Switchable, Reagent-Controlled Diastereodivergent Photocatalytic Carbocyclisation of Imine-Derived α-Amino Radicals.

A reagent-controlled stereodivergent carbocyclisation of aryl aldimine-derived, photocatalytically generated, α-amino radicals possessing adjacent conjugated alkenes, affording either bicyclic or tetracyclic products, is described. Under net reductive conditions using commercial Hantzsch ester, the α-amino radical species underwent a single stereoselective cyclisation to give trans-configured amino-indane structures in good yield, whereas using a substituted Hantzsch ester as a milder reductant afforded cis-fused tetracyclic tetrahydroquinoline frameworks, resulting from two consecutive radical cyclisations. Judicious choice of the reaction conditions allowed libraries of both single and dual cyclisation products to be synthesised with high selectivity, notable predictability, and good-to-excellent yields. Computational analysis employing DFT revealed the reaction pathway and mechanistic rationale behind this finely balanced yet readily controlled photocatalytic system.

Studying the place of technology to lower financial barriers for dietary change.

BACKGROUND: Current dietary self-monitoring systems assume users have access to healthy foods and resources to effectively implement and monitor dietary behavioral change. OBJECTIVES: The purpose of this qualitative study is to understand the specific financial-related barriers that caregivers of low socioeconomic status encounter when attempting to make dietary behavior change. METHODS: In this qualitative study, we conducted a focus group and 14 in-person interviews with the primary caregivers of low socioeconomic families. Participants were recruited from a community considered to be 'at risk' through high levels of exposure to multiple modifiable risk factors for cardiovascular disease. All participants were English-speaking caregivers, who had children under eight years old. The families lived in an urban, public housing community. The focus group and interviews were transcribed and coded during data analysis sessions, then analyzed for emergent themes. RESULTS: We abstracted three main themes from the data. The caregivers of 17 families: 1) feared trying healthier food alternatives because of possibly wasting the food; 2) planned meals only when they had enough time, space, and financial security; and 3) defined produce as luxury items and often could only afford staple food items, such as meat and grains. CONCLUSION: We challenge the community to design technological interventions to lower the financial barriers presented with existing information and communication technology available to low socioeconomic populations. In addition, we encourage interventions to foster a community's social capital to decrease feelings of isolation and increase opportunities for cooperation.

An audit of patients who have received imiquimod cream 5% for the treatment of anogenital warts.

With the licensing of the new drug Imiquimod cream 5% (Aldara 3M Health Care) for the treatment of anogenital warts and its inclusion into clinic guidelines, a case note review audit was performed of its use. The treatment of 52 patients was audited. Results showed that clinic guidelines were being followed and that patient outcomes in terms of clearance were at least as good as the quoted rates in the literature. Significant issues included firstly patient education-especially for those who had previously received ablative therapy. Secondly the length of time that therapy would be continued before a patient was deemed to be a non-responder to Imiquimod cream 5%, and if this was the case should the frequency of application be amended from the manufacturer's recommended regime of 3 times a week.

Integrating manual and movement therapy with philosophical counseling for treatment of a patient with amyotrophic lateral sclerosis: a case study that explores the principles of holistic intervention.

A patient (Travis) suffering from ALS received a holistic principle-based protocol that combined manual-movement techniques with philosophical counseling. After 4 sessions, he exhibited a remarkable improvement in head-neck alignment, balance/mobility, autonomic activity, and worldview for a 2-month span. These changes occurred only after his worldview underwent a shift from a dualistic split of mind and body to a nondualistic orientation. After this 2-month period of improvement, Travis' structural alignment and balance/mobility suddenly deteriorated rapidly. Yet, his enhanced worldview and autonomic tone continued through a final follow-up taken 17 weeks after the initial evaluation.

A three-paradigm treatment model using soft tissue mobilization and guided movement-awareness techniques for a patient with chronic low back pain: a case study.

