[A negative first-line work-up of Raynaud's phenomenon: And what if it were cancer?]. / Phénomène de Raynaud avec négativité du bilan de première intention : et si c'était un cancer ?

Raynaud's phenomenon is a transient paroxysmal vasomotor phenomenon affecting the extremities including manifestations of ischemia. It is a common phenomenon in the general population. In a routine clinical situation, the first step is to differentiate Raynaud's disease from a secondary Raynaud's phenomenon, the latter requiring complementary investigations. We report here the case of an 80-year-old woman who presented a secondary Raynaud's phenomenon. First-line investigations remained negative. A mammography was performed and revealed breast cancer. Raynaud's phenomenon disappeared after treatment of the breast carcinoma and did not recur during the 2-year follow-up.

Treatment satisfaction and efficacy of the rapid release formulation of sumatriptan 100 mg tablets utilising an early intervention paradigm in patients previously unsatisfied with sumatriptan.

AIMS: To evaluate treatment satisfaction, efficacy and functional ability of the rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg) in an early intervention paradigm in patients who were dissatisfied with low-dose sumatriptan and not completely satisfied with their current migraine regimen. METHODS: Experienced migraineurs who reported a mild migraine pain phase, dissatisfaction with the previous sumatriptan treatment and some dissatisfaction with their current treatment regimen had no experience with sumatriptan at the 100 mg dose were enrolled in an open-label, single group study. Subjects were instructed to treat four migraine attacks within 30 min of the onset of mild pain. Treatment satisfaction was measured with the Patient Perception of Migraine Questionnaire Revised version (PPMQ-R) questionnaire. RESULTS: More than half of the subjects were either very satisfied or satisfied with the efficacy of early intervention sumatriptan RT 100 mg after each attack and at the follow-up study visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects reported an ability to function normally within 4 h of taking the study medication. CONCLUSION: Subjects who were previously unsatisfied with lower doses of sumatriptan and less than very satisfied with their current treatment regimen were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in an early intervention paradigm. Results were consistent across four migraine attacks and at a follow-up visit. The treatment satisfaction results corresponded with positive results on efficacy measures and a functional status measure.

Efficacy and tolerability of sumatriptan tablets administered during the mild-pain phase of menstrually associated migraine.

Two randomised, double-blind, parallel-group, placebo-controlled clinical trials were conducted to assess the efficacy of sumatriptan tablets, 50mg and 100mg, for treatment during the mild-pain phase of a menstrually associated migraine among patients who typically experienced moderate to severe migraine preceded by an identifiable phase of mild pain. Subjects (n = 403 in Study 1 and n = 349 in Study 2) treated one menstrually associated migraine on an outpatient basis. The results demonstrate that sumatriptan tablets, 50 mg or 100 mg, were significantly more effective than placebo at conferring pain-free response 1 h and 2 h post-dose; migraine-free response (i.e. no pain and no associated symptoms) 2 h post-dose; returning patients to normal functioning 2 h post-dose; and conferring sustained freedom from pain from 2 through 24 h post-dose. Although the studies were not designed or statistically powered to show differences between the sumatriptan doses, a trend for slightly higher efficacy was observed for the 100-mg dose compared with the 50-mg dose on many measures. Both doses of sumatriptan were well-tolerated. The only adverse events reported in more than 2% of subjects in a treatment group were nausea, paresthesia, dizziness and malaise/fatigue, all of which were reported at incidences comparable to or slightly higher than those with placebo. Considered in the context of other findings, these data suggest that--with menstrually associated migraine as with non-menstrual migraine--optimal therapeutic benefit of sumatriptan tablets may be realised when they are administered during the mild-pain phase of an attack rather than delaying treatment until headache is moderate or severe.

