Ventilatory and upper-airway resistance responses to upper-airway cooling and CO2 in anaesthetised rats

The effects of upper airway (UA) cool air and CO₂ on breathing and on laryngeal and supraglottic resistances were studied in anaesthetised rats breathing spontaneously through a tracheostomy. Warm, humidified air containing 0, 5 and 9–10% CO₂ and cool, room-humidity air were delivered at constant flow to either the isolated larynx to exit through a pharyngotomy or to the supraglottic UA to exit through the mouth and/or nose (nose open or sealed). Spontaneous tracheal airflow and UA airflows, temperatures and pressures were recorded. CO₂ had no effect on breathing but caused a slight increase in laryngeal resistance which was abolished by cutting the superior laryngeal nerves (SLN). Cool air caused a decrease in respiratory frequency and/or peak inspiratory flow when applied to the isolated larynx or to the supraglottic airway with the nose closed. These effects were abolished by SLN section. With the nose open, the ventilatory inhibition was not abolished by SLN section. Cool air also caused substantial decreases in laryngeal and supraglottic resistances which were attenuated by SLN section and which persisted following recurrent laryngeal nerve section. In conclusion, whilst UA cooling inhibits breathing and decreases UA resistances, UA CO₂ has minimal effects.     

Infection with HTLV-III/LAV and transfusion-associated acquired immunodeficiency syndrome. Serologic evidence of an association

We studied patients with transfusion-associated acquired immunodeficiency syndrome (AIDS) and their blood donors for serologic evidence of infection with human T-cell lymphotropic virus type III/lymphadenopathy-associated virus with two enzyme-linked immunosorbent assays and a Western blot assay. All 19 patients with AIDS were seropositive by at least one test. In all 28 donor sets containing "high-risk" donors, at least one donor was seropositive by one or more tests. Of 255 donors not considered high risk, two (0.8%) were seropositive by all three tests. When 30 seropositive high-risk donors were evaluated a median of 29 months after donation, four (13%) had developed AIDS and eight (27%) had lymphadenopathy. Our findings support the hypothesis that human T-cell lymphotropic virus type III/lymphadenopathy-associated virus causes AIDS and indicate that seropositive high-risk donors may be at relatively high risk for developing AIDS or related conditions themselves.     

Somatosensory evoked potentials after sequential extremity stimulation: a new method for improved monitoring accuracy

A new method for improving the accuracy of somatosensory evoked potential (SEP) monitoring is described. Two extremities are stimulated at 5 Hz, with an interextremity stimulus interval of 100 ms. Information from a "control" extremity, such as an arm during scoliosis operation, may allow more rapid and accurate interpretation of changes in SEPs during intraoperative monitoring.     

Effects of lorazepam upon recollective experience in recognition memory

The effects of lorazepam (2 mg) and placebo upon recognition memory with and without conscious recollection were assessed in a cross-over study with normal volunteers. When recognising a word from study lists presented before and 1, 3 and 5 h after drug administration, subjects were required to indicate whether they could consciously recollect the word's prior occurrence or recognised it on the basis of knowing; in the absence of conscious recollection. Lorazepam only impaired word recognition which was accompanied by conscious recollection, and further, the level of this impairment correlated significantly with each of three different indices of subjects' arousal at the time of presentation of each list. Recognition in the absence of conscious recollection was not impaired but somewhat heightened by lorazepam, and these effects did not significantly relate to any index of arousal. These findings are interpreted as providing further support for the notion that recognition entails two distinct components, one based on contextual and associative information and related to conscious recollection, the other possibly based on a traceless perceptual or semantic memory system and related to feelings of knowing in the absence of conscious recollection. Implications are drawn for a contextual-encoding/retrieval account of lorazepam-induced amnesia.     

The future ain't what it used to be

Base salaries for all health care managers will rise an average of 4.0 to 4.5 percent from 1993 to 1994--less than in previous years. Why the slowdown?     

