Biomedical subjects

R A Anderson

Publications and source records attributed to R A Anderson.

At least 37 records · Page 2Linked to original sources

PubMed2003

Demonstration of progesterone receptor-mediated gonadotrophin suppression in the human male.

OBJECTIVE: Synthetic gestogens in combination with testosterone have potential as a male hormonal contraceptive, predominantly acting by augmenting suppression of gonadotrophin secretion. Little is known, however, of the effects of gestogens in the male. Gestogens have affinity for both androgen and progesterone receptors but the relative contribution of action at these two receptors in gonadotrophin suppression remains unclear. In this study the effects of progesterone, with no significant androgen-receptor affinity are compared to desogestrel, a synthetic gestogen with relatively low affinity for the androgen receptor, on gonadotrophin secretion in normal men. DESIGN: Subjects received either 50 mg progesterone intramuscularly (i.m.) or 300 micro g desogestrel orally daily for 7 days. Frequent blood sampling over 12 h was undertaken before and after drug administration. GnRH [100 micro g intravenously (i.v.)] was administered 2 h before the end of the frequent sampling period. SUBJECTS: Twenty healthy men were randomly allocated to the two treatment groups. RESULTS: Both progesterone and desogestrel administration resulted in decreases in the concentration of both LH and FSH secretion, as well as testosterone. Analysis of the pulsatile nature of LH secretion indicated that both treatments reduced LH pulse amplitude, and that progesterone reduced LH pulse frequency. Progesterone, but not desogestrel, treatment also reduced the increase in LH secretion in response to GnRH. CONCLUSIONS: The effects of progesterone were at least as marked as those of a maximally effective dose of desogestrel. As progesterone has negligible affinity for the androgen receptor, these results are compatible with the suppressive effects of synthetic 19-norgestogens on gonadotrophin secretion in the male being mediated via the progesterone receptor, with its androgenicity contributing minimally to gonadotrophin suppression.

Administration, Oral↗

PubMed2003

Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus.

BACKGROUND: Insulin therapy may influence cardiovascular disease (CVD) and lipid metabolism in type 2 diabetes (T2D). Exaggerated postprandial lipaemia (PPL) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress (OS) and endothelial dysfunction. We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty (17 M) T2D patients were studied (mean Hba1c 8.4%) at baseline, following 6 weeks of insulin lispro (0.2 Iu kg-1) and vitamin C 1-g daily. Eight-h lipid and glucose profiles were measured following a fatty meal. Endothelial function (flow-mediated vasodilatation: FMD) and OS were measured at fasting, 4 h and 8 h. MATERIALS AND METHODS: Glucose, body mass index, and total and LDL cholesterol remained unchanged. FMD improved. Placebo group: fasting, 1.1 +/- 1.2 to 4.2 +/- 1.1% (P < 0.001); 4-h, 0.3 +/- 1.2 to 3.1 +/- 0.9% (P < 0.01); 8-h, 0.7 +/- 1.1 to 3.76 +/- 1.1% (P < 0.001). Vitamin C group: fasting, 0.9 +/- 1.1 to 6.1 +/- 1.3% (P < 0.001); 4-h, 0.7 +/- 1.5 to 4.9 +/- 2.1% (P < 0.001); 8-h, 0.8 +/- 0.9 to 5.8 +/- 0.6% (P < 0.01). Post-prandial lipaemia was attenuated: TG area-under-curve (mmol L-1 8 h-1), 52.6 +/- 11 to 39.1 +/- 12.5 (placebo group), P < 0.02; and 56.9 +/- 8 to 40.1 +/- 10.3 (vitamin C group), P < 0.02. Oxidative stress was reduced, with greater changes in the vitamin C group. CONCLUSION: Insulin may thus exert vascular benefits in T2D, by modifying fasting and postprandial lipid metabolism resulting in reduced OS and improved EF. Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF.

Adult↗

PubMed2003

Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Müllerian hormone, inhibin B and ovarian ultrasound.

