Difficulties in the pre-operative diagnosis of phyllodes tumours of the breast: a study of 84 cases.

Eighty-four phyllodes tumours (71 benign, eight borderline and five malignant) diagnosed over a 16-year period were studied retrospectively, to assess the diagnostic value of the pre-operative modalities used. Mammography and ultrasound appearances were non-specific. The possibility of phyllodes tumour was raised in only 23% on fine needle aspiration cytology, and in 65% on core biopsy. Accuracy was better in smaller tumours, suggesting that larger tumours need more samples. For phyllodes tumours whose growth was measured, almost all had growth rates greater than for growing fibroadenomas. The pre-operative diagnosis of phyllodes tumours is difficult, and rapid growth and/or large size of apparent fibroadenomas may be the only imaging findings to suggest phyllodes tumour. It is important to review most fibroadenomas with ultrasound, to assess the rate of growth if any. Whole breast ultrasound showed that nearly one third of women with phyllodes tumours had concurrent fibroadenomas.

The diagnosis of breast cancer in women younger than 40.

This study examined how the diagnosis of breast cancer is different in young women. Records were retrieved for 239 women diagnosed with breast cancer before age 40 and compared with 2101 women aged 40 and over with breast cancer. On mammography, lesions in the younger women were more likely to be undetected or interpreted as benign, especially in women with dense breasts. However, there were 10 young women where impalpable cancers with microcalcification under 10 mm would not have been diagnosed without mammography. An abnormality was detected on ultrasound in 92.2% of cancers in young women, but was more likely to be considered benign than in older women. If ultrasound alone had been used in the young women, at least 18 cancers would have been missed. Ultrasound was useful for predicting the ultimate tumour size at pathology, and for detecting multifocality. There were 14 cases where the ultrasound appearance was indistinguishable from fibroadenoma. The importance of fine needle aspiration cytology in the diagnosis of focal lesions in young women (over 20 years) was confirmed. For symptomatic women, the proportion of breast malignancies under 10 mm was similar in the two groups. However, the younger group had significantly more poorly differentiated tumours.

Presentation and diagnosis of adolescent breast disease.

Breast disease in the adolescent female is fortunately uncommon, with most presenting lesions being benign. The type and frequency of breast problems in young women less than 20 years of age are discussed in this paper. There were 634 adolescent females (9-19 years) referred to the Wesley Breast Clinic between January 1990 and December 1999. Of these, 62.6% were aged 18-19 years. The commonest reason for referral was a lump or thickening in the breast (n=554, 87.4%). Six hundred and nineteen females had ultrasound performed, with 59% showing no abnormality. The commonest abnormality in the remainder was probable fibroadenoma (n=162). Twenty-two percent of the females in the study had fine needle aspiration performed; none showed suspicious cytology. Twenty-three females had an excision biopsy following their initial visit. Three of these were found to have benign phyllodes tumour. There were no malignancies detected, although one female had previous DCIS diagnosed elsewhere.

Breast cancers invisible on mammography.

BACKGROUND: A proportion of the cancers 'missed' at mammography are invisible even with the benefit of hindsight. The aim of the present study was to identify a group of women with proven breast cancer whose mammograms did not show a suspicious lesion even in retrospect (i.e. the truly mammographically occult cancers), and to compare them with mammogram-positive cancers. METHODS: A total of 1757 breast cancers was diagnosed at the Wesley Breast Clinic's Screening or Diagnostic Services between July 1987 and August 1997. One hundred and twenty cases were identified where, after independent review by two of the authors, no mammographic abnormality could be found in the region where the cancer was subsequently found. These 120 cases were compared with 1548 cancers considered to have a lesion visible on mammography, whether benign, indeterminate, suspicious or malignant in appearance. RESULTS: In 90% of the mammogram-negative cancers, a clinical abnormality led to further investigation, while the remainder were found incidentally on ultrasound. There were a higher proportion of dense breasts, and of women aged 40-49, in the mammogram-negative cancers than in the mammogram-positive cancers. The mammogram-negative cancers were of smaller size overall, but three of them were surprisingly large (7-11 cm). In both the mammogram-positive and -negative cancers approximately 60% were ductal invasive cancers. CONCLUSIONS: Where factors are present that make mammographically occult malignancy more likely (e.g. age 40-49 and dense breasts), women may be targeted for further investigation by other modalities. This is essential in the presence of a clinical abnormality.

