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T H Williams

Publications and source records attributed to T H Williams.

At least 19 recordsLinked to original sources
PubMed2000

Ethics gap in surgery.

BACKGROUND: Discussion of ethical issues occurs much less often in the surgical than in the medical literature. The reasons for this "ethics gap" are unknown. METHODS: Our clinical faculty ranked the ethical and legal acceptability of four treatment options in two cases of surrogate decision making. Only one option in each case was ethically and legally unacceptable (treating despite objection by the surrogate decision maker). RESULTS: Surprisingly often, faculty mistakenly believed the ethically unacceptable option to be acceptable, and the legally unacceptable option to be acceptable. Surgeons were not ethically different from other physicians. Surgeons (19 of 31, 62%), however, were significantly (p < 0.05) more likely than internists (18 of 51, 35%) or pediatricians (4 of 18, 22%) to believe, mistakenly, that operating on the baby without parental consent was legally acceptable. CONCLUSIONS: This pilot study did not identify why the surgical literature contains a relative dearth of ethics discussion. Broader investigations are needed, because it is important that we understand the reasons for the gap. Surgeons' strong ethic of personal responsibility for patients' welfare should be transmitted to young trainees, a goal best achieved by discussing and writing about ethics. Moreover, our legal data suggest that a gap may also exist between surgeons and other physicians in understanding health law.

Adult↗
PubMed1999

Innervation of the mitral valve is strikingly depleted with age.

Previous reports demonstrated that mammalian atrioventricular (AV) valves possess a dense nerve plexus, consisting of nerve subpopulations which differ from each other in densities and patterns of distribution in the valves, and which may have sensory or motor roles in valve function. Although there is extensive evidence that age-related changes occur in autonomic nerves of animals and humans (Daly et al. J. Pharm. Exp. Ther., 1988;245(3):798-803; Ingall et al. Aust. NZ J. Med., 1990;20:570-577; Tumer et al. Exp. Gerontol., 1992;27:301-307), and that these changes contribute to changes in cardiac function (Klausner and Schwartz Clin. Geriat. Med., 1985;1(1):119-114), there is little information about age-related changes in heart valve innervation. In this study, we used acetylcholinesterase (AChE) histochemistry to localize and compare qualitative and quantitative changes in the innervation of the mitral valves in young adult and aged animals of three species. Young adult and aged guinea pigs, mice, and Wistar and Fischer 344 rats were anesthetized with Nembutal, the hearts removed, and the mitral valves dissected out and processed for AChE localization. Camera lucida drawings of the AChE-positive nerves in representative segments of valve cusps were made directly from slides; these drawings were digitized and subjected to computer-assisted image analysis to obtain quantitative information about nerve plexus density in the valves. All three animal species showed profuse AChE-positive innervation in the mitral valves of young adult animals, and decreases in the density of this innervation in aged animals. The most striking loss of innervation, compared to the young adult, occurred in the mitral valves of aged Fischer 344 rats, in which large regions of the valves appeared virtually devoid of nerves. Further studies are needed to investigate whether and to what extent age-related losses in heart valve innervation affect valvular structure and function.

Acetylcholinesterase↗
PubMed1996

Tyrosine hydroxylase- and nitric oxide synthase-immunoreactive nerve fibers in mitral valve of young adult and aged Fischer 344 rats.

