PubMed Health⌕ Search

Biomedical subjects

J Haight

Publications and source records attributed to J Haight.

14 recordsLinked to original sources

Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease.

Initially identified in high-grade gliomas, mutations in the PTEN tumor-suppressor are also found in many sporadic cancers and a few related autosomal dominant hamartoma syndromes. PTEN is a 3'-specific phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) phosphatase and functions as a negative regulator of PI3K signaling. We generated a tissue-specific deletion of the mouse homolog Pten to address its role in brain function. Mice homozygous for this deletion (PtenloxP/loxP;Gfap-cre), developed seizures and ataxia by 9 wk and died by 29 wk. Histological analysis showed brain enlargement in PtenloxP/loxP;Gfap-cre mice as a consequence of primary granule-cell dysplasia in the cerebellum and dentate gyrus. Pten mutant cells showed a cell-autonomous increase in soma size and elevated phosphorylation of Akt. These data represent the first evidence for the role of Pten and Akt in cell size regulation in mammals and provide an animal model for a human phakomatosis condition, Lhermitte-Duclos disease (LDD).

Animals↗

Nitric oxide accumulation in the nonventilated nasal cavity.

BACKGROUND: Nasal nitric oxide is present in high concentrations in the upper airway relative to the lower respiratory tract. OBJECTIVE: To explore the rate of nitric oxide accumulation in the nonventilated nasal cavity. METHODS: In 9 healthy subjects previously trained to close the soft palate, steady-state plateau nitric oxide levels were recorded while air was aspirated through the nasal airway in series at a constant flow rate. Nitric oxide was then allowed to accumulate in the nasal cavity by occluding both nares and keeping the velum closed. After varying occlusion times, peak nitric oxide levels and a second plateau were ascertained. RESULTS: While the subjects aspirated air at a constant flow, there was a slow rise to a first nitric oxide plateau. On opening to the analyzer after the accumulation period, the peak nitric oxide level was several times higher than the initial plateau (range, 2810-19008 ppb) and then slowly returned to previous plateau levels. There was no significant difference between initial and second plateau nitric oxide levels for any period. The accumulated nitric oxide peak increased in direct proportion to the accumulation time (P<.001). CONCLUSIONS: Nitric oxide concentrations accumulate in the nonventilated nasal cavity in proportion to the time of nonventilation. Peak nasal nitric oxide values after accumulation are similar to published sinus nitric oxide measurements obtained by direct puncture. These results suggest an important alternative source of nitric oxide in humans.

Adult↗

Does snoring contribute to presbycusis?

It is well known that hearing acuity decreases with age. The precise mechanism responsible for this phenomenon, called presbycusis, is unknown. One hypothesis advanced to explain this loss of acuity implicates chronic exposure to snoring noise. Consequently, the purpose of this study was to investigate whether snoring is associated with hearing loss. We examined 219 patients (63 women and 156 men) referred to our sleep disorders center. All of the patients underwent nocturnal polysomnography with measurements of snoring, as well as standard audiometry (i.e., measurement of hearing thresholds at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 3 kHz, 4 kHz, 6 kHz, and 8 kHz). Snoring was quantified by measuring three parameters: snoring index (SI = number of snores/h of sleep), average nocturnal sound intensity (dBav), and maximum nocturnal sound intensity (dBmax). We used simple correlation analysis to investigate the relationship between snoring and hearing thresholds; multiple linear regression analysis to determine individual contributions of age, sex, and snoring to the variability in hearing thresholds; and comparison tests to determine whether mild snorers had less hearing impairment than severe snorers. None of these statistical tests demonstrated that snoring was a significant determinant of hearing. We conclude that snoring is not associated with hearing loss and is therefore unlikely to account for presbycusis.

Adolescent↗

Postural changes in respiratory airflow pressure and resistance in nasal, hypopharyngeal, and pharyngeal airway in normal subjects.

We investigated the effect of posture on nasal and pharyngeal resistance in 12 healthy subjects studied during wakefulness. Airway pressure and airflow were measured with subjects seated and in dorsal and left lateral recumbency, during inspiration and expiration. We found that pharyngeal resistance was approximately four to six times lower than the nasal resistance. Only pharyngeal resistance was significantly increased upon assumption of a supine posture, from 0.02 +/- 0.01 Pa/mL per second when seated to 0.06 +/- 0.05 Pa/mL per second in dorsal recumbency and to 0.05 +/- 0.04 Pa/mL per second in left lateral recumbency. Mean nasal and pharyngeal resistances doubled upon assumption of a supine posture, but this difference was not statistically significant. There was no significant difference in pharyngeal resistance between inspiration and expiration. Finally, there was a strong linear relationship between pharyngeal pressure and pharyngeal resistance (r = .98, p<.0001). We concluded that in normal awake subjects 1) pharyngeal resistance increases with assumption of a supine posture, 2) the walls of the pharynx are not compliant enough to alter their resistance in response to inspiratory and expiratory pressure changes, and 3) it may be possible to infer pharyngeal resistance from measurements of pressure alone, without measurement of airflow.

