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PubMed1995

Cortical control of human soleus muscle during volitional and postural activities studied using focal magnetic stimulation.

The surface-recorded electromyographic (EMG) responses evoked in the ankle musculature by focal, transcranial, magnetic stimulation of the motor cortex were studied in healthy human subjects. Such soleus evoked motor responses (EMRs) were characterised over a wide range of background levels of motor activity and using different stimulus intensities. EMRs were recorded during predominantly (1) volitional and (2) postural tasks. In the former task subjects were seated and voluntarily produced prescribed levels of soleus activation by reference to a visual monitor of EMG. In the latter task subjects assumed standing postures without EMG feedback. Comparison of the EMRs of soleus, traditionally considered a slow anti-gravity extensor muscle, during these tasks was used to evaluate its cortical control in primarily volitional versus primarily postural activities. The form of soleus EMRs produced by single magnetic cortical stimuli comprised an initial (approx. 30 ms) increase and subsequent (approx. 50 ms) depression of EMG. Cortical stimulation could elicit substantial excitatory soleus EMG responses; for example, responses evoked by mild, magnetic stimuli (125% threshold for inducing a response in the relaxed muscle) as subjects exerted full voluntary plantarflexor effort averaged almost 20% of the maximum M-wave which could be elicited by an electrical stimulus to the posterior tibial nerve. Excitatory EMRs could be elicited in the voluntarily relaxed soleus muscle of the majority of subjects during sitting. The amplitude of soleus responses, induced by threshold stimuli for the relaxed state or approximately 125% threshold intensity, increased approximately linearly with background EMG over a wide range of volitional contraction levels. By contrast, there was no systematic change in the latency of excitatory soleus EMRs with increasing voluntary effort. The excitatory responses evoked in the voluntarily relaxed soleus of seated subjects by magnetic stimulation were regularly facilitated by incremental, voluntary contraction of the contralateral ankle extensors in a graded manner. However, such facilitation of responses was not observed when subjects voluntarily activated the muscle in which EMRs were elicited. The pattern of the responses elicited in soleus by magnetic stimulation during the postural task generally resembled that found during the volitional task. The amplitudes of excitatory soleus EMRs at a given stimulus intensity, obtained when subjects stood quietly, leaned forwards or stood on their toes to produce differing levels of ankle extensor contraction, increased with background EMG.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

An in vivo and in vitro trial of aclarubicin in metastatic breast cancer: a novel approach to the study of analogs.

Aclarubicin is an anthracycline antibiotic that differs from doxorubicin in its structure, mechanism of action, and preclinical toxicity profile, especially its reduced cardiotoxicity. We therefore conducted a side-by-side in vivo and in vitro trial of this agent in metastatic breast-cancer patients and their biopsied tumor specimens, respectively. Aclarubicin (100 mg/m2) was given by intravenous infusion every 3 weeks to 22 patients with objectively measurable metastatic breast cancer, 15 of whom had not previously received doxorubicin. The dose-limiting toxicity consisted primarily of leukopenia and severe nausea and vomiting. No objective response was observed in the 19 evaluable patients. After disease progression, 10 of the 15 doxorubicin-naive patients were treated with doxorubicin; 6 patients achieved a partial response, including 4 who responded to doxorubicin alone and 2 who responded to doxorubicin in combination with thiotepa and vinblastine. Tumor specimens were obtained from 14 of the 22 patients prior to the start of therapy and were tested for in vitro sensitivity to aclarubicin and doxorubicin using a soft agar colony-forming assay. Adequate colony growth occurred in 9 of 14 cultured tumor specimens. All 9 specimens, including 3 obtained from doxorubicin-naive patients, demonstrated in vitro resistance to aclarubicin. In all, 1 of 3 specimens taken from doxorubicin-naive patients demonstrated in vitro sensitivity to doxorubicin, whereas 6 tumor specimens obtained from patients who had undergone prior doxorubicin therapy demonstrated in vitro resistance. The patient whose tumor demonstrated in vitro doxorubicin sensitivity responded to a doxorubicin regimen after failing aclarubicin treatment; in vitro doxorubicin resistance correlated with clinical resistance in all cases. We conclude that aclarubicin is inactive in metastatic breast cancer at the dose and schedule used. Side-by-side in vivo and in vitro trials are feasible and could be useful in the development of investigational agents with activity greater than that of aclarubicin and, particularly, in the evaluation of analogs of clinically active drugs.

Aclarubicin↗
PubMed1990

Behaviors, beliefs, and intentions in skin cancer prevention.

This study investigated knowledge, behaviors, and health beliefs of Australian university students (n = 312) regarding skin cancers and evaluated the effects of videotaped presentations. Students' knowledge and health beliefs were assessed, and they then viewed either an informational video, an emotionally involving video, or a control video. Knowledge and beliefs were assessed immediately and 10 weeks later. Postvideo skin protection intentions increased significantly from prevideo assessment among the two intervention groups compared to the controls. Maintenance of skin protection intentions was higher with the emotional video. Health belief variables, particularly perceived barriers, were significant predictors of knowledge, intention, and behavior. However, other variables such as skin type and previous experience with skin cancer were more important. Females had greater knowledge and stronger intentions to prevent skin cancer than males but reported fewer high-risk behaviors.