Using confocal fluorescence microscopy we studied, in whole mounts of heart mitral valves of young adult and aged Fischer 344 rats, the distribution of nerves containing the catecholamine marker tyrosine hydroxylase (TH) or the synthetic enzyme marker for nitric oxide, nitric oxide synthase (NOS). TH-IR was localized in two separate nerve plexuses which do not intermingle. The 'major' plexus arose from the annulus region, traversed the basal zone of the valve, and ramified in the intermediate zone to form a dense network of fine fibers. The 'minor' plexus was restricted to the distal zone and originated from bundles that ascended the chordae tendineae to enter the valve cusp. A concentric zone located between the major and minor plexuses was devoid of TH-IR nerve fibers. Both plexuses demonstrated (i) nerves that contained numerous varicosities along the length of each fiber, (ii) many terminal axons and (iii) different shaped terminal axon endings. With age, the density of TH-IR innervation in the mitral valve was markedly reduced; and nerve fibers of the minor plexus were limited to the chordae tendinae, without extending into the valve cusp itself. NOS-IR fibers in the mitral valve formed a loose network that extended from the annulus to more than halfway down the cusp. The varicose beads of the terminal NOS-IR axons appeared to become progressively smaller and less intensely fluorescent until they disappeared at the terminal endings, which showed no specializations. No NOS-IR fibers were observed in the distal zone of the valve leaflet or in the chordae. In the aged mitral valve, the density of NOS-IR nerves was decreased, as compared with NOS-IR innervation in the young adult valve. The existence of TH and NOS as well as other signal molecule markers in heart valve nerves and the disparate patterns of their distribution and localization provide evidence supporting the theory that heart valve nerves form a complex reflexogenic control system in the mitral heart valve. In summary, two distinct neural architectures are described for TH-IR and NOS-IR valve nerves, respectively. The former are believed to be axons dedicated to sympathetic motor functions. The NOS-IR valve nerves may have sensory and/or postganglionic parasympathetic motor functions. An implication of these findings is that different, but perhaps related, valve functions may be mediated by separate, dedicated circuits.

Adrenergic Fibers↗
PubMed1994

Disposition and metabolism of Ro 24-4736 in the rat.

Ro 24-4736, a new platelet activating factor antagonist, is currently under preclinical and clinical development. The tissue distribution of the 14C-label in male rats following a single intravenous dose of 1.0 mg/kg of 14C-Ro 24-4736 indicated appreciable uptake by the liver, kidney, heart and gastrointestinal tract. Peak plasma and tissue concentrations were seen at 5 minutes after dosing except for the small intestine (4 hrs) and abdominal fat, stomach and large intestine (4 hrs). Thereafter, the 14C-label rapidly declined in all tissues. At 48 hours, only 3.5% of the dose was present in the tissues, and 6.1% in the lumen of the gastrointestinal tracts. The excretion of 14C was essentially completed; 94% of the administered 14C was excreted in the feces and 4.0% in the urine. Overall recoveries of the administered 14C label ranged from 96 to 116%. The purified major 14C-labelled component in the fecal extracts yielded essentially the same NMR spectrum as authentic Ro 24-4736 which accounted for 11% of the dose. In vitro incubations of Ro 24-4736 with rat liver 9S supernatant in an NADPH generating system produced two metabolites. NMR spectra indicated that one metabolite was hydroxylated at carbon-1 while the other one contained a hydroxyl at carbon-10 of the parent molecule. Interestingly, the sites of hydroxylation were at carbons C1, and C10 bearing the protons guarding the bay area of the phenanthrenoid ring, rather than carbons of the phenyl-methyl-thienotriazolodiazepine moiety.

Animals↗
PubMed1993

Bile alcohol glucuronides: regioselective O-glucuronidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol.

A facile and regiocontrolled procedure for the preparation of 5-beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol-3-O-beta-D-glucuronide and its corresponding C-26 analogue is described. The method involves direct coupling of bile alcohols, namely, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol to methyl (tetra-O-acetyl-beta-D-glucopyranuronate) in the presence of a Lewis acid, tin(IV) chloride, in dichloromethane. The resulting anomeric pairs of 1,2-trans- and 1,2-cis-glucuronides of tetrols were resolved by analytical and preparative thin-layer chromatography, and their identities were established by high-resolution 1H NMR spectroscopy and by chemical-ionization and fast-atom-bombardment mass spectrometry. The method described has a practical advantage over the traditional two-step synthesis involving bromides as it is more efficient and uses inexpensive and less toxic materials. It is suggested that these compounds will be useful for studying permeability of the blood-brain barrier in cerebrotendinous xanthomatosis (CTX).

Cholestanols↗
PubMed1993

Functional and morphological characteristics of neuronal substance P in the canine gastroesophageal junction.

