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Biomedical subjects

J Milliken

Publications and source records attributed to J Milliken.

At least 19 recordsLinked to original sources

Broadband diffuse optical spectroscopy measurement of hemoglobin concentration during hypovolemia in rabbits.

Serial blood draws for the assessment of trauma patients' hemoglobin (sHgb) and hematocrit (sHct) is standard practice. A device that would allow for continuous real-time, non-invasive monitoring of hemoglobin and tissue perfusion would potentially improve recognition, monitoring and resuscitation of blood loss. We developed a device utilizing diffuse optical spectroscopy (DOS) technology that simultaneously measures tissue scattering and near-infrared (NIR) absorption to obtain non-invasive measurements of oxy- (Hb-O(2)), deoxyhemoglobin (Hb-R) concentrations and tissue hemoglobin concentration (THC) in an animal model of hypovolemic shock induced by successive blood withdrawals. Intubated New Zealand White rabbits (N = 16) were hemorrhaged via a femoral arterial line every 20 min until a 20% blood loss (10-15 cc kg(-1)) was achieved to attain hypovolemia. A broadband DOS probe placed on the inner thigh was used to measure muscle concentrations of Hb-O(2) and Hb-R, during blood withdrawal. THC and tissue hemoglobin saturation (S(T)O(2)) were calculated from DOS [Hb-O(2)] and [Hb-R]. Broadband DOS-measured values were compared against traditional invasive measurements: systemic sHgb, arterial oxygen saturation (S(a)O(2)) and venous oxygen saturation (S(v)O(2)) drawn from arterial and central venous blood. DOS and traditional invasive measurements versus blood loss were closely correlated (r(2) = 0.96) showing a decline with removal of blood. S(T)O(2) and [Hb-O(2)] followed similar trends with hemorrhage, while [Hb-R] remained relatively constant. These measurements may be limited to some extent by the inability to distinguish between hemoglobin and myoglobin contributions to DOS signals in tissue at this time. Broadband DOS provides a potential platform for reliable non-invasive measurements of tissue oxygenated and deoxygenated hemoglobin and may accurately reflect the degree of systemic hypovolemia and compromised tissue perfusion.

Animals↗

Two-dimensional and 3-dimensional optical coherence tomographic imaging of the airway, lung, and pleura.

BACKGROUND: Methods for obtaining real-time in vivo histologic resolution by means of noninvasive endoscopic optical imaging would be a major advance for thoracic surgical diagnostics and treatment. Optical coherence tomography is a rapidly evolving technology based on near-infrared interferometry that might provide these capabilities. The purpose of this study is to investigate the feasibility of real-time 2- and 3-dimensional optical coherence tomographic imaging of airway, pleural, and subpleural lung tissues in normal, inflammatory, and malignant animal models and patients with known or suspected airway malignancy. METHODS: Freshly excised lungs and pleural tissue obtained from rabbits with inhalation lung injury and induced empyema, metastatic sarcomas, and pleural sarcomas and from patients with airway disease were imaged by using 2- and 3-dimensional optical coherence tomography with a prototype superluminescent diode optical coherence tomographic system constructed in our laboratory. Lungs and pleural tissue were subsequently processed for standard hematoxylin and eosin histology for comparison with optical coherence tomography. RESULTS: Optical coherence tomographic imaging achieved an ex vivo resolution of 10 microm and an in vivo resolution of about 30 microm with a depth penetration of 1 to 2 mm with 2- and 3- dimensional reconstruction capabilities. Tumors as small as 500 microm were detectable with optical coherence tomography. The acquired images closely matched histologic images, demonstrating details at the level of mucosal layers, glands, alveoli, and respiratory bronchioles. CONCLUSIONS: Optical coherence tomography with near-infrared interferometric methods enables near real-time in vivo near-histologic resolution optical imaging. With further advances, optical coherence tomography has the potential for real-time accurate and early pleural and subpleural diagnostics by using small-diameter flexible fiberoptic endoscopic probes for a wide range of thoracic surgical applications.

