Plasma and tumor gastrin in patients with primary hyperparathyroidism

It is well known that primary hyperparathyroidism is often associated with peptic ulcer. The purpose of this study is to confirm the relationship between the gastrin-levels before and after parathyroidectomy in fourteen patients with primary hyperparathyroidism, and to determine the localization of gastrin in the surgically resected parathyroid tumor. The results obtained were as follows: 1) Three patients had peptic ulcer (gastric ulcer and duodenal ulcer), the incidence being 21%. 2) The basal serum gastrin levels were 123.0% +/- 68.1 pg/ml before operation and decreased to 90.2 +/- 44.5 pg/ml after operation. In the 3 patients with slightly elevated gastrin levels, the mean level before operation was 209.1 +/- 61.2 pg/ml. The gastrin level decreased to 116.4 +/- 62.0 pg/ml after operation. 3) Gastrin immunoreactivity was detected in 10 out of 14 tumors and its localization was at the periphery of tumor cells. From these results, we conclude that extragastric gastrin secretion from parathyroid tumors may be one of the cause of peptic ulcer in patients with primary hyperparathyroidism.     

Skip mediastinal nodal metastases in non-small cell lung cancer

Objective: To reveal the incidence and clinical significance of mediastinal nodal metastases without N1-station nodal metastases (‘skip-N2 metastases’) in non-small cell lung cancer (NSCLC). Methods: A total of 450 NSCLC patients who underwent tumor resection with a systemic mediastinal nodal dissection were retrospectively reviewed. p53 status and proliferative activity represented as proliferative index (PI) were also examined immunohistochemically. Results: Skip-N2 metastases were documented in 49 (13%) patients of all 450 patients; among 334 patients without N1-nodal involvement, 18% patients had skip-N2 metastases. The postoperative survival of skip-N2 patients was almost same as that for patients with metastases to both N1 and N2 nodes. Skip-N2 metastases were significantly more frequent in male patients and squamous cell carcinoma patients. In addition, the mean PI for tumor with skip-N2 metastases was significantly higher than that for any other pathologic nodal (pN)-status diseases. Combined with histologic type and PI, the incidences of skip-N2 metastases for adenocarcinoma showing lower PI were only 5% (7/137) of all patients and 7% (7/94) of patients without N1-nodal involvement. Conclusions: N1 nodal status is not a useful predictor of N2 nodal status in NSCLC, because skip-N2 metastases were documented in 18% patients showing no N1-nodal involvement. However, N1 node-guided dissection might be performed in patients with adenocarcinoma showing lower PI, because the incidence of skip-N2 metastases was extremely low.     

Effect of nasal continuous positive airway pressure treatment on plasma adrenomedullin levels in patients with obstructive sleep apnea syndrome: roles of nocturnal hypoxia and oxidant stress.

Obstructive sleep apnea syndrome (OSAS) is recognized as one of the risk factors of hypertension and cardiovascular disorders. In the current study, we hypothesized that the hypoxic stress and oxidative stress caused by obstructive sleep apnea would increase circulating adrenomedullin (ADM) levels in untreated OSAS patients as compared to an age and body mass index (BMI)-matched control group and an age-matched, but normal-BMI control group. We further hypothesized that nasal continuous positive airway pressure (nCPAP) treatment may decrease OSAS-induced hypoxic stress, oxidative stress and ADM levels. To examine these hypotheses, we measured circulating ADM and reactive oxygen species (ROS) from leukocytes before and after nCPAP therapy in OSAS patients. The circulating levels of ADM and amount of ROS in untreated OSAS patients were significantly greater than those in the controls. No differences in ADM levels were found between the increased-BMI controls and normal-BMI controls. We observed that nCPAP treatment decreased sleep apneas, nocturnal oxyhemoglobin desaturation, the circulating ADM, and ROS production by leukocytes in OSAS patients. The ADM levels were associated with the magnitude of oxyhemoglobin desaturation rather than the number of sleep apneas. These observations suggest that nCPAP therapy could reduce OSAS-induced nocturnal hypoxemia, generation of ROS, and ADM in patients with OSAS.     

In vivo presynaptic and postsynaptic striatal dopamine functions in idiopathic normal pressure hydrocephalus.