It is not uncommon for physical therapists to report difficulty in treating certain subjects with chronic idiopathic low back pain. The purpose of this case study is to present a three-paradigm model of intervention that may be adapted to the treatment of such cases. The model consists of: 1) relaxation paradigm, consisting of pain modulation procedures; 2) corrective paradigm, involving manual techniques and exercise to correct specific faulty biomechanical alignment(s) eg., pelvic asymmetry); and 3) integrative paradigm, utilizing guided movement/mobilization techniques for improving the subject's overall pattern of posture and movement. The case study of a young adult with chronic low back pain correlated with unilateral innominate bone rotation is presented to illustrate the three-paradigm approach. Over six sessions, the subject received a corrective (sessions 1-3) and an integrative treatment protocol (sessions 4-6) consisting of Rolf's method of soft tissue mobilization and Alexander's system of guided movement-awareness techniques. Before and after each session and after a 4-week follow-up, the subject was assessed for sacroiliac joint pain using a compression technique, anterior rotation of the innominate bones, pelvic angle in the standing position, and vagal tone as determined from heart rate variability. The therapist's visual analysis of sit-to-stand movement and the subject's self-reports of pain were noted. A corrective paradigm protocol of soft tissue mobilization and exercise was unsuccessful in eliminating the subject's assessed anterior rotation of the innominate bone and associated low back pain for more than 1-2 days posttreatment. Only after the implementation of a third paradigm movement/mobilization protocol did the subject begin to exhibit sustained improvement through a 4-week follow-up. Interpretations of the results, appropriate selection of corrective and integrative protocols, and physiological mechanisms are discussed.

Stroke services in general practice--are they satisfactory?

BACKGROUND: The contribution of general practice and primary care teams to stroke care has received surprisingly little attention despite research evidence on the importance of coordinated care. AIM: To determine general practitioners' (GPs') and their patients' satisfaction with hospital and community services for stroke patients in Grampian Region, Scotland. METHOD: A questionnaire survey of 138 stroke patients and their GPs was carried out six weeks after each patient was discharged home between June 1995 and January 1996. Outcomes measured were GP and patient satisfaction with services, Barthel Index, Hospital Anxiety and Depression scores, London Handicap Score, and Homsat and Hospsat scores (satisfaction with stroke services). RESULTS: Response rates of 95% (131) for GPs and 91% (125) for patients were obtained. GPs and patients were generally satisfied with services. Stroke patients were more likely to have had contact with their GP than with any other service. Adverse comments from GPs focused on problems with hospital discharge letters. At six weeks, patients received an average of 2.5 community services and 1.5 hospital services, but there was wide variation across disability groups. CONCLUSIONS: Levels of satisfaction were high, but the wide range and variation in services used by patients emphasized the complexity of the primary care of stroke patients; the need for coordination, review and effective links with hospital; and the key role of the GP.

Understanding practice management: a qualitative study in general practice.

Reports a qualitative study of practice managers' roles and responsibilities in eight practices in the Grampian region of Scotland. Observes wide variations in the roles and responsibilities of managers associated with the size and fundholding status of the practice. Notes that larger practices had better developed management structures allowing the managers to delegate tasks and undertake a more proactive planning and executive role, and that medium and smaller practices had less well developed management structures and managers were more likely to act as practice administrators with limited autonomy. Concludes that practice managers are playing an increasingly important role in general practice. Also that the influential role of the practice manager in the development of practice policies and the transfer of administrative responsibilities from the partners to the manager have all contributed to a change in general practitioners' perceptions of the practice manager.

Molecular cytogenetics of chronic myeloid leukemia with atypical t(6;9) (p23;q34) translocation.

We report the molecular cytogenetic analysis of a case of Philadelphia (Ph)-negative, BCR-positive chronic myeloid leukemia (CML) which appeared by conventional cytogenetics to have a t(6;9)(p23;q34) as the sole cytogenetic abnormality. Neither conventional nor pulse-field Southern blots detected any rearrangement of the DEK or CAN genes which are often fused in acute myeloid leukemia (AML) with t(6;9)(p23;q34). However, rearrangements of both BCR and ABL genes were detected. The breakpoint in BCR was located in the major translocation cluster region between exons b1 and b3. ABL rearrangements were detected with an ABL exon 1B probe and with a probe located 5' of the entire ABL gene. Comigration between the rearranged fragments obtained with M-bcr-5' and ABL exon 1B probes was observed, implying that the entire ABL gene was fused to the 5' part of the BCR gene. Fluorescence in situ hybridization (FISH) analyses using BCR and ABL probes showed that in 20% of metaphases BCR and ABL signals were present on one chromosome 6 at 6p23, whilst in 80% of metaphases BCR and ABL signals were identified on both copies of chromosome 6. Furthermore, FISH analysis with a whole-chromosome 22 paint demonstrated that chromosome 22 material was present on both copies of chromosome 6. These data indicate a complex Philadelphia translocation involving chromosome band 6p23 and duplication of the whole aberrant chromosome. The nature of the gene locus on 6p23, involved in this rearrangement, remains unknown. A similar translocation has been previously reported in a case of CML, which also lacked DEK and CAN gene rearrangements implying that abnormalities of 6p23 involving genes other than DEK may be a recurrent abnormality in CML.

