Th2-type cytokines, hypereosinophilia, and interleukin-5 in HIV disease.
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Cytokines↗
Biomedical subjects
R Rosso
Publications and source records attributed to R Rosso.
Quantitative monitoring of blood supply to knee joint transplants in dogs.
BACKGROUND: Transplantation of vascularized knee joints has become technically feasible, but graft rejection as well as failures of the vascular anastomoses remain critical hazards. We therefore tested the potential of repetitive non-invasive duplex sonography to detect changes of the arterial blood flow following canine knee joint transplantation. METHODS: Four transplantations and, as controls, 4 replantations of intact canine knee joints were performed. The follow-up was 6 months. During this period, repetitive duplex sonography measurements as well as tests of knee joint function were performed. Six months postoperatively, angiographies were performed and all joints were explanted for histological investigation. RESULTS: The luminal diameters of the implanted popliteal artery remained constant in the transplanted animals (preop. 2.6 +/- 0.2 mm, 6 months postop. 2.7 +/- 0.2 mm) but decreased in the autografted controls (preop. 2.9 +/- 0.3 mm, postop. 2.0 +/- 0.3 mm). The time-averaged velocity of the popliteal artery blood flow decreased in both groups 1 month postoperatively. Subsequently, blood flow velocity recovered in transplanted animals but remained low in replanted controls. Significant arterial wall thickening was also detected in transplanted animals as compared to controls. Six months postoperatively, hypervascularization of transplanted joints was confirmed by angiography and thickening of the arterial wall by histology. Furthermore, histology identified mild to chronic allograft rejection in all transplanted joints in spite of controlled cyclosporin A trough level immunosuppression. CONCLUSIONS: Chronic rejection of transplanted vascularized knee joints appears to be associated with vessel wall thickening and hypervascularization rather than with vascular rarefaction (picture of the 'arbre mort') that is characteristic of the rejection of most parenchymatous organs. Duplex sonography appears to be sensitive in detecting the corresponding changes of blood supply.
Angiography↗
Effect of granulocyte-macrophage colony-stimulating factor on prevention of mucositis in head and neck cancer patients treated with chemo-radiotherapy.
Twenty-nine previously untreated patients with squamous cell carcinoma of the oral cavity and pharynx underwent a treatment program with four courses of chemotherapy alternated with three courses of radiotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered at a dose of 5 micrograms/mg subcutaneously on the same day as radiation treatment in order to prevent mucositis. No grade 4 mucositis was reported; only four episodes of grade 2 mucositis and thirteen grade 2. Comparing these results with historical patients treated with the same chemotherapy-radiation program but without GM-CSF, the authors concluded that GM-CSF is an effective treatment for preventing mucositis produced by chemotherapeutic and/or radiotherapeutic interventions in patients at high risk of oropharyngeal mucosal damage.
Aged↗
Randomized phase III trial evaluating the role of erythropoietin in the prevention of chemotherapy-induced anemia.
PURPOSE: Although erythropoietin (EPO) is known to be useful in treating chemotherapy-induced anemia, few data are available on its potential preventive role. The aim of this study was to evaluate the ability of EPO in preventing the development of clinically significant anemia in patients treated with chemotherapy. PATIENTS AND METHODS: Sixty-two early-stage breast cancer patients undergoing accelerated adjuvant chemotherapy were randomized to receive EPO 150 U/kg three times a week or no additional treatment. Chemotherapy consisted of six cycles of cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF) intravenously on day 1, every 2 weeks with the support of granulocyte colony-stimulating factor (G-CSF), 5 microg/kg subcutaneously from day 4 to day 11. RESULTS: Throughout the six cycles of chemotherapy, EPO-treated patients maintained stable values of hemoglobin, whereas control patients developed a progressive anemia. At the end of chemotherapy, the mean (+/- SD) hemoglobin decrease in the control group was 3.05 g/dL (+/- 1.0; 95% confidence interval [CI], 2.6 to 3.5), whereas in the EPO group it was 0.8 (+/- 1.4; 95% CI, 0.3 to 1.4). Clinically significant anemia (hemoglobin < or = 10 g/dL) occurred in 16 patients (52%; 95% CI, 33 to 69) in the control arm and in no patient (0%; 95% CI, 0 to 14) in the EPO arm (P = .00001). CONCLUSION: EPO prevents anemia in patients undergoing chemotherapy. Further trials are required to identify subsets of patients in which the preventive use of this drug could be cost-effective.
