Blockade of tumour necrosis factor-α in experimental autoimmune encephalomyelitis reveals differential effects on the antigen-specific immune response and central nervous system histopathology.

In various autoimmune diseases, anti-tumour necrosis factor (TNF)-α treatment has been shown to reduce both clinical disease severity and T helper type 1 (Th1)1/Th17 responses. In experimental autoimmune encephalomyelitis (EAE), however, the role of TNF-α has remained unclear. Here, C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 and treated with anti-TNF-α, control antibody or vehicle. The clinical disease course, incidence and severity were assessed. On day 20 after immunization the antigen-specific Th1/Th17 response was evaluated by enzyme-linked immunospot (ELISPOT) in spleen and central nervous system (CNS). Also, the extent of spinal cord histopathology was analysed on semi- and ultrathin sections. Our results demonstrate that anti-TNF-α treatment reduced the incidence and delayed the onset of EAE, but had no effect on disease severity once EAE had been established. Whereas anti-TNF-α treatment induced an increase in splenic Th1/Th17 responses, there was no effect on the number of antigen-specific Th1/Th17 cells in the spinal cord. Accordingly, the degree of CNS histopathology was comparable in control and anti-TNF-α-treated mice. In conclusion, while the anti-TNF-α treatment had neither immunosuppressive effects on the Th1/Th17 response in the CNS nor histoprotective properties in EAE, it enhanced the myelin-specific T cell response in the immune periphery.

The South Asian monsoon-pollution pump and purifier.

Air pollution is growing fastest in monsoon-affected South Asia. During the dry winter monsoon, the fumes disperse toward the Indian Ocean, creating a vast pollution haze, but their fate during the wet summer monsoon has been unclear. We performed atmospheric chemistry measurements by aircraft in the Oxidation Mechanism Observations campaign, sampling the summer monsoon outflow in the upper troposphere between the Mediterranean and the Indian Ocean. The measurements, supported by model calculations, show that the monsoon sustains a remarkably efficient cleansing mechanism by which contaminants are rapidly oxidized and deposited to Earth's surface. However, some pollutants are lofted above the monsoon clouds and chemically processed in a reactive reservoir before being redistributed globally, including to the stratosphere.

Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats.

Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner.

Two methods for assessing the risk-factor composition of the HIV-1 epidemic in heterosexual women: southeast England, 1988-1991.

OBJECTIVE: The prevalence of HIV-1 in the heterosexual population in southeast England between 1988 and 1991 was examined using two methods. DESIGN AND METHODS: First, district neonatal seroprevalence was compared on a geographical basis to social and demographic variables reflecting risk-factor prevalence. Second, over the same period eight children who developed AIDS within the first 12 months of life were born. RESULTS: The differences in seroprevalence between districts could be explained by the proportion of livebirths to women born in parts of Africa. An estimated 92% of neonatal seropositives could be associated with this demographic variable. The proportions of livebirths to women born in other countries, the prevalence of notified injecting drug use, and area measures of social deprivation, were only poorly related to HIV seroprevalence, and had no additional explanatory value. Seven of the eight (87.5%) children who developed AIDS in the first year were born to black women from Africa. CONCLUSIONS: Both methods suggest that a high proportion of heterosexually transmitted HIV in southeast England has been imported.

Transplacental effects of 3,5-dimethyl-3'-isopropyl-L-thyronine on fetal hypothyroidism in primates.

Pregnant Rhesus monkeys treated with 131I at midgestation become hypothyroid and produce fetuses without demonstrable thyroid tissue. In an effort to prevent both maternal and fetal hypothyroidism, we treated 131I-treated pregnant monkeys with 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a thyroid hormone analog with structural changes which facilitate placental transfer. Five pregnant monkeys were treated with 131I (mCi/kg) at 83-87 days of gestation. One week later, three monkeys were started on treatment with DIMIT (10 micrograms kg-1 day-1, im) and two on im L-T4 (2 micrograms kg-1 day-1). Treatment was continued until delivery by Caesarian section at 152-157 days of gestation. None of the DIMIT-treated mothers became clinically hypothyroid, nor did they have elevated serum TSH concentrations despite low serum levels of T3 and T4. T4-treated mothers were also maintained clinically and biochemically euthyroid. At delivery, infants of DIMIT-treated mothers had normal respiratory function and skeletal maturation. Basal and TRH-stimulated TSH concentrations were suppressed in two of the three infants. By contrast, both T4-treated infants resembled untreated cretinous newborns and died soon after delivery from respiratory failure. Serum TSH concentrations were elevated and skeletal maturation was markedly delayed in these animals. We conclude that DIMIT administration to 131I-treated monkeys prevents clinical and biochemical hypothyroidism in the mother and prevents the major clinical manifestations of cretinism in the fetus.

