Behavioural variability, physical activity, rumination time, and milk characteristics of dairy cattle in response to regrouping.

In the commercial dairy industry worldwide, it is common practice to periodically regroup cows as part of their management strategy within housed systems. While this animal husbandry practice is intended to improve management efficiency, cows may experience social stress as a result of the social environment changes, which may have an impact on their behavioural patterns, performance, and welfare. We investigated whether regrouping altered dairy cows' behaviour and impacted their cortisol concentration (a physiological marker of stress), oxytocin, milk yield, and quality in a robotic milking system. Fifty-two lactating cows (17 primiparous; 35 multiparous) were moved in groups of 3-5 individuals into established pens of approximately 100 cows. Behaviour of the regrouped cows was directly observed continuously for 4 h/day across 4-time blocks (day-prior (d-1), day-of regrouping (d0), day-after (d + 1), and 6-days after (d + 6) regrouping). Cows were categorised as being with others, alone, or feeding every 2.5 min prior to the assessment of behavioural dynamics. Milk yield (MY) and composition, total daily activity, and rumination time (RUM) data were extracted from the Lely T4C management program (Lely Industries, Maassluis, the Netherlands), and milk samples were collected for cortisol and oxytocin concentration analyses; data were analysed using linear mixed-effect modelling. Primiparous cows were less likely to be interacting with others on d + 1 than d-1 compared with multiparous. However, average bout duration (minutes) between being alone and feeding activity states were similar on d-1, d + 1, and d + 6, for both primiparous and multiparous cows. A reduction in the average alone and feeding bout duration was observed on d0. Multiparous cows spent significantly more total time being alone on d0 compared to d-1. Neither regrouping nor parity statistically influenced milk DM content, energy, or cortisol concentration. Primiparous cows produced 3.80 ±â€¯2.42 kg (12.2%) less MY on d + 1 compared to their d-1, whereas multiparous cows did not change MY. A significant decrease of 0.2% fat was found in both parity groups following regrouping and remained low up to d + 6. Daily activity in both parity groups increased significantly and RUM reduced after regrouping. A significant decrease in oxytocin concentration was observed in all cows on d + 1. The results, specifically for primiparous cows, indicated a negative impact of regrouping on social interactions, due to changes in the social environment which may lead to short-term social instability. Multiparous cows may benefit from previous regrouping experiences.

Disentangling the effects of obesity and high-fat diet on glucose homeostasis using a photoperiod induced obesity model implicates ectopic fat deposition as a key factor.

OBJECTIVE: Obesity in laboratory rodents is generally induced by feeding them a high fat diet (HFD). This model does not permit separation of the impact of the HFD from the resultant obesity on metabolic defects such as impaired glucose homeostasis. In Brandt's voles we have previously shown that exposure to long photoperiod (LD: 16L: 8D) induces obesity even when they are fed a low fat diet. We show here that these voles are largely resistant to HFD. This model therefore permits some separation of the effects of HFD and obesity on glucose homeostasis. The objective was therefore to use this model to assess if glucose homeostasis is more related to diet or obesity METHODS: Male voles, which were 35 days old and born in LD, were exposed to SD and a low fat diet for 70 days. We then randomly separated the animals into 4 groups for another 63 days: SL (short day and low fat diet: n = 19) group; SH (short day and high-fat diet, n = 20) group; LL (long day and low-fat diet, n = 20) group; LH (long day and high-fat diet, n = 18) group. Glucose tolerance tests (GTT) were performed after treatment for 56 days, and body compositions of the voles were quantified at the end by dissection. RESULTS: Consistent with our previous work LD voles were more obese than SD voles. Although total body weight was independent of dietary fat content, HFD did have an effect on fat storage. Photoperiod induced obesity had no effect on glucose homeostasis, and the fat content in both the liver and muscle. In contrast, HFD induced adiposity was linked with elevated fat deposition in muscle (but not in liver) and led to impaired glucose tolerance. CONCLUSIONS: The contrasting effects of diet and photoperiod were consistent with the predictions of the 'lipotoxicity hypothesis'. This may contribute to our understanding of why some human individuals are able to be obese yet remain metabolically healthy.

