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Biomedical subjects

J M Williams

Publications and source records attributed to J M Williams.

At least 19 recordsLinked to original sources
PubMed1995

The relationship between premorbid neuroticism, cognitive dysfunction and persistence of depression: a 1-year follow-up.

In a previous report of patients with unipolar major depressive disorder, we found that deficits in autobiographical memory predicted depression levels over a 7-month interval. This follow-up examined predictors of recovery as defined by a period of 8 weeks with no or minimal symptoms of depression and examined the extra predictor variable, neuroticism. In a sample of 21 patients, episode duration was significantly correlated with high levels of premorbid neuroticism, dysfunctional attitudes and overgeneral autobiographical memories produced in response to emotionally negative cue words. When severity of depression was partialled out, high N score was significantly but independently correlated with each of these cognitive variables. The implication of these attitudinal and information processing biases were explored.

Adult↗
PubMed1995

Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells.

The immunosuppressive drug, rapamycin, interferes with an undefined signaling pathway required for the progression of G1-phase T-cells into S phase. Genetic analyses in yeast indicate that binding of rapamycin to its intracellular receptor, FKBP12, generates a toxic complex that inhibits cell growth in G1 phase. These analyses implicated two related proteins, TOR1 and TOR2, as targets of the FKBP12-rapamycin complex in yeast. In this study, we have used a glutathione S-transferase (GST)-FKBP12-rapamycin affinity matrix to isolate putative mammalian targets of rapamycin (mTOR) from tissue extracts. In the presence of rapamycin, immobilized GST-FKBP12 specifically precipitates similar high molecular mass proteins from both rat brain and murine T-lymphoma cell extracts. Binding experiments performed with rapamycin-sensitive and -resistant mutant clones derived from the YAC-1 T-lymphoma cell line demonstrate that the GST-FKBP12-rapamycin complex recovers significantly lower amounts of the candidate mTOR from rapamycin-resistant cell lines. The latter results suggest that mTOR is a relevant target of rapamycin in these cells. Finally, we report the isolation of a full-length mTOR cDNA that encodes a direct ligand for the FKBP12-rapamycin complex. The deduced amino acid sequence of mTOR displays 42 and 45% identity to those of yeast TOR1 and TOR2, respectively. These results strongly suggest that the FKBP12-rapamycin complex interacts with homologous ligands in yeast and mammalian cells and that the loss of mTOR function is directly related to the inhibitory effect of rapamycin on G1- to S-phase progression in T-lymphocytes and other sensitive cell types.

Amino Acid Sequence↗
PubMed1995

The alpha isoform of protein kinase C inhibits histamine-stimulated adenylate cyclase activity in a particulate fraction of the human gastric cancer cell line HGT-1.

The isoform of protein kinase C responsible for the inhibition of histamine-stimulated adenylate cyclase by the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), has been investigated in a particulate fraction prepared from the human gastric cancer cell line HGT-1. The alpha and epsilon isoforms of protein kinase C were detected in HGT-1 cells and in a 40,000 x g particulate fraction by immunoblotting procedures. The inhibitory effect of TPA on histamine-stimulated adenylate cyclase was enhanced by the presence of Ca2+, but decreased in a concentration-dependent manner by anti-peptide antibody to protein kinase C alpha, but not to protein kinase C epsilon. Addition of Ca2+ and TPA to the 40,000 x g particulate fraction stimulated the phosphorylation of the protein kinase C substrate myelin basic peptide 4-14. Protein kinase C alpha is probably the isoform responsible for inhibition of histamine-stimulated adenylate cyclase in HGT-1 cells.

Adenylyl Cyclase Inhibitors↗
PubMed1995

How does cognitive therapy prevent depressive relapse and why should attentional control (mindfulness) training help?

There is encouraging evidence that structured psychological treatments for depression, in particular cognitive therapy, can reduce subsequent relapse after the period of initial treatment has been completed. However, there is a continuing need for prophylactic psychological approaches that can be administered to recovered patients in euthymic mood. An information-processing analysis of depressive maintenance and relapse is used to define the requirements for effective prevention, and to propose mechanisms through which cognitive therapy achieves its prophylactic effects. This analysis suggests that similar effects can be achieved using techniques of stress-reduction based on the skills of attentional control taught in mindfulness meditation. An information-processing analysis is presented of mindfulness and mindlessness, and of their relevance to preventing depressive relapse. This analysis provides the basis for the development of Attentional Control Training, a new approach to preventing relapse that integrates features of cognitive therapy and mindfulness training and is applicable to recovered depressed patients.