Adult↗
PubMed1991

Comparison of dual photon and dual energy X-ray bone densitometers in a clinic setting.

In clinical practice, decisions must be made about whether and how to convert to newer technologies. To address this issue, two separate studies were conducted. We evaluated the relationships between results of lumbar spine measurements using two dual photon absorptiometry (DPA1 and DPA2) instruments and one dual energy X-ray (DXA) instrument with the same subjects (49 volunteers), and also in 65 patients who were measured on the DPA1 and DXA machines. Second, we measured the lumbar spine and the proximal femur in three groups of 12 female volunteers three times on one instrument within 1 week. We purposely simulated a busy clinic setting with different technologists, older radioactive sources, and a heterogeneous patient group. The comparison study indicated a significant difference between the mean bone density values reported by the machines, but the results were highly correlated (R2 = 0.89-0.96). The short-term precision errors (coefficients of variation) differed among the instruments, ranging from 1.3% (DXA of the spine) to 5.1% (DPA1 of the spine), and in the femoral neck, 2.3% and 2.4% (DXA and DPA1, respectively) versus 3.5% by DPA2. This study emphasizes the differences between instruments, the potential for greater error in busy clinic environments, and the apparent superiority of dual energy X-ray absorptiometry under these less than ideal conditions.

Absorptiometry, Photon↗
PubMed1984

Female orgasmic experience: a subjective study.

Human female orgasm was studied by collecting and analyzing the subjective orgasmic histories of 30 women, ages 18 to 59 years. Virtually all of the 93% who reported they had experienced orgasm also reported some level of conscious control over whether or not they reached orgasm. Women differed widely as to preferred types of physical stimulation and/or mental activities to facilitate orgasm. Orgasms were experienced as centered in the clitoral and/or vaginal areas. Women over 40 were more likely to have experienced orgasm in more than one anatomic site than were women aged 18 to 29. Marital status, religion, occupation, educational level, experiences of pregnancy and childbirth, various reported characteristics of relationships with partners, and early sexual experience were not associated with where orgasm is experienced within the body or with other variables of adult orgasmic experience. The variation among women as to how orgasm is best reached, differences in where it is experienced within the body, and the reasons why an individual woman experiences orgasms differently over time remain poorly understood phenomena.

Adolescent↗
PubMed1993

The assessment of vertebral bone macroarchitecture with X-ray computed tomography.

On a macroscopic scale, the structural characteristics of whole bone are likely dependent on the distribution of typically applied loads to the bone surface, the full bone shape, the thickness of the cortex at the various surface positions, and the distribution of cancellous bone material. X-ray computed tomography is presently the best available method for assessing the macroarchitecture of bone in-vivo. Fine detail, three-dimensional CT methods are available to measure regional bone mineral density (rBMD) in contiguously spaced small volumes and have been applied to the assessment of macroarchitecture in vertebrae. The more detailed rBMD methods produce radiation exposures to the subject similar to lumbar radiography and substantially higher than traditional QCT. The cancellous bone within lumbar vertebral bodies has been found in cross-sectional studies to have increased density in the inferior, posterior and lateral regions. Notably, regions with higher density at age 40 have a larger decline with age. The vertebral body cortex declines with age at a slower rate than observed for cancellous bone; however, the decline with age of cortical bone appears to vary substantially amongst subjects. The amount of cortical bone in the anterior portion of the body is less than in the lateral portion, which may explain previous discrepancies in assessing the fraction of vertebral body bone in the cortex.

Adult↗
PubMed1976

NMR-studies of triiodothyropropionic acid in ethanol-HCl.

The barrier to rotation in the N-acetyl methyl ester of the thyroxine was found to be 8.6 kcal mol-1. Previous experiments determining the barrier to rotation in triiodothyropropionic acid in HCl-ethanol were shown to be in error.

Ethanol↗
PubMed1988

Distal axonopathy in streptozotocin diabetes in rats.

We noted the earliest morphological changes in the motor endplates 8 weeks after the induction of streptozotocin diabetes in rats. Morphometric measurements showed reduced axonal areas of the lateral plantar and the sciatic nerves in the diabetic rats 28 but not 2 and 8 weeks after the experiment. These findings suggested distal axonopathy.

Animals↗
PubMed1995

Breast cancer after breast augmentation with silicone implants.