The influence of tumor size and pre-treatment staging on outcome following radiation therapy alone for stage I non-small cell lung cancer

From 1970 through 1987, 77 patients with Stage I lung cancer were treated with definitive radiation therapy (RT) alone at the Fox Chase Cancer Center or the Hospital of The University of Pennsylvania. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of premorbid medical problems or patient refusal. The median age was 72 years, although 10 patients were over 80. The histologic cell type was squamous in 44, adenocarcinoma in 15, large cell in 3, adenosquamous in 1, non-small cell in 11, and bronchioli-alveolar in 3. Tumor size was retrievable in 75 patients and 25 were less than or equal to 3 cm, 41 from 3-6 cm, and 9 greater than 6 cm. Diagnostic staging varied during the study period. Twelve patients, evaluated with a CT scan of the chest, including the liver, and a bone scan were classified as having "excellent" staging, 24 patients with conventional tomography, liver-spleen scan and a bone scan had "good" staging, and 41 patients were staged less rigorously. The RT was of megavoltage energy in all patients. The median dose was 60 Gy. The mediastinum was treated in all but eight patients who had poor pulmonary function. Survival was measured from the date of pathologic diagnosis. The actuarial 3-year survival rate of the entire group of patients is 17% with a median survival time of 20 months. Of the 61 deaths, 51 were due to disease and 10 were due to intercurrent disease without evidence of tumor recurrence. The actuarial 3-year disease-specific survival (DSS) was 22%. The 3-year disease-specific survival for patients with tumors less than 3 cm and from 3-6 cm was 30% and 17%, respectively. All nine patients with tumors greater than 6 cm were dead of disease. Local progression occurred in 33 patients, resulting in a 44%, 3-year actuarial freedom from local progression. The median time to local failure was 28 months and there were no local failures after 3 years in the 18 patients eligible for observation beyond this point. Of the patients with "excellent" staging, only 2 of 12 were dead of disease compared with 22 of 24 with "good" staging and 30 of 41 of the remainder. In this large group of Stage I non-small cell lung cancer, thorough pre-treatment staging and smaller tumor size are associated with a more favorable outcome.     

Design of a "minimAl" homeodomain: the N-terminal arm modulates DNA binding affinity and stabilizes homeodomain structure.

This report investigates the sequence specificity requirements for homeodomain structure and DNA binding activity by the design and synthesis of a "minimAl" homeodomain (for minimalist design and alanine scanning mutagenesis) which contains the consensus residues and in which all nonconsensus residues have been replaced with alanine. The murine homeodomain Msx served as the prototype for the minimAl homeodomain, Ala-Msx. We show that Ala-Msx binds to DNA specifically, albeit with lower affinity than Msx. A derivative of the minimAl homeodomain, Ala-Msx(NT), which contains a native rather than an alanine-substituted N-terminal arm, has similar DNA binding affinity as Msx. We show that the native N-terminal arm stabilizes the tertiary structure of the minimAl homeodomain. Although Ala-Msx resembles a molten-globule protein, the structure of Ala-Msx(NT) is similar to Msx. The requirement for an intact N-terminal arm is not unique to the minimAl homeodomain, since the N-terminal arm also promotes high-affinity binding activity and appropriate tertiary structure of Msx. Therefore, the homeodomain "scaffold" consists of consensus residues, which are sufficient for DNA recognition, and nonconsensus residues in the N-terminal arm, which are required for optimal DNA binding affinity and appropriate tertiary structure. MinimAl design provides a powerful strategy to probe homeodomain structure and function. This approach should be of general utility to study the sequence specificity requirements for structure and function of other DNA-binding domains.     

Flow cytometry in the exploration of the physiopathology of occupational lung disease

Flow cytometry is a simple analytical technique used for the investigation of cells taken from various sources. Cells are identified by both their physical characteristics and the presence or absence of specific molecules on the cell surface. These molecules may be either phenotypic, or induced by a specific stimulus. Flow cytometry has been used to identify the nature and extent of the immune response in several occupational respiratory conditions including occupational asthma, irritant induced respiratory problems, and asbestos related lung disease. Also, it may be of value in monitoring workplace exposure to some hazardous materials. Although of limited diagnostic value at present, the technique has provided an insight into the modulation of immune cells, and their function, in people exposed to hazardous materials in the workplace. In this review, the principals of flow cytometry will be explored and the use of flow cytometry to investigate occupational respiratory disease will be discussed.