BACKGROUND: Treatment of cancer during childhood may result in loss of primordial follicles from the ovary. METHODS: Ten cancer survivors and 11 controls with regular menstrual cycles, in addition to 10 cancer survivors and 10 controls taking the combined oral contraceptive pill (COCP) were recruited. Subjects were investigated on days 3-5 of a menstrual cycle, or week 3 of COCP administration before and 24 h after administration of 225 IU FSH. RESULTS: Serum FSH levels were elevated in cancer survivors with regular menstrual cycles (7.5 +/- 1.4 versus 4.2 +/- 0.3 IU/l; P = 0.02), while anti-Müllerian hormone (AMH) levels were lower (13.0 +/- 3.0 versus 21.0 +/- 3.4 pmol/l; P < 0.05). Other hormone levels were unchanged. Ovarian volume was smaller in cancer survivors than controls (3.0 +/- 0.5 versus 5.0 +/- 0.8 ml; P < 0.05), but antral follicle count (AFC) was similar. During COCP administration, inhibin B remained undetectable in six cancer survivors after FSH administration, whereas all controls showed a rise in inhibin B levels. The AFC was lower in cancer survivors than in controls (4.2 +/- 0.8 versus 7.2 +/- 0.8; P = 0.02). Ovarian volume was low in both groups, but did not differ between them. CONCLUSIONS: The study results demonstrate both hormonal and biophysical evidence of partial loss of the ovarian reserve in young cancer survivors. This was detected both in women with normal menstrual cycles and during COCP administration.

Adolescent↗

PubMed2002

Biomarkers of exposure to cyanogens in horses with grass sickness.

To test the hypothesis that equine grass sickness may be associated with the ingestion of cyanogenic glycosides from white clover (Trifolium repens), the concentrations of whole blood cyanide, and plasma and urinary thiocyanate, the main metabolite of cyanide, were measured in 12 horses with acute grass sickness and 10 horses with subacute grass sickness, and in 43 control horses, of which 21 were co-grazing with cases of acute grass sickness, 12 grazed pastures where grass sickness had not been reported, and 10 were stabled horses. The healthy horses which grazed with cases of acute grass sickness had higher concentrations of blood cyanide, and plasma and urinary thiocyanate than the other control horses, consistent with an increased exposure to cyanogens. The horses with grass sickness had no evidence of a recent intake of cyanogens, but may have been exposed to increased levels of cyanogens before they became anorexic.

Animals↗

PubMed2002

Investigation of a novel preparation of testosterone decanoate in men: pharmacokinetics and spermatogenic suppression with etonogestrel implants.

We have investigated the pharmacokinetics and effects on the male reproductive axis of a novel preparation of testosterone decanoate (TD) with a progestogen implant. Twenty healthy Chinese men were administered TD (400 mg intramuscular 4 weekly) with two subcutaneous (SC) etonogestrel implants. Trough testosterone concentrations rose with repeated administration. Peak concentrations 1 week after the fourth injection were 31 +/- 2 nmol/liter. Both LH and FSH were rapidly suppressed and continued to fall during treatment. Spermatogenesis was also suppressed, to <or=1 x 10(6)/mL in all men with 16 (80%) azoospermic at 12 weeks. Treatment was associated with an increase in weight, and also increases in hemoglobin concentration (9%) and hematocrit (15%). No subjects withdrew from the study, although the study was terminated after subjects had completed 12 to 18 weeks as some men were found to have elevated liver enzyme tests. These data demonstrate that the pharmacokinetics of TD are improved compared to previous injectable testosterone preparations, although peak testosterone concentrations rise briefly into the supraphysiological range. The speed and degree of spermatogenic suppression suggest that this combination has promise as an effective male contraceptive.

Adult↗

PubMed2002

Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone.

BACKGROUND: Suppression of spermatogenesis to azoospermia is required for effective hormonal male contraception, but the degree of suppression varies between ethnic groups. We here report the first study of hormonal suppression of spermatogenesis in two African centres using a regimen of oral progestogen with depot testosterone. METHODS A total of 31 healthy men (21 black) were recruited in Cape Town and 21 men in Sagamu, Nigeria. Subjects were randomized to take either 150 or 300 micro g desogestrel daily p.o. with testosterone pellets. In Cape Town, desogestrel was administered for 24 weeks with 400 mg testosterone re-administered 12 weekly. In Sagamu, desogestrel was administered for 52 weeks with 200 mg testosterone (later increased to 400 mg) re-administered 12-weekly. RESULTS: In Cape Town, 22 men completed at least 20 weeks treatment. Azoospermia was achieved in 8/10 and 8/12 men in the 150 micro g and 300 micro g desogestrel groups. Four men in Sagamu withdrew. Azoospermia was achieved in all 17 men in the two groups. There were no significant changes in lipoprotein or haemoglobin concentrations in any group. CONCLUSION: These data demonstrate that the combination of oral desogestrel with depot testosterone is an effective regimen for suppression of spermatogenesis in African as in Caucasian and Chinese men, with azoospermia achieved in a total of 83/98 (85%) men.