Differentiation of impaired gait seen in idiopathic normal pressure hydrocephalus (iNPH) from parkinsonian gait is sometimes a great challenge and important for future medication in the clinical setting. To investigate dopaminergic contribution to its pathophysiology, two aspects of the trans-synaptic dopamine functions in the striatal region in eight iNPH patients na?ve to dopaminergic drugs were examined using positron emission tomography with a presynaptic marker [11C]CFT ([11C]2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) that binds to dopamine transporter and a postsynaptic marker [11C]raclopride that binds to D2 receptor. Quantitative values of binding potentials (BPs) for [11C]CFT and [11C]raclopride were compared between patients and eight age-matched healthy subjects. The BPs and magnetic resonance imaging-based morphometric measures in iNPH were used for correlation analyses between the magnitude of binding of these in vivo markers and clinical severity of the patients. Analysis of variance showed significant reduction in [11C]raclopride binding in the putamen and nucleus accumbens (P<0.05, corrected for multiple comparison) and unchanged striatal [11C]CFT binding in iNPH. The dorsal putamen [11C]raclopride binding correlated negatively with gait severity (r=0.720, P<0.05), and the nucleus accumbens [11C]raclopride binding correlated positively with emotional recognition score (r=0.727, P<0.05) in the disease group. No significant relationship was observed between BPs and morphometric measures. The current result of the postsynaptic D2 receptor reduction along with preserved presynaptic activity in the nigrostriatal dopaminergic system reflects a pathophysiology of iNPH. Postsynaptic D2 receptor hypoactivity in the dorsal putamen may predict the severity of gait impairment in iNPH.     

Initial lithium augmentation improves the antidepressant effects of standard TCA treatment in non-resistant depressed patients

The hypothesis was tested that an initial lithium-tricyclic antidepressant (TCA) combination has a better antidepressant effect than standard TCA treatment in non-refractory depression at the beginning of an episode. Twenty bipolar melancholic type depressed inpatients under lithium-TCA treatment were compared with 20 patients with the same diagnosis and TCA-placebo treatment for 5 weeks under double-blind conditions. All patients were male. Initial lithium-TCA treatment reduced depressive symptoms significantly more than antidepressant treatment with TCA and placebo after 5 weeks, but not in weeks 1 or 2. It can be concluded that lithium augmentation of TCA treatment should be started even at the beginning of antidepressant TCA treatment to provide a better treatment response in those patients who will profit from long-term lithium prophylaxis, e.g. bipolar patients with melancholic type depression.     

Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders.

We evaluated regional blood flow and oxygen metabolism in the cerebral and cerebellar cortices of 15 patients with unilateral major cerebral artery occlusive disorders with PET. These patients showed a cortical blood flow asymmetry in middle cerebral artery distribution. Only subcortical abnormalities were detected on computed tomography. Nine patients showed crossed cerebellar hypoperfusion, a reduction in contralateral cerebellar blood flow, while six did not. No difference in the degree of cerebral blood flow asymmetry existed between the two patient groups. However, oxygen metabolism asymmetry was more pronounced and was more closely matched to blood flow asymmetry in patients with crossed cerebellar hypoperfusion. These findings suggest that a major cause of cerebral cortical blood flow reduction is reduced metabolic demand in patients with crossed cerebellar hypoperfusion. Crossed cerebellar hypoperfusion may have clinical significance as a reflection of the cerebral metabolic state on blood flow images.     

Scopolamine abolishes cerebral blood flow response to somatosensory stimulation in anesthetized cats: PET study

The effect of the cholinergic blocker, scopolamine on the cerebral blood flow (CBF) response to vibrotactile stimulation of a fore paw was studied using high-resolution positron emission tomography and H₂¹⁵O in 5 pentobarbital-anesthetized cats. Before scopolamine injection, the CBF response to the stimulation was found in the contralateral somatosensory cortex (mean ratio (contralateral/ipsilateral) control: stimulated1.02 ± 0.02: 1.17 ± 0.05; P < 0.01). After intravenous injection of scopolamine (0.35 mg/kg), the CBF response was abolished. However, the cerebral metabolic rate of glucose (CMRGlu) response to the same stimulation was unchanged after scopolamine injection in the same cats. We concluded that scopolamine abolishes the CBF response but not neuronal response to stimulation. We suggest that cholinergic mechanisms may play an important role for mediating CBF coupling to neuronal activity during physiological stimulation.     

A brainstem variant of reversible posterior leukoencephalopathy syndrome (RPLS) presenting with visual disturbance]

A 40-year-old woman noticed blurred vision of the right eye. The optic disc edema of bilateral eyegrounds was noted, and brain MRI showed abnormal signals of the brainstem at a neurosurgical clinic. On her first visit, blood pressure was as remarkably high as 250/130 mmHg. Neurologically, only optic disc edema of bilateral eye-grounds was found. Both T2-weighted MRI and FLAIR showed hyperintense signal areas mainly from the ventral pons to medulla oblongata. These areas were not enhanced with gadolinium. About three weeks after the administration of an antihypertensive agent, brain MRI revealed no abnormal signal. About three months later, the blurred vision disappeared and ophthalmological abnormalities subsided. We diagnosed her with a brainstem variant of RPLS, presenting with visual disturbance caused by hypertensive retinopathy.