A severe case of hyperemesis gravidarum necessitating prolonged total parenteral nutrition

A patient with severe hyperemesis gravidarum persisting throughout pregnancy is described. She had marked abnormalities of liver function and failed to respond to conservative management. Total parenteral nutrition was used to maintain her nutritional status as well as that of the foetus. Her vomiting continued and was complicated by severe oesophagitis. On delivery her symptoms settled, but she later developed an oesophageal stricture. Changes in liver function tests are described.     

急性心肌梗死早期QT间期JT间期离散度与近期严重心律失常的关系

目的 :探讨AMI早期QT间期离散度、JT间期离散度与严重心律失常的关系。方法 :测定 46例AMI患者心梗发生后第 3d的QT间期离散度 (QTd)和JT间期离度 (JTd)。并与30例正常人的对照组比较。结果 :AMI组QTd、JTd、QTcd较对照组显著增大 (P <0 0 1 )。住院期间严重室性心律失常发生组 (1 8例 )的QTd、JTd、QTcd较无严重室性心律失常组 (2 8例 )明显增大 (P <0 0 1 ) ,且发生室颤的 9例患者QTd、JTd、QTcd比无室颤的明显增大 (P <0 0 1 )。结论 :早期测定AMI患者QTd、JTd、QTcd对患者近期严重室性心律失常的发生有预测意义     

Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents

1. Gabapentin (neurontin) is a novel antiepileptic agent that binds to the α₂δ subunit of voltage-dependent calcium channels. The only other compound known to possess affinity for this recognition site is the (S)-(+)-enantiomer of 3-isobutylgaba. However, the corresponding (R)-(−)-enantiomer is 10 fold weaker. The present study evaluates the activity of gabapentin and the two enantiomers of 3-isobutylgaba in formalin and carrageenan-induced inflammatory pain models.
2. In the rat formalin test, S-(+)-3-isobutylgaba (1–100 mg kg⁻¹) and gabapentin (10–300 mg kg⁻¹) dose-dependently inhibited the late phase of the nociceptive response with respective minimum effective doses (MED) of 10 and 30 mg kg⁻¹, s.c. This antihyperalgesic action of gabapentin was insensitive to naloxone (0.1–10.0 mg kg⁻¹, s.c.). In contrast, the R-(−)-enantiomer of 3-isobutylgaba (1–100 mg kg⁻¹) produced a modest inhibition of the late phase at the highest dose of 100 mg kg⁻¹. However, none of the compounds showed any effect during the early phase of the response.
3. The s.c. administration of either S-(+)-3-isobutylgaba (1–30 mg kg⁻¹) or gabapentin (10–100 mg kg⁻¹), after the development of peak carrageenan-induced thermal hyperalgesia, dose-dependently antagonized the maintenance of this response with MED of 3 and 30 mg kg⁻¹, respectively. Similar administration of the two compounds also blocked maintenance of carrageenan-induced mechanical hyperalgesia with MED of 3 and 10 mg kg⁻¹, respectively. In contrast, R-(−)-3-isobutylgaba failed to show any effect in the two hyperalgesia models.
4. The intrathecal administration of gabapentin dose-dependently (1–100 μg/animal) blocked carrageenan-induced mechanical hyperalgesia. In contrast, administration of similar doses of gabapentin into the inflamed paw was ineffective at blocking this response.
5. Unlike morphine, the repeated administration of gabapentin (100 mg kg⁻¹ at start and culminating to 400 mg kg⁻¹) over 6 days did not lead to the induction of tolerance to its antihyperalgesic action in the formalin test. Furthermore, the morphine tolerance did not cross generalize to gabapentin. The s.c. administration of gabapentin (10–300 mg kg⁻¹), R-(−) (3–100 mg kg⁻¹) or S-(+)-3-isobutylgaba (3–100 mg kg⁻¹) failed to inhibit gastrointestinal motility, as measured by the charcoal meal test in the rat. Moreover, the three compounds (1–100 mg kg⁻¹, s.c.) did not generalize to the morphine discriminative stimulus. Gabapentin (30–300 mg kg⁻¹) and S-(+)-isobutylgaba (1–100 mg kg⁻¹) showed sedative/ataxic properties only at the highest dose tested in the rota-rod apparatus.
6. Gabapentin (30–300 mg kg⁻¹, s.c.) failed to show an antinociceptive action in transient pain models. It is concluded that gabapentin represents a novel class of antihyperalgesic agents.