Gonadotropin-independent precocious puberty ("testotoxicosis"): influence of maturational status on response to ketoconazole.

Three boys, 5.0-7.4 yr of age, with clinical and biochemical features consistent with familial gonadotropin-independent precocious puberty ("testotoxicosis") were treated with the antifungal drug ketoconazole in a dose of 200 mg every 8 h. Serum testosterone levels fell significantly within 24 h in all three patients, with reciprocal changes in serum 17-hydroxyprogesterone, consistent with inhibition of C17-20 lyase activity. However, after 1-3 months of continuing treatment, an "escape" phenomenon occurred, characterized by progressive increases in serum LH, FSH, and testosterone concentrations. Furthermore, for the first time, a marked pubertal-type LH response was found after GnRH administration in contrast to the absent response consistently found in all patients before ketoconazole therapy. Combination treatment with ketoconazole and the GnRH analog buserelin resulted in restoration of pituitary and gonadal hormone concentrations to the upper range of normal for prepubertal children. We hypothesize that the advanced state of maturation of the boys in this study [mean bone age, 13.2 +/- 0.8 (+/- SE) yr] was the major contributing factor to this escape, with the set-point of the GnRH pulse generator (gonadostat) functioning at the adult level of sensitivity. Such escape may limit the successful use of ketoconazole alone. These data together with evidence of normal testosterone responses to hCG during ketoconazole therapy indicate that in testotoxicosis, pituitary and gonadal receptors are functionally intact, with appropriate negative feedback relationships.

Concordant Graves' disease after bone marrow transplantation: implications for pathogenesis.

The current working hypothesis on the pathogenesis of autoimmune disease focuses on the interactions between susceptibility genes and environmental stimuli. In Graves' disease it is postulated that aberrant expression of HLA class II antigens on thyroid epithelial cells permits the presentation of specific thyroid antigen to activated lymphocytes. Evidence suggests that thyrocyte HLA-DR expression is secondary to the production of cytokines by presensitized T-lymphocytes. A 20-yr-old woman and her 18-yr-old brother presented with classical findings of Graves' disease with ophthalmopathy within a year of each other. Diagnosis was confirmed by demonstration of elevated serum levels of T4 and T3, strongly positive titers of TSH binding inhibitory immunoglobulins, and histological examination after subtotal thyroidectomy. Eight years previously, acute life-threatening aplastic anemia in the brother led to therapeutic transplantation of bone marrow from his sister. After the procedure, 100% of his peripheral leucocytes were genotype 46,XX. HLA typing performed before transplantation and 2 months after thyroidectomy in the female indicated complete identity with her brother's leukocytes for class I and class II antigens. Thyroid autoantibodies at this time were weakly positive. Although the concordance of thyroid disease in these patients could be due to chance, the patients were of different sexes, the family history was negative, and neither the probands nor the first degree relatives bore the HLA-DR3/B8 antigens. We propose that the male passively acquired a clone of programmed or activated lymphocytes from his sister and that his hyperthyroidism was not primarily dependent on exposure to specific thyroid-derived antigen.

Pharmacokinetic characteristics of the gonadotropin-releasing hormone analog D-Ser(TBU)-6EA-10luteinizing hormone-releasing hormone (buserelin) after subcutaneous and intranasal administration in children with central precocious puberty.

