The correct answer is to initiate treatment with L-dopa, since the clinical picture described is of a parkinsonism whose diagnosis is exclusively clinical. The rest of the answers can be made for differential diagnosis, but the performance of complementary tests does not justify delaying the initiation of treatment.

The [HIDDEN] is to initiate treatment with L-dopa, since the clinical picture described is of a parkinsonism whose diagnosis is exclusively clinical. The rest of the answers can be made for differential diagnosis, but the performance of complementary tests does not justify delaying the initiation of treatment.

An 85-year-old woman consults for fatigue and weakness especially in the mornings. She is sometimes unsteady when walking and has to sit down to regain her balance. On two occasions she has had to sit down to keep from falling but denies symptoms of dizziness. She has arterial hypertension, urinary incontinence and osteoarthritis. Her treatment is hydrochlorothiazide (25 mg/d), oxybutynin (10 mg/d), lisinopril (10 mg/d), calcium (1500 mg/d) and paracetamol (3 g/d). On examination he has a blood pressure of 115/70 mm Hg, pulse 80 bpm. His movements are slow. He has a moderate hand tremor. She can get up from the chair slowly but without needing to lean on her arms. She walks slightly leaning forward with little swinging of the arms. Turns slowly but without losing balance. She is unable to stand on one foot. Which of the following possible actions would you perform first?

Measure blood pressure lying down and standing up.

InternalMed_Harrison

A 76-year-old woman presented with a several-month history of diarrhea, with marked worsening over the 2–3 weeks before admission (up to 12 stools a day). Review of systems was negative for fever, orthostatic dizziness, nausea and vomiting, or headache. Past medical history included hypertension, kidney stones, and hypercholesterolemia; medications included atenolol, spironolactone, and lovastatin. She also reliably consumed >2 L of liquid per day in management of the nephrolithiasis. The patient received 1 L of saline over the first 5 h of her hospital admission. On examination at hour 6, the heart rate was 72 sitting and 90 standing, and blood pressure was 105/50 mmHg lying and standing. Her jugular venous pressure (JVP) was indistinct with no peripheral edema. On abdominal examination, the patient had a slight increase in bowel sounds but a nontender abdomen and no organomegaly.

[Three Japanese cases of hypnic headache].

We described three cases of hypnic headache with successful treatment by lithium carbonate or caffeine. This is the first detail report of Japanese cases. An endocrinological test and rhythm analyses of ambulatory blood pressure (ABP) and heart rate variability in a case suggested possible association between hypnic headache and hypothalamic-pituitary dysfunction. Case 1: A 48-year-old female migraineur complained of new-onset nocturnal headaches. Her headache awakened her from sleep between 1 AM and 2 AM. The headache occurred 3-4 times per week and lasted from 1 hour to 2 hours. The headache were moderate intensity and bilateral dull throbbing pain that located in the forehead to temples. There was no accompanying symptoms such as nausea, phonophobia, photophobia, nor the other autonomic features including conjunctival injection or tearing during the headache attacks. Physical and neurological examinations showed normal results except slight weakness and mild dysesthesia of the left arm due to a vertebral disk herniation at C5/6 level. In the pituitary endocrinological test, the prolactin level remarkably increased in response to the TRH loading. The single cosinor analysis demonstrated significant circadian rhythm of ABP parameters. However, the analysis did not demonstrate any significant circadian rhythm of Holter ECG parameters of time domain analysis and frequency analysis. Receiving 200 mg lithium bicarbonate before sleep, her nocturnal headache completely disappeared. Case 2: A 68-year-old woman had been followed up by her chronic tension-type headache since her forties. At her 66-years, she suffered from a new nocturnal headache. She awoke from sleep by the headache about 3 AM and the headache lasted 30 min. Moderate, dull headache located on her left temple to parietal head, 3-4 times/week. She was able to go back asleep without any medication after spontaneous headache cessation. She first complained the nocturnal headache at the 10 months later of the new headache appearance. She received 200 mg caffeine just before sleep and her headache has been disappeared. Case 3: 70-year-old women had been regularly visited our clinics for her migraine and chronic tension-type headache. She received amitriptyline and her headaches was well controlled. At her 69 years, she complained nocturnal headache. It occured every other day. The headache was moderate pulsative dull pain on the occipital region and lasted 90 minutes without any autonomic symptoms. Headache began between midnight and 1 AM. She told us her new nocturnal headache one year later of the onset. Oral caffeine (200 mg) just before sleep did not improve her headache and caused insomnia. Receiving 100 mg lithium before sleep, her hypnic headache disappeared completely. These three cases are compatible with the diagnostic criteria proposed in ICHD-II. There were some patients with hypnic headache in Japan and neurologists should pay attentions to this form of benign headache, because some beneficial treatments are currently available.

Neurology_Adams

These are among the simplest and most important tests of autonomic function and most laboratories have automated techniques to quantitate them. McLeod and Tuck state that in changing from the recumbent to the standing position, a fall of more than 30 mm Hg systolic and 15 mm Hg diastolic is abnormal; others give figures of 20 and 10 mm Hg. They caution that the arm on which the cuff is placed must be held horizontally when standing, so that the decline in arm pressure will not be obscured by the added hydrostatic pressure. As emphasized in Chap. 17 on syncope, the determination of blood pressure in orthostatic testing is ideally done by having the patient remain supine for as long as it is practical before testing, and shifting from a supine to standing position, without the interposition of sitting. Moreover, blood pressure is most informative if measured immediately after standing and again at approximately 1 and 3 min. The expected response is a momentary and slight increase in

Diagnosis and management of carbon monoxide poisoning in the emergency department.

An 89-year-old female is found by her family, lying unconscious on her kitchen floor after they had been unable to reach her by phone for several hours. EMS is activated and when the paramedics arrive, they note that the gas oven is on, and there is thin, gray smoke coming from around the door. The house gas supply is turned off, windows are opened, and the family and the patient are immediately evacuated from the home. En route to the hospital, the patient is placed on high-flow oxygen at 15 liters per minute by non-rebreather mask. Her bedside glucose determination is 229 mg/dL. Vital signs are within normal limits during transport. She opens her eyes to sternal rub, and makes spontaneous movements of all extremities. Upon arrival to the ED, the patient becomes more alert and is able to respond to your questions. She tells you that she remembers putting a tray of calzones into the oven, after which she has no recall of the day's events. She has a past medical history of "well-controlled" hypertension, hyperlipidemia, and non-insulin-dependent diabetes. Her medications include hydrochlorothiazide 25 mg daily, lisinopril 10 mg daily, simvastatin 20 mg daily, and metformin 1000 mg twice daily. On physical examination, weight is 65 kg, blood pressure is 97/50 mm Hg, heart rate is 113 beats per minute, respiratory rate is 22 breaths per minute, temperature is 37.1 degrees C (98.8 degrees F), and oxygen saturation is 99% on 15 liters per minute via non-rebreather mask. She appears her stated age. Cardiopulmonary examination is remarkable only for tachycardia. Her abdomen is soft and non-tender with normal bowel sounds. Her skin is warm and dry, and there is no peripheral edema. Her cranial nerves are intact, with briskly reactive, symmetric pupils. Motor and sensory examination is non-focal, and cerebellar testing is notable only for an intention tremor on finger-nose-finger test. Gait is normal and speech is fluent and without errors. Laboratory testing shows a hemoglobin of 10.3 g/dL and a leukocyte count of 11.7 x 10(9)/L. Electrolyte results fall within the normal range, and her serum creatinine is 1.7 mg/dL. Qualitative CK-MB and troponin I tests are positive, and the sample has been sent to the STAT lab for quantitative testing. Serum carboxyhemoglobin level is 15% with normal serum pH on an arterial blood gas. An ECG reveals deep, down-sloping inferior and lateral ST-segment depressions which were not present on a routine cardiogram 1 month prior. You have many questions about this patient's care. What symptoms and physical signs need to be addressed and treated? What additional diagnostic testing should be performed? What treatment regimen is appropriate and what should be avoided? What are the risks or delayed complications from her illness? Are there special considerations for this or other patient populations?

