Dull Headache Research Articles

A case of advanced gastrointestinal stromal tumor (GIST)presenting with paraneoplastic syndrome

4242 Background: Paraneoplastic syndromes are common manifestations of many malignancies but have not been reported with gastrointestinal stromal tumors (GIST). Methods: This is a case report of a 51 y/o white male with GIST. Results: The patient presented with dull persistent headache and diplopia. Eye examination revealed diffuse bilateral sixth nerve palsy. Routine laboratory tests and a spinal tap analysis were non-revealing. CT and MRI of the brain were normal. MRI of the orbits showed a mild, diffuse inflammation and thinckening of the extraocular muscles. The patient was treated with prednisone and improved. A few weeks later, the patient developed pleuritic pain and CT of the abdomen revealed a large paraduodenal mass and a second mass measuring 5x8 cm in the left lobe of the liver. The patien had complete resection of the paraduodenal mass and a left hepatic lobectomy. Pathology was consistent with GIST and the surgical margins were free of tumor involvement. The patient was followed without treatment with serial CT scans and also had open liver biopsies which were negative at the time of an incidental cholecystectomy. He remained symptom free for 6 years. Headache and diplopia returned and improved with prednisone. Restaging with CT and PET revealed a new mass in the right lobe of the liver. Biopsies revealed a c-kit positive tumor similar in morphology and immunohistochemical staining to the initial GIST. The patient responded to imatinib with resolution of the PET scan findings though CT continued to demonstrate a large mass. The headache and diplopia have not recurred following discontinuation of the prednisone. Conclusions: The temporal links between symptomatology and the original and recurrent tumors support the hypothesis that the headache and diplopia represent a paraneoplastic syndrome previously unreported for patients with GIST. No significant financial relationships to disclose.

A case of advanced gastrointestinal stromal tumor (GIST)presenting with paraneoplastic syndrome

4242 Background: Paraneoplastic syndromes are common manifestations of many malignancies but have not been reported with gastrointestinal stromal tumors (GIST). Methods: This is a case report of a 51 y/o white male with GIST. Results: The patient presented with dull persistent headache and diplopia. Eye examination revealed diffuse bilateral sixth nerve palsy. Routine laboratory tests and a spinal tap analysis were non-revealing. CT and MRI of the brain were normal. MRI of the orbits showed a mild, diffuse inflammation and thinckening of the extraocular muscles. The patient was treated with prednisone and improved. A few weeks later, the patient developed pleuritic pain and CT of the abdomen revealed a large paraduodenal mass and a second mass measuring 5x8 cm in the left lobe of the liver. The patien had complete resection of the paraduodenal mass and a left hepatic lobectomy. Pathology was consistent with GIST and the surgical margins were free of tumor involvement. The patient was followed without treatment with serial CT scans and also had open liver biopsies which were negative at the time of an incidental cholecystectomy. He remained symptom free for 6 years. Headache and diplopia returned and improved with prednisone. Restaging with CT and PET revealed a new mass in the right lobe of the liver. Biopsies revealed a c-kit positive tumor similar in morphology and immunohistochemical staining to the initial GIST. The patient responded to imatinib with resolution of the PET scan findings though CT continued to demonstrate a large mass. The headache and diplopia have not recurred following discontinuation of the prednisone. Conclusions: The temporal links between symptomatology and the original and recurrent tumors support the hypothesis that the headache and diplopia represent a paraneoplastic syndrome previously unreported for patients with GIST. No significant financial relationships to disclose.

Clinical assessment of ramosetron HCl oral preparation in the treatment of nausea and vomiting induced by cisplatin: A multicenter, randomized, parallel-design, double-blind comparative study with ondansetron HCl