Aftercare↗
PubMed1995

The emergency department log as a simple injury-surveillance tool.

STUDY OBJECTIVE: To describe the development of an injury-surveillance system based on the emergency department log. SETTING: An ED with 40,000 visits annually, tertiary care center. PARTICIPANTS: All patients to our ED during a 6-month period. ED logs are used to collect basic information such as demographics, chief complaint, mode of arrival, and disposition. Our log was modified for collection of injury-related information such as whether the ED visit was because of an injury and, if so, the mechanism of injury. A list of 16 mechanism-of-injury codes was developed on the basis of review of existing literature and on a 1-month review of injuries in our population. The ED log data were entered into a database, and descriptive analysis was performed. RESULTS: A list of mechanisms of injury was developed that, when implemented, was successful in coding 93% of injured patients in our ED population. The expansion of the ED log for collection of injury data required minimal training and cost. An example of the data obtained is presented to demonstrate the type of information available. Of the 18,742 patients, the ED log identified 5,067 patients (27%) as having been injured. Most were male (2,972 of 5,067 [59%]), and most were between 15 and 40 years of age (2,857 of 5,067 [61%]). Common mechanisms of injury included falls (907 of 5,067 [19%]), transportation (706 of 5,067 [15%]), cuts or punctures (332 of 5,067 [7%]), sports (323 of 5,067 [7%]), and assaults (245 of 5,067 [5%]). CONCLUSION: With minimal training and cost, the ED log can be adapted for collection of injury data on all patients seen in the ED.

Abstracting and Indexing↗
PubMed1994

Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase.

Selective inhibition of the inducible isoform of prostaglandin G/H synthase (cyclooxygenase-2; COX2; EC 1.14.99.1) can be achieved with compounds of the general form of aryl methyl sulfonyls and aryl methyl sulfonamides. DuP 697 and NS-398 are representative examples of these compounds. Both inhibit the constitute (COX1) and inducible (COX2) isoforms of the enzyme with equal potency shortly after mixing, but their potencies increase with time for COX2 selectively. This time-dependent inhibition follows first-order kinetics, and the rate constant for inactivation of COX2 is dose dependent for both compounds. Kinetic analysis allows us to determine KI and kinact (the maximal rate of inactivation) for each inhibitor. The potency of both compounds is substrate concentration dependent, as expected for time-dependent competitive inhibitors. COX2 that has been incubated with these inhibitors, and then extensively dialyzed against buffer, shows no recovery of enzyme activity, while complete recovery of activity is seen for COX1. Thus, these inhibitors irreversibly inactivate COX2 with time, while showing minimal reversible inhibition of COX1. We isolated these inhibitors after long incubation with excess enzyme and subsequent denaturation of the enzyme. Both inhibitors showed no loss of potency resulting from interactions with COX2, suggesting that inhibition is not mediated by covalent modification of the enzyme. These data suggest that binding of these inhibitors to COX2 induces a slow structural transition of the enzyme that results in its selective inactivation.

Animals↗
PubMed1994

The dose-related effect of intradiscal chymopapain on rabbit intervertebral discs.

STUDY DESIGN: This study analyzed the histological and biochemical responses of intervertebral disc tissue to intradiscal injection of varying amounts of chymopapain. OBJECTIVE: To determine the appropriate amount of chymopapain needed to accomplish effective degradation of proteoglycans (PG) in the nucleus pulposus of intervertebral discs. SUMMARY OF BACKGROUND DATA: Chymopapain is an accepted treatment alternative for patients with disc herniations. The recommended clinical dose of 2,000-4,000 pKats per injection is derived from early animal studies and empirical results in man. A lower effective dose could reduce the complication rate while providing similar clinical results. METHODS: Twenty to 4,000 pKat of chymopapain was injected into rabbit discs, and the level of keratan sulfate (KS) epitope in serum was measured at different times after the injection. The animals were killed after 6 days and the injected and two neighboring discs were examined histologically. RESULTS: The serum KS level did not change appreciably after injection of 20 pKat, rose moderately at 100 and 200 pKat, and rose strongly at 500 pKat. Doses greater than 500 pKat did not result in further increase in the KS level. CONCLUSION: Degradation of the disc proteoglycans is dose dependent and reaches a maximum at 500 pKat. Higher doses appear not to cause further loss of aggrecan molecules, and injection of more than 1,000 pKat produces significant annular destruction.