Evaluation of the Dizzy and Unbalanced Patient -- History and Physical

Vital signs Frank hypotension Orthostatic hypotension (defined as blood pressure drop from sitting to standing:  systolic blood pressure decrease of 20 mm Hg or a diastolic blood pressure decrease of 10 mm Hg) Delayed orthostatic hypotension (usually detected on tilt-table testing)

Orthostatic hypotension

Diagnosis Orthostatic hypotension can be confirmed by measuring a person's blood pressure after lying flat for 5 minutes, then 1 minute after standing, and 3 minutes after standing. Orthostatic hypotension is defined as a fall in systolic blood pressure of at least 20 mmHg or the diastolic blood pressure of at least 10 mmHg between the supine reading and the upright reading. Also, the heart rate should be measured for both positions. A significant increase in heart rate from supine to standing may indicate a compensatory effort by the heart to maintain cardiac output. A related syndrome, postural orthostatic tachycardia syndrome (POTS), is diagnosed when at least a 30 bpm increase in heart rate occurs with little or no change in blood pressure. A tilt table test may also be performed.

[A 77-year-old woman with myoclonus and epilepsy].

We present a 77-year-old woman with myoclonus and epilepsy. She was well until 35 years of age, when she noted an onset of trembling of the legs upon standing. Her symptom slowly progressed, and she felt a difficulty in standing when she was 39-year-old. She had a major motor seizure without an apparent focal onset when she was 46-year-old. She also developed tremor in her hands, and she felt difficulty in holding a glass filled with water. She was admitted to our service for the first time in 1965 when she was 51-year-old. She showed wide-based ataxic gait with truncal titubation. In finger to nose test, myoclonic jerks were induced in the upper extremities. Otherwise neurological examination was unremarkable. She was treated with primidone and phenobarbital, and was discharged for out patient follow up. Her symptoms slowly progressed, and gait and station became more difficult. Mentally she was sound. Three months prior to the present admission, she developed more difficulty in gait, and decrease in food intake. On the 14th of September in 1991, she was seen by a local physician who found an abnormal shadow in her chest X-ray, and she was admitted to our service for further work-up on September 18, 1991. On admission, the patient was a chronically ill and emaciated woman. Her blood pressure was 140/84 mmHg, heart rate 115/minutes and regular, and the body temperature 36.9 degrees C. The palpebral conjunctivae were anemic. No cervical adenopathy was noted. The lung fields were clear, and no heart murmur was audible. The abdomen was soft, and no organomegaly was present. On neurologic examination, she looked somnolent with disorientation to time and place. Her memory was poor, and she could not do well serial 7s. The disc was flat and the ocular movements appeared intact. Other cranial nerves were also unremarkable. She showed diffuse muscle wasting. She was unable to stand or walk. Maintaining the sitting position was also difficult. She was able to raise her arms, but almost unable to move her lower extremities. The precise muscle testing was impossible. No abnormal involuntary movement was seen. Finger to nose test could not be performed.(ABSTRACT TRUNCATED AT 400 WORDS)

[Merits of paracetamol in osteoarthritic hypertensive patients].

Nonsteroidal anti-inflammatory drug (NSAID) side effects can impair quality of life in patients with osteoarthritis. Due to its particular mechanism of action, paracetamol might bypass these negative effects. To determine both the role of paracetamol in the treatment of osteoarthritis patients and optimal combination of antihypertensives and antirheumatics for these patients. A prospective clinical trial in a family practice included 110 treated hypertensives aged over 55 years: 50 controls and 60 also taking NSAIDs for osteoarthritis. This 3-month study compared two antihypertensives, lisinopril/hydrochlorothiazide fixed combination and amlodipine, with two NSAIDs, ibuprofen and piroxicam, and with paracetamol. Following clinical work-up and NSAID discontinuation for at least 3 days (run-in period of only 3-7 days), osteoarthritis subjects were randomized to 1-month periods of ibuprofen (400-600 mg t.i.d.) or piroxicam (10-20 mg o.d.) with one month of paracetamol (1000 mg t.i.d.) in the middle as a "wash-out" interval, continuing the prescribed amlodipine (5-10 mg o.d.) or lisinopril/hydrochlorothiazide fixed drug combination (10/6.25-20/12.5 mg o.d.), while control subjects (hypertensives with no osteoarthritis) were just keeping their antihypertensive therapy. Blood pressure was measured with standard mercury sphygmomanometer and with an automatic device, in standing, sitting and supine position. The intensity of arthritic pain (on a visual analogue scale from 1 to 10, where 0 means "no pain" and 10 "the worst pain you may imagine") and the patient's quality of life estimate (on a visual analogue scale from 1 to 10, where 0 means "general condition excellent" and 10 "the worst possible") were recorded. Blood pressure control was unchanged in the amiodipine group across the study periods and impaired in the lisinopril/ hydrochlorothiazide group during either ibuprofen or piroxicam, but not during paracetamol. In the amlodipine +/- ibuprofen subgroup, the reduction of the average pain intensity score throughout the study was significant (chi2 = 8.250; df 3; P = 0.037). In the lisinopril/hydrochlorothiazide +/- piroxicam subgroup, the assessed quality of life differed significantly (chi2 = 9.716; df 3; P = 0.018), while in the amlodipine +/- ibuprofen and amlodipine +/- piroxicam subgroups the changes were marginal (chi2 = 6.936; df 3; P = 0.072 and chi2 = 7146; df 3; P = 0.065, respectively).

[A 74-year-old woman with parkinsonism and dementia who died four years after the onset].

