Fat Embolism in Patients with Fractured Hips

Fat embolism was assessed at necropsy and correlated with clinical findings in the patients who died among 854 with fractured hips admitted to hospital between 1967 and August 1971. Sixteen cases of clinical importance were found, eight of which were judged to have been fatal or to have seriously contributed to death. Frequencies were as follows: 2·4 to 3·3% among 424 patients with subcapital fractures; 0·7 to 0·8% in the 405 with trochanteric fractures; 4·1 to 7% among subjects treated without operation, representing 30% of those who died within seven days; and 0·9 to 1·1% among patients treated by pinning, nailing, or nail-plating. The higher frequency in the conservatively treated group is probably related to selection of poor-risk subjects. Fat embolism was found in 6·8 to 8·0% of those with subcapital fractures treated by primary Thompson''s arthroplasty which utilizes acrylic cement, and in none of those given Moore''s prostheses for which cement is not used. Study of a larger group after Moore''s prosthesis is required to establish its lack of special risk. Fat embolism accounted for all the deaths within seven days of Thompson''s arthroplasty and for most within 14 days; it was clearly related to surgery in some cases.A possible explanation of the hazard of Thompson''s arthroplasty is that fat globule entry is enhanced by a rise of intramedullary pressure due to proximal occlusion of the reamed marrow cavity. A controlled trial of the effect of venting the marrow cavity on the frequency of fat embolism is warranted. It is possible that the acrylic monomer may also contribute to venous entry of medullary fat. The higher-age group of those with subcapital fractures and associated chronic cardiac and pulmonary disease might make them more susceptible to fat embolization than those in whom arthroplasty is also carried out for chronic hip disease.     

Malignant Lymphomas of Waldeyer's Ring: Natural History and Survival after Radiotherapy

The natural history of 292 consecutive cases of reticulum cell sarcoma and lymphosarcoma of Waldeyer''s ring and the survival rate after radiotherapy are reported. In our institute since 1928 from 30 to 35% of pharyngeal neoplasms have been lymphomas, and of these 55% have been reticulum cell sarcomas, 21% lymphosarcomas, and 1% Hodgkin''s disease. This high incidence may probably be ascribed to the fact that in all malignant lymphomas, irrespective of the clinical presentation, a systematic biopsy of the whole Waldeyer''s ring was carried out. Pharyngeal lymphomas were confined to Waldeyer''s ring in 19·6% of cases, with initial spread to contiguous cervical nodes in 43·8%, to distant nodes in 24·2%, and to extranodal tissues in 12·4%. Lymphography showed abnormal retroperitoneal lymph nodes in 38·3% of cases. There was gastrointestinal involvement either initially or later in 17·6% of cases. High-energy radiation therapy to both sides of the neck was the treatment of choice for local and regional disease. It achieved a five-year survival rate of 41·9% in the group of 97 patients treated during the past decade. The incidence of relapse (recurrence and new manifestations) was highest in the first year after treatment.     

Use of 4% Chlorhexidine Detergent Solution (Hibiscrub) and Other Methods of Skin Disinfection

In a comparison of three antiseptic detergent preparations for hand washing, Hibiscrub, a 4% chlorhexidine detergent solution, caused a significantly greater estimated immediate reduction of skin flora (86·7% ± 3·0) than was obtained with Dermofax, a 0·75% chlorhexidine detergent solution (55·5% ± 5·1), or with Disadine scrub, a povidone iodine detergent preparation (68% ± 6·8). After six applications the mean estimated reductions of skin flora were 99·2% ± 0·2 for Hibiscrub, 97·7% ± 0·7 for povidone iodine, and 91·8% ± 1·6 for Dermofax.After a series of hand washings with Hibiscrub, as with a hexachlorophane detergent preparation, a further large reduction of skin flora, shown by bacterial counts of hand sampling, was obtained by a second phase of disinfection consisting of two minutes'' application on gauze swabs of 0·5% chlorhexidine digluconate in 70% ethanol; a further wash with Hibiscrub, in place of alcoholic chlorhexidine, for the second phase of disinfection caused an increase rather than a reduction in the yield of bacteria on skin sampling. Unlike this “two-phase” disinfection, the application for 30 minutes of compresses soaked in 10% aqueous povidone iodine or in 0·5% aqueous chlorhexidine digluconate did not cause a greater reduction in skin flora than that obtained by the conventional two minutes'' application on gauze of 0·5% chlorhexidine in 70% ethanol.Chlorocresol (0·3%) liquid soap (the base used for Ster-Zac liquid hexachlorophane soap) caused a mean reduction of skin flora when used for hand washing of 29% after one application and 72% after six applications spread over two days. This formulation, though less active and more variable as a detergent skin antiseptic than chlorhexidine, hexachlorophane, or povidone iodine detergent preparations, is an inexpensive disinfectant soap which could be useful in catering establishments. Alcoholic cetrimide applied as for disinfection of an operation site caused a reduction of skin flora greater than that shown by aqueous cetrimide but comparable to that shown by 70% ethyl alcohol in previous experiments.     

