Wyeth Ayerst Research Articles

Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy: A Randomized Trial.

Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown. To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups. Subgroup analyses of the randomized Women's Health Initiative Estrogen-Alone Trial. (ClinicalTrials.gov: NCT00000611). 40 U.S. clinical centers. 9939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. Conjugated equine estrogens (CEE) (0.625 mg/d) or placebo for a median of 7.2 years. Incidence of coronary heart disease and invasive breast cancer (the trial's 2 primary end points), all-cause mortality, and a "global index" (these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture) during the intervention phase and 18-year cumulative follow-up. The effects of CEE alone did not differ significantly according to BSO status. However, age modified the effect of CEE in women with prior BSO. During the intervention phase, CEE was significantly associated with a net adverse effect (hazard ratio for global index, 1.42 [95% CI, 1.09 to 1.86]) in older women (aged ≥70 years), but the global index was not elevated in younger women (P trend by age = 0.016). During cumulative follow-up, women aged 50 to 59 years with BSO had a treatment-associated reduction in all-cause mortality (hazard ratio, 0.68 [CI, 0.48 to 0.96]), whereas older women with BSO had no reduction (P trend by age = 0.034). There was no significant association between CEE and outcomes among women with conserved ovaries, regardless of age. The timing of CEE in relation to BSO varied; several comparisons were made without adjustment for multiple testing. The effects of CEE did not differ by BSO status in the overall cohort, but some findings varied by age. Among women with prior BSO, in those aged 70 years or older, CEE led to adverse effects during the treatment period, whereas women randomly assigned to CEE before age 60 seemed to derive mortality benefit over the long term. The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs.

FORMULATION AND EVALUATION OF VENLAFAXINE HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLET

Aim: The term modified-release drug product is used to describe products that alter the timing and/or the rate of release of the drug substance.Objective: The objective of the present study was to formulate and evaluate the sustained release matrix tablet of venlafaxine hydrochloride.Methods: Venlafaxine hydrochloride is a structurally novel antidepressant for oral administration. It is widely prescribed for the treatment of depression, generalized anxiety disorder, and social anxiety disorder. Venlafaxine hydrochloride is currently available as immediate release tablet and as an extended release capsules under the brand names of Effexor (WYETH AYERST) and Effexor XR (WYETH AYERST). The biological half-life of venlafaxine very short (5 h) and the dose is to be taken 2–3 times a day and the recommended maximum daily dose is 75–450 mg/day. Venlafaxine hydrochloride is an antidepressant and so it is to be taken for quite a long period. Hence, to reduce the dosing frequency, simple, lower cost sustained release tablets of venlafaxine were preferred for the development.Conclusion: The venlafaxine hydrochloride sustained release matrix tablets shown controlled release profile as per the release profile ofthe innovator is EffexorTm_XR. The sustained release of this matrix tablet reduces the dosing frequency and reduces the side effects, bywhich in a long-term therapy, it may be useful as a product with patient compliance for the treatment of major depression disorder.

Multiple Mechanisms Are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

The number of distinct signaling pathways that can transactivate the epidermal growth factor receptor (EGFR) in a single cell type is unclear. Using a single strain of human mammary epithelial cells, we found that a wide variety of agonists, such as lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factor-alpha, require EGFR activity to induce ERK phosphorylation. In contrast, hepatocyte growth factor can stimulate ERK phosphorylation independent of the EGFR. EGFR transactivation also correlated with an increase in cell proliferation and could be inhibited with metalloprotease inhibitors. However, there were significant differences with respect to transactivation kinetics and sensitivity to different inhibitors. In particular, IGF-1 displayed relatively slow transactivation kinetics and was resistant to inhibition by the selective ADAM-17 inhibitor WAY-022 compared with LPA-induced transactivation. Studies using anti-ligand antibodies showed that IGF-1 transactivation required amphiregulin production, whereas LPA was dependent on multiple ligands. Direct measurement of ligand shedding confirmed that LPA treatment stimulated shedding of multiple EGFR ligands, but paradoxically, IGF-1 had little effect on the shedding rate of any ligand, including amphiregulin. Instead, IGF-1 appeared to work by enhancing EGFR activation of Ras in response to constitutively produced amphiregulin. This enhancement of EGFR signaling was independent of both receptor phosphorylation and PI-3-kinase activity, suggestive of a novel mechanism. Our studies demonstrate that within a single cell type, the EGFR autocrine system can couple multiple signaling pathways to ERK activation and that this modulation of EGFR autocrine signaling can be accomplished at multiple regulatory steps.

