Counting on U training to enhance trusting relationships and mental health literacy among business advisors: protocol for a randomised controlled trial.

BACKGROUND: Financial distress is thought to be a key reason why small-medium enterprise (SME) owners experience higher levels of mental health conditions compared with the broader population. Business advisors who form trusting, high-quality relationships with their SME clients, are therefore well placed to: (1) help prevent/reduce key sources of financial distress, (2) better understand the business and personal needs of their clients and, (3) recognise the signs and symptoms of mental health conditions and encourage help-seeking where appropriate. The aim of this study is to compare the effectiveness of relationship building training (RBT) combined with mental health first aid (MHFA) training for business advisors with MHFA alone, on the financial and mental health of their SME-owner clients. METHODS: This is a single blind, two-arm randomised controlled trial. Participants will be business advisors who provide information, guidance and/or assistance to SME owner clients and are in contact with them at least 3 times a year. The business advisors will invite their SME-owner clients to complete 3 online surveys at baseline, 6- and 12-months. Business advisors will be randomised to one of two conditions, using a 1:1 allocation ratio: (1) MHFA with RBT; or (2) MHFA alone, and complete 3 online surveys at baseline, 2- and 6-months. Primary outcomes will be measured in the business advisors and consist of the quality of the relationship, stigmatizing attitude, confidence to offer mental health first aid, quality of life and provision of mental health first aid. Secondary outcomes will be measured in the SME owners and includes trust in their business advisors, the quality of this relationship, financial wellbeing, financial distress, psychological distress, help-seeking behaviour, and quality of life. To complement the quantitative data, we will include a qualitative process evaluation to examine what contextual factors impacted the reach, effectiveness, adoption, implementation, and maintenance of the training. DISCUSSION: As there is evidence for the connections between client trust, quality of relationship and financial and mental wellbeing, we hypothesise that the combined RBT and MHFA training will lead to greater improvements in these outcomes in SME owners compared with MHFA alone. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04982094 . Retrospectively registered 29/07/2021. The study started in February 2021 and the recruitment is ongoing.

Maximal stomatal conductance to water and plasticity in stomatal traits differ between native and invasive introduced lineages of Phragmites australis in North America.

The fitness costs of reproduction by clonal growth can include a limited ability to adapt to environmental and temporal heterogeneity. Paradoxically, some facultatively clonal species are not only able to survive, but colonize, thrive and expand in heterogeneous environments. This is likely due to the capacity for acclimation (sensu stricto) that compensates for the fitness costs and complements the ecological advantages of clonality. Introduced Phragmites australis demonstrates great phenotypic plasticity in response to temperature, nutrient availability, geographic gradient, water depths, habitat fertility, atmospheric CO2, interspecific competition and intraspecific competition for light. However, no in situ comparative subspecies studies have explored the difference in plasticity between the non-invasive native lineage and the highly invasive introduced lineage. Clonality of the native and introduced lineages makes it possible to control for genetic variation, making P. australis a unique system for the comparative study of plasticity. Using previously identified clonal genotypes, we investigated differences in their phenotypic plasticity through measurements of the lengths and densities of stomata on both the abaxial (lower) and adaxial (upper) surfaces of leaves, and synthesized these measurements to estimate impacts on maximum stomatal conductance to water (gwmax). Results demonstrated that at three marsh sites, invasive lineages have consistently greater gwmax than their native congeners, as a result of greater stomatal densities and smaller stomata. Our analysis also suggests that phenotypic plasticity, determined as within-genotype variation in gwmax, of the invasive lineage is similar to, or exceeds, that shown by the native lineage.

Robust fluidic connections to freestanding microfluidic hydrogels.

