A longitudinal study of body mass index and lens opacities. The Framingham Studies

OBJECTIVES: Chlorpromazine is a known modulator of tumor necrosis factor (TNF)-alpha production. TNF-alpha is thought to be a key mediator in the development of the multiple organ dysfunction syndrome (MODS). We investigated the effect of chlorpromazine on the development of zymosan-induced MODS in mice and on plasma TNF-alpha concentrations and production capacity of TNF-alpha by peritoneal cells. DESIGN: Prospective, controlled laboratory study on zymosan-induced generalized inflammation in mice. SETTING: Animal research laboratory. SUBJECTS: C57BL/6 mice received daily doses (4 mg/kg body weight) of chlorpromazine, beginning 2 days before or 5 days after zymosan administration. In additional groups, the daily chlorpromazine dose of 4 mg/kg started 5 days after zymosan was increased 2 days later to 8 or 16 mg/kg/day. MEASUREMENTS AND MAIN RESULTS: The animals were monitored for survival, condition, body weight, and body temperature. Twelve days after zymosan was administered, all surviving animals were killed to obtain plasma, organs, and peritoneal cells. Plasma concentrations of TNF-alpha and lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells were measured. Organ weights were recorded as an indicator for organ damage. Although survival was not improved when the animals were treated with chlorpromazine, the chlorpromazine-treated survivors showed improved body weight and temperature when compared with the animals receiving zymosan only. Also, the organ weights and lung damage improved significantly in the treated group. Chlorpromazine was most effective when started before zymosan administration. When administered afterward, clinical improvement declined with the dose. In all cases, circulating TNF-alpha and production of TNF-alpha by peritoneal macrophages were lowered toward control values. CONCLUSION: Chlorpromazine mitigates the development of zymosan-induced MODS, possibly by reducing macrophage TNF-alpha production.     

Certainty of paternity and paternal investment in eastern bluebirds and tree swallows

Extra-pair paternity is common in many socially monogamous passerine birds with biparental care. Thus, males often invest in offspring to which they are not related. Models of optimal parental investment predict that, under certain assumptions, males should lower their investment in response to reduced certainty of paternity. We attempted to reduce certainty of paternity experimentally in two species, the eastern bluebird, Sialia sialis, and the tree swallow, Tachycineta bicolor, by temporarily removing fertile females on two mornings during egg laying. In both species, experimental males usually attempted to copulate with the female immediately after her reappearance, suggesting that they experienced the absence of their mate as a threat to their paternity. Experimental males copulated at a significantly higher rate than control males. However, contrary to the prediction of the model, experimental males did not invest less than control males in their offspring. There was no difference between experimental and control nests in the proportion of male feeds, male and female feeding rates, nestling growth and nestling condition and size at age 14 days. We argue that females might have restored the males' confidence in paternity after the experiment by soliciting or accepting copulations. Alternatively, males may not reduce their effort, because the fitness costs to their own offspring may outweigh the benefits for the males, at least in populations where females cannot fully compensate for reduced male investment. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.     

A double-blind, placebo-controlled study of intranasal apomorphine spray as a rescue agent for off-states in Parkinson''s disease

Physico-chemical and morphologic parameters of skin layers and subcutaneous tissue in lymphedematous limb were studied in vivo using magnetic resonance imaging. High resolution images were obtained with a depth resolution of about 70 microm, using a specific surface gradient coil specially designed for skin imaging and connected to a standard whole-body imager at 1.5 T. Twenty-one patients with unilateral lower extremity lymphedema (11 primary and 10 secondary) were examined. Skin thickness, relaxation times, and relative proton density were calculated in lymphedematous limbs and in contralateral extremities. In diseased limbs, the average skin thickness (2.17 mm) was significantly larger (p = 1.5 x 10(-4)) than that of contralateral limb (1.14 mm). Major cutaneous alterations due to lymphedema took place in dermis. In lymphedematous dermis, the significant increase of relaxation time values could be due to a shift in the equilibrium of water inside this tissue in relation to the interactions between macromolecules and water molecules. In lymphedematous epidermis our results showed an increase in the number of free water protons. Information about water and fat distribution in lymphedema was also obtained using chemical shift weighted images. Our results demonstrated a water retention diffusely spread over the entire dermis, and an important fluid retention located in the interlobular spacing and beside the superficial fascia. Inside the subcutis, the mean thickness of the superficial fat lobules was increased more than that of the deep fat lobules. From all the various measurements we could not distinguish primary from secondary lymphedema.     

Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B

BACKGROUND: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. METHODS: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. RESULTS: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. CONCLUSION: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.     

Jozef B. Cohen: 1921-1995

The distribution of alleles with various CTG-repeat numbers was studied and the haplotypes for polymorphic sites HhaI and HinfI of mouse muscle protein kinase (DMPK) were analyzed in inhabitants of northwestern Russia and in patients with myotonic dystrophy (90 and 18 chromosomes, respectively). Twelve normal alleles with the triplet-repeat number from 5 to 24 were identified and the alleles with five (42.5%) and 11-13 (37%) repeats were found to be predominant. The bimodal distribution revealed is similar to those described earlier for other populations, however, the frequencies of individual alleles differed from those in populations of Europe and Central Russia. No significant differences in frequencies of CTG alleles were found in 32 normal chromosomes involved in compounds with the mutant chromosomes (i.e., in patients with myotonic dystrophy) as compared to their frequencies in the population. However, almost all mutant chromosomes (16 of 18) had the same haplotype for intragenic polymorphic sites: HhaI-; HinfI+. This haplotype was also inherent in 91% of all chromosomes with CTG5 and all chromosomes with a CTG number more than 15. Possible evolution of chromosomes with different numbers of triplet repeats mediating their expansion and impairing the function are discussed.     

