N100 evoked potential latency variation and startle in schizophrenia.

The contribution of evoked potential (EP) latency jitter, a measure of CNS temporal variability, on startle and EP gating defects in schizophrenic subjects has not been characterized. The amplitude of the N100/P200 EP complex (peak to trough) derived using a time-locked averaging procedure, N100 EP latency jitter derived from single trial analysis, acoustic startle response and clinical symptoms were measured in 51 schizophrenic subjects. N100 latency jitter was inversely correlated with N100/P200 EP amplitude in both cross-sectional and longitudinal analysis. Subjects with elevated EP gating ratios (>0.5) had similar latency jitter values for initial (S1) and test (S2) stimuli, while subjects with a low gating ratio (0-0.5) had a lower level of S1 latency jitter. Temporal variability thus plays a significant and complex role in previously reported sensory gating deficits in schizophrenic subjects.

Colonic and breast carcinomas--association or metastases? Report of a case.

There is an increased incidence of colonic carcinoma in patients with breast carcinoma but colonic involvement secondary to breast carcinoma can also occur. The differentiation of the organ or origin (breast vs colon) of the abdominal tumour can be difficult and may benefit from the use of immunohistochemical staining with monoclonal antibodies that react preferentially with colon cancer (JGT) and breast cancer (3E1.2, BC2,BC3). Measurement of Mammary Serum Antigen (MSA) level as detected by the anti-breast monoclonal antibody (3E1.2) was also useful in the classification of tumours of uncertain origin.

The use of tissue expansion for immediate breast reconstruction after mastectomy.

A series of 139 patients who had a total mastectomy underwent breast reconstruction using the method of tissue expansion. In 127 patients a tissue expander was inserted at the time of mastectomy and in 12 patients this was done as a delayed procedure. The reconstruction was successfully completed in 87% of cases and the patient acceptance of this method of reconstruction has been high. We believe that tissue expansion should be offered to all women having immediate reconstruction after total mastectomy and that it also has a significant role in delayed breast reconstruction after mastectomy.

Corpus callosum section disrupts motor behaviour strategies during visual discrimination learning in rat.

Monocularly patched rats were trained on a series of visual tilt discriminations ordered from simple to difficult to measure the angular difference threshold of each eye. The stereotyped running pattern which the animal made was also recorded. Callosal section disrupted a preoperatively established running pattern and produced an ocular neglect; the animal's performance dropped to chance when it used the eye ipsilateral to the preferred side of approach.

Management of primary, operable breast cancer in Victoria.

The study aimed to describe the surgical treatment in cases of primary, operable breast cancer in Victoria. All patients who were entered in a population-based cancer registry and who met the entry criteria over a six-month period were identified. In respect of each patient, the treating surgeon completed a questionnaire about patient characteristics, investigations, tumour description, surgery, radiotherapy and chemotherapy. For 716 eligible cases, 635 (89%) questionnaires were returned by 200 treating surgeons; this gave a mean rate of 6.3 breast-cancer patients per surgeon per year. Most (61%) surgeons treated one to four breast-cancer patients per year and only 4% of surgeons treated more than 20 breast-cancer patients each. Little systematic difference was found in the treatment approach that was adopted by the surgeons with heavy or light case-loads of patients with breast cancer. Twenty-two per cent of patients underwent breast-conserving operations. Virtually all the remainder underwent mastectomy, most commonly modified radical mastectomy.

Sequential alternating medroxyprogesterone acetate and epirubicin in the treatment of advanced breast cancer.

A phase II trial of sequential oral medroxyprogesterone acetate (MPA) and epirubicin was performed in 12 postmenopausal women with advanced breast cancer. Patients received MPA at a dose of 500 mg twice daily by mouth for 25 days. Following a 3-day washout, epirubicin was administered in a dose of 75 mg/m2. After a 3-week hiatus, the cycle was recommenced with MPA. Responses were evaluated at the end of the first 25-day period of MPA and following the end of the first cycle. Partial responses were obtained in two patients (17%)--one after the first 25 days of MPA and the other at the end of the first cycle. One of the patients had chest wall disease and the other had hepatic involvement with ascites. Minimal toxicity was experienced from this regimen and the response durations were 2 and 7 months. The response rate reported here does not warrant the further development of sequential therapy. The dose intensity of both MPA and epirubicin are compromised and may be the cause of this low response rate.