Background: Nausea and vomiting induced by anticancer drugs cause considerable stress to patients and complicate drug administration and/or cause patients to refuse further courses of therapy. Oral antiemetics, such as ondansetron HCl, were developed to provide a wider selection of drugs to treat chemotherapy-induced nausea and vomiting. Ramosetron HCl oral preparation (intraoral disintegrator) was specially formulated to be taken without water. Studies have shown that ramosetron oral preparation has potent inhibitory effects on cisplatin-induced vomiting. Objective: This multicenter, randomized, parallel-design, double-blind comparative study examined the efficacy, tolerability, and usefulness of ramosetron oral preparation compared with ondansetron HCl oral preparation in inhibiting nausea/vomiting (including retching) induced by the anticancer drug cisplatin. Methods: Japanese inpatients aged ≥20 years with cancer were eligible. Patients received either a single IV administration or ≤4-hour IV infusion of cisplatin ≥50 mg/m 2 (including concomitant use with other anticancer drugs) at 30 participating centers in Japan. All patients were randomized to receive 1 tablet each of ramosetron 0.1 mg and ondansetron placebo or ondansetron HCl 4 mg and ramosetron placebo simultaneously 1 hour before administration of cisplatin therapy. Patients were observed for 24 hours from the start of cisplatin infusion. The severity of nausea was assessed and the number of vomiting episodes was recorded for each patient. The causal relationships between all adverse events and study drugs were assessed. Results: This study was performed in 151 patients hospitalized at 30 institutions. The ramosetron group (group R) included 75 patients; the ondansetron group (group O), 76. Of these, 150 (75 in each group) were included in the analysis of tolerability, and 136 (67 and 69 patients in groups R and O, respectively; 75 women, 61 men) were included in the analysis of clinical efficacy/usefulness. In the latter analysis, the percentages of patients exhibiting ≤2 vomiting episodes 0 to 24 hours after cisplatin infusion were 74.6% ( 50 67 ) in group R and 63.8% ( 44 69 ) in group O. The percentages of patients displaying mild nausea or none 0 to 24 hours after infusion were 68.7% ( 46 67 ) and 63.8% ( 44 69 ), respectively. Although no significant differences in the incidences of nausea and vomiting were observed between the 2 groups, both effects were slightly more prevalent in group R than group O. Drug-related adverse events included mild or moderate dull headache (2 patients in group R), moderate painful headache (1 in group O), and moderate fever (1 in group R). Conclusions: Both ramosetron 0.1 mg and ondansetron 4 mg oral preparations showed satisfactory antiemetic effects when given 1 hour before cisplatin therapy and were judged clinically useful in this group of patients.

Effects of beraprost sodium (Dorner) in patients with diabetes mellitus complicated by chronic arterial obstruction.

The effects of the prostaglandin I2 derivative beraprost sodium (Dorner) on ankle pressure index (AP; ankle joint-to-upper extremity systolic pressure ratio), subjective symptoms, and intermittent claudication were investigated in diabetic patients with arteriosclerosis obliterans (ASO). Forty patients (25 men and 15 women), mean age 63.9 years, were enrolled in this study. ASO was grade I in 30 patients, grade II in seven, grade III in one, and grade IV in two according to the Fontaine classification. They were administered six tablets (20 microg/tablet) of beraprost sodium daily for 6 months. At 3 and 6 months, API had significantly increased and symptoms such as coldness, numbness, and lack of feeling in the lower extremities were significantly improved. Ten evaluable patients increased ambulatory distance by approximately threefold, suggesting an improvement in intermittent claudication. Adverse reactions were experienced by five (12.5%) of the 40 patients (one case each of headache, dull headache, pain in the posterior region of the neck, heartburn, stomach discomfort, and anemia), but all were mild and resolved without treatment. Beraprost sodium was shown to improve API and symptoms in the lower extremities in diabetic patients with ASO, suggesting that it is useful in treating peripheral circulatory disorders in such patients.

Study on the Discrepancy in Responses Given by Patients to Questions Regarding Subjective Symptoms.

A cross-sectional study was conducted using the data obtained from a QOL study of Carvedilol to ascertain how the patients' answers on subjective symptoms change depending on how the questions were asked and who asked them. The patients in the present study received Carvedilol for six months, and were then questioned about six subjective symptoms (headache, dull headache, dizziness, palpitation, stiff shoulder, and malaise) by both physicians and pharmacists. The physicians mainly asked patients about the severity of each symptom, whereas the pharmacists asked about the frequency of each symptom. The results showed a discrepancy between the answers given to physicians and those given to pharmacists. The factors associated with the discrepancies in the answers included age, employment and standard of living. The results of the present study suggest that, in order to gather information about subjective symptoms from patients, it is necessary to consider the following factors: how patients are questioned, how they can answer the questions, how much time is spent with patients, and how to should patient privacy be protected.

Neurologic and visual symptoms in essential thrombocythemia: efficacy of low-dose aspirin.