Adult↗
Primary mediastinal B-cell lymphoma: update of its clinicopathologic features.
The peculiar clinical, histomorphological and biological characteristics of PMBCL are reviewed. Special emphasis is given to the frequent aggressive clinical behaviour of this lymphoma in which conventional prognostic factors seem inadequate to identify high risk cases. The need for new clinical and/or biological prognostic markers is stressed.
Biomarkers, Tumor↗
[A phase II multicenter study of gemcitabine in non small cell lung cancers].
Gemcitabine is a novel pyrimidine nucleoside whose activity has been demonstrated on solid tumors. We report here the results of a multicentre phase II trial of gemcitabine in chemonaive patients with inoperable non small cell lung cancer (NSCLC). Gemcitabine was given weekly at a dose of 1,250 mg/m2 administered as a 30 min intravenous infusion, for 3 weeks followed by 1 week of rest (1 cycle). All the 161 patients included were evaluable for toxicity and 151 of them were evaluable for efficacy. The majority of patients had a stage IIIb (31.1%) or stage IV (64.6%) disease; 10.6%, 83.2% and 6.2% of patients had a WHO performance status (PS) 0, 1, and 2, respectively. Adenocarcinoma accounted for 52.2% of cases and squamous cell carcinoma for 43.5% of cases. Three complete responses and 30 partial responses gave an objective response (OR) rate of 21.8% (95% confidence interval; 15.5-29.3%). All responses were validated by an independent Oncology Review Board. Median duration of response was 7.6 months. Median time to progression was 4.6 months (3.3 months in non responders and 7.6 months in responders). Median survival was 7.3 months in non responders and 13.4 months in responders (p < 0.001), which gave an overall median survival of 8.9 months (95% CI: 0.1-21.9 months) in the entire study population. An improvement of symptoms and personal state was also observed. Treatment was well tolerated. Neutropenia was the only dose limiting toxicity. WHO grade 3 or 4 neutropenia occurred in 19.6% and 5.7% of patients, respectively. With a 21.8% OR rate, this multicentre study confirms the activity of gemcitabine as a single agent in patients with inoperable NSCLC. Its good tolerance and original mode of action make gemcitabine a drug of choice in the therapeutic strategy of these tumors.
Adult↗
[Gastrointestinal hemorrhage and diverticula of the jejunum--presentation of a case report and review of the literature].
Gastrointestinal bleeding due to jejunal diverticulosis is an uncommon emergency condition that has been encountered recently in one patient. The case of this patient treated with an emergency laparotomy and a segmentary small bowel resection is here presented. The clinical significance, proper diagnostic evaluation, and treatment of the hemorrhagic complication of jejunal diverticular disease are reviewed.
Aged↗
Docetaxel vs mitomycin plus vinblastine in anthracycline-resistant metastatic breast cancer.
This nonblinded, multicenter, randomized phase III study compares the median time to progression (primary endpoint), response rate, and quality of life, safety, and survival of docetaxel (Taxotere) vs mitomycin (Mutamycin) plus vinblastine (Velban) in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. Patients were randomized to receive an intravenous infusion of either 100 mg/m2 of docetaxel for 1 hour every 3 weeks, or 12 mg/m2 of mitomycin every 6 weeks plus 6 mg/m2 of vinblastine every 3 weeks. This preliminary analysis presents data on 200 patients among 392 patients recruited. Median time to progression was longer in the group treated with docetaxel compared with the mitomycin/vinblastine group (17 vs 9 weeks). The overall response rates were higher with docetaxel (28% vs 13%, respectively), and fewer patients in the docetaxel group had progressive disease as their best overall response (29% vs 48%). As expected, thrombocytopenia was more common in the mitomycin/vinblastine group, and neutropenia occurred more frequently in the docetaxel group. Severe fluid retention in the docetaxel group (8.7%) resulted in treatment discontinuation in 5 patients (5%). Severe thrombocytopenia (12%) and constipation (6%) led to treatment discontinuation in 7 and 3 patients, respectively, in the mitomycin/vinblastine group. Based on this preliminary analysis, docetaxel appears to be equally as safe as and more active than mitomycin/ vinblastine in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. These results are subject to cautious interpretation because this analysis was conducted on the first 200 patients who finished the study treatments, and these preliminary results may underestimate response and overstate treatment discontinuation rates. Thus, the final analysis on the entire patient population is necessary to confirm these preliminary findings.
