Supplements of interest for sport-related injury and sources of supplement information among college athletes.

PURPOSE: This study examined incidence of sport-related injury, interest in supplements to treat injury, and sources of supplement information among 145 college athletes (89 males, 56 females). MATERIALS AND METHODS: A survey was used to assess sport-related injuries, interest in three categories of supplements to treat injury, and sources of supplement information among college athletes who used athletic training room and weight training facilities. Pearson chi2 was used to evaluate differences in frequency distribution of responses by sex. RESULTS: Sport-related injuries were experienced by 91% of athletes (93% males, 88% females). Overall, 17% of participants were interested in supplements to improve circulation, 34% for joint and soft tissue repair, and 22% to reduce inflammation. Significant sex differences were not found for any supplements in any categories evaluated. Males were more likely than females to rely on strength coaches (37%, 20%) for supplement information. Athletic trainers (71% of athletes), coaches (60%), and physicians (41%) were the primary professionals, and the internet (79%), magazines (68%), and television (52%) the most popular sources of media for supplement information. CONCLUSIONS: The majority of athletes experience injury during their college athletic career and 17% to 34% express an interest in supplements for injury treatment. Athletes would benefit from scientifically sound guidance to identify appropriate supplements for injury treatment and internet sites for supplement information. Future research should identify if athletes are more likely to increase supplement use when they are injured or if supplement use is more prevalent among athletes who are prone to injury.

Moderated multiple regression for interactions involving categorical variables: a statistical control for heterogeneous variance across two groups.

Moderated multiple regression (MMR) arguably is the most popular statistical technique for investigating regression slope differences (interactions) across groups (e.g., aptitude-treatment interactions in training and differential test score-job performance prediction in selection testing). However, heterogeneous error variances can greatly bias the typical MMR analysis, and the conditions that cause heterogeneity are not uncommon. Statistical corrections that have been developed require special calculations and are not conducive to follow-up analyses that describe an interaction effect in depth. A weighted least squares (WLS) approach is recommended for 2-group studies. For 2-group studies, WLS is statistically accurate, is readily executed through popular software packages (e.g., SAS Institute, 1999; SPSS, 1999), and allows follow-up tests.

Evidence for an atrial natriuretic peptide-like gene in plants.

The presence of a gene found in the animal kingdom expressing a peptide hormonal system in plants has never been demonstrated. However, there is at least one potential hormonal system in plants (i.e., the atrial natriuretic peptide-like hormonal system) based upon high-performance gel permeation chromatography and radioimmunoassay evidence. In plants, atrial natriuretic-like peptides enhance the flow of water up stems to leaves and flowers. The present investigation was designed to determine within plants the presence of the atrial natriuretic peptide (ANP) gene as defined by Southern blot hydridization, indicating the presence of the ANP gene sequence, and by Northern blots assessing the ability of this gene to express ANP prohormone mRNA. Southern blots of English ivy (Hedra helix) genomic DNA revealed that the ANP gene sequence was present in its roots, stems, and leaves. Northern blot analysis of total plant RNA isolated from leaves, roots, and stems of Hedra helix revealed a single 0.85-kilobase prohormone ANP transcript in stems similar to that detected in rat heart. Semiquantitative analysis suggested that ANP gene expression was less in English ivy compared with that of rat heart atria but similar to the amount found in extra atrial rat tissues when corrected for total RNA when quantitated by 2D scanning. The demonstration of the ANP gene sequences and expression of the ANP-like gene in plants suggests that plants and animals may have evolved much more similarly than previously thought.

Prospective evaluation of the Batista procedure with circulating atrial natriuretic peptides.