A double antibody RIA was developed for the measurement of the long-acting GnRH agonist D-Ser(TBU)6EA10GnRH (buserelin). The antibody, raised in rabbits against a buserelin-hemocyanin conjugate, reacted with the intact molecule and also molecular fragments containing the C6-9 tetrapeptide sequence and permitted the measurement of buserelin activity in serum and urine. Natural GnRH, LH, and FSH did not cross-react in this assay system. The assay was applied to samples obtained from children receiving buserelin for the management of central precocious puberty either by once daily injection of 30 micrograms/kg or by nasal spray (in; 200 micrograms every 8 h). Urine and serum samples, chromatographed on Sephadex G-25, contained immunoreactive material corresponding closely in molecular size to [125I]buserelin. In unextracted serum samples taken at intervals after sc therapy in 11 girls, the peak immunoreactive buserelin levels of 52.2 +/- 14.8 ng/ml (mean +/- SEM) occurred at 30 min. The half-time of elimination was 74.9 +/- 36.9 min. Approximately 30% of the dose was detected in urine collected for 3 h after injection. Similar data were obtained in 3 normal adults given 10 micrograms/kg buserelin, iv. By contrast, after the administration of 200 micrograms buserelin by metered nasal spray, the mean peak serum concentration in 10 girls was 100-fold less (0.65 +/- 0.14 ng/ml), although the halftime of elimination was almost identical. Only 0.73% of the nasal dose was excreted by 3 h. Calculated relative bioavailability data indicated maximal nasal absorption of 6%. However, absorption after nasal administration varied greatly, and in 2 children, serum and urinary concentrations of buserelin after supervised administration were negligible. We conclude that in buserelin therapy, in the dose used in this study, does not represent optimal treatment for the initial management of patients with precocious puberty. The success of in therapy in sustaining initial effects of buserelin given by sc administration presumably reflects changes in receptor sensitivity induced by sc treatment.

Intranasal and subcutaneous treatment of central precocious puberty in both sexes with a long-acting analog of luteinizing hormone-releasing hormone.

The chronic administration of the long-acting LHRH agonist analog D-Ser(TBU)6-LHRH-EA10 (HOE 766, Buserelin) suppresses pituitary gonadotropin secretion. Since a similar analog was shown to be effective in the short term parenteral treatment of idiopathic precocious puberty in girls (10), we used Buserelin both intranasally and sc to treat patients of both sexes with idiopathic and secondary central precocious puberty to test its efficacy, safety, and potential for long term use. Six girls and two boys presented with advanced skeletal maturity, accelerated growth velocity, Tanner stage II-IV pubertal development, and pubertal levels of sex steroids and gonadotropins. Patients were treated for 6 months sc and up to 5 months intranasally. Optimal doses ranged from 10-20 micrograms/kg X day in girls and 30 micrograms/kg X day in boys, with marked individual variation. During sc therapy, there was significant suppression of growth velocity (P less than 0.001), serum gonadotropins (P less than 0.001), 17 beta-estradiol (P less than 0.005), and testosterone as well as clinical and behavioral improvement. The rate of bone maturation was reduced. All effects were reversed after discontinuation of therapy for 1 month in one girl. No reduction in efficacy was seen after changing four girls and one boy to intranasal therapy, but improved acceptability and compliance were reported by parents. Apart from withdrawal bleeding in one girl and transient acceleration of puberty in two patients during the initial phase of treatment, no serious unwanted effects occurred. Antibodies to native LHRH were not detected after 6 months of therapy. These results confirm the efficacy and safety of Buserelin by intranasal and sc routes in patients with sexual precocity and indicate a need for long term studies.

Identifying and separating the effects of practice and of cognitive ageing during a large longitudinal study of elderly community residents.

In protracted longitudinal studies of cognitive changes in old age volunteers must be repeatedly tested. Even with intervals of several years between assessment, this raises the possibility that improvements due to practice mask other changes. This problem is much more acute in brief studies of cognitive changes associated with progressive pathologies such as Alzheimer's disease or the effects of clinical interventions. Both types of study also encounter problems of selective dropout of frail and less able individuals leaving relatively 'elite' survivors. An analysis of data from repeated testing at 2-3 years intervals on the AH4 (1) intelligence test is presented to illustrate how a random effects model can be used to identify and disassociate age-related changes and practice effects at the population level, after effects of selective dropout and of background demographical variables have been taken into consideration. This analysis also provides some new, substantive empirical findings. Age-related changes are relatively slight between 49 and 70 years but much more marked between 70 and 80 years. Even with assessment points, several years apart the population average effect of practice is large relative to that of age-related change. Variation between individuals increases as samples age, providing the first clear evidence from a longitudinal study for marked individual differences in trajectories of cognitive ageing.