Evaluation of the acute behavioral effects and abuse potential of a C8-C9 isoparaffin solvent.

We hypothesized that the abuse potential of certain types of inhalants could be evaluated in animals by determining the overlap in their profile of behavioral effects with that of CNS depressant drugs and other depressant-like abused inhalants. For our first attempt in evaluating a solvent with an unknown abuse potential we tested ISOPAR-E. ISOPAR-E is a mixture of predominantly C8-C9 isoparaffinic hydrocarbons that is being used more and more frequently as a solvent in industrial and consumer products, including, but not limited to, typewriter correction fluids. Presently, nothing is known about the potential for abuse of products containing this solvent. In the present studies, we compared the volatility of ISOPAR-E and the abused solvent 1,1,1-trichloroethane (TCE) in our exposure systems. Additionally, five behavioral procedures were conducted in mice to compare the effects of the two compounds. The results demonstrate that: (1) ISOPAR-E was less volatile than TCE; (2) ISOPAR-E produced a somewhat different profile of effects than did TCE as assessed with a functional observational battery; (3) unlike TCE, ISOPAR-E did not affect performance on tests of motor coordination; (4) TCE and ISOPAR-E produced concentration-related decreases in schedule-controlled operant performance with recovery from TCE being somewhat more rapid; (5) ISOPAR-E produced cross dependence in TCE-dependent mice; and (6) both TCE and ISOPAR-E produced substantial levels of ethanol-lever responding in a drug discrimination procedure, although the ethanol-like effects of ISOPAR-E only occurred at response rate decreasing concentrations. Overall, there was a poorer separation of behavioral and lethal concentrations for ISOPAR-E than for TCE. Although a somewhat different profile of behavioral effects was obtained with ISOPAR-E and TCE, we cannot say with certainty if enough similarities exist with abused inhalants to predict that ISOPAR-E would be subject to depressant-like abuse. Nonetheless, the feasibility of preclinical assessment of abuse potential of inhalants was demonstrated.

Functional observational battery comparing effects of ethanol, 1,1,1-trichloroethane, ether, and flurothyl.

Several recent reports have demonstrated that acute solvent exposure in animals produces a profile of neurobehavioral effects similar to that of classical CNS depressant drugs such as the barbiturates and ethanol. The present investigation further delineated the behavioral pharmacology of three solvents [1,1,1-trichloroethane (TCE), ether, and flurothyl] using a functional observational battery (FOB) composed of 21 qualitative and quantitative measures of behavior. The profiles of acute effects produced by TCE and ether were similar to one another and similar to the profile of effects produced by the IP administration of ethanol. This profile of depressant effects included changes in posture, decreased arousal, disturbances in gait, decreased forelimb grip strength, increased landing foot splay, and impaired psychomotor coordination. Flurothyl exposure also produced dose-related effects on many of the measures in the FOB; however, unlike the depressant vapors, flurothyl did not affect measures of muscle tone and equilibrium such as forelimb grip strength and landing foot splay, or measures of sensorimotor reactivity, including the touch response and tail pinch response. In addition, flurothyl produced handling-induced convulsions in some mice. Recovery from the acute effects of these vapors was rapid and began within minutes of removal from the exposure chamber. These results provide further evidence that exposure to certain solvents produces a profile of reversible effects qualitatively similar to that produced by depressant drugs and alcohol, and that the FOB can be used to compare and contrast profiles of depressant and excitatory effects of inhalants.

Familial tumoral calcinosis. A clinical, histopathologic, and ultrastructural study with an analysis of its calcifying process and pathogenesis.