     

Effect of chronic ethanol treatment in vivo on excitability in mouse cortical neurones in vitro

1. The effects of cessation of chronic ethanol ingestion on seizure activity in vivo and on the characteristics of the evoked synaptic potentials in cortical neurones in vitro have been investigated in mice. Withdrawal from chronic ethanol treatment increased handling seizure ratings in mice between 4 and 16 h post-withdrawal. This ethanol-induced increase in seizure rating was unaffected by carbamazepine (30 mg kg⁻¹) but significantly reduced at a higher concentration (130 mg kg⁻¹).
2. Intracellular recordings were made from cortical layer II neurones in vitro from control mice and from mice following chronic ethanol ingestion. Evoked synaptic potentials were generated in these neurones through intralaminar stimulation.
3. Neurones from control mice displayed an evoked potential consisting of a fast excitatory postsynaptic potential (e.p.s.p.) mediated by AMPA-type glutamate receptors and an inhibitory postsynaptic potential (i.p.s.p.) mediated via GABA_A receptors. Application of pentylenetetrazole (PTZ) or bicuculline onto these neurones inhibited the i.p.s.p., caused a large increase in both the amplitude and duration of the e.p.s.p. and initiated spontaneous excitatory activity. The resulting large evoked e.p.s.p. was mediated via both NMDA- and AMPA-type glutamate receptors.
4. Most neurones (77%) from ethanol treated mice displayed an evoked potential which comprised a large e.p.s.p. and no i.p.s.p. The e.p.s.p. consisted of several distinct components and in addition these neurones displayed spontaneous paroxysmal depolarizing shifts. This multi-component e.p.s.p. was mediated through both NMDA- and AMPA-type glutamate receptors. A population (23%) of neurones from ethanol treated mice exhibited evoked potentials which possessed both inhibitory and excitatory components and these neurones were effectively identical to those obtained from control mice.
5. Carbamazepine reduced the duration of the e.p.s.p. in neurones from ethanol treated mice and in PTZ-treated control neurones.
6. Prolonged ethanol ingestion is known to create a neurochemical imbalance in cortical neurones resulting in abnormal neurotransmission. The present study highlights the functional consequences that arise as a result of these neurochemical changes leading to over-excitation of neurones and pronounced epileptiform activity.

     

Loss of heterozygosity on chromosome-8 in squamous-cell carcinomas of the head and neck

LOH studies provide evidence for the implication of novel TSGs in human tumours. The p arm of chromosome 8 has been reported to harbour tumour suppressor genes (TSGs) which are very likely to be involved in the development of colon, lung, bladder and hepatocellular carcinomas. In addition, the c-myc proto-oncogene which is located on the 8q arm, has been found to be overexpressed in SCCHN. In the present study we have investigated the incidence of loss of heterozygosity (LOH) in chromosome 8 in 37 tumour specimens of squamous cell carcinomas of the head and neck (SCCHN), using a bank of 11 polymorphic microsatellite markers. The aim of this work was to assess whether there was an 8p TSG(s) in SCCHN, as reported in other tumours and also to investigate whether other areas of chromosome 8 exhibit a high LOH. A relatively high incidence of LOH was found for the markers D8S87 (29%) on 8p12 and ANK1 (20%) on 8p21.2-p11. These two markers are located in the area in which TSG(s) for other cancers have been previously described. When the data on D8S87 and ANK1 were analyzed together it was found that 13/35 (37%) of the SCCHN specimens had a loss at one or other of these markers, thus indicating that a putative TSG(s) in this region may play a role in the development of the SCCHN. No correlation was found between the LOH data and any of the clinicopathological parameters. We also investigated the incidence of c-myc amplification in 144 SCCHN specimens but only 4% were found to have an amplified c-myc allele, thus indicating that the overexpression of c-myc in SCCHN was not the result of gene amplification.     

Allele loss on chromosome-3 in squamous-cell carcinoma of the head and neck correlates with poor clinical prognostic indicators

Cytogenetic studies in squamous cell carcinoma of the head and neck (SCCHN) have identified a clustering of breakpoints in a number of chromosomes, including chromosome 3. We have undertaken a loss of heterozygosity analysis (LOH) of 36 SCCHN and six solid tumours which were not squamous cell, and their respective normal specimens, using a bank of microsatellite markers, with the aim of identifying specific sites of frequent loss on chromosome 3. The analysis was undertaken with 12 microsatellite markers, 10 of which are on the p arm of chromosome 3. Allelic loss greater than 10% was seen at four sites; D3S1269 (13%), D3S1079 (23%), D3S659 (23%) and D3S1293 (31%). None of this series of tumours showed loss of the whole chromosome, however 47% of the tumours analysed had LOH at one or more loci. The highest incidence of LOH was found at D3S1293 in the 3p24-p25 region. The second highest region with LOH was found at D3S1079 and D3S659 at 3p13. The remaining markers telomeric and centromeric to these two regions were found to have a LOH of less than 10%. Furthermore, we found a strong association between loss of one marker on chromosome 3 in these SCCHN and poor clinical prognostic indicators; such as site, pathological differentiation, positive nodes at pathology (p<0.05) and TNM status (p<0.05). This study has identified two regions in SCCHN that are most likely to be important in the development of squamous cell carcinoma of the head and neck at 3p24-p25 and 3p13 and may indicate sites of novel tumour suppressor genes in this disease.     