Naratriptan as short-term prophylaxis of menstrually associated migraine: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine the efficacy of naratriptan 1-mg and 2.5-mg tablets twice daily compared with placebo as short-term prophylaxis of menstrually associated migraine. BACKGROUND: Approximately 60% of women with migraine report headaches associated with their menstrual cycles. Results from an open-label study suggest that short-term administration of sumatriptan is useful in the prophylaxis of menstrually associated migraine. METHODS: A randomized, double-blind, three-arm, parallel-group, placebo-controlled study was conducted in women aged 18 years or older with a history of migraine with or without aura, as defined by the International Headache Society, of at least 6 months. Two dose strengths of naratriptan (1 mg, 2.5 mg) or identical-appearing placebo tablets (1:1:1) were administered twice daily for 5 days starting 2 days prior to the expected onset of menses across four perimenstrual periods. End points included the number of menstrually associated migraines, total migraine days, peak headache severity, lost work/activity time, migraine-related quality of life, and incidence of adverse events. RESULTS: Overall, the intent-to-treat population comprised 206 women (naratriptan 1 mg, n = 70; naratriptan 2.5 mg, n = 70, and placebo, n = 66); 171 women treated four perimenstrual periods. Significantly more perimenstrual periods per subject treated with naratriptan, 1 mg, were headache-free compared with placebo (50% versus 25%, P =.003). Naratriptan, 1 mg, significantly reduced the number of menstrually associated migraines (2.0 versus 4.0, P <.05) and menstrually associated migraine days (4.2 versus 7.0, P <.01) compared with placebo. More patients treated with naratriptan, 1 mg, were headache-free across all treated perimenstrual periods compared with placebo (23% versus 8%). No difference in headache severity was observed in breakthrough headaches. The incidence and severity of adverse events was similar across treatment groups. Naratriptan, 2.5 mg, was not statistically superior to placebo for any measure. CONCLUSIONS: Naratriptan, 1 mg, with tolerability similar to placebo, is an effective, short-term, prophylactic treatment for menstrually associated migraine.

[Prevalence of duplex ultrasonography detectable venous thrombosis in patients with suspected or acute pulmonary embolism]. / Prévalence de la thrombose veineuse diagnostiquée par échographie-doppler des membres inférieurs dans la suspicion d'embolie pulmonaire et dans l'embolie pulmonaire confirmée.

OBJECTIVES: Duplex ultrasonography performance in detecting embolic foci has not been proven satisfactory compared with phlebography or autopsic findings. In case of suspected pulmonary embolism, the embolic focus is only discovered in 11 to 18% of the cases compared with more than 30% with phlebography. For overt acute pulmonary embolism, the discovery rate is in the 30 to 45% range versus 70 to 80% with phlebography or autopsy findings. This discrepancy might result from the fact that duplex ultrasonographic explorations are generally limited to the deep collectors at the cruropopliteal level. The purpose of this study was to assess the prevalence of duplex ultrasonography detected venous thrombosis in patients with suspected or acute pulmonary embolism when the exploration includes the entire venous system from the inferior vena cava to the ankles and examines not only the deep collectors but also the muscle and superficial networks. MATERIAL AND METHODS: This study included all patients with suspected pulmonary embolism referred to the emergency unit from January 1, 1995 through December 31, 1998. The patients' hospital files were used to determine the suspected pulmonary embolism population. The acute pulmonary embolism population was defined as the patients whose files contained documented proof of pulmonary embolism (highly probable ventilation/perfusion pulmonary scintigraphy, positive pulmonary angiography, positive proximal angioscan). Thrombosis of the deep venous collectors with or without associated superficial or muscular localization was classed as "deep venous thrombi" and superficial or muscular thrombosis without involvement of the deep collectors was classed as "other venous thrombi". Subpopliteal thrombosis was classed as distal and popliteal or suprapopliteal thrombosis as proximal. RESULTS: The suspected pulmonary embolism group included 352 patients, 118 men and 234 women aged 67.6 +/- 15.4 and 70.8 +/- 20.0 years respectively (m +/- SD). The acute pulmonary embolism group included 60 patients, 17 men and 43 women aged 66.2 +/- 12.5 and 69.7 +/- 16.6 years respectively. Overall prevalence of duplex-ultrasound detected venous thrombosis was 30.4% (107/352) (95%CI: 25.6-35.2) in the suspected pulmonary embolism group and 80% (48/60) (95%CI: 69.9-90.1) in the acute pulmonary embolism group. Deep venous thrombi reaching the collectors and proximal thrombi predominated. Prevalence of "other venous thrombi" and distal venous thrombi were 6.5% (23/352) and 11.4% (40/352) respectively in the suspected pulmonary embolism group and 15.0% (9/60) and 26.7% (16/60) in the acute pulmonary embolism group. The frequency of asymptomatic venous thrombosis of the lower limbs, irrespective of the localization, was 42.1% (45/107) in the suspected pulmonary embolism group and 52.1% (25/48) in the acute pulmonary embolism group. CONCLUSIONS: The prevalence of duplex-ultrasonography detected venous thrombosis in patients with suspected or proven pulmonary embolism found in this series was equivalent to the rates reported in phlebography and autopsy series. The prevalence was higher than usually reported for duplex-ultrasonography studies limited to the cruro-popliteal level. The difference came from the "other venous thrombi" and "distal deep venous thrombi" discovered by exploring the superficial and muscular networks and the calves. This study demonstrates the contribution of duplex-ultrasonography to the diagnostic strategy for pulmonary embolism.