We describe histopathologic and ultrastructural changes in tumoral calcinosis (TC) occurring in seven siblings from a single family. Tumoral calcinosis appears to be triggered by bleeding followed by aggregation of foamy histiocytes. These in turn are transformed, with participation of collagenolysis, into cystic cavities lined by osteoclast-like giant cells and histiocytes--the lesion resembling adventitious bursae. Movement and friction, forces generated from the periarticular location of the TC lesions, putatively are key to this transformation. Concomitantly, two calcifying events develop, possibly driven by concurrent hyperphosphatemia or endogenous hypervitaminosis D. One occurs on membranous fragments in antiprotease-containing large cytoplasmic vesicles within osteoclast-like giant cells and mononuclear cells lining the TC cavities; the second, in the TC locules on membranous and cellular debris derived from cavity-lining cells and erythrocytes. The TC cavities ultimately fill with calcified material, losing their synovial-like lining, become encapsulated by fibrous tissue, and ossify. Hydroxyapatite may gain entrance to capillary lumens and embolize to the lung. We conclude that TC represents a disordered reparative process that often is exaggerated because episodes of bleeding, caused by TC-induced vascular injury, provoke development of new lesions. The capricious response of TC to treatment is correlated with its morphologic features.

Inhaled 1,1,1-trichloroethane-produced physical dependence in mice: effects of drugs and vapors on withdrawal.

1,1,1-Trichloroethane (TCE), a widely used and abused solvent, was investigated for its ability to produce physical dependence in mice. Cessation of 4 days of continuous inhalation of TCE (500-4000 ppm) resulted in a withdrawal syndrome characterized by handling-induced convulsions and increased susceptibility to pentylenetetrazol-induced convulsions. The severity of withdrawal convulsions was diminished by 30 to 60 min of reexposure to 2000 to 4000 ppm TCE or to the vapor of another widely used and abused solvent, toluene (1000-2000 ppm). Ethanol (1-2 g/kg), midazolam (0.3-1 mg/kg) and pentobarbital (30 mg/kg) were also effective in decreasing the withdrawal severity; however, chlorpromazine (3 mg/kg) and phenytoin (30 mg/kg) were without effects. These data suggest that TCE has the ability to produce physical dependence of the central nervous system depressant drug type. Taken together with other evidence for similarities in the pharmacological and behavioral effects of TCE and depressant drugs of abuse, these data support the hypothesis that the basis for TCE abuse may be its ability to produce ethanol- and depressant drug-like effects.

Effects of methoxyflurane and flurothyl in mice trained to discriminate pentylenetetrazol from saline.

A procedure is described for training mice to discriminate 30mg/kg pentylenetetrazol (PTZ) from saline when lever pressing was maintained under a fixed-ratio 20 schedule of milk presentation. To define the pharmacological profile of the PTZ stimulus in mice, generalization testing was conducted with oxazepam and Ro 15-4513 (sarmazenil). Consistent with data obtained by others in rats, oxazepam (1mg/kg) blocked the PTZ stimulus whereas Ro 15-4513 substituted for PTZ, but only at a dose (2mg/kg) that also decreased rates of responding. The effects of both a depressant and excitatory vapor in this model were also determined. The volatile anesthetic methoxyflurane (1000-2000 ppm) blocked the discriminative stimulus effects of PTZ in a concentration-dependent manner, while the convulsant vapor flurothyl (900 ppm) produced greater than 90% PTZ-lever responding without disrupting rates of responding. The PTZ-like discriminative stimulus effects of flurothyl were dose-dependently blocked by oxazepam (0.03-1.0mg/kg). As has been shown in numerous previous studies in rats, PTZ could be established as a discriminative stimulus in mice. PTZ discrimination could be blocked by a benzodiazepine agonist and shares some properties with a benzodiazepine inverse agonist. Substitution and antagonism studies can also be performed with vapors, illustrating the utility of this model for comparing their behavioral effects to those of more widely studied drugs.

Techniques for the management of burn contractures with the Ilizarov Fixator.

The Ilizarov fixator was used to correct chronic burn deformities of the foot and ankle. These contractures can be classified as "simple" or "complex" based on associated deformities and musculoskeletal function. The simple, undirectional deformities of equinus, cavus, rockerbottom, and toe dislocations are fairly easy to correct and maintain. Correction and maintenance of complex deformities with varus or valgus angulation, bone abnormality, or muscle loss are more difficult.

Effects of drugs of abuse on acquisition of behavioral chains in squirrel monkeys.