Semi-quantitative assessment of tibial blood flow and distribution in response to surgical intervention using first pass radionuclide angiography and intravascular vital dye

The acute vascular response in bone to surgical trauma was investigated utilizing a sheep model. Blood flow and distribution were determined using two methods; perfusion of the vasculature with an intravascular vital dye (Disulphine blue) prior to euthanasia and by radionuclide angiography (RNA) before and after each surgical intervention. The pattern of Disulphine blue distribution provided a good indication of local perfuslon and response to surgical trauma (drilling holes). Radionuclide angiography provided a dynamic image of the vascular response to surgical trauma. The generation of time activity curves of the first pass of radionuclide bolus enabled calculation of the relative blood flow through selected regions.

For both techniques areas of ischaemia were apparent which were directly related to the location of screw holes. We conclude that factors other than bone plate contact influence the ischaemia that develops in bone subsequent to the application of bone plates.     

Should accident and emergency nurses request radiographs? Results of a multicentre evaluation.

OBJECTIVE--To evaluate whether waiting time in accident and emergency (A&E) departments is shortened when experienced nurses request peripheral limb radiographs before a patient is assessed by a doctor. DESIGN--Simultaneous prospective trial in four A&E departments in the United Kingdom with doctors and nurses requesting radiographs; 2000 patients were randomly allocated to either a "Nurse First" or "Doctor First" category. SUBJECTS--Patients older than 5 years presenting with recent peripheral limb injuries. MAIN OUTCOME MEASURES--Timing of the various stages of a patient's passage through the A&E department comparing the orthodox route with a group of patients in whom an experienced A&E nurse had the option of requesting a radiograph before a medical assessment. RESULTS--There was a significant reduction in the time spent in A&E when no radiograph was requested (P << 0.001). The mean time saved in the "Doctor First" (DF) group was 51 min, and in the "Nurse First" (NF) group 36 min. For those who were sent for an x ray 14 min was saved by getting the patient to see the nurse first. However, because the overall referral rate for x rays was greater in the NF group, (78% of patients compared with 74% of the DF group, a significant 4% increase (P = 0.05) this potential benefit was largely lost. Overall the average waiting time in the DF group of 92.5 min (95% confidence interval: 89.2 to 96.1 min) was reduced to 88.5 min (95% CI:85.2 to 91.8 min) in the NF group, a non-significant saving of 4 min. There was no overall difference between the proportion of relevant abnormalities reported by the radiologists for the DF or NF groups (G2 = 0.739, 1df, P = 0.30); however, there was a significant association between the number of relevant abnormalities reported by the radiologists and the different hospitals (G2 = 9.7626, 3df, P = 0.02). Hospital C had the highest abnormality rate reported by the radiologists in both the DF (45%) and the NF (51%) groups. The most time saved in A&E was in the DF category when comparing those who did not have an x ray [58 (CI 54-63) min] with those who did [109 (CI 104-114) min], a saving of 51 min. The corresponding time saved in the NF category between those who did not have an x ray [59 (CI 53-65) min] and those who did [95 (CI 91-99) min] was 36 min. CONCLUSIONS--14 min can be saved by getting the patient to see the nurse first; however, because nurses in three out of four hospitals requested more radiological examinations than doctors, overall only 4 min waiting time was saved when peripheral limb radiographs were requested by nurses. The findings are somewhat against expectations but do identify that specific training and constant monitoring is essential if nurses are to request peripheral limb radiographs, as reflected in hospital C results.     

Long-term outcome and cost-effectiveness of parenteral nutrition for acute gastrointestinal failure

Although there are several published audits of long-term home parenteral nutrition for chronic gastrointestinal failure, there is little data concerning the long-term outcome following prolonged in-patient parenteral nutrition for an episode of acute gastrointestinal failure. Between 1983 and 1 July 1993, 162 patients received total parenteral nutrition (TPN) in our unit for acute gastrointestinal failure for a total of 4997 patient days and using 192 central venous catheters. Over the 10 years there were 11 mechanical complications resulting in one death. Although the overall catheter infection rate was 5.7%, in the last 4 years it was 0%, associated with a reduction in the frequency of site dressing and change of giving set from three times to once weekly. All patients had lost more than 10% of their body weight before TPN. In the non-malignant group, fed for more than 21 days (mean 50 days), the 10-year survival was 74% at a cost of 4723 pounds sterling per year of life saved. In the malignant group, the 5-year survival was 27% at a cost of 8351 pounds sterling per year of life saved. These costs compare favourably with other technologies, such as dialysis for acute renal failure. Better patient selection, fewer complications and lower costs are obtained when this treatment is carried out by an expert team.