Minimal volume,hypotense resuscitation

Large volume fluid resuscitation attempting to normalise physiological parameters in hypovolaemic shock has become the accepted management practice during the last 30 years. This doctrine, based on research in the 1950s, teaches that shock increases mortality, aggressive resuscitation improves outcome and normalisation of vital signs protects against multiple organ dysfunction. The wide acceptance of this doctrine is demonstrated by the central role it plays in the American College of Surgeons Advanced Trauma Life Support (ATLS) course and its Australian equivalent the Early Management of Severe Trauma (EMST) course. During the late 1980s, a number of animal research papers demonstrated severe limitations to the earlier work performed in the 1950s and proposed an alternative approach using hypotense or minimal fluid resuscitation. Controlled haemorrhagic shock is hypovolaemic shock in which the source of the bleeding is easily controlled without operation and hence aggressive fluid resuscitation can be pursued with minimum risk. Uncontrolled haemorrhagic shock is hypovolaemic shock due to bleeding which cannot be controlled without surgery. The restoration of blood pressure towards normal levels may lead to dislodgement of thrombus and loss of vascular spasm in damaged vessels, with a subsequent increase in blood loss. It is in this situation that hypotense resuscitation is thought to be of most value. Hypotense resuscitation is defined as the use of fluid resuscitation to maintain blood pressure at lower than normal levels which are sufficient to maintain life, but minimise the risk of exacerbating internal bleeding. Prompted by animal research a number of human studies have been undertaken to clarify the role of fluid resuscitation in uncontrolled haemorrhage. At present, there is wide acceptance of the use of hypotense or minimal volume resuscitation for ruptured abdominal aortic aneurysm and a recent demonstration that morbidity and mortality are decreased by the use of hypotense resuscitation in penetrating truncal trauma. There are however many other clinical situations that may produce uncontrolled haemorrhagic shock about which we have little clinical data to predict appropriate levels of fluid resuscitation. These include ectopic pregnancy, gastro-intestinal haemorrhage and blunt multi-system trauma. This paper will analyse the animal studies that demonstrate the physiological effects of the various fluid resuscitation regimes and discuss all the clinical papers on the subject of hypotense resuscitation. An attempt will then be made to integrate this data into current Australian practice and give broad guidelines on the modern management of uncontrolled haemorrhagic shock, based on minimal volume or hypotense resuscitation.     

The epidemiology of hypertension in family practice in Cape Town

A prevalence study of hypertension in 8 family practices in low socio-economic areas of Cape Town examined 1,046 patients over the age of 15 years. The crude prevalence rate of hypertension was 20.26%. There was no significant sex difference. Systolic pressure, diastolic pressure and hypertensive status increased with age and body mass index (BMI). There were complex relationships with regard to sex in that the female sex was predictive of hypertensive status after the age of 45 years unexplained by differences in BMI. After adjusting for age, BMI and sex differences, widowhood, poor education, obesity, a family history of hypertension or stroke and a past history of hypertension were significant predictors of hypertensive status. Smoking status, occupational social class or property ownership were not predictive. Fifty-one per cent of hypertensive subjects were treated. Of those receiving treatment, 30% were controlled resulting in a control prevalence of only 18%. Younger male subjects were better controlled by treatment. A strong need for improved diagnosis and treatment of hypertension in family practice exists in this region.     

CAG repeat number governs the development rate of pathology in Huntington's disease

We compared the number of CAG repeats, the age at death, and the severity of neuropathology in 89 Huntington's disease brains. We found a linear correlation between the CAG repeat number and the quotient of the degree of atrophy in the striatum (the brain region most severely affected in Huntington's disease) divided by age at death, with an intercept at 35.5 repeats. The largest CAG repeat length, therefore, at which no pathology is expected to develop is 35.5. These results imply that striatal damage in Huntington's disease is almost entirely a lineaar function of the length of the polyglutamine stretch beyond 35.5 glutamines multiplied by the age of the patient. Thus, it is predicted that the pathological process develops linearly from birth. Analysis of other measures of striatal function could test this hypothesis and might determine when treatment for CAG repeat diseases should start.     

石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

Outcome of laparoscopic Nissen fundoplication in patients with disordered preoperative peristalsis.

BACKGROUND: A 360 degrees or Nissen fundoplication remains controversial in patients with disordered peristalsis, some surgeons preferring a partial wrap to minimise postoperative dysphagia. AIM: To evaluate symptoms and manometric outcome in patients with disordered peristalsis after Nissen fundoplication. PATIENTS: In an initial series of 345 patients studied prospectively, 31 patients who had undergone a Nissen fundoplication had disordered peristalsis. Using preoperative manometry, patients were classified as: equivocal primary peristalsis (eight patients); abnormal primary peristalsis (four patients); abnormal maximal contraction pressure (13 patients); abnormal primary peristalsis and maximal contraction pressure (six patients). METHODS: Postoperatively, patients underwent a barium meal, oesophageal manometry and standardised clinical review by a blinded scientific officer. RESULTS: Twenty eight (90%) patients had satisfaction scores of at least 8 out of a maximum of 10 and all would undergo surgery again. Whereas 15 (48%) patients had dysphagia scores greater than 4/10 preoperatively, only two (6%) had these scores at one year. Improved peristalsis was seen in 78% of postoperative manometric studies, and mean preoperative lower oesophageal sphincter pressure increased from 6.6 (range 0-21) mm Hg to 19 (4-50) mm Hg. CONCLUSIONS: These results are similar to the overall group of 345 patients and suggest that disordered peristalsis, and possibly even absent peristalsis, is not a contraindication to Nissen fundoplication as performed in these patients.     

Varicella in a gorilla

Naturally occurring varicella was observed in a young gorilla in captivity. The isolate was demonstrated to be varicella-zoster virus by restriction enzyme analysis.     

Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial

To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.