Two stage audit of cerebrovascular and coronary heart disease risk factor recording: the effect of case finding and screening programmes.

The level of recording of risk factors for cardiovascular disease by general practitioners in north east Scotland has been audited. The effect of the audit on recording levels has also been determined by means of a second audit one year later. Twenty four practices in Grampian took part in the study, each auditing a random selection of 100 records of male patients aged 35-64 years. The risk factors chosen were blood pressure, smoking habit, alcohol consumption, weight and height. Blood pressure was recorded in the majority of the records (68.0%) and the mean level of recording of all of the risk factors increased between the two audits. The increase in the recording of smoking habit, alcohol consumption and weight was statistically significant. Practices with organized systems of data collection had higher levels of risk factor recording than those without. The levels of recording achieved were thus dependent on factors that existed in the practices prior to the study. This suggests that to increase recording levels, future educational intervention should be aimed at changes of motivation.

Grampian Health Board's joint drug formulary.

OBJECTIVE: To develop a model for creating a joint general practice-hospital formulary, using the example of ulcer healing drugs. DESIGN: A joint formulary development group produced draft guidelines based on an earlier hospital formulary, which were sent to interested local general practitioners for consultation. Revised guidelines were then drawn up and forwarded to the health board's medicines committee for approval and distribution. SETTING: Grampian Health Board. SUBJECTS: Nine members of joint formulary development group plus local general practitioners who were invited to comment on a list of 11 ulcer healing drugs. MAIN OUTCOME MEASURE: Degree of coincidence of drugs selected by hospital doctors and general practitioners. RESULTS: The ulcer healing drugs selected by the panel of general practitioners and by hospital doctors were highly coincident. The cost of one day's treatment with drugs varied considerably between hospital and general practice--for example, one drug cost 46p in hospital and 1 pounds in general practice and another cost 1.26 pounds in hospital and 1.01 pounds in general practice. Overall, six drugs cost more in hospital and five cost more in general practice. CONCLUSIONS: A joint formulary for use in hospitals and general practice in a health board can be devised fairly simply by consultation as virtually the same drugs are used in both types of practice. It should influence the health board's expenditure on drugs and affect the choice of drugs when a patient is discharged from hospital or is referred to any hospital in the region.

Colony stimulating activity in the serum of patients with multiple myeloma is enhanced by interleukin 3: a possible role for interleukin 3 after high dose melphalan and autologous bone marrow transplantation for multiple myeloma.

Sera from 36/37 multiple myeloma patients and 19/21 sera from patients with other solid or liquid tumours had granulocyte-macrophage colony stimulating activity (CSA) towards normal human donor bone marrow whereas 1/16 sera from normal donors had this activity. Unlike human rhGM-CSF and GM-CSF from 5637 (human bladder cell line) conditioned medium which is heat stable, CSA from serum is heat labile (56 degrees C/30 min). In multiple myeloma patients, CSA was detectable more than 2 years after treatment with 'high dose melphalan. Although multiple myeloma patients, at relapse, have sufficient CSA in their serum to produce maximal stimulation of GM-CFUc from normal donor bone marrow in vitro, their own GM population responds poorly. The results suggest that the failure of patients own bone marrow to respond to endogenous CSA may be due to damage to the stem cells of the marrow or the failure of precursor cells to respond to CSA. Addition of rhIL-3 to myelomatous serum increased the number of GM-CFUc from both normal and myelomatous bone marrow but did not stimulate the growth of MY-CFUc significantly. The results suggest that rhIL-3 may assist bone marrow recovery in multiple myeloma patients after intensive chemotherapy.

Evidence that multiple myeloma may be regulated by homeostatic control mechanisms: correlation of changes in the number of clonogenic myeloma cells in vitro with clinical response.

Myeloma colonies (MY-CFUc) could be grown in vitro for 6 months (median time) after a group of 12 myeloma patients had reached complete remission (CR). In a second group of 25 patients MY-CFUc increased in 17/25 and GM-CFUc in 20/25 patients after cyclophosphamide even though 24/25 patients had a partial response to VAMP and one was in CR. These data suggest that cell killing by cyclophosphamide stimulates residual tumour cells into proliferation and adds further support to the idea that myeloma is under some degree of homeostatic control which may be analogous to that in normal bone marrow. Although lymphoplasmacytoid myeloma cells may be more drug resistant than plasmacytoid myeloma cells in vitro, it was not possible to conclude that the emergence of lymphoplasmacytoid cells at relapse was indicative of resistance to further treatment.