Resuscitation preferences among patients with severe congestive heart failure: results from the SUPPORT project. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments

BACKGROUND: Previous studies have shown wide variation in plasma dexamethasone (DEX) concentrations following a standard 1-mg dexamethasone suppression test (DST), and significantly lower DEX concentrations in DST nonsuppressors compared with suppressors, suggesting that DEX pharmacokinetics/bioavailability is an important variable associated with DST nonsuppression. METHODS: To determine the effect of plasma DEX levels on the DST in Chinese depressives, we measured plasma DEX and post-DEX cortisol levels at 4:00 PM in a group of 50 depressed outpatients, 28 anxiety outpatients, and 33 normal subjects during the course of 1-mg oral overnight DST. RESULTS: We found a significant difference in the plasma DEX levels between DST nonsuppressors and suppressors in the depression group and overall subject population, and a significant negative correlation between the plasma DEX and cortisol levels in the depression, anxiety, and total groups. Within a DEX "window", the DST performance was enhanced, whereas the relationships between plasma DEX and post-DEX cortisol levels remained equally strong. CONCLUSIONS: Our findings support a relationship between plasma DEX and post-DEX cortisol levels, a relationship that might be superimposed on the hypothalamic-pituitary-adrenal axis. Comparing our "window" range with those of previous studies, we suggest that Chinese depressives may have lower limits of plasma DEX window, and that ethnicity may be an intervening variable in both DST response and pharmacokinetics of DEX.     

Test/retest reproducibility of iodine-123-betaCIT SPECT brain measurement of dopamine transporters in Parkinson's patients

Iodine-123-beta-CIT has been used as a probe of dopamine transporters in Parkinson's disease patients using SPECT. We studied the test/retest reproducibility of SPECT measures in Parkinson's disease patients and healthy controls obtained after injection of [123I])beta-CIT in part to assess the utility of this tracer for longitudinal evaluation of striatal dopamine transporters as a marker of disease progression. METHODS: Seven Parkinson's disease patients and seven healthy control subjects participated in two [123I]beta-CIT SPECT scans separated by 7-21 days. Subjects were imaged at 24 hr post injection of 360 MBq (9.7 mCi) of [123I]beta-CIT. Two outcome measures were evaluated; 1) the ratio of specific striatal (activity associated with DA transporter binding) to nondisplaceable uptake, also designated V3," and 2) the total specific striatal uptake (%SSU) expressed as a percentage of injected radiotracer dose. For both measures, test/retest variability was calculated as the absolute difference of test minus retest divided by the mean of test/retest and expressed as a percent. In addition, the reproducibility of left and right striatal asymmetry and putamen:caudate ratios were determined. RESULTS: The two outcome measures demonstrated excellent test/retest reproducibility for both the Parkinson's disease and healthy subject groups with variability of striatal V3" = 16.8 +/- 13.3% and percent striatal uptake = 6.8 +/- 3.4% for Parkinson's disease patients and V3" = 12.8 +/- 8.9% and %SSU = 7.0 +/- 3.9% for control subjects. There were no statistically significant differences in test/retest variability between control subjects and Parkinson's disease patients for either outcome measure. The reproducibility of left/right asymmetry indices and putamen-to-caudate ratios showed no patient versus control subject differences. The asymmetry index had greater test/retest variability than the other outcome measures. CONCLUSION: These data suggest that SPECT imaging performed at 24 hr postinjection of [123I]beta-CIT permits calculation of reliable and reproducible measures of dopamine transporters in both Parkinson's disease patients and control subjects and supports the feasibility of using [123I]beta-CIT in the evaluation of disease progression in Parkinson's disease.     

Arthroscopic transglenoid multiple suture repair: 2 to 8 year results in 150 shoulders

Although treatment for hypertension is readily available, poor control of hypertension is a major health problem frequently manifested in late life. Researchers believe that one of the major causes of uncontrolled hypertension is failure to take medication as directed. In this preliminary study, the medication-taking behaviors of 48 adults diagnosed with hypertension, ranging in age from 35 to 87, were recorded for 2 months with credit card-sized bar-code scanners. The social-cognitive model (Park, 1992) for understanding medication adherence, which proposes that medication adherence is governed by both beliefs and cognitive factors, was used as a basis for this research. Therefore, measures of health behaviors, attitudes about health and medication taking, and cognitive function were recorded, as well as blood pressure readings. The main findings were that (a) the oldest-old and groups of middle-aged adults were the most nonadherent, whereas the young-old were more likely to adhere than the other age groups; (b) high blood pressure readings predicted adherence to antihypertensive medications; and (c) medication beliefs influenced adherence in some situations.     

Independent segregation of von Hippel-Lindau disease and cerebral cavernomas

A probable diagnosis of von Hippel-Lindau disease was made in a two generation family in which the proband had a phaeochromocytoma, renal cysts, and multiple cerebral cavernomas. His sister had multiple similar cerebral vascular lesions and his father died from renal carcinoma aged 42. Although the family did not satisfy the conventional diagnostic criteria for von Hippel-Lindau disease, an underlying germline mutation in the von Hippel-Lindau disease tumour suppressor gene was identified in the proband. Molecular genetic analysis not only confirmed the putative diagnosis of the disease in the proband but also showed that the cerebral vascular lesions segregated independently from the von Hippel-Lindau disease mutation. This report exemplifies how molecular genetic investigations can enhance the diagnosis and management of families with suspected von Hippel-Lindau disease, particularly when the manifestations, as in this family, are not typical.