The specific functions of the numerous substance P (SP) nerve fibers present within the gastrointestinal tract are not clearly defined. This study examines both functional aspects and distribution of immunoreactive SP (IR-SP) in the canine gastroesophageal junctional (GEJ) region. Lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) were monitored before and after topical application of 2 ml capsaicin (8-methyl-N-vanillyl-6-nonenamide) to the distal esophageal mucosa of anesthetized dogs. Animals then underwent a capsaicin desensitization protocol over a 12-day period. The responses of monitored variables were compared on Day 1 and Day 12 of repetitive capsaicin application. Immunohistochemistry and radioimmunoassay (RIA) were performed on GEJ segments to study the distribution and content of IR-SP in both control (untreated) and capsaicin-treated dogs. The IR-SP was extracted from tissue for RIA and analysis by reverse-phase high-performance liquid chromatography (HPLC). On Day 1, a 2-ml capsaicin application stimulated increases in LESP (44.3 +/- 7.8 cm H2O; P < 0.05), MAP (48 +/- 8.7 mm Hg; P < 0.05), PR (52.6 +/- 20.5 beats/min; P < 0.05), and RR (26.3 +/- 15.6 breaths/min; P > 0.2). No response was observed on Day 12 of treatment. This was accompanied by a 43.3% decrease of IR-SP content in the mucosa of the distal esophagus of desensitized animals. Capsaicin applied at greater concentrations on Day 12 stimulated a return of responses (P < 0.05). Ganglia, cell bodies, nerve fascicles, and neurites stained positively for IR-SP. IR-SP content was markedly higher in esophageal mucosa than in gastric mucosa (P < 0.05). The authenticity of the IR-SP molecule was confirmed by elution time on HPLC. In conclusion, repetitive capsaicin application induced a state of homologous desensitization which was accompanied by a partial depletion of mucosal SP. The GEJ region contains a high SP content with a broad neural distribution. These findings are consistent with the hypothesis that SP may act as a neurotransmitter for chemonociceptive stimuli in the canine distal esophagus.

Animals↗
PubMed1993

Hypertrophy of rat sensory ganglion neurons following intestinal obstruction.

BACKGROUND: Neuroplastic changes following ileum hypertrophy have been reported in intrinsic enteric neurons. The hypothesis in the present study was that intestinal hypertrophy induces neuronal changes in dorsal root ganglia (DRG). METHODS: Under sodium pentobarbital anesthesia, partial obstruction was produced in the rat by tying a plastic ring around the terminal loop of ileum. Fast Blue (FB) (Sigma, St. Louis, MO) was injected into the obstructed ileum wall, and the rat was perfused after 8 days. DRG were immunostained and examined to identify and measure sizes of perikarya containing FB and/or calcitonin gene-related peptide (CGRP) or FB and/or substance P (SP). RESULTS: Of the DRG neurons that projected to the ileum in control or obstructed animals, approximately 50% were CGRP-immunoreactive (IR) and 30% were SP-IR (colchicine pretreatment was not used). Neurons that projected to the obstructed ileum were increased in size compared with neurons in nonobstructed controls. Some of these neurons were CGRP-IR or SP-IR; some were large FB-labeled neurons that were not SP-IR or CGRP-IR. CONCLUSIONS: The morphology of sensory autonomic neurons in adult animals is influenced by dynamic interactions with the targets they innervate, whether directly or transneuronally.

Animals↗
PubMed1992

Stereoselective synthesis of (24R and 24S) 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentols and (25R and 25S) 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentols using a modified osmium-catalyzed Sharpless asymmetric dihydroxylation process.

Described herein are the stereoselective syntheses of the (24R, 24S) and (25R, 25S) isomers of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentols and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentols by using a modified osmium-catalyzed Sharpless asymmetric dihydroxylation process. Also presented herein are the results of lanthanide-induced CD Cotton effect measurements and 1H- and 13C-nuclear magnetic resonance studies of (24R, 24S) and (25R, 25S)-5 beta-cholestanepentols and their derivatives. These compounds were required to study the biosynthesis of cholic acid from cholesterol.

Cholestanols↗
PubMed1991

Tachykinins in the canine gastroesophageal junction.

