Physiological responses and manual performance in humans following repeated exposure to severe cold at night

We evaluated human physiological responses and the performance of manual tasks during exposure to severe cold (–25°C) at night (0300–0500 hours) and in the afternoon (1500–1700 hours). Thirteen male students wearing standard cold protective clothing occupied a severely cold room (–25°C) for 20 min, and were then transferred to a cool room (10°C) for 20 min. This pattern of exposure was repeated three times, for a total time of exposure to extreme cold of 60 min. The experiments were started either at 1500 hours or 0300 hours and measurements of rectal temperature, skin temperature, blood pressure, performance in a counting task, hand tremor, and subjective responses were made in each condition. At the end of the experiment at night the mean decrease in rectal temperature [0.68 (SEM 0.04)°C] was significantly greater than that at the end of the experiment in the afternoon [0.55 (SEM 0.08)°C, P<0.01]. After the second cold exposure at night the mean increase in diastolic blood pressure [90 (SEM 2.0) mmHg] was significantly greater than that at the end of the second cold exposure in the afternoon [82 (SEM 2.8) mmHg, P<0.01]. At the end of the second cold exposure at night, mean finger skin temperature [11.8 (SEM 0.8)°C] was significantly higher than that at the comparable time in the afternoon [9.0 (SEM 0.7)°C, P<0.01]. Similarly for the toe, mean skin temperature at the start of the second cold exposure at night [25.6 (SEM 1.5)°C] was significantly higher than in the afternoon [20.1 (SEM 0.8)°C, P<0.01]. The increased skin temperatures in the periphery resulted in increased heat loss. Since peripheral skin temperatures were highest at night, the subjects noted diminished sensations of thermal cold and pain at that time. Manual dexterity at the end of the first cold exposure at night [mean 83.7 (SEM 3.6) times·min^–1] had decreased significantly more than at the end of the first cold exposure in the afternoon [mean 89.4 (SEM 3.5) times·min^–1, P<0.01]. These findings of a lowered rectal temperature and diminished manual dexterity suggest that there is an increased risk of both hypothermia and accidents for those who work at night. Electronic Publication     

Hand and finger skin temperatures in convective and contact cold exposure

The present study aimed at investigating the spatial variability of skin temperature (T _sk) measured at various points on the hand during convective and cold contact exposure. A group of 8 subjects participated in a study of convective cooling of the hand (60 min) and 20 subjects to contact cooling of the finger pad (5 min). Experiments were carried out in a small climatic chamber into which the hand was inserted. For convective cold exposure,T _sk was measured at seven points on the palmar surface of the fingers of the left hand, one on the palmar surface and one on the dorsal surface of the hand. The air temperature inside the mini-chamber was 0, 4, 10 and 16°C. With the contact cold exposure, the subjects touched at constant pressures an aluminium cube cooled to temperatures of –7, 0 and 7°C in the same mini-chamber. ContactT _sk was measured on the finger pad of the index finger of the left hand. TheT _sk of the proximal phalanx of the index finger (on both palm and back sides), and of the middle phalanx of the little finger was also measured. The variation ofT _sk between the proximal and the distal phalanx of the index finger was between 1.5 to 10°C during the convective cold exposure to an air temperature of 0°C. Considerable gradients persisted between the hand and fingers (from 2 to 17°C at 0°C air temperature) and between the phalanges of the finger (from 0.5 to 11.4°C at 0°C air temperature). The onset of cold induced vasodilatation (CIVD) on different fingers varied from about 5 to 15 min and it did not always appear in every finger. For contact cold exposure, whenT _sk on the contact skin cooled down to nearly 0°C, the temperature at the area close to the contact skin could still be 30°C. Some cases of CIVD were observed in the contact skin area, but not on other measuring points of the same finger. These results indicated that local thermal stimuli were the main determinents of CIVD. Representative hand skin temperature may require five or more measuring points. Our results strongly emphasised a need to consider the large spatial and individual variations in the prediction and modelling of extremity cooling.     

Viral titers in nasal lining fluid compared to viral titers in nasal washes during experimental rhinovirus infection

BACKGROUND: The concentration of rhinovirus in nasal wash specimens from infected volunteers peaks at 48-72 h after inoculation. The volume of expelled nasal fluid peaks at the same time, raising the question of whether the viral concentration in nasal wash reflects viral replication in nasal cells or merely the production of an increased volume of nasal fluid during a cold. OBJECTIVES: To determine the amount of rhinovirus in nasal lining fluid during colds before the nasal fluid has been diluted in a nasal wash. STUDY DESIGN: Rhinovirus titers were determined in nasal wash specimens collected daily for five days from 14 subjects with type16 rhinovirus infection. The urea concentration in nasal lining fluid equals that in blood. By determining the urea concentration in a nasal wash and comparing it to the urea concentration in blood from the same subject, it was possible to determine the amount of dilution of the nasal lining fluid. The dilution factor (reciprocal of the dilution) was then used to calculate the viral concentration in undiluted nasal lining fluid. RESULTS: The dilution factor in 70 nasal washes varied from 5 to 64. The viral GMTs (+S.E.) in nasal washes were 1.79 (+0.3) TCID(50)/ml at 24 h, 3.11 (+0.15) at 48 h, and 2.61 (+0.3) at 72 h. The viral GMTs in nasal lining fluid, based on urea adjusted values, paralleled those in nasal washes but were approximately one log higher. Virus concentrations returned to near baseline values by day 5. CONCLUSIONS: The temporal pattern of rhinovirus shedding observed in nasal wash specimens, with a peak in virus concentration at 48-72 h after infection, is a true indication of virus production in nasal cells and not an artifact of the increased amount of nasal fluid produced during the early phase of a cold.     