Biomimetic scaffolds approaching physiological scale, whose size and large cellular load far exceed the limits of diffusion, require incorporation of a fluidic means to achieve adequate nutrient/metabolite exchange. This need has driven the extension of microfluidic technologies into the area of biomaterials. While construction of perfusable scaffolds is essentially a problem of microfluidic device fabrication, functional implementation of free-standing, thick-tissue constructs depends upon successful integration of external pumping mechanisms through optimized connective assemblies. However, a critical analysis to identify optimal materials/assembly components for hydrogel substrates has received little focus to date. This investigation addresses this issue directly by evaluating the efficacy of a range of adhesive and mechanical fluidic connection methods to gelatin hydrogel constructs based upon both mechanical property analysis and cell compatibility. Results identify a novel bioadhesive, comprised of two enzymatically modified gelatin compounds, for connecting tubing to hydrogel constructs that is both structurally robust and non-cytotoxic. Furthermore, outcomes from this study provide clear evidence that fluidic interconnect success varies with substrate composition (specifically hydrogel versus polydimethylsiloxane), highlighting not only the importance of selecting the appropriately tailored components for fluidic hydrogel systems but also that of encouraging ongoing, targeted exploration of this issue. The optimization of such interconnect systems will ultimately promote exciting scientific and therapeutic developments provided by microfluidic, cell-laden scaffolds.

Photosynthetic pathway and ecological adaptation explain stomatal trait diversity amongst grasses.

• The evolution of C(4) photosynthesis in plants has allowed the maintenance of high CO(2) assimilation rates despite lower stomatal conductances. This underpins the greater water-use efficiency in C(4) species and their tendency to occupy drier, more seasonal environments than their C(3) relatives. • The basis of interspecific variation in maximum stomatal conductance to water (g(max) ), as defined by stomatal density and size, was investigated in a common-environment screening experiment. Stomatal traits were measured in 28 species from seven grass lineages, and comparative methods were used to test for predicted effects of C(3) and C(4) photosynthesis, annual precipitation and habitat wetness on g(max) . • Novel results were as follows: significant phylogenetic patterns exist in g(max) and its determinants, stomatal size and stomatal density; C(4) species consistently have lower g(max) than their C(3) relatives, associated with a shift towards smaller stomata at a given density. A direct relationship between g(max) and precipitation was not supported. However, we confirmed associations between C(4) photosynthesis and lower precipitation, and showed steeper stomatal size-density relationships and higher g(max) in wetter habitats. • The observed relationships between stomatal patterning, photosynthetic pathway and habitat provide a clear example of the interplay between anatomical traits, physiological innovation and ecological adaptation in plants.

Drought limitation of photosynthesis differs between C3and C4grass species in a comparative experiment.

Phylogenetic analyses show that C4 grasses typically occupy drier habitats than their C3 relatives, but recent experiments comparing the physiology of closely related C3 and C4 species have shown that advantages of C4 photosynthesis can be lost under drought. We tested the generality of these paradoxical findings in grass species representing the known evolutionary diversity of C4 NADP-me and C3 photosynthetic types. Our experiment investigated the effects of drought on leaf photosynthesis, water potential, nitrogen, chlorophyll content and mortality. C4 grasses in control treatments were characterized by higher CO2 assimilation rates and water potential, but lower stomatal conductance and nitrogen content. Under drought, stomatal conductance declined more dramatically in C3 than C4 species, and photosynthetic water-use and nitrogen-use efficiency advantages held by C4 species under control conditions were each diminished by 40%. Leaf mortality was slightly higher in C4 than C3 grasses, but leaf condition under drought otherwise showed no dependence on photosynthetic-type. This phylogenetically controlled experiment suggested that a drought-induced reduction in the photosynthetic performance advantages of C4 NADP-me relative to C3 grasses is a general phenomenon.

Effects of chronic hepatitis C infection on the treatment of breast cancer patients.

