Time course of pulmonary artery pressure during sleep in sleep apnoea syndrome: role of recurrent apnoeas

Recent results in animals have suggested that repetition of hypoxaemic stimuli may result in a progressive increase in pulmonary arterial pressure (Ppa). The purpose of the present study was to investigate the effects of recurrent obstructive apnoeas on Ppa. We have, therefore, examined the nocturnal trend of Ppa in seven obstructive sleep apnoea syndrome (OSAS) patients and in five snorers. Mean Ppa was measured before, at the start, at the end and after the selected apnoeas. The analysis was performed for each 1 h period for at least 7 h throughout the night on at least 10 randomly selected apnoeas per hour. In snorers, 100 randomly chosen values were measured during every hour of the night. In the morning after the nocturnal study, the Ppa responses to acute hypoxia and hypercapnia were measured. No Ppa changes throughout the 7 h were found during sleep in snorers [Ppa slope:-0.002+/-0.10 mmHg x h(-1)]. In OSAS patients a small but significant increase in Ppa throughout the night was noted, affecting the values before [Ppa slope: 0.7+/-0.16 mmHg x h(-1)], at the start of apnoea [Ppa slope: 0.530.1 mmHg x h(-1)] as well as at the end [Ppa slope: 0.44+/-0.08 mmHg x h(-1)] and in the postapnoeic period [Ppa slope: 0.55+/-0.1 mmHg x h(-1)]. When we limited the analysis to nonrapid eye movement (NREM) sleep, a trend in progressive Ppa was also present, irrespective of changes in apnoea duration and apnoea desaturation. The Ppa rise during the night was not affected by diurnal Ppa pulmonary vascular response to hypoxia and hypercapnia or indices of sleep apnoea severity. We conclude that in obstructive sleep apnoea, pulmonary artery pressure progressively increases during the night, reflecting the cumulative effects of apnoeas and nocturnal hypoxaemia.     

Laser in situ keratomileusis: literature review of a developing technique

We reviewed papers published in peer-reviewed journals describing techniques and results of laser in situ keratomileusis (LASIK) and summarized the instruments used, nomograms, preoperative and postoperative refractions, predictability, outcome, safety, and complications. We performed a similar review of abstracts published in the abstract books of the 1996 meeting of the International Society of Refractive Surgery, the 1997 meeting of the Association for Research in Vision and Ophthalmology, and the 1997 meeting of the American Society of Cataract and Refractive Surgery. The number of LASIK and photorefractive keratectomy (PRK) patients described in the abstracts were sorted by city. Mean weighted latitudes were calculated and compared for each procedure. The mean preoperative refraction in the papers was -12.59 diopters (D), which was statistically higher than that in the abstracts, -8.71 D (P < .001), and the mean postoperative refraction, -1.10 and + 0.93 D, respectively. The mean percentage of cases within +/- 1.00 D was 67.0% in the papers and 82.5% in the abstracts. Uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 49.2% of eyes in the papers and 83.2% of those in the abstracts; a UCVA of 20/20 or better was achieved in 22.0 and 56.6%, respectively. The portion of eyes that lost two or more lines of best corrected visual was 8.0% in the papers and 0.9% in the abstracts. Complications in the papers included irregular flap (4.0%), incomplete cut (2.5%), free cap (4.9%), perforated lenticule (2.6%), short flap (3.0%), sliding flap (1.4%), interface debris (6.8%), central island (5.3%), decentration (4.7%), epithelial ingrowth (4.3%), induced astigmatism (5.1%), wrinkles (5.9%), haze (8.7%), night vision problems (14.0%), and reoperation (8.2%), Mean latitude for LASIK cases (27.00 degrees +/- 13.73 [SD] was significantly lower than that for PRK cases (42.85 +/- 11.7 degrees). Visual outcomes of LASIK surgery show significant improvements when recent abstracts are compared with published papers. This may reflect continued improvement in the surgical techniques, surgeons' skills, and visual outcomes.     

Gene therapy strategies for AIDS-related malignancies

AIDS-related malignancies (ARM) include AIDS-defining cancers such as Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical carcinoma. In addition, certain other malignancies are also increased with human immunodeficiency virus (HIV) infection. New antiretroviral agents and better prophylaxis and treatment of HIV-related opportunistic infections are prolonging the lives of HIV-infected individuals. There will thus likely be a continued rise in the incidence and prevalence of ARM in the long term, even if effective antiretroviral and other AIDS-related therapies reduce their appearance in the short term. There are presently no curative regimens for the common ARM, with the possible exception of some lymphomas. Survival is shortened by most, and treatment is often toxic and poorly tolerated. Gene therapies may thus offer a useful adjunct to conventional treatment strategies for selected ARM. Although some gene therapy strategies may work well in the HIV setting, the chronic viral infection, immunodeficient status of the host, the tendency for HIV-infected individuals to have altered drug metabolism and an increased rate of adverse drug reactions will likely present special challenges. This review summarizes the state-of-the-art in the fledgling field of gene therapy for ARM, and explores areas for future research.     

