Changes in immune function following surgery for esophageal carcinoma.

Changes in immune function due to surgical injury have been well-documented. Immunosuppression is one of the causes of infectious complications leading to organ dysfunction in critical illness. It is not known what kind of surgery in the daily clinical practice causes immunosuppression. Stress response and immune function following surgery for esophageal carcinoma, assuming a highly-stressed operation, were studied and then compared with the stress response and immune function following gastric surgery, a moderately-stressed procedure. Forty patients who underwent esophagectomy and 39 patients receiving gastric operation were studied. The concentrations of serum interleukin-6 (IL-6) were measured preoperatively, at 1, 2, and 6 h, and at 1, 3, and 10 d after operation. Total protein, serum albumin, rapid turnover protein, serum CRP, and cortisol were measured before operation and at 1, 3, 7, and 21 d after operation. ConA- and PHA-stimulated lymphocyte proliferation, IgA, IgG, and IgM were also measured preoperatively, and on 7 and 21 d following surgery. The patients were fed exclusively by total parenteral nutrition (TPN). A striking rise of IL-6 was observed, with a peak in both groups at 1 to 6 h following operation. The peak values were 419+/-30 pg/mL, which was approximately twice as high in the esophagectomy patients as in the gastrectomy patients (195+/-40 pg/mL). CRP and cortisol also increased after operation, and these increases were also significantly greater in the esophagectomy patients. ConA- and PHA-stimulated lymphocyte proliferation decreased significantly 7 d after esophagectomy (P<0.05), but was unchanged in the patients receiving gastrectomy. Suppression of cellular immunity correlated significantly with serum cortisol, and was preceded by a rise in serum IL-6. The IgA, IgG, and IgM levels, however, remained unchanged from their preoperative values throughout the study in both groups. Nutritional status in terms of serum protein, albumin, and rapid turnover protein, decreased postoperatively, but there was no difference between the two groups. It is, therefore, concluded that cell-mediated immunosuppression, preceded by a hyperinflammatory response, is an observable reaction in patients following esophageal surgery, but not in patients undergoing gastric surgery.     

Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes

Organic anion transporter 1 (OAT1) is the para-aminohippurate (PAH) transporter in the basolateral membrane of the proximal tubule. The present study investigated whether or not nonsteroidal anti-inflammatory drugs (NSAIDs) are transported by OAT1. All of the NSAIDs tested inhibited [14C]PAH uptake via OAT1 expressed in Xenopus laevis oocytes. Ibuprofen, indomethacin, salicylurate, and naproxen showed the strongest potency to inhibit [14C]PAH uptake (Ki approximately 2-10 microM); acetylsalicylate, salicylate, and phenacetin exhibited moderate potency (Ki approximately 300-400 microM), and acetaminophen (paracetamol) exhibited the weakest inhibitory potency (Ki approximately 2 mM). Radiolabeled acetylsalicylate, salicylate, and indomethacin were taken up by OAT1 and the uptake rate of these three NSAIDs was enhanced by the outwardly directed dicarboxylate gradient. The efflux of the preloaded [14C]PAH from the oocytes via OAT1 was trans-stimulated by PAH and glutarate added to the media. The addition of salicylate, acetylsalicylate, or salicylurate into the media also trans-stimulated the efflux of PAH, whereas indomethacin did not. The present study indicates that OAT1 is responsible for the renal uptake and secretion of NSAIDs.     

Effects of chronic administration of glucocorticoid on midazolam pharmacokinetics in humans.

Midazolam (MDZ) is metabolized by CYP3A. Glucocorticoids are potent inducers of CYP3A in humans. The possible interaction between intravenous MDZ and chronically administered glucocorticoids was investigated during surgery in patients. MDZ (0.2 mg/kg) was administered intravenously to 8 patients taking glucocorticoid chronically and 10 patients not taking glucocorticoid. In patients taking glucocorticoid, the AUC0-infinity and CL of MDZ was decreased to 63.9% (16.3 +/- 10.5 vs 25.5 +/- 20.7 microg x min/mL) and increased to 127.5% (16.7 +/- 10.7 vs 13.1 +/- 8.3 mL/min/kg) of that in the control group, respectively. The terminal t1/2 values of MDZ were similar in two groups. In patients taking glucocorticoid, the AUC0-infinity of 1'-hydroxymidazolam (1'-OH MDZ) was 66.7% of that in the control group (7.6 +/- 2.6 vs 11.4 +/- 9.7 microg x min/mL), and the terminal t1/2 of 1'-OH MDZ was significantly (p < 0.01) decreased (1.8 +/- 0.5 vs 3.0 +/- 0.8 hr). Accumulative urinary excretion of 1'-OH MDZ glucuronide was increased to 157.6%. These observations might be results from induction of CYP3A4 and/or UDP-glucuronosyltransferase by glucocorticoids.     