Adult↗

Diagnosis of obstructive sleep apnea using a portable transducer catheter.

As an initial step in simplifying the diagnosis of sleep apnea with a view toward using portable equipment in the home setting, we examined the efficacy of a portable transducer catheter that measures intrathoracic pressure. This catheter, connected to a miniature data-logger, can be introduced nasally into the airway, and the data so collected can be acquired, stored, and analyzed off-line. We tested this catheter against standard nocturnal polysomnography in 10 patients suffering from obstructive sleep apnea. We found that by using a combination of the raw pressure signal and an envelope pressure signal, we accurately identified apneas and hypopneas, and classified them as obstructive, central, and mixed. For the 10 subjects studied, the polysomnographic apnea/hypopnea index was 34 + 30, versus 32 + 28 obtained by analysis of the pressure tracings. Analysis of 200 respiratory events identified one-by-one from polysomnograms and pressure tracings revealed close correspondence between the two methods. The average duration of apneas was 22.1 + 6.7 s as measured by polysomnography, versus 21.9 + 6.6 s as measured from pressure tracings. Furthermore, there was excellent agreement between the two methods (kappa = 0.89, 95% confidence limits = 0.84 to 0.94). We conclude that our technique for identifying apnea based on measurements of intrathoracic pressure using a thin, portable transducer catheter is a promising method for simplifying the diagnosis of this disorder.

Adult↗

Changes in pharyngeal properties after uvulopalatopharyngoplasty.

Uvulopalatopharyngoplasty is a commonly used modality for surgical treatment of snoring and obstructive sleep apnea. Although this procedure is thought to alter pharyngeal properties, its effect on pharyngeal mechanics has not been studied. The acoustic reflection technique was used to measure pharyngeal area at functional residual capacity and residual volume before and after uvulopalatopharyngoplasty in eight patients referred because of loud snoring. We also calculated the lung volume dependence of pharyngeal area, defined as the percent change in pharyngeal area between functional residual capacity and residual volume, normalized to the area at functional residual capacity. This parameter, which may be related to pharyngeal collapsibility, was obtained before and after uvulopalatopharyngoplasty. Preoperative sleep studies showed that one patient had obstructive sleep apnea (apnea index greater than 10). Uvulopalatopharyngoplasty resulted in a significant increase (p less than 0.01) in pharyngeal area (from 3.14 +/- 0.71 cm2 to 4.25 +/- 1.07 cm2) and residual volume (from 2.49 +/- 0.53 cm2 to 3.91 +/- 0.83 cm2). Following uvulopalatopharyngoplasty, the pharynx became stiffer, as manifested by a reduction in lung volume dependence of pharyngeal area from 19 +/- 12% to 8 +/- 13% (p less than 0.05). Six patients, including the patient with obstructive sleep apnea, reported improvement in snoring. Two patients reported worsening in snoring. One of the two was found to have reduction in pharyngeal area and lung volume dependence of pharyngeal area, and an increase in apnea index from 3 to 33. In selected snorers, uvulopalatopharyngoplasty results in improvement in snoring with a concomitant increase in pharyngeal area and a tendency toward lower pharyngeal collapsibility.

Adult↗

Mechanical ventilation during laryngeal surgery: an evaluation of the Carden tube.

The effectiveness and safety of the Carden tube-oxygen injector system for ventilation was studied in 18 high-risk patients with obstructive airways disease during microlaryngeal surgery. Blood gas studies during operation demonstrated a mean Pao2 of 65.6 kPa (493 torr) and a mean PaCO2 of 4.5 kPa (34 torr) during mechanical ventilation. No serious complications were noted during operation. Fifty per cent of the patients had postoperative hypercapnia and in two the trachea was re-intubated. Airway maintenance and ventilation are discussed in detail and it is concluded that the Carden tube-oxygen injector system is a safe and convenient method for ventilating the lungs of patients with pulmonary disease who require microlaryngeal surgery.

Adult↗

Follow-up families who experience a perinatal death.