Animals↗

Behavioral risk reduction in a declining HIV epidemic: injection drug users in New York City, 1990-1997.

OBJECTIVES: This study assessed trends in HIV risk behaviors among injection drug users in New York City from 1990 to 1997. METHODS: Injection drug users were recruited continuously from a large drug detoxification treatment program (N = 2588) and a research storefront located in a high-drug-use area (N = 2701). Informed consent was obtained, and a trained interviewer administered a structured interview covering sociodemographics, drug use history, HIV risk behavior, and participation in syringe exchange. RESULTS: Trends were assessed for 5 risk behaviors in the 6-month period before the interview. The 3 injection risk behaviors declined significantly over time at each site (all P < .01). When data were pooled across sites, all 5 risk behaviors declined significantly over time (all P < .01). Participation in syringe exchange programs and in HIV counseling and testing increased greatly from 1990 to 1997. CONCLUSIONS: The continuing risk reduction among injection drug users indicates a "declining phase" in the large HIV epidemic in New York City. HIV prevention programs appear to be making an important contribution to the declining phase.

Adult↗

Audio-computer interviewing to measure risk behaviour for HIV among injecting drug users: a quasi-randomised trial.

BACKGROUND: We aimed to assess audio-computer-assisted self-interviewing (audio-CASI) as a method of reducing under-reporting of HIV risk behaviour among injecting drug users. METHODS: Injecting drug users were interviewed at syringe-exchange programmes in four US cities. Potential respondents were randomly selected from participants in the syringe exchanges, with weekly alternate assignment to either traditional face-to-face interviews or audio-CASI. The questionnaire included items on sociodemographic characteristics, drug use, and HIV risk behaviours for 30 days preceding the interview. We calculated odds ratios for the difference in reporting of HIV risk behaviours between interview methods. FINDINGS: 757 respondents were interviewed face-to-face, and 724 were interviewed by audio-CASI. More respondents reported HIV risk behaviours and other sensitive behaviours in audio-CASI than in face-to-face interviews (odds ratios for reporting of rented or bought used injection equipment in audio-CASI vs face-to-face interview 2.1 [95% CI 1.4-3.3] p=0.001; for injection with borrowed used injection equipment 1.5 [1.1-2.2] p=0.02; for renting or selling used equipment 2.3 [1.3-4.0] p=0.003). INTERPRETATION: Although validation of these self-reported behaviours was not possible, we propose that audio-CASI enables substantially more complete reporting of HIV risk behaviour. More complete reporting might increase understanding of the dynamics of HIV transmission and make the assessment of HIV-prevention efforts easier.

Adult↗

Reduction aortoplasty for moderately sized ascending aortic aneurysms.

Enlargement of the ascending aorta may coexist with concomitant valvular, coronary, or other cardiac diseases. If dilation is moderate (i.e., <6 cm diameter) and another cardiac procedure is being performed, we have reduced the diameter of the ascending aorta with an S-shaped incision and excision of the curves of the "S" as a modified Z-plasty. We have performed the procedure in 23 patients with concomitant procedures including aortic valve replacement in 21 (1 as a pulmonary autograft), coronary bypass in 1, and resection of subaortic stenosis in 1. There were 15 males and 8 females with a mean age of 53 years (range 8-67 years). The mean maximal preoperative diameter on transesophageal echocardiography was 5.0+/-0.7 cm (range 3.2-6.6 cm). The mean intraoperative postreduction diameter was 3.1+/-0.6 cm (range 2.1-4.1) (p<0.01). All patients tolerated their procedures well. Sixteen patients were studied by transthoracic echocardiography postoperatively. These patients had a mean intraoperative postreduction diameter of 2.9+/-0.65 cm that increased to 3.1+/-0.45 cm (p = NS) after a mean follow-up of 9.9+/-12.6 months. Of these, seven patients were studied >1 year postoperatively. Their mean intraoperative postreduction diameter of 2.9+/-0.5 cm increased to 3.1+/-0.35 cm (p = NS) after a mean follow-up of 22.1+/-9.2 months. No known recurrences of the aneurysms have occurred. We feel this technique is valid in patients with moderate aortic dilation undergoing concomitant cardiac procedures and in whom more aggressive aortic interventions are not warranted.