Anti-epileptic Drugs for Acute Bipolar Depression: Applying Data to Clinical Practice

<P>Despite the emergence of several new options for the treatment of bipolar disorder within the last decade, the treatment of acute depressive episodes associated with bipolar disorder remains severely limited, both in terms of regulatory approvals and rigorous evidence-based pharmacotherapies. When compared with the manic phase of the illness, treatment options are narrowed in the depressive phase. The historical emergence and use of anti-epileptic drugs (AEDs) within psychiatry to treat mental illness, particularly bipolar disorder, is an example of both serendipitous discovery and subsequent controlled study in continued efforts to expand viable treatment options for patients with bipolar disorder. Investigations into the use of AEDs to treat the depressive phase of bipolar disorder have been met with both failures and limited successes.</P> <H4>ABOUT THE AUTHORS</H4> <P>Dr. Muzina is vice chair for research and education, Department of Psychiatry and Psychology, Cleveland Clinic Lerner College of Medicine at Case, Cleveland, OH. Dr. Gajwani is clinical director, Mood Disorders Program, University Hospitals of Cleveland Clinic Health System, and assistant professor of psychiatry, Case Western Reserve University School of Medicine, Cleveland. Dr. Kemp is research fellow, Mood Disorders Program, University Hospitals of Cleveland Clinic Health System. Dr. Gao is assistant professor of psychiatry, Case Western Reserve University School of Medicine. Dr. Calabrese is director, Mood Disorders Program, University Hospitals of Cleveland Clinic Health System; director, Bipolar Disorders Research Center, University Hospitals Case Medical Center; and professor of psychiatry, Case Western Reserve University School of Medicine.</P> <P>Address reprint requests to: David J. Muzina, MD, Cleveland Clinic Department of Psychiatry and Psychology, 9500 Euclid Ave, P57, Cleveland, OH 44195; or e-mail <a href="mailto:muzinad@ccf.org">muzinad@ccf.org</a>.</P><P> Dr. Muzina disclosed relevant financial relationships with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Pfizer, and Repligen. Dr. Gajwani disclosed relevant financial relationships with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cyberonics, Forest Laboratories, and Pfizer. Dr. Kemp disclosed relevant financial relationships with Abbott Laboratories and Bristol-Myers Squibb. Dr. Gao disclosed a relevant financial relationship with AstraZeneca. Dr. Calabrese disclosed relevant financial relationships with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Ciba-Giegy, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Parke-Davis, Sandoz Pharmaceuticals, Shire, SmithKline Beecham, TAP, Teva, UCB Pharma, and Wyeth Ayerst.</P>

Atypical Antipsychotics in Bipolar Depression: Applying Emerging Evidence to Clinical Practice