BACKGROUND: Although epidemiological studies have failed to demonstrate an increased incidence of breast cancer in women who had undergone prior prosthetic augmentation mammoplasty (PAM), it has been reported that when breast cancer arises in this group it presents mostly in a palpable form and at a more advanced stage. This is thought to be secondary to suboptimal mammographic evaluation caused by the masking effect of the implant. This study was undertaken to determine, in our experience, whether breast cancer arising in women who had undergone PAM could be detected in a prepalpable form by mammography and whether it presented at a more advanced stage as compared with nonaugmented women with breast cancer. METHODS: The charts of 22 patients, treated by at least one of the authors, in whom 23 breast cancers developed after PAM (group A) were retrospectively reviewed. The comparison groups consisted of 611 nonaugmented patients who underwent 636 procedures for the treatment of primary breast cancer at our institution (group B) and the surveillance, epidemiology, and end results (SEER) data (group C). Parameters studied were mode of detection, tumor size, axillary lymph node involvement, and histopathology. RESULTS: No significant differences between the groups were found in mean tumor size (group A vs. group B), the incidence of preinvasive cancer (group A vs. group B) or axillary lymph node involvement (group A vs. group B and group A vs. group C). Breast-preserving surgery was performed significantly less in augmented patients (group A vs. group B). CONCLUSION: We conclude that prepalpable and preinvasive breast cancer can be detected in the PAM patient by mammography and that the stage of presentation in this group is not significantly different than in nonaugmented patients. Total mastectomy is preferred over breast-preserving procedures for the treatment of breast cancer in the PAM patient.

Adult↗
PubMed1995

Internal mammary node status: a major prognosticator in axillary node-negative breast cancer.

BACKGROUND: The internal mammary lymph nodes (IMN) have received little attention in recent years, yet are a well-documented site of metastasis and a major prognostic factor in early-stage breast cancer. METHODS/RESULTS: Ten-year follow-up of the final 195 patients treated by extended radical mastectomy (ERM) in this practice (selected largely on the basis of medial tumor location, and comprising 15% of all patients treated from 1965 to 1978) found IMN+ in 24% of all cases: 36% of AX+ versus 18% of AX- patients (p = 0.0023). In a multivariate analysis, the disease-free survival impact of IMN+ (p = 0.004) was second only to axillary node involvement (p < 0.0005), and surpassed tumor size (p = 0.077). IMN+ was equally frequent for tumors less than, or greater than, 2 cm (24%), and was not significantly related to patient age. Among AX- patients, there was a twofold greater risk of recurrence or death at 10 years for IMN+ than for IMN-. Among T1N0 patients, 19.6% were IMN+. CONCLUSIONS: Failure to consider IMN status in the steadily enlarging cohort of T1N0 breast cancers may result in the undertreatment of a significant proportion of stage I patients. Systemic adjuvant therapy should be considered for T1N0 patients with central or medial tumors.

Adult↗
PubMed1996

Molecular cloning of the mouse gene coding for carbonic anhydrase IV.

Carbonic anhydrase IV (CA IV) is expressed on apical surfaces of renal tubular epithelium and endothelium of specialized capillary beds. It plays a key role in bicarbonate reabsorption in kidney and in CO2 transport in other tissues. The human cDNA and genomic sequences have been cloned and characterized. Here we report the cloning and characterization of the entire mouse CA IV gene (contained in two overlapping lambda clones), which should enable generation of targeting constructs for disrupting the mouse CA IV gene to produce mouse models for in vivo analysis of CA IV gene function. The gene is approximately 8.2 kb long and contains eight exons ranging from 54 to 434 bp in length. The first exon (exon 1a) encodes the signal sequence. Exons 1b through 7 encode the remaining coding sequences. Exon 7 encodes the C terminus of the membrane-associated protein, as well as the 242-bp 3' untranslated sequence. The nucleotide sequence alignment between mouse and rat CA IV cDNAs reveals 84% identity. The nucleotide sequence alignment between mouse and human CA IV shows 69% identity in the coding region and all of the exon-intron boundaries are conserved, as are the sizes of the introns. The corresponding mouse and human exons are similar, except for the length of the untranslated regions in exons 1a and 7 and two small insertion/deletion events in exons 1a and 4. The 5' flanking region of the mouse gene (-300 to -1) is GC rich and contains 16 CpG dinucleotides. A TATA box sequence and several transcription factor binding sequences are identified upstream of exon 1a. Comparison of the nucleotide sequences surrounding the TATA box (-300 to -1) between mouse and human CA IV genes revealed 70% identity, indicating that regulatory sequences are as highly conserved as coding sequences between mouse and human CA IV genes.

Animals↗
PubMed1981

Malignant retrorectal tumors: 28 years' experience at Memorial Sloan-Kettering Cancer Center.

From 1949 to 1977, 39 patients with localized malignant retrorectal tumors were treated at Memorial Sloan-Kettering Cancer Center. Chordomas were the most frequent histologic type (38 per cent of patients) followed by neurogenic tumors (15 per cent) chondrosarcomas, hemangiopericytomas, and embryonal adenocarcinomas (8 per cent each). Treatment consisted of surgical excision in 28 patients (18 of whom received adjuvant radiotherapy and/or chemotherapy). Ten patients were treated nonsurgically, receiving radiation and/or chemotherapy alone. Large tumors were most successfully managed by a combined surgical approach consisting of exploratory celiotomy, rectal mobilization, and bilateral hypogastric artery (with middle sacral artery and vein) ligation, followed by transsacral tumor excision with incontinuity sacrectomy. For all treated patients, survival at 5, 10, 15 and 20 years was 69 per cent, 50 per cent, 37 per cent and 20 per cent, respectively. Long-term disease-free survival (17 to 25 years post treatment) was noted in six patients. [Key words: Tumor(s), retrorectal, malignant; Tumor(s), treatment].

Adolescent↗