Assessment of variance components models on pedigrees using cholesterol, low-density, and high-density lipoprotein measurements

Plasma total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) measurements on 402 individuals in 62 randomly selected families from the Columbia Medical Plan population were used to select the "best" model among a series of multifactorial models using the maximum likelihood method described by Lange et al [1976]. These models included both genetic and nongenetic components of variance. The most parsimonious model for each trait was selected and examined using a goodness-of-fit statistic designed by Hopper and Mathews [1982] to test the assumptions of this technique. A simple additive genetic model was the most plausible for all three measurements, suggesting a strong role for genetic factors in determining lipid and lipoprotein levels in these data. Goodness-of-fit statistics for these models were examined and showed little evidence of deviation from the assumption of multivariate normality within pedigrees. This approach of selecting the most parsimonious model among a series of competing models and then assessing its goodness-of-fit has many applications in studying familial aggregation of quantitative traits.     

Activation dependence and kinetics of force and stiffness inhibition by aluminiofluoride,a slowly dissociating analogue of inorganic phosphate,in chemically skinned fibres from rabbit psoas muscle

Summary To examine the mechanism by which aluminiofluoride, a tightly binding analogue of inorganic phosphate, inhibits force in single, chemically skinned fibres from rabbit psoas muscle, we measured the Ca²⁺-dependence of the kinetics of inhibitor dissociation and the kinetics of actomyosin interactions when aluminiofluoride was bound to the crossbridges. The relation between stiffness and the speed of stretch during small amplitude ramp stretches (< 5 nm per h.s.) was used to characterize the kinetic properties of crossbridges attached to actin; sarcomere length was assessed with HeNe laser diffraction. During maximum Ca²⁺-activation at physiological ionic strength (pCa 4.0, 0.2 m /2), stiffness exhibited a steep dependence on the rate of stretch; aluminiofluoride inhibition at pCa 4.0 (0.2 m /2) resulted in an overall decrease in stiffness, with stiffness at high rates of stretch (10³–10⁴ nm per h.s. per s) being disproportionately reduced. Thus the slope of the stiffness-speed relation was reduced during aluminiofluoride inhibition of activated fibres. Relaxation of inhibited fibres (pCa 9.2, 0.2 m /2) resulted in aluminiofluoride being trapped and was accompanied by a further decrease in stiffness at all rates of stretch which was comparable to that found in control relaxed fibres. In relaxed, low ionic strength conditions (pCa 9.2, 0.02 m /2) which promote weak crossbridge binding, stiffness at all rates of stretch was significantly inhibited by aluminiofluoride trapped in the fibre. To determine the Ca²⁺-dependence of inhibitor dissociation, force was regulated independent of Ca²⁺ using an activating tropinin C (aTnC). Results obtained with aTnC-activated fibres confirmed that there is no absolute requirement for Ca²⁺ for recovery from force inhibition by inorganic phosphate analogues in skinned fibres; the only requirement is thin filament activation which enables active crossbridge cycling. These results indicate that aluminiofluoride preferentially inhibits rapid equilibrium or weak crossbridge attachment to actin, that aluminiofluoride-bound crossbridges attach tightly to the activated thin filament, and that, at maximal (or near-maximal) activation, crossbridge attachment to actin prior to inorganic phosphate analogue dissociation is the primary event regulated by Ca²⁺.     

Intermediate filament expression by normal and diseased human corneal epithelium

Cicatricial conjunctivitis may be a sequel to systemic disorders (eg, Stevens-Johnson syndrome, cicatricial pemphigoid) or local disorders such as chemical burns. The cicatrisation is often associated with corneal epithelial changes that cause visual loss. These have been attributed to encroachment of the conjunctival epithelium over the cornea. However, the epithelial anomalies are poorly understood. We investigated the corneal epithelial changes in cicatricial conjunctivitis with an immunohistochemical study of intermediate filaments in normal and pathological specimens. Our results show that the normal corneal epithelium is immunoreactive for cytokeratin 3 (CK 3) but not cytokeratin 19 (CK 19), whereas normal conjunctival epithelium is CK 3 negative and CK 19 positive. Conjunctiva artificially transposed over the cornea (after therapeutic conjunctival flap reconstruction) retained the normal pattern of conjunctival cytokeratin expression (CK 3 negative, CK 19 positive). Conversely, the entire corneal epithelium exhibited the normal cytokeratin pattern (CK 3 positive, CK 19 negative) in 82% of Stevens-Johnson, 80% of cicatricial pemphigoid, and 69% of chemical burns specimens. The findings suggest that conjunctival encroachment is not responsible for the changes at the corneal surface in cicatricial conjunctivitis and that the abnormal corneal epithelium is derived from native corneal cells in these diseases.     

