Cerebrovascular Changes in Patients With Headache During Antiserotoninergic Treatment

SYNOPSISCBF and cerebral vasomotor responses to 5% CO₂ and 100%O₂ inhalation were evaluated in 88 patients with headache (56 migraineurs, 17 cluster, 15 non-vascular) before and during acute versus chronic administration of (1) methysergide (single dose 0.047 mg/kg for acute and 0.071 mg/kg/day for chronic) or (2) cyproheptadine (single dose 0.092 mg/kg for acute and 0.139 mg/kg/day for chronic). Acute treatment with methysergide produced decreases [−4.5%] in F₁ values (fast or gray matter flow). Chronic treatment (3–12 weeks) produced increases (%7.9%). These CBF changes only occurred among migraineurs and were not seen in cluster and non-vascular headache patients. In migraineurs methysergide induced F₁ increases were asymmetric between hemispheres. This asymmetry was not seen in patients with non-vascular headache. Methysergide induced biphasic F₁ changes specific for migraineurs, implies rapid and excessive stimulation of cerebrovascular serotoninergic receptors, followed by excessive and asymmetric blockade. Acute treatment with cyproheptadine produced increases (+3.9%) in F₁ values. Chronic treatment (3–12 weeks) produced decreases (−8.6%) Since cyproheptadine is Known to alter cholinergic, histaminergic and serotonergic receptors, it is concluded that acute cyproheptadine treatment may stimulate and chronic treatment may block both cholinergic and histaminergic receptors so that any serotonergic effects in the opposite direction are masked. Vasomotor responses were not altered in any of the headache groups by either methysergide or cyproheptadine, so that serotoninergic receptors do not appear to participate in excessive cerebral vasodilator CO₂ responses seen in migraineurs.     

Migraine and Cluster Headache Treatment With Calcium Antagonists Supports a Vascular Pathogenesis

SYNOPSIS
Clinical research during the past four years in this and other laboratories has demonstrated therapeutic effectiveness of three different calcium channel blockers in the prophylaxis of migraine and cluster headaches. The drugs are nimodipine, nifedipine and verapamil. Clinical observations and cephalic hemodynamic responses correlated before and during treatment with nimodipine show extremely low incidences for development of tolerance and/or side effects plus normal glucose tolerance and calcium dependent insulin secretion before and during nimodipine therapy. The results confirm potent and highly selective calcium entry blockade of cephalic smooth muscle receptors by nimodipine. Nifedipine and verapamil showed less therapeutic effectiveness in controlling headaches, higher incidence for development of tolerance and side-effects with less consistent cephalic hemodynamic changes. Taken together these observations during treatment of migraine and cluster with calcium antagonist support Wolff's theory of vascular head pain.     

Treatment of Tension-type Headache With Tizanidine Hydrochloride: Its Efficacy and Relationship to the Plasma MHPG Concentration

Seventy-eight patients with tension-type headache (TH) were treated with tizanidine hydrochloride (tizanidine). Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and serum free fatty acids (FFA) levels in these patients were determined before the treatment with tizanidine. Eighteen healthy volunteers composed the control group. Four weeks after the treatment with tizanidine 24 (31%) of 78 patients showed excellent improvement (excellent group); 28 (35%) showed moderate improvement (moderate group); 18 (23%) showed mild improvement (mild group); 7 (10%) showed no improvement and one (1%) showed worsening of her headache (no change and worsened group). The plasma MHPG levels in the excellent group were significantly higher than in the other groups, including the control group. The serum FFA levels in the excellent group were significantly higher than in the controls. In this study, 66% of the patients reported improvement in their headaches. Some patients with TH had high plasma MHPG levels and these patients in particular showed excellent improvement after the administration of tizanidine. Though there may be a placebo response to some extent, the clinical usefulness of tizanidine for TH seems to be excellent. Further study is necessary concerning the pharmacological effect of tizanidine and plasma MHPG levels in patients with TH.     