Gonadotropin-independent precocious puberty.

Gonadotropin-independent precocious puberty presents a challenge in diagnosis and management and in the elucidation of its pathophysiologic basis. Current therapeutic strategies reflect the fact that, irrespective of the underlying mechanism, the clinical and biochemical aspects of the disease process are consequences of gonadal autonomy. In MAS and in testotoxicosis, the most successful therapeutic maneuvers have focused on the local inhibition of steroidogenesis. Despite the positive reports on the use of MPA and cyproterone acetate, long-term experience with these preparations has been generally unsatisfactory, and there is a consensus that testolactone or ketoconazole represent optimal management. Although ketoconazole use, in our experience, has not been associated with any adverse effects either on liver function or on cortisol metabolism, the risk potential is always there. Nevertheless, its effects are dramatic in boys with testotoxicosis, and its mode of action allows for easy monitoring of its efficacy. Testolactone use in MAS, and in combination with spironolactone in testotoxicosis, appears to be relatively safe and reasonably effective. However, because serum testosterone levels are not lowered during treatment, assessment of efficacy depends largely on long-term evaluation of growth rate and of skeletal maturation. The etiology of these disorders remains unclear. The McCune-Albright syndrome is a multisystem disease and sporadic in nature. The organ involvement--ovary, thyroid, adrenal glands, bone, and kidney--is reminiscent of pseudohypoparathyroidism, ironically also bearing Albright's name (Albright's hereditary osteodystrophy, AHO). It is well established that in this syndrome, organ hypofunction associated with the AHO phenotype is caused by deficiency or dysfunction of the G-(or N) regulatory protein essential for production of intracellular cAMP and induction of specific protein kinases. The hypothesis that MAS is caused by abnormal regulation of the membrane receptor/kinase complex would seem logical. Despite its clinical similarity to MAS, the mechanism underlying testostoxicosis is clearly different. This disease is autosomal dominant and is expressed clinically only in boys. Its effects are confined to the production of gonadal autonomy. However, it is difficult to theorize how such autonomy could arise. The enzymatic reactions converting cholesterol to testosterone within the testis or adrenal gland are acquired typically through autosomal recessive inheritance, including the initial rate-limiting step of desmolase side-chain cleavage.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiodarone therapy effects on childhood thyroid function.

Thyroid function was systematically evaluated in 15 consecutive children (mean age 13.7 years, range 0.5 to 19.5 years) before and serially during treatment with amiodarone (Cordarone), a potent antiarrhythmic agent. Amiodarone is known to affect thyroid homeostasis by competitive inhibition of 5'-monodeiodinase, which converts L-thyroxine (T4) to triiodothyronine (T3) and reverse T3 (rT3) to 3,3'-diodothyronine (T2), and also by the direct effects of its high iodine content (37% by weight). Clinical and/or biochemical evidence of hypothyroidism occurred in three patients, two of whom required treatment with L-thyroxine. An additional patient had persistent hyperthyroxinemia but no clinical evidence of hyperthyroidism. Results from the patients who remained euthyroid showed characteristic alterations in serum thyroid function tests. These included significant increases in serum T4, rT3, basal thyroid-stimulating hormone and thyroid-stimulating hormone response to thyrotropin-releasing hormone testing. These changes were considered to be compensatory adjustments by the pituitary-thyroid axis to competitive inhibition of 5'-monodeiodinase by the amiodarone. Routine screening of thyroid function is needed to allow early detection of hypothyroidism when these compensations fail to occur.

Acute severe postischemic myocardial depression reversed by triiodothyronine.

