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Biomedical subjects

D Sherman

Publications and source records attributed to D Sherman.

At least 19 recordsLinked to original sources
PubMed1992

A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes.

BACKGROUND: Although psychoactive medications have substantial side effects in the elderly, these drugs are used frequently in nursing homes. Few interventions have succeeded in changing this situation, and little is known about the clinical effects of such interventions. METHODS: We studied six matched pairs of nursing homes; at one randomly selected nursing home in each pair, physicians, nurses, and aides participated in an educational program in geriatric psychopharmacology. At base line we determined the type and quantity of drugs received by all residents (n = 823), and a blinded observer performed standardized clinical assessments of the residents who were taking psychoactive medications. After the five-month program, drug use and patient status were reassessed. RESULTS: Scores on an index of psychoactive-drug use, measuring both the magnitude and the probable inappropriateness of medication use, declined significantly more in the nursing homes in which the program was carried out (experimental nursing homes) than in the control nursing homes (decrease, 27 percent vs. 8 percent; P = 0.02). The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes (32 percent vs. 14 percent); the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent, and for antihistamine hypnotics, 45 percent vs. 21 percent. In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities, but they were more likely to report depression. Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory. Most other measures of clinical status remained unchanged in both groups. CONCLUSIONS: An educational program targeted to physicians, nurses, and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents.

Aged↗
PubMed1992

Cytochrome c binding affects the conformation of cytochrome a in cytochrome c oxidase.

Second derivative absorption spectroscopy has been used to assess the effects of complex formation between cytochrome c and cytochrome c oxidase on the conformation of the cytochrome a cofactor. When ferrocytochrome c is complexed to the cyanide-inhibited reduced or mixed valence enzyme, the conformation of ferrocytochrome a is affected. The second derivative spectrum of these enzyme forms displays two electronic transitions at 443 and 451 nm before complex formation, but only the 443-nm transition after cytochrome c is bound. This effect is not induced by poly-L-lysine, a homopolypeptide which is known to bind to the cytochrome c binding domain of cytochrome c oxidase. The effect is limited to cyanide-inhibited forms of the enzyme; no effect was observed for the fully reduced unliganded or fully reduced carbon monoxide-inhibited enzyme. The spectral signatures of these changes and the fact that they are exclusively associated with the cyanide-inhibited enzyme are both reminiscent of the effects of low pH on the conformation of cytochrome a (Ishibe, N., Lynch, S., and Copeland, R. A. (1991) J. Biol. Chem. 266, 23916-23920). These results are discussed in terms of possible mechanisms of communication between the cytochrome c binding site, cytochrome a, and the oxygen binding site within the cytochrome c oxidase molecule.

Animals↗
PubMed1992

Reversible plane xanthoma, vasculitis, and peliosis hepatis in giant lymph node hyperplasia (Castleman's disease): a case report and review of the cutaneous manifestations of giant lymph node hyperplasia.

A patient is described who had generalized plane xanthomas, cutaneous vasculitis, peliosis hepatis, and intraabdominal giant lymph node hyperplasia of the plasma cell type. After excision of the abdominal mass, the xanthomas resolved and the liver returned to its normal size, but the patient continued to develop skin lesions. A review is presented of the cutaneous manifestations of giant lymph node hyperplasia.

Adult↗
PubMed1992

Collaboration.

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Gastroenterology↗
PubMed1991

Resolution of the electronic transitions of cytochrome c oxidase: evidence for two conformational states of ferrous cytochrome alpha.