<P>Bipolar I disorder is an omnipresent illness affecting around 1% of the population. More pressing is the increasing recognition that this figure grows much higher when combined with the prevalence for bipolar II disorder (3.7%) and perhaps reaches greater than 6% when an expanded spectrum of bipolar disorder is considered. The course of illness followed by many patients with bipolar disorder often is chronic, marked by predominance of depressive episodes or symptoms, and significant disability particularly due to depressive morbidity. Additionally, suicidality is more common in bipolar depression (BD) than in mania.</P> <H4>ABOUT THE AUTHORS</H4> <P>Dr. Muzina is vice chair for research and education, Department of Psychiatry and Psychology, Cleveland Clinic Lerner College of Medicine at Case, Cleveland, OH. Dr. Gajwani is clinical director, Mood Disorders Program, University Hospitals of Cleveland Clinic Health System, and assistant professor of psychiatry, Case Western Reserve University School of Medicine, Cleveland. Dr. Kemp is research fellow, Mood Disorders Program, University Hospitals of Cleveland Clinic Health System. Dr. Gao is assistant professor of psychiatry, Case Western Reserve University School of Medicine. Dr. Calabrese is director, Mood Disorders Program, University Hospitals of Cleveland Clinic Health System; director, Bipolar Disorders Research Center, University Hospitals Case Medical Center; and professor of psychiatry, Case Western Reserve University School of Medicine. </P> <P>Address reprint requests to: David J. Muzina, MD, Cleveland Clinic Department of Psychiatry and Psychology, 9500 Euclid Ave, P57, Cleveland, OH 44195; or e-mail <a href="mailto:muzinad@ccf.org">muzinad@ccf.org</a>. </P> <P>Dr. Muzina disclosed relevant financial relationships with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Pfizer, and Repligen. Dr. Gajwani disclosed relevant financial relationships with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cyberonics, Forest Laboratories, and Pfizer. Dr. Kemp disclosed relevant financial relationships with Abbott Laboratories and Bristol-Myers Squibb. Dr. Gao disclosed a relevant financial relationship with AstraZeneca. Dr. Calabrese disclosed relevant financial relationships with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Ciba-Giegy, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Parke-Davis, Sandoz Pharmaceuticals, Shire, SmithKline Beecham, TAP, Teva, UCB Pharma, and Wyeth Ayerst.</P>

Abnormal Uterine Bleeding

ABOUT THE AUTHOR Dr. Bradley is the Director of Hysteroscopic Services in the Department of Obstetrics and Gynecology, The Cleveland Clinic Foundation, Cleveland, Ohio. AUTHOR DISCLOSURE The author has disclosed that she has no significant relationship or financial interest in any commercial companies that pertain to this educational activity. Dr. Bradley is on the speaker’s bureau for Microsulis, Biosphere, Ortho McNeil, and Wyeth Ayerst.

Oestrogen plus progestogen increased coronary heart disease and breast cancer events in postmenopausal women

(2002) JAMA 288, 321; Writing Group for the Women’s Health Initiative Investigators. . Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health...

β‐Amyloid immunization approaches for Alzheimer's disease

AbstractAlzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of β‐amyloid (Aβ) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that Aβ plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the Aβ cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against Aβ transgenic mice with spontaneously developing Aβ pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42‐amino acid Aβ emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of Aβ plaque formation in younger animals and a marked reduction of the Aβ burden in older animals. The effects on Aβ plaques were accompanied by a reduction of Aβ‐associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the Aβ immunization of transgenic animals normalize or reduce the cognitive impairment associated with Aβ pathology. Interestingly, effective removal of brain Aβ plaques was also obtained by peripherally administering Aβ antibodies. The mechanism with which the vaccine increases Aβ clearance is not fully understood. Centrally, the vaccine appears to activate Aβ phagocytosis by microglial monocytes. Peripherally, serum Aβ antibodies bind and sequester Aβ, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN‐1792) composed of preaggregated human Aβ42 peptide and a highly purified saponin derivative (QS‐21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN‐1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic Aβ vaccination strategies are being pursued, including immuno‐conjugates and monoclonal antibodies. The future of these and other Aβ immunization approaches depend on a clear understanding of the mechanism of Aβ clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150–162, 2002. © 2002 Wiley‐Liss, Inc.

Veno‐occlusive disease after an anti‐CD33 therapy (gemtuzumab ozogamicin)

Veno‐occlusive disease after an anti‐CD33 therapy (gemtuzumab ozogamicin)

Feeding preterm infants after hospital discharge: effect of diet on body composition.

