Hormone replacement therapy in menopausal women: Past problems and future possibilities.

Oral administration of conjugated equine estrogens (CEE) with and without the synthetic progestin medroxyprogesterone acetate (MPA) in postmenopausal women is associated with side-effects that include increased risk of stroke and breast cancer. The current evidence that transdermal administration of estradiol may provide a safer alternative to orally administered CEE is reviewed. Transdermally administered estradiol has been shown to be an efficacious treatment for hot flushes possibly without the increase in blood clotting that is associated with administration of oral CEE.

Oral implications of diabetes mellitus.

The importance of diabetes care in the dental practice is only as important as the dentist wants it to be. Practicing dental professionals must prepare themselves for the increase in the diabetic patient population and the extensive medical care that they require to curtail the development of complications. Dentist's training in preventive healthcare philosophy makes them aptly suited to play a significant role as part of the "Diabetes Team.

The potential of 5-hydryoxytryptophan for hot flash reduction: a hypothesis.

Hormone replacement therapy (HRT) is contraindicated in women with a history of breast cancer or a high risk of breast cancer development. Recent results from large clinical trials, such as the Women's Health Initiative, have demonstrated increased risks of thromboembolic events and a moderate increased risk of breast cancer in women using conjugated estrogens and progestogens. There is a need for viable non-hormonal alternative treatments to HRT, such as nutritional and botanical therapies, in this population of women, who tend to experience more significant vasomotor symptoms.

A pilot study to examine a combination botanical for the treatment of menopausal symptoms.

Objective: Hormone replacement therapy has become a controversial treatment for symptoms of menopause, leading many women and their physicians to search for safer, effective alternatives. Certain botanicals are known to contain phytoestrogenic activity, which may be helpful in alleviating menopausal symptoms. We report the results of a study using a combination botanical supplement to treat menopausal symptoms.

Pilot of a pathway to improve the care of imminently dying oncology inpatients in a Veterans Affairs Medical Center.

We report on the implementation of a previously developed clinical pathway for terminally ill patients, Palliative Care for Advanced Disease (PCAD), on a Veterans Administration (VA) acute care oncology unit, comparing processes of care and outcomes for patients on and off the pathway. The PCAD pathway is designed to identify imminently dying patients, review care goals, respect patients' wishes, assess and manage symptoms, address spirituality, and support family members. Retrospective chart reviews from 15 patients who died on PCAD, 14 patients who died on general wards during the same time, and 10 oncology unit patients who died prior to PCAD revealed that PCAD patients were more likely to have documentation of care goals and plans of comfort care (P=0.

Improving end-of-life care: development and pilot-test of a clinical pathway.

Prior studies have revealed deficiencies in the care provided to patients dying from advanced medical illnesses in acute care hospitals. These deficiencies are best addressed through system change, which may include the development of clinical pathways and quality improvement models. The Palliative Care for Advanced Disease (PCAD) pathway was developed by an interdisciplinary team and includes a carepath, a daily flowsheet, and a physician order sheet with standard orders for symptom control.

End of life care and decision making: how far we have come, how far we have to go.

While enormous progress has been made in improving the quality of care and the decision-making process for patients at the end of life, as a society we still have far to go to ensure that dying patients and their families have a comfortable and dignified death. In particular, reexamination and reconfiguration of our current decision framework is essential as our elderly population with chronic disease and slowly fatal conditions expands. With less certain disease paths and more complex and ambiguous choices, the growth of this geriatric population challenges us to develop a broader conceptualization of end of life care planning, so that end of life considerations are integrated into a larger anticipatory framework addressing options and needs as patients gradually decline.

Remodeling the cell surface distribution of membrane proteins during the development of epithelial cell polarity.

The development of polarized epithelial cells from unpolarized precursor cells follows induction of cell-cell contacts and requires resorting of proteins into different membrane domains. We show that in MDCK cells the distributions of two membrane proteins, Dg-1 and E-cadherin, become restricted to the basal-lateral membrane domain within 8 h of cell-cell contact. During this time, however, 60-80% of newly synthesized Dg-1 and E-cadherin is delivered directly to the forming apical membrane and then rapidly removed, while the remainder is delivered to the basal-lateral membrane and has a longer residence time.

Mechanism for regulating cell surface distribution of Na+,K(+)-ATPase in polarized epithelial cells.

Restriction of sodium, potassium adenosine triphosphatase (Na+,K(+)-ATPase) to either the apical or basal-lateral membrane domain of polarized epithelial cells is fundamental to vectorial ion and solute transport in many tissues and organs. A restricted membrane distribution of Na+,K(+)-ATPase in Madin-Darby canine kidney (MDCK) epithelial cells was found experimentally to be generated by preferential retention of active enzyme in the basal-lateral membrane domain and selective inactivation and loss from the apical membrane domain, rather than by vectorial targeting of newly synthesized protein from the Golgi complex to the basal-lateral membrane domain. These results show how different distributions of the same subunits of Na+,K(+)-ATPase may be generated in normal polarized epithelial and in disease states.