Neurologic and visual symptoms frequently occurred in 56 reported patients with essential thrombocythemia (ET). They may either precede or follow the well-known microcirculatory complications of ET of acroparesthesias, erythromelalgia, and acrocyanosis or ischemia of one or more toes. In comparison with transient ischemic attacks in patients with vascular risk factors, the usual neurologic presentation of ET consists of brief attacks of sudden cerebral or visual dysfunction, which can be either well localized or diffuse and entirely nonspecific. A dull and throbby headache usually lasting for several hours frequently accompanies the neurologic symptoms. Visual symptoms are less frequent and include transient monocular blindness and global symptoms such as scintillating scotomas and attacks of blurred vision. Neurologic and visual symptoms may leave minor sequelae but are generally nondisabling. The striking similarity to migraine, together with the absence of vascular risk factors and the striking efficacy of aspirin treatment supports the hypothesis that the ischemic neurologic and visual symptoms in ET are caused by shear rate-induced intravascular activation and aggregation of platelets with subsequent transient sludging or occlusion of the cerebral arterial microvasculature. Available data show that both the erythromelalgic distress and the ischemic neurologic attacks in ET are completely abolished by control of platelet function with low dose aspirin alone or reduction of platelet counts to normal as well as by the combination of platelet reducing therapy and low-dose aspirin. Early recognition and appropriate treatment of neurologic symptoms in patients with ET is therefore of great clinical relevance.

Pravastatin治療3年間を目標とした長期使用成績調査の結果について

The present investigation was undertaken to evaluate the long-term safety and efficacy of Pravastatin (trade name Mevalotin; Sankyo), one of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors currently marketed. The investigation was carried out under conditions of general clinical practice at 15 metropolitan private clinics in Tokyo. The subjects of this investigation were 306 hyperlipidemic patients who received Pravastatin during the period of July 1, 1990 through November 30, 1991. Among these, 28 cases were excluded from long-term treatment, at a point 3 months after commencement of medication.Safety evaluation was performed on all 306 medicated subjects, although the evaluation of efficacy was restricted to 278 cases who continued medication for more than three months. 190 cases (68.3%) continued to receive the Pravastatin administration over 3 years during the specified term. In 88 cases, medication was terminated after more than three months but less than three years. The reasons for termination or drop-out are as follows; attendance was abandoned due to personal reasons (64 cases, 74.7%), drug change (6 cases, 6.8%), changed diet therapy alone (3 cases, 3.4%), and other miscellaneous causes (15 cases, 17%). From the safety aspect, adverse drug events were observed in 6 cases (2.0%) and abnormal laboratory tests were detected in 11 cases (3.6%, 18 items) among all 306 medicated cases. Specifically, the adverse drug events included; gastrointestinal disorders (4 cases), dizziness and dull headache (1 case) and eruption (1 case). The detected abnormal loboratory tests were mainly as follows; an elevation of CPK (5 cases, 1.6%), and an elevation of GOT/GPT and/or γ-GTP (4 cases, 1.3%). No new adverse drug reaction or laboratory abnormality other than those known at the time of government approval were observed during the medicated term. Due to adverse drug events and/or laboratory abnormalities, four cases discontinued their drug regimen during the first 3 months treatment, and in four cases medication was halted after 3 months treatment, although nine other patients continued on medication because of the disappearance of such adverse events and/or laboratory abnormalities.Concerning efficacy, total-cholesterol, LDL-cholesterol and triglyceride showed significant decreases and HDLcholesterol showed significant increases at each time point examined at 6 months' intervals, compared with baseline values. The levels were maintained for 48 months until the final examination.Thus, over the three years, the long-term safety and efficacy of Pravastatin were confirmed by this prospective, multiclinical, open clinical trial.

Rapid and sustained relief of migraine attacks with intranasal lidocaine: preliminary findings.

In a noncontrolled study, 23 migraine headache patients were treated with intranasal instillation of 0.4 mL of a 4% lidocaine solution during attacks of varying intensities. Evaluated were pretreatment and posttreatment changes in pain intensity, nausea, and side effects. Posttreatment intensity ratings significantly improved over pretreatment ratings, as determined by a Sandler A analysis (0.077; P < .0005). Migraine attacks were aborted in 12 of 23 patients, of which 8 were completely relieved within 5 minutes. In no case did an aborted attack return to more than a dull level within 24 hours, as determined by follow-up telephone calls. A successful response of migraine attacks to lidocaine treatment was more apt to occur in patients having migraine solely, when compared to migraine patients who also had daily dull headaches; the difference was not significant. Unilateral attacks, however, were significantly more treatment-responsive when compared to bilateral attacks (X2 = 3.85; P = .05). Nausea, associated with migraine attacks in 6 of 12 responders, was similarly aborted by lidocaine in 5 of 6 patients. Other side effects included mild nasal and eye burning of short duration (seconds), and oropharyngeal numbness of approximately 20 minutes' duration. Despite the abrupt and absolute relief of migraine attacks afforded by lidocaine in most of our study patients, its level of efficacy awaits results of double-blind, placebo-controlled studies. Our findings raise new questions regarding the differential pathogenesis of migraine and cluster headache attacks.(ABSTRACT TRUNCATED AT 250 WORDS)