Administration, Oral↗

PubMed2002

Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men.

BACKGROUND: Effective hormonal male contraception requires a high prevalence of spermatogenic suppression, which has proved particularly difficult in Caucasian populations. We have investigated the combination of oral desogestrel with depot testosterone in Caucasian and Chinese men. METHOD: Thirty men in Edinburgh and 36 men in Shanghai received 150 or 300 microg desogestrel p.o. daily for 24 weeks with 400 mg testosterone pellets s.c. on day 1 and at 12 weeks. RESULTS: Eight men withdrew before completing 24 weeks treatment. Testosterone concentrations remained within the normal range. Spermatogenesis was profoundly suppressed in all men. Azoospermia was achieved by a higher proportion of men in the 300 microg desogestrel group: 28/28 men versus 22/31 men (P < 0.05). All Caucasian men in the 150 microg group achieved sperm concentrations of < 1 x 10(6)/ml whereas three men in the Shanghai group maintained sperm concentrations of > 3 x 10(6)/ml. Fifteen men continued on this regimen for a subsequent 24 weeks: all remained azoospermic for the duration of treatment. High-density lipoprotein cholesterol fell by 15% in Caucasian men, but was unchanged in the Chinese men; both groups showed some weight gain. CONCLUSION: This combination of oral desogestrel with depot testosterone maintains physiological testosterone concentrations with consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men and therefore has many of the properties necessary for a contraceptive preparation for men.

Administration, Oral↗

PubMed2002

Investigation of suppression of the hypothalamic-pituitary-gonadal axis to restore spermatogenesis in azoospermic men treated for childhood cancer.

BACKGROUND: Does suppression of the hypothalamic-pituitary-gonadal (HPG) axis restore spermatogenesis in men rendered azoospermic following treatment of childhood cancer? METHODS: Seven men with azoospermia secondary to treatment for childhood cancer, median age (range), 22.2 (18-25.3) years, aged 10.4 (4.4-13.3) years at original diagnosis, participated. Each subject underwent semen analysis and testicular biopsy, followed by treatment with medroxyprogesterone acetate (MPA), 300 mg i.m. repeated after 12 weeks, with 800 mg testosterone pellets s.c. on day 1 to suppress the HPG axis. Hormone and semen analysis was performed every 6 weeks for 48 weeks. A second testicular biopsy was performed at week 48. RESULTS: Before HPG axis suppression, mean +/- SEM plasma LH was 9.0 +/- 1.8 U/l, testosterone 17.9 +/- 1.5 nmol/l and FSH 22.4 +/- 4.4 U/l. Median (range) venous plasma and seminal plasma inhibin B levels were 10.0 (7.8-35) and 11.2 (7.8-770) ng/l respectively. During HPG suppression, FSH and LH levels were undetectable for > or =12 weeks followed by a gradual return to pretreatment concentrations by 48 weeks. All men remained azoospermic at study completion and complete absence of germ cells on biopsies was demonstrated by immunocytochemistry for all specimens pre- and post-HPG axis suppression. CONCLUSIONS: HPG axis suppression with MPA-testosterone for > or =12 weeks did not restore spermatogenesis in azoospermic men treated with gonadotoxic radiotherapy and chemotherapy for childhood cancer.

Adolescent↗

PubMed2002

Mandelic acid condensation polymer: novel candidate microbicide for prevention of human immunodeficiency virus and herpes simplex virus entry.

Presently marketed vaginal barrier methods are cytotoxic and damaging to the vaginal epithelium and natural vaginal flora when used frequently. Novel noncytotoxic agents are needed to protect men and women from sexually transmitted diseases. One novel candidate is a mandelic acid condensation polymer, designated SAMMA. The spectrum and mechanism of antiviral activity were explored using clinical isolates and laboratory-adapted strains of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). SAMMA is highly effective against all CCR5 and CXCR4 isolates of HIV in primary human macrophages and peripheral blood mononuclear cells. SAMMA also inhibits infection of cervical epithelial cells by HSV. Moreover, it exhibits little or no cytotoxicity and has an excellent selectivity index. SAMMA, although not a sulfonated or sulfated polymer, blocks the binding of HIV and HSV to cells by targeting the envelope glycoproteins gp120 and gB-2, respectively, and also inhibits HSV entry postattachment. SAMMA is an excellent, structurally novel candidate microbicide that warrants further preclinical evaluation.

