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Biomedical subjects

P Whitworth

Publications and source records attributed to P Whitworth.

14 recordsLinked to original sources
PubMed2003

Use of methotrexate in juvenile idiopathic arthritis.

Methotrexate (MTX) has transformed the outlook for children with juvenile idiopathic arthritis (JIA). Most of the evidence from uncontrolled clinical trials suggests that MTX is an effective agent for treating active JIA. Data from controlled clinical trials suggests that MTX has statistically significant effects on patient centred disability measures in JIA patients with active arthritis. Although we would like a much larger study directed evidence base for our use of the drug, the studies that have been done are sound and have been followed by a change in clinical expectations and advice that speak of qualitative evidence from clinical practice, confirming the scientifically acquired data. Randomised controlled multicentre trials using sufficient numbers of patients, including functional assessment and quality of life measures, are needed to confirm the long term efficacy and safety of MTX in JIA.

Adolescent↗
PubMed2001

Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study.

Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.

Adolescent↗
PubMed2000

State-of-the-art lymph node staging for breast cancer in the year 2000.

Axillary staging for breast cancer is vitally important for determining appropriate adjuvant hormone and chemotherapy. In the absence of distant metastases, axillary lymph node status remains the most accurate predictor of clinical outcome. Sentinel lymph node biopsy is a minimally invasive approach with enhanced accuracy and less morbidity than conventional axillary dissection. The stage is now set for the sentinel lymphadenectomy staging to move from state-of-the-art care to the standard care in coming years.

Axilla↗
PubMed2000

Credentialing issues with sentinel lymph node staging for breast cancer.

Sentinel lymphadenectomy (SL) is a minimally invasive approach for staging patients with breast cancer. SL, when performed in lieu of axillary dissection, is associated with less morbidity and is potentially more cost effective and more accurate than the historical axillary dissection in the detection of regional nodal metastases. The credentialing and privileging of SL, as with any surgical procedure, is by the policies of the local hospital or institution. The suggested credentialing criteria for local hospitals has been an area of controversy. Herein the authors outline the credentialing controversy and suggest criteria for the implementation of sentinel lymph node staging for breast cancer.

Breast↗
PubMed2000

The details of successful sentinel lymph node staging for breast cancer.

Sentinel lymphadenectomy is an effective and accurate tool for staging breast cancer. In recent years the details of a successful program have become better defined. The authors outline practical considerations for the performance of successful sentinel lymph node staging from a multidisciplinary perspective.

Breast Neoplasms↗
PubMed1995

Cognitive behavior therapy, relaxation training, and tricyclic antidepressant medication in the treatment of depression.

Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another. This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy. To test the uniqueness hypothesis, relaxation training, a nonpharmacologic, noncognitive treatment, was chosen as a comparison for cognitive behavioral therapy as well as drug therapy. Treatment duration was 16 weeks. The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied. For both cognitive behavioral therapy and relaxation training, outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis. The posttreatment scores on the Beck Depression Inventory of 82% of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score < or = 9 which was not significantly greater than that for the group receiving relaxation training (73%), so a unique effect was not demonstrated for cognitive behavioral therapy. The outcome for tricyclic antidepressant medication (29% improved to criteria) was significantly worse than that for cognitive behavioral therapy. The patient's pretreatment initial expectancy was not predictive.

Adolescent↗
PubMed1993

The immunogenic properties of drug-resistant murine tumor cells do not correlate with expression of the MDR phenotype.

Alterations in the immunogenic properties of tumor cells frequently accompany selection for multiple-drug-resistant (MDR) variants. Therefore, studies were performed to examine the hypothesis that overexpression of membrane P-glycoprotein, commonly observed in MDR tumor cells, is associated with enhanced immunogenic properties. Immunogenicity was determined by (a) the ability of drug-sensitive parental UV2237M fibrosarcoma cells and drug-resistant UV2237M variant cells to immunize normal mice against rechallenge with parental tumor cells and (b) the ability of normal syngeneic mice to reject cell inocula that caused progressive tumor growth in immunocompromised mice. Variant UV2237M cell lines included subpopulations selected for a six- to ten-fold increase in mRNA for P-glycoprotein and expression of the MDR phenotype (resistance to doxorubicin) and cells sensitive to doxorubicin (and no expression of MDR properties) but resistant to ouabain. All UV2237M drug-resistant cells were highly immunogenic in immunocompetent mice, regardless of their MDR phenotype. Additional studies showed that CT-26 murine adenocarcinoma cells, sensitive or resistant to doxorubicin (expressing high levels of P-glycoprotein), injected into normal syngeneic Balb/c mice produced rapidly growing tumors. The data do not demonstrate a correlation between the immunogenic properties of drug-resistant tumor cells and the expression of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Prescribing therapy for depression: the role of learned resourcefulness, a failure to replicate.