Akinesia and axial rigidity without limb rigidity: an intermediate form between progressive supranuclear palsy and pure akinesia of Imai and Narabayashi

We report five patients with atypical parkinsonism characterized by freezing phenomenon, akinesia and axial rigidity without limb rigidity or tremor. These patients were selected from 252 patients with parkinsonism who were referred to our clinic from 1986 to 1993. They have common clinical features consisting of freezing phenomena involving all four extremities, especially in the initiation of walking, and marked axial rigidity; otherwise, neither supranuclear ophthalmoparesis nor nuchal dystonia was noted. Their clinical features did not change over several years except in one patient who later developed typical manifestations of progressive supranuclear palsy (PSP). Levodopa was of no effect on their symptoms. After excluding other possibilities, it is our conclusion that they represent an atypical form of PSP lying between the pure akinesia of Imai and Narabayashi and the typical form of PSP.     

Chronic hypertension induced by streptozotocin in rats

Summary An intravenous injection of 40 or 65 mg/kg streptozotocin induced not only diabetes but also severe hypertension in rats. Whereas the hyperglycemia developed fully within a few days after the injection of streptozotocin, the hypertension progressively advanced and reached maximum level several weeks after the treatment and lasted more than 20 weeks. Twenty mg/kg streptozotocin did not induce hyperglycemia but significantly increased blood pressure several weeks after the treatment. Arrest of growth, polyuria, glycosuria, hyperlipemia and lenticular cataracts developed in the animals treated with 40 or 65 mg/kg streptozotocin, but in none of the animals treated with 20 mg/kg. In histological examinations in the 24th week after the treatment, degranulation and necrosis in the pancreatic -cells, and vacuolization and deposition of PAS-positive materials in the renal proximal tubules were found in the animals treated with 40 or 65 mg/kg streptozotocin.     

Dynamic acquisition with a three-headed SPECT system: application to technetium 99m-SQ30217 myocardial imaging

A method for SPECT data acquisition, "continuous repetitive rotation acquisition," was developed with a high-sensitivity three-headed SPECT system. The method was applied to the dynamic imaging of 99mTc-SQ30217, a new myocardial imaging agent. After acquisition and reconstruction of SPECT data every minute, projection images at arbitrary intervals were used for tomographic reconstruction to determine the best timing of SPECT imaging in 99mTc-SQ30217. Based on a comparison of several possible acquisition intervals, SPECT data acquisition within 9 min after injection is recommended because of high myocardial uptake (myocardium-to-lung ratio, 2.83 +/- 0.42 (mean +/- s.e.m.) at 3-6 min) and relatively low hepatic uptake (myocardium-to-liver ratio, 0.85 +/- 0.13 at 3-6 min). The rate constant of the clearance of 99mTc-SQ30217 from the myocardium obtained by SPECT was: k1 = 0.249 +/- 0.050 per min (average half-life = 2.8 min) and k2 = 0.012 +/- 0.004/min (average half-life = 58 min). The continuous repetitive rotation acquisition SPECT study appears useful for imaging SQ30217 with its rapidly changing myocardial distribution.     

