New insights into the therapy and pathophysiology of patients with obstructive sleep apnoea syndrome

Abstract The objective of this study was to investigate the effects of obstructive sleep apnoea on: (i) PaCO₂ levels; (ii) coagulation systems (plasma fibrinogen levels and whole blood viscosity); and (iii) heat shock proteins (HSPs) levels, which are also called stress proteins, in patients with obstructive sleep apnoea syndrome (OSAS). Patients treated with or without nasal continuous positive airway pressure (NCPAP) had arterial blood gases, plasma fibrinogen, haematocrit, serum total protein and changes in PaCO₂ (estimated by transcutaneous PaCO₂) measured before and after polysomnography. Heat shock protein 72 levels in peripheral blood mononuclear cells were also measured during sleep with and without NCPAP. OSAS patients with hypercapnia demonstrated significant increases in PaCO₂ in the morning compared with the previous night. In such OSAS patients, treatment with NCPAP resulted in a normalization of the 20 mg/dL increase in fibrinogen levels which had been seen previously in the morning after sleep. Basal HSP 72 levels (08.00 pm before sleep) were high in OSAS patients compared to normal subjects and progressively decreased during sleep in the absence of NCPAP therapy. NCPAP relieved disabling day-to-day symptoms in addition to improving cardiovascular morbidity in patients with OSAS. Therefore it is important to understand the effects of OSAS on various organ systems as the prevalence of patients with OSAS is high.     

Alteration of Activities of Hepatic Antioxidant Defence Enzymes in Developing Chick Embryos After Glucocorticoid Administration - A Factor to Produce Some Adverse Effects?

Liver tissue is one of the principal targets of glucocorticoids, therefore changes in the balance between hepatic oxidative and reductive capacity may greatly influence adverse effects of glucocorticoid therapy. In this study, effects of glucocorticoid on the activities of hepatic antioxidant defence enzymes were examined by using developing chick embryos. After the administration of 0.25 μmol hydrocortisone sodium succinate, a typical glucocorticoid, to 15-day-old chick embryos, glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase in the liver generally began to decrease at around 4 h, reaching 60–70% of control levels between 24 and 48 h. These changes were observed much earlier than the elevation of the hepatic thiobarbituric acid reacting substance (TBARS) level which began to increase from 20 h, reaching about six times the control level at 48 h after hydrocortisone administration. Conversely, the elevated TBARS level decreased back to the normal level with the recoveries of these enzyme activities. Furthermore, it was found that the aniline hydroxylase activity, measured as a marker of oxidative activity, began to increase after around 12 h. These results suggested that TBARS levels were possibly produced by the suppression of antioxidant defence abilities and the significant induction of oxidative activity in the liver by glucocorticoid. As the elevated TBARS in the liver can be distributed to tissues, TBARS will be involved in the occurrence of some of the glucocorticoid-induced adverse effects such as cataract formation.     

A study of prognosis in 52 cases with juvenile rheumatoid arthritis

The prognosis in 52 patients with juvenile rheumatoid arthritis (JRA) was studied. There were 35 cases of systemic onset, 12 of polyarticular onset and 5 of pauciarticular onset. Thirteen systemic cases developed a polycyclic course with chronic polyarthritis. Many monocyclic JRA in systemic cases subsided within 1 year. There were no instances of polyarticular cases or pauciarticular cases that shifted to other type. However, there were many cases with a long active polyarticular JRA and with remission at an early stage in the pauciarticular type. The stage and class were I or II in 90% of cases with a good prognosis for the joints, but there were some serious cases. Transient carditis or iritis which developed at an early stage subsided later. The intractable systemic cases had drug-induced complications. The cases with steroid-induced complications tended to be chronic. One death in a systemic case was caused by hepatic failure.     

Impact of dementia on cancer discovery and pain

Background: Dementia is clinically noted to influence both reporting and experience of cancer pains. However, no systemic evaluation of this aspect has been reported. The aim of the present study was to retrospectively evaluate how dementia modified the cancer discovery process, frequency of cancer pain reports and analgesic‐narcotic use at a large psychiatric hospital. Methods: We reviewed all the records of cancer patients with and without dementia treated at the surgical ward of Matsuzawa Hospital from 1993 to 2004. Psychiatric diseases other than dementia, brain metastasis and alcoholism, as well as leukaemia and skin cancer, were excluded. Patients' communicativeness as to pain was ascertained from nursing records. Results: A total of 134 cancer patients with and without dementia (50 demented and 84 non‐demented) were included. Demented patients were accidentally discovered to have cancer (48%) or by an unexpected unfolding of clinical signs (44%), whereas most non‐demented patients (63%) voluntarily sought medical evaluation (P= 0.000). Overall, 76% of non‐demented patients had cancer pains (stages I and II, 64%; stages III and IV, 84%), whereas just 22% of demented patients had cancer pains (stages I and II, 16%; stages III and IV, 26%; P= 0.000). Non‐demented patients showed stage‐dependent requirements for both non‐narcotic analgesics (stages I and II, 64%; stages III and IV, 84%) and narcotics (stages I and II, 0%; stages III and IV, 41%). Demented patients required much less analgesics (stages I and II, 11%; stages III and IV, 13%), with only one stage IV patient requiring narcotics (P= 0.000). Conclusion: Dementia greatly modifies the cancer discovery process, reduces prevalence of cancer pain and analgesic requirement.     

