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Traditionally, when a negative specimen radiograph is obtained during biopsy of a nonpalpable breast lesion, immediate re-excision is performed in an attempt to successfully remove the lesion. Based on a retrospective study of the biopsy results of 792 nonpalpable breast lesions, the authors suggest delaying the re-excision, despite a negative specimen x-ray, until postoperative mammography confirms the persistence of the lesion. Utilization of this approach was associated with a comparably low incidence of missed lesions (3%) and had the added advantages of preserving breast tissue and decreasing operative time.

SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons.OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries.DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs.RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages.CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

Background The mechanisms by which surgical injury fosters tumor growth are examined. Methods TA3Ha mouse breast tumor line and its subline (TA3AD) differing in their metastatic abilities as tested by two models were used. In model a, TA3Ha/TA3AD tumors were grown in the mammary fat pads of mice and then surgically removed with a curative intent. In model b, TA3Ha/TA3AD cells were injected intravenously into mice subjected to liver or spleen wedge resection. Frequency of tumor formation at various sites was assessed. Expression of integrin, immunoglobulin, and proteoglycan cell adhesion receptors on TA3Ha and TA3AD cells was examined by flow cytometry. The roles of these receptors in metastasis were examined by blocking them by selected ligands and/or antibodies. Results Frequencies of local recurrence and axillary metastasis after surgical resection, were 43% (32/74), and 37% (27/74) with TA3Ha tumors and 4% (1/29) at both sites with TA3AD tumors. Tumors at surgically injured spleen and the liver were seen in 75% (141/189) and 45% (107/240) of the mice with TA3Ha cells and in 8% (3/38) and 10% (4/42) of the mice with TA3AD cells. α5 and CD44 receptors were expressed by TA3Ha cells but not by TA3AD cells. Other receptors examined were similarly expressed by both cell lines. Blocking of α5 receptor by fibronectin reduced tumor implantation in a dose-dependent manner. Conclusions The data suggest a correlation among the ability to implant at surgically injured sites, to form local recurrence, and to express the fibronectin receptor subunit. © 1996 Wiley-Liss, Inc.

The purpose of the present study was to determine the relative efficacy of pre-, peri-, and postoperative chemotherapy in the prevention of breast cancer relapse and prolongation of host survival. The studies were performed using an experimental mouse breast cancer model. TA3Ha mouse mammary adenocarcinoma was transplanted into the mammary fat pad of syngeneic mice to obtain tumors in their natural organ. The tumors were surgically excised with a “curative” intent. A single treatment with 10 mg/kg doxorubicin was given intravenously pre-, peri-, or postoperatively. Among 74 mice whose tumors were resected but no doxorubicin was given, local recurrence, axillary metastasis, and lung metastasis were seen in 43%, 37%, and 16% of the mice, respectively. Seventeen (23%) mice had no evidence of disease. Doxorubicin given 4 days preoperatively reduced the rate of growth of primary tumor. Local recurrence was reduced in these mice by 30% and metastasis to the axillary lymph nodes and lung was completely prevented. Disease-free survival was increased to 70% (P < 0.01). Similar beneficial effects were obtained when chemotherapy was administered 2 days prior to surgery. The peri-operative chemotherapy group showed 8% (2/26) local recurrence, 4% axillary metastasis, and 0% lung metastasis. Proportion of mice without any evidence of disease increased to 92% (P < 0.00001). Chemotherapy given 4 days postoperatively resulted in 63% (10/16) local recurrence, 38% axillary metastasis, and 6.3% lung metastasis. Only 38% of the mice were disease-free. Thus in the model studied, perioperative chemotherapy offers the best chance for reduced recurrence and for improved disease-free survival. © 1996 Wiley-Liss, Inc.

The pathogenesis of local recurrence in breast cancer is not well understood. Breast-conserving surgery is particularly prone to local recurrence as it leaves behind breast tissue that may harbour occult cancer, and lends itself to enhanced intraoperative shedding of cancer cells due to narrower resection margins and transection of lymphatic channels. A review of clinical breast cancer studies as well as experimental research strongly suggests that these persisting cancerous cells are unlikely to develop into clinically evident disease if their environment remains unstimulated. However, an inordinately high local recurrence rate occurs at the surgical scar, and such recurrence must be triggered by the release of growth factors and cytokines into the healing wound. These factors can stimulate any available cancer cells which express the proper growth factor receptors. Perioperative strategies to neutralize this tumour cell-growth factor interaction should maximize local control.