A proposed treatment of end-stage heart disease is partial left ventricular resection (i.e., Batista procedure). To determine if congestive heart failure objectively improves after this procedure, we prospectively evaluated partial left ventriculectomy with objective plasma markers of the severity of congestive heart failure (i.e., three N-terminal atrial natriuretic peptide prohormone radioimmunoassays and atrial natriuretic peptide radioimmunoassay) prior to and during the 12 months after partial left ventriculectomy. The four measured atrial natriuretic peptides improved in 30% of the subjects at 1 month post-surgery. Eighty percent of the subjects, however, had higher circulating atrial natriuretic peptides (P<0.01) at 3, 6, and 12 months than prior to surgery indicating that their congestive heart failure was objectively worse than prior to surgery. Likewise, at 3, 6, and 12 months post-surgery the ejection fractions were not significantly better than prior to surgery. By 6 months the subjects with the highest circulating atrial natriuretic peptides had died (60% of subjects). In conclusion, congestive heart failure improves within 1 month in some patients but then deteriorates at 3, 6, and 12 months after the Batista procedure. There was no survival benefit with 60% of the patients expiring within 6 months after the Batista procedure.

Comparison of vessel dilator and long-acting natriuretic peptide in the treatment of congestive heart failure.

BACKGROUND: Long-acting natriuretic peptide (LANP; proANF 1-30) and vessel dilator (proANF 31-67) enhance sodium and water excretion in healthy human beings. The current investigation was designed to compare the beneficial effects of LANP and vessel dilator in persons with congestive heart failure (CHF). METHODS AND RESULTS: LANP and vessel dilator (100 ng/kg body weight/min, respectively) were given intravenously for 60 minutes to subjects with New York Heart Association class III CHF (n = 17) while their urine volume and sodium and potassium excretion were monitored. Vessel dilator increased urine flow more than 5-fold, which was still increased (P <.001) 3 hours after stopping its infusion. Vessel dilator enhanced sodium excretion 3-fold in subjects with CHF (P <.01), which was still significantly (P <.01) elevated 3 hours after infusion. The effects of LANP were diminished, with urine flow only increasing 2-fold (P <.05). The fractional excretion of sodium increased maximally 6-fold secondary to vessel dilator and 3-fold with LANP. The CHF control patients had no changes in the above parameters. Part of the diminished response to LANP was found to be caused by its rapid decrease in the circulation of individuals with CHF. CONCLUSIONS: These results indicate that vessel dilator has significant beneficial diuretic and natriuretic properties, which are not diminished, whereas the effects of LANP are diminished in human beings with CHF compared with healthy individuals.

Elevated atrial natriuretic peptides and early renal failure in type 2 diabetic Goto-Kakizaki rats.

The present investigation was designed to determine if atrial natriuretic peptides (ANPs) are increased in a spontaneous model of non-obese type 2 diabetes, the Goto-Kakizaki (GK) rat. Four peptide hormones originating from the ANP prohormone were increased twofold (P < .05) to sixfold (P < .01) in the circulation of GK rats compared with nondiabetic Wistar rats from which the GK colony was originally derived. Thus, ANP, long-acting natriuretic peptide (LANP), vessel dilator, and kaliuretic peptide were (mean +/- SE) 497 +/- 78, 1,285 +/- 105, 457 +/- 45, and 385 +/- 87 pg/mL in GK rats, versus 78 +/- 23, 542 +/- 77, 137 +/- 26, and 134 +/- 33 pg/mL, respectively, in Wistar rats. In evaluating the cause of the increased ANPs, the blood volume of GK rats (16.2 +/- 0.4 mL) was significantly (P < .01) increased compared with Wistar rats (9.5 +/- 0.3 mL). The ventricles of GK rats were not dilated when examined by transthoracic echocardiography, but the venous system was markedly distended. GK rats had a 48% to 79% decrease in renal function (ie, increased serum creatinine and blood urea nitrogen [BUN]) compared with Wistar rats. These results indicate that circulating ANPs are increased in the GK spontaneously diabetic rat secondary to (1) increased blood volume, which leads to increased synthesis and release of ANPs, and (2) renal failure, which results in a delayed metabolic processing of these peptides. The early combined increases of the four atrial peptides collectively may contribute to the hyperfiltration that occurs in early diabetes mellitus.