Adolescent↗

Intra-aortic balloon pump: indications and complications.

Results obtained with intra-aortic balloon pumps (IABPs) at Harbor-UCLA Medical Center from 1990 to 1995 were reviewed to analyze the indications for its use as well as the incidence and types of vascular complications that occurred. Of 86 patients (53 men and 33 women) in whom pumps were used, 66 underwent coronary bypass, 14 underwent valve replacement, and 6 underwent both coronary bypass/valve replacement. Thirteen (15%) deaths occurred (8 coronary bypass patients, 4 valve replacement patients, and 1 coronary bypass/valve replacement patient). The indications for IABP were broadly classified as prophylactic or inability to wean. Prophylactic IABP placement preoperatively occurred in 35 (41%) patients for profound ventricular dysfunction (27 patients), compelling coronary anatomy including critical left main disease (7 patients), and unstable angina (1 patient). Inability to wean occurred in 51 (59%) patients. Three patients (3.5%) developed major vascular complications resulting in limb ischemia. All three underwent thrombectomies, fasciotomies, and above-knee amputations; two patients subsequently died. Vascular reconstruction was performed in two patients as a direct result of their vascular process. All three vascular complications occurred in women. Besides gender, there was no difference between IABP patients with or without vascular complications in terms of age or presence of diabetes, hypertension, smoking history, obesity, or known peripheral vascular disease. These results indicate that IABPs are effective both prophylactically and intraoperatively in patients who would not otherwise survive cardiac surgery.

Coronary Artery Bypass↗

Prognostic significance of c-erbB-2 oncogene in axillary node-negative breast cancer.

BACKGROUND: With the advent of screening mammography more breast cancer will be detected at an earlier stage, apparently confined to the breast with no nodal involvement. However, 30% of these will recur due to micrometastases present at the time of diagnosis. Chemotherapy and tamoxifen have been shown to improve disease-free survival in axillary node-negative patients but not overall survival. In the search for a useful predictor of breast cancer recurrence the relationship between c-erbB-2 expression and recurrence and survival was examined. METHODS: Eighty-eight axillary node-negative breast cancer patients were followed up for at least 5 years. RESULTS: There was a significant relationship between c-erbB-2 expression and both tumour recurrence (P<0.001) and poorer survival (P=0.003). In a Cox multiple regression analysis, c-erbB-2 staining remained the only significant prognostic variable for recurrence (P=0.002) and survival (P=0.032). Tumour recurrence in c-erbB-2-positive cases tended to occur early in the course of follow up and was associated with poorer survival. CONCLUSION: C-erbB-2 was found to be a useful prognostic indicator for early recurrence and poorer survival in axillary node-negative breast cancer patients.

Adult↗

Extracorporeal methods of vascular control for difficult IVC procedures.

Surgical procedures in the juxtaheptic and intrapericardial inferior vena cava (IVC) are difficult because of the complexity of achieving vascular control in the area. We describe 10 patients with a variety of pathologies in this region who underwent venovenous bypass (VVB) or cardiopulmonary bypass with hypothermic circulatory arrest (CBCA). Renal cell carcinoma with IVC extension was present in three patients (with tumor extension into the right atrium in two), adrenal adenocarcinoma in one, septic IVC thrombus in one, and blunt IVC/hepatic trauma in five. Those patients without atrial involvement underwent VVB with a mean bypass time of 40 minutes (range 12-144). Those patients with tumor extension into the right atrium underwent CBCA with systemic hypothermia to 18(0)C, total body exsanguination for a bloodless field, and removal of the tumor by cavotomy and right atriotomy. The mean bypass, aortic cross-clamp, and circulatory arrest times were 152, 92, and 36 minutes, respectively. Eight of the 10 patients did well and went home within 4 weeks of surgery. Two patients died, one from metabolic sequelae of exsanguinating IVC injury (VVB) and one from sepsis 2 weeks postoperatively (CBCA).