BACKGROUND: Although hepatitis C (HCV) is the most common blood-borne infection in the United States, little information exists about treatment of breast cancer in the setting of chronic HCV. PATIENTS AND METHODS: The databases of the University of Texas M.D. Anderson Cancer Center (MDACC) Tumor Registry, Department of Breast Medical Oncology, and Department of Laboratory Medicine were cross-referenced for patients with breast cancer, who were also identified as having HCV. Eligible patients had a diagnosis of invasive breast cancer, breast cancer treatment at MDACC, and a diagnosis of HCV. RESULTS: During chemotherapy, 25% of patients experienced elevations in aminotransferases and 44% of patients required dose reductions/delays in chemotherapy. More than 60% of the patients who received chemotherapy demonstrated a grade 2 or greater complication. However, 92% of patients were able to complete the number of cycles specified in the initial chemotherapy plan. CONCLUSIONS: As the majority of these breast cancer patients completed the initial chemotherapy plan, this study indicates that breast cancer patients with HCV can be treated with cytotoxic therapy. Comparison with historical controls showed similar rates of hepatic toxicity in the presence (or absence) of HCV, indicating that incidence of transaminitis may not be significantly affected by HCV.

Social work practice with people with disabilities in the era of disability rights.

Social workers, especially those in health care and rehabilitation systems, must consider practice changes necessitated by recent legislation and the growing activism of disability rights groups. The authors review essential elements of the emerging sense of both oppression and empowerment that is occurring for many people with disabilities and groups; consider key aspects of ADA and other perti nent legislation that place new emphases on the self-determination of people with disabilities; and discuss what implications changing practice roles might have for social workers' relationships and patterns of interaction with other professionals in medical, health care and rehabilitation settings. The authors outline a beginning effort at designing a conceptual framework that promotes practice that: (1) maximizes clients' involvement in exploring an expanded range of options and choices; (2) prepares clients to be more effective in dealings with professionals, bureaucrats and agencies that often do not understand nor appreciate their need for self-determination; and (3) at the organizing level, mobilizes and helps to empower groups of people with disabilities to consider policy and program alternatives that can improve their situation. This framework may also be useful in work with people who have other long term care needs, chronic conditions.

Diuretic therapy in congestive heart failure.

The principal goals of treatment of the patient in heart failure are the relief of their symptoms and improvement in their prognosis. Of all antiheart failure drugs currently available, the diuretics are therapeutically superior in their efficacy in relieving clinical symptoms and signs. Whether administered intravenously or orally, all diuretics result in a substantial reduction in the raised pulmonary vascular pressures in combination with a small reduction in cardiac output. Diuretics stimulate release of renin with subsequent activation of the renin-angiotensin-aldosterone system, particularly if used in large doses, although their quantitative impact on the neuroendocrine profile at different stages of heart failure remains to be defined. In patients with mild heart failure, diuretics reduce plasma catecholamine concentrations, but their sympatholytic effects in more severe cases are unknown, as are their effects on the metabolically active tissues in these patients. Diuretic resistance can be circumvented by segmental nephron blockade with a combination of low-dose diuretics that simultaneously block sodium reabsorption in the proximal tubule, the loop of Henle, the distal tubule, and the collecting duct. Diuretics improve symptoms of breathlessness and signs of peripheral edema in patients with congestive heart failure in direct relationship to the induced diuresis. These benefits are frequently associated with a substantial improvement in patients' appreciation of quality of life and economic capacity. There are few adverse reactions to chronic diuretic therapy, but the serum electrolytes should be monitored for hypokalemia and hypomagnesemia. The impact of diuretics on prognosis of patients with congestive heart failure is unknown; however, diuretics have been a major ingredient of the therapies used in all the survival trials with vasodilators, angiotensin-converting enzyme inhibitors, and beta-blocking drugs. In addition to their clinical benefits, diuretics are the most cost-effective treatment of any single drug group currently available for the treatment of patients with congestive heart failure.

Diuretics in cardiovascular therapy: the new clinicopharmacological bases that matter.

