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Biomedical subjects

J C Sherman

Publications and source records attributed to J C Sherman.

16 recordsLinked to original sources
PubMed2006

Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study.

CONTEXT: Hypopituitarism in women is characterized by profound androgen deficiency due to a loss of adrenal and/or ovarian function. The effects of testosterone replacement in this population have not been reported. OBJECTIVE: The objective of the study was to determine whether physiologic testosterone replacement improves bone density, body composition, and/or neurobehavioral function in women with severe androgen deficiency secondary to hypopituitarism. DESIGN: This was a 12-month randomized, placebo-controlled study. SETTING: The study was conducted at a general clinical research center. STUDY PARTICIPANTS: Fifty-one women of reproductive age with androgen deficiency due to hypopituitarism participated. INTERVENTION: Physiologic testosterone administration using a patch that delivers 300 microg daily or placebo was administered. MAIN OUTCOME MEASURES: Bone density, fat-free mass, and fat mass were measured by dual x-ray absorptiometry. Thigh muscle and abdominal cross-sectional area were measured by computed tomography scan. Mood, sexual function, quality of life, and cognitive function were assessed using self-administered questionnaires. RESULTS: Mean free testosterone increased into the normal range during testosterone administration. Mean hip (P = 0.023) and radius (P = 0.007), but not posteroanterior spine, bone mineral density increased in the group receiving testosterone, compared with placebo, as did mean fat-free mass (P = 0.040) and thigh muscle area (P = 0.038), but there was no change in fat mass. Mood (P = 0.029) and sexual function (P = 0.044) improved, as did some aspects of quality of life, but not cognitive function. Testosterone at physiologic replacement levels was well tolerated, with few side effects. CONCLUSIONS: This is the first randomized, double-blind, placebo-controlled study to show a positive effect of testosterone on bone density, body composition, and neurobehavioral function in women with severe androgen deficiency due to hypopituitarism.

Adrenal Insufficiency↗
PubMed2001

Expanding cavitand chemistry: the preparation and characterization of [n]cavitands with n>=4.

The preparation of cavitands composed of 4, 5, 6, and 7 aromatic subunits ([n]cavitands, n=4-7) is described. The simple, two-step synthetic procedure utilized readily available starting materials (2-methylresorcinol and diethoxymethane). The two cavitand products having 4 and 5 aromatic subunits exhibited highly symmetric cone conformations, while the larger cavitands (n = 6 and 7) adopt conformations of lower symmetry. 1H NMR spectroscopic studies of [6]cavitand and [7]cavitand revealed that these hosts undergo exchange between equivalent conformations at room temperature. The departure of these two cavitands from cone conformations is related to steric crowding on their Ar-O-CH2-OAr bridges and is predicted by simple molecular mechanics calculations (MM2 force field). X-ray diffraction studies on single crystals of the [4]cavitand, [5]cavitand, and [6]cavitand hosts afforded additional experimental support for these conclusions.

Ethers, Cyclic↗
PubMed2000

Restricted motion of guests confined in carceplexes and capsules.

Guest orientation within carceplexes and capsules was determined qualitatively from NMR data, and the molecular mobility of guests was determined via coalescence of (1)H NMR signals. Both are highly dependent on guest size and shape, as is interconversion of twistomers. Incarceration of 1,4-thioxane results in a large (1.8 kcal/mol) constraint on thioxane's conformational mobility (chair-to-chair interconversion). Similar conformational constraints (1.6 kcal/mol) were determined for 1,4-dioxane both when incarcerated in carceplex 1b and when encapsulated reversibly in capsule 3b. Encapsulation-induced conformational constraints of this magnitude are unprecedented, and are particularly striking for the noncovalently linked capsules.

Magnetic Resonance Spectroscopy↗
PubMed1999

Design of proteins using rigid organic macrocycles as scaffolds.

