Small for gestational age associated with short stature during adolescence

This study examined the relationship between intrauterine growth retardation and adolescent stature in a sample of 1510 White subjects (754 males and 756 females) who were evaluated at birth and at the ages of 15, 16, and 17 years. The subjects were classified into two groups based on birthweight, small for gestational age (SGA) and appropriate for gestational age (AGA), corresponding respectively to values below the 10th, and between the 11th and 99th, percentiles of gestational age and sex. Results showed that boys and girls born prematurely (gestational age < 37 weeks of gestation) attained the same stature as those born at full term (>37 weeks of gestation). In contrast, those born SGA were significantly shorter than their counterparts born AGA. The average reduction in stature was 4.9 cm for males and 2.9 cm for females. When the analysis included adjustments for parental stature (and adolescent's age at menarche for females), the average reduction in stature equaled about 3.5 cm for males and 2.0 cm for females. It is thus concluded that the stature deficit reflects a reduction in growth rate rather than delay in maturation. © 1994 Wiley-Liss, Inc.     

Relation of psychological vulnerability factors to posttraumatic stress disorder symptomatology in bone marrow transplant recipients

OBJECTIVE: Prior research suggests that the diagnosis and treatment of cancer can result in the development of symptoms of posttraumatic stress disorder (PTSD). Based on Lazarus and Folkman's model of stress, the current study examined whether trauma appraisals, coping, social support, and social constraint were associated with the severity of PTSD symptoms in cancer patients who had undergone bone marrow transplantation (BMT). METHODS: Participants were 23 males and 79 females treated with BMT an average of 20 months previously (range = 3-62 months). Past and current psychiatric diagnoses were assessed through a structured clinical interview. PTSD symptomatology and other psychological variables were assessed using standardized self-report measures. RESULTS: Results indicated that 5% of participants met diagnostic criteria for current PTSD. Participants reported an average of three to four symptoms of PTSD (range = 0-16). Univariate analyses confirmed predictions that increased PTSD symptomatology would be associated with more negative appraisals of the BMT experience, greater use of avoidance-based coping strategies, lower levels of social support, and greater social constraint (p < .05). Regression analyses indicated that each of these variables accounted for significant (p < .05) variability in PTSD symptomatology above and beyond relevant demographic and medical variables. CONCLUSIONS: Results of the present study confirm and extend prior research regarding the prevalence of PTSD and PTSD symptoms among patients treated for cancer. In addition, the study identified a set of theoretically derived psychological characteristics that seem to place patients at risk for greater PTSD symptomatology after BMT.     

Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease

The idiopathic inflammatory bowel diseases (IBDs), consisting of Crohn's disease and ulcerative colitis, are complex genetic disorders involving chronic inflammation of the intestines. Multiple genetic loci have been implicated through genome-wide searches, but refinement of localization sufficient to undertake positional cloning efforts has been problematic. This difficulty can be obviated through identification of ancestrally shared regions in genetic isolates, such as the Chaldean population, a Roman Catholic group from Iraq. We analyzed four multiply affected American Chaldean families with inflammatory bowel disease not known to be related. We observed evidence for linkage and linkage disequilibrium in precisely the same region of chromosome band 1p36 reported previously in an outbred population. Maximal evidence for linkage was observed near D1S1597 by multipoint analysis (MLOD = 3.01, P = 6.1 x 10(-5)). A shared haplotype (D1S507 to D1S1628) was observed over 27 cM between two families. There was homozygous sharing of a 5 cM portion of that haplotype in one family and over a <1 cM region in the second family. Homozygous sharing of this haplotype near D1S2697 and D1S3669 was observed in one individual in a third multiply affected family, with heterozygous sharing in a fourth family. Linkage in outbred families as well as in this genetic isolate indicates that a pathophysiologically crucial IBD susceptibility gene is located in 1p36. These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder.     

The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?