The effects of anteromedial cortex lesions on pattern discrimination learning in rat.

The visual angular difference threshold of rats with unilateral anteromedial cortex lesions was measured. The stereotyped running pattern and preoperatively preferred side of approach in a two-choice visual discrimination apparatus was recorded for each animal. Lesions in the hemisphere ipsilateral to the preferred approach side did not affect either the running pattern or the angular difference threshold. However, there was a general reduction in the detection of the positive stimulus throughout the scale. Lesions in the contralateral hemisphere produced a transient reversal of the side preference with an overall loss of S + detection in the field contralateral to the side approached.

Monocular pattern discrimination learning after unilateral lesions of anteromedial cortex in rat.

Monocularly patched rats were trained on a series of visual tilt discriminations ordered from simple to difficult to measure the angular difference threshold of each eye. Preoperatively there was no difference between discrimination performance for either eye. Unilateral lesions of anteromedial cortex did not alter the monocular angular difference threshold. However, there was a reduction in discrimination performance for all angular difference comparisons. Animals showed a visual neglect for stimuli in the field contralateral to the lesion. The neglect was independent of the eye used for the discrimination.

Immunolymphoscintigraphy for the detection of lymph node metastases from breast cancer.

The presence of metastases in the regional lymph nodes is the major prognostic factor in breast cancer in the absence of overt distant metastases and is also an important indicator of the need for adjuvant therapy in "early" breast cancer. Currently, the accurate assessment of axillary lymph node status requires axillary dissection which has an associated morbidity. An alternative method of identifying patients who are "node positive" has been developed by means of immunolymphoscintigraphy with s.c. administered radioiodinated monoclonal antibody. The 131I-labeled anti-breast cancer antibody (RCC-1; 400 micrograms) and cold iodine-labeled "blocking" antibody (Ly-2.1; 2 mg which is nonreactive with breast cancer) were injected s.c. into both arms and scintigraphy images were obtained 16-18 h after the injection, using the axilla contralateral to the side of the breast cancer as the control. Studies were reported as positive (and therefore indicative of lymph node metastases) if the amount of background-subtracted radioactive count in the axilla of interest exceeded the normal side by a radio equal to or greater than 1.5:1.0 as assessed by computer analysis. In 38 of 40 patients the findings on scintigraphy were correlated with operative and histopathological findings on the axillary dissection specimen or cytological findings of fine needle aspiration of axillary lymph nodes. In a prospective study of 26 patients, the method is more sensitive (86%) and specific (92%) than preoperative clinical assessment (57% sensitivity, 58% specificity) in the detection of axillary lymph node metastases; and by combining both modalities of assessment, there was an improvement in the sensitivity (100%) but a deterioration in the specificity (50%). There was no significant complication from this essentially outpatient procedure and only 1 of 40 patients developed a human anti-mouse antibody response. This novel and safe method of imaging may become a most useful adjunct in the surgical management of breast cancer.

The detection of axillary lymph node metastases from breast cancer by radiolabelled monoclonal antibodies: a prospective study.

In a prospective study to assess the accuracy of monoclonal immunoscintigraphy for the detection of axillary lymph node metastases in breast cancer, two murine monoclonal antibodies that react with human breast cancer (3E1.2 and RCC-1) were labelled with 131iodine, and the radiolabelled antibody was injected subcutaneously into the interdigital spaces of both hands of 40 patients, 36 of whom had breast cancer and the remaining four of whom had fibroadenoma (the normal, contralateral axilla was used as a control). Of the patients with breast cancer, the findings from the scintigraphy images were correlated with histopathology or cytology of the axillary lymph nodes; images were regarded as positive and hence indicative of lymph node metastases if the amount of background-subtracted radioactive count in axilla on the side of breast cancer exceeded the contralateral normal side by a ratio greater than or equal to 1.5:1.0 as assessed by computer analysis. Using this method, immunoscintigraphy had an overall sensitivity of 33% (23% with 131I-3E1.2 and 50% with 131I-RCC-1) for the detection of lymph node metastases and a specificity of 63% (67% with 131I-3E1.2 and 60% with 131I-RCC-1) with problems of non-specific uptake by presumably normal lymph nodes. The results of immunoscintigraphy obtained with 131I-RCC-1 (IgG) were superior to 131I-3E1.2 (IgM) although the accuracy of immunoscintigraphy using 131I-RCC-1 (56%) was not much better than preoperative clinical assessment (50%). However, there were cases when immunoscintigraphy using radiolabelled antibody (IgM or IgG) detected axillary lymph node metastases not suspected by clinical examination. Thus it appears that while immunoscintigraphy may be a useful adjunct to preoperative clinical assessment and is simple and safe, a major improvement in its accuracy is needed before it can replace axillary dissection and histological examination in the accurate staging of axilla in breast cancer.