Lower esophageal sphincter (LES) effects produced by the mammalian tachykinins were evaluated in anesthetized dogs. The distribution and content of substance P (SP) and neurokinin A (NKA) in the region of the canine gastroesophageal junction was also studied. SP and NKA stimulated a linear dose-dependent contraction of the LES after intra-arterial administration. Neurokinin B (NKB) failed to stimulate an increase in LES pressure (LESP). SP was characterized by an immediate but short-lived contraction followed by a period of relaxation. NKA stimulated a potent LES contraction that was slow in onset but long-lasting. On an equimolar basis, both SP and NKA were approximately 100 times more potent LES stimulants than bethanechol or phenylephrine. Pretreatment with atropine (muscarinic blockade) or tetrodotoxin (neural blockade) inhibited the effect produced by SP. NKA appeared to stimulate LES contraction independent of neural or cholinergic mechanisms. Radioimmunoassay revealed a regional variation in tachykinin content in the gastroesophageal junction. Ganglia, cell bodies, nerve fascicles, and neurites stained specifically for both SP and NKA. The variable effects, potencies, and mechanisms of action observed in this study suggest the presence of specific tachykinin receptor subtypes in the gastroesophageal junction. Both SP and NKA were found to have a broad neural distribution in this region. These findings suggest that the tachykinins may play an important role in neuroregulation of LES smooth muscle.

Animals↗
PubMed1991

Self-induced nonequivalence in the 1H-NMR spectra of the (+)- and (-)-isomers of a cannabinoid ketone intermediate.

The 1H-NMR spectra in deuteriochloroform of racemic and optically pure (trans)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-3-pentyl-6H-dibenz o [b,d]pyran-9(8H)-one (1) are nonsuperimposable, while nonracemic mixtures of the (+)- and (-)-isomers show two sets of signals for the phenolic and aromatic protons in ratios directly proportional to the enantiomeric composition of the mixture. This is a new example of "self-induced nonequivalence" or "diastereomeric solute-solute interaction," a known but seldom reported phenomenon. The magnitude of the chemical shift differences are dependent on the ratios of the two enantiomers while the chemical shift delta values are concentration dependent. The overall effect was clearly observable even at a concentration of 0.01 M. In a practical sense, optical purities of samples of the cannabinoid ketone (1) are readily determined by 1H-NMR without the use of additional chiral shift reagents.

Cannabinoids↗
PubMed1991

Alterations of the intestinal innervation in mice infected with Schistosoma mansoni.

Schistosomiasis mansoni is a parasitic disease in which granulomas form around schistosome eggs in the liver and intestines. The purpose of this study was to determine the alterations in the intrinsic innervation of the distal ileum and proximal colon resulting from schistosomiasis. Using murine schistosomiasis mansoni, we examined light microscopic preparations stained with osmium-zinc iodide or the dihydronicotinamide adenine dinucleotide: nitro BT oxidoreductase (NADH) method. We also examined specific populations of peptidergic nerves (vasoactive intestinal polypeptide and substance P) using an avidin-biotin complex (ABC) immunohistochemical technique. We found that granulomas focally destroyed the enteric nerves. Occasionally nerves were found within granulomas, particularly at the periphery of the lesions. Nerve cell bodies close to granulomas had altered staining, which included increased staining for vasoactive intestinal polypeptide. The distribution of nerve injury varied between the 2 enteric segments studied. In the distal ileum, the principal injury was to the myenteric plexus; whereas, the submucous and mucosal plexuses were predominantly damaged in the proximal colon. The physiologic significance of this injury to the enteric nerves requires elucidation.

Animals↗
PubMed1990

Variations in atrioventricular valve innervation in four species of mammals.