Nasal mucosa in natural colds: effects of allergic rhinitis and susceptibility to recurrent sinusitis

The mechanisms of virus-induced airway hyperresponsiveness in asthma and allergy and the failure of host defence in patients suffering from secondary airway infections are still largely unknown. The aim of this study was to examine whether the presence of allergic rhinitis or susceptibility to recurrent sinusitis affects the structural and cellular changes in nasal mucosa during natural colds and convalescence. We compared the mucosal changes in biopsy samples during acute natural colds (days 2-4 of illness) and convalescence (3 weeks later) in patients with allergic rhinitis (n = 9), patients with susceptibility to sinusitis (n = 19) and healthy controls (n = 20). We saw similarly increased numbers of mucosal T and B lymphocytes and mast cells and increased vascular density during the acute colds compared to convalescence in all the three groups. The allergic subjects had elevated levels of eosinophils in the acute phase (P = 0.03), and the allergic and sinusitis-prone subjects had elevated levels of epithelial T cells (P = 0.04) and low levels of mast cells (P = 0.005) in convalescence compared to the control group. The sinusitis-prone subjects lacked intraepithelial cytotoxic cells in convalescence. In the allergic subjects, the reticular basement membrane was thicker in the acute phase compared to the convalescence (P = 0.05). These results suggest that various cells of the airways, including inflammatory and structural cells, are involved during viral respiratory infections in subjects with allergic rhinitis. The small numbers of mast cells and cytotoxic lymphocytes in the sinusitis-prone subjects may be related to their susceptibility to bacterial complications.     

Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies, II

We have previously described complement-independent killing of human B lymphocytes by two IgM MoAbs derived from the VH4-34 (VH4.21) gene. Analysis of 17 independently derived VH4-34-encoded MoAbs shows that B cell toxicity is not limited to the two described MoAbs, but is a general property shared by a subset of MoAbs derived from the VH4-34 gene. As observed by two independent microscopy techniques, giant membrane pores were formed on target B cells within 10–15 min of exposure to cytotoxic VH4-34-derived MoAbs. Toxicity by individual MoAb correlated directly to its B cell binding intensity measured by FACS, i.e. stronger the binding greater the killing. Sequence analysis showed that V_H region in germ-line or in near germ-line configuration was necessary but not sufficient for B cell binding. In addition, a particular sequence motif enriched in basic amino acids in the CDR3 may be required to supplement the reactivity mediated by the V_H region of the MoAb molecule. VH4-34-encoded antibodies that fulfil the above sequence requirements have cold agglutinin activity towards the i antigen of cord erythrocytes. In vivo, such anti-i/anti-B cell antibodies are rarely detected in healthy adults, but serum levels are dramatically elevated in selective pathological conditions, such as systemic lupus erythematosus and infectious mononucleosis. This strict regulation may be related to the novel and rapid mechanism of human B cell toxicity demonstrated by antibodies encoded by a single human V_H gene.     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Summary Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4° C or +23° C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG∶NA and 5-HIAA∶5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

Gross efficiency of muscular work during step exercise at -15°C and 21 °C

In an effort to assess the effect of ambient temperature on the gross efficiency (Eff_g) of step exercise 12 subjects performed a modified step test either at —15 °C or 21°C ascending to three different heights (corresponding to light, moderate and heavy work), for 20 min each with a frequency of 18 steps min^-1. Heart rate (HR), rectal temperature, skin temperatures and heat flux from skin were continuously measured. Oxygen consumption was measured during the last 5 min of each step height and perceptions of thermal sensation were recorded. The results indicate that, while using conventional clothing adequate in these temperatures, Eff_g is altered in a contradictory manner. At —15°C Eff_g increased with increasing work load, whereas at 21°C it decreased when the work load increased. The highest Eff_g (heavy work at —15°C and light work at 21°C) values are reflected as rather similar rectal temperatures (37.4–37.7°C) and identical mean skin temperatures (32.8 °C) as well as the same (slightly warm) thermal sensation of the legs. At — 15 °C the lowest Eff_g in light work was probably hue to the need to warm up the muscles. At 21°C, on the contrary, the activation of heat dissipation systems was probably responsible for the lowest Eff_g in heavy work.     

Cardiac responses to pressor challenges in congenital central hypoventilation syndrome

Summary Question of the Study   Congenital central hypoventilation syndrome (CCHS) subjects exhibit diminished respiratory-related heart rate variation in addition to defining characteristics of CO₂ insensitivity and reduced ventilatory drive during sleep. Loss of cardiovascular and breathing coupling may diminish blood pressure influences on breathing; such influences may be determined by evaluating cardiorespiratory responses to different pressor challenges.
Patients and Methods   Ten children with CCHS and 10 age- and gender-matched controls were subjected to a forehead cold pressor challenge and to Valsalva maneuvers. Heart and respiratory rates and variability during 30-s baseline and 120-s challenge periods were assessed with scatterplot displays and by analysis of variance procedures.
Results   Cold pressor challenges enhanced breathing efforts and increased respiratory-related heart rate variation in controls but not in CCHS patients, while lower frequency heart rate variability increased in both controls and CCHS subjects. Heart rate variation resulting from voluntary expiratory efforts was present but slightly reduced in CCHS. Respiratory and cardiac rate trends differed in control and CCHS cases.
Conclusions   More-rapidly changing heart rate variation from spontaneous or reflexively-induced sources is diminished in CCHS but remains intact from voluntary expiratory ­efforts, as does slower variation. Loss of reflexive influences on breathing from blood pressure changes may attenuate a source of respiratory drive.