The TriAGe+ Score for Vertigo or Dizziness: A Diagnostic Model for Stroke in the Emergency Department.

BACKGROUND: Vertigo or dizziness is a common occurrence, but it remains a challenging symptom when encountered in the emergency department (ED). A diagnostic score for stroke with high accuracy is therefore required. METHODS: A single-center observational study (498 patients) was conducted. The predictor variables were derived from a multivariate logistic regression analysis with Akaike information criterion. The outcome was the occurrence of stroke. We evaluated the utility of a new diagnostic score (TriAGe+) and compared it with the ABCD2 score. RESULTS: The cohorts included 498 patients (147 with stroke [29.4%]). Eight variables were included: triggers, atrial fibrillation, male gender, blood pressure ≥140/90 mm Hg, brainstem or cerebellar dysfunction, focal weakness or speech impairment, dizziness, and no history of vertigo or dizziness or labyrinth or vestibular disease. We derived the TriAGe+ score from these variables. In the cohort, the prevalence of stroke increased significantly using the diagnostic score: 5.9% for a score of 0-4; 9.1% for 5-7; 24.7% for 8-9; and 57.3% for 10-17. At a cutoff value of 10 points, the sensitivity of the score was 77.5%, the specificity was 72.1%, and the positive likelihood ratio was 3.2. When the cutoff was defined as 5 points, the score obtained a high sensitivity (96.6%) with a good negative likelihood ratio (.15). The new score outperformed the ABCD2 score for the occurrence of stroke (C statistic, .818 versus .726; P < .001). CONCLUSIONS: The TriAGe+ score can identify the occurrence of stroke in patients with vertigo or dizziness presenting to the ED.

Websites offer helpful information concerning consultation with headache specialists.

Patients with severe primary headache may benefit from consultation with headache specialists, but doctor attendance rates in Japan are very low. More headache patients might consult headache specialists if these specialists were more widely recognized by the public. To determine what information prompted patients to seek consultation with a headache specialist, we questioned 256 primary headache patients about the source of the helpful information concerning consultation with headache specialists. From 191 patients, a total of 235 responses to the questionnaire were obtained. The most common response was 'websites' (33.2%), followed by 'professionals' (23.8%), 'acquaintances' (20.9%), 'print media' (6.8%) and 'TV/radio' (3.4%). Patients who indicated websites showed the most severe pain and highest impact of headache, and accounted for 52.4% of those with cluster headaches. Development of websites concerning headache specialists would seem likely to increase doctor attendance rates for patients with primary headache.

Somatostatin type 2A receptor immunoreactivity in human pancreatic adenocarcinomas.

Somatostatin and its analogs have been included in experimental treatment protocols for advanced pancreatic adenocarcinoma based on their known antisecretory and antiproliferative properties. Somatostatin receptor type 2 (sstr2A) mediates antiproliferative actions of somatostatin and has the strongest affinity to the therapeutically used somatostatin analog--octreotide. We investigated localization of sstr2A in 27 pancreatic adenocarcinomas in relation to tumor histological features and neuroendocrine differentiation confirmed by immunoreactivity for chromogranin A (CgA), chromogranin B (CgB), or somatostatin. Immunoreactivity for sstr2A generally coincided with tumor neuroendocrine differentiation demonstrated by staining for CgA and was present on the cell membranes of pancreatic islet cells and endocrine cells occasionally present in the wall of normal pancreatic ducts. Thirteen pancreatic adenocarcinomas contained cells immunoreactive for sstr2A in numbers ranging from occasional single cells, cell clusters, or carcinoma duct segments. In two cases, cells immunoreactive for sstr2A and CgA represented more than 30 and 10% of the total tumor cell population (case 1 and 15, respectively). Case 1 fulfills the diagnostic criteria of mixed ductal endocrine carcinoma. We conclude that immunohistochemical staining for a generic neuroendocrine marker such as CgA would facilitate identification of a subgroup of pancreatic adenocarcinomas expressing sstr2A receptors. Future studies need to evaluate the responsiveness of these tumors to somatostatin analogue treatment.

Pancreatectomy combined with superior mesenteric-portal vein resection for adenocarcinoma in pancreas.