こう原病に伴う皮膚潰ように対するシロスタゾールの有用性

The clinical usefulness of cilostazol, a platelet aggregation inhibitor, in the treatment of skin ulcer was evaluated in 31 patients with collagen diseases, including 16 patients with systemic sclerosis, 7 with SLE, 2 with MCTD and 6 with other subtypes of the disease. This evaluation followed administration of the drug at a daily dose of 100mg (50mg×2) for 8 successive weeks.Twenty-four patients, excluding 7 patients with protocol violations, were included in the efficacy evaluation. The size of skin ulcer significantly decreased from 6.6±6.7mm (mean ± SD) to 3.8 ± 3.2mm at 2 weeks of treatment and to 2.2 ± 2.9mm at 8 weeks of treatment. The appearance of granuloma, and redness, swelling, spontaneous pain and haphalgesia were significantly improved at 2 weeks of treatment and thereafter. The final global improvement rating revealed an assessment of“moderately improved”or better in 87.5% (21/24) of the 24 patients. Adverse reactions were experienced by 48.4% (15/31 patients) : headache in 29%, palpitation or tachycardia in 9.7%, dull headache in 6.5% and tinnitus in 3.2%. Treatment was discontinued due to adverse reactions in 19.4% (6 patients) of the 31 patients.Overall usefluness, which was assessed based on the final global improvement rating and overall safety, revealed an assessment of“useful”or better in 83.3% (20/24 patients), indicating that cilostazol is useful in the treatment of skin ulcer accompanying collagen diseases.

Transient neurologic and ocular manifestations in primary thrombocythemia.

We report the presenting neurologic and visual symptoms in 17 patients with primary thrombocythemia. Poorly localizing symptoms occurred in 14 patients: transient unsteadiness in 13, dysarthria in eight, and scintillating scotomata in four. Nine patients had focal symptoms: transient monocular blindness in two patients, transient mono- or hemiparesis in six, and both of these in one patient. The attacks all had a sudden onset, occurred sequentially rather than simultaneously, lasted for a few seconds to several minutes, and were usually associated with a dull or pulsatile headache. A causal platelet-mediated arterial thrombosis was evident in 15 patients. There were no recurrences of thrombotic or ischemic events during long-term treatment of 12 patients with aspirin and during cytostatic reduction of platelet count to normal in seven patients. We conclude that low-dose aspirin and reduction of platelet count to normal are effective, but coumarin is ineffective, in the treatment and prevention of arterial thrombosis in thrombocythemia.

慢性副鼻腔炎に対するロキシスロマイシン少量長期投与

Twenty patients with chronic sinusitis were given one tablet (150 mg) of roxithromycin (RXM) once a day for three months. Rates of improvement of subjective symptoms (disappearance or improvement) after the three-month therapy were: nasal obstruction 92.3% nasal dripping 81.25%, postnasal dripping 94.4%, sensation of foul odor 100.0%, and headache and dull headache 90.0%. Objective findings improved as follows: flare of the nasal mucosa 80.0%, edema and swelling of the nasal mucosa 85.0%, volume of nasal discharge 90.0%, property of nasal discharge 95.0%, and volume of postnasal dripping 87.5%. Average score of the subjective symptoms and objective findings in ten areas were significantly lowered after three-months of RXM therapy compared with those before therapy. Many aspects of the nonantibacterial actions considered inherent in RXM remain obscure, but this long-term, low-dose RXM therapy seemed to be effective in treating chronic sinusitis.