Sodium channel expression and assembly during development of retinal ganglion cells.

Acquisition of functional Na+ channels is a critical event in the development of a neuron because it allows the generation of conducted action potentials. alpha subunit mRNA is first detected in developing rat retina at 1% of its maximum level on embryonic day 15, 4 days after the first ganglion cells are formed. alpha subunit protein is detected in the axons of the ganglion cells at this time, but beta 1 subunits, beta 2 subunits, and high affinity saxitoxin binding sites are not detected until after birth.

Biochemical properties of sodium channels in a wide range of excitable tissues studied with site-directed antibodies.

Antibodies against a peptide (SP19) corresponding to a highly conserved, predicted intracellular region of the sodium channel alpha subunit bind rat brain sodium channels with a similar affinity as the peptide antigen, indicating that the corresponding segment of the alpha subunit is fully accessible in the intact channel structure. These antibodies recognize sodium channel alpha subunits from rat or eel brain, rat skeletal muscle, rat heart, eel electroplax, and locust nervous system. alpha subunits from all these tissues except rat skeletal muscle are substrates for phosphorylation by cAMP-dependent protein kinase.

Beta 2 subunits of sodium channels from vertebrate brain. Studies with subunit-specific antibodies.

The sodium channel purified from rat brain is composed of three subunits: alpha (Mr 260,000), beta 1 (Mr 36,000), and beta 2 (Mr 33,000). alpha and beta 2 subunits are linked through disulfide bonds. Procedures are described for preparative isolation of the beta 1 and beta 2 subunits under native conditions.

A comparative trial of moxalactam plus ticarcillin and clavulanic acid or piperacillin as empiric antibiotic therapy for febrile cancer patients.

Resistance of bacteria to beta-lactam antibiotics remains a difficult clinical problem that can be compounded in infected patients with serious underlying illness, especially those who are immunocompromised. In a prospective randomized safety and efficacy trial, febrile cancer patients received either ticarcillin disodium combined with the beta-lactamase inhibitor clavulante potassium (Timentin, Beecham Laboratories, Bristol, TN) plus moxalactam (T+M), or piperacillin plus moxalactam (P+M) as initial empiric antimicrobial therapy. Sixty-six febrile episodes in 53 patients were studied.

Localization of sodium channels in axon hillocks and initial segments of retinal ganglion cells.

Affinity-purified antibodies against the sodium channel from rat brain were employed to localize sodium channels in the retina by immunocytochemical procedures. In rat retina, intense staining was observed in the ganglion cell axon layer and light staining was detected in fibers of the inner plexiform layer. In frog retina, only the ganglion cell axon layer was stained.

Antiemetic efficacy of high-dose dexamethasone versus placebo in patients receiving cisplatin-based chemotherapy: a randomized double-blind controlled clinical trial.

The antiemetic effect of short courses of high-dose dexamethasone was compared with that of placebo in 64 patients receiving cisplatin-based cancer chemotherapy, in a double-blind randomized clinical trial. All patients were receiving cisplatin for the first time. Dexamethasone was given intravenously (IV) at a dose of 20 mg, two hours before and 3, 6, 9, and 12 hours after chemotherapy.

Antigenic differences among the voltage-sensitive sodium channels in the peripheral and central nervous systems and skeletal muscle.

Antisera prepared against the voltage-sensitive sodium channel purified from rat brain are able to distinguish antigenic differences between the sodium channels in peripheral nerve tissue, the central nervous system, and in skeletal muscle. These results indicate that, in spite of many well-documented similarities among the sodium channels of all excitable tissues, there are biochemical differences that may prove important in future studies of the regulation and molecular mechanisms of electrical excitability.

Hypercalcemia in prostatic carcinoma. Report of eight cases.

Hypercalcemia is a rare complication of disseminated carcinoma of the prostate. To our knowledge, only three such patients have had their cases previously reported in the English language literature. Eight patients with prostatic cancer and hypercalcemia were seen at Montefiore Hospital and Medical Center, Bronx, NY, within the last six years.

Effect of tamoxifen treatment on cortisol metabolism and the course of the disease in advanced breast cancer.

Twenty-nine postmenopausal women with advanced breast cancer were treated with Tamoxifen, a nonsteroidal antiestrogen. The effect of the drug on the plasma concentration, production rate, and metabolism of cortisol was measured, and the relationship of the changes in these parameters to the course of the disease was investigated. After six weeks of Tamoxifen treatment the plasma cortisol concentration and the cortisol-binding globulin concentration increased by 26 and 64%, respectively, but the production rate of cortisol and the urinary excretion of its tetrahydro metabolites THF, ATHF, and THE decreased by 35 and 13%, respectively; all of these changes were statistically significant.