STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : VI. VARIATIONS IN GROWTH AND MALIGNANCY OF TRANSPLANTED TUMORS. PART 1. RESUTLTS OF TRANSPLANTATION FOR THE FIRST TWENTY GENERATIONS.

A report is given of the results obtained by intratesticular inoculation of a malignant tumor of the rabbit based on a study of the first twenty generations. The subject is presented from the standpoint of variations in growth and malignancy as they occurred with continued transplantation. Essential features of the experimental conditions and of clinical and postmortem observations are condensed and recorded graphically. On analyzing the results of these experiments, it was found that many changes had occurred in the behavior of the tumor during transplantation, but that the changes were of a very irregular character and as a rule did not proceed constantly in any given direction. Moreover, the evidence as to the effect of transplantation on the growth and malignancy of the tumor was contradictory in that there was a great deal of evidence to show that there had been a decided increase in the activity and capacity for growth on the part of the tumor cells. But, with the exception of a few generations, there was an apparent reduction in the incidence and percentage distribution of secondary tumors, while the death rate was unaltered or actually diminished. It was believed that this paradoxical situation afforded a basis for an explanation of the results that had been obtained by transplantation.     

PENETRATION OF NORMAL MUCOUS MEMBRANES OF THE RABBIT BY TREPONEMA PALLIDUM AND THE INFLUENCE OF THIS MODE OF INFECTION UPON THE COURSE OF THE DISEASE

Experiments were carried out with three strains of Treponema pallidum to determine whether infection could be produced by applying an emulsion, rich in spirochetes, to normal mucous membranes of rabbits and whether an infection produced in this manner differed in any respect from one produced by other methods of inoculation. It was found that a simple instillation of a spirochete emulsion into the conjunctival sac or the sheath was all that was necessary to obtain an infection. Still, the infection produced in this manner differed from that produced by intracutaneous or testicular inoculations in that it tended to pursue a mild or asymptomatic course and frequently without the development of a characteristic chancre. It is pointed out that these experiments may have a bearing on problems pertaining to obscure and atypical cases of human syphilis as well as the more immediate question of the infectivity of Treponema pallidum.     

STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : I. THE SPONTANEOUS TUMOR AND ASSOCIATED ABNORMALITIES.

A malignant tumor which developed at the site of a primary syphilitic lesion in the scrotum of a rabbit, about 4 years after inoculation, and eventually led to the death of the animal, has formed the basis for an extensive series of investigations beginning with the study of the spontaneous tumor. The present report contains the clinical history of the animal from the time of inoculation to its death and the results of pathological examinations. The most important events recorded may be summarized as follows: 1. A mild but persistent syphilitic infection with an occasional relapse and the eventual development of chronic inflammatory lesions in the skin associated with atypical epithelial proliferations. 2. The occurrence, at about the same time, of extensive degenerative changes in the dermis accompanied by an atypical growth of hair follicles, with the production of diffuse and nodular areas of thickening and induration (scleroderma). 3. The development of a growth in the skin of the left scrotum which recurred after removal and spread diffusely over adjacent parts of the skin, and metastasized to the regional lymph nodes and to internal organs. 4. The transplantation of the growth to other rabbits by intratesticular inoculation and the successful propagation of the growth over a period of nearly 2 years (twenty generations). 5. The development of a cachexia and of pressure phenomena from metastases involving the cervical and lumbar regions of the spinal column which eventually led to the death of the animal. 6. The discovery, post mortem, of an extensive leucoplakia of the tongue and buccal mucosa, chronic inflammatory lesions in the esophagus with atypical epithelial proliferation, and a nodular growth in the left testicle differing in character from that in the scrotum. 7. The presence of extensive degenerative changes in the vascular system, degeneration of the parenchymatous organs, atrophy of the thymus and lymphoid system, with chronic lymphadenitis, atrophy, degeneration, and necrosis of the suprarenals, and atrophy and hyperplasia of the thyroid with chronic thyroiditis. The conclusion was reached that the growth in the scrotum represented a neoplasm of epithelial origin which was composed of cells allied to those found in the bulb and root sheath of the hair. No explanation was offered for the origin or unusual malignancy displayed by the tumor pending the introduction of experimental data. It was stated, however, that the evidence presented was sufficient to warrant the assumption that the factor of foremost importance in the development of the tumor was constitutional rather than local.     

EXPERIMENTAL SYPHILIS IN THE RABBIT : VI. AFFECTIONS OF BONE,CARTILAGE, TENDONS,AND SYNOVIAL MEMBRANES. PART 1. LESIONS OF THE SKELETAL SYSTEM.