The acute effects of various drugs of abuse on the acquisition of chains of behavior were assessed in squirrel monkeys trained to respond on three keys for food. Each new session the monkeys acquired a different four-response chain by responding sequentially on three keys in the presence of four different stimuli. Incorrect responses inactivated the keys and darkened the chamber for 10 s (time-out). Dose-effect curves were obtained by administering the drugs intramuscularly before the session and recording their effects on the rate and accuracy of responding. Cocaine, d-amphetamine, and delta 9-tetrahydrocannabinol all decreased the accuracy and rate of responding within the dose range of 0.56-3 mg/kg. The highest dose of morphine tested (3 mg/kg) produced parallel decreases in the accuracy and rate of responding in some monkeys but had no effect at lower doses. These drugs decreased within-session accuracy though clearly acquisition did occur, but high doses of caffeine (30 and 56 mg/kg) prevented acquisition and recovery of performance and, furthermore, at 30 mg/kg these effects were observed in the absence of decreases in the rate of responding. The drugs of abuse tested all produced dose-related decreases in both the accuracy and rate of responding, and the decreases in accuracy were primarily observed only at doses that also decreased response rates. Therefore, based on these results from nonhuman primates each of these drugs has the potential to alter learning particularly when doses that disrupt other behaviors are administered.

Heterotopic bone formation in thermal burns.

Heterotopic bone is a rare complication of burns. The factors to be considered in its development are the percentage of burn, the location of burn, the length of bed confinement, osteoporosis, superimposed trauma, and genetic predisposition. Characteristically, heterotopic bone develops between one and three months after the acute burn. It may continue to proliferate as long as there are open wounds but it tends to regress once the burn wound has healed. If it has bridged a joint it may be surgically excised after the burn has healed. The more extensive the heterotopic bone the poorer the prognosis for restoration of motion after excision. Prevention of heterotopic bone appears to be linked in part to early mobilization of the patient and recovery from the postburn hypermetabolic and catabolic state.

CNS depressant effects of volatile organic solvents.

Volatile chemicals used widely as solvents can produce acute effects on the nervous system and behavior after inhalation exposure, and many are subject to abuse. This review considers the nature of the acute effects of volatile organic solvents by comparing their actions to those of classical CNS depressant drugs such as the barbiturates, benzodiazepines and ethanol. Like CNS depressant drugs, selected inhalants have been shown to have biphasic effects on motor activity, disrupt psychomotor performance, have anticonvulsant effects, produce biphasic drug-like effects on rates of schedule-controlled operant behavior, increase rates of punished responding, enhance the effects of depressant drugs, serve as reinforcers in self-administration studies and share discriminative stimulus effects with barbiturates and ethanol. Toluene and 1,1,1-trichloroethane, as well as subanesthetic concentrations of halothane, have been the most extensively studied; however, it is unclear whether important differences may exist among solvents in their ability to produce a depressant profile of acute effects. The possibility that selected solvents can have acute effects similar to those of depressant drugs may shed light on the nature of their acute behavioral toxicology and on their abuse.

The effects of cocaine in combination with other drugs of abuse on schedule-controlled behavior in the pigeon.

The present experiment sought to provide information regarding the consequences of combining cocaine with other drugs of abuse. The effects of cocaine alone and in combination with d-amphetamine, caffeine, morphine or delta-9-tetrahydrocannabinol were determined in five male white Carneaux pigeons responding under a multiple fixed-ratio 30, fixed-interval 600 schedule (mult FR FI). Drug interactions were studied by redetermining the cocaine dose-response curve in the presence of various fixed doses of the other drugs. Under the mult FR FI schedule, when cocaine (1 to 10 mg/kg) was combined with inactive doses of d-amphetamine (0.1, 0.3, 1.0, and 1.8 mg/kg), caffeine (10, 30, and 100 mg/kg), morphine (0.3, and 1.0 mg/kg), and delta-9-tetrahydrocannabinol (0.1 mg/kg), the FR and FI response rate dose-response curves were not shifted relative to the cocaine-alone curves. When cocaine was combined with an active dose of a drug which decreased response rate when given alone (0.3 mg/kg delta-9-tetrahydrocannabinol and 3 mg/kg morphine), the position of the response rate dose-response curves shifted compared to the cocaine-alone curves. The most frequent and consistent outcome of these interactions can be described as less than or approximately equal to an effect-additive interaction. Thus, these data indicate that the potential consequences of coabusing cocaine with the drugs tested in the present experiment can most often be predicted from the effects of each drug when taken alone.