In this series of studies, the innervation patterns of whole-mount preparations of bicuspid and tricuspid valves were studied by light microscopy in the mouse, rat, guinea pig, and opossum. The acetylcholinesterase-positive networks of nerve fibers showed many similarities in the basic patterns of valve innervation in all of the species studied, but several interspecies variations were observed. The basal zone of the valve adjacent to the fibromuscular atrioventricular ring displayed the most dense plexus of nerves, with acetylcholinesterase-positive fibers being seen across the width of the valve. In the intermediate zone of the valve, less dense plexuses of nerve fibers were found; and these were more numerous in the cuspal areas and less numerous in the intervening commissural areas. In the distal portions of the valve, nerve networks arborized extensively, with some of their nerve fibers extending toward the chordae tendineae and the free edges of the valve cusps. Only in the guinea pig and opossum did these fibers reach the free margin of the valve cusp, where they either ended directly as free nerve endings or lay parallel to the free edge of the cusp, often running between adjacent chordae tendineae. Although the patterns of innervation were similar in both bicuspid and tricuspid valves, the innervation density of the bicuspid valve was greater than that of the tricuspid valve for each species examined. A distinguishing feature of guinea pig and opossum tricuspid valves was that their chordae tendineae were relatively more prominent and more densely innervated than the bicuspid chordae tendineae. Free nerve endings with no light microscopic evidence of specialization were present throughout the bicuspid and tricuspid valves of all species studied. Some nerve endings in the opossum showed evidence of specialization, with brush-like arborizations leading to presumed free terminals seen chiefly in the distal zone of the valve cusps. Although some general tendencies were apparent, we have demonstrated that interspecies heterogeneity exists in the terminal networks of the atrioventricular valves of mouse, rat, guinea pig, and opossum.

Animals↗
PubMed1990

Peritoneal cystic mesothelioma: successful treatment of a difficult disease.

After several unsuccessful attempts at surgical resection, a case of cystic mesothelioma (multilocular mesothelial cyst of the peritoneum) was treated by a combination of conservative surgical resection and sclerosive therapy with tetracycline. At 4-year followup evaluation no recurrence was noted. Surgical excision with adjunct sclerosive therapy appears to be an alternative to radical surgery and may decrease the incidence of recurrence in some cases of peritoneal multilocular cysts.

Combined Modality Therapy↗
PubMed1989

Collateral sprouting of somatostatin-immunoreactive axons after partial deafferentation of the central nucleus of the rat amygdala.

These experiments utilize a paradigm developed to study plastic responses of peptidergic neurons in a discrete brain area following deafferentation. The central nucleus of the amygdala (CNA) is richly innervated by somatostatin-immunoreactive (SS-I) terminal axons. In the course of preliminary light microscopic (LM) investigations by this laboratory, changes were observed in the density of presumed SS-I terminals in the rat CNA after lesioning the medial input. The LM finding of increased density of presumed SS-I terminals in the CNA at the 10-day post-lesion stage underscored the need for a quantitative electron microscopic (EM) study of the SS-I components, including an evaluation of synaptic events at different survival periods. At the 3-day post-lesion stage, EM examination showed degenerating axons in the lesioned CNA, many already engulfed by astrocytes. None of the degenerating profiles were SS-I, supporting the view that the lesion did not interrupt, to any significant extent, SS-I axons entering the nucleus. EM surveys of the 10-day post-lesion material demonstrated that degenerated profiles had almost completely disappeared. Numbers of SS-I axon terminals, particularly of smaller-sized profiles, were increased by 22% over control value. Synaptic frequency was decreased by 16% below control value. Numbers of SS-I terminals making synapses were increased 3.4% above control value. At the 30-day post-lesion stage, the total number of SS-I terminal axons had increased 86% over controls, whereas the synaptic frequency had decreased by about a third below controls. The absolute number of SS-I terminals engaging in synapses had increased by 24% over controls. The 90-day post-lesion CNA showed a further increase in the number of SS-I axon profiles: 136% over control value. The synapse-to-axon ratio (synaptic frequency) of 27% was similar to that observed for the CNA from the unlesioned side or from unoperated animals. At this stage the number of SS-I synapses had increased by 135% over controls. This model presents many possibilities for studying neuroplasticity, particularly involving peptidergic neurons of the central autonomic nervous system.

Amygdala↗
PubMed1989

Efficacy of neonatal ocular prophylaxis for the prevention of chlamydial and gonococcal conjunctivitis.