Zambia faces overlapping tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics; however, care for co-infected patients often occurs through separate, vertical programs.To establish a program to integrate TB and HIV services in Lusaka primary care centers.In collaboration with the Zambian Ministry of Health, TB-HIV integration activities began in December 2005 and were expanded to seven health centers by March 2007. Principal activities included developing staff capacity to manage co-infected patients, implementing HIV testing within TB departments and establishing referral systems between departments.Using a provider-initiated approach, 2053 TB patients were offered HIV testing. Seventy-seven per cent agreed to be tested; 69% of those tested were HIV-infected. Of these, 59% were enrolled in HIV care. The proportion of antiretroviral treatment (ART) program enrollees who were TB-HIV co-infected increased by 38% after program implementation. The median CD4 count among co-infected patients was 161 cells/microl, with 88% eligible for ART.Integration of HIV testing and referral services into urban primary care centers identified many co-infected patients and significantly increased the proportion of TB patients among people accessing HIV care. Ongoing challenges include maximizing the number of patients accepting HIV testing and overcoming barriers to enrollment into HIV care.

BACKGROUND: Zambia faces overlapping tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics; however care for co-infected patients often occurs through separate vertical programs. OBJECTIVE: To establish a program to integrate TB and HIV services in Lusaka primary care centers. METHODS: In collaboration with the Zambian Ministry of Health TB-HIV integration activities began in December 2005 and were expanded to seven health centers by March 2007. Principal activities included developing staff capacity to manage co-infected patients implementing HIV testing within TB departments and establishing referral systems between departments. RESULTS: Using a provider-initiated approach 2053 TB patients were offered HIV testing. Seventy-seven per cent agreed to be tested; 69% of those tested were HIV-infected. Of these 59% were enrolled in HIV care. The proportion of antiretroviral treatment (ART) program enrollees who were TB-HIV co-infected increased by 38% after program implementation. The median CD4 count among co-infected patients was 161 cells/microl with 88% eligible for ART. CONCLUSION: Integration of HIV testing and referral services into urban primary care centers identified many co-infected patients and significantly increased the proportion of TB patients among people accessing HIV care. Ongoing challenges include maximizing the number of patients accepting HIV testing and overcoming barriers to enrollment into HIV care.

Serial ultrasound biometry and Doppler flow velocity waveform analysis were used to measure the effects of maternal smoking in a prospective study of 535 pregnancies. Smoking was associated with significant reductions in maternal weight gain, birthweights and placental weights. Decreased fetal biparietal diameter measurements were observed in pregnancies of smoking women; this effect was maximal at 24 weeks' gestation, was restricted to male fetuses and was not associated with altered head circumferences after birth. Umbilical artery and uteroplacental systolic/diastolic ratios were similar in pregnancies of smoking and non-smoking women, indicating that the effects of smoking on placental vascular resistance are periodic rather than continuous. The findings of this study confirm the need for studies of fetal growth to include prenatal measurements obtained by high resolution ultrasound imaging, rather than relying on findings obtainable by examination of the infant after birth.

In vivo animal research (1-3) has demons t ra ted that cancer cells can have a dramatic and clinically significant interact ion with a fresh surgical wound. We have demons t ra t ed that circulating carc inoma cells can be di rected to a site that was historically refractory for that cancer by surgically injuring that site just before the intravenous injection of carc inoma cells. We have demons t ra ted that tum o r cells would implant and grow at a surgically injured liver, spleen, cecum, bone, or kidney in 50 to 75% of animals compared with essentially no metastatic rate to these sites in an un in ju red animal (1, 4, 5). The cancer cells would be attracted not just to the in jured organ, but to exactly the in jured site. Fur thermore , the injured area t ended to be the single site of greatest tumor b u r d e n of all metastatic foci. Fisher and colleagues have shown that factors locally released by the surgical resection of a carc inoma can stimulate cancer cells at a distant site (6, 7). This interact ion between cancer cells and the surgical wound env i ronment has impor tan t implications on results of surgical therapy of malignancies. The attraction to and stimulation of mal ignant ceils by the growth substances released f rom the surgical wound are felt to be a major obstacle to our ability to cure cancer by surgery alone. To ascertain whe the r the surgical extirpation of breast cancer facilitates local and distant tumor