Feeding preterm infants after hospital discharge: effect of diet on body composition.

The Heart and Estrogen/progestin Replacement Study (HERS)

The heart and estrogen/progestin replacement study (HERS) was a randomized, double-blind, placebo-controlled clinical trial supported by Wyeth–Ayerst for $40 million [1]. The objective of the trial was to determine whether daily treatment with 0.625 mg conjugated estrogens and 2.5 mg medroxyprogesterone acetate would reduce coronary heart disease events in women with preexisting coronary disease. A total of 2763 women (average age 66.7 years) were enrolled in 20 US clinical centers and randomized to treatment and placebo beginning in February, 1993, and ending in July, 1998. Overall, there were 172 myocardial infarctions and coronary deaths in the hormone group and 176 in the placebo group, obviously no overall difference. However, over time, differences were recorded (Table 1). Thus, there was an increase in events in the first year (mostly in the first 4 months), and after 2 years of treatment, the appearance of a beneficial impact (although the annual relative risks did not achieve statistical significance, the test for the trend was significant). The authors attribute the increasing beneficial impact noted with increasing duration of treatment to a favorable effect on lipids, an 11% decrease in LDL-cholesterol and a 10% increase in HDL-cholesterol after 1 year, compared with the levels in the placebo group. In addition, a number of overall observations were recorded (Table 2). The increased risk of venous thromboembolism reported in observational studies was confirmed (although these women were a high risk group for this problem). The increased risk of gall bladder disease did not reach statistical significance. There were no differences in the incidences of breast cancer, endometrial cancer, other cancers and fractures (however, the size and duration of the study did not allow meaningful conclusions in these categories). The authors concluded that combined estrogen–progestin therapy does not reduce the risk of coronary events in postmenopausal women with pre-existing coronary disease. The results of the HERS trial are surprising in view of the overwhelming evidence from observational studies that postmenopausal hormone therapy prevents coronary heart disease. The authors offer two possible explanations for the difference between the HERS trial and previous observational studies. First, they point out the common and favorite criticism of the observational studies: selection bias, specifically that healthier women choose to use postmenopausal hormone therapy and, therefore, develop less coronary heart disease. Indeed, women who choose to use hormone therapy have been reported to have a better cardiovascular risk profile compared to nonusers [2]. This question has been addressed by the Lipid Research Clinics study, the Leisure World Study, and the Nurses Health Study [3–5]. These epidemiologists have concluded that their evidence strongly indicates that, in women receiving estro-

Elevation of erythrocyte redox potential linked to galactonate biosynthesis: Elimination by Tolrestat

Alternate pathways of galactose metabolism were explored in erythrocytes from normal subjects and patients with galactose-1-phosphate uridylyltransferase (GALT) deficiency incubated with galactose. Micromolar quantities of galactonate accumulated in both normal and mutant cells linearly with time up to 5 hours and with concentrations of galactose up to 25 mmol/L. Galactitol also was found at levels less than one third of the galactonate level, while galactose-1-phosphate concentrations comparable to those of galactonate were found in galactosemic cells. Concomitant with the formation of these galactose metabolites, the erythrocyte redox potential based on measurement of lactate and pyruvate increased fourfold in both cell types. This was due to a 60% to 72% decrease in pyruvate and a 24% to 26% increase in lactate. The oxidation of galactose to galactonate, which is known to generate NADH, is the most likely explanation for the increase in the redox state. The aldose reductase inhibitor (ARI), Tolrestat (Wyeth Ayerst Research, Princeton, NJ), at 70 μmol/L inhibited the formation of both galactonate and galactitol in both cell types without affecting galactose-1-phosphate, and eliminated the increase in the redox potential as indicated by restoration of pyruvate and lactate levels to the levels obtained before exposure of the cells to galactose. A functioning galactonate pathway is a route of galactose disposal in patients with GALT deficiency, but by altering the cellular redox potential, it may also contribute to galactose toxicity.