From a study of a series of rabbits inoculated with two old strains of Treponema pallidum, it was found that localized infection of bones and tendons was of frequent occurrence and led to the formation of a variety of lesions. The bones usually involved were those of the face and the feet and legs. Most often the lesions arose from the periosteum but developed also within the bone or marrow cavities and at lines of epiphyseal union. Grossly, the periosteal lesions were of two types—one being a circumscribed, indurated, and nodular mass and the other a process of a more diffuse character. Histologically, the lesions presented the typical appearance of syphilitic granulomata composed of more or less distinct layers which corresponded roughly with structural divisions of the periosteum. The composition of lesions of membrane and of cartilage bones differed somewhat in this respect, especially in the development of an osteoclastic layer. Invasion of the bone with absorption and necrosis were constant features of periosteal affections and were most marked in the case of the facial bones and the small bones of the feet. Lesions in the bone and marrow cavities were detected chiefly by radiographs or by the occurrence of bone destruction in the absence of periosteal involvement. They were characterized by a loss of structural detail in the bone, rarefication, increased fragility, necrosis, pathological fracture, and epiphyseal separation associated with more or less granulomatous reaction. Histologically, the bone lesions presented essentially the same picture as those of the periosteum, while the lesions which arose from the marrow cavities were composed chiefly of polyblastic infiltrations. In this group of affections, the most important were those which developed at the epiphyses. The destructive effects produced by all classes of lesions varied from a slight surface erosion or rarefication to extensive necrosis resulting in the formation of bony defects or in disintegration or fracture of the bone. These conditions differed very decidedly with the particular bones involved. Of especial importance in this connection was the occurrence of a peculiar form of mass necrosis which at times resulted in the destruction of considerable areas of bone even in parts where the granulomatous type of lesion was comparatively slight. The most characteristic injuries were the saddle-nose deformities and the epiphyseal separation in the small bones of the tarsus and hind feet. The marks of permanent injury were, on the whole, comparatively slight, but they also differed both with the degree of the original injury and with the bone affected. Granulomatous lesions of tendons or tendon sheaths were occasionally seen, and in a few instances, lesions of synovial cavities were demonstrated microscopically.     

THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE : V. CHANGES IN THE ENDOTHELIAL CELLS OF THE LYMPH NODES AND LIVER IN SPLENECTOMIZED ANIMALS RECEIVING HEMOLYTIC SERUM.

In a large proportion of dogs that have been splenectomized for periods of two weeks or more, one finds a great increase in the number of endothelial cells of the lymph nodes. In most splenectomized dogs that succumb to an injection of hemolytic immune serum within forty-eight hours, the sinuses of the lymph nodes contain large numbers of endothelial cells, phagocytic for red cells. This is not seen in normal dogs receiving hemolytic serum. Likewise a similar power of phagocytosis is seen frequently in the stellate cells of the capillaries of the liver. Both in the lymph nodes and the liver these cells appear to be formed in situ; we find no evidence that they have been transported to these organs. Such findings suggest the development of a compensatory function on the part of the lymph nodes and possibly of the liver. Normally the spleen contains cells which have the power to engulf and presumably to destroy the red blood corpuscles. In certain pathological conditions this function is frequently greatly augmented and may sometimes be shared by the lymph nodes, for example, in typhoid fever, as was first clearly shown by Mallory. Our observations suggest that in the absence of the spleen, this function of forming red blood corpuscle-phagocyting cells, normally a minor activity of the lymph nodes, becomes highly developed in the latter organs, and that these cells, and the stellate cells of the liver, thus assume, in part at least, the function of destroying red blood corpuscles by phagocytosis. In view of the somewhat limited material at our disposal, we offer this, not as definitely conclusive, but as evidence which, in connection with the work of others, is highly suggestive of the possibility of the lymph nodes assuming some of the function of the spleen. Whether this activity of the endothelial cells of the lymph nodes and the liver has any bearing on the anemia that follows splenectomy and on the occurrence of spontaneous jaundice in the late periods after splenectomy, is not yet clear.     

Influence of exclusive breastfeeding on hippocampal structure,satiety responsiveness,and weight status

Longer exclusive breastfeeding duration has been associated with differences in neural development, better satiety responsiveness, and decreased risk for childhood obesity. Given hippocampus sensitivity to diet and potential role in the integration of satiety signals, hippocampus may play a role in these relationships. We conducted a secondary analysis of 149, 7–11‐year‐olds (73 males) who participated in one of five studies that assessed neural responses to food cues. Hippocampal grey matter volume was extracted from structural scans using CAT12, weight status was assessed using age‐ and sex‐adjusted body mass index (%BMI_p85), and parents reported exclusive breastfeeding duration and satiety responsiveness (Children''s Eating Behaviour Questionnaire). Separate path models for left and right hippocampus tested: (1) the direct effect of exclusive breastfeeding on satiety responsiveness and its indirect effect through hippocampal grey matter volume; (2) the direct effect of hippocampal grey matter volume on %BMI_p85 and its indirect effect through satiety responsiveness. %BMI_p85 was adjusted for maternal education, yearly income, and premature birth while hippocampal grey matter volume was adjusted for total intercranial volume, age, and study from which data were extracted. Longer exclusive breastfeeding duration was associated with greater bilateral hippocampal grey matter volumes. In addition, better satiety responsiveness and greater left hippocampal grey matter volume were both associated with lower %BMI_p85. However, hippocampal grey matter volumes were not associated with satiety responsiveness. Although no relationship was found between breastfeeding and child weight status, these results highlight the potential impact of exclusive breastfeeding duration on the hippocampal structure.     