The aims of this study were to investigate morbidity, mortality, and survival of patients with ductal adenocarcinoma of the pancreas who underwent pancreatectomy without (group 1) or with (group 2) en bloc portal vein resection and to study the degree of carcinoma invasion of the portal vein in group 2. The medical records of 46 and 28 patients in groups 1 and 2, respectively, were reviewed. In addition, the degree of invasion of the wall of the portal vein was categorized histologically into three types: type I, transmural invasion involving the intima; type II, invasion of the wall of the vein without intimal involvement; and type III, compression of the wall of the vein by surrounding carcinoma without true invasion. The morbidity and mortality in group 1 (26% and 4%) were not different from those in group 2 (32% and 4%). Similarly, there was no difference in survival between the two groups. Survival tended to vary directly with the depth of invasion of the wall of the portal vein: type I 6.8 +/- 1.9 months; type II 15.3 +/- 6.4 months; type III 20.6 +/- 13.0 months. These findings suggest that en bloc resection of the pancreas and the portal vein does not increase mortality and morbidity after pancreatectomy; survival after en bloc resection was similar to that of patients not requiring portal vein resection. Combined resection of the pancreas with the portal vein could be an option in the treatment of pancreatic cancer with direct invasion of the portal vein.

Role of intraoperative insulin monitoring in surgical management of insulinoma.

BACKGROUND AND PURPOSE: Precise localization and surgical excision is the therapeutic strategy for insulinomas. However, it is often difficult to localize the insulinomas, because of their small size. Surgeons may not localize and remove all of them together, particularly in patients with multiple insulinomas. We reviewed our experience to confirm the efficacy of blood glucose and intraoperative immunoreactive insulin (IRI) monitoring for surgical management of insulinomas. PATIENTS AND METHODS: Thirty-nine patients with insulinoma were surgically treated in our department. Perioperative blood glucose monitoring was performed in 14 patients, intraoperative quick IRI assay of the peripheral blood in 10 patients, and assay of a portal sample in 4 patients by an IMX analyzer. RESULTS: Rebound response of blood glucose to insulinoma removal was not always noted (8/14; 57%). Seven of ten patients showed a decrease of peripheral serum IRI levels within 15 minutes after removal of the insulinoma. The other two patients showed a rebound response of peripheral blood glucose or portal IRI. All the patients who had intraoperative monitoring of peripheral blood and peripheral and portal IRI had no recurrent insulinoma syndrome after surgical removal of their insulinomas. CONCLUSION: Combined monitoring of peripheral blood glucose and peripheral and portal IRI are helpful in the surgical management of insulinomas, as they can indicate that no insulinoma remains.

[A case of HTLV-1 associated myelopathy (HAM) with pseudopseudohypoparathyroidism].

We report a case of HTLV-1 associated myelopathy (HAM) with pseudopseudohypoparathyroidism (PPHP). A 57-year-old woman, without a history of blood transfusion, was admitted with numbness and pain in her legs. Pain sensation in both legs was reduced and tendon reflexes were exaggerated. She exhibited spastic gait. The diagnosis of HAM was made because of positive antibody for HTLV-1 in blood and CSF. She also had features of Albright syndrome (short stature, round face, and short fourth metatarsals) without abnormal calcium and phosphorus metabolism, leading to the diagnosis of PPHP. Brain CT revealed bilateral calcification of the basal ganglia. Although HAM rarely accompanies pseudohypoparathyroidism (PHP), there are few reported cases of HAM associated with PPHP. The exact mechanism of HAM is not known, but it is thought to involve an immune-related process. Since PHP is considered to induce a state of mild immunosuppression through reduction of 1,25-dihydroxyvitamin D3, it is possible that susceptibility to HAM could be augmented in the presence of PHP. If PPHP should be an incomplete form of PHP, a similar mechanism may be involved in the association of PPHP and HAM.

The antiangiogenesis effect of interleukin 12 during early growth of human pancreatic cancer in SCID mice.

Interleukin 12 (IL-12) is a heterodimeric cytokine that exerts a potent antitumor effect through its pleiotropic actions. It was recently reported that IL-12 has also a potent antiangiogenic effect through the induction of IFN-gamma, which triggers the production of chemokines such as IP-10 that has been shown to have antiangiogenesis properties. In this study we transfected the IL-12 gene into a human pancreatic adenocarcinoma cell line (PK-1). PK-1 cells transfected with the green fluorescence protein (gfp) gene were used as positive controls. The in vitro growth curve and in vivo tumor growth of transfectants (IL-12/PK-1 and gfp/PK-1) were compared with those of parental cells. The SCID mice used in this study were administered antiasialo GM-1 Ab (100 microg, i.p., twice weekly) to deplete the remaining immunoeffector cells, NK cells. Using a skinfold chamber model, we observed and recorded tumor angiogenesis by intravital microscopy. In vitro growth of IL-12/PK-1 and gfp/PK-1 cells was not different from that of wild-type PK-1 cells (wt/PK-1). However, IL-12 transfected PK-1 cells did not develop into tumors as did the wt/PK-1 cells after subcutaneous inoculation in antiasialo GM-1 Ab administered SCID mice. The growth of IL-12/PK-1 tumors was restored in mice treated with anti-IL-12 antibody. We found that IL-12/PK-1, in contrast to gfp/PK-1 and wt/PK-1, failed to initiate an angiogenic response, as observed in the skinfold chamber model. These results indicate that the antiangiogenesis effect of IL-12 alone, without immune system involvement, is sufficient to block the growth of human pancreatic cancer.