Diuretics in current use include early distal tubular (i.e., thiazide-type), loop (i.e., furosemide-type), and potassium-and-hydrogen-retaining substances. Available oral formulations of diuretics differ in terms of their renal excretory potency in man, as formally assessed through the effect of a single dose on 24-hour natriuresis in healthy subjects. The 2.5 mg formulation of the loop diuretic torasemide does not increase mean 24-hour natriuresis, and it is therefore considered a very-low-dose formulation. Amiloride 5 mg and torasemide 5 mg and 10 mg, which increase mean 24-hour natriuresis by less than 40%, are considered low-dose or low-potency diuretic formulations of diuretic substances. Hydrochlorothiazide 25 and 50 mg, furosemide 40 and 80 mg, and torasemide 20 mg, which increase mean 24-hour natriuresis by more than 40%, are considered high-dose or high-potency formulations. A rebound in natriuresis follows the early-after-dosing increase in this variables caused by loop diuretics; hence many oral formulations of loop substances are less potent natriuretics than most oral formulations of thiazide-type diuretics. Hydrochlorothiazide 25 mg and furosemide 80 mg have similar natriuretic potencies. During once-daily administration of diuretic formulations of diuretics to subjects without edema and normal renal function, the increases in 24-hour natriuresis and diuresis that follow the first dose disappear or attenuate markedly. This is due to neuroendocrine reactions to diuretic-induced sodium loss and its attendant hemodynamic shifts. Some of these reactions, e.g. the increase in plasma aldosterone that takes place, account for an elevation in kaliuresis that occurs during once-daily treatment with a high-dose formulation of a thiazide-type diuretic. Common fixed-dose combinations of a thiazide-type or a loop diuretic and a potassium-and-hydrogen-retaining substance generally do not change kaliuresis, but they increase natriuresis strikingly. Thiazide-type and loop diuretics decrease and increase calciuresis respectively; none of these actions wanes during prolonged administration. Plasma renin activity and aldosterone do not rise in response to very-low-dose formulations of loop diuretics taken once daily. Glomerular filtration rate tends to fall in the course of once-daily administration of high-dose formulations of diuretics, but not during prolonged once-daily treatment with very-low-dose formulations of loop diuretics.

Hemodynamic differences between metoprolol and carvedilol in hypertensive patients.

Resting hemodynamics were measured before, at 2 and 24 h after the first dose, and after 4 weeks of monotherapy with either metoprolol or carvedilol in a randomized single-blind study. We analyzed results from 24 hypertensive patients (30-68 years of age) with adequate blood-pressure lowering on monotherapy. Acutely, both drugs lowered systolic blood pressure and heart rate. Whereas metoprolol reduced cardiac output and increased both systemic and femoral artery resistance, carvedilol did not alter cardiac output but led to reductions in the systemic and regional resistances. After 4 weeks of therapy, cardiac output remained reduced and vascular resistances increased in the metoprolol group, whereas in carvedilol patients cardiac output continued to be unchanged and the trend for vascular resistances to be decreased persisted. Acutely and chronically the differences in the hemodynamic effects of the two medications were statistically significant. The study results indicate that carvedilol's vasodilatory action is not subject to tolerance development. Chronic afterload reduction associated with the decrease in systemic vascular resistance may lead to additional savings in myocardial oxygen consumption, a beneficial feature particularly in those patients with concomitant ischemic heart disease. It may also have a favorable influence on concentric cardiac hypertrophy and changes in the walls of arteriolar resistance vessels.

Efficacy and tolerability of amlodipine in the general practice treatment of essential hypertension in an asian multinational population.