The mechanisms by which surgical injury fosters tumor growth are examined.TA3Ha mouse breast tumor line and its subline (TA3AD) differing in their metastatic abilities as tested by two models were used. In model a, TA3Ha/TA3AD tumors were grown in the mammary fat pads of mice and then surgically removed with a curative intent. In model b, TA3Ha/TA3AD cells were injected intravenously into mice subjected to liver or spleen wedge resection. Frequency of tumor formation at various sites was assessed. Expression of integrin, immunoglobulin, and proteoglycan cell adhesion receptors on TA3Ha and TA3AD cells was examined by flow cytometry. The roles of these receptors in metastasis were examined by blocking them by selected ligands and/or antibodies.Frequencies of local recurrence and axillary metastasis after surgical resection, were 43% (32/74), and 37% (27/74) with TA3Ha tumors and 4% (1/29) at both sites with TA3AD tumors. Tumors at surgically injured spleen and the liver were seen in 75% (141/189) and 45% (107/240) of the mice with TA3Ha cells and in 8% (3/38) and 10% (4/42) of the mice with TA3AD cells. alpha 5 and CD44 receptors were expressed by TA3Ha cells but not by TA3AD cells. Other receptors examined were similarly expressed by both cell lines. Blocking of alpha 5 receptor by fibronectin reduced tumor implantation in a dose-dependent manner.The data suggest a correlation among the ability to implant at surgically injured sites, to form local recurrence, and to express the fibronectin receptor subunit.

Both normal and neoplastic breast tissues are stimulated by endocrine and paracrine hormones. Epidemiological studies have demonstrated the significant role that hormones, growth factors and cytokines have in the promotion, progression and recurrence of breast cancer. Significant variations in the hormonal environment occur based on age, the cyclical changes occurring during the menstrual cycle and (mammographically determined) variations in breast composition. These variations have a significant influence on rates of local recurrence of breast cancer and survival. This review analyses data relevant to these issues and suggests means by which operative results may be improved.

The purpose of the present study was to determine the relative efficacy of pre-, peri-, and postoperative chemotherapy in the prevention of breast cancer relapse and prolongation of host survival. The studies were performed using an experimental mouse breast cancer model. TA3Ha mouse mammary adenocarcinoma was transplanted into the mammary fat pad of syngeneic mice to obtain tumors in their natural organ. The tumors were surgically excised with a "curative" intent. A single treatment with 10 mg/kg doxorubicin was given intravenously pre-, peri-, or postoperatively. Among 74 mice whose tumors were resected but no doxorubicin was given, local recurrence, axillary metastasis, and lung metastasis were seen in 43%, 37%, and 16% of the mice, respectively. Seventeen (23%) mice had no evidence of disease. Doxorubicin given 4 days preoperatively reduced the rate of growth of primary tumor. Local recurrence was reduced in these mice by 30% and metastasis to the axillary lymph nodes and lung was completely prevented. Disease-free survival was increased to 70% (P0.01). Similar beneficial effects were obtained when chemotherapy was administered 2 days prior to surgery. The peri-operative chemotherapy group showed 8% (2/26) local recurrence, 4% axillary metastasis, and 0% lung metastasis. Proportion of mice without any evidence of disease increased to 92% (P0.00001). Chemotherapy given 4 days postoperatively resulted in 63% (10/16) local recurrence, 38% axillary metastasis, and 6.3% lung metastasis. Only 38% of the mice were disease-free. Thus in the model studied, perioperative chemotherapy offers the best chance for reduced recurrence and for improved disease-free survival.