We have designed and synthesized new three-helix template-assembled synthetic proteins (TASPs) 1a-c. The template was the rigid cyclotribenzylene (CTB) macrocycle 2, which has C3 symmetry. Thiol moieties on the CTB template were used to link cysteine-containing peptide strands 3a-c via disulfide bonds. With designed peptide strands of 15 and 18 residues in length, the structure of TASPs 1a-c were determined to be helical in water according to circular dichroism (CD) spectroscopy. The helicities of TASPs 1a-c were unchanged over large ranges of pH (2-12) and salt concentrations (0-2 M KCl). TASPs 1a-c were also extremely resistant to chemical denaturants: it requires a guanidine hydrochloride (GnHCl) concentration of 7.4 M for TASPs 1a-c to lose 50% of their helicity. The major force for stabilization of TASPs 1a-c is the hydrophobic bundling of the helices.

Amino Acid Sequence↗
PubMed1998

The cerebellar cognitive affective syndrome.

Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.

Adult↗
PubMed1998

Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency.

GH replacement of adults with acquired GH deficiency (GHD) results in body composition changes including increases in lean mass and bone mineral density. However, the effects of long-term GH therapy on cognitive function are largely unknown, and there are conflicting data regarding quality of life. We performed a randomized, double-blind, placebo-controlled study of GH replacement in adults with GHD and measured cognition and sense of well-being using standardized psychometric tests before and after therapy. Forty men (median age 51 yr, range 24-64 yr) with a history of pituitary disease were randomized to GH therapy (starting dose, 10 +/- 0.3 micrograms/kg per day: mean treatment dose, 4 +/- 2 micrograms/kg per day) vs. placebo for 18 months, and GH doses were adjusted according to serum insulin growth factor-I levels. At baseline, the patients displayed a full-scale intelligence quotient (IQ) score nearly 1 SD above the normal mean. Mean scores on all cognitive tests fell within normal limits, and on many tests, fell above the mean. On tests of verbal learning and delayed visual memory, mean test scores fell below the mean (although within normal limits), suggestive of a relative compromise in the area of memory performance. Following 18 months of GH replacement therapy, there were no significant changes in cognitive function or quality of life. We conclude that acquired GHD in adult men is not associated with significant alterations in cognitive function as assessed by standardized tests, and chronic low-dose GH replacement therapy does not result in significant beneficial effects on cognitive function or quality of life. Although previous studies have suggested that GH replacement in adults with acquired GHD may improve quality of life, our data do not support the use of physiological GH replacement in GHD men for this indication.

Adult↗
PubMed1997

Cerebellar cognitive affective syndrome.

There has been persistent uncertainty as to whether lesions of the cerebellum are associated with clinically significant disturbances of behavior and cognition. To address this question, 20 patients with diseases confined to the cerebellum were studied prospectively over a 7-year period and the nature and severity of the changes in neurological and mental function were evaluated. Neurological examination, bedside mental state testing, neuropsychological studies, and anatomic neuroimaging were administered at the time of presentation and during follow-up assessments. Behavioral changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis and, in some cases, overwhelmed other aspects of the presentation. These changes were characterized by an impairment of working memory, planning, set shifting, verbal fluency, abstract reasoning, and perseveration; visual-spatial disorganization, visual memory deficits, and logical sequencing; and a bland or frankly inappropriate affect. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. This newly defined clinical entity is called the cerebellar cognitive affective syndrome. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits than link frontal, parietal, temporal, and limbic cortices with the cerebellum.

Adult↗
PubMed1996

Delayed complications thirty-six years after hemispherectomy: a case report.

PURPOSE: To describe a late complication of hemispherectomy in a patient in whom symptoms of hydrocephalus developed 36 years after her left-sided hemispherectomy, the longest delay on record. METHODS: Hemispherectomy has been successfully used in the treatment of intractable epilepsy associated with infantile-type hemiplegia for a half century. Of the patients, however, up to 33% have late increased cerebrospinal fluid pressure complications attributed to superficial cerebral hemosiderosis. Through a retrospective case analysis, we describe such complications in a 52-year-old woman with cognitive impairment, gait instability, urinary incontinence, and right hemineglect 36 years after her initial procedure. RESULTS: Quantitative, objective measures of cognition and gait-laboratory testing confirmed the patient's favorable clinical response to ventriculoperitoneal shunting, as well as the complete resolution of her symptoms, including the atypical occurrence of right-sided hemineglect. CONCLUSIONS: This case uniquely demonstrates the clinical features of a late complication of hemispherectomy while documenting the longest reported delay for developing such adverse sequelae. We also emphasize the need for more extensive follow-up studies to assess the extent of posthemispherectomy complications.