Second-derivative absorption spectra are reported for a variety of oxidation and ligation states of bovine cytochrome c oxidase (ferrocytochrome-c:oxygen oxidoreductase, EC 1.9.3.1). The high resolving power of the second-derivative method allows us to assign the individual electronic transitions of cytochrome alpha and cytochrome alpha 3 in many of these states. In the fully reduced enzyme, one observes a single electronic transition at 444 nm, corresponding to the Soret transition for both ferrous cytochrome alpha and ferrous cytochrome alpha 3. When the cytochrome alpha 3 site is occupied by an exogenous ligand (CN or CO), one observes two absorption bands assignable to the ferrous cytochrome alpha chromophore, one at ca, 443 nm and the other at ca, 450 nm. The appearance of the 450-nm band is dependent only on ligand occupancy at the cytochrome alpha 3 site and not on the oxidation state of the cytochrome alpha 3 iron. These results can be interpreted either in terms of a heterogeneous mixture of two ferrous cytochrome alpha conformers in the cytochrome alpha 3-ligated enzyme or in terms of a reduction in the effective molecular symmetry of the ferrous cytochrome alpha site that results in a lifting of the degeneracy of the lowest unoccupied molecular orbital associated with the Soret pi,pi* transition of cytochrome alpha. In either case, the present data indicate that ferrous cytochrome alpha can adopt two distinct conformations. One possible structural difference between these two states could be related to differences in the strength of hydrogen bonding between the ferrous cytochrome alpha formyl oxygen and a proton donor from an unidentified amino acid side chain of the enzyme. The implications of such modulation of hydrogen-bond strength are discussed in terms of possible mechanisms of proton translocation and electron transfer in the enzyme.

Animals↗
PubMed1990

Preirradiation chemotherapy of supratentorial malignant primary brain tumors with intracarotid cis-platinum (CDDP) and i.v. BCNU. A phase II trial.

Thirty patients with histologically verified malignant supratentorial gliomas were treated with a preirradiation chemotherapy protocol consisting of two courses of intracarotid (i.c.) CDDP, 90 mg/m2, followed by i.v. BCNU, 200 mg/m2. Side effects from therapy were mild and self-limiting; no irreversible retinal or neurologic toxicity could be attributed to i.c. chemotherapy. Of the 27 patients who completed the chemotherapy portion of the protocol, tumor size on postchemotherapy computed tomography (CT) was decreased by greater than 50% in 13% as compared to the postoperative CT scan; in only 4% was the CT scan unequivocally increased in size. Twenty-five (83%) patients completed the entire protocol. Median time to tumor progression and survival in patients who completed the protocol was 53 (range of 13-130+) and 61 (range of 29-130+) weeks, respectively. Twenty-four percent of patients still have not demonstrated tumor progression at intervals greater than 1 year after diagnosis as judged by clinical and radiographic criteria. Tumor recurrences were always contiguous to the original tumor bed. We conclude that preirradiation chemotherapy may be administered safely and with low morbidity. Further study to determine an optimal timing between chemotherapy and radiation therapy is warranted.

Adult↗
PubMed1990

Magnesium sulfate suppresses electroencephalographic manifestations of CNS oxygen toxicity.

We studied the effects of parenteral magnesium sulfate (MgSO4) administration on electroencephalographic seizures induced by hyperbaric oxygen (HBO) in awake rats. Sixteen rats chronically implanted with electrocorticographic electrodes were preinjected i.p. with either vehicle or 3 mmol/kg MgSO4 (the latter resulted in serum levels of 3.5-5.5 mmol/liter) and then exposed to 6 ATA O2 in a pressure chamber. The time to develop an electric ichtal seizure was measured and compared to that in the same animal receiving the alternate treatment 3 days later. Mean and median times after the magnesium treatment were almost double those of vehicle administration. A central anticonvulsive action of magnesium, which should be investigated over the entire HBO range, is indicated.

Animals↗
PubMed1989

Varicella-zoster virus glycoprotein oligosaccharides are phosphorylated during posttranslational maturation.