The role of neck muscles in the body's response to the "whiplash" type of motion which occurs during frontal impact has been studied. This type of motion was simulated by a sudden backward pull of a subject's head. Head and neck response to low-level acceleration has been researched by recording the externally applied force, the head accelerations in the median sagittal plane, and the electrical activity in the sternomastoid muscle (EMG) as functions of time. The resultant acceleration-time curve and recorded EMG have been analyzed, with numerical values of applied resistance to the external force recorded. An analog computer model was built incorporating resistance developed by two main variable: 1) the elasticity coefficient; 2) the active damping factor. Together these two variables, combined with a resistance function, enable us to measure the resistance of the head/neck response. Using this model, variations in magnitude of these two components were studied under six varying conditions of impact: 1) length of warning time; 2) type of instruction given to the subject; 3) amount of previous experience on the part of the subject in similar situations; 4) anticipation of impact by the subject; 5) magnitude and kind of impact; 6) presence or absence of a preload.

This article reviews the reasons for prolonged hospital stay following interval laparoscopic sterilization from an international data set. If longer hospital stays were to be a frequent occurrence, this procedure, generally an outpatient procedure, could drain scarce hospital resources in developing countries. Among 18,900 interval laparoscopic sterilizations performed in 1971-78, 64 women remained in the hospital for 3 or more nights after the procedure. Laparotomy required during the procedure was the reason for the prolonged stay in 36 (56.2%) of the 64 cases. The majority of these cases involved bleeding, surgical difficulties, and bowel or bladder injury. The remaining 28 women were kept in the hospital for observation for various reasons, including anesthesia-related problems, bleeding, abdominal or back pain, suspected bowel or bladder injury, and suspected uterine perforation. 45 (70.3%) of the 64 cases received general anesthesia compared with 28.6% of the women who did not require prolonged hospitalization. The longest hospital stay was 32 days, and there were no deaths in this series. The overall incidence of prolonged hospitalization was 3.4/1000 procedures. The incidence was lowest for the most commonly used tubal occlusion techniques (electrocoagulation, clip, tubal ring) and highest for newer methods such as needlescopy electrocoagulation and the EL Kady method. In addition, risk factors such as obesity and abnormal pelvic conditions were observed more frequently amoung the women with prolonged hospital stays. These results indicate that prolonged hospitalization following interval laparoscopic sterilization is a rare event and is most often associated with laparotomy.

Any blow to the head may be injurious because it is the manner of response to the blow rather than the blow itself that produces the injury potential. Impacts to inanimate objects or to the heads of anesthetized animals produce data that are simplified by the fact that the involved mass is a constant, and the contact time is consistently negligible. On the football field, all the muscles in the body of the player are tensed at the snap of the ball, and the involved mass varies widely during the resulting prolonged contact time. This causes variable accelerations, variable forces and variable velocity changes as well as a varying mass which can only be measured, therefore, according to the impulse momentum theorem, Ft = deltaMV.

Statistics on catastrophic head and neck injuries in football provide a more realistic indication of the incidence of serious injuries occurring on the football field than do the fatality figures. These statistics, however, provide no clues for preventing such injuries. Moreover, research using head models, anesthetized animals, cadaveric heads, and estimates of brain tolerance to impact based on studies of actual injuries to the heads of humans has produced conflicting data with respect to the goal of improving the safety record of the sport. To reconcile the data and to provide some solutions to the problem of serious injuries on the playing field, we reviewed the data collected in the laboratory and correlated it with the information obtained from telemetry studies. As a result of combining these two data sources, we concluded that injuries on the playing field occur at either end of the spectrum of offered resistance: when too much resistance is offered and when little or no resistance is offered. We demonstrated that, by avoiding either of these extremes, serious injuries to the head and neck can be reduced considerably. Finally, we discussed the importance of preprogrammed responses by the experienced, well-conditioned athlete. These allow the athlete to avoid either extreme of resistance and, thereby, protect him from injury. Clearly, the data obtained from laboratory and telemetry studies will prove instrumental in effecting changes in the sport of football. As a result of these studies, we can hope for alterations in the design of the helmet, enlightened coaching techniques, and rule revisions--all of which will serve to make football a safe sport.

We report two patients with inflammatory bowel disease in whom intravenous corticotropin therapy was complicated by bilateral adrenal hemorrhage. In one, the initial presentation was acute and unilateral, simulating colonic perforation and/or abscess. The diagnosis was made only at exploratory laparotomy. In the second patient, the presentation was subacute; multiple episodes of adrenal hemorrhage occurred subsequent to the course of corticotropin, and ultimately, hypoadrenalinism developed. Pertinent clinical and computed tomographic findings are reviewed.