The left hemisphere and the selection of learned actions

The ability of recombinant preparations of equine herpesvirus type 1 (EHV-1) glycoprotein D (gD) to elicit specific antibody and T lymphocyte responses in the BALB/c mouse model of respiratory infection was investigated. Recombinant gD (rgD) expressed as a glutathione-S-transferase (GST) fusion protein in Escherichia coli elicited both high titer neutralizing antibody (nAb) and CD4 T cell proliferative responses following subcutaneous or intranasal immunization, but elicited only a weak antibody response after intraperitoneal immunization. Protection against respiratory tract infection with pathogenic EHV-1 RacL11 was observed in mice immunized subcutaneously with GST-gD. Furthermore, the degree of protection correlated to the titer of nAb and the T cell response observed. Finally, GST-gD was more effective in protecting against respiratory RacL11 infection if delivered intranasally. These results confirm that gD plays an important role in eliciting the protective immune response against EHV-1 infection, and indicate that subunit vaccines containing preparations of gD may be very effective if delivered directly to the upper respiratory tract.     

Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study

OBJECTIVE: To examine whether estrogen replacement therapy (ERT) prevents worsening of radiographic knee osteoarthritis (OA) in elderly women. METHODS: A total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were followed up from biennial examination 18 (1983-1985) to examination 22 (1992-1993). Data on postmenopausal ERT were obtained every 2 years. Subjects were classified into 3 groups according to their estrogen use at biennial examination 18: never users (n = 349), past users (n = 162), and current users (n = 40). Women received anteroposterior weight-bearing knee radiographs at examinations 18 and 22. Using the Kellgren and Lawrence criteria, global radiographic knee OA was assessed, (grade range 0-4) and individual radiographic features, such as osteophytes and joint space narrowing, were scored from 0 to 3. Worsening was defined as either development of radiographic OA that was not present at baseline (incident OA) or progression of baseline radiographic OA by > or =1 Kellgren and Lawrence grade (progressive OA). Potential confounding factors included age, body mass index, weight change, smoking, knee injury, physical activity level, and bone mineral density at the femoral neck. RESULTS: During 8 years of followup, 17.4% of knee radiographic scores worsened by 1 grade and 5.8% by 2 or 3 grades among never users of ERT. Among current estrogen users, only 11.7% of knee radiographic scores worsened by 1 grade and none worsened by more than 1 grade. After adjusting for age and other potential confounding factors, the relative risk of incident radiographic knee OA in comparison with never users of estrogen was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% CI 0.1-3.0) in current users. Current use of estrogen also showed a trend toward decreased risk of progressive knee OA compared with never use (odds ratio [OR] 0.5, 95% CI 0.1-2.9). When both incident and progressive radiographic knee OA cases were combined, current ERT use had a 60% decreased risk compared with never use (OR 0.4, 95% CI 0.1-1.5). CONCLUSION: This is the first prospective cohort study to examine the effects of ERT on radiographic knee OA. The results indicate that current use of ERT had a moderate, but not statistically significant, protective effect against worsening of radiographic knee OA among elderly white women. These findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in OA.     

Foreign serum-induced pancreatitis in mice. II. Secretory disturbances of acinar cells

As previously reported, pancreatic acinar cell necrosis and inflammation develop in mice a few hours after one intraperitoneal injection of foreign serum. However, sublethally injured acinar cells exhibited notable increases in both zymogen granule numbers and amylase activity, observed within 3 hours and increasing with time. These two changes were coupled with a progressive decrease in the secretory response to pilocarpine and were preceded by significant disturbances in pancreatic tissue concentrations of sodium and potassium. We conclude that (1) the granule increase results from an induced disturbance of the granule exocytosis mechanism while granule formation continues and, therefore, (2) the granule secretory process is more sensitive to the serum injury mechanism than is the zymogen synthesis process. Although the granule increases developed in acinar cells throughout most of the nonnecrotic gland and persisted for at least 24 hours, acinar cell necrosis was maximal in extent--approximately 25% of the gland in severest form--by 12 to 15 hours. We conclude, therefore, that the increase in granules is neither the primary determinant nor initiator of acinar cell death. The latter is likely caused by disturbed plasma membrane functions, sufficient in some cells to result in lethal changes in ion and fluid composition. The injury mechanism, which permits granule formation to go on in the face of impaired granule exocytosis, is yet to be worked out. The possibilities are discussed in relationship to the reactivity of foreign sera for target cell plasma membranes.     

Effect of 5-hydroxytryptamine on the peripheral chemoreceptors in the rat

5-Hydroxytryptamine (5-HT), in the doses of 2-5 mug/kg injected into the carotid body area, produced a significant increase in the respiratory rate and carotid sinus nerve activity. Selective ablation of the ipsilateral carotid sinus nerve abolished the respiratory stimulation produced by the drug. On the other hand, the same doses of 5-HT injected into the ascending aorta did not produce stimulation of respiration when the carotid sinus nerves were sectioned. The activity of the aortic nerves did not increase after injecting the drug into the ascending aorta or at the root of the right subclavian artery. These results indicate that 5-HT stimulates the chemoreceptors in the carotid body of the rat. The lack of responses to the injections of the drug in the aortic or subclavian region was due to the absence of chemoreceptors in these regions of the rat.