The ventral tegmental area (VTA) and in particular VTA dopamine (DA) neurons are postulated to play a central role in reward, motivation and drug addiction. However, most evidence implicating VTA DA neurons in these functions is based on indirect electrophysiological characterization, rather than cytochemical identification. These physiological criteria were first established in the substantia nigra pars compacta (SNc), but their validity in the VTA is uncertain. In the current study we found that while 88 ± 2% of SNc neurons labelled by the neuronal marker NeuN were co-labelled for the catecholamine enzyme tyrosine hydroxylase (TH), a much smaller percentage (55 ± 2%) of VTA neurons co-expressed TH. In addition, using in vitro whole-cell recordings we found that widely accepted physiological criteria for VTA DA neurons, including the hyperpolarization-activated inwardly rectifying non-specific cation current ( I _h), spike duration, and inhibition by DA D2 receptor agonists, do not reliably predict the DA content of VTA neurons. We could not distinguish DA neurons from other VTA neurons by size, shape, input resistance, I _h size, or spontaneous firing rate. Although the absence of an I _h reliably predicted that a VTA neuron was non-dopaminergic, and I _h(−) neurons differ from I _h(+) neurons in firing rate, interspike interval (ISI) standard deviation, and ISI skew, no physiological property examined here is both sensitive and selective for DA neurons in the VTA. We conclude that reliable physiological criteria for VTA DA neuron identification have yet to be determined, and that the criteria currently being used are unreliable.     

Alternate paths from epidermal growth factor receptor to Akt in malignant versus nontransformed lung epithelial cells: ErbB3 versus Gab1

In many human lung adenocarcinoma cell lines, a pathway involving epidermal growth factor receptor (EGFR), ErbB2 and ErbB3 receptors, phosphatidyl inositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3-beta (GSK3-beta), and cyclin D1 controls cell growth, survival, and invasiveness. We have investigated this pathway in paired transformed/nontransformed cell lines from murine peripheral lung epithelium, E9/E10 and A5/C10. The E9 and A5 carcinoma lines expressed ErbB3 and transforming growth factor-alpha (TGF-alpha) and responded to TGF-alpha stimulation with protein complex formation including the p85 regulatory subunit of PI3K, activation of Akt, phosphorylation of GSK3-beta, and increased cyclin D1 protein and the cell cycle. ErbB3 and TGF-alpha were not detected in the nontransformed E10 and C10 cell lines. Nevertheless, exposure of E10 or C10 cells to TGF-alpha activated PI3K and Akt and increased cyclin D1 and cell growth. The effector pathway from the EGFR to PI3K in these nontransformed cells included the adaptor Grb2, the docking protein Gab1, and the phosphatase Shp2. Gab1 was highly expressed in E10 and C10 cells but not in the malignant E9 and A5 sister lines. Complexes of EGFR/Grb2/Gab1/Shp2 after TGF-alpha stimulation were prominent only in E10 and C10 cells. Thus, alternate pathways downstream of EGFR regulate mitosis in these paired malignant versus nontransformed lung cell lines.     

A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes.

BACKGROUND. Although psychoactive medications have substantial side effects in the elderly, these drugs are used frequently in nursing homes. Few interventions have succeeded in changing this situation, and little is known about the clinical effects of such interventions. METHODS. We studied six matched pairs of nursing homes; at one randomly selected nursing home in each pair, physicians, nurses, and aides participated in an educational program in geriatric psychopharmacology. At base line we determined the type and quantity of drugs received by all residents (n = 823), and a blinded observer performed standardized clinical assessments of the residents who were taking psychoactive medications. After the five-month program, drug use and patient status were reassessed. RESULTS. Scores on an index of psychoactive-drug use, measuring both the magnitude and the probable inappropriateness of medication use, declined significantly more in the nursing homes in which the program was carried out (experimental nursing homes) than in the control nursing homes (decrease, 27 percent vs. 8 percent; P = 0.02). The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes (32 percent vs. 14 percent); the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent, and for antihistamine hypnotics, 45 percent vs. 21 percent. In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities, but they were more likely to report depression. Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory. Most other measures of clinical status remained unchanged in both groups. CONCLUSIONS. An educational program targeted to physicians, nurses, and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents.     

Serodiagnosis of viral hepatitis A by a modified competitive binding radioimmunoassay for immunoglobulin M anti-hepatitis A virus.