Restless Legs Syndrome,with Particular Reference to its Occurrence After Gastric Surgery

There is a higher incidence of restless legs syndrome (Ekbom''s syndrome) in patients after gastric surgery (11·3%) and with diabetes mellitus (17·0%) and uraemia (17·3%) than in patients who have been diagnosed as having a psychonoeurosis (4·0%) and in controls (2·0%). Three patients with malabsorption syndrome complained of restless legs, but these patients had abnormal neurological signs. The incidence after gastric surgery and in diabetes mellitus and uraemia remained high even when patients with any abnormal neurological signs were excluded.     

Australia (Hepatitis-Associated) Antigen in Patients Attending a Venereal Disease Clinic

A total of 1,650 patients attending the venereal disease department at St. Mary''s Hospital, London, have been tested for Australia antigen. Twenty-three positive results were obtained, or 1·39%, which is more than 10 times the rate noted by others in blood donor populations in the U.K. and U.S.A. The positive rates among female patients and European male heterosexual patients were 0·36% and 0·19% respectively. High rates were obtained for homosexual patients (3·8%) and non-European heterosexual patients (3·1%). The reasons for the higher rates found in these groups merit further study.     

Blood Angiotensin II Levels of Normal and Hypertensive Subjects

A specific radioimmunoassay for angiotensin II has shown that its normal concentration in arterial blood is 2·4±1·2 (S.D.) mμg./l00 ml.; the venous level is consistently below this value, being usually 50–75% of it. Definite rises in blood angiotensin II levels were found in some patients with hypertension, both essential and secondary to renal disease. Extremely low levels were observed in two anephric women, and in one patient with Conn''s syndrome. This radioimmunoassay offers a valuable alternative to renin bioassay in evaluation of the role of the renal pressor system in clinical disorders associated with hypertension and aldosteronism.     

Blood Muramidase Activity in Colorectal Cancer

The serum muramidase levels were measured in 128 patients with primary or metastatic colorectal cancer, 166 tumour-free patients after resection of a colorectal cancer, and 172 controls. Muramidase levels over 10 μg/ml were detected in 30%-39% of the tumour-bearing patients, in 8·2% of the tumour free, and in only 1·7% of the controls (normal level 6·68 ± 1·42 μg/ml). Long-term follow up indicated that raised levels may occur as a transient phenomenon in recurrent or metastatic disease. The likely relation of abnormal serum muramidase activity and stimulation of the reticuloendothelial system is discussed.     

Serum and Urinary Folate in Liver Disease

During the active phase of viral hepatitis urinary folate loss was found to be 8·0 to 48·3 (mean 31·1) μg./day, compared with a normal urinary folate excretion of 0·1 to 18·0 (mean 9·5) μg./day. In cirrhosis and cardiac failure with congestive hepatomegaly the corresponding values were 25·8 to 55·0 (mean 35·7) μg./day and 2·5 to 61·6 (mean 26·9) μg./day, respectively. Urinary folate loss may be a significant factor in the aetiology of folate deficiency of chronic liver disease, particularly when dietary intake is poor.After prolonged dialysis in Visking casing urinary folate was almost totally dialysable, but an appreciable fraction of serum folate was not, even after 72 hours. The dialysable (free) folate fraction of serum and urine disappeared maximally during the first six hours'' dialysis, and was virtually cleared after 24 hours'' dialysis; clearance curves in normal individuals and in liver disease were comparable. The non-dialysable serum folate fraction was of similar magnitude in all subjects studied, in spite of marked variation in total folate, and probably represented protein-bound folate.     