OBJECTIVE: To evaluate the efficacy and tolerability of once-daily amlodipine (Pfizer Pharmaceuticals Inc.) alone or in combination with other antihypertensive drugs in an Asian population with essential hypertension. PATIENTS: An open study was undertaken in 165 male and 158 female patients with uncomplicated hypertension (diastolic blood pressure 95 to 115mm Hg). Patients were recruited from 41 general practices in seven Asian countries and received amlodipine 5mg daily for 4 weeks and then 10mg once daily for a further 4 weeks if the target diastolic blood pressure of /=10mm Hg had not been achieved. This one-step dose-adjustment period was followed by a 4-week maintenance period on a constant dose. Amlodipine was the sole medication in 284 patients and was added to other antihypertensive drugs in 39 patients uncontrolled on previous medication. RESULTS: 263 patients, including 131 males, were evaluated for efficacy at the final treatment visit. 166 (63%) patients achieved the target reduction in diastolic blood pressure with amlodipine 5mg once daily, while 84 patients achieved the target reduction with 10mg once daily. Systolic and diastolic blood pressure reductions were similar irrespective of gender or age, and there were no significant changes in resting heart rate in any subgroup. In 68 patients who underwent ambulatory monitoring, the systolic and diastolic blood pressures were reduced by once-daily amlodipine throughout the 24-hour period without change in the intrinsic circadian pattern. Amlodipine was well tolerated in all patient subgroups; adverse events accounted for less than 1% of treatment discontinuations, and there were no hospitalisations or deaths during the study. Investigators rated both the antihypertensive efficacy and tolerability of amlodipine as excellent or good in 93% of patients. CONCLUSION: In 263 Asian patients with uncomplicated essential hypertension treated in general practice, once-daily amlodipine in a dose of 5 or 10mg provided significant antihypertensive efficacy either as monotherapy or in combination with other antihypertensive drugs while maintaining a favourable tolerability profile regardless of gender or age.

Comparison of the hemodynamic effects of metoprolol and carvedilol in hypertensive patients.

Metoprolol and carvedilol are widely used in the treatment of hypertension, but no randomized comparison of their hemodynamic activity has been previously reported. Their comparative effects on heart rate, systemic blood pressure, and echocardiographically determined aortic and femoral artery blood flow were measured at rest and at 2 and 24 hours after the first dose of each drug, and again after 4 weeks of sustained monotherapy in 12 male and 12 female patients, aged 36-68 years with uncomplicated sustained hypertension according to a randomized single-blind protocol. Nine patients in each drug group achieved the target diastolic blood pressure of < 90 mmHg on the initial doses of each drug; this was achieved in the remainder following doubling of each dose. Neither drug occasioned withdrawal of any patient due to adverse reactions. Both drugs significantly reduced heart rate, although the reduction at 2 hours was significantly greater after metoprolol than after carvedilol. Both drugs reduced systolic pressure throughout the study; the reduction at 2 hours was significantly greater after carvedilol than after metoprolol. In contrast, the diastolic blood pressure was persistently reduced only by carvedilol. The cardiac output, determined as the aortic systolic blood flow, after carvedilol was not significantly different from pretreatment values throughout the study but was significantly reduced in the metoprolol-treated patients at each point of measurement. After metoprolol the systemic and femoral vascular resistances derived from conventional formulae were consistently and significantly increased over pretreatment values throughout the study and were significantly greater than in the carvedilol group at all measurement points. The hemodynamic differences between these two beta-blocking drugs may be explained by the additional vasodilator activity of carvedilol associated with its alpha 1-adrenoceptor blocking activity. The long-term clinical and prognostic implications of these pharmacodynamic differences between beta-adrenoceptor antagonists with and without additional vasodilator activity in the treatment of hypertensive patients remain to be determined.

Congestive heart failure. Towards a comprehensive treatment.

Heart failure constitutes an increasing health hazard with major demands on health care resources. Recent major advances in drug treatment have yet to be translated into increased survival of heart failure patients in the community at large. Failure of diagnosis is a major factor in delaying early and adequate treatment. Echocardiography probably provides the most reliable and inexpensive instrument to confirm the diagnosis and pinpoint the mechanical components of the syndrome. The targets for therapeutic intervention may be categorized (i) haemodynamic, neuroendocrine and metabolic disorders (ii) symptoms and quality of life, (iii) morbidity and mortality risks. Symptoms and quality of life are the prime concerns of the physician in the treatment in the individual patient. Selection of anti-heart failure drugs used should be based on knowledge of the impact on the pathophysiological disorders and on the morbidity and mortality risks. Diuretics, vasodilators and ACE-inhibitors are now accepted as standard treatment, particularly when used in combination. Controversy continues to surround the efficacy of digitalis glycosides; they improve symptoms in some patients but their impact on morbidity and mortality risks is still uncertain. Even with standard treatments, may practical therapeutic questions remain, one of which is what is the most efficacious dose of each anti-heart failure drug which, when used in combination, will give the maximum improvement in quality of life and greatest extension of survival? Despite available treatment with diuretics, digitalis, vasodilators and ACE-inhibitors, the morbidity and mortality risks of congestive heart failure remain high. None of these drug groups significantly modulates the excessive excitation of the sympathoadrenal system, one of the two major neuroendocrine hazards of heart failure. For this reason, amongst the many newer drugs in development, the beta-adrenoceptor antagonists hold considerable promise as the next step towards a more comprehensive treatment of congestive heart failure.