Brain↗
PubMed1993

Circular dichroism analysis of a synthetic peptide corresponding to the alpha, alpha-corner motif of hemoglobin.

The alpha, alpha-corner is a helix-turn-helix super-secondary structural protein motif where the two alpha-helices cross at approximately right angles. This motif has been observed in a wide variety of proteins and thus, has been proposed to be a protein folding initiator. We sought to test this hypothesis by synthesizing a peptide corresponding to the alpha, alpha-corner of the alpha-chain of horse methemoglobin (residues 80-108) and examining its structure by circular dichroism. We found that the alpha, alpha-corner peptide is moderately helical in water and fully helical in trifluoroethanol, as solvent that approximates the hydrophobic surroundings of the excised portion of the protein. The helicity of our synthetic peptide suggests that the alpha, alpha-corner may in fact have some stability on its own and thus, may be capable of initiating protein folding.

Amino Acid Sequence↗
PubMed1993

Children are in control.

We argue on the basis of recent experimental results that modular principles of universal grammar (UG) play a continuous role in the first language acquisition of control. Our results involve both comprehension and production data from 108 3- to 8-year old children who are acquiring English. The results provide evidence against the hypothesis that there is a "stage" at which children do not know fundamental grammatical principles of control, or fail to apply the basic structural analysis relevant to control. We suggest that previous proposals for this hypothesis have been misled by (1) attention to only one aspect of the knowledge of control, namely choice of antecedent in comprehension of the embedded null subject in these structures and (2) misinterpretation of the nature of the principle by which children overgeneralize the choice of object as antecedent in control structures. Although the new results do replicate delay in acquisition with the unique subject-control verb "promise", they suggest that this delay is caused by a need to integrate modular principles of UG with language-specific principles by which the lexicon and syntax (constituent structure and case) are related. The overgeneralization of choice of object as antecedent is shown to reflect a continuous principle of syntactic minimality.

Child↗
PubMed1993

Buprenorphine versus morphine for patient-controlled analgesia after cholecystectomy.

Buprenorphine is an opioid agonist-antagonist that has emerged as an option for postoperative analgesia. We compared the postoperative hospital course of patients undergoing open cholecystectomy who received buprenorphine hydrochloride with those who received morphine sulfate. Patients in both groups administered the analgesic using a patient-controlled analgesia infusion device. Comparison of the two groups demonstrated no difference with respect to clinical indicators of intestinal motility, visual analog pain scores and hospitalization period. Postoperative nausea occurred more frequently in the buprenorphine group, but the difference was not significant. We concluded that the patient-controlled analgesia device is a valuable tool for comparing different analgesics. Both analgesics tested provide adequate analgesia with a similar postoperative course.

Adolescent↗
PubMed1992

Effect of experimental hemorrhagic shock on hepatic drug elimination.

OBJECTIVE: Exogenous substrates were used to measure hepatic function for the purposes of determining organ dysfunction and to evaluate the effect of experimental hemorrhagic shock with resuscitation on hepatic drug elimination. DESIGN: Prospective, controlled, non-randomized crossover trial. INTERVENTIONS: Eleven chronically instrumented immature swine were studied using a fixed-volume hemorrhage model (45 mL/kg blood removal over 15 mins) followed by resuscitation with lactated Ringer's solution at three times the volume of shed blood. One week before and immediately after hemorrhage and resuscitation, hepatic function markers (indocyanine green and antipyrine) were simultaneously administered intravenously. MEASUREMENTS: Physiologic data and blood samples were collected over 12 hrs after drug administration. Drug clearances, volumes of distribution, and half-lives were determined. MAIN RESULTS: For indocyanine green, there was no substantial change in pharmacokinetics from preshock to postshock, suggesting minimal change in hepatic blood flow. For antipyrine, clearance was decreased by 30% after shock and resuscitation (p = .05), suggesting that oxidative metabolism was acutely impaired. CONCLUSIONS: The information indicates that hepatic oxidative drug metabolism may be impaired early after hemorrhagic shock and that dosages of drugs in this class should be carefully examined when administered to patients who have sustained injury with hemorrhagic shock.