Antiviral Agents↗

PubMed2002

Male contraception.

The provision of safe, effective contraception has been revolutionized in the past 40 yr following the development of synthetic steroids and the demonstration that administration of combinations of sex steroids can be used to suppress ovulation and, subsequently, other reproductive functions. This review addresses the current standing of male contraception, long the poor relation in family planning but currently enjoying a resurgence in both scientific and political interest as it is recognized that men have a larger role to play in the regulation of fertility, whether seen in geopolitical or individual terms. Condoms and vasectomy continue to be popular at particular phases of the reproductive lifespan and in certain cultures. Although not perfect contraceptives, condoms have the additional advantage of offering protection from sexually transmitted infection. The hormonal approach may have acquired the critical mass needed to make the transition from academic research to pharmaceutical development. Greatly increased understanding of male reproductive function, partly stimulated by interest in ageing and the potential benefits of androgen replacement, is opening up other avenues for investigation taking advantage of nonhormonal regulatory pathways specific to spermatogenesis and the reproductive tract.

Condoms↗

PubMed2002

Developmental changes in expression of myeloid cell leukemia-1 in human germ cells during oogenesis and early folliculogenesis.

The regulation of germ cell number in the developing ovary is central to female reproduction. Members of the Bcl-2 family of proapoptotic and antiapoptotic proteins have been implicated in this process in rodents. We investigated the expression of Mcl-1, Bcl-2, Bax, and BAD at 13-21 gestational wk in the human fetal ovary and of Mcl-1 in the adult ovary. mRNA expression of Mcl-1 and its short form Mcl-1s, Bcl-2, Bax, and BAD was demonstrated in fetal ovary by RT-PCR. Hybridization array analysis suggested a selective increase in Mcl-1 expression between 14 and 18 wk gestation, which was confirmed by quantitative PCR. There was a corresponding change in the expression of Mcl-1 protein, detected by immunohistochemistry, from germ cells at the periphery of the ovary at 14-16 wk to the largest germ cells, including oocytes within newly formed primordial follicles, at 21 wk. Mcl-1 was also expressed by oocytes of primordial and preantral follicles in the adult. Bax and BAD immunostaining was detected in both somatic and germ cells in the fetal ovary, whereas Bcl-2 was restricted to somatic cells: no changes in expression were observed. Apoptotic cells, detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, were observed in all fetal ovaries but were infrequent. These results confirm that Bcl-2 family members are differentially expressed in several cell types within the developing human ovary. Increased mRNA expression and the changing distribution of Mcl-1 in germ cells as they develop into primordial follicles as well as persistence in the growing oocyte in the adult may indicate an important role for this survival/antiapoptotic factor throughout germ cell development and maturation.

Carrier Proteins↗

PubMed2002

Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception.

The coadministration of a progestogen with testosterone increases the degree of suppression of spermatogenesis and is one approach to the development of hormonal male contraception. Depot formulations may allow a reduction in dosage, minimizing adverse effects. We have investigated the effects of a sc implant containing the progestogen etonogestrel (Implanon) with depot testosterone on spermatogenesis in normal men. Twenty-eight men were randomized to receive either one or two etonogestrel implants, removed after 24 wk. All men additionally received 400 mg testosterone pellets on d 1 and at 12 wk. Four men withdrew during the study, three because of side effects. Testosterone concentrations remained within the physiological range during treatment, although they were overall slightly reduced, compared with pretreatment. Both groups showed marked suppression of spermatogenesis, nine men in each group achieving azoospermia (64% and 75% in the one- and two-implant groups, respectively). Sperm concentrations in 13/14 men in the two-implant group fell to 0.1 x 10(6)/ml or less. Spermatogenic suppression was more variable in the one-implant group, with partial recovery in three men. Incomplete suppression of spermatogenesis in the one-implant group was associated with less complete suppression of gonadotropins. There were no significant changes in body weight, hemoglobin, hematocrit, or high-density lipoprotein cholesterol concentrations during treatment. These data demonstrate that etonogestrel implants with depot testosterone provide effective suppression of spermatogenesis with reduced metabolic effects and are, therefore, a promising approach to the development of long-acting yet reversible male contraception.

Adult↗

PubMed2002

Expression and localization of inhibin alpha, inhibin/activin betaA and betaB and the activin type II and inhibin beta-glycan receptors in the developing human testis.