We report a 74-year-old woman with parkinsonism and dementia, who died 4 years after the onset of the disease. She was well until 70 years of the age (1993) when she noted slowness in the movement in her left hand. She also developed gait disturbance and the similar symptoms spread to the right upper and lower extremities. Two years after the onset, she had difficulty in walk, and was admitted to our hospital on March 9, 1995. Her daughter had the onset of hand tremor at 50 years of the age and gait disturbance at 52. Her gait improved after levodopa treatment, but her MRI revealed a liner T2-high signal lesion along the outer surface of each putamen. On admission, the patient was alert but slighted demented. Higher cerebral functions were normal. She had a masked face and small voice. Her gait was of small step without arm swing. Retropulsion was present. Rigidity was noted in the neck but not in the limbs. She was bradykinetic but tremor was absent. She was treated with levodopa/carbidopa, dops, and bromocriptine with considerable improvement and was discharged on March 30, 1995. On January 19, 1996, she developed fever and hallucination; she became more akinetic and admitted again. She showed marked dementia and stage IV parkinsonism. She was treated by supportive measures with improvement in the general condition, but she was found to have a gastric cancer for which a subtotal gastrectomy was performed on March 11, 1996. Post-operative course was uneventful, but her parkinsonism progressed to stage V. She was transferred to another hospital on May 13, 1996. In July 21, 1996, she developed dyspnea and fever and was admitted to our hospital again. She was somnolent. Rigidity was moderate to marked and she was unable to stand or walk. By supportive cares, her general condition improved and was discharged to home on November 4, 1996. She developed fever on June 13, 1997 and admitted to our service again. Her BP was 150/90 mmHg. She was alert but markedly demented. Laboratory examination revealed increases in liver enzymes (GOT 75 IU/l, GPT 101 IU/l) and renal dysfunction (BUN 68 mg/dl, creatinine 3.27 mg/dl). Subsequent hospital course was complicated by renal failure and thrombocytopenia (33,000/ml). She expired on July 1, 1997. The patient was discussed in a neurologic CPC, and a chief discussant arrived at the conclusion that the patient had diffuse Lewy body disease and her daughter striatonigral degeneration. Some participants thought both the patient and her daughter had diffuse Lewy body disease. Post-mortem examination revealed marked degeneration of the substania nigra and the locus coeruleus. The medial part of the nigra also showed marked cell loss. Lewy bodies were found in the remaining nigral and coeruleus neurons. Cortical Lewy bodies were very few and the striatum was intact. Pathologic diagnosis was Parkinson's disease. Dementia was in part attributed to the marked degeneration of the medial part of the substantia nigra.

Comparison of supine and seated orthostatic hypotension assessments and their association with falls and orthostatic symptoms.

Orthostatic hypotension (OH) based on a change from seated-to-standing blood pressure (BP) is often used interchangeably with supine-to-standing BP. The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a randomized trial of vitamin D3 supplementation and fall in adults aged ≥70 years at high risk of falls. OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mmHg, measured at pre-randomization, 3-, 12-, and 24-month visits with each of 2 protocols: seated-to-standing and supine-to-standing. Participants were asked about orthostatic symptoms, and falls were ascertained via daily fall calendar, ad hoc reporting, and scheduled interviews. Among 534 participants with 993 paired supine and seated assessments (mean age 76 ± 5 years, 42% women, 18% Black), mean baseline BP was 130 ± 19/68 ± 11 mmHg; 62% had a history of high BP or hypertension. Mean BP increased 3.5 (SE, 0.4)/2.6 (SE, 0.2) mmHg from sitting to standing, but decreased with supine to standing (mean change: -3.7 [SE, 0.5]/-0.8 [SE, 0.3] mmHg; P-value < 0.001). OH was detected in 2.1% (SE, 0.5) of seated versus 15.0% (SE, 1.4) of supine assessments (P < 0.001). While supine and seated OH were not associated with falls (HR: 1.55 [0.95, 2.52] vs 0.69 [0.30, 1.58]), supine systolic OH was associated with higher fall risk (HR: 1.77 [1.02, 3.05]). Supine OH was associated with self-reported fainting, blacking out, seeing spots and room spinning in the prior month (P-values < 0.03), while sitting OH was not associated with any symptoms (P-values ≥ 0.40). Supine OH was more frequent, associated with orthostatic symptoms, and potentially more predictive of falls than seated OH.

[A 64-year-old woman with progressive gait disturbance and dementia for one year].

We report a 64-year-old Japanese woman who died one year after the onset of progressive gait disturbance and dementia. She noted a difficulty in holding a glass and hand tremor in June of 1996 when she was 63 years old. In July of 1996, she tended to lean toward left when she walked. She also noted truncal titubation. In November of 1996, she started to have visual hallucination and delusion in which she said "I see something is flying on the wall.", "Somebody has come into my room", and things like that. She was admitted to our service on November 22, 1996. On admission, she was alert and general physical examination was unremarkable. Neurologic examination revealed disturbance in recent memory. Hasegawa's dementia rating scale was 22/30. She showed vivid visual hallucination with colors in which she saw faces of dwarfs and angels, a space ship, and others. Higher cerebral functions were normal. She showed left oculomotor palsy which was a sequel of an aneurysm and subarachnoid hemorrhage nine years before. Otherwise cranial nerves were unremarkable. She showed ataxic gait, limb ataxia, truncal titubation, and postural hand tremor. She had no weakness and no muscle atrophy. Deep tendon reflexes were within normal limits. Plantar response was flexor. Sensation was intact. Laboratory examination was also unremarkable. Complete survey for occult malignancy was negative. CSF was under a normal pressure and cell count was 1/microliter, total protein 27 mg/dl, and sugar 68 mg/dl. Cranial CT scan was unremarkable. MRI was not obtained because of the presence of an aneurysm clip in the left internal carotid-posterior communication artery junction. She showed progressive deterioration in her mental function. By January 1997, she became unable to stand or walk with marked dementia. Repeated CSF exams and cranial CT scans were unremarkable. She suffered from several episodes of aspiration pneumonia. A trial of three days methylprednisolone pulse therapy was given starting on March 7, 1997, which was of no effect on her neurologic status. On March 28, 1997, she was intubated because of acute respiratory distress syndrome. In April 2, her body temperature rose to 38 degrees C. On April 9, 1997, her blood pressure dropped and resuscitation was unsuccessful. She was pronounced dead on the same day. The patient was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had primary leptomeningeal lymphoma. Other possibilities entertained among the audience included brain stem encephalitis of unknown type, carcinomatous cerebellar degeneration plus limbic encephalitis, Creutzfeldt-Jakob disease, thalamic degeneration, and progressive multifocal leukoencephalopathy. Post-mortem examination revealed thickening and clouding of the leptomeninges; Gram-positive diplococci were found in the leptomeninges. This meningitis appeared to have been an complication in the terminal stage of her illness. Microscopic examination revealed astrocytosis in the midbrain tegmentum. Cerebral cortices showed only mild astrtocytosis. No cerebellar atrophy was seen and Purkinje cells were retained which excluded paraneoplastic cerebellar degeneration. Neuropathologic diagnosis was bacterial meningitis, however, the presence of brain stem encephalitis prior to the onset of bacterial meningitis could not be excluded. It is interesting to note that the diagnosis of the primary neurologic disease of this patient was not easy even after autopsy. As autopsy permission was obtained only for the brain, it was not clear whether or not this patient had an occult malignancy somewhere in her body, however, there was no evidence to indicate paraneoplastic degeneration of the central nervous system. As the patient did not have meningeal signs until one month before her death, it is difficult to ascribe her entire neurologic problems to her meningitis. Finally, her visual hallucination was vivid and colorful; we thought this might have been

[Variation of several volume regulating hormones during 21 d - 6 degrees head-down bed rest].

Objective To investigate variations of plasma renin activity, a prostaglandin I2 (PGI2) during 21 d -6 degrees head-down tilt (HDT) with and without lower body negative pressure (LBNP). -6 degrees head-down tilt for 21 d were used to simulate weightlessness. 12 healthy male, aged 23.7 +/- 5.0, were equally and randomly divided into control group (CON) and LBNP group. The latter subjected to LBNP (-30 mm Hg, 1 h/d) in the last week of HDT. Samples of plasma were taken before HDT and on the 2nd, 4th, 11th and 22nd day during HDT. Compare to control levels, Ald declined significantly on the 2nd (CON -30%, P < 0. 05; V. S. LBNP -38%, P < 0.01), and increased significantly on the 11th day (CON +30%, P < 0.05; LBNP +48%, P < 0.01). PRA reached peak value on the 4th day (P < 0.05), and declined to below the control level on the 22nd day. PGI2 increased constantly during HDT, and increased significantly on the 22nd day (CON P < 0.01), 11th, 22nd (LBNP P < 0.05). No apparent difference was found between groups after LBNP concerning PRA and Ald; and PGI2 didn't increase further in LBNP group. Conclusion HDT induced a timely increasing in PRA and Ald, constant increasing in PGI2.