A competitive binding radioimmunoassay (CBA) for antibody to hepatitis A virus (HAV) was evaluated and compared with a standard solid-phase radioimmunoassay for anti-HAV, CBA was found to be sensitive and specific for the detection of anti-HAV, as demonstrated by the 98% concordance of CBA and solid-phase radioimmunoassay test results. The standard CBA test was modified for the differential detection of acute (immunoglobulin M) and convalescent (immunoglobulin G) anti-HAV by incorporation of a step in which immunoglobulin G anti-HAV was preferentially absorbed with S. aureus cells (protein A). The modified CBA test was shown to be capable of differentiating between acute- and convalescent-phase sera. The modified CBAM test was able to detect immunoglobulin M anti-HAV up to approximately 4 weeks after the onset of illness.     

Selection of a mutant S1 gene during reovirus persistent infection of L cells: role in maintenance of the persistent state

LR-7 cells, variant L cells derived from a type 3 reovirus persistently infected (p.i.) carrier culture (R. Ahmed, W. M. Canning, R. S. Kauffman, A. H. Sharpe, J. V. Hallum, and B. N. Fields, Cell 25, 325-332, 1983) were used to define the viral genes critical for maintenance of the persistent state. A cloned viral isolate (L/C virus) derived from the p.i. culture replicated normally in LR-7 cells, while wild-type (wt) viruses of the three reovirus serotypes replicated less efficiently. To identify the viral gene(s) permitting enhanced replication of L/C virus in LR-7 cells, viral reassortants were prepared by mixed infection of L cells with L/C virus and type 1 wt. Study of the one-step growth curves and final yields of large numbers of reassortants in both L cells and LR-7 cells revealed that the presence of the S1 gene from L/C virus was critical for normal viral replication in LR-7 cells. However, this phenotype was suppressed by the simultaneous presence in reassortants of both the M2 and S4 genes from the type 1 wt parent. The critical change in the S1 gene occurred by passage 13 (63 days) after initiation of the carrier culture. Although multiple mutations are present in the viral population from p.i. cultures, certain specific mutations can be identified as critical for maintenance of the persistent state.     

藏汉民族线粒体基因组全序列的比较研究

目的 以藏汉民族线粒体基因组全序列为基础,进行Haplogroup构建和系统发生分析,在全序列水平上比较核苷酸的变异,阐释可能的变异机制和蕴含的生物学意义.方法 采用Applied Biosystems 3730DNA自动测序仪分别对40名藏族和50名汉族的标本进行线粒体DNA序列测定,应用phredPhrap 16.0软件进行全序列拼接,并以rCRS(revised Cambridge Reference Sequence)为标准与测定序列进行比对分析;根据MTTO-MAP的标准,通过Network方法进行Haplogroup构建和系统发生的分析,并结合其它方法对产生的数据进行深入解读.结果 数据分析结果显示:在系统发生上,藏汉民族90个线粒体DNA序列归类到13个Haplogroups,除M9以外,其它各Haplogroup出现频率之间比较差异无统计学意义;通过两个民族的线粒体DNA全序列比对,发现21个分布频率有统计学意义的变异位点,其中的5个为新变异位点;另外,对D-Loop区的5个突变位点进行了单倍型构建,90个标本可分为2种Supertype,发现在藏汉民族之间Supertypel和Supertype 2的分布频率均有统计学意义.结论 藏汉民族在种族起源和系统发生上具有较近的母系遗传关系;在全序列有统计学意义的位点究竟是适应性或者中性选择,抑或是一种病理性突变尚需深入的探讨.     

Cognitive impairment. Can it predict the course of hospitalized patients?

All patients admitted to three medical services at the New York Hospital during a one-month period were screened with Folstein's Mini-Mental State Examination. The prevalence of cognitive impairment was 19.8% (23 of 116). Cognitively "impaired" patients, ie, those with a Folstein score less than 24, were older, sicker, and less physiologically stable than the cognitively "intact." The in-hospital mortality (17 versus 5%) and morbidity (39 versus 18%) rates were higher for the cognitively "impaired" patients; these differences could be explained by the greater severity of illness, instability, and comorbidity found in these patients. Cognitively "impaired" patients were particularly susceptible to respiratory complications. Cognitively "impaired" patients had longer lengths of hospital stay, spent more time in hospital awaiting placement, and were more likely to be discharged to a nursing home or require home assistance than their cognitively "intact" counterparts. Three-month mortality rates were also higher for the cognitively "impaired" patients (30 versus 15%). These findings suggest that cognitive impairment on admission may be regarded as a marker for patients with poorer prognoses.