Animals↗
PubMed1991

Alpha-helix stabilization by natural and unnatural amino acids with alkyl side chains.

Knowledge of the role of individual side chains in forming different secondary structures such as the alpha-helix would be useful for prediction of protein structure from sequence or de novo protein design. Experimental and theoretical studies on natural and synthetic peptides and proteins indicate that individual side chains differ in their helix-forming potential. Four aliphatic side chains occur in the standard complement of amino acids: alanine and leucine are helix stabilizing, whereas isoleucine and valine are weakly destabilizing. We have synthesized a series of helical peptides containing unnatural aliphatic side chains having two to four carbons to explore some of the factors involved in alpha-helix stabilization and the basis for selection of the natural set. We find that linear side chains with two, three, or four carbons are as strongly helix stabilizing as the single methyl in alanine and that all linear side chains are stronger helix promoters than leucine. In addition, a t-butyl side chain is significantly more helix destabilizing than the sec-butyl side chain of isoleucine, the isopropyl side chain of valine, or even the unrestricted side chain of glycine. These results provide experimental evidence that restriction in conformational freedom of a side chain imposed by alpha-helix formation is a major component of the role of a side chain in stabilizing helical structure.

Amino Acids↗
PubMed1989

Syntactic and semantic contributions to sentence comprehension in agrammatism.

Five aphasic subjects, who demonstrated agrammatic speech, and eight control subjects were presented with a sentence-picture matching task in which the factors of syntactic complexity, semantic reversibility, and sentence plausibility were independently varied. A subset of the sentences was patterned after that presented by A. Caramazza and E. Zurif (1976, Brain and Language, 5, 572-583) who concluded that Broca's aphasics rely on semantic constraints instead of syntactic information for sentence comprehension. Our aphasic subjects showed the same pattern of performance on this subset of sentences. However, the results from the full set of sentence materials we tested show that the aphasic subjects could perform some sentence level syntactic analyses, even when syntactic information conflicted with semantic constraints. The aphasic subjects correctly interpreted most active and passive sentences. They failed, however, to assign thematic roles and adjectives in center-embedded relative sentences, and instead relied on nonsyntactic information. These results show that both semantic and syntactic information contributed to sentence comprehension in the aphasic subjects we tested, in contrast to previous claims that syntactic and semantic processes are completely dissociated in this population.

Aged↗
PubMed1989

Percutaneous peritoneal lavage in blunt trauma patients: a safe and accurate diagnostic method.

We reviewed the records of 395 patients seen from January 1983 through May 1988, who after sustaining blunt thoracoabdominal trauma had diagnostic peritoneal lavage (DPL) performed percutaneously by the Seldinger wire technique of Lazarus and Nelson. The test was considered grossly positive if 10 cc of blood were aspirated from the catheter immediately after its insertion into the peritoneal cavity. Microscopic criteria for positivity included more than 100,000 RBC or 500 WBC/cc of lavage return, elevated amylase or bilirubin, or the presence of vegetable fibers or bacteria. Seventy-two (18%) of the patients were true positives and 315 (80%) were true negatives. There were four false positives (1.3%) and one false negative (0.2%), giving the test a sensitivity of 99% and a specificity of 98%. Complications occurred in three patients, for a rate of 0.8%, and included catheter insertion into a large ovarian dermoid cyst, needle perforation of the ileum, and needle perforation of the sigmoid colon. This technique of DPL can consistently be performed much more rapidly than the open method. Therefore we conclude that percutaneous DPL is as accurate as, as safe as, and quicker than open DPL for determining intra-abdominal injury in blunt trauma patients.

Abdominal Injuries↗