Influence of environmental factors and parity on milk yield dynamics in barn-housed dairy cattle.

We investigated the effects of environmental factors on average daily milk yield and day-to-day variation in milk yield of barn-housed Scottish dairy cows milked with an automated milking system. An incomplete Wood gamma function was fitted to derive parameters describing the milk yield curve including initial milk yield, inclining slope, declining slope, peak milk yield, time of peak, persistency (time in which the cow maintains high yield beyond the peak), and predicted total lactation milk yield (PTLMY). Lactation curves were fitted using generalized linear mixed models incorporating the above parameters (initial milk yield, inclining and declining slopes) and both the indoor and outdoor weather variables (temperature, humidity, and temperature-humidity index) as fixed effects. There was a higher initial milk yield and PTLMY in multiparous cows, but the incline slope parameter and persistency were greatest in primiparous cows. Primiparous cows took 54 d longer to attain a peak yield (mean ± standard error) of 34.25 ± 0.58 kg than multiparous (47.3 ± 0.45 kg); however, multiparous cows yielded 2,209 kg more PTLMY. The best models incorporated 2-d lagged minimum temperature. However, effect of temperature was minimal (primiparous decreased milk yield by 0.006 kg/d and multiparous by 0.001 kg/d for each degree increase in temperature). Both primiparous and multiparous cows significantly decreased in day-to-day variation in milk yield as temperature increased (primiparous cows decreased 0.05 kg/d for every degree increase in 2-d lagged minimum temperature indoors, which was greater than the effect in multiparous cows of 0.008 kg/d). Though the model estimates for both indoor and outdoor were different, a similar pattern of the average daily milk yield and day-to-day variation in milk yield and milk yield's dependence on environmental factors was observed for both primiparous and multiparous cows. In Scotland, primiparous cows were more greatly affected by the 2-d lagged minimum temperature compared with multiparous cows. After peak lactation had been reached, primiparous and multiparous cows decreased milk yield as indoor and outdoor minimum temperature increased.

Limits to sustained energy intake. XXXII. Hot again: dorsal shaving increases energy intake and milk output in golden hamsters (Mesocricetus auratus).

Golden hamsters have four times the body size of mice, raise very large litters and are required to produce large quantities of milk during the 18-day lactation period. We have previously proposed that they may be prone to being limited by their heat dissipation capacity. Studies where lactating females are shaved to elevate their heat dissipation capacity have yielded conflicting data so far. With their short pregnancy of ∼18 days, the large litters and the reported high skin temperatures, they may serve as an ideal model to elucidate the role of epilation for energy budgets in lactating mammals. We shaved one group of lactating females dorsally on the sixth day of lactation, and tested if the elevated heat dissipation capacity would enable them to have higher energy intakes and better food-to-milk conversion rates. Indeed, we observed that females from the shaved group had 6% higher body mass and 0.78°C lower skin temperature than control females during lactation. When focusing on the phase of peak lactation, we observed significantly higher (10%) gross energy intake of food and 23.4% more milk energy output in the shaved females, resulting in 3.3 g higher individual pup weights. We conclude that shaving off the females' fur, even though restricted to the dorsal surface, had large consequences on female energy metabolism in lactation and improved milk production and pup growth in line with our previous work on heat dissipation limitation. Our new data from golden hamsters confirm heat dissipation as a limiting factor for sustained metabolic rate in lactation in some small mammals and emphasise the large effects of a relatively small manipulation such as fur removal on energy metabolism of lactating females.

Limits to sustained energy intake XXIV: impact of suckling behaviour on the body temperatures of lactating female mice.