Synthesis and biological evaluation of 2-arylbenzofuran derivatives as potential anti-Alzheimer’s disease agents

Alzheimer''s disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and β-secretase inhibitory activity. The IC₅₀ value of compound 20 against acetylcholinesterase inhibition (0.086 ± 0.01 µmol·L⁻¹) is similar to donepezil (0.085 ± 0.01 µmol·L⁻¹) and is better than baicalein (0.404 ± 0.04 µmol·L⁻¹). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 ± 0.03 µmol·L⁻¹). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD.     

Results of Early Mobilization and Discharge after Myocardial Infarction

A total of 342 patients with acute myocardial infarction who were admitted to a coronary care unit are reviewed to assess the results of early mobilization and discharge. The mean duration of admission was 8·4 days and 89% of the survivors were discharged from hospital by the tenth day. The inpatient mortality was 15·5%. An additional 6·7% died during the six weeks'' follow-up period, giving a total mortality of 22·2%. Altogether, 7·6% of patients were readmitted. Venous thromboembolic phenomena occurred in 3·5% during the inpatient period. Of patients who were eligible 62% were back at work five months after their myocardial infarction. We think the results justify a short hospital admission period for acute myocardial infarction.     

Surgical Treatment of Severe Attacks of Ulcerative Colitis,with Special Reference to the Advantages of Early Operation

The management and outcome of 258 severe attacks of ulcerative colitis from 1952 to 1969 has been reviewed. If remission did not occur during an initial course of intensive medical treatment, including administration of corticosteroids, operation (generally ileostomy with proctocolectomy or subtotal colectomy) was performed. This took place some 12 to 17 days after admission as a rule during the years 1952-63, but usually within five to seven days from 1964 to 1969.Roughly half the attacks underwent spontaneous remission during the two periods, but the medical mortality was 4·8% in the former and 0·7% in the latter, the operative mortality 20·0 and 7·0%, and the overall mortality 11·3 and 4.5% respectively. The lowering of the mortality was particularly striking in severe first attacks and in severe attacks in patients over 60 years of age.Perforation of the colon was found in 21 cases, or nearly 20% of 112 patients coming to operation during attacks, being commoner in the first period (32·5%) than in the second (11·1%). The immediate mortality of all such operations was 11·6%; in cases with perforation it was 28·6%.Acute colonic dilatation was observed in 28 cases. All but one were treated by emergency colectomy, at which the colon was noted to be perforated in 11. The mortality of these operations was 18·5%.Follow-up of the 140 patients who survived without coming to operation during their attacks shows that 52 (37·1%) subsequently underwent surgical treatment either during further attacks or electively.Though all 258 attacks were thought at the time to be due to ordinary ulcerative colitis, subsequent pathological examination of operative specimens derived from 98 patients who came to urgent or subsequent operation during the 1964-9 period revealed that the lesion in the large bowel was Crohn''s disease in 17 instances.     

Clinical Problems: Hepatitis in Dialysis Units in the United Kingdom

A prospective study of hepatitis in 20 dialysis units in the United Kingdom showed that the number of units with outbreaks increased from one in 1968 to three in 1969 and the overall attack rate rose from 1·7 to 5·3% in patients and from 0·5 to 1·3% in staff.In July 1969 a pilot study of patients'' sera showed that all of the outbreaks were associated with Australia (Au) antigen. Au antigen was not detected in the unaffected units or in one unit in which there were several patients with abnormal liver function.In January 1970 systematic prospective testing for Au antigen was begun. Au antigen was detected in single patients in five more of the 20 units. The transfer of the affected patients to isolation for dialysis seemed to prevent the spread of infection in the units. The incidence of hepatitis in 1970 was 5·6% in patients and 0·4% in staff.     