Adolescent↗
[Benign symmetrical lipomatosis: Madelung's disease].
Multiple symmetrical lipomatosis, or Madelung's disease, is a rare disease of unknown etiology. It is characterized by the presence of loose adipose tissue deposits localized in the cervical region and in the upper body. The neoformations grow slowly and their initial consequence is purely esthetic. They can, however, lead to compression of the laryngeal-tracheal area and of the esophagus. This disease normally affects middle-aged males from the Mediterranean area with a history of alcohol abuse. Although most cases have been sporadic, a few authors have indicated that the disorder may be hereditary. It is thought that this pathology originates from an alteration in lipid metabolism. Surgical removal of the lipomatose mass is the treatment of choice even though there are frequently recurrences. A case is presented of a rare laryngeal localization of this disease and diagnosis and treatment are discussed.
Albuterol↗
Chemotherapy for relapsed head and neck cancer: paclitaxel, cisplatin, and 5-fluorouracil in chemotherapy-naive patients. A dose-finding study.
The aim of this trial was to identify the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered via a 3-hour infusion day 1, together with cisplatin 20 mg/m2/d days 1 to 3 and 5-fluorouracil 200 mg/m2/d bolus days 1 to 3 every 21 days. The prophylactic administration of colony-stimulating factors was not allowed. Twenty-three patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck previously treated with surgery and/or radiotherapy were accrued. None had received chemotherapy previously. No grade 3/4 hematologic toxicity at nadir or other limiting toxicities were recorded with paclitaxel at 100 to 135 mg/m2 (six patients, 26 courses). Seven patients (six evaluable, 22 courses) were treated with 160 mg/m2. Grade 4 neutropenia at nadir with fever lasting 3 days was observed in one patient. Nonhematologic toxicities, including temporary peripheral neuropathy, asthenia, myalgias, vomiting, and mucositis were generally mild. Three patients were treated with 180 mg/m2 (eight courses). Grade 4 neutropenia at nadir was recorded in all patients and was febrile in two. Seven patients (six evaluable, 23 courses) were treated with paclitaxel 160 mg/m2, cisplatin 25 mg/m2/d, and 5-fluorouracil 250 mg/m2/d. Grade 4 febrile neutropenia at nadir was recorded in one patient. One episode of grade 4 mucositis and two episodes of grade 3 diarrhea were also recorded. Overall, eight responses (38%) were observed. In conclusion, the combination of paclitaxel 160 mg/m2, cisplatin 25 mg/m2/d, and 5-fluorouracil 250 mg/m2/d for 3 consecutive days can be administered safely without growth factor support. This regimen merits further investigation in a phase II trial.
Adult↗
Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck.