[Therapeutic behavior to follow in the following clinical case: treatment of type 2 diabetes].

A 62-year old woman with obesity, high blood pressure and type 2 diabetes mellitus (DM2) was referred to a Vascular Risk Unit of the Internal Medicine Department due to elevated HbA1C (8.1%) in spite of having taken metformin (850 mg/12h) and glipizide (10 mg/12 h) regularly. She tries to exercise daily (walking 30 min) and has lost weight (from 5 to 12 kg) several times, but always regains what she has lost. Furthermore, she monitors her glucose levels in fasting every two weeks and generally has between 120 and 160 mg/dL. Her high blood pressure is being treated with enalapril/HCTZ and she also takes aspirin 100mg/day and simvastatin 20 mg/day. It is seen in her family background that one brother died suddenly at 50 years of age. Her physical examination shows a BMI of 32.4 Kg/m(2), and she has no edemas in the lower limbs. Her BP is 154/82 mmHg and creatinine 0.9 mg/dL. She has no microalbuminuria and her liver function is normal. What treatment do you think would be the more appropriate? 1 - Add glitazones. 2 - Add incretin mimetics (GLP 1/ DPP-4). 3 - Slow acting insulin.

Orthostatic vital signs

A patient is considered to have orthostatic hypotension when the systolic blood pressure falls by more than 20 mm Hg, the diastolic blood pressure falls by more than 10 mm Hg, or the pulse rises by more than 20 beats per minute within 3 minutes of standing References Medical signs Physical examination

[A 57-year-old woman with gait disturbance, headache, character change, convulsion, and coma].

We report a 57-year-old woman with progressive gait disturbance, headache, character change, convulsion and coma. She was well until 55 years of age, when she noted an onset of unsteady gait. At times she experienced transient weakness in her right hand, which was followed some difficulty in articulation. She was admitted to our service for the work up on April 6, 1992. Neurologic examination at that time revealed an alert Japanese lady in no acute distress. She was oriented to all spheres, however, she was somewhat bradyphrenic and had some disturbance in recent memory. Higher cerebral functions appeared intact. The visual acuity and visual fields were normal as were the optic fundi. Pupils were round and isocoric reacting promptly to light. Ocular movement was full, however, horizontal nystagmus was noted upon right lateral gaze. The sensation of the face was intact. She showed right facial paresis of the central type. Hearing was intact. She showed slurred speech and some difficulty in swallowing. The tongue was deviated to the right. Her gait was wide based and unsteady; tandem gait was difficult, however, walking on toes and on heels were performed well. No cerebellar ataxia was noted, but she showed some clumsiness in her right hand. Deep reflexes were symmetric and normally reactive; plantar response was extensor bilaterally. Sensation was intact; no meningeal sign was elicited. Routine laboratory work up was unremarkable; the CSF was under a borderline pressure (180 mmH2O) and contained 39 mg/dl of protein and 59 mg/dl of sugar. Cranial CT scan revealed diffuse low density areas involving bilateral cerebral white matter as well as the brain stem; MRI revealed high signal intensity lesions in those areas; gadolinium enhancement was negative; cortical sulci were effaced and the anterior part of the left lateral ventricle was compressed without deviation of the midline structure. The patient was treated with steroid pulse therapy without effect. She was discharged for out patient follow up, however, she developed a convulsion which was followed by loss of consciousness, and was admitted again to our service. She had never gained consciousness after this episode, and remained in the state of akinetic mutism. Follow-up CT and MRI did not show much change, although the area of high signal density lesions slightly enlarged on June 1, 1993. Her clinical course was complicated by drug induced bone marrow suppression and nephrotic syndrome. She expired on September 8, 1993 after developing sudden drop of blood pressure and bradycardia.(ABSTRACT TRUNCATED AT 400 WORDS)

Orthostatic reactions in the 85-year olds.

Testing of the orthostatic reaction is recommended in the examination of elderly fallers. This test usually includes blood pressure and instantaneous heart rate measurement but is difficult to perform in very elderly people according to the guidelines suggested for younger subjects. One reason for this is that old people often stand up slowly. The use of a tilt table, which enables a rapid change in posture from recumbent to erect position, is tempting as it could provide a method for a better standardized test. To study the usefulness of the tilt table as well as the degree of orthostatic reaction in the very elderly, we examined a sample of 85-year olds who did not suffer from falls. All were tested both with the tilt table and with active rising. The drop in blood pressure was equal in the two test types, but the increase in heart rate was significantly larger in active rising. Many test subjects were afraid of the tilt table, and two developed cardiac arrhythmia, i.e., atrial fibrillation, during the test. In our opinion, active rising is the method of choice in old persons. While the test subjects were in unusually good health for their age and thus could provide a suitable reference group for this test, the systolic blood pressure dropped considerably in several during the test. Criteria and indexes developed for younger subjects are not useful, and different evaluation criteria should be developed for the very elderly.

Breathlessness with pulmonary metastases: a multimodal approach.