Comparison of mammary serum antigen (MSA) with beta 2-microglobulin (beta 2M) and carcinoembryonic antigen (CEA) assays in patients with breast cancer.

Serum levels of mammary serum antigen (MSA), beta 2-microglobulin (beta 2M) and carcinoembryonic antigen (CEA) were evaluated in 186 subjects to assess their use in the diagnosis and monitoring of breast cancer, either singly or in combination. Raised MSA levels (greater than 300 I.U.) were detected in 79% of patients with Stage I/II breast cancer, compared with 25% for beta 2M (greater than 2000 micrograms/l) and 12% for CEA (greater than 5 ng/ml) levels respectively. Of 53 patients with Stage III/IV breast cancer, 98% (MSA), 55% (beta 2M) and 64% (CEA) had raised levels. In 25 patients followed over 3-9 months, the changes in MSA levels correlated with the clinical course of the disease in 23/25 (92%), compared with 7/25 (28%) using beta 2M, and 9/25 (36%) using CEA assays. The overall sensitivity, specificity and accuracy in detecting breast cancer were 88%, 95% and 99% for MSA; 39%, 90% and 96% for beta 2M; and 38%, 95% and 98% for CEA, respectively. MSA and beta 2M assays in combination enhanced the sensitivity in the detection of breast cancer (93%) especially early breast cancer, while maintaining specificity (90%). MSA seems to be superior to beta 2M or CEA as a tumour marker in breast cancer and its levels seem to correlate with tumour burden. While it appears that beta 2M or CEA measurements used alone are of little value in the current management of breast cancer, beta 2M may be a helpful adjunct to enhance the sensitivity of MSA assay especially in early breast cancer.

Comparison of mammary serum antigen assay with mammography in patients with breast cancer.

Mammary serum antigen levels and two-view xeromammography were evaluated in a study of 97 patients who presented at a specialist breast clinic in a major teaching hospital, in order to determine their single and combined value in the detection of breast cancer. Raised mammary serum antigen levels (greater than 300 inhibition units) were found in 76% of patients with stage-1 (including carcinoma-in-situ) and stage-II breast cancer compared with 54% of patients whose mammograms were suggestive of cancer (probability of carcinoma, greater than 50%). Four patients with carcinoma-in-situ had elevated mammary serum antigen levels, but their mammograms did not suggest the presence of cancer (probability of carcinoma, less than 50%). The over-all sensitivity, specificity and predictive value of a positive test-result in detecting breast cancer were 76%, 82% and 72%, respectively, for the mammary serum antigen test, and 54%, 88% and 74%, respectively, for mammography. When the mammary serum antigen test and mammography were used together, a combined evaluation enhanced the sensitivity in the detection of breast cancer (89%) but with a concomitant reduction in specificity (72%). The mammary serum antigen test was superior to mammography in the detection of breast cancer in this study and may prove to be a useful adjunct to conventional methods of clinical assessment and to mammography for the detection of breast cancer.

Application of mammary serum antigen assay in the management of breast cancer: a preliminary report.