Varicella-zoster virus (VZV)-infected human embryonic lung fibroblasts (HELF) do not release infectious virions into their growth medium. Extracellular virions are pleomorphic, suggesting that they are partially degraded before their release from cells. To examine the intracellular pathway of viral maturation, [2-3H]mannose-labeled virus-encoded glycoproteins were isolated from VZV-infected HELF. Oligosaccharides attached to the glycoproteins were processed to complex-type units, some of which were phosphorylated. The major intracellular site of accumulation of VZV gpI was found to be perinuclear and to correspond to that of the cation-independent mannose 6-phosphate (Man 6-P) receptor. Subsets of VZV-containing cytoplasmic vacuoles were coated, Golgi-associated, or accessible to endocytic tracers. Phosphorylated monosaccharides protected HELF from the cytopathic effect of VZV in proportion to their ability to block Man 6-P receptor-mediated endocytosis. These data suggest that the unusual phosphorylated oligosaccharides mediate an interaction between VZV and Man 6-P receptors of the host cell; this interaction may be responsible for withdrawal of newly synthesized virions from the secretory pathway and for their diversion to prelysosomal structures.

Cytopathogenic Effect, Viral↗
PubMed1989

Response to ifosfamide and mesna: 124 previously treated patients with metastatic or unresectable sarcoma.

European and American investigators have reported response rates of 38% to 83% for ifosfamide alone in pretreated sarcomas. In a phase II trial of ifosfamide 2.0g/m2 days 1 to 4 with mesna uroprotection in 124 patients with previously failed sarcomas, four (3%) responded completely (95% exact confidence interval, 1% to 8%) and 26 (21%) had a complete or partial response (95% exact confidence interval, 14% to 29%). The median time to progression was 5 and 9 months for partial and complete responders, respectively. In the subset of soft tissue sarcomas, the response rate for the patients receiving bolus administration was 26%, compared with 9% for the patients receiving a continuous infusion schedule (P = .03). The response rates among patients with soft tissue and bony sarcomas with a performance score of 0-2 and 0-1 prior to chemotherapy administration were 20% and 40%, respectively. Somnolence or confusion developed in 19%. Neurotoxicity was significantly associated with poor performance status (P less than .01), elevated creatinine (P less than .01), and low bicarbonate levels (P = .05). A serum bicarbonate less than 20 developed in 31% of the patients and was significantly associated with older age (P = .01), elevated creatinine (P = .02), and female sex (P = .06). Hematuria was significantly associated with no uroprotection (the first four patients did not receive mesna because it was unavailable), but was not associated with prior cyclophosphamide, pelvic radiotherapy, age, or bolus v continuation infusion schedule. Thus, ifosfamide is active in failed sarcomas and warrants further study in previously untreated patients with sarcoma.

Adolescent↗
PubMed1988

Ovine fetal and adult atrial natriuretic factor metabolism.

Studies were conducted to quantify ovine fetal and adult atrial natriuretic factor (ANF) metabolism. A total of 14 pregnant ewes with singleton fetuses were prepared with vascular catheters. In protocol 1, six fetuses (mean gestation, 131 +/- 1 days) received intravenous infusions of synthetic human ANF (hANF, 100 ng.min-1.kg-1) for 60 min. Mean basal fetal plasma ANF levels increased from 180 +/- 44 pg/ml to a steady-state level of 1,233 +/- 192 pg/ml. In protocol 2, five fetuses (mean gestation, 130 +/- 1 days) received successive 40-min infusions of hANF at 5, 25, and 100 ng.min-1.kg-1. Although basal fetal plasma ANF levels (522 +/- 135 pg/ml) were greater than those observed in protocol 1, fetal plasma ANF levels increased to 1,580 +/- 295 pg/ml at the highest infusion rate. In both protocols 1 and 2, basal fetal plasma ANF levels were three- to fourfold greater than maternal levels. The fetal plasma ANF clearance rates calculated from protocol 1 and from the 25- and 100-ng.min-1.kg-1 infusions from protocol 2 were similar (89 +/- 10, 120 +/- 31, and 116 +/- 38 ml.min-1.kg-1, respectively) and were combined to yield a mean estimated fetal plasma ANF clearance rate of 102 +/- 11 ml.min-1.kg-1. In protocol 3, adult plasma ANF levels increased from 137 +/- 36 to 4,142 +/- 776 pg/ml in response to ANF infusion at 200 ng.min-1.kg-1. The mean plasma ANF clearance rate calculated for the adult animals was 59 +/- 12 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Enalapril, hydrochlorothiazide, and combination therapy in patients with moderate hypertension.