Clinical study of growing up aneurysms: report of 25 cases

Twenty-five cases of patients with growing up aneurysms are reported. Growth of the aneurysm was confirmed by repeated angiography within 1 month in 11 cases (short-term group), and for over 1 month in the other 14 cases (long-term group) following the initial angiography. Clinical history, shape and growth pattern of aneurysms, as well as hemodynamic factors that effect the growth were investigated in each group. The aneurysms were classified according to the shape into dome-type (smooth contour) and bleb-type (irregular contour). In all cases of the short-term group, the first angiography was performed because of rupture of the aneurysm. In this group, 4 cases bled again because of enlargement or the development of an aneurysmal bleb. Growth rate and the initial size of the aneurysm did not effect the potential of re-rupture. In the long-term group, 9 cases out of 14 (64.3%) had "non-ruptured aneurysm" at the time of first angiography. In the follow up, 5 cases were ruptured (two because of re-bleeding and three for the first time). In 3 out of these 5 cases, a bleb was demonstrated on initial angiography, and in another case, a bleb was demonstrated in follow-up angiography. Only one case ruptured because of the growth of the aneurysmal dome. Most of the aneurysms that rupture, in the follow-up survey, showed a larger growth rate in comparison with aneurysms that did not rupture. Many cases of this long-term group were associated with hypertension or vascular abnormalities which would effect the aneurysmal growth.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognosis of the Lennox Syndrome—Long-Term Clinical and Electroencephalographic Follow-up Study, Especially with Special Reference to Relationship with the West Syndrome

The long-term clinical and electroencepha-lographic follow-up studies were carried out for more than three years, up to 14 years in the longest, on 116 cases with Lennox syndrome. And the results of systematic study on changing patterns and outcome have been reported. The follow-up examination was performed also on West syndrome which is closely related with Lennox syndrome; especially the relationship between both syndromes regarding prognosis has been clarified.

• 1 According to the long-term follow-up on 116 cases with Lennox syndrome, there were 98 cases (84.5%) having mental defect. The remaining of seizure was observed in 71 cases (61.2%) and persisted as Lennox syndrome except for one case.
• 2 Generally speaking, the cases with age of onset before two years old showed unfavorable outcome.
• 3 There were 42 cases (36.2%), which were converted from West syndrome and showed markedly unfavorable prognosis in regard to intelligence as well as the remaining of seizure. (31 cases, 77.5%)
• 4 On the other hand, in 23 idiopathic cases, which showed no developmental retardation before onset of seizure, had favorable outcome, and the remaining of seizure was observed in eight cases (34.8%). However, even in such cases, it was noticed that those displaying mental defect at the follow-up attained 14 cases (60.9%). That is to say, it was clarified that persistence of even minor seizures induced mental deterioration.
• 5 The cases with favorable prognosis showed usually a typical slow spike-and-wave pattern electroencephalographically, whereas those with poor prognosis showed mostly an asymmetric or disorganized slow spike-and-wave pattern.
• 6 In many cases displaying signs of brain atrophy with pneumoencephalogram and accompanying overt neurological signs at the initial examination, prognosis is obviously poor.
• 7 From the follow-up examination on 94 cases with West syndrome for three to 15 years, there were 51 cases (54.3%) which was transformed into Lennox syndrome. Among them, those cases with the remaining of seizure at the time of follow-up were 44 (46.8%) out of 94 cases, of which 37 cases (83.8%) had remaining seizure as Lennox syndrome.
• 8 From the above results, it is emphasized that Lennox and West syndromes show close relationship with each other and that a study should be done on the interrelation between their prognosis.

     

Apparently unprovoked seizures precipitated by prefebrile condition

We investigated the clinical features of the patients whose body temperature exceeded 38 degrees C, in 0.5-6 hours after an afebrile seizure (prefebrile seizure). Patients with meningoencephalitis and epilepsy were excluded from this study. From May 1995 to April 1997, seven cases of prefebrile seizures admitted to PL hospital. Three of the 7 had a status and one had a cluster of seizures. Five patients had had several febrile seizures prior to the onset of prefebrile seizures. One developed epilepsy during the follow-up period. We speculate that prefebrile seizures have several factors of complex febrile seizures and require a careful follow-up.     

Effects of small dose of brotizolam on P300

Nine healthy men (mean age, 22.2 years) participated in two experimental sessions cross-overed randomly in a double blind manner; one with a placebo and the other with 0.125 mg of brotizolam (BTZ) administered in the morning. Resting electroencephalogram and event-related potential under oddball paradigm was recorded before and 1, 2, 4, 6 and 8 h after the administration. Mean 30-msec bin amplitude from 240 msec to 450 msec after the stimulus was compared between placebo and drug sessions in order to observe P300. Brotizolam reduced the amplitude of P300 at 6 h after administration. It was noted that the effects of BTZ were most marked at Fz.