Reoperation for recurrent metastatic brain tumors.

Results of reoperation in 48 patients who developed recurrent brain metastases between January 1984 and April 1993 are presented. Median time from first craniotomy to diagnosis of recurrence (time to recurrence) was 6.7 months. Median Karnofsky performance scale (KPS) score prior to reoperation was 80. Recurrence was local in 30 patients, distant in 16 patients, and both local and distant in two patients. Median survival time after reoperation was 11.5 months. There were no operative mortalities. Multivariate analysis revealed that presence of systemic disease (p = 0.008), KPS scores less than or equal to 70 (p = 0.008), time to recurrence of less than 4 months (p = 0.008), age greater than or equal to 40 years (p = 0.51), and primary tumor type of breast or melanoma (p = 0.028) negatively affected patient survival time. These five factors were used to develop a grading system (Grades I-IV). Patients categorized in Grade I had a 5-year survival rate of 57%, whereas the median survival time of patients in Grades II, III, and IV was 13.4, 6.8, and 3.4 months, respectively (p < 0.0001). Overall, 26 patients developed a second recurrence after reoperation. Seventeen patients underwent a second reoperation, whereas nine did not. Patients undergoing a second reoperation survived a median of 8.6 additional months versus 2.8 months for those who did not (p < 0.0001). This study concludes that reoperation for recurrent brain metastasis can prolong survival and improve quality of life. A second reoperation can also increase survival. Five factors influence survival: status of systemic disease, KPS score, time to recurrence, age, and type of primary tumor. The grading system using these five factors correlates with survival time. Reoperation should be approached with caution in Grade IV patients because of their poor prognosis.

Refocus on diuretics in the treatment of heart failure.

Diuretics have long been accepted as the traditional first-line treatment of the patient with symptomatic heart failure whatever its aetiology or dysfunctional stage. Their acceptance in this role is based on the rapid improvement in congestive symptoms experienced by most patients, which is arguably greater than that induced by any other currently available anti-heart failure drug. This symptomatic efficacy and their universal clinical acceptance as first-step treatment for the patient with symptoms of heart failure has precluded formal examination of their impact on prognosis. Evidence from indirect studies suggests that when used alone they may not be able to prevent clinical deterioration, possibly due to excitation of the renin-angiotensin-aldosterone system. When such excitation is suppressed by concomitant administration of angiotensin-converting enzyme inhibitors, relief of congestive symptoms is enhanced and the morbidity and mortality risk of heart failure significantly reduced. Studies on the mechanisms of diuretic resistance have demonstrated the synergy of diuretic activity when low doses of diuretics acting at different sites of the nephron are used in combination. Diuretics remain the cornerstone of treatment for symptoms in congestive heart failure but their overall efficacy is substantially improved when combined with ACE inhibitors.

Sarcoma metastatic to the brain: results of surgical treatment.

We report on 21 patients surgically treated for intraparenchymal brain metastasis from sarcoma, including six osteosarcomas, four leiomyosarcomas, three malignant fibrous histiocytomas, two alveolar soft-part sarcomas, two Ewing's bone sarcomas, one extraskeletal osteosarcoma, one extraskeletal Ewing's sarcoma, and two unclassified sarcomas. Median survival after craniotomy was 11.8 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 15.7 versus 6.6 months for those with a Karnofsky performance score < or = 70. Patients. undergoing complete resection survived 14.0 versus 6.2 months for patients undergoing incomplete resection. Patients with evidence of lung metastases at the time of surgery survived 11.8 months, which was similar to the 10.5-month survival for patients with disease limited to the brain. The two patients with alveolar soft-part sarcoma are alive at 16 and 25 months after surgery. We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from alveolar soft-part sarcoma may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis, whereas the presence of concurrent lung metastases is not a contraindication to surgery.