経口ｐｒｏｓｔａｃｙｃｌｉｎ誘導体ｂｅｒａｐｒｏｓｔ ｓｏｄｉｕｍ（ＴＲＫ‐１００）の第Ｉ相臨床試験 単回投与試験

A phase I study by single oral administration of beraprost sodium (TRK-100), a prostacyclin derivative, was performed in 32 healthy male volunteers. The safety, pharmaco-kinetics, and pharmacological effects were studied in two single oral administration clinical trials.Study 1 was performed in 12 volunteers to investigate the safety and pharmacokinetics of TRK-100. The 12 men received 50, 100, and 200 μg of TRK-100 at intervals of two wk.Study 2 was performed in 20 volunteers, randomly divided into three groups, to investigate the pharmacological effects and safety of TRK-100 at the dose of 25, 50, and 100μg. The results were as follows:1) Subjective symptoms: Facial flushing, feeling of congestion, dull headache, headache, and sleepiness, etc., appeared in some subjects. These symptoms were observed more frequently in the groups receiving 100 and 200μg. Almost all symptoms disappeared within 2 or 3 hr after administration.2) Physical and laboratory tests: Plasma calcification time and prothrombin time were prolonged slightly. But no abnormality was observed in other test items.3) Pharmacokinetics: Following a single oral administration of 100 and 200μg, Cmax was twice as high in the group receiving 200μg as in the group receiving 100μg. Tmax was 1. 42 hr in the group receiving 100μg and 1.07 hr in the group receiving 200μg. T1/2 was 1.11 hr and 0.89 hr, respectively.4) Pharmacological effect: TRK-100 inhibited platelet aggregation induced by ADP, collagen, and epinephrine dose-dependently.The above results indicated the safety and pharmacological effects of TRK-100 in single oral administration in healthy male volunteers.

Short-term therapeutic prognosis of cognitive impairment with cerebrovascular diseases in chronic stages

Utilizing data from seven independent double-blind controlled trials for cerebrovascular diseases (CVD) in chronic stages, a study was performed to describe the short-term prognosis of cognitive impairment with CVD patients and to identify correlating factors. 943 patients out of 2,818 with CVD (cerebral infarction, cerebral hemorrhage and brain arteriosclerosis) were selected. The subjects had more than moderate intellectual deterioration, i.e., less than 21.5 points on Hasegawa's dementia scale (HDS) at the baseline of the trials. The improvement rate was estimated at 11% (102/943) with more than a 10 point change on HDS in 8 weeks and 34% (322/943) with more than a 5 point change. Long duration of illness, old age, severe initial global severity rating and severe initial cognitive impairment were correlated significantly with aggravation of cognitive impairment. However, sex, type of CVD, complication and rehabilitation were not markedly related with aggravation. In addition, it appeared clear that there was a tendency of improving cognitive impairment on patients with severe subjective symptoms (vertigo, headache, dull headache, feeling of congestion), anxiety, irritability in consequence of the covariance analysis of adjusting for duration of illness, age, global severity and initial cognitive impairment. On the other hand, incontinence, impairment of activities of daily living (excretion), motor weakness and low total protein correlated significantly with aggravation. These findings might be explained on the basis of changes in stages from reversible to irreversible with cognitive impairment, the contribution of aging and the influence of peripheral symptoms.

新しいβ１選択性β遮断薬塩酸ｂｅｖａｎｔｏｌｏｌの日本人健常成人における薬物動態と薬理作用

Clinicopharmacological study of bevantolol, a newly developed β1-selective β-blockingagent was carried out in Japanese healthy male volunteers. The pharmacokinetics, pharmacodynamics, and safety were investigated after single and once-daily repeated oraladministration of 100 mg and 200 mg of bevantolol. The following results were obtained.(1) The time to the maximum plasma concentration (tmax) on an empty stomach was about 0.7 hr and the elimination half-life in α-phase (t1/2α) and in β-phase (t1/2β) were about 1. 4 hr and 9 to 10 hr, respectively. The area under the plasma concentration curve (AUC) and the maximum plasma concentration (Cmax), which showed about a threefold interindividual variation, were about two times greater after the 200 mg dose than after the100 mg dose.(2) On a full stomach, tmax was prolonged to 2 hr. No sign of accumulation was noted after seven days of once-daily repeated doses.(3) The reduction in resting blood pressure after dosing of bevantolol was mild, while pulse rate decreased singnificantly. Fall in blood pressure after postural change from supine to standing position was not evident.(4) Exercise-induced tachycardia and increase in rate-pressure product were significantly attenuated by bevantolol. A high correlation existed between the percent reduction [%R] HR in exercise-induced tachycardia and the logarithm of the plasma concentration of bevantolol.(5) Resting fingertip blood flow measured by venous occlusion plethysmography did not decrease after repeated doses of 100 mg of bevantolol.(6) Regarding subjective symptoms, complaints of headache, dull headache, and gastrointestinal disturbance were noted in some subjects. No profound influence was recognized on the clinical laboratory data. After repeated doses of 100 mg of bevantolol, one subject developed transient loss of consciousness accompanied by a fall in blood pressure and pulse rate. Therefore, careful attention should be paid when the drug isused.