Quantification of Campylobacter spp. in Chicken Rinse Samples by Using Flotation prior to Real-Time PCR

Real-time PCR is fast, sensitive, specific, and can deliver quantitative data; however, two disadvantages are that this technology is sensitive to inhibition by food and that it does not distinguish between DNA originating from viable, viable nonculturable (VNC), and dead cells. For this reason, real-time PCR has been combined with a novel discontinuous buoyant density gradient method, called flotation, in order to allow detection of only viable and VNC cells of thermotolerant campylobacters in chicken rinse samples. Studying the buoyant densities of different Campylobacter spp. showed that densities changed at different time points during growth; however, all varied between 1.065 and 1.109 g/ml. These data were then used to develop a flotation assay. Results showed that after flotation and real-time PCR, cell concentrations as low as 8.6 × 10² CFU/ml could be detected without culture enrichment and amounts as low as 2.6 × 10³ CFU/ml could be quantified. Furthermore, subjecting viable cells and dead cells to flotation showed that viable cells were recovered after flotation treatment but that dead cells and/or their DNA was not detected. Also, when samples containing VNC cells mixed with dead cells were treated with flotation after storage at 4 or 20°C for 21 days, a similar percentage resembling the VNC cell fraction was detected using real-time PCR and 5-cyano-2,3-ditolyl tetrazolium chloride-4′,6′-diamidino-2-phenylindole staining (20% ± 9% and 23% ± 4%, respectively, at 4°C; 11% ± 4% and 10% ± 2%, respectively, at 20°C). This indicated that viable and VNC Campylobacter cells could be positively selected and quantified using the flotation method.     

Raised plasma intact parathyroid hormone concentrations in young people with mildly raised blood pressure

To study the role of parathyroid gland activity in early primary hypertension plasma concentrations of intact parathyroid hormone were measured in 90 untreated young subjects, aged 16-29, with stable mildly raised blood pressure and in 40 normotensive control subjects selected from the same population in Zoetermeer, The Netherlands. Intact parathyroid hormone concentration was significantly higher in the hypertensive than the normotensive group (2.34 (SE 0.11) pmol/l v 1·47 (0·13)pmol/l, respectively; difference 0·87 pmol/l; 95% confidence interval 0·55 to 1·21; p<0·0001). Serum total calcium concentration was 2·36 (0·01) mmol/l in the hypertensive group and 2·42 (0·01) mmol/l in the normotensive group (difference 0·06 mmol/l; 95% confidence interval 0·02 to 0·09; p=0·02). Urinary calcium excretion over 24 hours did not differ significantly between the two groups (4·17 (0·28) mmol/24 h in the hypertensive group and 3·89 (0·39) mmol/24 h in the normotensive group; difference 0·28 mmol/24 h; 95% confidence interval -0·66 to 1·22). In the hypertensive group both systolic and diastolic blood pressures increased slightly though significantly with intact parathyroid hormone concentrations. No obvious associations between serum calcium concentration and blood pressure were observed.These findings support the view that enhanced activity of the parathyroid gland may play a part in the early stage of primary hypertension.     

Streptokinase in Recent Myocardial Infarction: A Controlled Multicentre Trial

In this controlled multicentre trial treatment with either streptokinase or heparin was allocated at random to patients suffering from myocardial infarction of less than 24 hours'' duration. Treatment with either drug was standardized and lasted for 24 hours. A total of 764 patients entered the trial; 34 patient charts were rejected (including all 28 charts from one centre) because of data failure. On retrospective analysis of the 730 remaining patients the two groups were found to have been comparable at the start.The total hospital mortality was 18·5% of 373 patients allotted to streptokinase treatment and 26·3% of 357 given herapin. The mortality after infusion (24 hours) was 10·6% of 340 patients treated with streptokinase and 17·8% of 320 given herapin (P=0·011). Reinfarction in hospital after the 24-hour period of infusion occurred significantly less often in patients treated with streptokinase (P=0·036). Bleeding from puncture sites and pyrexia occurred more frequently during streptokinase treatment.After exclusion of those patients whose diagnosis was unconfirmed on retrospective assessment, the total hospital mortality rate was 19·0% of 357 patients treated with streptokinase and 27·4% of 339 treated with heparin (P=0·011). These results indicate that in recent myocardial infarction streptokinase was superior to heparin in reducing mortality and reinfarction rate during an average period of six weeks in hospital.     