Case Study  Sarah is a 58-year-old breast cancer survivor, social worker, and health-care administrator at a long-term care facility. She lives with her husband and enjoys gardening and reading. She has two grown children and three grandchildren who live approximately 180 miles away. SECOND CANCER DIAGNOSIS  One morning while showering, Sarah detected a painless quarter-sized lump on her inner thigh. While she thought it was unusual, she felt it would probably go away. One month later, she felt the lump again; she thought that it had grown, so she scheduled a visit with her primary care physician. A CT scan revealed a 6.2-cm soft-tissue mass in the left groin. She was referred to an oncologic surgeon and underwent an excision of the groin mass. Pathology revealed a grade 3 malignant melanoma. She was later tested and found to have BRAF-negative status. Following her recovery from surgery, Sarah was further evaluated with an MRI scan of the brain, which was negative, and a PET scan, which revealed two nodules in the left lung. As Sarah had attended a cancer support group during her breast cancer treatment in the past, she decided to go back to the group when she learned of her melanoma diagnosis. While the treatment options for her lung lesions included interleukin-2, ipilimumab (Yervoy), temozolomide, dacarbazine, a clinical trial, or radiosurgery, Sarah's oncologist felt that ipilimumab or radiosurgery would be the best course of action. She shared with her support group that she was ambivalent about this decision, as she had experienced profound fatigue and nausea with chemotherapy during her past treatment for breast cancer. She eventually opted to undergo stereotactic radiosurgery. DISEASE RECURRENCE  After the radiosurgery, Sarah was followed every 2 months. She complained of shortness of breath about 2 weeks prior to each follow-up visit. Each time her chest x-ray was normal, and she eventually believed that her breathlessness was anxiety-related. Unfortunately, Sarah's 1-year follow-up exam revealed a 2 cm × 3 cm mass in her left lung, for which she had a surgical wedge resection. Her complaints of shortness of breath increased following the surgery and occurred most often with anxiety, heat, and gardening activities, especially when she needed to bend over. Sarah also complained of a burning "pins and needles" sensation at the surgical chest wall site that was bothersome and would wake her up at night. Sarah met with the nurse practitioner in the symptom management clinic to discuss her concerns. Upon physical examination, observable signs of breathlessness were lacking, and oxygen saturation remained stable at 94%, but Sarah rated her breathlessness as 7 on the 0 to 10 Borg scale. The nurse practitioner prescribed duloxetine to help manage the surgical site neuropathic pain and to assist with anxiety, which in turn could possibly improve Sarah's breathlessness. Several nonpharmacologic modalities for breathlessness were also recommended: using a fan directed toward her face, working in the garden in the early morning when the weather is cooler, gardening in containers that are at eye level to avoid the need to bend down, and performing relaxation exercises with pursed lip breathing to relieve anxiety-provoked breathlessness. One month later, Sarah reported relief of her anxiety; she stated that the fan directed toward her face helped most when she started to feel "air hungry." She rated her breathlessness at 4/10 on the Borg scale. SECOND RECURRENCE: MULTIPLE PULMONARY NODULES  Sarah's chest x-rays remained clear for 6 months, but she developed a chronic cough shortly before the 9-month exam. An x-ray revealed several bilateral lung lesions and growth in the area of the previously resected lung nodule. Systemic therapy was recommended, and she underwent two cycles of ipilimumab. Sarah's cough and breathlessness worsened, she developed colitis, and she decided to stop therapy after the third cycle. In addition, her coughing spells triggered bronchospasms that resulted in severe anxiety, panic attacks, and air hunger. She rated her breathlessness at 10/10 on the Borg scale during these episodes. She found communication difficult due to the cough and began to isolate herself. She continued to attend the support group weekly but had difficulty participating in conversation due to her cough. Sarah was seen in the symptom management clinic every 2 weeks or more often as needed. No acute distress was present at the beginning of each visit, but when Sarah began to talk about her symptoms and fear of dying, her shortness of breath and anxiety increased. The symptom management nurse practitioner treated the suspected underlying cause of the breathlessness and prescribed oral lorazepam (0.5 to 1 mg every 6 hours) for anxiety and codeine cough syrup for the cough. Opioids were initiated for chest wall pain and to control the breathlessness. Controlled-release oxycodone was started at 10 mg every 12 hours with a breakthrough pain (BTP) dose of 5 mg every 2 hours as needed for breathlessness or pain. Sarah noted improvement in her symptoms and reported a Borg scale rating of 5/10. Oxygen therapy was attempted, but subjective improvement in Sarah's breathlessness was lacking. END OF LIFE  Sarah's disease progressed to the liver, and she began experiencing more notable signs of breathlessness: nasal flaring, tachycardia, and restlessness. Opioid doses were titrated over the course of 3 months to oxycodone (40 mg every 12 hours) with a BTP dose of 10 to 15 mg every 2 hours as needed, but her breathlessness caused significant distress, which she rated 8/10. The oxycodone was rotated to IV morphine continuous infusion with patient-controlled analgesia (PCA) that was delivered through her implantable port. This combination allowed Sarah to depress the PCA as needed and achieve immediate control of her dyspneic episodes. Oral lorazepam was also continued as needed. Sarah's daughter moved home to take care of her mother, and hospice became involved for end-of-life care. As Sarah became less responsive, nurses maintained doses of morphine for control of pain and breathlessness and used a respiratory distress observation scale to assess for breathlessness since Sarah could no longer self-report. A bolus PCA dose of morphine was administered by Sarah's daughter if her mother appeared to be in distress. Sarah died peacefully in her home without signs of distress.

How far should we lower blood pressure in the elderly.

In the last few years several large intervention trials have addressed the treatment of hypertension in the elderly and how far blood pressure should be lowered in such patients. The positive results of intervention against high blood pressure in the elderly has resulted in a positive attitude towards treatment and today this is an accepted and highly effective medical intervention. Both stroke and coronary morbidity have been shown to be positively affected as has total mortality. The specific issue, how far to lower blood pressure in the elderly was probably best addressed in the Hypertension Optimal Treatment (HOT) stduy in which about a third of the patients, i.e. >6,000 patients, were > or =65 years of age. In most of the early intervention studies of antihypertensive treatment in elderly patients diuretics or beta-blockers or the two in combination were used as the therapy by which blood pressure was lowered. However, novel therapies, in particular calcium antagonists, have shown benefits of the same magnitude as the older therapies, e.g. in the STONE trial, the Syst-Eur study, the Syst-China study and the STOP-Hypertension-2 study. In the latter study a regimen based on either of two ACE inhibitors was also shown to be equally effective as conventional treatment, based on diuretics and/or betablockers, in the elderly. These trials will be briefly reviewed here as will the SCOPE study which is an ogoing trial in which hypertensive patients aged 70-89 years are being treated with an angiotensin II receptor antagonist under double-blind and placebo-controlled conditions. It can be concluded that a wealth of information, based on large intervention trials, has been accumulated during the last decade. It is quite obvious that the elderly hypertensive patients benefit from antihypertensive treatment to at least the same extent as the young and middle-aged. It appears that blood pressure ought to be lowered down to normotensive values also in the elderly in order to minimize their risk if cardiovascular complications, although more studies would be welcome to address this issue specifically in the elderly.

Nefopam abuse.

To report 3 patients who abused nefopam, a central analgesic that inhibits serotonin, norepinephrine, and dopamine reuptake. CASE 1: A 42-year-old white woman with migraines started nefopam therapy about 10 years ago. She now obtains nefopam by prescription forgery and self-administers intramuscular nefopam 300 mg/d. She experiences anticholinergic effects of nefopam and, when attempting withdrawal, depressive symptoms. CASE 2: A 40-year-old white woman with osteoporosis has injected 120 mg of nefopam intramuscularly daily for several years. When she tried to increase doses due to worsening of her symptoms, she experienced tremor, involuntary movements, and dry mouth, and became aggressive. She then resumed the initial doses. She now reports symptoms of depression when attempting withdrawal. CASE 3: A 33-year-old white man, with a history of alcohol and benzodiazepine dependence and ileostomy, and an implanted drug delivery system, has been prescribed nefopam. Fifteen days after therapy was initiated, his daily consumption was 840 mg/d, and further increased to 1840 mg/d. He experienced violent behavior, agitation, facial dysesthesia and myoclonus, tremor of fingers, and sweating. He did not attempt withdrawal. The patients described above are drug-dependent according to the Diagnostic and Statistical Manual, 4th Edition. All patients developed a pharmacodynamic tolerance phenomenon, which can develop rapidly. Violent behavior, tremor after massive intake, and depressive symptoms during withdrawal are similar to those reported with psychostimulant abuse. When abused, nefopam has primarily psychostimulant-like effects, which are probably linked to its dopamine reuptake inhibition properties.

[What is the most relevant definition of orthostatic hypotension: systolic blood pressure drop, diastolic blood pressure drop, or both?].