Evaluation of Headache Intensity and Treatment Associated With Subarachnoid Hemorrhage

The purpose of this study was to determine the maximum daily patient-reported pain scores for those patients who experienced subarachnoid hemorrhage (SAH) and to assess how medications were used. A retrospective review of the electronic records of patients who experienced SAH was performed to evaluate patient demographics and comorbidities. The daily pain scores were statistically significant on day 5. Morphine equivalent dosing for day 1 admissions was as follows: patients with a Hunt and Hess (HH) score of I = 2.69, II = 5.52, and III = 0.86 (P = .009). Patients with SAH with an HH score of I and II had similar headaches but received more acetaminophen than patients with an HH score of III.AU     

Renal Effects of Aliskiren Compared With and in Combination With Irbesartan in Patients With Type 2 Diabetes, Hypertension, and Albuminuria

OBJECTIVE

We investigated whether the antiproteinuric effect of the direct renin inhibitor aliskiren is comparable to that of irbesartan and the effect of the combination.

RESEARCH DESIGN AND METHODS

This was a double-blind, randomized, crossover trial. After a 1-month washout period, 26 patients with type 2 diabetes, hypertension, and albuminuria (>100 mg/day) were randomly assigned to four 2-month treatment periods in random order with placebo, 300 mg aliskiren once daily, 300 mg irbesartan once daily, or the combination using identical doses. Patients received furosemide in a stable dose throughout the study. The primary end point was a change in albuminuria. Secondary measures included change in 24-h blood pressure and glomerular filtration rate (GFR).

RESULTS

Placebo geometric mean albuminuria was 258 mg/day (range 84–2,361), mean ± SD 24-h blood pressure was 140/73 ± 15/8 mmHg, and GFR was 89 ± 27 ml/min per 1.73 m². Aliskiren treatment reduced albuminuria by 48% (95% CI 27–62) compared with placebo (P < 0.001), not significantly different from the 58% (42–79) reduction with irbesartan treatment (P < 0.001 vs. placebo). Combination treatment reduced albuminuria by 71% (59–79), more than either monotherapy (P < 0.001 and P = 0.028). Fractional clearances of albumin were significantly reduced (46, 56, and 67% reduction vs. placebo). Twenty-four-hour blood pressure was reduced 3/4 mmHg by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P < 0.001/P = 0.002), and 10/6 mmHg by the combination (P = 0.001/P < 0.001). GFR was significantly reduced 4.6 (95% CI 0.3–8.8) ml/min per 1.73 m² by aliskiren, 8.0 (3.6–12.3) ml/min per 1.73 m² by irbesartan, and 11.7 (7.4–15.9) ml/min per 1.73 m² by the combination.

CONCLUSIONS

The combination of aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.Albuminuria is the best available surrogate parameter in the treatment of diabetic nephropathy. Degree of proteinuria is associated with risk of renal and cardiovascular events (1). Proteinuria reduction is associated with a slowing of the decline in renal function (2). Blockade of the renin-angiotensin-aldosterone system (RAAS) is the cornerstone treatment of incipient and overt diabetic nephropathy, and in type 2 diabetes angiotensin II receptor blockers (ARBs) such as irbesartan are considered standard treatment after the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA) 2 Study (3) and Irbesartan Diabetic Nephropathy Trial (IDNT) (1).Aliskiren represents a new principle of blocking the RAAS, inhibiting renin directly and acting at the rate-limiting step. The drug is approved for treatment of hypertension but has also shown renoprotective potential in patients with type 2 diabetes and albuminuria (4,5).Combining an ARB and a direct renin inhibitor could offer improved RAAS blockade by acting both at the receptor level and at the first step of the cascade. We compared the antiproteinuric effect of maximal recommended doses of aliskiren, irbesartan, and the combination in patients with type 2 diabetes and albuminuria. We also assessed the impact of the treatments on RAAS components and biomarkers of inflammation, endothelial dysfunction, and cardiovascular risk.     