BACKGROUND: In 1992, we reported the first analysis of a randomized trial comparing alternating radiotherapy and chemotherapy with radiotherapy alone in the treatment of squamous cell carcinoma of the head and neck. The results of that 3-year analysis indicated that the combined treatment had superior efficacy. PURPOSE: After an additional 2 years of follow-up, we again compared the efficacy of the two treatment regimens, with attention paid to differences in overall survival, progression-free survival, and locoregional relapse-free survival. METHODS: One hundred fifty-seven patients with untreated, unresectable squamous cell carcinoma of the head and neck were randomly assigned to receive either chemotherapy (four courses of cisplatin [20 mg/m2] and fluorouracil [200 mg/m2], given daily for 5 consecutive days during weeks 1, 4, 7, and 10) plus radiotherapy (three courses of 20 Gy each, given in fractions of 2 Gy per day during weeks 2-3, 5-6, and 8-9) or radiotherapy alone (70 Gy total dose, given in fractions of 2 Gy per day, 5 days per week). Eighty patients received the combined therapy, and 77 were treated with radiotherapy alone. Responses, failures, and toxic effects associated with the two treatment regimens were compared. Overall survival, progression-free survival, and locoregional relapse-free survival were calculated according to the Kaplan-Meier method; the logrank test was used to compare survival parameters between the two patient groups. Reported P values are two-sided. RESULTS: As reported previously, toxic effects associated with the combined therapy included both chemotherapy- and radiotherapy-related effects; however, the incidence and severity of mucositis were nearly identical among patients in the two treatment arms. The combined treatment was associated with a statistically significant increase in the frequency of complete response (i.e., the disappearance of clinically detectable disease for at least 4 weeks) (43% for the combined-treatment group compared with 22% for the radiotherapy-only group; P = .037, chi-squared test). Five-year estimates of overall survival in the combined-treatment group compared with the radiotherapy-only group were 24% (95% confidence interval [CI] = 14%-40%) and 10% (95% CI = 4%-24%), respectively (P = .01, logrank test). The estimates of progression-free survival at 5 years in the combined-treatment group compared with the radiotherapy-only group were 21% (95% CI = 11%-37%) and 9% (95% CI = 3%-22%), respectively (P = .008, logrank test). Finally, the 5-year estimates of locoregional relapse-free survival were 64% (95% CI = 36%-84%) in the combined-treatment group and 32% (95% CI = 10%-65%) in the radiotherapy-only group (P = .038, logrank test). CONCLUSIONS AND IMPLICATIONS: The superiority of alternating chemotherapy and radiotherapy over radiotherapy alone in treating unresectable squamous cell carcinoma of the head and neck seen at 3 years was confirmed at 5 years. However, additional trials must be conducted before considering the combined approach as standard therapy.
Antimetabolites, Antineoplastic↗
A shift to Th0 cytokine production by CD4+ cells in human longevity: studies on two healthy centenarians.
Centenarians, particularly healthy centenarians, constitute the example of successful aging and the study of their immune status can help to define the endpoint of the changes occurring throughout life. We characterized T cell clones (TCC) of two healthy centenarians, studying their phenotypes and production of representative Th1 and Th2 cytokines (IFN-gamma and IL-4) and compared them with TCC obtained by three young normal subjects; in all 180TCC were analyzed. In young donors, 35TCC were CD4+, 56CD8+ and 2 were alpha beta +CD4-CD8- (double negative). In centenarians, we obtained 46CD4+TCC, 38CD8+, 2CD4+CD8+ (double positive) and 1 gamma delta + double negative. Of the young subjects' TCC, 71% produced IFN-gamma but no IL-4 (Th1 pattern) and this prevalence decreased to 39% in TCC from the centenarians. The number of clones showing the opposite Th2 pattern was similar in young and aged donors (3 out of 93TCC and 2 out of 87TCC, respectively). The intermediate profile of TCC producing both IL-4 and IFN-gamma (Th0) was found in 25.8% of clones from young people, but it almost doubled to 58.6% in centenarians. The analysis shows that the Th profiles of CD8+TCC is nearly superimposable in the two groups, whereas a major shift from a Th1 to a Th0 pattern is presented by CD4+TCC. The balance provided by a majority of CD4+TCC showing a Th0 pattern may ensure both humoral and cell-mediated defences. In CD8+TCC, however, a Th1 pattern still is present, possibly for efficient generation of cytotoxic responses. These findings should be extended by studying other centenarians and elderly subjects.
Aged↗
Tamoxifen and interferon-beta for the treatment of metastatic breast cancer.
It has been demonstrated, both in breast cancer cell lines and in metastatic breast cancer patients with cutaneous lesions that could be biopsied, that treatment with interferon beta (IFN-B) can increase expression of both estrogen (ER) and progesterone receptors (PgR). To evaluate the efficacy and toxicity of the combination of IFN and tamoxifen, 33 metastatic breast cancer patients were treated with the following regimen: IFN-B, 6.0 million units intramuscularly IU 3 times a week for two consecutive weeks followed by IFN-B 6.0 million IU im 3 times a week with concomitant tamoxifen 20 mg orally daily. Patients were pre and postmenopausal with median age of 60 years, median ECOG PS of 0, either ER positive or unknown, and had not received prior hormone therapy for metastatic disease. Overall objective response was observed in 9 (27%) patients. Complete response was observed in 2 cases and partial response in 7 patients. Median duration of response was 7 months (range 2-10). A higher response rate was observed in patients with predominantly soft tissue disease (38%) compared to patients with either dominant bone (18%) or visceral lesions (17%). Toxicity was mild and reversible: low grade fever in 30% of patients and flu-like symptoms in 9% of cases. It appears that IFN-B does not improve the efficacy of tamoxifen in an unselected population of metastatic breast cancer.