Working with parents of aggressive preschoolers: an integrative approach to treatment.

In this article, we briefly review contributory factors within the child, parent-child interaction, and parents that have been put forward to explain the causes of aggressive problems in children. We then review various treatment approaches that have been used with this population and identify which component--the child, parent, or interaction--is targeted in each approach. A case example is provided to illustrate our perspective on treatment. We use a structured interview to categorize the mother's perceptions and subjective experience of her child and their relationship. Associations between the mother's perception of the relationship with her child, her parenting behavior, and the behavior of the child are discussed.

Maternal attachment and sensitivity in an at-risk sample.

This study investigated the relationship between adult attachment status and maternal sensitivity in a sample of 30 at-risk mother-child dyads. The children were 18-42 months old with an equal distribution of boys and girls that were at risk for compromised development due to a number of social, emotional and environmental factors. Using the Adult Attachment Interview (AAI; George, Kaplan, & Main, 1985) it was found that only 17% of the mothers were classified as autonomous, while 83% were classified as anxious regarding attachment. Sensitivity was measured using the Emotional Availability Scales (EAS) (Biringen, Robinson, & Emde, 1993). Each mother-child pair was video-taped in their home during a 30-minute interactional sequence in which they played with a given set of toys. Only the results from the Maternal Sensitivity Scale are reported here. Mothers who were free to evaluate their attachment experiences on the AAI were most sensitive. Mothers who showed anxiety in evaluating attachment, as a group, while undoubtedly caring and concerned, were less sensitive. There was, however, wide variability within the group of mothers with anxious attachment representations, Preoccupied mothers showing the least optimal interactions.

Symptomatic pharmacotherapy of migraine.

This review summarizes data on the effectiveness of various symptomatic migraine pharmacotherapies and makes recommendations for treatment. A wide variety of agents are available for the symptomatic treatment of migraine headache, including over-the-counter analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), combination products, opiates, ergot alkaloids, corticosteroids, dopamine antagonists, and triptans. In the stepped-care approach, simple analgesics and NSAIDs are the recommended first step for the treatment of mild-to-moderate migraine headaches. Patients who do not respond to first-step treatments may be given ergots, combination products, dopamine antagonists, or triptans as the second step. Corticosteroids or opiates may be used as rescue treatment in patients who do not respond to second-step treatment. A stratified approach to care individualizes treatment based on the severity of the headache and other patient-specific factors. In a stratified approach, dihydroergotamine or triptans may be the first-step treatment for patients who present with a history of severe migraines that have responded poorly to previous treatments. Sumatriptan was the first triptan approved for the symptomatic treatment of migraine headache; newer triptans include zolmitriptan, naratriptan, and rizatriptan. Since sumatriptan is rapidly absorbed by the subcutaneous route, its time to onset of effect is shortest. Among triptan drugs that are administered orally, the relative time to onset may be shorter with rizatriptan than sumatriptan. Naratriptan has a longer time to onset but is associated with a lower rate of migraine recurrence than other triptans. graine headache, ergot alkaloids, triptans,

X-inactivation and marker studies in three families with incontinentia pigmenti: implications for counselling and gene localisation.

Familial incontinentia pigmenti (IP) is an X-linked dominant disorder with an extremely variable clinical presentation. Ambiguous diagnosis can complicate genetic counselling and attempts to refine the gene location in Xq28. Marked skewing of X-inactivation patterns is a hallmark of IP and provides a means for investigating uncertain cases. We have conducted X-inactivation studies in three families where Xq28 marker studies were at odds with the original clinical assessment. The results indicate that no recombination between the disease locus and Xq28 loci has occurred and suggest that mosaicism is responsible for the discrepancy in one family.

Selective serotonin reuptake inhibitors for migraine prophylaxis.

The objective of this study was to assess the efficacy of sertraline in migraine prophylaxis. Other selective serotonin reuptake inhibitors have been studied for migraine prophylaxis, but this is the first report with sertraline. Twenty-seven subjects were enrolled and baseline assessment of migraine frequency and severity were measured over a 4-week period. Subjects were then randomized to receive placebo or sertraline in a double-blind fashion with headache frequency and severity measured over an 8-week period. Subjects completed a daily diary reporting the occurrence, severity, and degree of impairment associated with migraine. The headache index, a composite measure of migraine frequency and severity, scores did not significantly improve between assessments at baseline (20.8 +/- 14.88), 8 weeks (17.6 +/- 12.27), and 12 weeks (16.7 +/- 6.38) in the treatment group (n=6) (P=0.956). This finding is compared to other studies with the serotonin selective reuptake inhibitors, fluoxetine, fluvoxamine, and paroxetine. The authors believe that the selective serotonin reuptake inhibitors are not as effective as conventional migraine prophylaxis medications such as beta-blockers, tricyclic antidepressants, or divalproex sodium, but that in patients with comorbid depression who have failed conventional therapy selective serotonin reuptake inhibitors may be effective.