The purpose of this study was to determine the effects of triiodothyronine (T3) on postischemic left ventricular performance and high-energy phosphate content in a severe injury model. Isolated working rat hearts (n = 63) received 20 mL of hyperkalemic NIH No. 1 cardioplegia and were subjected to 20 minutes of ischemia at 37 degrees C. Treated hearts were reperfused with T3-supplemented modified Krebs-Henseleit buffer. Control hearts did not receive T3 supplementation. All treated hearts (n = 44) performed work after ischemia, whereas 26% (5/19) of the control hearts were not able to perform any left ventricular work after ischemia. Comparisons with preischemic values demonstrated significant progressive hemodynamic recovery with increasing concentrations of T3 (0, 0.06, 0.15, and 0.60 ng/mL) with concomitant recovery of left ventricular stroke work index (63%, 72%, 89% [p less than 0.05], and 99% [p less than 0.05], respectively). There were corresponding increases in recovery of aortic flow, systolic pressure, cardiac index, and stroke volume index (p less than 0.05). There were no significant changes in coronary sinus flow or heart rate in any group compared with preischemic values. Comparisons of postischemic high-energy phosphate concentrations also demonstrated no change between treated and untreated groups (p greater than 0.05). We conclude that administration of T3 in a severe left ventricular injury model significantly augments rapid ventricular recovery with no change in postischemic high-energy phosphate concentrations.

Pretreatment with nicardipine preserves ventricular function after hypothermic ischemic arrest.

Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100 micrograms/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37 degrees C or 93 minutes at 24 degrees C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25 micrograms/kg significantly increased (p less than 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37 degrees C), 76% to 90% (24 degrees C); cardiac output, 61% to 90% (37 degrees C), 62% to 84% (24 degrees C); stroke work, 49% to 95% (37 degrees C), 50% to 92% (24 degrees C); and adenosine triphosphate, 76% to 87% (37 degrees C), 58% to 68% (24 degrees C). Progressive increases in postischemic function at 37 degrees and 24 degrees C were seen as the dose of nicardipine was increased from 0 to 25 micrograms/kg and decreased function was seen with a pretreatment dose greater than 25 micrograms/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations.

Cardiopulmonary bypass and thyroid function: a "euthyroid sick syndrome".

The purpose of this prospective study was to define the effect of cardiopulmonary bypass on the concentrations of thyroid hormones and metabolites. Blood samples were obtained from 14 patients preoperatively, at specific times throughout cardiopulmonary bypass, and serially to 24 hours postoperatively. Thyroid-stimulating hormone, thyroid-binding globulin, total thyroxine, triiodothyronine (T3), and reverse T3, an inactive metabolite of thyroxine, were measured by radioimmunoassay. Free T3 was assayed by equilibrium dialysis. Values of total T3 and free T3, the active hormone, were significantly depressed (75% and 50%, respectively) up to 24 hours after bypass (p less than 0.05). Reverse T3 demonstrated a greater than fourfold rise at 8 and 24 hours postoperatively (p less than 0.05). Thyroid-binding globulin was decreased at all sampling times (p less than 0.05). Thyroid-stimulating hormone, thyroxine, and free thyroxine levels remained within normal ranges at all sampling times. These results indicate that cardiopulmonary bypass simulates the "euthyroid sick syndrome" as seen in severely burned patients and critically ill patients, which is characterized by depression of T3 and free T3 concentrations with a concomitant increase in reverse T3 levels and normal concentrations of thyroid-stimulating hormone, thyroxine, and free thyroxine. The hemodynamic effects of primary hypothyroidism are well established. These data provide further support for investigational trials of intravenous administration of T3 in the prevention or treatment of low cardiac output syndrome after cardiopulmonary bypass.

Surgical treatment of lung cancer in patients with human immunodeficiency virus.

BACKGROUND: Since January 1986, more than 20 patients have been seen at the University of Miami/Jackson Memorial Medical Center and the Miami Veterans Administration Medical Center with concurrent human immunodeficiency virus infection and bronchogenic carcinoma. Four of these patients were treated surgically with curative intent. METHODS: The histories, records, operative reports, and pathology reports of the 4 patients were reviewed. RESULTS: The 4 surgically treated patients had stage I T1 N0 M0 lung cancer. Three patients had T4 cell counts of less than 200/microL and were managed by lobectomy. These patients died 5, 3 1/2, and 5 months postoperatively. More recently, a fourth patient had a T4 cell count of 963/microL and was treated with wedge resection. He is currently alive 12 months postoperatively. CONCLUSIONS: It is concluded that surgically treated patients with lung cancer, human immunodeficiency virus infection, and T4 cell counts lower than 200/microL have high mortality and morbidity. Although it may be best to base surgical intervention on the stage of the patient's human immunodeficiency virus infection, further analysis is essential to determine which subgroup of human immunodeficiency virus-positive patients, if any, would benefit from surgical treatment of lung cancer.