Motuporamines A−C, Cytotoxic Alkaloids Isolated from the Marine Sponge Xestospongia exigua (Kirkpatrick)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTMotuporamines A−C, Cytotoxic Alkaloids Isolated from the Marine Sponge Xestospongia exigua (Kirkpatrick)David E. Williams, Peter Lassota, and Raymond J. AndersenView Author Information Departments of Chemistry and Oceanography, Earth & Ocean Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada, and Oncology and Immunology Division, Wyeth Ayerst Research, 401 North Middletown Road, Pearl River, New York 10965 Cite this: J. Org. Chem. 1998, 63, 14, 4838–4841Publication Date (Web):June 18, 1998Publication History Received24 February 1998Published online18 June 1998Published inissue 1 July 1998https://doi.org/10.1021/jo980355pCopyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views439Altmetric-Citations49LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (62 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Carbene compounds,Carbon,Mixtures,Organic compounds,Resonance structures Get e-Alerts

Low risk of drug interactions with venlafaxine

Recent studies of venlafaxine [Wyeth Ayerst], one of the new dual-acting antidepressants, have indicated that the drug has a low risk of interactions with drugs that are substrates for the cytochrome P450 3A4 (CYP3A4) and 1A2 (CYP1A2) isoenzyme pathways. These studies were prompted by the US FDA’s concern regarding the adverse consequences of drug interactions with the CYP3A4 substrate terfenadine. The results of the venlafaxine studies were presented at the 98th meeting of the American Society for Clinical Pharmacology and Therapeutics [San Diego, California, March 1997].

A Limited Sampling Strategy for Estimating Sirolimus Area-Under-the-Concentration Curve

Sirolimus (SRL), a promising new immunosuppressive macrolide (1)(2)(3), displays unpredictable pharmacokinetic properties in humans. Measurement of a single trough concentration may reflect total drug exposure for drugs with consistent bioavailability and elimination properties, but not for drugs such as SRL that have variable bioavailability and unpredictable elimination characteristics. For such agents, area-under-the-concentration–time-curve (AUC) measurements have been used to estimate total drug exposure because they often correlate with pharmacodynamic effects (4)(5)(6). Although the relation between SRL AUC, the therapeutic effects of SRL, and toxicity has not been investigated, such a study might help elucidate the optimal therapeutic regimen for the drug. Sampling regimens for full pharmacokinetic profiles are frequently not clinically feasible because of both time and cost restraints. Therefore, limited sampling strategies have been devised to obtain reasonable estimates of drug exposure. Limited sampling AUC strategies have been used to monitor the exposure of patients to oil-based (Sandimmune®; Sandoz, Basel, Switzerland) (7)(8) or microemulsion (Neoral®, Sandoz) (9) formulations of cyclosporine (CsA) and to chemotherapeutic agents such as cyclophosphamide (10). The present report describes a clinically reliable sampling strategy to predict the AUC values for SRL to more efficiently evaluate the clinical significance of total exposure. In our study, 27 renal transplant recipients underwent a total of 77 full SRL pharmacokinetic profiles during the first year after the transplant procedure; 7 patients underwent pharmacokinetic profiling before the transplant procedure. SRL was administered once daily in a nonaqueous mixture (Rapamune®) provided by Wyeth–Ayerst Research, Princeton, NJ. …