Shared parenting: assessing the success of a foster parent program aimed at family reunification.

OBJECTIVE: There were two main objectives of the study: (1) To assess the effectiveness of a model of family reunification which united the role of parent aide and foster parent; and (2) to determine which characteristics of the families with children in care were associated with reunification. METHOD: A multisite project known as the Shared Parenting Project recruited families from five child protection agencies to participate in a program in which foster parents became extended rather than substitute families. Families were tested before the program began on a number of sociodemographic, psychological, and family measures. The success of the program was determined by whether the child was able to return home of if the program facilitated permanency planning. The success of the project was also examined by considering the relationship between returning home and a number of risk factors measured in the families with children in care. RESULTS: Very few families who met the criteria for the project could be recruited and only 31% of the participants completed the program and returned home. The process of permanency planning was facilitated in another 50% of the cases. The more stable families with less risk factors were more likely to complete the program successfully and to have their children return home. CONCLUSIONS: The results indicate that although the treatment model has excellent potential with less at-risk families it could not meet the treatment needs of the majority of families with children in foster care in the five child protection agencies. It is recommended that this model could be most helpful offered through parent aides attached to community support agencies that could provide respite care, support, and resources to families as needed thus avoiding the child having to be placed in care.

Linkage analysis in 16 families with incontinentia pigmenti.

A locus for the X-linked dominant genodermatosis incontinentia pigmenti (IP) has been linked to markers in Xq28. Here we report high lod scores for markers spanning the interval DXS52-DXYS154 using 16 families, providing further evidence for a single major X-linked IP locus.

Repeat CT or MRI in posttraumatic headache.

Repeat CT or MRI of the brain should be considered in posttraumatic headache. We describe two patients with posttraumatic headache who had negative CT scans on initial presentation. One patient later had bilateral subdural hematomas on CT, and the other had temporal lobe hemorrhage on MRI. We recommend considering repeat CT or MRI for persisting posttraumatic headache and mental status change.

Secondary syphilis and headaches.

Secondary syphilis is associated with headaches. We describe two patients with headache from secondary syphilis and we recommended considering this in the differential diagnosis and evaluation of the headache patient.

A study of X chromosome activity in two incontinentia pigmenti families with probable linkage to Xq28.

Linkage analysis was carried out in two British families with incontinentia pigmenti (IP). Both showed exclusion at several markers in Xp and proximal Xq and showed probable linkage to the DXS52 and F8C loci in Xq28. This suggests that in these families the disease locus is IP2. Using a method based on the androgen receptor gene, and confirming the results where possible at the PGK-1 and DXS255 loci, it was shown that in affected females the maternally inherited X chromosome, where it could be identified, is inactive in the majority of cells.

Two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY) studies of nucleotide conformations in creatine kinase complexes: effects due to weak nonspecific binding.

The conformations of the adenosine moiety of MgADP and MgATP bound to rabbit muscle creatine kinase were investigated by two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY). The effects arising from adventitious binding of the ligands to the enzyme on the measurements were delineated. It was shown that, with sample protocols typically used thus far with the TRNOE method (enzyme, approximately 1 mM; ligand, approximately 10 mM), the TRNOESY pattern for the nucleotides with creatine kinase is similar to that with gamma-globulin and bovine serum albumin, which do not have specific nucleotide binding site(s). Measurements of NOE between the H1'-H2' proton pair as a function of ligand concentrations with the enzyme-ligand ratio kept constant at 1:10 showed that, for ligand concentrations over about 3-4 mM, weak nonspecific binding makes a significant contribution to the observed NOE. Thus the NOE values relevant for the determination of the nucleotide conformation at the active site were measured at nucleotide concentrations of about 1.5 mM. The TRNOE buildup curves for all the ligand-proton pairs were analyzed using a complete relaxation matrix approach. The interproton distances derived from the NOE's were then used as constraints in elucidating the ligand structure by using the program CHARMm. The NOE-determined structures of both MgADP and MgATP bound to creatine kinase correspond to an anti conformation with the glycosidic angle (O'4-C'1-N9-C8) chi = 51 +/- 5 degrees. The ribose pucker nominally representative of these data is a O4'T with a phase angle of pseudorotation (p) of 70.5 degrees.