The agreed definition of orthostatic hypotension (OH) is a drop of 20 mmHg systolic and/or 10 mmHg diastolic blood pressure (BP) within the first 3 min of erect posture. For elderly people, a question can be raised about diastolic BP relevance in OH's definition. To determinate HO's prevalence and risks factors considering systolic blood pressure (SBP)'s drop, or diastolic blood pressure (DBP)'s drop, or either. We assessed OH for 554 consecutive, ambulatory, elderly subjects, attending a geriatric outpatient clinic. OH was defined as a SBP drop>20mmHg (SBP-OH), or a DBP drop>10 mmHg (DBP-OH), or a drop in either (SBP. DBP-OH). OH's prevalence and risks factors were determined. In this population, 76 +/- 6 years of age, (70% hypertension), SBP-OH's prevalence was 17%, DBP-OH's prevalence was 12% and SBP. DBP-OH's prevalence was 25%. OH's risks factors varied considering OH's definition. After adjusting for significant determinants, SBP-OH's risk factors were: Antihypertensive therapy (OR=2.95; IC 95%: 1.21-4.04), age>75years (OR=2.11; IC 95%: 1.22-3.66), anti-hypertensive poly therapy (OR=2.01; IC 95%: 1.39-2.92) and SBP level (OR=1.16; IC 95%: 1.01-1.33). Considering DBP-OH, the only significant risk factor was DBP's level (OR=2.64; IC 95%: 1.89-3.68). SBP. DBP-OH was only determined by anti-hypertensive poly therapy (OR=1.61; IC 95%: 1.13-2.29) and DPB level (OR=1.32; IC 95%: 1.08-1.60). For elderly people, OH's prevalence and risks factors vary considering OH's definition. SBP's drop seems to be more relevant than DBP's drop. A long term follow up is necessary to determine if SBP-OH is correlated with HO' s side effects and to establish the dangerous level of SBP' s drop.

Case 294.

History A 50-year-old woman presented to the emergency department of our hospital with a 2-day history of lower limb pain associated with unusual asthenia and diffuse arthralgia over the past 3 weeks. She was a native of Guinea and had lived in France for most of her life, working as a personal care assistant. Her only medical history of note was an occurrence of fetal death at 12 weeks gestation when she was 35 years old. She had bilateral lower limb swelling, without changes in skin temperature or color. All proximal and distal arterial pulses were felt. General physical examination findings were otherwise unremarkable. Her laboratory tests showed a decreased hemoglobin concentration of 8.9 g/dL (normal range, 12-16 g/dL), a decreased platelet count of 45 × 10<sup9</sup/L (normal range, 150-400 × 10<sup9</sup/L), a C-reactive protein level of 158 mg/L (normal range, <5 mg/L) and a d-dimer level of 2000 mg/L (normal range, <500 mg/L). Compression US of the lower limbs revealed bilateral calf vein thrombosis involving the fibular and posterior tibial veins. Curative anticoagulation using low-molecular-weight heparin (enoxaparin, subcutaneous injection of 100 units per kilogram of body weight twice a day) was started. The day after the start of anticoagulation therapy, the patient reported dyspnea and acute chest and abdominal pain. Her vital signs were assessed, and she had elevated blood pressure and increased heart rate and respiratory rate, but she remained afebrile. Her cardiac auscultation was unremarkable, besides tachycardia. Skin examination revealed small areas of necrosis on the fingertips of her right hand. Laboratory studies were repeated and showed an increase in serum creatinine level from a baseline value of 0.49 mg/dL to a new value of 1.01 mg/dL (normal range, 0.6-1.1 mg/dL), an apparition of low-grade proteinuria of 0.43 g per day (normal range, <0.3 g/day), and a high serum troponin level of 1066 ng/L (normal range, <14 ng/L), whereas electrocardiography showed no ST segment modification and echocardiography revealed a moderately altered left ventricular ejection fraction (45%). There was no coronary occlusion seen at emergency coronarography. Contrast-enhanced CT of the chest, abdomen, and pelvis was performed (Figs 1, 2) together with cardiac MRI (Figs 3, 4).

When should orthostatic blood pressure changes be evaluated in elderly: 1st, 3rd or 5th minute?

Detection of orthostatic hypotension (OH) is very important in geriatric practice, since OH is associated with mortality, ischemic stroke, falls, cognitive failure and depression. It was aimed to determine the most appropriate time for measuring blood pressure in transition from supine to upright position in order to diagnose OH in elderly. Comprehensive geriatric assessment (CGA) including Head up Tilt Table (HUT) test was performed in 407 geriatric patients. Orthostatic changes were assessed separately for the 1st, 3rd and 5th minutes (HUT1, HUT3 and HUT5, respectively) taking the data in supine position as the basis. The mean age, recurrent falls, presence of dementia and Parkinson's disease, number of drugs, alpha-blocker and anti-dementia drug use, and fasting blood glucose levels were significantly higher in the patients with versus without OH; whereas, albumin and 25-hydroxy vitamin D levels were significantly lower (p<0.05). However, different from HUT3 and HUT5, Charlson Comorbidity Index and the prevalence of diabetes mellitus were higher, the use of antidiabetics, antipsychotics, benzodiazepine, opioid and levodopa were more common (p<0.05). Statistical significance of the number of drugs and fasting blood glucose level was prominent in HUT1 as compared to HUT3 (p<0.01, p<0.05). Comparison of the patients that had OH only in HUT1, HUT3or HUT5 revealed no difference in terms of CGA parameters. These results suggests that orthostatic blood pressure changes determined at the 1st minute might be more important for geriatric practice. Moreover, 1st minute measurement might be more convenient in the elderly as it requires shorter time in practice.

Case 294: Catastrophic Antiphospholipid Syndrome.

History A 50-year-old woman presented to the emergency department of our hospital with a 2-day history of lower limb pain associated with unusual asthenia and diffuse arthralgia over the past 3 weeks. She was a native of Guinea and had lived in France for most of her life, working as a personal care assistant. Her only medical history of note was an occurrence of fetal death at 12 weeks gestation when she was 35 years old. She had bilateral lower limb swelling, without changes in skin temperature or color. All proximal and distal arterial pulses were felt. General physical examination findings were otherwise unremarkable. Her laboratory tests showed a decreased hemoglobin concentration of 8.9 g/dL (normal range, 12-16 g/dL), a decreased platelet count of 45 × 10<sup9</sup/L (normal range, [150-400] × 10<sup9</sup/L), a C-reactive protein level of 158 mg/L (normal range, <5 mg/L), and a d-dimer level of 2000 mg/L (normal range, <500 mg/L]). Compression US of the lower limbs revealed bilateral calf vein thrombosis involving the fibular and posterior tibial veins. Curative anticoagulation using low-molecular-weight heparin (enoxaparin, subcutaneous injection of 100 units per kilogram of body weight twice a day) was started. The day after the start of anticoagulation therapy, the patient reported dyspnea and acute chest and abdominal pain. Her vital signs were assessed, and she had elevated blood pressure and increased heart rate and respiratory rate, but she remained afebrile. Her cardiac auscultation was unremarkable, besides tachycardia. Skin examination revealed small areas of necrosis on the fingertips of her right hand. Laboratory studies were repeated and showed an increase in serum creatinine level from a baseline value of 0.49 mg/dL to a new value of 1.01 mg/dL (normal range, 0.6-1.1 mg/dL), an apparition of low-grade proteinuria of 0.43 g per day (normal range, <0.3 g/ day), and a high serum troponin level of 1066 ng/L (normal range, <14 ng/L), whereas electrocardiography showed no ST segment modification and echocardiography revealed a moderately altered left ventricular ejection fraction (45%). There was no coronary occlusion seen at emergency coronarography. Contrast-enhanced CT of the chest, abdomen, and pelvis was performed (Figs 1, 2) together with cardiac MRI (Figs 3, 4).