We conducted a retrospective study by telephone interview (10 to 22 months later) of 26 families who had experienced a perinatal death. Six of 26 mothers had a prolonged grief reaction (12 to 20 months). Those mothers with a surviving twin or subsequent pregnancy less than five months following the death were at higher risk for a prolonged grieving period than were those without subsequent pregnancy or one more than six months later. Half of the families obtained information about the cause of death and risk of recurrence only during hospitalization; subsequent contact, weeks to months later, provided additional information for the other half. Twenty-two of 26 mothers met predetermined criteria for having an adequate understanding of cause of death and risk of recurrence; four of 26 knew neither. Sixty percent of the mothers who had adequate understanding and who had no prolonged grief response felt totally dissatisfied or only partially satisfied with the information they received and the way they received it. Follow-up contact by phone or in person increased understanding significantly; mothers who had had in-person follow-up were more likely to be satisfied with the information they received.

Attitude to Death↗

Traumatic bilateral renal artery thrombosis.

Although unilateral traumatic renal artery thrombosis may be more common than was once thought, bilateral traumatic renal artery thrombosis is rare, with only thirteen previously reported cases. Time is of the essence in diagnosing this condition, so that in the proper clinical setting one may be able to proceed quickly to arteriography. However, the prognosis at present still remains poor.

Accidents, Traffic↗

Sudden failure of swimming in cold water.

To investigate the effect of cold water on swimming four men who declared themselves good swimmers were immersed fully clothed on separate days in water at 23.7 degrees and 4.7 degrees C. The time that they were able to swim in the cold water was much shorter than in the warm. The two shortest swims ended after 1.5 and 7.6 minutes, before rectal temperature fell, when the men suddenly floundered after developing respiratory distress with breathing rates of 56-60/min. The other cold swims, by the two fattest men, ended less abruptly with signs of general and peripheral hypothermia.It is concluded that swimming in cold water was stopped partly by respiratory reflexes in the thin men and hypothermia in the fat, and partly by the cold water's high viscosity. The longer swimming times of the fat men are attributed largely to their greater buoyancy enabling them to keep their heads above water during the early hyperventilation.The findings explain some reports of sudden death in cold water. It is clearly highly dangerous to attempt to swim short distances to shore without a life-jacket in water near 0 degrees C.

Adult↗

Computed tomography of lingual thyroid.

The CT findings of a lingual thyroid are presented. A round, well-defined, homogeneously enhancing mass at the base of the tongue suggested the diagnosis leading to the confirmatory isotope scan.

Choristoma↗

Nasal nitric oxide: a comparison of measurement techniques.

Nasal nitric oxide measurement may be a surrogate marker of upper airway inflammation. There is, however, no standardized measurement technique; and this led us to examine measurement techniques for acceptability and reproducibility. In five subjects we examined the flow dependence of nasal NO. In 13 healthy volunteers, nasal NO was measured on-line by five methods: 1) Tidal nasal and oral breathing: NO sampling during exclusive nasal followed by exclusive oral tidal breathing; 2) Fixed flow exhalation: NO sampling during exclusive nasal followed by exclusive oral exhalation at 100 mL/second from total lung capacity; 3) Nasal-oral aspiration: air aspirated from the mouth via both nares at 100 mL/second with glottis closure; 4) Aspiration from one nares: air aspirated from one nares at 3.3 mL/second using nitric oxide analyzer sample line with velum closure; 5) Nasal Insufflation: NO sampled at one nares as air insufflated into the other nares at a flow of 100 mL/second with velum closure. Acceptability of all methods was assessed by subjects and technicians. Nasal NO concentration showed a significant inverse correlation with transnasal flow rate. All methods showed excellent reproducibility as assessed by the intraclass correlation coefficient except tidal breathing, which showed highly variable breath-to-breath NO levels, although mean breath values were reproducible. Mean nasal NO concentrations with methods 1, 2, 3, 4, and 5 were 32.1, 50.2, 62.8, 1381, and 60.0 ppb, respectively. Velum closure was not always achieved in methods 4 and 5, whereas methods 1 and 2 required separate nasal and oral procedures. Method 5 had reduced acceptability. NO concentrations were similar with methods that used the same airflow (2, 3, and 5). Nasal NO can be sampled in different ways with excellent reproducibility. In view of the flow dependence of nasal NO, it is vital to use a constant flow rate, and lower airway NO contribution must be excluded or subtracted. The fixed flow exhalation appears to be the preferred method as it is highly reproducible and acceptable.

Analysis of Variance↗