Studies on the Clonogenicity of Human Myeloma Cells in vitro.

Myeloma is a disease of the B cell lineage which is characterized by the presence of excess numbers of isotypic plasma cells in the bone marrow and a serum paraprotein which is also isotypic for individual patients. These critieria may be accompanied by bone pain and often renal impairment. Until recently the median survival for patients treated with conventional chemotherapy was 2 years, however at the Royal Marsden Hospital (RMH) the use of VAMP (vincris-tine, 0.4 mg daily, days 1-4), adriamycin 9 mg/m(2) daily, days 1-4) and methylprednisolone (1 g/m(2) daily, days 1-5) followed by high-dose melphalan at 140 mg/m(2) or 200 mg/m(2) with autologous bone marrow transplantation has increased this survival time to 5 years in previously untreated patients(1,2). During the past 5 years the myeloma practice at the RMH has increased considerably and regular bone marrow aspirates from patients provide the material for in vitro studies. At present there: are approximately 160 patients whose disease is available for monitoring in vitro and approximately 15 myelomatous bone marrow are processed each week. The principal questions that need to be answered in myeloma is why do some patients fail to respond to chemotherapy and why does a further group become refractory to treatment at relapse. These problems encompass a need to examine drug-induced or endogenous drug resistance and to study the lineage of the disease. The development of an in vitro assay for myeloma colony formation by our group is enabling these questions to be investigated(3,4).

Standardization of core data for practice annual reports: a pilot study.

To investigate the feasibility of a standardized practice annual report, nine general medical practices in Grampian region collected data over a four month trial period. The definitions for core data used were arrived at after considerable consultation and discussion. They were found to be workable indicators of practice activity enabling comparisons to be made between practices. Three practices reported that they were completing forms more accurately and that this had led to increased item of service income. The results from this study show smaller variations than have been previously reported and there is a case to be made for the pooling and collation of such defined core data. Analysis of this practice activity would provide the stimulus for further research.

Intensive treatment of multiple myeloma and criteria for complete remission.

50 previously untreated patients with multiple myeloma received two-phase treatment: repeated cycles of 4 day infusion with vincristine, doxorubicin, and methylprednisolone (VAMP) followed by high-dose melphalan (HDM), with autologous bone marrow transplantation where possible. The overall response rate was 74% (37/50), with 25 patients (50%) achieving complete haematological and biochemical remission. These remissions were associated with a good quality of life as measured by performance status, pain grade, and the reversal of humoral immunosuppression. 6 patients died during the VAMP phase and there was 1 death related to HDM. The achievement of complete remission, as defined here, in such a high proportion of patients is exceptional and may represent a useful advance in the management of myeloma.

In vitro studies of ways to overcome resistance to VAMP--high dose melphalan in the treatment of multiple myeloma.

Myeloma colonies (MY-CFUc) from 7/24 patients undergoing treatment with VAMP (vincristine, adriamycin and methyl prednisolone) and high dose melphalan (HDM) were melphalan-resistant. It was not possible to conclude that VAMP induced melphalan resistance in MY-CFUc, but that resistance is endogenous in some myeloma cell populations. In 12/13 of the same patients of whom four had MY-CFUc which were melphalan resistant, the sensitivity of MY-CFUc and GM-CFUc to busulphan was similar. Thus resistance of MY-CFUc to melphalan did not confer resistance to busulphan. MY-CFUc from 1/7 of a second group of patients were adriamycin-resistant. This resistance was removed when the cells were treated with a combination of verapamil (3 micrograms/ml) and adriamycin. Verapamil also enhanced the toxicity of adriamycin to MY-CFUc from two patients where there was no evidence for adriamycin resistance. In these three patients the sensitivity of both MY-CFUc and GM-CFUc was similar after treatment with verapamil. Verapamil did not affect the uptake or efflux of 3H-daunorubicin in sensitive and resistant RPMI-8226 cells (myeloma) and peripheral blood mononuclear cells from a normal donor; neither did it affect the binding of 3H-daunorubicin to nucleic acid. It is concluded that verapamil may be a useful adjuvant to VAMP chemotherapy and that busulphan may provide an alternative to melphalan in patients whose myeloma cells are melphalan resistant.