Work in 1985 by Simons, Lustman, Wetzel, and Murphy showed that a patient's score on Rosenbaum's self-control scale predicted differential response to treatments for depression, with a high score predicting a good outcome with talking therapy and a low score a good outcome with drug therapy. This study of 37 patients did not replicate those findings. Using the same paradigm, we predicted response correctly 7 times and incorrectly 16 times, a clear failure. A valid method for choosing the best treatment for a patient with major depression remains to be found.

Adult↗
PubMed1990

The effects of acute and chronic lithium treatment on pilocarpine-stimulated phosphoinositide hydrolysis in mouse brain in vivo.

1. Measurements were made of the in vivo formation of inositol phosphates in the brains of C57/B1/601a mice treated acutely or chronically with lithium chloride (LiCl). 2. A single injection of LiCl (10 mEquiv kg-1, s.c.) 18 h before death increased the accumulation of [3H]-inositol phosphates ([3H]-Ins P's) in the brains of mice injected i.c.v. with [3H]-myo-inositol 24 h previously. 3. Pilocarpine (200 mg kg-1, i.p.) injected 15 min before death further enhanced the formation of [3H]-Ins P's in the brains of LiCl-treated, but not saline-treated, mice. The enhancement due to pilocarpine was abolished by injection of atropine sulphate (10 mg kg-1, i.p.) 10 min earlier. 4. Chronic (14 days) LiCl feeding produced an accumulation of [3H]-Ins P's significantly less than that due to a single injection of LiCl, but the response to pilocarpine was markedly greater in mice chronically fed with LiCl when compared with mice acutely injected with LiCl. 5. Mass measurements of endogenous inositol 1,4,5 triphosphate revealed increases due to pilocarpine and chronic LiCl feeding alone. A combination of the two treatments produced levels greater than either alone. 6. These results demonstrate that LiCl treatment enhances both basal and pilocarpine-stimulated inositol phospholipid hydrolysis in vivo and this might be relevant to its therapeutic effects.

Animals↗
PubMed1990

Lithium amplifies inhibitions of inositol phospholipid hydrolysis in mammalian brain slices.

1. We have examined the effects of lithium chloride (LiCl) on inhibitions of inositol phospholipid hydrolysis in guinea-pig and rat brain slices by assessing the accumulation of [3H]-inositol phosphates ([3H]-InsP), in vitro. 2. In guinea-pig and rat cerebral cortex slices the accumulation of total [3H]-inositol phosphates due to the cholinoceptor agonist carbachol was inhibited by the excitatory amino acid L-glutamate, but only when LiCl was present. 3. The effects of LiCl were time and concentration-dependent. Significant inhibitions of the carbachol response by glutamate (in the presence of LiCl) being evident only after 20-30 min of stimulation at LiCl concentrations above 1.2 mM. 4. N-methyl-D-aspartate (NMDA), in the absence of LiCl, enhanced the response to carbachol at low concentrations of the amino acid and inhibited the response at higher concentrations. In the presence of 5 mM LiCl, only the inhibitory phase was observed. 5. In rat cerebral cortex slices, aluminium fluoride inhibited [3H]-InsP accumulation in the presence of carbachol, noradrenaline and a depolarising concentration of KCl and these inhibitions were more marked when LiCl was present. The response to histamine was unaffected. 6. The data presented provide evidence that LiCl amplifies inhibitions of inositol phospholipid hydrolysis due to receptor and non-receptor mediated stimuli, although the mechanism underlying the effect is, as yet, obscure.