Lung Metastasis of Intraosseous Meningioma prior to Craniotomy

A 38-year-old female was admitted, because of a dull headache and a slowly growing, hard, fixed mass in the vertex area. Severe papilledema was noted. Plain roentgenograms of the skull showed thickening of the outer table and diploe at the vertex. Selective external carotid angiography demonstrated enlarging branches of both the superficial temporal artery and middle meningeal artery entering the region of the thickened skull and forming a homogeneous tumor stain. The superior sagittal sinus was obscured beneath the thickened skull. Computerized tomography revealed no intracranial mass lesion. Chest X-ray film showed multiple coin lesions in both the lung fields. During the operation, an intraosseous meningioma was found as well as isolated small intradural tumors. The superior sagittal sinus was grossly collapsed without any tumor masses. These tumors were totally removed (grade 1 removal after Simpson). The postoperative course was uneventful. An open biopsy of one of the lung tumors was performed. The skull, falx and lung tumors were identical in histological appearance and showed typical features of meningotheliomatous meningioma. Without histologically malignant features, meningioma rarely metastasizes. Only 10 cases of metastatic meningioma without craniotomy were reported in the literature from 1941 to 1983. In the present case the lung metastasis seems most likely hematogenous. The route by which the small falx tumors were seeded is not clear.

Tolfenamic acid and ergotamine abuse.

SYNOPSISThirteen migraine patients using ergotamine tartrate on a daily basis for their headaches were found to have developed the so called “ergotamine headache,” a dull constant headache always reappearing if the patient did not take their daily doses. They were treated with tolfenamic acid, an inhibitor of prostaglandin synthesis and action, combined with chlordiazepoxide during the acute withdrawal phase after discontinuing their daily habit of taking ergotamine. As a whole, the results of the discontinuation of the use of ergotamine were encouraging in the group of these patients showing a serious medical problem. None of the patients relapsed into ergotamine abuse, and during the subsequent 3–6 months nine of the patients also treated their migraine attacks solely with tolfenamic acid.

Meningioma Associated with Subdural Hematoma

Intracranial hemorrhages associated with meningiomas are extremely rare. A 36-year-old man was admitted with complaints of a dull headache, nausea, vomiting and a slight disorientation which persisted for a few weeks. CT showed a right subdural hematoma or effusion and high density areas in the right middle fossa and in the Sylvian fissure respectively. Right carotid angiography showed a very large avascular zone. On trepanation, a large subdural hematoma surrounded by typical outer and inner membranes was encountered and about 150 ml of dark brownish fluid was removed. A few days after the operation the same complaints as mentioned above reappeared and trepanation was repeated. Right fronto-temporal craniotomy was performed 8 days after the 2nd operation. During the operation a large subdural hematoma surrounded by firm capsules was found in the right fronto-parieto-temporal region. Part of a tumor originating from the right lateral third of the sphenoidal ridge protruded through the inner membrane into the hematoma cavity. A few small tumors were also found within the hematoma cavity. Most of the hematoma capsules and the tumor masses were removed and also another tumor mass growing in the Sylvian fissure was partially resected. Histological examinations showed the tumor to be a meningotheliomatous meningioma with sarcomatous changes. The patient died less than one month after the last operation. Postmortem examination disclosed numerous metastatic tumor masses throughout the central nervous system. Including the present case, a total of 15 reported cases of meningiomas associated with intracranial hematomas were reviewed and discussed.