Abdominal Neoplasms↗
Erythropoietin and granulocyte-macrophage colony-stimulating factor allow acceleration and dose escalation of cyclophosphamide/epidoxorubicin/5-fluorouracil chemotherapy: a dose-finding study in patients with advanced breast cancer.
To verify whether the association of granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) would allow both the acceleration and the dose escalation of the cyclophosphamide/epidoxorubicin/5-fluorouracil (CEF) regimen as first-line therapy in advanced breast cancer patients, we conducted a dose-finding study. Cohorts of three consecutive patients received cyclophosphamide (Ctx, dose range 800-1400 mg/m2), epidoxorubicin (Epidx, dose range 70-100 mg/m2), and 5-fluorouracil (5-Fu, 600 mg/m2, fixed dose) given as an intravenous bolus on day 1 every 14 days; GM-CSF at 5 micrograms/kg given as a subcutaneous injection from day 4 to day 11; and EPO at 150 IU/kg given as a subcutaneous injection three times a week. In no single patient was any dose escalation allowed. A total of 14 patients entered the study. At the 4th dose level (Ctx 1400 mg/m2, Epidx 100 mg/m2, 5-Fu 600 mg/m2), two patients had dose-limiting mucositis and one patient developed dose-limiting neutropenia. Therefore, the 3rd cohort received the maximum tolerated dose, i.e. Ctx at 1200 mg/m2, Epidx at 90 mg/m2, and 5-Fu at 600 mg/m2, given every 18.5 (+/-2.5) days. Toxicity was moderate and manageable in an outpatient setting. Only 1 admission at the 4th dose level was required. Throughout the 4 dose levels there was no toxicity-related death; grade IV leukopenia ranged from 24% to 75% of cycles and grade IV thrombocytopenia ranged from 6% to 8%. No grade IV anemia was recorded. Increasing the doses of Ctx and Epidx while maintaining a fixed dose of 5-Fu with the support of both EPO and GM-CSF allows safe acceleration and dose escalation of CEF chemotherapy. Further controlled studies will evaluate the activity and efficacy of this strategy.
Adult↗
Activity of gemcitabine in patients with non-small cell lung cancer: a multicentre, extended phase II study.
Gemcitabine is a novel nucleoside analogue with activity in solid tumours. This study assessed the objective response rate to gemcitabine given weekly intravenously at a dose of 1250 mg/m2 for 3 weeks followed by 1 week of rest (one cycle) in chemonaive patients with inoperable non-small cell lung cancer (NSCLC). 161 patients with NSCLC were recruited from 10 sites in nine countries. Most patients had stage IIIb (31.3%) or IV (64.6%) disease, and 93.8% had a performance status of 0 or 1 according to the WHO scale. Of 151 evaluable patients, there were 3 complete responses and 30 partial responses lasting at least 4 weeks for an objective response rate of 21.8% (95% CI 15.5-29.3%). All responses were validated by an extramural Oncology Review Board. The mean duration of response was 8.8 months. The mean survival for all patients (16.1% of patients still alive 26 months after last patient started treatment) was 11.5 months. Improvements were also observed in secondary efficacy parameters such as performance status, weight, analgesic requirement, pain, and other disease-related symptoms including cough, dyspnoea, haemoptysis, anorexia, somnolence and hoarseness. Haematological and non-haematological toxicity was mild given the biological activity of gemcitabine. This study confirms gemcitabine as one of the most active agents in NSCLC with the added benefit of a modest toxicity profile and ease of administration on an out-patient basis. Gemcitabine is a suitable candidate for combination chemotherapy in patients with NSCLC.