The acute effects of caffeine, cocaine and d-amphetamine on the repeated acquisition responding of pigeons.

The acute effects of caffeine, cocaine and d-amphetamine on the repeated acquisition of a four-response chain were investigated in pigeons. Subjects responded on three response keys under different predetermined sequences. Food was presented upon the completion of the four-response sequence under a fixed-ratio schedule. Incorrect responses resulted in a five-second timeout. No consistent increases in within session percent correct were observed following caffeine or d-amphetamine administration. However, cocaine (1.0 mg/kg) did produce consistent increases in within session percent correct. At higher doses of cocaine, d-amphetamine and caffeine the effects observed were similar in that there was a decrease in response rate and percent correct. The drugs did differ in the dose (potency) which decreased response rate and percent correct. Following all three drugs if percent correct was decreased there was a concurrent decrease in response rate.

Inventory of potential reconstructive needs in the patient with burns.

The rehabilitation and reconstruction of patients who survive large burns is an arduous task. To facilitate it we have devised an inventory form to accurately record the somatic abnormalities caused by burns and also the severity and location of burns. This form was used in the assessment of 25 pediatric patients with massive burns. It was found to be a very useful tool that allowed the identification of more specific functional and esthetic deformities than is possible with currently available forms. It also served as a template for the systematic planning of reconstructive procedures.

Characteristics of successful and unsuccessful applicants to orthopedic residency training programs.

In 1985 there were 288 applicants for the ten postgraduate Year 1 orthopedic residency positions in Galveston and San Antonio, of which 119 (41%) applicants successfully obtained a residency position in one of 76 orthopedic programs approved by the Accreditation Council for Graduate Medical Education. Successful applicants were younger and had higher Medical College Admissions Test scores, National Board of Medical Examiners, Part I (NBME-I) scores, and medical school grade point averages than unsuccessful applicants. Variables that increased acceptance rates were medical student status, an NBME-I score above 500, class rank in the top 40%, and membership in Alpha Omega Alpha honor society. Foreign citizenship and prior residency experience in a different specialty strongly decreased acceptance rates. Variables that did not affect acceptance rates were: gender, military experience, marital status, graduate degree, research, publications, or NBME-II scores.

Structure-activity relationships of arylcyclohexylamines as discriminative stimuli in pigeons.

The effects of a variety of arylcyclohexylamines, opioid drugs and other drugs were studied for phencyclidine-like effects in pigeons trained to discriminate phencyclidine (PCP) from saline. There was a good correlation between the relative potency of arylcyclohexylamines as PCP-like discriminative stimuli in pigeons and these drugs as discriminative stimuli in rats. Substitution of methyl groups on the piperidine or cyclohexyl rings of PCP reduced potency, but not efficacy, whereas substitution of hydroxyl groups decreased both potency and efficacy. Replacement of the phenyl ring with a thienyl ring increased PCP-like activity, but replacement of the piperidine ring with a pyrrolidine ring or a morpholine ring decreased potency. Compounds with methyl or ethyl groups on the nitrogen atom replacing the piperidine ring also were active. These data suggest that N-alkyl substitutions decrease potency but not efficacy, whereas hydroxylation of the cyclohexyl ring decreases efficacy as well. The data also support the suggestion that size of the aromatic ring is also a determinant of PCP-like activity. Both optical isomers of cyclazocine and N-allylnormetazocine were active as PCP-like discriminative stimuli, although the (-)-isomer was more potent than the (+)-isomer for cyclazocine and the reverse was true for N-allylnormetazocine. The pigeon shows less stereospecific activity with these drugs than the rat and especially the squirrel monkey. A variety of other opioid-like chemical structures, as well as other drugs such as d-amphetamine and pentobarbital, were inactive as PCP-like discriminative stimuli.

Subcapital fracture of the hip following an intertrochanteric fracture. A case report and literature review.

A 42-year-old alcoholic man who had a normal femoral head histologically incurred a subcapital fracture four months after surgical treatment of an intertrochanteric fracture of the same hip. Subcapital fracture of the hip following intertrochanteric fracture is an unusual occurrence, with possibly as few as 11 cases documented in the literature. Affected persons are usually elderly females with severe osteoporosis. Though unusual, the fracture is obvious and not difficult to treat.