Transient cerebral ischemia: Diagnostic considerations

I T IS difficult to determine how long the premonitory symptoms of stroke have been recognized by medical writers and neurologists. It is probable that their recognition came hand in hand with the developing understanding of the varieties of apoplexy; the differentiation between cerebral infarction or acute cerebral softening and cerebral hemorrhage. Certainly, as early as the middle of the last century the premonitory symptoms of cerebral softening or cerebral infarction were written about and recognized in such authoritative references as Gowers’s textbook, A Manual of Diseases of the Nervous System. In his edition of 1893, he states as follows, “In thrombosis from atheroma on the other hand, the premonitory symptoms are frequent. They depend on the interference with the supply of blood due to the disease of the vessels. They may exist for months before the onset or only for a few hours. The most common are dull general headache, giddiness, tingling, numbness, slight weakness in one half of the body, sometimes limited to a single limb and often, but not always corresponding in seat to the subsequent paralysis; less commonly. there is defective articulation or some mental change, failure of memory or irritability due to the general malnutrition of the brain that is produced by widespread arterial disease. In all cases, there presence is far more significant than their absence.“’ This description by Gowers would certainly be well recognized as quite accurate by most medical and neurologic clinicians in 1979. Wilson, in his textbook on neurology noted that “Premonitory signs, lacking in embolism, are often conspicuous in thrombotic cases, more so than in hemorrhagic; days or weeks beforehand, they may give the observer an inkling of what is likely to occur. Here are comprised headache, not infrequently on the same side as the commencing damage, vertigo, defective memory, transient confusion of thought and more specifically heaviness or momentary weakness, numb feeling or other paresthesia in the limb or limbs on the verge of becoming involved. Whether such symptoms constitute minor antecedent attacks or merely indicate general vascular trouble is immaterial; they are the straws which show how the intracranial wind is blowing.“2 Hunt, in his classic 1914 article pointing out the importance of carotid occlusion in the genesis of stroke, wrote that “it is also important to note that the visual disturbance and vascular changes in the optic nerve may precede other organic cerebral symptoms, the collateral circulation, failing to develop in the distribution of the ophthalmic artery. Unilateral headaches and vertigo, especially in assuming the upright posture, epileptiform attacks, failing memory, attacks of threatened hemiplegia, cerebral intermittent claudication are some of the vascular symptoms that should suggest the possibility of carotid obstruction.“3 These descriptions of symptoms are clearly identifiable today with what we consider to be transient ischemic attacks. Between the time of these writings and 1950, there was some recognition of the fact that patients with stroke often had preceding symptoms that suggested a threatened stroke. These were generally believed to be related to cerebral vasospasm. It was only with more careful and detailed inspection of the state of patients with stroke and their premonitory symptoms beginning in 1951 that a better understanding of transient ischemic attacks was possible. In 1951, Miller Fisher4 wrote that frequently in his autopsy studies of patients with occlusion of the cervical portion of the internal carotid artery, patients had reported premonitory fleeting symptoms including paresthesia, paralysis, monocular blindness, and aphasia. In his series of seven patients with carotid occlusion in the neck, ali patients but one had experienced transient numbness, tingling, speechlessness, unilateral blindness, or dizziness. These symptoms, Fisher pointed out were very characteristic of the onset of carotid occlusion. He also pointed out

Case 43-1978

Presentation of CaseA 28-year-old man was admitted to the hospital because of hypertension.He was well until seven years previously, when mild hypertension was found; no treatment was prescribed. He began to experience fatigue, exertional dyspnea and occasional dull occipital headaches. Two months before admission examination elsewhere disclosed a murmur over the posterior thoracic area. A pulmonary arteriographic examination was reported to show coarctation of the aorta. He was referred to this hospital.The patient was a Korean national who was studying in the United States. An uncle had hypertension. There was no personal history of epistaxis, claudication or . . .

KW-1062 treatment of respiratory tract infections (author's transl)

The clinical efficacy of the new aminoglycoside antibiotic, KW-1062, was studied in patients suffering from respiratory tract infections which comprised pneumonia in 67 cases and flare-up of chronic bronchitis in 46 cases.The favorable response rate was found to be 85 percent in pneumonia (100 percent in mild, 89 percent in moderate and 75 percent in severe cases) and 67 percent in flare-up of chronic bronchitis (100 percent in mild, 67 percent in moderate and 47 percent in severe cases).Tinnitus occurred in one patient, and one experienced dull headache. In one patient, renal toxicity developed. In five patients, slight increase in serum transaminases was observed. In all patients, these reactions were of transient nature. No allergic reactions such as eruption and drug fever were encountered during the study.Taking into consideration that half the patients had the underlying respiratory disorders and infections in patients of this type were regarded as “intractable”, it is judged from the clinical data that KW-1062 is useful for the treatment of respiratory tract infections at the dosages studied (2.5 to 3.5mg/kg administered twice or three times a day).