Leukoencephalopathy in normal and pathologic aging: 1. CT of brain lucencies

Central white matter lucencies are commonly seen in CT scans of elderly patients. Reports in the literature have implicated demyelination due to subcortical vascular disease (Binswanger disease) as the cause of these lucencies. Binswanger disease, however, is thought to be rare. Because of this apparent discrepancy we decided to determine the incidence and to attempt to define the clinical significance of the CT white-matter changes in a study population at New York University Medical Center. The studies of 275 normal and demented subjects, ages 23 to 85 years, were reviewed. All subjects received neurologic, psychiatric, and medical evaluation, formal psychometric evaluation of their cognitive status, and a CT scan. CT scans were evaluated for the presence and severity of white-matter changes (leukoencephalopathy). The incidence and severity of white-matter changes increased significantly with age (p less than 0.01). Leukoencephalopathy was consistently more common in demented patients than in normal subjects, but the difference was not statistically significant, and the severity of the leukoencephalopathy was not related to the severity of dementia (p less than 0.05). Five patients (ages 74 to 95 years) with a clinical diagnosis of Alzheimer disease who had CT evidence of lucencies were examined at autopsy. Neuropathology demonstrated extensive changes of Alzheimer disease in one brain and mild-to-moderate changes in the other four brains; areas of white-matter rarefaction were present in all brains, with microscopic evidence of arteriolar hyalinization. This study demonstrates that leukoencephalopathy is strongly related to the aging process and is seen in both "normal" and cognitively impaired individuals who have no other evidence of vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flexor Tenosynovectomy for Recurrent Carpal Tunnel Syndrome: A Retrospective Case Series of 108 Hands

Background: The etiology of recurrent carpal tunnel syndrome (CTS) is unclear, and outcomes following secondary surgery in this demographic have been poorer than primary surgery. Fibrosis and hypertrophy have been identified in the flexor tenosynovium in these patients. The authors use flexor tenosynovectomy (FTS) for recurrent CTS after primary carpal tunnel release and present a review of these patients. Methods: A retrospective chart review was performed of 108 cases of FTS for recurrent CTS from 1995 to 2015 by 4 attending surgeons at one institution. Demographic information, symptoms, and outcomes were among the data recorded. A phone survey was conducted on available patients where the shortened version of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH) and satisfaction were assessed. Results: Average office follow-up was 12 months. Average age was 57.5 years. A total of 104 (96%) reported symptom improvement and 48 (44%) reported complete symptom resolution. Forty patients were available for long-term follow-up at an average 6.75 years postoperatively via phone interview. Average QuickDASH score was 31.2 in these patients. Thirty-six (90%) of 40 patients were initially satisfied at last office visit, and 31 (78%) of 40 were satisfied at average 6.9 years, a maintenance of satisfaction of 86%. Satisfied patients were older (58 years) than unsatisfied patients (51 years). Conclusion: Both long-term satisfaction and QuickDASH scores in our cohort are consistent with or better than published results from nerve-shielding procedures. The authors believe a decrease in both carpal tunnel volume and potential adhesions of fibrotic or inflammatory synovium contributes to the benefits of this procedure. This remains our procedure of choice for recurrent CTS.     

In vitro and in vivo cytotoxicity of rhodamine 123 combined with hyperthermia

Because both Rhodamine 123 (R123) and hyperthermia have been shown to be cytotoxic, we examined their effect, independently and in combination, on five different human malignant cell lines in vitro and on cultured melanoma cells grown intradermally in nude mice. The cell lines examined include two human melanomas, UCLA-SO-M14 and UCLA-SO-M21, the colon cancer cell line HT29, the human lung cancer cell line P3, and the human breast cancer cell line B231. R123 and hyperthermia, when used in combination, were found to be cytotoxic for these five different human malignant cell lines in vitro. The two agents together appear to enhance the cytotoxic effect of each alone, as documented by synergistic ratios ranging from 2.31 to 45 for the different cell lines. In the "nude" mouse model, animals were treated with a combination of R123 and hyperthermia (43 degrees C for 90 min). A statistically significant (P = 0.04) decrease in tumor growth rate was observed when compared with the rate of tumor growth in untreated animals. The results suggest a potential role for R123 in combination with hyperthermia in the treatment of malignant cells.     

乳头腺管口挑拨治疗急性乳腺炎32例

0　引言　急性乳腺炎是产后妇女的常见病 .我们采用针头挑拨治疗急性乳腺炎 32例 ,疗效显著 .1　临床资料　患者 32例 ,年龄 2 3～ 34 (平均 2 5 .3)岁 ,均为产后哺乳产妇 .其中患乳胀痛为共有症状 .伴发热 10例 ;右侧乳腺炎 14例 ,左侧乳腺炎 16例 ,双侧乳腺炎 2例 ;外上象限胀痛 6例 ,外下象限胀痛 8例 ,内上象限胀痛 7例 ,内下象限胀痛 6例 ,二象限同时胀痛 5例 .乳头均无破损 .患者取卧位 ,显露患乳 ,乳头以碘伏严密消毒后 ,术者持五号针头以指腹常规触诊患乳 ,触摸到肿胀部位后 ,沿乳腺管走行方向找到对应的乳头腺管口 ,以针尖轻轻挑拨…