Local cerebral hemodynamic changes through the angiographic stages of moyamoya disease.

In order to elucidate the cerebral hemodynamic changes that occur in Suzuki's six angiographic stages of moyamoya disease, local cerebral blood flow (LCBF) during the stable state and CO2 responsiveness of LCBF (L-CO2R: delta %LCBF/delta PaCO2) were measured by the Xenon CT-CBF method. Nineteen patients with moyamoya disease (mean age: 36.8 +/- 11.6 years) and 11 age-matched normal volunteers were studied. The LCBF during the steady state at all stages was not significantly different from that in normal volunteers. At stage 6, however, the LCBF was slightly decreased in the anterior part of the brain, resulting in loss of "hyperfrontality." On the other hand, the L-CO2R in the anterior part of the brain tended to diminish with progression through the stages. Especially in the frontal cortex, the L-CO2R at stage 5 was significantly less than that in normal volunteers (p < 0.01) or at stage 3 (p < 0.05). In conclusion, the cerebrovascular reserve in the anterior circulation became insufficient after stage 4, although the posterior circulation was well maintained. Revascularization surgery involving the anterior circulation may be crucial to prevent ischemic events.

Distinguishing patients with senile dementia of Alzheimer type and normal elderly subjects utilizing xenon CT-CBF and multivariate analysis.

Local cerebral blood flow (LCBF) was measured in 17 patients with senile dementia of Alzheimer type (SDAT) and 17 normal controls, utilizing stable xenon computed tomography (Xe CT-CBF). In patients with SDAT, LCBF values were decreased in the cerebral cortex and subcortical structures including the thalamus, basal ganglia and white matter of both hemispheres. Linear discriminant function analysis of LCBF values separated patients with SDAT from normal elderly subjects, with an error of 8.8%. Variables helpful in distinguishing SDAT patients from normal subjects were LCBF values for the frontal and temporal cortex. Multiple regression equation for predicting cognitive performance scores from LCBF values showed the best correlations with LCBF values for the frontal and occipital cortex and thalamus. Xe CT-CBF measurements provide useful information concerning diagnosis and brain function in patients with SDAT.

[The role of preoperative staging for pancreatic cancer].

Despite the poor prognosis of pancreatic carcinoma patients, surgical resection remains the only potentially curative treatment. As it has been demonstrated that extended radical surgery does not lead to a better prognosis, accurate staging to select those patients who may benefit from resection is essential. According to the report of a national survey of pancreatic cancer in 1997, patients with S0 or S1, RP0 or RP1, and N0 or N1 disease have longer survival periods compared with patients with S2, RP2, and N2 disease. Therefore patients classified as Stage I, Stage II, or Stage III are recognized as candidates for surgical resection. Patients classified as Stage IVb because of positive P factor or positive H factor are selected for conservative treatment such as chemotherapy and irradiation. It remains to be clarified whether patients classified as Stage IVa should undergo surgical resection or not. Future prospective randomized studies of patients with Stage IVa disease will reveal whether surgical resection or chemoradiation is effective. Helical CT is useful to evaluate S and RP factors for definitive preoperative staging. CT-AP can reveal occult metastases to the liver. These preoperative evaluations should be evaluated along with histological findings.

[X-Linked Charcot-Marie-Tooth disease with a new mutation (Thr191Ala) in the connexin32].

We report a 59-year-old man with X-linked Charcot-Marie-Tooth (CMT) disease and a new point mutation in the connexin32 gene. The patient first noticed mild gait disturbance five years previously. On admission, he exhibited muscle atrophy and weakness in the distal part of both legs, mild muscle atrophy of both hands without weakness, and a minimal reduction of touch sensation in the right dorsal foot. Nerve conduction velocity of the peripheral nerves was diffusely reduced. Electromyography exhibited high-amplitude, long-duration, polyphasic motor unit potentials in the muscles of the extremities. Fibrillation potential and positive sharp wave were present in the affected muscles. Cerebrospinal fluid protein was slightly elevated. The polyneuropathy did not respond to high-dose corticosteroid treatment, and showed very slow progression. His parents were not consanguineous. His father and two sons were healthy, but similar illness (more severe) was suspected in his younger brother. Gene analysis (Southern hybridization) did not reveal any duplication or deletion in the CMT 1 A-REP region. However, a novel mutation (Thr191Ala) was detected in the connexin32. Although more than 160 mutations in the connexin 32 gene have been identified worldwide, approximately ten mutations have so far been reported in Japan. In comparison with X-linked CMT patients with other connexin32 mutations, the present case was characterized by late onset and mild neurological manifestation. Gene analysis provides a useful tool for diagnosing cases with slowly progressive, motor dominant polyneuropathy of unknown origin.

Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer.

BACKGROUND: The prognosis of patients with resected pancreatic cancer remains poor. This study evaluated the effect of adoptive immunotherapy (AIT) using intraportal infusion of lymphokine-activated killer (LAK) cells after curative resection and intraoperative radiation therapy (IORT) on advanced pancreatic cancer. METHODS: Twenty-nine consecutive patients with advanced pancreatic cancer (Japan Pancreas Society stage III or IV) were divided into two groups. The control group (n = 17) underwent tumour resection and IORT. The treatment group (n = 12) underwent resection, IORT and intraportal infusion of LAK cells combined with recombinant interleukin 2 (rIL-2). The incidence of liver metastasis and the survival rate of these two groups were compared. RESULTS: Although the overall survival between groups was not statistically different (P = 0.082), there were more patients (four) alive 3 years after operation in the test group (36 per cent versus zero), and the incidence of liver metastases in the treatment group was significantly lower (three of 12 versus ten of 15; P < 0.05). LAK therapy influenced survival positively in multivariate analysis. CONCLUSION: These preliminary observations suggest that AIT warrants further study as a possible adjuvant for patients undergoing curative resection and IORT for pancreatic cancer.

Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection.

Immunosuppressive potentials of the blockade of intercellular adhesion molecule-1 (ICAM)-1/leukocyte function-associated antigen 1 (LFA-1) were examined in a murine islet allotransplantation model by using blocking monoclonal antibodies (MAbs) against these molecules. Isolated islets from ICR mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Antibodies were administered immediately after transplantation at a dose of 100 micrograms/mouse/d for 3 or 7 d. In non-treated mice, islet grafts were rejected within 16 d, but the treatment with an anti-ICAM-1 MAb (KAT-1) alone, with anti-LFA-1 MAb (KBA) alone, or with both MAbs significantly prolonged the graft survival. In particular, the combination of KAT-1 and KBA in a 7-d course produced a marked prolongation and induced indefinite graft survivals over 100 d in 88% of recipients. Expression of cytokine transcripts within the islet allografts was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). In the mice treated with KAT-1 and KBA, the transcripts for Th1 cytokines (interleukin 2 [IL-2] and interferon gamma [IFN-gamma]) were not detected, but the expression of Th2 cytokines (IL-4 and IL-10) was enhanced and persisted over 140 d. In contrast, Th1 cytokines were dominantly expressed in the grafts from untreated mice. These results indicate that administration of anti-ICAM-1 and/or anti-LFA-1 MAbs prolongs murine islet allograft survival potentially by indicating a Th2 deviation.

Total number and size distribution of hepatic metastases of carcinoma.

OBJECTIVE: To quantify the susceptibility of carcinoma to hepatic metastases by studying autopsy livers with carcinoma metastases, the primary sites of which were mostly the digestive organs. STUDY DESIGN: We developed a stereologic method of estimating the total number, N, and the size distribution of metastatic tumors in the liver based on a geometric model of spherical nodules with varying radii, r. This method proved to be sufficiently reliable by disector analysis simultaneously performed in some cases; it gave an approximate result. This method was applied to the 31 autopsy cases. Correlation and regression analyses were performed among N, the mean radius of nodules, rmean, and conventional pathologic features of the primary tumor. RESULTS: The estimates of N ranged from 10 to 3.2 x 10(5). A close negative correlation was confirmed between N and rmean. Neither significant correlation nor regression was observed among N and the other pathologic factors of the primary tumors. CONCLUSION: N turned out to serve as a useful index for evaluating the metastatic potential of a carcinoma. However, investigation has yet to be made to determine biologic factors in the primary tumor closely associated with N.

Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: differences in clinical characteristics and surgical management.