Inhibins and activins have roles in the regulation of cell proliferation and differentiation in a variety of tissues. This study investigated the distribution of the three inhibin/activin subunits (alpha, betaA and betaB) and their receptors in the human testis between week 13 and week 19 of gestation using RT-PCR and immunohistochemistry. mRNA for all three subunits and for the activin type II receptors ActRIIA and ActRIIB was detected at all stages of gestation examined. Sertoli cells showed intense immunostaining for the alpha subunit and some staining for the betaB subunit, whereas only the betaB subunit was detected in gonocytes. No betaA subunit staining was detected within the tubules. All three subunits were localized to interstitial Leydig cells. Cells of the rete testis and the epididymal epithelium also showed immunostaining for betaB; however, staining for the other subunits was weak or absent. Peritubular cells showed intense immunostaining for the beta-glycan inhibin receptor, which was also localized to interstitial cells, but was not detected within the tubular compartment, rete testis or epididymal epithelium. ActRIIA was detected in gonocytes and in interstitial cells; ActRIIB was distributed widely. These data indicate that fetal Leydig and Sertoli cells have the potential to produce both activins and inhibins, whereas gonocytes may produce only activin B. The distribution of activin and inhibin receptors implies that the intratubular compartment and developing duct system are sites of action of activin B but not inhibin at this stage of development, whereas both activins and inhibins may be involved in the development and function of the peritubular and interstitial cells.

Actins↗

PubMed2001

Expression of COX-2 and PGE synthase and synthesis of PGE(2)in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors.

This study was designed to investigate the possible role of cyclo-oxygenase-2 (COX-2) and prostaglandin E(2)(PGE(2)) in endometrial adenocarcinoma. COX-2 RNA expression was confirmed in various grades of adenocarcinoma by ribonuclease protection assay. COX-2 and microsomal glutathione-dependent prostaglandin E synthase (mPGES) expression and PGE(2)synthesis were localised to the neoplastic epithelial cells and endothelial cells. In order to establish whether PGE(2)has an autocrine/paracrine effect in adenocarcinomas, we investigated the expression of 2 subtypes of PGE(2)receptors, namely EP2 and EP4, by real time quantitative PCR. Expression of EP2 and EP4 receptors was detected in adenocarcinomas from all grades of differentiation and was significantly higher than that detected in normal secretory phase endometrium (P< 0.01). The fold induction of expression in adenocarcinoma compared with normal secretory phase endometrium was 28.0 +/- 7.4 and 52.5 +/- 10.1 for EP2 and EP4 receptors respectively. Immunohistochemistry localised the site of expression of EP4 receptor in neoplastic epithelial cells and in the endothelium of carcinomas of all grades of differentiation. Finally, the functionality of the EP2/EP4 receptors was assessed by investigating cAMP generation following in vitro culture of adenocarcinoma tissue in the presence or absence of 300 nM PGE(2). cAMP production in response to PGE(2)was significantly higher in carcinoma tissue than that detected in normal secretory phase endometrium (3.42 +/- 0.46 vs 1.15 +/- 0.05 respectively; P< 0.001). In conclusion, these data suggest that PGE(2)may regulate neoplastic cell function in an autocrine/paracrine manner via the EP2/EP4 receptors.

Adenocarcinoma↗

PubMed2001

Clinical studies: inhibin in the adult male.

The current generation of inhibin assays have allowed the demonstration that inhibin B is the long-postulated testicular factor comprising the feedback inhibitory pathway between the testis and FSH secretion. The inverse relationship between inhibin B and FSH secretion is seen in both normal men and in testicular pathologies. Although inhibin B concentrations are increased by gonadotrophin administration, adult secretion is only partly gonadotrophin dependent and appears more closely related to the presence of germ cells. Thus, inhibin B concentrations are maintained at least at 30% of normal following gonadotrophin suppression, but fall to undetectable levels following loss of all germ cells, e.g. by testicular irradiation. The direct positive correlation between inhibin B and sperm concentration in normal men indicates that inhibin B quantitatively reflects the number of spermatozoa being released. Data from studies of infertile men undergoing testicular biopsy is providing information as to the particular stages of spermatogenesis involved. These intercellular relationships may underlie the relative resistance of inhibin B to suppression by some hormonal contraceptive regimens, despite azoospermia being induced. Inhibin B is also present in seminal plasma. There is a far wider range of concentration in seminal plasma than in blood and the significant relationship with sperm concentration indicates that inhibin secretion into the ejaculate is a marker of the functional activity of the seminiferous tubule. This relationship with sperm production may be a useful marker in some contexts, as changes are more dynamic than in the circulating hormone.