Opinions differ concerning the efficacy of prophylaxis against neonatal chlamydial and gonococcal conjunctivitis. From January 1986 through June 1988, we gave all infants born at Kings County Hospital Medical Center one of three prophylactic agents -- silver nitrate drops, erythromycin ophthalmic ointment, or tetracycline ophthalmic ointment. The treatments were rotated monthly. Gonococcal ophthalmia occurred in 8 of the 12,431 infants born during the study (0.06 percent), 1 in the silver nitrate group, 4 in the erythromycin group, and 3 in the tetracycline group (P not significant). Seven of these infants were born to women who had received no prenatal care. From September 1985 through December 1987, we screened 4357 pregnant women for cervical chlamydial infection, of whom 341 (8 percent) had positive cultures. Of their offspring, 230 were evaluated for neonatal chlamydial conjunctivitis; the incidence was 20 percent in the silver nitrate group, 14 percent in the erythromycin group, and 11 percent in the tetracycline group (P not significant). We conclude that neonatal ocular prophylaxis with either erythromycin or tetracycline ophthalmic ointment does not significantly reduce the incidence of chlamydial conjunctivitis in the offspring of mothers with chlamydial infection as compared with silver nitrate, and that better management of maternal chlamydial infection is therefore required. We also conclude that there is a small but appreciable incidence of neonatal gonococcal ophthalmia that could be prevented by better prenatal screening and treatment of maternal gonococcal infection.

Chlamydia Infections↗
PubMed1989

Distribution of immunoreactive substance P in opossum esophagus.

We localized immunoreactive substance P and measured its content throughout the opossum esophagus. Substance P-like immunoreactive nerve fibers were more abundant in muscularis mucosae than in the longitudinal smooth muscle layer and more abundant in the latter than in the circular smooth muscle layer. The distribution of substance P-like immunoreactive nerve fibers in the circular muscle layer of the esophagogastric junction was comparable to that of the esophageal body. Immunoreactive fibers were also found on and in arteries, submucosal glands, and epithelium, but none were seen in striated muscle. Both the myenteric and submucous plexuses contained substance P-like immunoreactive nerve cell bodies and processes. In the muscularis propria, the content of substance P-like immunoreactive peptide (pg/mg protein, means +/- 1 SE) in the smooth muscle region of the esophageal body (5.9 +/- 0.6) exceeded that in the striated muscle region (2.5 +/- 0.2) and at the esophagogastric junction (1.8 +/- 0.5), but the latter two values were similar (P less than 0.05). Mucosal content of substance P in the region of the esophagogastric junction (1.2 +/- 0.1) differed from that of the smooth muscle region of the esophageal body (9.2 +/- 2.6) but not (P greater than 0.05) from that of the striated-muscle region (5.9 +/- 1.0). The broad distribution and diversity of immunoreactive structures suggest that substance P may have both sensory and motor functions in the esophagus.

Animals↗
PubMed1989

Comparison of two rapid microscopic methods and culture for detection of Chlamydia trachomatis in ocular and nasopharyngeal specimens from infants.

The data available for the diagnosis of chlamydial infections in infants which compare direct fluorescent-monoclonal-antibody stains (DFAs) with culture are limited to one reagent, MicroTrak (Syva Inc., Palo Alto, Calif.). We therefore performed a comparison of Pathfinder (Kallestad Diagnostics, Chaska, Minn.) and MicroTrak with chlamydia culture. Paired conjunctival and nasopharyngeal specimens for DFAs and cultures were obtained from 56 infants less than 1 month of age with conjunctivitis. The sensitivities for detecting C. trachomatis in conjunctival specimens with MicroTrak and Pathfinder were 93.8 and 88.2%, respectively, and the specificities were 87.5 and 94.9%, respectively. The DFA tests on nasopharyngeal specimens from infants with conjunctivitis did not perform as well. The sensitivities for Pathfinder and MicroTrak were 33 and 50%, respectively. There were a total of six patients with culture-positive chlamydial conjunctivitis whose nasopharyngeal specimens were DFA positive and culture negative; four of the specimens were positive by both DFAs. These six discordant specimens were further evaluated by preparing pellets and smears of the original culture specimens. All six contained typical fluorescing elementary bodies when stained with the Syva DFA reagent.

Chlamydia Infections↗