HYPOTHESIS: Intraductal papillary mucinous tumors (IPMTs) of the pancreas may be meaningfully construed as representing 2 clinically distinct subtypes: main duct tumors (MDT) and branch duct tumors (BDT). DESIGN: Retrospective study. SETTING: University hospital from January 1988 through December 1994. PATIENTS AND INTERVENTION: We reviewed diagnostic findings and late results of surgical treatment in 30 patients with IPMT. RESULTS: The tumor was located in the head of the pancreas more often in BDT than in MDT (65% [11/17] and 23% [3/13], respectively). Of the 13 patients with MDTs, 12 (92%) had intraductal papillary adenocarcinoma (noninvasive and minimally invasive types) and/or carcinoma in situ (carcinoma in situ: low papillary and/or flat tumor cells), and 3 (23%) had stromal invasion. Of the 17 patients with BDTs, 5 (29%) had intraductal papillary adenocarcinoma and/or carcinoma in situ. Two pancreatoduodenectomies and 8 pylorus-preserving pancreatoduodenectomies were performed in 10 of the 17 patients with BDTs, distal pancreatectomy in 7 patients with MDTs, and total pancreatectomy in 4 patients with MDTs. The 5-year survival rates were 47% for MDT and 90% for BDT. Four of 6 patients with MDTs who died had local recurrence. One patient died of liver metastasis and 1 of esophageal cancer. Only 1 patient with BDT of the 2 who died had recurrent disease. CONCLUSIONS: Intraductal papillary mucinous tumors may be composed of 2 clinically distinct subtypes: MDTs and BDTs. Initially, although distal pancreatectomy can be recommended for most MDTs, the need for cancer-free margins in this more aggressive type may necessitate total pancreatectomy. Pylorus-perserving pancreatoduodenectomies is recommended for most BDTs, but, because these tumors are more often adenomas, a good prognosis can be expected.

Transient vasodilatory effects of adrenomedullin on cerebral parenchymal microvessels in cats.

We studied the effects of adrenomedullin, structural homology of calcitonin gene-related peptide (CGRP), on the cerebral parenchymal microvessels in cats by our photoelectric method. Adrenomedullin significantly increased cerebral blood volume (CBV) at 0.5 and 1 min after intracarotid injection (0.01-1 nmol/kg, maximum; +0.71 vol% for 0.1 nmol/kg adrenomedullin). Adrenomedullin antagonist, adrenomedullin22-62 (0.01-10 nmol/kg), caused no significant changes in CBV and mean arterial blood pressure. Preinjection of 10 nmol/kg adrenomedullin22-52 blocked the vasodilatory effect of 0.01 nmol/kg adrenomedullin (P < 0.05). Pretreatment of 1 nmol/kg CGRP8-37, which has antagonistic activity against CGRP, also inhibited the vasodilatation of adrenomedullin. The degree of CBV reduction after adrenomedullin22-52 injection was greater than that after CGRP8-37 injection. Adrenomedullin has no major role in the maintenance of resting tone of intracerebral parenchymal vessels. Intravascularly administered adrenomedullin dilates cortical microvessels mainly through the specific adrenomedullin receptor.

Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma.

CONCLUSION: Abnormality of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 appears to play a limited role in pancreatic ductal carcinogenesis. BACKGROUND: Recently, a human G/T-specific TDG gene was identified. This protein acts in a system correcting G/T mispairs to G/C pairs. TDG was mapped to chromosome bands 12q22-q24.1, one of the regions frequently lost in pancreatic cancer. Therefore, there is the possibility that the TDG gene on 12q is one of the genes responsible for pancreatic ductal carcinogenesis. METHODS: Nucleotide sequences of the entire coding region of the TDG gene were analyzed in 21 human pancreatic cancer cell lines. mRNA expression of the TDG gene was also analyzed by Northern hybridization in several human tissues and 21 human pancreatic cancer cell lines. RESULTS: Decreased levels of mRNA expression were detected in the pancreatic cancer cell lines, but no somatic mutations were observed.

[Therapeutic strategy for the recurrence of pancreatic cancer following pancreatectomy].

It is well-known that the patients with pancreatic cancer are vulnerable for recurrence such as local relapse and liver metastasis after surgical resection. We revealed that a patient with local relapse without liver metastasis showed better prognosis as compared with a patient having liver metastasis. We usually adapt further therapeutic intervention for local recurrence using external radiation therapy accompanied with 5FU infusion as a radiosensitizer, if the patient is not revealed with liver metastasis. On the other hand, there is no effective intervention for liver metastasis accompanying pancreatic cancer, as small lesions of multiple liver metastases progress rapidly. We insert the tip of catheter in proper hepatic artery in order to infuse MMC once a week at outpatient clinic. However, we were not yet able to evaluate the effect of arterial infusion therapy.