The isolation and properties of epithelial-cell `ghosts' from rat small intestine

1. The preparation of gram quantities of isolated epithelial-cell `ghosts'' from mucosal scrapings of rat small intestine is described. The method involves dispersing the tissue by gentle homogenization in 6% dextran in Krebs–Ringer phosphate, pH7·4, followed by filtration through nylon cloth and sedimentation by low-speed centrifuging. 2. The isolated epithelial-cell `ghosts'' contained all of the DNA, but only 52% of the protein and 53–57% of the RNA of the original homogenate. They contained most of the activity of the following enzymes found in the homogenate: aminopeptidase (71%); alkaline β-glycerophosphatase (82%); invertase (92%); adenosine triphosphatase (93–116%); acid β-glycerophosphatase (83%); nonspecific esterase (76%); succinate dehydrogenase (96%). Only small proportions of the total lactate-dehydrogenase (10%) and phosphoglucose-isomerase (2%) activities found in the homogenate were recovered in the isolated cell `ghosts''. 3. The epithelial-cell `ghost'' preparation did not respire unless cofactors and substrates were added, and did not consume glucose or produce lactic acid from glucose. 4. The effect of varying the composition of the homogenization medium was studied. Concentrations of dextran (mol.wt. 15×10⁴) from 1 to 12%, solutions of dextrans (all at 6%) with mol.wt. varying between 3·6×10⁴ and 2×10⁶, and a solution of 8% polyethylene glycol (mol.wt. 4000) served equally well for the production of epithelial-cell `ghosts''. Two of these solutions, however, 12% dextran (mol.wt.15×10<sup>4</sup>) and 6% dextran (mol.wt. 2×10<sup>6</sup>), were too viscous to allow the complete sedimentation of the cell `ghosts'' at low relative centrifugal forces. Omission of either Krebs–Ringer phosphate or dextran from the medium resulted in almost complete cell breakage during the homogenization. 5. The isolated cell `ghosts'' were used as a starting material for subcellular fractionation of rat intestinal mucosa by differential centrifugation. The distributions of protein and succinate-dehydrogenase activity among the fractions were compared with corresponding values in fractions isolated by differential centrifugation of mucosa homogenized in 0·3m-sucrose–5mm-EDTA, pH7·4. The method in which cell `ghosts'' were used as starting material gave a better separation and cleaner fractions than the method in which untreated mucosal scrapings were used.     

Technetium-99m in the Diagnosis of Thyrotoxicosis

The thyroid uptake at 20 minutes of intravenously administered Technetium-99^m (^99mTc) was measured in 117 patients with a standard scintillation counter. Patients were divided into three groups on the basis of clinical assessment, four-hour ¹³¹I uptake, triiodothyronine (T-3) resin uptake, and protein-bound iodine measurements.In 31 patients with no evidence of thyroid disease the mean ^99m Tc uptake was 1·8% ±S.D. 1·1%. In 32 patients with thyroid enlargement who were euthyroid the mean uptake was 2·5% ±S.D. 2·2%. In 54 thyrotoxic patients the mean uptake was 17·7% with a range of 4·1 to 44%, all cases having an uptake above the upper limit of normal (4·0%). These results agree closely with reported uptake studies using scanning techniques. In seven patients the extrathyroidal neck activity was measured by using a scanner, and the mean was 6·3% of the extrathyroidal total body radioactivity comparing favourably with an assumed 6% used in our calculations.We have shown that the measurement of the thyroid uptake of ^99mTc with a scintillation counter is of value, and that it is not necessary to use scanning techniques in the diagnosis of thyrotoxicosis. Advantages of ^99m Tc are minimal radiation, reduction in patient and laboratory time, and low cost.     