Predictive Factors of Re-restenosis after Repeated Sirolimus-Eluting Stent Implantation for SES Restenosis and Clinical Outcomes after Percutaneous Coronary Intervention for SES Restenosis

Sirolimus-eluting stent (SES) is established to be effective in reducing restenosis. Repeat revascularization, however, is still required in up to 5–8% of patients. In this study, we analyzed clinical and angiographic variables that might be related with SES re-restenosis and variables related with re-restenosis after repeat SES implantation for SES restenosis. We also assessed clinical outcomes at 2-year follow-up after percutaneous coronary intervention (PCI) for SES restenosis. Repeat revascularization for SES restenosis was performed in 113 patients with 140 lesions. Of the 140 lesions, follow-up coronary angiography (CAG) was performed on 117 lesions (101 patients) and revealed 46 SES re-restenotic and 71 non-re-restenotic lesions. In multivariate analysis, SES-in-SES-strategy and reference diameter before the second PCI were independent predictors of re-restenosis after PCI for SES restenosis. However, the reference diameter was the only independent predictor of re-restenosis after SES-in-SES. Major adverse cardiac events (MACE) at 2 years were found in 44 patients (43.5%), and target lesion revascularization (TLR) was performed in 33.7% of patients after SES restenosis. In conclusion, the incidence of MACE and TLR was relatively high in patients with SES restenosis, but the placement of another SES on larger-diameter vessels may be an effective strategy for the second PCI .     

Correlation of middle latency auditory evoked potentials and cerebral blood flow changes

Abstract  The purpose of this study is to find the correlation between middle latency auditory evoked potentials (MLAEP) and sound activated single photon emission computed tomography (SPECT) studies. This study was performed on six normal right-handed volunteers with a mean age of 35.2 ± 7.6 years, using the split-dose technique. First, a SPECT study was performed on subjects in blinded, awake and silent states. After bilateral ears were stimulated with a click sound, MLAEP and a second SPECT study were performed. Subtraction of the first SPECT from the second SPECT revealed a statistically significant increase of cerebral blood flow (CBF) in the bilateral superior temporal region. Bilateral Na amplitudes of MLAEP had a statistically significant and good correlation with the percentages of CBF changes in the bilateral superior temporal region. The superior temporal cerebral blood flow activation can be expressed by electrophysiological activation. Moreover, correlation during the left Na components and left frontal and occipital lobe are discussed.     

A case of Sheehan's syndrome with delirium

Abstract A 53 year old woman was brought to a psychiatric clinic because of delirium. Upon immediate examination, severe hyponatremia (105 mEq/L) was detected. She was suspected of having internal diseases and referred to our university hospital. When she reached our hospital she was delirious and showed excitement and agitation. Her electroencephalogram showed low voltage θ waves (20 μV) in all leads. She was hospitalized and diagnosed with acute tonsillar abscess and panhypopituitarism based on various endocrine tests. Her past history suggested that Sheehan's syndrome had developed after child-bearing at age 31, resulting in panhypopituitarism. After administration of antibiotics, the fever and tonsillar abscess gradually recovered, and the correction of electrolytes improved the level of consciousness, suggesting that the hyponatremia had been closely related to the clouding of consciousness. As the subsequent administration of Cortisol kept the patient's serum sodium levels within the normal range, a decrease in plasma Cortisol seemed to be the major cause of the hyponatremia. Psychological symptoms of panhypopituitarism often included abulia, apathy and occasionally coma. However, it is rare for a patient with panhypopituitarism to be misdiagnosed as having a psychiatric disease with delirium. This rare case is presented.     

The nocturnal secretion of cardiac natriuretic peptides during obstructive sleep apnoea and its response to therapy with nasal continuous positive airway pressure

The nocturnal secretion profile of the newly identified natriuretic peptide (NP), brain natriuretic peptide (BNP), was studied in 14 patients with obstructive sleep apnoea syndrome (OSAS) (apnoea hypopnoea index: 60.5±3.4, mean±SE) during two separate nights before and during nasal continuous positive airway pressure (NCPAP) therapy. Plasma levels of NPs (atrial natriuretic peptides; ANP and BNP) were measured at 2-h intervals during sleep. Simultaneously, blood pressure was measured by a non-invasive method (Finapres^®, Ohmeda, Englewood, CO, USA) and urine was collected for determing volume and catecholamine levels. Urinary and serum sodium concentration were determined before and after the study. Eight non-snoring subjects were also studied for the investigation of normal nocturnal profiles of BNP levels. To understand the discrete secretion profiles of the two NPs during sleep, blood was sampled from an additional seven patients every 5 min over a 30-min period around 00.00 and 04.00 hours before NCPAP. In patients with OSAS, plasma BNP levels increased from the beginning of sleep (22:00 h) to the morning (06:00 h) before NCPAP therapy (P< 0.01, anova ). Baseline BNP levels were not significantly correlated with patient's clinical and poly- somnographic parameters. However, in the latter half of the sleep period (02:00–06:00 h), increases in BNP levels during the night before NCPAP therapy were significantly correlated with blood pressure elevations (systolic: r=0.784 P< 0.01, diastolic: r=0.587 P< 0.01) and with apnoea duration (r=0.582 P< 0.01). In normal subjects BP and BNP levels were not changed significantly during sleep. Plasma BNP levels were well correlated with concomitant ANP levels (P< 0.001). NCPAP therapy reduced ANP and BNP levels during sleep and in the morning (P< 0.01). Plasma levels of BNP at 5 min intervals before NCPAP therapy revealed few variations. On the other hand, ANP levels fluctuated over the 30-min period. Changes in BNP levels during sleep in the patients with OSAS may be related to blood pressure variations, but may be too small to play a significant physiological role in regulating diuresis in OSAS. Further work is required to determine the precise role of dual natriuretic system in cardiovascular load and natriuresis in OSAS.