Magnesium ion is beneficial in hypothermic crystalloid cardioplegia.

The role of magnesium ion and its relation to the calcium concentration of cardioplegic solutions was reexamined in this study. Isolated rat hearts were used with an oxygenated modified Krebs-Henseleit bicarbonate buffer as perfusion medium. The hearts were arrested for 20 minutes at 37 degrees C or 90 minutes at 24 degrees C. Treatment groups received one dose of nine possible cardioplegic solutions containing magnesium (0, 1.2, or 15 mmol/L) and calcium (0.05, 1.5, or 4.5 mmol/L). Ninety-six percent of the 75 magnesium-treated hearts recovered, regardless of the calcium concentration, in contrast to a 52% recovery rate in the 69 hearts that did not receive magnesium. The addition of 15 mmol/L Mg2+ to a cardioplegic solution containing no magnesium but 0.05 mmol/L Ca2+ significantly increased (p less than 0.01) the percent recovery of the following parameters of cardiac function: systolic pressure, 74% to 93% (37 degrees C), 64% to 98% (24 degrees C); cardiac output, 76% to 101% (37 degrees C), 71% to 102% (24 degrees C); stroke work, 64% to 104% (37 degrees C), 52% to 99% (24 degrees C); and adenosine triphosphate level, 75% to 83% (37 degrees C), 58% to 90% (24 degrees C). There were significant reductions (p less than 0.03) in percent recovery (37 degrees C and 24 degrees C) of cardiac output, stroke work, and adenosine triphosphate level in the groups that contained 0 or 15 mmol/L Mg2+ as the calcium concentration was increased from 0.05 to 4.5 mmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical treatment for cardiac rhabdomyomas in children.

Cardiac rhabdomyomas are the most common cardiac tumor in children. These tumors may cause obstruction to blood flow, valvular insufficiency, and cardiac arrhythmias. We present two cases of cardiac rhabdomyomas in infants that were managed surgically and review the literature. Without surgical intervention, the prognosis for symptomatic cardiac rhabdomyomas is dismal, with eventual death likely due to heart failure or arrhythmias. As our two cases indicate, surgical treatment may improve this prognosis. Pediatric cardiac rhabdomyomas should be resected when the tumors cause hemodynamic compromise or cardiac arrhythmias.

A randomized trial of postoperative five-versus three-drug chemotherapy after mastectomy: a Cancer and Leukemia Group B (CALGB) study.

The Cancer and Leukemia Group B (CALB) has conducted a randomized study of adjuvant chemotherapy in patients with breast cancer who have involved axillary nodes at the time of mastectomy. Five-drug treatment (CMFVP) was compared with three-drug treatment (CMF). For patients with more than three involved nodes, the CMFVP regimen produced a significantly prolonged disease-free survival in comparison to the CMF regimen.

Birth weight and body mass index in childhood, adolescence, and adulthood as predictors of blood pressure at age 36.

STUDY OBJECTIVE: The purpose of this study was to investigate the relation between blood pressure at age 36, and birth weight and body mass index (BMI) in childhood, adolescence and adulthood. DESIGN: Prospective longitudinal survey over a period of 36 years in England, Scotland, and Wales. PARTICIPANTS: A nationally representative sample consisting of 3332 men and women born in one week in March 1946. Altogether 82% of these subjects had complete data for the present analysis. MAIN RESULTS: There was an inverse linear relation between birth weight and blood pressure at age 36. The relation between BMI and blood pressure at age 36 was initially inverse and became increasingly positive throughout life. Weight gain in childhood was positively associated with adult blood pressure, although less important than weight change in later life. The associations between blood pressure and birth weight, and blood pressure and adult BMI were independent, and together they accounted for no more than 4% of the variation in adult blood pressure. Both low birth weight (birth weight < or = 2.5kg) and high BMI at age 36 (BMI > 30kg/m2) were associated with hypertension (> 140/90mmHg), but the per cent population risk of hypertension attributable to low birth weight was less than 5%, and to high BMI less than 12%. CONCLUSIONS: Low birth weight and high BMI at age 36 were independently related to high blood pressure. A reduction in the percentage of low birthweight babies born in the fourth decade of this century would only have a negligible effect on the incidence of adult hypertension 30-40 years later.