The objective of this study was to investigate the potential causes of high body temperature (Tb) during lactation in mice as a putative limit on energy intake. In particular we explored whether or not offspring contributed to heat retention in mothers while suckling. Tb and physical activity were monitored in 26 female MF1 mice using intraperitoneally implanted transmitters. In addition, maternal behaviour was scored each minute for 8 h d(-1) throughout lactation. Mothers that raised larger litters tended to have higher Tb while nursing inside nests (P < 0.05), suggesting that nursing offspring may have influenced heat retention. However, Tb during nursing was not higher than that recorded during other behaviours. In addition, the highest Tb during the observation period was not measured during nursing behaviour. Finally, there was no indication that mothers discontinued suckling because of a progressive rise in their Tb while suckling. Tb throughout lactation was correlated with daily increases in energy intake. Chronic hyperthermia during lactation was not caused by increased heat retention due to surrounding offspring. Other factors, like metabolic heat produced as a by-product of milk production or energy intake may be more important factors. Heat dissipation limits are probably not a phenomenon restricted to lactation.

Oxidative costs of reproduction: Oxidative stress in mice fed standard and low antioxidant diets.

Lactation is one of the most energetically expensive behaviours, and trade-offs may exist between the energy devoted to it and somatic maintenance, including protection against oxidative damage. However, conflicting data exist for the effects of reproduction on oxidative stress. In the wild, a positive relationship is often observed, but in laboratory studies oxidative damage is often lower in lactating than in non-breeding animals. We hypothesised that this discrepancy may exist because during lactation food intake increases many-fold resulting in a large increase in the intake of dietary antioxidants which are typically high in laboratory rodent chow where they are added as a preservative. We supplied lactating and non-breeding control mice with either a standard or low antioxidant diet and studied how this affected the activity of endogenous antioxidants (catalase, superoxide dismutase; SOD, and glutathione peroxidise; GPx) and oxidative damage to proteins (protein carbonyls, PC) in liver and brain tissue. The low antioxidant diet did not significantly affect activities of antioxidant enzymes in brain or liver, and generally did not result in increased protein damage, except in livers of control mice on low antioxidant diet. Catalase activity, but not GPx or SOD, was decreased in both control and lactating mice on the low antioxidant diet. Lactating mice had significantly reduced oxidative damage to both liver and brain compared to control mice, independent of the diet they were given. In conclusion, antioxidant content of the diet did not affect oxidative stress in control or reproductive mice, and cannot explain the previously observed reduction in oxidative stress in lactating mammals studied in the laboratory. The reduced oxidative stress in the livers of lactating mice even under low antioxidant diet treatment was consistent with the 'shielding' hypothesis.

Limits to sustained energy intake. XX. Body temperatures and physical activity of female mice during lactation.

Lactating animals consume greater amounts of food than non-reproductive animals, but energy intake appears to be limited in late lactation. The heat dissipation limit theory suggests that the food intake of lactating mice is limited by the capacity of the mother to dissipate heat. Lactating mice should therefore have high body temperatures (Tb), and changes in energy intake during lactation should be reflected by variation in Tb. To investigate these predictions, 26 mice (Mus musculus) were monitored daily throughout lactation for food intake, body mass, litter size and litter mass. After weaning, 21 days postpartum, maternal food intake and body mass were monitored for another 10 days. Maternal activity and Tb were recorded every minute for 23 h a day using implanted transmitters (vital view). Energy intake increased to a plateau in late lactation (days 13-17). Daily gain in pup mass declined during this same period, suggesting a limit on maternal energy intake. Litter size and litter mass were positively related to maternal energy intake and body mass. Activity levels were constantly low, and mice with the largest increase in energy intake at peak lactation had the lowest activity. Tb rose sharply after parturition and the circadian rhythm became compressed within a small range. Tb during the light period increased considerably (1.1 ° C higher than in baseline), and lactating mice faced chronic hyperthermia, despite their activity levels in lactation being approximately halved. Average Tb increased in relation to energy intake as lactation progressed, but there was no relationship between litter size or litter mass and the mean Tb at peak lactation. These data are consistent with the heat dissipation limit theory, which suggests performance in late lactation is constrained by the ability to dissipate body heat.

Predicting non-cardiac aetiology: a strategy to allocate rescue breathing during bystander CPR.