Point of view: why hypertension is overdiagnosed and overtreated in 1987.

1. The decision whether arterial blood pressure (BP) is elevated or normal is usually based on inadequate data: few readings in the presence of great variability of BP; levels higher in the presence of the doctor; and diastolic BP often higher sitting and standing than lying. 2. Assessments of response and of the need for increases in drug dosage are also based on insufficient data. 3. Increased morbidity and mortality from stroke and heart attack, and incomplete correction with treatment have been interpreted as suggesting further benefit from aggressive reduction of BP to 'normal' in all patients. 4. The emergence of powerful drugs with few side-effects, and the promise of lowering office BP to 'normal' as monotherapy, has removed the hesitation to treat 'mild' hypertension. 5. Attempts to lower sitting office diastolic BP to 'normal' have led to increasing drug dosage, dose-related, drug-specific side-effects, and lethargy due to hypotension. 6. Newer self-measurement BP units can be used easily by most patients, cost less than five visits to the doctor and provide a cheap method of obtaining sufficient data on which to base informed management decisions. Supported by normal echocardiographic left ventricular mass, normal 'home BP' (including lying diastolic) permits many mild hypertensives to remain off medications. 7. Non-drug therapy avoids or reduces long-term drug therapy, with its side-effects.

[A case report of dementia with cluttering-like speech disorder and apraxia of gait].

A 57-year-old woman presented with a slowly progressive gait disturbance in 1992 (53 years of age). Over the next year, she gradually began to talk less, but her speech itself became more rapid than before. He speech was frequently too fast even for family members to understand. In 1997, she was admitted to our hospital. On admission, the patient was disoriented but able to follow simple verbal commands, to name things, and to write simple words. Neither apraxia, aphasia, hemispatial neglect, nor a corpus callosum disconnection syndrome was observed. There was no muscle weakness or atrophy. She showed a positive Babinski sign with mild spasticity in the legs and Gegenhalten, but no rigidity. Her speech was monotonous and abnormally fast (cluttering-like speech). Her speech became faster and faster toward the end of sentences, skipping several syllables or even words. She was unable to speak slowly and clearly, even when efforts were made to pace her speech to the speed set by the examiner. She was able to stand only with a wide base of support and body flexion. When standing, she was unable to place one foot directly beside the other; as she tried to have one foot near the other, the former repelled the latter. She had great difficulties in taking her first step forward, and showed rapid freezing of gait even when she managed to succeed in starting. She was able to imitate walking or bicycling with her legs unloaded, indicating that her gait disturbance was a kind of apraxia of gait. Her intelligence was somehow difficult to assess because of her peculiar speech disturbance. However, her family members had noticed her memory disturbance and personality change (offensiveness) since 3 to 4 years before the admission. Moreover, she was defective not only on Hasegawa Damentia Scale-Revised but also on Raven's Colored Progressive Matrices which estimates non-verbal intelligence. It was also noted that she was inattentive and lazy in thinking on questionnaires. Thus we considered that she was at least mildly demented and the type of dementia was of frontal pathology. Laboratory data were all normal except for the head MRI, which demonstrated prominent and thinness of the corpus callosum from the anterior part of the body to splenium without any other brain lesions that could cause the thinness secondarily. Our case resembles two cases reported by Sunohara et al in 1985, together comprising a unique clinical feature. Although Sunohara et al did not refer to the thinness of the corpus callosum in their cases, the clinical profiles in our case and theirs raise the possibility that they form a new disease entity. A further study in a large number of similar cases, including autopsies will provide a conclusion.

Neurology_Adams

Treatment of orthostatic hypotension consists of adequate hydration (at least 1.5 L of fluids per day) with high salt intake, up 8 g of sodium per day, small and frequent meals (to reduce postprandial hypotension) and compression stockings or corset. Fainting can sometimes be avoided by the countermaneuvers of having the patient tightly cross his legs upon standing. Medical treatment can be initiated if nonmedical approaches fail. The peripherally acting alpha agonist, midodrine can be started at 2.5 mg q4h, slowly raising the dose to 5 mg q4h, taking the last dose before about 7 p.m. to void supine hypertension while asleep. The mineralocorticoid fludrocortisone acetate (Florinef) alleviates orthostatic hypotension by volume expansion due to the sodium retention by kidneys. Florinef can be started at dose 0.1 mg daily which may be slowly (over weeks) titrated up 0.9 mg daily. Fludrocortisone may cause hypokalemia and should be used cautiously in patients with severe supine

[Glucocorticoid monotherapy for Cogan syndrome?].

A 27-year-old woman suddenly developed persistent rotatory dizziness with unsteadiness on standing and walking, associated with symptoms relating to the autonomic nervous system, all signs and symptoms disappearing without treatment in 3 days. Ten days before this episode she had noticed progressive bilateral impairment of hearing accompanied by tinnitus. Caloric and audiometric tests confirmed bilateral impairment of the audiovestibular organ. A week later she also developed bilateral iritis and papillitis. The constellation of ocular and audiovestibular signs suggested Cogan's syndrome. Under high-dosage glucocorticoid treatment (initially 1,000 mg/d prednisolone intravenously for 3 days, then 100 mg/d orally in decreasing doses down to 10 mg daily) the ocular signs improved, but the bilateral hearing impairment persisted. A recurrence occurred after 5 months, while on a prednisolone dosage of 10 mg daily, together for the first time with arthralgias, suggesting systemic involvement. Although the symptoms quickly subsided when dosage was increased to 100 mg daily, repeated attempts at dose reduction brought about renewed exacerbation at 70 mg daily. As the necessary high steroid dosage led to severe side effects, an immunosuppressive drug was added (100 mg cyclophosphamide and 20 mg prednisolone, both daily; later 5 mg methotrexate weekly and 4 mg prednisolone every other day). The symptoms had not recurred when re-examined 7 months later.

[An elderly case of hypertension with persistent orthostatic hypotension].

The authors report the successful control of labile hypertension associated with orthostatic hypotension in a 75-year-old male patient, by means of L-DOPS, a synthetic precursor of norepinephrine in combination with antihypertensive drugs. He had been known to be hypertensive for 15 years and developed a persistent floating sensation 2 years age. Despite good control of hypertension after admission, orthostatic hypotension was still observed. Passive tilt produced a blood pressure reduction of 60/20 mmHg. Spectral analysis of heart rate variability showed a disturbance in the activation of the sympathetic nervous system. Treatment with L-DOPS attenuated the blood pressure reduction in response to passive tilt (35/12 mmHg) and improved the sympathetic response. Because of an increase in blood pressure by L-DOPS, addition of either a calcium channel blocker or an angiotensin-converting enzyme inhibitor was necessary. These combinations of treatment successfully controlled blood pressure as well as orthostatic hypotension.

Treatment with electromagnetic fields reverses the long-term clinical course of a patient with chronic progressive multiple sclerosis.

