A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

EFFECT OF CROSS-FOSTERING ON NEONATAL SODIUM BALANCE AND ADULT BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar-Kyoto (WKY) rat foster mother (denoted SHRX), as cross-fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR. 2. The electrolyte content of WKY rat and SHR dams’ milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross-fostered WKY rat and SHR pups. 3. The milk sodium concentration fell in both strains (WKY rat: 31.8 ± 2.0 to 15.2 ± 1.2 mmol/L; SHR 31.9 ± 2.5 to 18.2 ± 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P< 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation. 4. Spontaneously hypertensive rat pups ingested less milk (P<0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4–15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 ± 3.6 vs 59.7 ± 2.6 μmol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 ± 7.0 μmol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 ± 6.4 vs 200.1 ± 9.5p, mol/g bodyweight, respectively; P<0.05) or SHRX pups (200.0 ± 18.0 μmol/g bodyweight; P<0.05). 5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross-fostering is effective in lowering blood pressure. This is consistent with the reported up-regulation of the renin-angiotensin system observed in SHR at this time and may have a long-term influence on blood pressure.     

Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms

Summary One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind, placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid (TXA) in the management of ruptured intracranial aneurysms. The incidence of recurrent haemorrhage between active and placebo groups was identical (12%) and the mortality from recurrent haemorrhage was 7% and 5%, respectively. The overall incidence of cerebral infarction before surgery, at discharge and at 6 months follow-up was greater in the TXA group (27%) than in the control group (11%). Post-operative cerebral ischaemia was significantly more frequent in the active, 18 of 29 as compared to 6 of 32 patients, in the placebo group. In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow (CBF) on the side of the ruptured aneurysm in the TXA treated group. It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group. There was no significant difference in the incidence of cerebral vasospasm, hydrocephalus, visual disturbances and gastrointestinal disturbances.More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5% level. Given that disability was due to either vasospasm or recurrent haemorrhage then a patient under TXA treatment was significantly more likely to have disability due to vasospasm (p<0.04); the reverse was true for the placebo patient (p<0.05).     

THE EFFECT OF HYPERTENSIVE EPISODES AND CARDIAC HYPERTROPHY ON THE CANINE CARDIAC BAROREFLEX

1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation. 2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention. 3. Echocardiographically determined LV mass (mean ± s.e.m.) was 116.0 ± 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 ± 8.1 g (P= 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 ± 0.06 at baseline to 1.54 ± 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the ‘steady-state’ drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 ± 0.43 beats/min per mmHg at baseline to 3.10 ± 0.45 beats/min per mmHg (P= 0.067) after 6 weeks of compression. This gain reduction became significant after β-adrenoceptor blockade with propranolol (3.13 ± 0.55 vs 2.32 ± 0.25 beats/min per mmHg; P= 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r= 0.96; P<0.001) during the 6 week compression period. 5. The MAP-HR reflex changes in this model mimic those present in hypertension and implicate cardiac hypertrophy as one possible mediator.     

Grip and pinch strength among selected adult occupational groups

A survey of 402 normal subjects (203 men, 199 women) was conducted to assist in distinguishing potential differences in norms of hand strength. Norm data had previously been collected from mixed occupational groups, but in the present study it was hypothesised that people involved in heavy manual work on a daily basis might possess greater hand strength than others. The volunteers were adults working in industry and agriculture; they were subdivided into occupational categories. Measurements of grip, key and palmar pinch using the Jamar dynamometer and B and L pinch gauge were collected, using the protocol described by Mathiowetz. Volunteers also rated their individual hand strength job requirements subjectively. Mean values were established with regard to age, sex, dominance, occupational group and subjective rating. Significant differences were found with regard to age and sex but not to dominance; there was no evidence of differences between occupational groups or between subjective rating and individual scoring, i.e. volunteers who perceived their job as requiring a high degree of strength did not achieve higher test measurements than others. A high interrater reliability was demonstrated when comparing these follow-up measurements with the original data. It was concluded that, for clinical and rehabilitative purposes, therapists can interpret assessment of outcome most accurately by comparing patients' results with the existing norm data.     