AIMS: Optimal care for out-of hospital cardiac arrest (OHCA) patients may depend on the underlying aetiology of OHCA. Specifically chest compression only bystander CPR may provide greater benefit among those with cardiac aetiology and chest compressions plus rescue breathing may provide greater benefit among those with non-cardiac aetiology. The aim of this study was to generate a simple predictor model to identify OHCA patients with non-cardiac aetiology in order to accurately allocate rescue breathing. METHODS: We used two independent cohorts of OHCA patients from a randomized pre-hospital trial and a prospective hospital registry (total n=3086) to assess whether the characteristics of age, gender and arrest location (private versus public) could sufficiently discriminate non-cardiac aetiology. We used logistic regression models to generate a receiver operator curve and likelihood ratios. RESULTS: Overall, 965/3086 (31%) had a final diagnosis of a non-cardiac cause. Using 8 exclusive groups according to age, gender, and location, the frequency of non-cardiac aetiology varied from a low of 16% (55/351) among men >age 50 in a public location up to 58% (199/346) among women <60 in a private location. Although each characteristic was predictive in the logistic regression model, the area under the curve in the receiver operating curve was only 0.66. The associated positive likelihood ratios ranged from 1 to 3 and the negative likelihood ratios ranged from 1 to 0.4. CONCLUSION: The results highlight the challenge of accurately identifying non-cardiac aetiology by characteristics that could be consistently used to allocate bystander rescue breathing.

Faecal corticosterone concentrations indicate that separately housed male mice are not more stressed than group housed males.

Mice account for over 80% of all animals used in experimentation. This study investigated how different housing conditions affected stress levels by measuring both corticosterone levels, using non-invasive faecal collection, and behaviour. Sixty outbred MF1 male mice were used which were separated into five different housing conditions at the beginning of the study, (A) individually housed, floor area 490 cm(2) per individual, (B) groups of three mice, floor area 163 cm(2) per individual, (C) groups of three mice, floor area 320 cm(2) per individual, (D) groups of six mice, floor area 160 cm(2) per individual, (E) groups of six mice, floor area 230 cm(2) with extra height per individual to allow visual contact. Mice in all housing conditions were provided with a basic enrichment of paper bedding and a plastic house. The results from this study showed that singly housed mice reduced their corticosterone levels over time after separation reaching a minimum from 14 days onwards. Groups of 6 mice housed together showed no difference over time. Also there was no significant difference in corticosterone levels between the different housing densities, with no differences for aggression or stereotypical behaviour suggesting that there is no ideal group density for this strain and sex of mouse. Providing additional enrichment to the cages caused a significant decrease in corticosterone levels for group housed mice, but individually housed mice remained unaffected by increasing their enrichment level. They spent significantly more time sleeping in the enhanced cage but without any reduction in stereotypical behaviour. For group housed mice, additional enrichment should be mandatory to reduce stress levels and therefore increase their welfare standards, while singly housed mice required only basic levels of enrichment and should be separated from their group for a minimum of 2 weeks before measurements are taken.

Comparison of the cost of short flights in a nectarivorous and a non-nectarivorous bird.

Although most birds are accustomed to making short flights, particularly during foraging, the flight patterns during these short periods of activity differ between species. Nectarivorous birds, in particular, often spend time hovering, while non-nectarivorous birds do not. The cost of short flights is likely therefore to differ between nectarivorous and non-nectarivorous birds because of the different energetic contributions of different flight types to the behaviour. The 13C-labelled bicarbonate technique was used to measure the energy cost of short flights in the nectarivorous Palestine sunbird Nectarinia osea (mean mass 6.17+/-0.16 g, N=8) and the non-nectarivorous starling Sturnus vulgaris (mean mass 70.11+/-1.11 g, N=9). The technique was initially calibrated in five individuals for each species at temperatures ranging from 1 to 35 degrees C, by comparing the isotope elimination rate to the metabolic rate measured simultaneously by indirect calorimetry. The cost for short intermittent flight was then measured by encouraging birds to fly between two perches at either end of a narrow corridor (perch distance for sunbirds, 6 m; for starlings, 5 m), and measuring the amount of isotope eliminated during the flight. The isotope elimination rate was interpolated onto the calibration equation to predict flight cost, as a direct calibration could not be performed during flight. Mean energy expenditure during flight was 1.64+/-0.32 W in sunbirds, while in starlings the flight costs averaged 20.6+/-0.78 W. Energy cost of flight relative to basal metabolic rate was substantially greater in the starling than the sunbird. Phylogenetic analysis of different modes of flight in these and additional species suggests that differences in flight behaviour may cause these elevated costs in slow flying non-nectarivores such as starlings, compared to birds that are more prone to short intermittent flights like the sunbirds.