Importance of Side Effects in Opioid Treatment: A Trade-Off Analysis With Patients and Physicians

This study examined the relative impact of pain relief and opioid side effects on patients' and physicians' preferences for medication. An Internet survey was completed by 618 patients (302 acute pain, 316 chronic pain) and 325 physicians (83 primary care, 80 pain specialists, 41 oncologists, 40 general surgeons, 40 orthopedic surgeons, 20 rheumatologists, 21 neurologists). Respondents completed an Adaptive Conjoint Analysis (ACA) exercise in which they indicated their relative preference for 20 pairs of hypothetical opioid pain medications described by varying levels of pain relief and side-effect incidence. Almost all patients (96% of chronic, 92% of acute) reported experiencing at least 1 side effect while on opioid medication, but physician-estimated incidence rates of most opioid side effects were much lower than those reported by patients. Opioid side effects, rather than pain relief, explained the majority of variance for medication preference for both patients (74% for chronic, 73% for acute) and treating physicians (73% for chronic, 74% for acute) in this exercise. Nausea and vomiting were major determinants of opioid medication preference, with each explaining as much of the variance in preference as did pain relief (21% to 25%). Nausea and vomiting were the most important side effects based on the amount of pain relief that respondents were willing to give up for reducing the incidence of side effects. The importance of side effects was confirmed in an open-ended question where 51% of patients and 58% of physicians identified side-effect reduction as an unmet need for pain medications.     

Non-Compliance With Follow-Up and Improvement After Treatment at a Headache Center

SYNOPSIS
Two telephone surveys were conducted at a major headache center into patient compliance with follow-up end perceived treatment efficacy. The first survey addressed compliance with the recommendation to follow-up after the initial evaluation. Of a group of 316 consecutive patients, 40.5% had not complied with the recommended follow-up visit. Reasons for the non-compliance were given by 60.3%; most frequently mentioned were dislike of the clinician seen and seeking care elsewhere.
The second survey concerned 75 patients who had returned at least once to the center for follow-up. When asked about the efficacy of the treatment received, 76.0% reported improvement of their headaches, with 32.0% reporting more than 75% improvement. In addition, 87.5% of the patients reported a decrease in the use of analgesic and/or ergotamine medications.
We conclude that treatment of chronic headache is not a priori a hopeless situation and that in the patient compliance with the recommendation to follow-up, in particular the patient-clinician relationship is a critical factor.     

Identification and Treatment of Sleep Apnea in Patients With Chronic Headache

This study investigates the relationship between nocturnal or morning headache and obstructive sleep apnea syndrome (sleep apnea). It is not known if headache of any type is more common in patients with sleep apnea than in other patients, but morning headache is a symptom of sleep apnea. A method is needed for identifying patients with chronic headache who might benefit from evaluation and treatment of sleep apnea. We performed a retrospective assessment of frequency of morning headache in patients grouped according to final diagnosis: sleep apnea (n=72), periodic leg movements of sleep (n=28), and psychophysiologic insomnia (n=42). Prospective overnight sleep studies were obtained in a different group of 19 patients who presented for evaluation of headache. We selected certain patient characteristics as possibly indicative of sleep apnea-related headache. The retrospective study showed that 24% of patients with sleep apnea had frequent morning headache, which was not different from the other groups. In the separate group of 19 patients with chronic headache and suspected sleep disorder, 17 had sleep apnea. Nasal continuous positive airway pressure was prescribed to 14 patients. Marked improvement in headache occurred and persisted in 4 patients and moderate improvement in 3. Responders to therapy were more likely to have vascular headaches than mixed or tension headaches, more severe sleep apnea, and a nocturnal or morning timing to their headaches. However, there was large overlap in severity of sleep apnea and likelihood of response. We conclude that morning headache is not more common in sleep apnea than in other sleep disorders. However, over 30% of patients with chronic headache and other symptoms of sleep apnea have significant improvement in headache after treatment of sleep apnea.     