Atrial natriuretic peptide increases urodilatin in the circulation.

BACKGROUND: Urodilatin is a 32-amino-acid (AA) peptide formed in the kidney. METHODS: High-performance gel permeation chromatography and high-pressure liquid chromatography evaluation of plasma followed by sensitive urodilatin and atrial natriuretic peptide (ANP) assays revealed that urodilatin does circulate distinctly from ANP. RESULTS: Urodilatin circulates at very low levels (i.e 9-12 pg/ml). Infusion of ANP increased the circulating concentration of urodilatin 135-fold (p < 0.001), suggesting that some of the effects of ANP may be mediated by urodilatin while long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide did not affect urodilatin in healthy humans (n = 30). Only ANP decreased the renal clearance of urodilatin (60-75%, p < 0.01). Urodilatin was metabolized into peptides smaller than 5 AAs as well as excreted intact into urine. CONCLUSION: Urodilatin circulates and is increased by ANP in humans.

Disposition of vessel dilator and long-acting natriuretic peptide in healthy humans after a one-hour infusion.

The present investigation was designed to determine half-lives, distribution phases and metabolic clearance of two new cardiac peptide hormones in humans. Long-acting natriuretic peptide (LANP) and vessel dilator were infused at 100 ng/kg of b.wt./min concentrations for 60 min with their respective concentrations measured by specific radioimmunoassays in plasma during and for 3 hr after infusion. The half-life of vessel dilator was 107 min, whereas the half-life of LANP was 28 min. The average time that the respective peptides were retained in the body (mean residence time) was 214 +/- 34 min for vessel dilator and 178 +/- 12 min for LANP, which indicates that they are widely distributed outside the initial space (i.e., circulation). The metabolic clearance normalized to 1.73 m2 body surface area was 241 ml/min for vessel dilator and 249 ml/min for LANP. The total body clearance normalized to 1.73 m2 body surface area was 130 ml/min for vessel dilator and 293 ml/min for LANP. The significantly (P < .001) longer half-lives and slower metabolic clearance of LANP and vessel dilator compared with atrial natriuretic factor (half-life, 2.5 min, metabolic clearance, 582-2,581 ml/min/1.7 m2) explain why these peptides circulate at concentrations 15- to 24-fold higher than atrial natriuretic factor in healthy humans.

Atrial natriuretic peptides increase calcitonin gene-related peptide within human circulation.

Long-acting natriuretic peptide (LANP), vessel dilator, and atrial natriuretic factor (ANF) (each infused at 100 ng/kg body weight [BW].min for 60 minutes) increased the circulating concentration of calcitonin gene-related peptide (CGRP) threefold to fourfold in 30 healthy humans. Within 30 minutes of stopping ANF infusion, the CGRP circulating concentration had returned to preinfusion levels, whereas its increase secondary to the other atrial peptides was still significant 2 to 3 hours after cessation of their infusions. There was a 50% decreased excretion (P < .001) of CGRP into the urine secondary to LANP and vessel dilator, which correlated with the increase of CGRP in the circulation. The ANF-induced 50% decreased CGRP excretion occurred after the circulating concentration of CGRP had returned to preinfusion levels. Kaliuretic peptide did not affect CGRP circulating concentration or excretion into urine. These data suggest that LANP and vessel dilator inhibit the metabolic breakdown of CGRP as part of their mechanism of increasing CGRP in plasma, whereas the ANF effect of increasing CGRP in plasma appears to be secondary to stimulating the release of CGRP.

Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators.