Aluminum↗
PubMed1989

Effects of lithium on inositol phospholipid hydrolysis and inhibition of dopamine D1 receptor-mediated cyclic AMP formation by carbachol in rat brain slices.

The in vitro and ex vivo effects of lithium on muscarinic cholinergic inositol phospholipid hydrolysis and muscarinic cholinergic inhibition of dopamine D1-receptor-stimulated cyclic AMP formation were examined in rat brain slices. Following chronic lithium feeding, carbachol-stimulated inositol phosphate accumulation was reduced ex vivo in slices of cerebral cortex but not in striatal slices. Lithium (1 mM) in vitro had no direct effect on dopamine D1-receptor-stimulated cyclic AMP formation, but enhanced the inhibitory effect of carbachol on the D1 response, in striatal slices, and this was not significantly altered by prior lithium feeding. Lithium therefore has effects on two discrete muscarinic responses in rat brain which are apparently maintained after chronic exposure to the ion and might be relevant to its antimanic actions.

Animals↗
PubMed1988

Lithium selectively inhibits muscarinic receptor-stimulated inositol tetrakisphosphate accumulation in mouse cerebral cortex slices.

The in vitro effects of Li on agonist- and depolarization-stimulated accumulation of inositol phosphates were determined in mouse cerebral cortex slices. Of the agents examined, only the cholinergic agonist carbachol produced a significant accumulation of inositol tetrakisphosphate (InsP4) in the absence of Li. Lithium at 5 mM enhanced the accumulation of inositol monophosphate (InsP1) and inositol bisphosphate (InsP2) due to all the stimuli used and potentiated inositol trisphosphate (InsP3) accumulation due to histamine and noradrenaline, although at lower Li concentrations, carbachol-stimulated InsP3 accumulation was reduced. Li also enhanced InsP4 accumulation in the presence of noradrenaline, histamine, and elevated KCl level but, in marked contrast, reduced carbachol-stimulated InsP4 accumulation with an IC50 of 100 microM. There was a significant time delay between the initiation of carbachol stimulation and the beginning of the InsP4 inhibition due to Li. The phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate did not mimic the effects of Li. The results suggest that muscarinic receptor-mediated InsP4 production might be one of the targets for the therapeutic action of Li.

Animals↗
PubMedDate not supplied

Improved lymphatic mapping technique for breast cancer.

Breast sentinel lymph node biopsy is becoming more common. However, the best injection technique is not well established. Currently the gold standard is peritumoral injection. However, for upper outer quadrant tumors there is considerable axillary "shine through" which makes the identification of the radioactive sentinel lymph node difficult. We undertook a study to compare an injection in Sappey's subareolar plexus to the gold standard of peritumoral injection. Between December 1997 and March 1998, 85 patients with breast cancer were enrolled in the study. All patients were injected with 2 cc of normal saline containing 1.0 mCi of unfiltered technetium sulfur colloid in Sappey's subareolar plexus in the clock position of the breast cancer. In the operating room the patients underwent a peritumoral injection of 5 cc of 1% isosulfan blue. All blue and radioactive lymph nodes were identified and removed. The majority of the tumors were in the upper outer quadrant and were diagnosed by core biopsy. Only half of the patients had palpable tumors and approximately 25% had previous upper outer quadrant biopsy incisions. Peritumoral blue dye injection yielded an identification rate of 94%, with 99% of these being blue and radioactive. Three patients had radioactive lymph nodes with no blue lymph nodes identified. One of these patients had a micrometastasis. Injection in Sappey's subareolar plexus in the clock position of the tumor drained to the same sentinel lymph node as peritumoral injection. This injection technique solved the two major problems confronting the wide adoption of sentinel lymph node biopsy for breast cancer staging. First, it eliminates axillary "shine through" which will allow nonspecialist surgeons to more easily identify the radioactive axillary sentinel lymph node. Second, it allows for easier isotope injection by the technician or nuclear medicine physician, by eliminating the need for three-dimensional localization. This new technique should allow the majority of breast cancer patients who are treated by nonspecialist surgeons to be offered this less morbid, more accurate procedure.

Adult↗