extent of the melanoma patients. The intensity of immunostaining was greater for the TC vaccine when compared to the WT vaccine, indicating that these proteins are in a higher concentration in the TC vaccine. This new vaccine from IIB-MEL-J tissue culture cells provides a higher yield and a much more consistent source of potentially clinically relevant antigens without risk of infection or contamination by other irrelevant materials.

Transurethral microwave thermotherapy (Prostatron version 2.5) compared with transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: a randomized, controlled, parallel study.

OBJECTIVE: To compare transurethral microwave thermotherapy (TUMT) with urethral cooling in a high-energy protocol (Prostatron version 2.5), with transurethral resection of the prostate (TURP) for the treatment of symptomatic, uncomplicated, urodynamically obstructive benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients with moderate to severe symptomatic, uncomplicated BPH, unequivocally obstructed as assessed from the Abrams-Griffith nomogram, who were technically suitable for either form of treatment, were randomized into two groups of 30 patients each to undergo either TUMT or TURP. Five efficacy variables, i.e. the American Urological Association (AUA) symptom score, maximum flow rate (Qmax), post-void residual urine volume (PVR), voiding pressure at maximal flow (Pdet max) and prostatic volume determined by ultrasonography (PV) were measured initially and 6 months after treatment using a defined protocol. Complications were recorded during and up to 6 months after the treatment. As the variables were independent, the data were analysed using a paired t-test for each to assess the treatment effect for each group. RESULTS: After TURP, all the variables improved significantly; after TUMT, the symptoms improved both clinically and statistically (P < 0.001), with the mean AUA symptom score decreasing from 18.4 to 5.2. However, none of the objective variables improved after TUMT. The energy delivered under software control correlated poorly with prostatic volume (r = 0.322). TUMT had considerably lower morbidity than TURP, but failure of ejaculation occurred in four of 18 sexually active men after TUMT. CONCLUSIONS: Despite considerable improvement in their symptoms, TUMT using the Prostatron and Prostasoft v2.5 did not alleviate obstruction in patients with BPH. Patients treated using TUMT controlled by this software should be informed of the possibility of ejaculatory dysfunction.

Definition of chemiluminescence and superoxide production responses of bovine neutrophils to selected soluble and particulate stimulants, and comparisons with the responses to Pasteurella haemolytica.

We defined methods for use of luminol-dependent chemiluminescence (LDCL) and superoxide anion (O2-) production as parameters of the oxidative metabolism of neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how variations in blood sample handling, agonist preparation, individual variability, and age of calves influenced the LDCL and O2- responses to certain agonists, and defined concentrations of soluble and particulate agonists that maximally stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses, particularly LDCL, were characterized by marked day-to-day variability, differed greatly within and between calves, were partially age-dependent, and were partially dependent on the individual agonist. Superoxide anion production had substantially less variability. We compared the in vitro oxidative (LDCL and O2-) responses of neutrophils isolated from neonatal calves stimulated by defined concentrations of the agonists--latex, phorbol myristate acetate, calcium ionophore, and opsonized zymosan--with responses to formylated oligopeptides and zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or nonpathogenic, enhanced the LDCL and O2- responses of stimulated neutrophils although P haemolytica was a less potent stimulant of oxidative functions than were nonbiological agonists. We conclude that the generation of reactive oxygen species by bovine neutrophils in response to P haemolytica is highly dependent on the presence of opsonins and is greatly enhanced in live vs killed bacteria. Furthermore, the in vitro generation of reactive oxygen species, including O2- by stimulated neutrophils, may be of biologic importance if similar events occur in vivo, and could have a major role in the pathogenesis of the acute lung injury associated with pneumonic pasteurellosis.

Effects of supplemental dietary sodium chloride and restricted drinking water on mink.

Thirty-six male mink were fed diets that contained 0, 1, 2 or 4% supplemental salt (sodium chloride) and were given drinking water ad libitum for 7 d. Three mink on each diet were then placed on ad libitum, 50% ad libitum or 25% ad libitum drinking water for the next 14 d. Ad libitum water consumption was directly proportional to the salt content of the diets. Feed consumption was inversely related to the level of dietary salt, although water restriction had a greater effect in reducing feed consumption than did the supplemental salt. The clinical signs of salt toxicity-water restriction observed were increased thirst, mild dehydration, decreased feed consumption, decreased body weight, rough coat, crusty nose and eyes, irritability in the early stage, and lethargy in the later stages. In general, serum and urinary sodium and chloride ion concentrations increased with increasing dietary salt concentrations. Expressed as a percent of brain weight, liver, spleen, kidney and heart weights of mink fed supplemental salt were less than the control weights. Adrenal gland weights increased in response to water restriction. Brain sodium concentrations were not affected by salt supplementation when drinking water was provided ad libitum. However, restricting drinking water generally resulted in increased brain sodium concentrations. Mild to moderate micro- or macrovesicular vacuolar changes were observed in the livers of some mink fed each level of dietary salt, but were especially prominent in the mink restricted in drinking water.

Prostatic heat treatments for urinary outflow obstruction.