不同时相化疗毒副作用的对比研究

为提高化疗疗效,降低其毒副作用,采用不同时相化疗并进行了对比研究。方法将收治标准内的30例患者分为2个疗程化疗,同一患者2次化疗药物剂量、方案保持不变。第1疗程为上午9时,第2疗程为午夜零时给药,2个疗程间隔时间为4周,然后观察2次不同时间化疗后的毒副作用,追踪观察时间为8周。结果表明零点化疗的毒副作用(胃肠道反应及血液毒性反应)明显低于上午9时化疗。     

吸烟与氯丙嗪治疗剂量、疗效、副反应的关系

对153例符合中国精神疾病分类与诊断标准第2版(CCMD—2)的精神分裂症患者进行吸烟与氯丙嗪治疗剂量、疗效及副反应关系的病例对照研究。结果表明,要使吸烟者达到与不吸烟者同样的治疗效果,吸烟者所需的氯丙嗪治疗剂量明显高于不吸烟者;吸烟可使氯丙嗪的疗效和副反应明显降低。     

Netilmicin: Clinical Efficacy, Tolerance, and Toxicity

Netilmicin, a new aminoglycoside antibiotic, has increased in vitro bactericidal activity against many strains of Enterobacteriaceae as compared to other aminoglycosides. It is a poor substrate for some of the common gentamicin-inactivating enzymes, and it has minimal toxicity in experimental animals. In 27 hospitalized patients, clinical cure was achieved in all, and the initial infecting organism persisted in only one. Therapeutic serum and urine levels were easily obtained in most patients. No ototoxicity was observed in two patients whose treatment required inordinately high serum levels and in whom other risk factors were present. Ototoxicity in 1 of 21 patients studied was unilateral, partially reversible, and not associated with high serum levels. Although nephrotoxicity occurred in 4 of 25 patients (16%), other host factors could have accounted for the toxicity in two patients. A new observation, not noted with other aminoglycoside antibiotics, was the elevation of serum alkaline phosphatase in 43% of the patients studied.     

三种不同固定方式治疗Pilon骨折临床疗效比较

[目的]评价切开复位接触性动力加压钢板（LC-DCP）、有限切开复位锁定钢板内固定（LCP）、有限切开复位有限内固定支架外固定（-OFS）治疗Pilon骨折的临床疗效.[方法]回顾性分析2006年1月至2011年1月本院收治的胫骨Pilon骨折患者的临床资料.根据Rdi-Allgwer分型Ⅱ型51例,Ⅲ型10例;应用LC-DCP方法治疗18例,LCP治疗21例,OFS治疗22例.应用MAZUR评分系统对上述三组进行踝关节功能评定.[结果]术后随访12~36个月,平均（12.3±3）个月,全部骨折愈合.LC-DCP组：踝关节功能评定优7例,良8例,可2例,差1例,优良率为83.3%;LCP组优9例,良9例,可2例,差1例,优良率为85.7%;OFS组：优9例,良10例,可2例,1例差,优良率为86.3%.三组优良率比较差异无统计学意义（P〉0.05）.[结论]对于Rdi-Allg werⅡ、Ⅲ型胫骨Pilon骨折根据软组织损伤情况,低能量损伤采用LC-DCP或LCP方法.对于高能量,开放性损伤者采用彻底清创、骨折复位,有限内固定加支架外固定可以降低手术后并发症,取得满意疗效.     

齐拉西酮与舒必利治疗精神分裂症疗效与安全性比较

目的比较齐拉西酮与舒必利治疗精神分裂症的疗效与安全性。方法120例精神分裂症患者随机分为2组,分别服用齐拉西酮[（130.35±30.75）mg/d;60例]或舒必利[（1.1±0.5）g/d;60例],疗程为8周。采用阳性和阴性症状量表（PANSS）、不良反应量表（TESS）与治疗前和治疗后第1、2、4、6、8周末分别评定疗效和不良反应。结果①齐拉西酮组的有效率为86.7%,舒必利组为83.3%,2组比较差异无统计学意义（P〉0.05）;②2组治疗8周后,PANSS总分、阳性症状分、阴性症状分及一般精神病理分与治疗前比较均有显著性差异（P〈0.05）,而治疗8周时2组减分率差异无统计学意义;③治疗8周后2组肝功能、心电图异常率比较,均差异无统计学意义（P〉0.05）。齐拉西酮组主要不良反应为嗜睡、恶心、便秘、厌食。舒必利组不良反应主要为心动过速、口干、便秘、体质量增加、锥体外系反应。结论齐拉西酮与舒必利在治疗精神分裂症时疗效相当,不良反应发生率基本一致,但临床表现各异。