Adult↗

PubMed2001

The relationships between post-prandial lipaemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes.

Post-prandial lipaemia (PPL) is a factor in atherogenesis and results in reversible endothelial dysfunction in healthy individuals. Oxidative stress and triglyceride (TG)-rich lipoproteins have been implicated. Type 2 diabetes (NIDDM) results in exaggerated PPL. We attempted to delineate the mechanisms of PPL induced, endothelial dysfunction (EF) and oxidative stress in 12 NIDDM and 12 matched healthy subjects. Subjects underwent a fat tolerance test, with endothelial function assessed by flow-mediated vasodilatation and oxidative stress measured by venous lipid-derived free radicals ex vivo and lipid peroxidation products over the postprandial phase. Fasting TG, post-prandial hypertriglyceridaemia and the TG enrichment of all lipoproteins was significantly greater in NIDDM. Post-prandial endothelial function inversely correlated with fasting HDL-C (r=-0.84, P=0.001) in both the control and NIDDM groups. The deterioration in EF in the NIDDM group also correlated with TG enrichment of VLDL and LDL. PPL in both groups also resulted in increased oxidative stress. The increment in free radicals correlated with TG enrichment of VLDL in both groups and was, therefore, greater in NIDDM. Thus, PPL -- with the production of TG-enrichment of VLDL -- results in endothelial dysfunction by an oxidative stress mechanism in both groups. The magnitude is greater in NIDDM. Fasting HDL-C appears to contribute to the protection of the endothelium against this phenomenon. Hence, exaggerated PPL associated with reduced HDL-C may be important in the pathogenesis of vascular disease, particularly in NIDDM.

Adult↗

PubMed2001

Intensity of case managers' participation in organizational decision making.

Prior research has indicated that registered nurse (RN) participation in decision making (PDM) is related to better outcomes in nursing homes and hospitals. Little is known, however, about the roles of community-based case managers (CMs), most of whom are RNs. Data from 68 prenatal case management programs were used to test hypotheses about the intensity of CM PDM and to describe their patterns of involvement in decision activities and mechanisms. CMs were most involved in the activity of "raising the issue" and least involved in "choosing the alternative." However, "choosing the alternative" was the strongest predictor of perceived CM influence over the final choice. When CMs were involved in informal meetings and chance encounters with administrators, they were more likely to be perceived as having influence over the final choices made. Intensity of CM PDM varied by decision level and content, supporting two of the three hypotheses. The findings are discussed in light of prior research and complexity theory.

Adult↗

PubMed2001

Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM).

Vaginal prophylactic methodology may prevent heterosexual transmission of the HIV and other sexually transmitted disease-causing organisms as well as unplanned pregnancies. A new delivery system (ACIDFORM) was designed with acid-buffering, bioadhesive, and viscosity-retaining properties to (1) maintain the acidic vaginal milieu (the low pH inactivates many pathogens and spermatozoa), (2) form a protective layer over the vaginal/cervical epithelium (minimizing contact with pathogenic organisms), and (3) provide long-term vaginal retention. A Phase I clinical study with ACIDFORM provided initial information about its safety and showed the formation of a layer over the vaginal/cervical epithelium [1; Amaral et al., Contraception 1999;60:361-6]. To study the properties of the gel (without active ingredient) in more detail, ACIDFORM's acid-buffering, bioadhesive, viscosity-retaining, and spermicidal properties were compared in vitro to marketed formulations, and its long-term stability was assessed. ACIDFORM, either when titrated with NaOH or when mixed directly with semen, is highly acid buffering and much more effective than Aci-Jel, a commercial acid-buffering vaginal product. ACIDFORM adheres well to two model membranes (excised sheep vagina and cellophane) and is more bioadhesive than Conceptrol, Advantage S, Replens, Aci-Jel, and K-Y jelly. On dilution, ACIDFORM also retains its viscosity better than these marketed products. ACIDFORM is spermicidal and is stable for at least 2 years. These results suggest that ACIDFORM has advantages over presently marketed vaginal delivery systems. The gel may either be useful by itself as an antimicrobial contraceptive product or as a formulation vehicle for an active ingredient with antimicrobial and/or contraceptive properties.

Acrylic Resins↗