A nonrandomized pilot study was done of 139 patients with symptomatic benign prostatic hyperplasia treated with 3 prostatic heating devices. Of the patients 19 underwent transrectal hyperthermia with the Biodan Prostathermer and in 15 the Primus Prostate Machine was used. At 2 1/2 years 7 of 19 patients (37%) patients in the Prostathermer group and 6 of 15 (40%) in the Primus group had adequate sustained improvement and had not undergone further treatment. At 1 year 55 of 100 patients (55%) treated with the Thermex-II section transurethral thermotherapy unit had a satisfactory result, with 40 (40%) having undergone transurethral resection of the prostate. The number of patients who failed therapy increased with each followup. Analysis of pretreatment parameters, including patient age, prostate size, peak urinary flow rate, post-void residual urine volume and symptom score, did not predict a successful outcome. Although these devices have minimal effect on peak urinary flow rate, a subset of patients enjoy symptomatic improvement.

New trends in the treatment of benign prostatic hyperplasia and carcinoma of the prostate.

Benign prostatic hyperplasia (BPH) is a very common condition affecting over 800,000 American males each year. A standard, effective, and well-proven therapy is prostatectomy. This surgical procedure is used to treat, in the United States, approximately 400,000 BPH patients annually. Major treatment benefit is expected in 70% to 80% of patients. Complications are seen in 20% of the surgically treated patients. Due to the advanced age of BPH patients and the presence of other serious coexisting medical problems, surgical therapy may be difficult to utilize. These patients, who present a high risk for surgery, are in need of alternative treatments. Alternative therapy in BPH patients with clinically important symptoms and signs of urinary outflow obstruction include treatment with pharmacological agents, balloon dilatation, laser beam therapy, transurethral thermal therapy, transrectal microwave hyperthermia, and transurethral microwave hyperthermia. These alternative treatment modalities are currently under intensive study. These new treatment modalities ultimately must be compared with the standard treatment, which is prostatectomy. Due to the unpredictable natural history of BPH, it is desirable that each Phase III study should contain a no-treatment observation-only arm. Adenocarcinoma of the prostate (CaP) has become a tumor, which first in frequency, and second in importance in cancer mortality statistics of American males. Local tumor control rates and long-term survivals, with radical prostatectomy or radiation therapy, have been excellent. There was, however, recent concern regarding a high incidence of microscopic local tumor recurrence following a definitive course of irradiation. Deep regional or intracavitary hyperthermia (HT) with phase steering may be of value as an adjuvant treatment to radiotherapy. This HT may increase the incidence of local tumor control obtained with radiotherapy. Phase I-II clinical studies are currently underway.

The effects of triclosan and zinc citrate, alone and in combination, on a community of oral bacteria grown in vitro.

A mixed-culture chemostat system has been used as a more stringent laboratory system for evaluation of the antimicrobial effects of Triclosan and zinc citrate. The inhibitors were added alone, and in combination, as a pulse (a high initial inhibitor concentration which decreased with time) or as a dose (concentration of inhibitor increased with time) to give maximum concentrations of 34.5 mumol/L Triclosan and 39.8 mumol/L zinc citrate. When dosed, Triclosan inhibited A. viscosus and all five Gram-negative species, whereas zinc citrate had less effect, probably due to complexation by media components. Similar effects were seen when Triclosan was pulsed, except that S. mutans was the most sensitive Gram-positive species and V. dispar was unaffected. However, when the inhibitors were dosed or pulsed in combination, marked complementary and additive inhibitory effects were observed, particularly against Gram-negative species, although S. gordonii and S. oralis were relatively unaffected. The data confirm that increased effects can be obtained with suitable combinations of antimicrobial agents and suggest that, under certain conditions, apparently broad-spectrum antimicrobial agents may be acting more selectively than hitherto suspected.

Use of biofeedback in treatment of psychogenic voiding dysfunction.

A young man with psychologic problems and a long history of social inadequacy presented with voiding dysfunction. Videocystometrography revealed a normal filling phase and normal initiation of voiding interrupted by considerable straining by the patient and marked sphincter electromyographic (EMG) activity. Temporary amelioration was achieved by infiltration of the sphincter with lignocaine hydrochloride and by biofeedback therapy. In such cases optimal results are expected from long-term behavioral therapy.

Identification and characterization of a GroEL homologue in Rhodobacter sphaeroides.

A protein closely related to the Escherichia coli GroEL protein has been isolated from Rhodobacter sphaeroides. Native and SDS-polyacrylamide gel electrophoresis of this protein have shown that it is present in the cell as a multimeric complex of Mr 670,000 which is composed of a monomer of Mr 58,000. Antisera raised against the Mr 58,000 polypeptide have been shown to cross-react with GroEL and the alpha subunit of the pea plastid chaperonin. The N-terminal amino acid sequence of the Mr 58,000 polypeptide is identical to that of GroEL at 15 of 19 residues and is also closely related to the alpha subunit of the pea plastid chaperonin, though less so to the beta subunit.

Retinal degeneration in cats fed casein. II. Supplementation with methionine, cysteine, or taurine.

All cats fed a taurine-free casein diet for 23 weeks have shown a nondetectable electroretinogram (ERG) in association with a plasma and retinal taurine deficiency. In the present study, the casein diet was supplemented with either taurine or taurine precursors (methionine or cysteine) for 23 weeks to see if retinal function would be preserved. Cats fed the casein diet supplemented with methionine or cysteine showed ERG's reduced in amplitude and delayed in implicit time and had plasma and retinal taurine levels that were well below normal by 23 weeks. Only those cats given taurine in the diet (i.e., those fed chow or casein supplemented with taurine) retained normal ERG function and normal plasma and retinal taurine concentrations. These findings establish a role for taurine in maintaining normal retinal function in the cat.