OBJECTIVES: The present investigation was designed to determine the best endogenous plasma marker of early congestive heart failure (CHF). METHODS: Forty volunteers with mild CHF (New York Heart Association Class I, n = 12), moderate (Class II, n = 8), or severe (Class III and Class IV, each = n of 5) and 10 age-matched healthy individuals had the simultaneous evaluation of their respective plasma samples by the following radioimmunoassays: atrial natriuretic peptide, ANP; three N-terminal ANP prohormone assays, i.e., proANPs 1-30, 31-67, and 79-98 with the numbers referring to their amino acid (a.a.) sequences in their 126 a.a. prohormone; brain (BNP) and C-natriuretic peptides; N-terminal BNP prohormone; adrenomedullin; neuropeptide Y and endothelin. RESULTS: ProANPs 31-67, 1-30 and 79-98 had 100% (P = 0.01), 83% (P = 0.09) and 50% (P = 0.74) sensitivity in differentiating Class I CHF subjects from healthy subjects. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y, and endothelin assays could not differentiate mild CHF subjects from healthy individuals. Logistic regression analysis revealed that only proANP 31-67 significantly (P = 0.0001) discriminated between early CHF (5226 +/- 377 pg/ml) and healthy individuals (1595 +/- 157 pg/ml). The positive and negative predicative values of proANP 31-67 were excellent (100% for each). The peptides measured in these assays were found to be independent markers of CHF with respect to left ventricular ejection fraction. CONCLUSIONS: ProANPs 31-67 is the most sensitive marker in discriminating NYHA Class I CHF subjects from healthy individuals. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y and endothelin radioimmunoassays cannot discern mild CHF. These peptides are independent of left ventricular ejection fraction.

Processing of long-acting natriuretic peptide and vessel dilator in human plasma and serum.

High performance-gel permeation chromatography (HP-GPC) evaluation of human plasma and serum incubated at 37 degrees C up to 24 h after the addition of long-acting natriuretic peptide (LANP) revealed a 25% decrease in LANP's peak at 2 h followed by an increase in plasma without EDTA at 8 h (p < 0.001). Vessel dilator's HP-GPC peak did not decrease until after 8 h of incubation. These findings help explain the prolonged half-lives and 6-24 higher plasma concentrations of vessel dilator and LANP compared to atrial natriuretic factor and kaliuretic peptide, which are completely degraded in plasma within 2 h.

Processing of kaliuretic peptide in human plasma and serum.

High performance-gel permeation chromotography (HP-GPC) evaluation of human plasma and serum incubated at 37 degrees C for 0, 0.5, 1, 1.5, 2, 4, 8, and 24 h after the addition of the human synthetic form of kaliuretic peptide revealed only a peak where the pure synthetic form of kaliuretic peptide elutes and that this peak decreased by 60% or greater in plasma-EDTA, plasma-heparin, and serum within 30 min. The metabolic processing of kaliuretic peptide in plasma-EDTA, plasma-heparin, and serum, respectively, was complete in 2 h with only 4%, 1%, and 2% of kaliuretic peptide's originally added concentration being still present.

A morphological study of differentiated hepatocytes in vitro.

A problem traditionally encountered with primary hepatocyte cultures is their rapid dedifferentiation, which is reflected not only in decreased liver-specific functions, but also in dedifferentiated morphology: the cells flatten, depolarize, and lose many of the surface characteristics of normal hepatocytes in vivo. However, culture conditions that maintain primary rat hepatocytes in a healthy and highly differentiated state were recently developed: the hepatocytes are cultured in Chee's Medium supplemented with dexamethasone and dimethyl sulfoxide (DMSO) on collagen-coated Permanox dishes. In addition to retaining labile hepatocyte-specific functions (e.g., P450 activity and albumin synthesis), these hepatocytes also have a differentiated morphology. They have numerous microvilli and are cuboidal and cluster into cords reminiscent of hepatic trabeculae. Their subcellular organelles have normal morphology, and specialized junctions and bile canaliculi form within the membranes of adjacent cells. Actin fibers cluster at these canalicular surfaces. These hepatocytes also synthesize blood clotting factors, which aggregate into fibrin meshworks between cells. Taken together, these morphological data suggest that these hepatocytes are polarized and generally have an appearance very similar to parenchymal cells in the liver, and that the same culture conditions that promote retention of liver-specific functions are also critical to the maintenance of physiological morphology. In contrast to other hepatocyte cultures, this differentiated morphology, including the polarized nature of the cells, is established without the use of serum or flexible or complex extracellular matrices and shows a close link between cellular architecture and tissue-specific function.