Practical guidelines for physicians in the management of febrile seizures

Recent studies have shown that adequate medication can prevent the recurrence of febrile seizures (FS). It has also been clarified that the vast majority of, though not all, FS patients follow a benign course. Then, questions arise as to whether or not FS should be prevented, particularly in light of the risks of side effects from drugs. Which kinds of FS can be prevented, if necessary? The guidelines presented here are aimed primarily at helping general practitioners in considering how to manage FS most appropriately. The guidelines stress that judgements should be individualized, while referring to a few specific ‘warning factors’. The guidelines follow a ‘laissez-faire’ principle for the majority of FS cases, whereas intermittent therapy with diazepam and continuous medication with either phenobarbital or valproate are indicated in other limited cases meeting respective definite criteria.     

Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function--the DICOF trial.

BACKGROUND: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management. AIM: To evaluate structured TTP for geriatric patients with impaired cognitive function. PATIENTS AND METHODS: A neuropsychological examination was performed on all patients over 54 years [n=102, age 68.6 +/- 8.7 years, diabetes duration 10.3 (0.03-35.4) years, HbA1c 10.3 +/- 1.7% (HPLC, Diamat, NR 4.5-6.3%), cognitive function 87.7 +/- 12.3 IQ points] who took part in TTP for insulin therapy. Patients with impaired cognitive function participated either in the standard TTP of Berger [n = 35, age 67.6 +/- 8.9 years, diabetes duration 9.9 (0.04-35.4) years, HbA1c 10.3 +/- 2.0%] or in the specialized structured geriatric DICOF-TTP [n=33, age 70.4 +/- 8.2 years, diabetes duration 10.4 (0.03-24.9) years, HbA1c 10.7 +/- 1.8%]. RESULTS: After TTP there were no differences in knowledge and ability for diabetes self-management (standard/DICOF: knowledge 11.0 +/- 2.6 vs. 12.2 +/- 2.7 points, P = 0.11; handling 14.9 +/- 3.3 vs. 15.9 +/- 2.5 points, P = 0.18). However, patients who took part in the DICOF programme showed better scores in satisfaction with the education programme [standard/DICOF 44.7 (31-57) vs. 52.5 (45-59) points, P < 0.001]. Six months later the DICOF participants showed better results regarding diabetes self-management (standard/DICOF: handling 12.5 +/- 4.1 vs. 15.9 +/- 3.1 points, P = 0.001). Both groups showed HbA1c decrease (8.3 +/- 1.4 vs. 8.5 +/- 1.3%, P=0.62) and similar incidence of acute complications. CONCLUSIONS: Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management.     

屈光性调节性内斜视综合治疗的效果

①目的:探讨综合治疗屈光性调节性内斜视的效果及其相关因素。②方法:对随机收集78例屈光性调节性内斜视病儿的综合治疗效果进行回顾性分析。③结果:经5年随访，73例(93．6％)维持正常眼位，149只(97．4％)弱视眼治愈，72例(92．3％)获得立体视功能。④结论:及时对屈光性调节性内斜视病儿进行综合治疗，建立和恢复其双眼单视功能，预后较好。     

Geste antagonistes in idiopathic lower cranial dystonia.

Geste antagonistes, or sensory tricks, are well described in focal dystonia affecting the neck, hand, and face. Improvement in dystonic movements is typically maintained while the trick is performed, but disappears when the geste ends. We investigated the phenomenological features of geste antagoniste maneuvers in 19 patients with idiopathic lower cranial dystonia who were prospectively evaluated over a period of 6 years. Of the 19, 10 were men, mean age of onset was 49.8 years, and the most commonly involved lower cranial area was the jaw (10 patients). In most patients, dystonia was task-specific. Taking advantage of the improvement with a sensory geste, we manufactured oral appliances that mimicked the geste in 8 patients, and 3 continue to use it.