Alcohol consumption in Dundee primigravidas and its effects on outcome of pregnancy

In a population based cohort study information on the consumption of alcohol was obtained from 95% of the 952 consecutive primigravidas who lived in the Dundee district and attended for antenatal care between May 1985 and April 1986. Before realising that they were pregnant more than 90% drank alcohol and 53% were cigarette smokers. During the first four months of pregnancy, however, the proportion of women drinking and smoking fell to 56% and 44%, respectively. Alcohol consumption of more than 120 g absolute alcohol/week (12 or more standard drinks) during pregnancy was related to shorter gestational age (-2·6 weeks), smaller head circumference (-18 mm), shorter (-21 mm) and lighter (-499 g) babies, and lower Apgar scores at five minutes (-0·4, all p<0·01). After adjustment for the effect of smoking, social class, mother''s size, and other confounding factors, however, an alcohol intake of more than 120 g/week was significantly related only to shorter gestational age (-2·0 weeks, p<0·001) and lower Apgar score at five minutes (-0·2, p<0·05). Alcohol intake in the region of 100-119 g/week was significantly related to smaller head circumference (-12 mm, p<0·05). Analysis by type of beverage consumed suggested that beer rather than wine or spirits was associated with a poorer outcome.As there was no detectable effect on pregnancy of alcohol consumption below 100 g/week, it is suggested that health education should be directed towards mothers who drink more than this amount.     

Weight loss in obese subjects on a restricted diet given BRL 26830A,a new atypical β adrenoceptor agonist

A double blind placebo controlled study was carried out in 40 subjects newly referred for treatment for obesity to determine the effects of the new thermogenic β adrenoceptor agonist BRL 26830A. The subjects were randomised to receive either BRL 26830A, 200 mg daily for two weeks then 400 mg daily, or placebo for 18 weeks, and all were instructed to follow a 3·35 MJ diet that was low in fat and high in fibre. Weight loss was 15·4 (SD 6·6) kg in subjects given BRL 26830A compared with 10·0 (5·9) kg in those given placebo (p=0·02). The relative weight loss was 0·93 (0·39)% a week with BRL 26830A and 0·61 (0·38)% with placebo (p=0·02). Urinary excretion of nitrogen was similar in both groups, whereas measurements of skinfold thickness indicated a 4·1 kg difference in the amount of fat lost, suggesting that weight loss with BRL 26830A was mainly from adipose and not lean tissue. BRL 26830A had no effect on resting pulse rate or pressor effects on either diastolic or systolic blood pressure. No significant differences were found between the two groups in serum cholesterol concentration, percentage of high density lipoprotein cholesterol, plasma concentrations of glucose and insulin, the ratio of glucose to insulin, serum concentrations of triiodothyronine and thyroxine, and creatinine clearance. Short term administration of BRL 26830A to six subjects who had taken the drug for 18 weeks showed that the expenditure of energy increased by 11·6% during the second hour after administration, which suggests that BRL 26830A may enhance weight loss thermogenically.BRL 26830A may be a useful drug in the treatment of obesity.     

Comparison of Effect on Tobacco Consumption and Carbon Monoxide Absorption of Changing to High and Low Nicotine Cigarettes

In 10 sedentary workers, smoking as they felt inclined over a five-hour period in the middle of a typical working day, changing to low nicotine cigarettes (<0·3 mg) caused an increase in the number and weight of cigarettes smoked, while changing to high nicotine cigarettes (3·2 mg) caused a decrease (P < 0·01). The average number and weight smoked in five hours for usual, low, and high nicotine brands were respectively 10·6 (6·00 g), 12·5 (6·52 g), and 6·7 (4·19 g). When smoking the usual brand the average blood carboxyhaemoglobin (COHb) increased 1·78% (from 6·38% to 8·16%). But on changing to either high or low nicotine cigarettes the COHb levels instead of increasing, tended to fall (P < 0·01). The average fall of 0·34% while smoking low nicotine cigarettes was due to the low carbon monoxide (CO) yield of these cigarettes, while the fall of 1·04% when smoking high nicotine cigarettes was attributable to reduced consumption. The findings support the view that smoking behaviour is modified to regulate nicotine intake. Besides having low tar and CO yields, the least harmful cigarettes for heavy smokers may be those with a high, rather than low, nicotine yield.