Caring for the elderly: a crisis on the horizon.

As baby boomers age, the proportion of elderly people will increase. Growing numbers of senior citizens coupled with shrinking budgets may force society to find alternatives to nursing homes, predicts a Des Moines geriatrician.

A role for cytokines in antigen presentation: IL-1 and IL-4 induce accessory functions of antigen-presenting cells.

Fixation of APC with 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide (ECDI) eliminates their ability to stimulate proliferation of alloreactive T cells or the D10 T cell clone, although a partial response, IL-4 production, was measured. However, if APC were activated before fixation, they could be ECDI-fixed and retain the ability to induce T cell proliferation. IL-1, IL-4 or LPS were capable of activating APC in this way, whereas IFN-gamma was not. This activation step occurred in 6 h, required protein synthesis, and was distinct from increases in Ia or IL-1. This suggests resting APC lack structures that are essential for inducing T cell proliferation.

Voice restoration after total laryngopharyngectomy and cervical esophagectomy using the duckbill prosthesis.

We have presented a series of 10 patients who were successfully rehabilitated using the tracheoesophageal puncture technique for voice restoration. These patients underwent total laryngopharyngectomy or laryngopharyngoesophagectomy and reconstruction with visceral transposition (five patients), myocutaneous flaps (four patients), and skin graft and cervical flaps (one patient). All patients were able to produce adequate voice and carry on a conversation. Clinical evaluation of voice quality and acoustic analysis of voice samples indicate that the voice obtained in these patients was intelligible, and had adequate intensity, low pitch, and limited pitch variation. There were no complications related to the voice restoration procedure. It appears from our data and the limited experience reported in the literature that the tracheoesophageal prosthesis can be used successfully and safely for the speech rehabilitation of patients who undergo total laryngopharyngectomy, cervical esophagectomy, or both, regardless of the reconstructive method used.

In vivo resistance of secondary antitumor immune response to cyclophosphamide: effects on T cell subsets.

We have analyzed the effects of high doses of cyclophosphamide (Cy) on primary and secondary antitumor immune response against immunogenic (tum-) variants of Lewis lung carcinoma (3LL) treated in vitro with UV light. Normal mice and mice previously immunized with tum- clones wer inoculated i.p. with Cy (200 mg/kg body weight) and 24 h later challenged intrafootpad with tum- or parental 3LL cells. Cy treatment suppressed the primary immune response of normal animals and allowed the growth of tum- cells. In contrast, Cy-treated immune mice rejected the tumor challenge. The in vivo treatment with Cy decreased the total number of lymphoid cells in the spleens, as well as the proportion of B lymphocytes; however, it increased the percentage of both Lyt2+ and L3T4+ lymphocytes. Thus, the immunosuppressive effects of Cy on the primary antitumor response could not be attributed to elimination of major T lymphocyte subpopulations. Although the treatment of immune mice with Cy did not significantly impair their antitumor resistance, nor the proportion of Lyt2+ and L3T4+ lymphocytes in their spleens, the in vitro generation of cytotoxic T lymphocytes (CTL) was markedly reduced. After Cy treatment, the proliferative ability of spleen cells in response to interleukin-2 (IL-2) was substantially impaired. Using monoclonal antibodies to the IL-2 receptor, we found that Cy-treated T lymphocytes failed to fully express the IL-2 receptor following in vitro stimulation with irradiated tumor cells. In line with these findings, the in vitro generation of CTL was not restored by addition of recombinant IL-2 to the cultures. In vivo experiments using purified functional subsets of immune T cells showed that Lyt1+, but not Lyt2+ lymphocytes were able to transfer antitumor immunity in normal irradiated recipients. Therefore, since Ly1+ T lymphocytes were responsible for the antitumor resistance in vivo, the Cy-induced impairment of CTL generation did not affect the ability of immune mice to reject a secondary tumor challenge.