Animals↗
PubMed1994

Clinical experience with the implantable cardioverter defibrillator.

The implantable cardioverter defibrillator has played an increasingly greater role in the management of episodes of sudden cardiac-related death related to ventricular tachycardia or ventricular fibrillation. This study reviews the cases of 142 patients who underwent insertion of an implantable cardioverter defibrillator, 104 who received a device alone (group I) and 38 who underwent insertion of the device in combination with other cardiac surgical procedures (group II). The overall operative mortality was 3.5% and this did not differ between the two groups. The complication rate was higher for group II than for group I patients, and consisted primarily of an increased incidence of atrial arrhythmias (53% versus 13%; p < 0.001). Late complications included three device infections requiring removal of the defibrillator. The late mortality did not differ between the two groups and was primarily related to congestive heart failure. Sudden cardiac-related death was an uncommon late event, with an actuarial freedom from sudden cardiac-related death of 98%, 97%, and 87% at 1, 2, and 5 years, respectively. The morbidity and mortality rate are low in association with the insertion of an implantable cardioverter defibrillator, even when this is combined with other cardiac surgical procedures. Its insertion is also associated with a low subsequent rate of sudden cardiac-related death.

Adult↗
PubMed1994

Embolectomy of a Bird's Nest Vena Caval Filter.

In this case report we describe a successful embolectomy of a partially migrated Bird's Nest Caval Filter with attached embolic material. We used transesophageal echocardiography to guide the surgical approach. The patient recovered uneventfully from both the embolectomy and the subsequent pelvic operation.

Echocardiography, Transesophageal↗
PubMed1994

Extracorporeal circulation in the management of severe tricyclic antidepressant overdose.

Extracorporeal circulation is a technique that provides precise control of circulation, oxygenation, temperature, and blood composition in patients suffering from cardiopulmonary failure. The investigators present the case of a near fatal tricyclic antidepressant overdose that failed to respond to standard therapy but was resuscitated using extracorporeal circulation.

Adult↗
PubMed1994

Intravenous magnesium in the treatment of hydrofluoric acid burns in rats.

STUDY OBJECTIVE: To gather preliminary data on the safety and efficacy of IV magnesium in a rat model of hydrofluoric acid burns. MODEL: Forty-seven anesthetized male rats (200 to 300 g) received a standardized burn with 52% hydrofluoric acid. INTERVENTIONS: Animals were anesthetized with 30 to 50 mg/kg ketamine IM and 1 to 3 mg/kg xylazine IM. A standardized chemical burn was created by topical application of 52% hydrofluoric acid. The rats were divided into four treatment groups: group 1 received no treatment; group 2 received intradermal injection of 10% calcium gluconate; group 3 received 80 mg/kg MgSO4 IV; and group 4 received 160 mg/kg MgSO4 IV. After the rats were killed, the burn lesions were excised and examined by a pathologist to determine the grade of burn (which was equal to the clinical degree of burn). MEASUREMENTS AND MAIN RESULTS: Microscopic examination of the burns revealed differences among the four groups. Five of 13 group 1 rats (37%) died within 24 hours of burn initiation. Of group 1 survivors, 50% had grade 2 burns, and the other 50% had grade 3 burns. In group 2, eight of 11 rats (73%) had grade 3 burns. Twenty-five percent of group 3 rats (three of 12) had grade 3 burns, and only 9% of group 4 rats (one of 11) had grade 3 burns. Only the difference in the rates of grade 3 burns for groups 2 and 4 was statistically significant. Although not statistically significant, burns in groups 3 and 4 tended to be smaller in diameter than burns in groups 1 and 2. CONCLUSION: High-dose IV magnesium sulfate reduces the severity of hydrofluoric acid burn compared with conventional intradermal calcium gluconate therapy. Early deaths appeared to be prevented by both calcium and magnesium therapies.

Animals↗
PubMed1994

Spontaneous cervical epidural hematoma.

Spontaneous cervical epidural hematoma is a rare cause of neck pain. We present the case of a 64-year-old woman who presented to the emergency department with neck pain from a partial Brown-Sequard syndrome secondary to spontaneous cervical epidural hematoma. The prompt recognition of this entity resulted in a favorable outcome.

Back Pain↗
PubMed1994

Formation of reactive oxygen metabolites in glomeruli is suppressed by inhibition of cAMP phosphodiesterase isozyme type IV.