It is estimated that 10-20% of patients with multiple sclerosis (MS) have a chronic progressive (CP) course characterized by an insidious onset of neurological deficits followed by steady progression of disability in the absence of symptomatic remission. To date no therapeutic modality has proven effective in reversing the clinical course of CP MS although there are indications that prolonged treatment with picotesla electromagnetic fields (EMFs) alters the clinical course of patients with CP MS. A 40 year-old woman presented in December of 1992 with CP MS with symptoms of spastic paraplegia, loss of trunk control, marked weakness of the upper limbs with loss of fine and gross motor hand functions, severe fatigue, cognitive deficits, mental depression, and autonomic dysfunction with neurogenic bladder and bowel incontinence. Her symptoms began at the age of 18 with weakness of the right leg and fatigue with long distance walking and over the ensuing years she experienced steady deterioration of functions. In 1985 she became wheelchair dependent and it was anticipated that within 1-2 years she would become functionally quadriplegic. In December of 1992 she began experimental treatment with EMFs. While receiving regularly weekly transcortical treatments with AC pulsed EMFs in the picotesla range intensity she experienced during the first year improvement in mental functions, return of strength in the upper extremities, and recovery of trunk control. During the second year she experienced the return of more hip functions and recovery of motor functions began in her legs. For the first time in years she can now initiate dorsiflexion of her ankles and actively extend her knees voluntarily. Over the past year she started to show signs of redevelopment of reciprocal gait. Presently, with enough function restored in her legs, she is learning to walk with a walker and is able to stand unassisted and maintain her balance for a few minutes. She also regained about 80% of functions in the upper limbs and hands. Most remarkably, there was no further progression of the disease during the 4 years course of magnetic therapy. This patient's clinical recovery cannot be explained on the basis of a spontaneous remission. It is suggested that pulsed applications of picotesla EMFs affect the neurobiological and immunological mechanisms underlying the pathogenesis of CP MS.

[Shy-Drager syndrome and the syndrome of inappropriate secretion of antidiuretic hormone].

We report a 52-year-old male patient with Shy-Drager syndrome (SDS) complicated by an occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The patient first developed impotence at the age of 48, accompanied by urinary incontinence, and episodes of dizziness while standing. The following year, the patient had developed a staggering gait and speech became monotonous. At age 52, the patient was admitted to the hospital after experiencing frequent episodes of syncope associated with complete loss of consciousness. Upon examination, blood pressure was 100/70 in a recumbent position, and 80/60 when standing. The pulse rate varied from 60 per minute to 62. The patient was alert. The alternating Horner sign was observed, and a paucity of facial movements was visible. His speech was slow and monotonous. Muscle tone was increased bilaterally. There was incoordination. A laboratory examination revealed reduced serum sodium levels of 127 mEq/L and increased sodium excretion with plasma hypoosmolality (262 mOsm/kg/H), urine hyperosmolality and low serum renin activity (0.2 ng/ml/h). Renal functions were normal and the levels of adrenocortical and thyroid hormones were normal. There were no abnormalities observed in the chest roentgenogram taken. The level of antidiuretic hormone (ADH) was unreasonably high (5.74 pg/ml). A water-load test demonstrated failure of both water diuresis and inhibition of ADH secretion. These data suggested that hyponatremia in this case was caused by SIADH. The correlation between plasma osmolality and the concentration of ADH suggested that osmolality that initiates ADH release appeared to have been reset to around 230 mOsm/kg lower than normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and tolerability of delapril plus indapamide versus lisinopril plus hydrochlorothiazide combination treatments in mild to moderate hypertension: a multicenter, randomized clinical study.

Several studies have shown that antihypertensive monotherapy is commonly insufficient to control blood pressure (BP) in hypertensive patients and that concomitant use of ≥2 drugs is necessary in ∼50% of these patients. The combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic, delapril plus indapamide (D + I), has been shown to be effective and tolerable, with no interaction between the 2 components. Another widely used combination of ACE inhibitor and diuretic is lisinopril plus hydrochlorothiazide (L + H). The aims of this study were to confirm the antihypertensive efficacy and tolerability of the fixed combination of D + I in mild to moderate hypertension, and to compare its therapeutic efficacy and tolerability with that of L + H. The antihypertensive efficacy and tolerability of a fixed combination of D + I (30-mg + 2.5-mg tablets once daily) or L + H (20-mg + 12.5-mg tablets once daily) in patients with mild to moderate hypertension were compared in a multinational, multicenter, randomized, 2-armed, parallel-group study. Eligible patients were aged 18 to 75 years and had a diastolic blood pressure (DBP) 95 to 115 mm Hg and a systolic blood pressure (SBP) ≤180 mm Hg, both measured in the sitting position. After a single-blind, placebo run-in period of 2 weeks, patients were randomized to receive 1 of the 2 treatments for a 12-week period. The primary efficacy end point was the BP normalization rate (ie, the percentage of patients with a sitting DBP ≤90 mm Hg) after 12 weeks of treatment. Secondary end points were as follows: (1) the responder rate (ie, the percentage of patients whose sitting DBP was reduced by ≥10 mm Hg from baseline or had a DBP ≤90 mm Hg after 12 weeks of treatment), (2) the percentage of patients with a DBP ≤85 mm Hg, and (3) changes in sitting SBP and DBP after 4, 8, and 12 weeks of treatment. A total of 159 hypertensive patients (88 women, 71 men) were randomized to receive D + I (44 women, 36 men; mean [SD] age, 53 [(11)] years) or L + H (44 women, 35 men; mean [SD] age, 55 [(10)] years). No significant between-group differences were found in any of the primary or secondary end points of the study. Both combinations induced a significant reduction in sitting DBP and SBP from baseline (P<0.001 for both groups at week 12), without significant differences between the groups. Five mild to moderate adverse drug reactions (ADRs) occurred in each treatment group. No patient dropped out of the study because of an ADR. This study showed no difference between D + I and L + H interms of antihypertensive efficacy or tolerability in patients with mild to moderate hypertension.

[Orthostatic hypotension in the aged].

Caird and his colleagues reported posture-dependent falls in systolic blood pressure of 20 mm Hg and more in 24% of a population aged 65 and above. In about 5% of the group, moreover, the falls were in excess of 40 mm Hg. Our investigations in 160 residents in an old people's home in the age range 59-88 years largely confirmed Caird's figures. Using Schellong's test we recorded systolic pressure falls of 20 mm Hg and more in 25% of our subjects. These cases of circulatory dysregulation were all manifestations of the hypodynamic form of the orthostatic syndrome. This means that only systolic blood pressure fell, diastolic pressure as well as heart rate being largely unaffected. The phenomenon appears to be due to age-related deterioration in circulatory regulation; at least no evidence has been found to suggest that it has a specific aetiology. In a double-blind cross-over study the effect of dihydroergotamine (DHE) was compared to placebo in 40 patients. Half the patients were given 2 mg DHE three times daily for 14 days and the other half placebo tablets; following 1 week's wash-out, the treatments were then reversed for a further 2-week period. Schellong's test (measurement of blood pressure and pulse after 10 min in the supine position and then after 1, 2, 5 and 10 min standing) was performed at the beginning and end of each treatment period. The average falls in upright systolic pressure for all 40 patients were as follows: before treatment 20 mm Hg (150 leads to 130); end of placebo period 19 mm Hg (147 leads to 128); end of DHE periods 7 mm Hg (145 leads to 138). The differences between the values recorded after treatment with DHE and the other two values are statistically significant (p less than 0.05). Similarly there was a significant difference in the numbers of patients experiencing dizziness during Schellong's test (16-17 out of 40 patients before treatment and after placebo, 6 out of 38 patients after DHE). From this finding conclusions can be drawn regarding the causes of vertigo in old age.