Tourniquet compression of a Norplant device

A 23-year-old right-handed White woman sustained an injury to her left gloved thumb in a collision during a recreational softball game. Examination the next day revealed tenderness about the ulnar collateral ligament and complete instability of the joint to stress of the ligament. She elected to have an ulnar collateral ligament repair to her left thumb under an axillary block. A tourniquet was padded well and placed over the patients Norplant device which was located in the medial aspect of the arm. The tourniquet calibrated immediately before the operation was elevated to 250 mmHg after exsanguination. Total tourniquet time was 72 minutes. The surgery proceeded uneventfully and the patient was placed in a thumb spica splint. Postoperatively the patient complained of pain over the area of the Norplant device. The moderately severe pain and tenderness persisted for 10 days. Based on the recommendation of the manufacturer (Wyeth Ayerst Laboratories Philadelphia PA) a xeroradiograph was obtained to evaluate the integrity of the capsules (Blood tests to determine if an implant had been ruptured are not commercially available). There was no evidence of damage to the Norplant device and the patients pain resolved on its own 10 days postoperatively. Before surgery the patient had regular menstrual cycles; one year postoperatively she has had two irregular menses and is not pregnant. She has a stable mobile thumb and is back to full activities with no further complaints of pain. There is no reference in the literature concerning tourniquet irritation of a Norplant device. The only study on tourniquet use and a Norplant device concerned the use of a tourniquet placed proximal to the device; it did not influence plasma concentration of levonorgestrel. Three cases of localized skin reaction immediately after implantation have been reported; in the case discussed here the device had been in place for over a year with no local tissue reaction. To avoid this complication the presence of subdermal implants should be noted in the preoperative history when considering upper extremity surgery.

Substance Use and Abuse/Alcoholism

Substance Use and Abuse/Alcoholism

Total Parenteral Nutrition in a Premature Rhinoceros Calf

A female black rhinoceros calf developed significant hypoglycemia (blood glucose, 30 mg/dL) and hypothermia (97 degrees F) within 48 hours of birth and refused to nurse. Normal gestation of the black rhinoceros is 15 months, but elongated hoof slippers and low birth weight (30 kg) suggested prematurity in this calf. Clinical symptoms of neonatal sepsis including lassitude and poor sucking continued in spite of the aggressive use of antibiotics, and the calf required mechanical ventilatory support on day 7. Nutritional support including enteral gavage feedings (Pedialyte/4 ounces of SMA [Wyeth Ayerst] with sucraflox) had been instituted and was supplemented with total parenteral nutrition on day 5. Central venous access was obtained via a jugular cutdown. The total parenteral nutrition included appropriate electrolytes and vitamins for the neonatal calf but did not include trace elements. The use of total parenteral nutrition by our zoos for therapeutic purposes is increasing. Experience with total parenteral nutrition in exotic animals such as the black rhinoceros is limited, yet this may be an important therapeutic modality in these animals, particularly those in danger of extinction.

Subdermal progestin implant contraception

Sustained-release progestin contraceptives are a new approach to meeting a worldwide need for more effective and acceptable birth control. These contraceptive systems provide low, stable levels of synthetic progestins for periods of months to several years. Unlike earlier injectable and oral contraceptives, they do not cause peaks in progestin levels beyond those required for effective contraception, nor do they employ estrogens. For these reasons, sustained-release progestin systems are without some of the health risks attributed to birth control pills, and they are more effective, as well as easy to use, and completely reversible. They share common side effects, the most frequent of which is irregular menstrual bleeding caused by the erratic shedding of hypotrophic endometrium. Despite this and other minor side effects, most users find the sustained-release systems acceptable alternatives to other methods of contraception. Permanent or biodegradable subdermal implants, injections, intrauterine and intracervical devices, and vaginal rings are all employed as delivery systems for contraceptive progestins. The Norplant (Wyeth Ayerst, Radnor, PA) system, consisting of six silastic tubes filled with levonorgestrel and implanted under the skin, was recently approved by the US Food and Drug Administration and is already used by more than a half million women worldwide. The other sustained-release systems are in various stages of development, at least several years away from general use. When these new methods complete clinical trials, women will be able to choose from among implants, injections, or pellets with various durations of action, all providing convenient, highly effective contraception with low risk to health.

Family and Couples Therapy

Family and Couples Therapy