The energy cost of loaded flight is substantially lower than expected due to alterations in flight kinematics.

The effect of experimentally increased wing loading on the energy cost of flight was examined in cockatiels Nyphicus hollandicus. Five individuals were flown for periods of approximately 2 min, while carrying additional payload mass amounting to between 5 and 20% of unloaded body mass. The energy cost of flight was measured using the 13C-labelled bicarbonate technique, which was also calibrated in a separate experiment on resting birds, by comparing the elimination rate of 13C in breath with a simultaneous measurement of oxygen consumption by indirect calorimetry. It was not possible to perform a similar calibration during flight when energy costs were higher, so we extrapolated the relationship from the resting calibration to predict flight cost. Flight cost in the pre-manipulated individuals averaged 16.7+/-1.8 W. Flight cost in the pre-manipulated birds was significantly related to the interaction between downstroke duration and flight speed. There was no significant increase in flight cost with increases in payload mass. The birds responded to payload masses between 5 and 15% of their unloaded body mass by decreasing flight speed relative to unloaded birds, while maintaining wing beat frequency (Fb). At a payload mass equivalent to 20% of body mass, however, the birds flew at higher speeds than unloaded controls, and had a significantly higher Fb, generated by a reduction in both the upstroke and downstroke durations. Wing amplitude was unaffected by the increase in loading. Using the measured flight parameters, the effect of loading was not significantly different than predicted using aerodynamic models.

The energetic cost of variations in wing span and wing asymmetry in the zebra finch Taeniopygia guttata.

Asymmetry is a difference in the sizes of bilaterally paired structures. Wing asymmetry may have an effect on the kinematics of flight, with knock-on effects for the energetic cost of flying. In this study the 13C-labelled bicarbonate technique was used to measure the energy expended during the flight of zebra finches Taeniopygia guttata, prior to and after experimental manipulation to generate asymmetry and a change in wing span by trimming the primary feathers. In addition, simultaneous high-speed video footage enabled differences in flight kinematics such as flight speed, wing amplitude, up- and downstroke duration and wing beat frequency to be examined. In 10 individuals, the primary feathers on the right wing were trimmed first, by 0.5 cm, and then by an additional 0.5 cm in six of these individuals. In a separate 'control' group (N=7), approximately 0.25 cm was trimmed off the primary feathers of both wings, to produce the same reduction in wing span as 0.5 cm trimmed from one wing, while maintaining symmetry. When birds were manipulated to become asymmetric they maintained flight speed. They also increased the left wing amplitude and decreased the right up- and downstroke durations to counteract the changes in wing shape, which meant that they had an increase in wing beat frequency. When the wing area was reduced while maintaining symmetry, birds flew with slower flight speed. In this case wing amplitude did not change and wing upstroke slightly decreased, causing an increased wing beat frequency. The mean flight cost in the pre-manipulated birds was 1.90+/-0.1 W. There was a slight increase in flight cost with both of the asymmetry manipulations (0.5 cm, increase of 0.04 W; 1.0 cm, increase of 0.12 W), neither of which reached statistical significance. There was, however, a significantly increased flight cost when the wing span was reduced without causing asymmetry (increase of 0.45 W; paired t-test T=2.3, P=0.03).

Cost of flight in the zebra finch ( Taenopygia guttata): a novel approach based on elimination of (13)C labelled bicarbonate.