Using a placebo baseline, positive controlled, double-blind, randomized titration to effect our study protocol, we assessed the antihypertensive actions of enalapril, hydrochlorothiazide, and their combination in 37 patients with moderate essential hypertension. Patients were maintained on their regular diets and received a placebo for 4 weeks. Patients with moderate systemic hypertension were randomized to receive enalapril monotherapy at a dose of 10 mg twice daily (n = 16), hydrochlorothiazide monotherapy at a dose of 25 mg twice daily (n = 15), or combination therapy consisting of 10 mg enalapril and 25 mg hydrochlorothiazide twice daily (n = 6). Therapy could be titrated to twice the starting dose. All treatment regimens reduced blood pressure, but only one patient had blood pressure normalized (diastolic blood pressure less than or equal to 90 mmHg) with enalapril (7%), two patients with hydrochlorothiazide (15%), and 80% of patients with combination therapy. The patients who had not achieved normal blood pressure received combination treatment, and after 8 additional weeks, more than 70% showed normal blood pressure. After one year of combination therapy, 92% of the patients continue to have normal blood pressure. Both the monotherapy and combination regimens were very well tolerated in this study. In conclusion, enalapril, hydrochlorothiazide, and their combination are effective in reducing blood pressure in patients with moderate hypertension. However, monotherapy is successful in normalizing blood pressure only in a small percentage of patients. Combination therapy achieved normalization of blood pressure in almost all patients, suggesting that most patients on regular diets with moderate hypertension may require a diuretic-ACE inhibitor combination rather than monotherapy to achieve effective blood pressure control.

Adult↗
PubMed1986

A combined light and electron microscopic immunocytochemical method for the simultaneous localization of multiple tissue antigens. Tyrosine hydroxylase immunoreactive innervation of corticotropin releasing factor synthesizing neurons in the paraventricular nucleus of the rat.

In order to study the morphological interrelationships between immunocytochemically identified neuronal systems, a double labelling procedure - suitable for correlative light and electron microscopic observations - is introduced. The technique is based on the consecutive use of the silver-gold (SG) intensified and non-intensified forms of the oxidized 3,3'-diaminobenzidine (DAB) chromogen in the framework of the peroxidase-antiperoxidase complex (PAP) indirect immunocytochemical procedure. The first tissue antigen is detected by the SG intensified DAB chromogen, which has a black color and high electron density. The structures containing the second antigen are visualized by the non-intensified DAB-endproduct, which is less electron-dense than the silver-gold amplified form and is brown. The metallic shield that forms around the labeled antibody sequences associated with the first antigen prevents non-specific binding of immunoglobulins used for the detection of the second tissue antigen. The application of this method for the simultaneous detection of tyrosine hydroxylase (TH)- and corticotropin releasing factor (CRF)-immunoreactive structures revealed that black colored TH-immunopositive fibers contacted brown colored CRF-synthesizing neurons in the hypothalamic paraventricular nucleus. The juxtaposition of TH- and CRF-containing elements was apparent in both thick vibratome (40 micron) and semithin (1 micron) sections. At the ultrastructural level, TH-positive terminals - labeled by silver-gold grains - were observed to establish asymmetric synapses with both CRF- and TH-immunoreactive neurons. The former finding indicates a direct, TH-immunopositive, catecholaminergic influence upon the hypothalamic CRF system, while the latter demonstrates the existence of intrinsic connections between TH-positive elements.

Animals↗
PubMed1978

Nasality and precision of articulation.

Two reading passages, one with nasal consonants and one without, were tape-recorded for 72 subjects: 34 selected as having precise articulation and 38 selected as having imprecise articulation. These speech samples were evaluated for degree of precision and also for degree of nasality by the psychological scaling method of equal-appearing intervals employing a 7-point scale. Analysis indicated a relationship between degree of precision and degree of unpleasant nasality, that is, a tendency for decreases in precision to be accompanied by increased nasality and a tendency for males to be more imprecise in articulation and more nasal than females.

Female↗