Lymphokine-activated killer cells. Analysis of progenitors and effectors.

IL-2 has been examined for its ability to regulate lymphokine-activated killer (LAK) activity. IL-2 is a potent activator of cytolytic activity against a wide array of tumor cells, including those from fresh autologous and allogeneic tumors. Using subpopulations of lymphoid cells that were separated on Percoll density gradients, and subsequently purified by immunoadsorbance, studies were performed to examine the phenotypes of progenitor and effector cells of human LAK cells and to compare them with the phenotype of activated NK cells. From these studies, it was evident that several lymphoid subsets, including CD3+, CDw16- and CD3-, CDw16+ cells could mediate LAK lysis of fresh tumor cells. Our examination of the kinetics of activation revealed that CDw16+, NKH1+ (NK-active) cells were maximally activated by 1-2 d. In contrast, CD3+ cells appeared not to achieve maximal cytolytic activity against fresh and cultured tumor cells until days 2-3. Using limiting-dilution frequency analysis, we showed that a large percentage of cytolytically active progenitors was present among the CDw16+, NKH1+ cells. The progenitor and effector cell frequencies appear to be 10-50 times higher in these populations compared to CD3+ cells. In addition, the selective blockage by mAb to the CD3 determinant of the T cell receptor complex indicated that these two effector cell phenotypes relied on different receptors to mediate their cytotoxic activity against tumor cells. Therefore, the accumulated data suggest that there is not a single unique progenitor of LAK activity, but rather that multiple subsets of lymphocytes become cytotoxic in response to IL-2. However, the NK cell population forms the largest single component of LAK cell activity in human peripheral blood.

Analysis of effector mechanisms against HTLV-I- and HTLV-III/LAV-infected lymphoid cells.

Acquired immunodeficiency syndrome is associated with a viral (HTLV-III/LAV)-mediated progressive depletion of a helper/inducer T4+ T cell subset, whereas acute T cell leukemia is associated with a viral (HTLV-I)-mediated growth of the same T cell subset. Because large granular lymphocytes (LGL) with natural killer (NK) activity have been shown to spontaneously lyse several virus-infected target cells, the ability of NK cells to lyse both HTLV-I- and HTLV-III/LAV-infected lymphoid cell lines and fresh lymphocytes was explored. Normal lymphocytes (T cells and LGL), with and without pretreatment with recombinant interleukin 2 (IL 2), as well as monocytes, with and without pretreatment with interferon-gamma were employed as effectors. Both IL 2-activated T cells and NK cells were cytolytic for HTLV-I-infected targets. However, only LGL demonstrated significant spontaneous activity against HTLV-I-infected targets. Similarly, LGL showed spontaneous cytolytic activity against HTLV-III/LAV-infected targets, and this cytotoxicity was considerably augmented by IL 2. In contrast, T cells and monocytes were unable to lyse HTLV-III/LAV targets, and only minimal activity was induced by activation. LGL cells, B cells, and monocytes were infectible in vitro by high titers of HTLV-III/LAV. However, levels of reverse transcriptase found in these cultures were significantly lower than the levels in T cell cultures. In contrast, only T cells were susceptible to infection by HTLV-I. Experiments with the use of cell cocultures showed that LGL afforded T cells protection from infection by HTLV-I (as indicated by lack of transformation and viral protein expression) but not from infection by HTLV-III/LAV. Collectively, these results indicate that NK cells may play a role in protecting cells against HTLV infection.