Amnesic Concentrations of the Nonimmobilizer 1,2-Dichlorohexafluorocyclobutane (F6, 2N) and Isoflurane Alter Hippocampal θ Oscillations In Vivo

Background: Drug-induced temporary amnesia is one of the principal goals of general anesthesia. The nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also termed 2N) impairs hippocampus-dependent learning at relative, i.e., lipophilicity-corrected, concentrations similar to isoflurane. Hippocampal [theta] oscillations facilitate mnemonic processes in vivo and synaptic plasticity (a cellular model of memory) in vitro and are thought to represent a circuit level phenomenon that supports memory encoding. Therefore, the authors investigated the effects of F6 and isoflurane on [theta] oscillations (4-12 Hz).

Methods: Thirteen adult rats were implanted with multichannel depth electrodes to measure the microelectroencephalogram and were exposed to a range of concentrations of isoflurane and F6 spanning the concentrations that produce amnesia. Five of these animals also underwent control experiments without drug injection. The authors recorded the behavioral state and hippocampal field potentials. They confirmed the electrode location postmortem by histology.

Results: The tested concentrations for isoflurane and F6 ranged from 0.035% to 0.77% and from 0.5% to 3.6%, respectively. Isoflurane increased the fraction of time that the animals remained immobile, consistent with sedation, whereas F6 had the opposite effect. Electroencephalographic power in the [theta] band was less when the animals were immobile than when they explored their environment. F6 suppressed the power of oscillations in the [theta] band. Isoflurane slowed [theta] oscillations without reducing total power in the [theta] band.     

The epidemiology of foot injuries in professional rugby union players

Background

Foot injuries represent a small but important proportion of injuries to professional rugby union players. There are no detailed epidemiological studies regarding these injuries. The aim of this study was to describe the epidemiology of foot injuries sustained by a cohort of professional rugby union players and identify areas that may be targeted for injury prevention in the future.

Methods

Medical personnel prospectively recorded injuries in professional Premiership rugby union players in England over four seasons. Injuries to the foot were identified and the time away from training and playing was reported.

Results

A total of 147 foot injuries were sustained resulting in 3542 days of absence in total. Acute events accounted for 73% of all foot injuries, with chronic, mostly overuse conditions, accounting for 25% (undiagnosed 2%). Chronic conditions led to proportionately more time away from training and playing (p = <0.001). Specifically, stress fractures in the foot accounted for 8% of the total foot injuries but 22% of the absence. Navicular stress fractures had the longest recovery time with the mean return to training and match play of 188 days.

Conclusion

In collision sports such as rugby, some injuries may be inevitable but clinicians should always be seeking ways to minimise their occurrence and impact. This study revealed a high proportion of morbidity associated with chronic and overuse foot injuries in these professional athletes. With greater attention paid to risk factors, some of these injuries, and importantly, recurrent injuries may be avoided.     

Postoperative and late survival outcomes after major amputation: findings from the Department of Veterans Affairs National Surgical Quality Improvement Program.

BACKGROUND: A surgical risk model is used to analyze postoperative mortality and late survival for older veterans who underwent above- or below-knee amputations in 119 Veterans Affairs (VA) hospitals from 1991 to 1995. METHODS: Preoperative medical conditions and laboratory values abstracted by the VA National Surgical Quality Improvement Program were linked to subsequent hospitalization and survival through 1999. Logistic regression and proportional hazards models were used to develop risk indexes for postoperative mortality and long-term survival. RESULTS: Thirty-day postoperative mortality was 6.3% for 1909 below-knee and 13.3% for 2152 above-knee amputees. Mortality varied greatly between the lowest-highest risk index quartiles (0.8%-18.4% for below-knee amputation and 2.3%-31.1% for above-knee amputation). Surviving patients had 10,827 subsequent VA hospitalizations during a median 32-month follow-up. Survival probabilities for below- and above-knee amputees were 77% and 59% at 1 year, 57% and 39% at 3 years, and 28% and 20% at 7.5 years. The lowest quartile of survival risk had a 61% five-year survival compared with 14% for the highest-risk quartile. CONCLUSION: A generic surgical risk model can be of use in stratifying prognosis after major amputation. The heavy burden of hospital use by these patients suggests the need for better disease management for this high-risk, high-cost patient population.