Several independent studies indicate that synthetic inhibitors of cyclic-3',5'-nucleotide phosphodiesterase (PDE) isozymes, especially inhibitors of PDE-IV, are potent agents which suppress generation of reactive oxygen metabolites (ROM) by NADPH oxidase in leukocytes. Recent studies also show that NADPH oxidase is present in all cell types populating glomeruli. In view of this, we investigated PDE isozymes and their relation to ROM in isolated rat glomeruli. Glomeruli have the capacity to hydrolyze cAMP by isozymes PDE-II, PDE-III and PDE-IV, whereas cGMP is hydrolyzed by PDE-I and PDE-V. Inhibitor of PDE-IV rolipram inhibited significantly (cca 40 to 50%) ROM generation in response to stimulation by phorbol myristate acetate (PMA). Inhibitor of PDE-III cilostamide had only minor suppressive effects and inhibitors of other PDE isozymes did not influence ROM generation. Rolipram (3 microM) suppressed ROM generation without detectable increase in cAMP content. Incubation of glomeruli with forskolin, which increased cAMP content in glomeruli tenfold, inhibited ROM generation to a similar degree as rolipram. The suppression of ROM generation by rolipram was prevented by Rp-cAMPS, a specific inhibitor of protein kinase A (PKA) activity. Further, incubation of glomeruli with rolipram elicited marked in situ activation of PKA (+ 100%), as documented by increase in the (-cAMP/+cAMP) PKA activity ratio. We suggest that selective inhibitor of PDE-IV rolipram acted via the cAMP-signaling pathway and suppressed ROM generation possibly via phosphorylating ras-type GTP-binding protein component of NADPH oxidase and thereby blocking assembly of functional NADPH oxidase complex.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Successful treatment of essential thrombocythaemia and recurrent abortion with alpha interferon.

A 27-year-old woman with essential thrombocythaemia (ET) had three miscarriages. She was treated with alpha interferon which was continued after she became pregnant again. The platelet count remained well controlled and at term she delivered a healthy baby with normal blood counts. The case demonstrates the effectiveness of IFN in preventing recurrent miscarriage associated with ET and the safety of IFN with respect to fertility and fetal development.

Abortion, Habitual↗
PubMed1994

Benzyl alcohol attenuates the pain of lidocaine injections and prolongs anesthesia.

BACKGROUND: Benzyl alcohol is reported to be painless on injection and to provide limited dermal anesthesia. Benzyl alcohol has also been recommended as an adjuvant to lidocaine to reduce lidocaine's injection pain. There is insufficient data on pain of injection and duration of anesthesia for lidocaine containing benzyl alcohol. OBJECTIVE: We conducted a randomized, placebo-controlled, double-blinded comparison of intradermal 1% lidocaine with 0.86% benzyl alcohol and plain 1% lidocaine for pain of injection and duration of anesthesia. METHODS: Twenty subjects received the above two agents plus normal saline with and without 0.9% benzyl alcohol, with all solutions adjusted to 375 +/- 13 mosm/L. RESULTS: Lidocaine containing benzyl alcohol was 27% less painful upon injection and provided anesthesia 29% longer than plain lidocaine. CONCLUSION: Benzyl alcohol is itself an effective anesthetic and can reduce the pain of injection for lidocaine without adversely affecting its anesthetic properties.

Adult↗
PubMed1994

Pain of injection and duration of anesthesia for intradermal infiltration of lidocaine, bupivacaine, and etidocaine.

BACKGROUND: Bupivacaine and etidocaine are local anesthetics said to be long acting based on nerve block data. There are insufficient data on pain of infiltration and duration of anesthesia when either is used for dermal infiltration to assess suitability for skin surgery. OBJECTIVE: We conducted a randomized, placebo-controlled, double-blinded comparison of intradermal 1% etidocaine, 0.5% bupivacaine, and 2% lidocaine for pain of injection and duration of anesthesia. METHODS: Twenty subjects received the above three agents plus normal saline, each with and without epinephrine 1:200,000, with all solutions adjusted to pH 5.95 +/- 0.15. RESULTS: Lidocaine hurt least and etidocaine hurt most. Adrenalized solutions were more painful than plain. For plain solutions bupivacaine lasted longest and lidocaine lasted shortest by far. For adrenalized solutions bupivacaine lasted 27% longer than lidocaine and 45% longer than etidocaine. CONCLUSION: Where epinephrine is contraindicated and long anesthesia matters, use plain bupivacaine. When epinephrine can be used, lidocaine lasts almost as long as bupivacaine and hurts less.

Adult↗