On three separate occasions, five zebra finches ( Taenopygia guttata) were injected intraperitoneally with 0.2 ml 0.29 M NaH(13)CO(3)solution and placed immediately into respirometry chambers to explore the link between (13)C elimination and both O(2) consumption (VO(2)) and CO(2) production (VCO(2)). Isotope elimination was best modelled by a mono-exponential decay. The elimination rate (k(c)) of the (13)C isotope in breath was compared to VO(2) (ml O(2)/min) and VCO(2) (ml CO(2)/min) over sequential 5-min time intervals following administration of the isotope. Elimination rates measured 15-20 min after injection gave the closest relationships to VO(2) ( r(2) =0.82) and VCO(2) ( r(2)=0.63). Adding the bicarbonate pool size (N(c)) into the prediction did not improve the fit. A second group of birds ( n=11) were flown for 2 min (three times in ten birds and twice in one) between 15 min and 20 min following an injection of 0.2 ml of the same NaH(13)CO(3) solution. Breath samples, collected before and after flight, were used to calculate k(c) over the flight period, which was converted to VO(2) and VCO(2) using the equation generated in the validation experiment for the corresponding time period. The energy expenditure (watts) during flight was calculated from these values using the average RQ measured during flight of 0.79. The average flight cost measured using the bicarbonate technique was 2.24+/-0.11 W (mean+/-SE). This average flight cost did not differ significantly from predictions generated by an allometric equation formulated by Masman and Klaassen (1987 Auk 104:603-616). It was however substantially higher than the predictions based on the aerodynamic model of Pennycuick (1989 Oxford University Press), which assumes an efficiency of 0.23 for flight. The flight efficiency in these birds was 0.11 using this model. Flight cost was not related to within-individual variation [general linear model (GLM) F(1,31)=1.16, P=0.29] or across-individual variations in body mass (GLM F(1,31)=0.26, P=0.61), wingspan (regression F(1,10)=0.01, P=0.94) or wing loading (regression F(1, 31)=0.001, P=0.99) in this sample of birds.

Can non-shivering thermogenesis in brown adipose tissue following NA injection be quantified by changes in overlying surface temperatures using infrared thermography?

We aimed to investigate whether infra red thermography (IRT) can be used to measure and quantify non-shivering thermogenesis (NST) in the short-tailed field vole Microtus agrestis, by directly comparing it with a standard method, i.e. metabolic response following Noradrenaline injection (NA). Mean skin surface temperature overlying Brown adipose tissue (BAT) depot was 0.82 degrees C higher than mean surface temperature that did not overly BAT. The difference in temperature increased by 1.26 degrees C after NA was administered. Mean skin surface temperature overlying BAT increased by 0.32 degrees C after NA was administered; however, surface temperature decreased by 1.32 degrees C after saline was administered. Mean skin surface temperature overlying BAT did not change significantly between warm and cold acclimated voles; in contrast metabolic peak following NA injection significantly increased in cold acclimated voles. There was no significant correlation between change in surface temperature after NA injection and metabolic peak following NA injection. The results of this study suggest that IRT is not a sensitive enough method to measure changes in NST capacity in BAT following NA injection, or to detect changes in NST capacity induced by cold acclimation. However, IRT can distinguish between skin surfaces overlying BAT and skin surfaces that do not.

An innovative approach to medical control: semiautomatic defibrillators with solid-state memory modules for recording cardiac arrest events.

We evaluated the use of microprocessor-based memory modules incorporated into automatic external defibrillators. These solid-state modules store information about each clinical use, including selected segments of the ECG rhythm and notations on defibrillator operation. A playback unit provides annotated printouts of the recorded information. The purpose of our evaluation was to determine whether this memory module could adequately support medical control "run-reviews" when compared with dualfunction (voice and ECG) tape recordings. A total of 41 resuscitation attempts by emergency medical technicians trained to defibrillate (EMT-Ds) were evaluated in five preselected performance areas: defibrillation skills, command and communication at the scene, patient assessment and support, safety, and speed. When performance was reviewed using the tape recordings, the average EMT-D performance score was 16.2 (maximum, 20); when reviewed using the printouts from the medical control modules, the average score, 7.2, was significantly lower (P less than .01). The lower scores with the medical control module occurred because not all five areas of skill could be evaluated adequately by the memory module approach. Assessment of the areas of communication/command at the scene, patient assessment/support, and safety required verbal tape recordings. The medical control module appeared superior to the tape recordings at providing a quick, convenient, and accurate evaluation of rhythm assessment, shock decisions, time intervals, and defibrillator performance. They make several features of medical control review easier and more convenient, and may encourage implementation of early defibrillation programs. We conclude, however, that medical control modules cannot replace on-scene tape recordings for adequate medical control of EMT-D programs.