A monoclonal antibody (3E1.2) based serum test using an enzyme immunoassay has been used to determine circulating levels of the breast cancer associated antigen--mammary serum antigen (MSA). Of 157 patients with early breast cancer (stage I and II) and 199 patients with advanced breast cancer (stage III and IV), 73 per cent and 87 per cent respectively had elevated MSA levels (i.e. greater than 300 inhibition units (IU). Furthermore, 40 of 44 patients (91 per cent) had a significant fall of MSA levels with reduction in tumour load by mastectomy. In addition, there was a correlation of MSA levels with the clinical course: changes in MSA levels correlated with changes in disease status (progressive disease, stable disease, disease regression) in 54 of 61 patients and antedated disease progression or recurrence by up to 8 months in some patients; and in 32 of 36 patients (89 per cent) with no clinical evidence of recurrence MSA levels did not vary by more than 25 per cent of the original MSA value over a period of 2-15 months. MSA is therefore a useful tumour marker in the diagnosis and staging of breast cancer. There is also evidence that serial estimations of MSA levels may be used to detect subclinical recurrence and the fluctuations in MSA levels might be useful in assessing response to therapy. Furthermore, it was also noted that surgical procedures such as fine needle aspiration biopsy or incisional biopsy could lead to a rise in MSA levels.

Comparison of mammary serum antigen (MSA) and CA15-3 levels in the serum of patients with breast cancer.

Serum levels of mammary serum antigen (MSA) and CA15-3 were evaluated in 135 individuals in order to determine their single and combined value in the diagnosis and monitoring of breast cancer. Raised MSA levels (greater than 300 IU) were found in 68% of patients with Stage I and II breast cancer compared to only 3% having raised CA15-3 levels (greater than 40 U ml-1). Of 38 patients with Stage IV breast cancer, 95% had raised levels of MSA and CA15-3 combined with each test individually detecting 82% of those with Stage IV disease. No correlation was found between MSA and CA15-3 levels. Four patients being treated for breast cancer were followed over a 5-17 week period; MSA levels correlated with disease course in 3 and CA-15 in 2. The overall sensitivity, specificity and accuracy in detecting breast cancer were 76%, 91% and 96% for MSA; and 47%, 95% and 97% for CA15-3 respectively. When both tests were used together combined evaluation gave the highest sensitivity (84%) and specificity (100%). MSA seems to be superior to CA15-3 for early breast cancer diagnosis and a combination of the two tests gave the best results for metastatic disease.

Psychological treatment of phobic anxiety associated with adjuvant chemotherapy.

A 50-year-old patient with breast cancer was about to withdraw from her adjuvant chemotherapy regimen because of a long-standing phobia about being injected, which had been compounded by anxieties that were associated with the severe side-effects of adjuvant chemotherapy. She experienced a conditioned nausea response to hospital and medical situations. A psychological programme that incorporated relaxation training, systematic desensitization by way of the patient's visual imagination and videotape modelling, allowed her to complete the course of chemotherapy and to feel less anxious in hospital and medical settings.

Effects of unilateral frontal eye-field lesions on eye-head coordination in monkey.

We studied the effects of unilateral frontal eye-field (FEF) lesions on eye-head coordination in monkeys that were trained to perform a visual search task. Eye and head movements were recorded with the scleral search coil technique using phase angle detection in a homogeneous electromagnetic field. In the visual search task all three animals showed a neglect for stimuli presented in the field contralateral to the lesion. In two animals the neglect disappeared within 2-3 wk. One animal had a lasting deficit. We found that FEF lesions that are restricted to area 8 cause only temporary deficits in eye and head movements. Up to a week after the lesion the animals had a strong preference to direct gaze and head to the side ipsilateral to the lesion. Animals tracked objects in contralateral space with combined eye and head movements, but failed to do this with the eyes alone. It was found that within a few days after the lesion, eye and head movements in the direction of the target were initiated, but they were inadequate and had long latencies. Within 1 wk latencies had regained preoperative values. Parallel with the recovery on the behavioral task, head movements became more prominent than before the lesion. Four weeks after the lesion, peak velocity of the head movement had increased by a factor of two, whereas the duration showed a twofold decrease compared with head movements before the lesion. No effects were seen on the duration and peak velocity of gaze. After the recovery on the behavioral task had stabilized, a relative neglect in the hemifield contralateral to the lesion could still be demonstrated by simultaneously presenting two stimuli in the left and right visual hemifields. The neglect is not due to a sensory deficit, but to a disorder of programming. The recovery from unilateral neglect after a FEF lesion is the result of a different orienting behavior, in which head movements become more important. It is concluded that the FEF plays an important role in the organization and coordination of eye and head movements and that lesions of this area result in subtle but permanent changes in eye-head coordination.