Adolescent↗
Lonidamine plus epirubicin and cyclophosphamide in advanced breast cancer. A phase II study.
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Adult↗
Phase I study of simultaneous dose escalation and schedule acceleration of cyclophosphamide-doxorubicin-etoposide using granulocyte colony-stimulating factor with or without antimicrobial prophylaxis in patients with small-cell lung cancer.
A phase I study was designed to assess whether dose intensity of an 'accelerated' cyclophosphamide-doxorubicin-etoposide (CDE) regimen plus granulocyte colony-stimulating factor (G-CSF) could be increased further, in an outpatient setting, by escalating the dose of each single drug of the regimen. Patients with previously untreated small-cell lung cancer (SCLC) received escalating doses of cyclophosphamide (C) 1100-1300 mg m-2 intravenously (i.v.) on day 1, doxorubicin (D) 50-60 mg m-2 i.v. on day 1, etoposide (E) 110-130 mg m-2 i.v. on days 1, 2, 3 and every 14 days for at least three courses. Along with chemotherapy, G-CSF (filgastrim) 5 micrograms kg-1 from day 5 to day 11 was administered subcutaneously (s.c.) to all patients. Twenty-five patients were enrolled into the study. All patients at the first dose level (C 1100, D 50, E 110 x 3) completed three or more cycles at the dose and schedule planned by the protocol and no 'dose-limiting toxicity' (DLT) was seen. At the second dose level (C 1200, D 55, E 120 x 3) three out of five patients had a DLT consisting of 'granulocytopenic fever' (GCPF). Another six patients were treated at this dose level with the addition of ciprofloxacin 500 mg twice a day and only two patients had a DLT [one episode of documented oral candidiasis and one of 'fever of unknown origin' (FUO) with generalised mucositis]. Accrual of patients proceeded to the third dose level (C 1300, D 60, E 130 x 3) with the prophylactic use of ciprofloxacin. Four out of six patients experienced a DLT consisting of GCPF or documented non-bacterial infection. Accrual of patients at the third dose level was then resumed adding to ciprofloxacin anti-fungal prophylaxis (fluconazole 100 mg daily) and anti-viral prophylaxis (acyclovir 800 mg twice a day) from day 5 to 11. Out of five patients treated three experienced a DLT consisting of severe leucopenia and fever or infection. With a simultaneous dose escalation and schedule acceleration it is indeed possible to take maximum advantage of G-CSF activity and to increase CDE dose intensity by a factor 1.65-1.80 for a maximum of 3-4 courses. The role of antimicrobial prophylaxis in this setting deserves to be investigated further.
Antibiotic Prophylaxis↗
Ultrasonic parameters of bone in young normals: effect of age and sex.
This study was carried out in order to investigate the early effects of ageing on both broadband ultrasound attenuation and speed of sound through the os calcis. A total of 217 normal subjects, subdivided into 113 fertile women (age range 18-51 years, mean +/- 1 SD=29.4 +/- 8.4 years) and 104 age-matched men (age range 20-49 years, mean +/- 29.3 +/- 7.1 years), were investigated. Mean broadband ultrasound attenuation values in men (127.3 +/- 12.8 dB MHz-1) were significantly higher than those found in women (118.3 +/- 17.2, P < 0.001), whereas no significant differences were found as far as mean speed of sound values was concerned. Both broadband ultrasound attenuation (r = -0.196, P < 0.046) and speed of sound (r = -0.226, P < 0.02) values were inversely related to age in men; only a decrease of speed of sound values with age was noted in women (r = -0.400, P < 0.001). Finally, there was a very high significant correlation between broadband ultrasound attenuation and speed of sound values in men (r = 0.458, P < 0.001), but this was lacking in women. Admitting that the measurement of broadband ultrasound attenuation is influenced not only by bone density but also by trabecular quantity, spacing and orientation, our results seem to indicate that, even during adulthood, and well before the deleterious effects of oestrogen lack become apparent, structural properties of skeletal tissue in female subjects are disadvantageous with respect to those found in male subjects. Furthermore, while there is a progressive and balanced involvement of both the elastic (as reflected by speed of sound) and the structural properties of skeletal tissue of men, an uncoupling between the two is typical of women.
Adolescent↗