Effect of pregnancy on prognosis for young women with breast cancer.

Breast cancer in women under 30 years old carries a poor prognosis, for reasons that have not been identified. This study aimed to identify prognostic factors in this age group. Special attention was paid to the history of pregnancy. The clinical presentation and course of breast cancer was documented for 407 women, aged 20-29 years, who registered between 1978 and 1988 at one of nine cancer centres. Eligible patients had histologically confirmed local or regional invasive breast carcinoma, and received part or all of their initial therapy at the participating hospital. For patients whose breast cancers were diagnosed during pregnancy, the risk of dying from breast cancer was significantly greater than that of women who had never been pregnant (relative risk 3.26 [95% CI 1.81-5.87], p = 0.0004). Adjustment for number of axillary nodes affected and tumour diameter reduced the relative risk only slightly (2.83 [1.24-6.45], p = 0.023). For each 1-year increment in the time between the latest previous pregnancy and breast cancer diagnosis, the risk of dying decreased by 15% (relative risk 0.85, p = 0.011). Thus concurrent or recent previous pregnancy adversely affects survival of breast cancer in young women. The size of the effect is such that it probably contributes substantially to the poor prognosis of breast cancer in this age group as a whole.

Occurrence and prognosis of contralateral carcinoma of the breast.

Of the 4,554 patients who registered at The University of Texas M. D. Anderson Cancer Center, Houston, Texas from 1965 to 1988 with a diagnosis of carcinoma of the breast and who underwent surgical treatment of at least one carcinoma of the breast at this institution, 142 had either a history of a prior carcinoma of the breast (metachronous; n = 55) or a contralateral carcinoma of the breast detected within four months of registration (synchronous; n = 87). We retrospectively studied the records of these 142 patients and found that the occurrence of bilateral carcinoma of the breast was low (3.1 percent), the frequency of metachronous carcinoma of the breast remained relatively constant over time, the nodal status of the second carcinoma of the breast correlated with the method of discovery rather than the stage of the first carcinoma of the breast and survival rates from the second carcinoma of the breast were similar for metachronous and synchronous disease. These data support the role of vigilant surveillance of the contralateral breast with screening at the time of initial diagnosis and during follow-up evaluation. Because the likelihood of detecting a second carcinoma of the breast at an early stage is high, with subsequent good survival rates, the use of prophylactic mastectomy should be very selective and based on the emotional needs of the patient.

Double-blind comparison of amlodipine and nifedipine retard in the treatment of mild to moderate hypertension.

The efficacy and safety profiles of amlodipine (5-10 mg once daily) and nifedipine retard (20-40 mg twice daily) were compared in 111 hypertensive patients (sitting DBP in 95-115 mmHg) during eight weeks of treatment in a randomised double-blind parallel group study. BP was measured 22-24 hours after the daily dose of amlodipine and 10-12 hours after a dose of nifedipine retard. Baseline sitting BPs of 175/105 mmHg and 168/104 mmHg were significantly reduced (P < 0.05) to 157/93 mmHg and 151/92 mmHg at the end of treatment in response to mean daily doses of amlodipine 7.3 mg and nifedipine retard 58.9 mg. There were no clinically significant changes in heart rate with either treatment. Three patients in the amlodipine group and five patients in the nifedipine retard group could not be considered in analysis. The total numbers of adverse events (considered related or possibly related to treatment) (42 vs. 36) as well as the numbers of patients experiencing such events (22 vs. 22) were similar in the amlodipine and nifedipine retard treated groups, respectively, but with a greater incidence of headaches in response to nifedipine retard and of oedema in response to amlodipine. Five patients in each treatment group discontinued therapy due to such events. Overall the results showed once daily amlodipine as equivalent to twice daily nifedipine retard in the management of mild to moderate hypertension.