Treatment of advanced cancer of the lower lip--the use of intraarterial or intravenous chemotherapy as basal treatment.

Since the linear accelerator was installed in Sydney Hospital in 1964, 27 patients who presented with previously untreated but advanced deep carcinoma of the lower lip have been treated with initial megavoltage or orthovoltage radiotherapy with or without follow-up surgery. In 17 of these, the tumor appears to have been eradicated, but in the other ten (approximately one-third), the tumor was not controlled. These results are similar to those reported from other major centers. Since January, 1974, six patients with the most advanced lesions have been treated with "basal" chemotherapy (in four cases given intra-arterially and in two cases given intravenously) prior to radiotherapy. Follow-up surgery in the form of block dissection was required in one patient, and wedge resection of a residual focus of tumor was required in a second patient, but all six patients remain well and free of disease, with from three to six years follow-up to date. A further seven patients with advanced recurrent lesions were also treated using "basal" chemotherapy as the initial treatment. In three of these the carcinoma remained uncontrolled, but in four the tumor appears to have been controlled with subsequent follow-up radiotherapy being used in two cases, surgery in a third, and intermittent chemotherapy in the fourth. The numbers of patients treated in this series are insufficient to allow conclusions to be drawn concerning present management methods. However, the trend of the results to date suggests that for advanced lesions, improved survival may well result from the combination of basal chemotherapy with subsequent radiotherapy and/or surgery.

Intra-arterial chemotherapy as basal treatment in advanced and fungating primary breast cancer.

Occasionally patients present with stage III breast carcinoma so advanced that local radiotherapy is unlikely to achieve more than a partial and temporary local regression. 3 such patients with grossly advanced cancer involving virtually the whole of the breast, skin, and underlying muscle were treated with a regimen of intra-arterial infusion chemotherapy as basal treatment before planned irradiation. All 3 patients responded significantly to intra-arterial chemotherapy and subsequent definitive radiotherapy seems to have resulted in total regression of tumour and involved nodes in 2 patients. In the 3rd patient the response of the tumour mass to subsequent radiotherapy was considerable but incomplete; subsequent surgical resection seems to have eradicated the small foci of residual disease buried in fibrous tissue in the breast and one axillary node. All patients were given routine adjuvant chemotherapy after completion of irradiation. A 4th patient with a huge fungating breast carcinoma which was bleeding and foul-smelling who also had evidence of liver metastasis (stage IV disease) was treated in a similar manner. Local tumour regression was achieved and although the patient still requires treatment for metastatic disease there is no evidence of residual carcinoma in the breast or axilla 12 months after treatment. Further investigation of this treatment seems worthwhile, since it may be effective not only in the management of large breast cancers but also in patients with less advanced disease who refuse mastectomy or wish to avoid it.

Hodgkin's disease: evaluation of staging procedures for abdominal involvement.

Results of preoperative assessment procedures and subsequent staging laparotomy are evaluated in 32 consecutive patients who presented with extra-abdominal Hodgkin's disease which was not already known to be in an advanced stage. Disease was found in the abdominal cavity of 10 of the 27 patients who presented with disease above the diaphragm, and of two of the five patients in whom disease presented in the inguinal nodes. In patients who initially presented with disease above the diaphragm, the spleen was involved in all 10 cases where abdominal disease was detected. Lymphography was not found to be reliable as a diagnostic aid in doubtful cases. Neither liver nor spleen scans were found to be helpful in assessment of these patients.