Adult↗

Modified venovenous bypass technique for resection of renal and adrenal carcinomas with involvement of the inferior vena cava.

Peripheric tumours with extension into the inferior vena cava pose difficult management problems. Venovenous bypass using a centrifugal pump to decompress the inferior vena cava may be useful adjunct during vascular isolation of the tumour. We have modified the technique by adding portal decompression to avoid visceral accumulation of toxic metabolites. We have used this technique in two patients who had intracaval extension of tumours, one renal and one adrenal carcinoma.

Adenocarcinoma↗

Survival after trauma pneumonectomy: the pathophysiologic balance of shock resuscitation with right heart failure.

Emergency pneumonectomy for trauma has a high mortality. Although exsanguination is a major factor leading to death, mortality remains high even after adequate resuscitation and is thought to be related to pulmonary edema and right heart failure. We present a series of nine patients who underwent pneumonectomy at Harbor-UCLA from penetrating (7) and blunt (2) trauma. Two patients survived; three initially survived the surgery but died postoperatively of hypoxemia and right heart failure; four died intraoperatively (2 from right heart failure and 2 from exsanguination). One survivor required open cardiac massage for asystole. Careful attention to prevent volume overloading before and during trauma pneumonectomy and maintaining a negative fluid balance postoperatively may contribute to survival in these patients.

Adolescent↗

Feasibility of ultrafast computed tomography in the early evaluation of coronary bypass patency.

Although ultrafast computed tomography (UFCT) is able to determine coronary artery bypass graft (CABG) patency, the clinical applicability in the early postoperative period has not been investigated. We prospectively studied 22 consecutive patients who developed angina-like chest pain, electrocardiogram (EKG) abnormalities, elevated creatine phosphokinase-MB fractions (CPK-MB fractions) (> 5%), or sudden cardiac death in the early post-CABG period. UFCT (flow mode) examinations from 4 to 28 days postoperatively were performed at six levels with 13 scans each. Indications for obtaining UFCT included chest pain (14), elevated CPK-MB (14), EKG abnormalities (10), and aborted sudden cardiac death (1). There were 78 grafts evaluated with 87 distal anastomoses. Sixty were saphenous vein grafts (SVG), 16 were left internal mammary artery (LIMA) grafts, 1 was a free right internal mammary artery (RIMA), and 1 was a right gastroepiploic artery. The 60 SVG included 9 sequential grafts with 18 distal anastomoses. UFCT identified 5 occluded nonsequential SVG and of these, 3 underwent coronary angiography confirming the UFCT findings. Visualization was inadequate to determine patency in 5/17 internal mammary artery (IMA) grafts, and all 5 were in the early part of this study and felt to be related to UFCT image protocol. All sequential grafts were determined to be patent on UFCT, although visualization was inadequate to determine if one or both of the outflow distal anastomoses were patent. Our series shows early nonsequential SVG occlusion at 5/51 (9.8%) in patients with postoperative clinical signs of possible graft occlusion. UFCT to determine the patency of proximal grafts is feasible in the early postoperative period. If UFCT is indeed a valid test for graft patency, then this study implies that most signs and symptoms of ischemia in the early postoperative period may not represent graft occlusion.

Adult↗

Syringe exchange: HIV prevention, key findings, and future directions.

HIV among injecting drug users (IDUs) has now been documented in over 60 countries in the world, and there are an additional 40 countries where injecting drug use has been reported including widespread epidemics in Southeast and southern Asia and in Latin America. At present HIV infection is almost always fatal, and there is no promise that a preventive vaccine will become available soon. Given the enormity of the HIV epidemic among IDUs and the critical need to reduce the spread of HIV transmission to and from IDUs, prevention efforts are essential. Syringe-exchange programs have become a major component of HIV prevention strategies in most developed countries and work within the philosophy of harm reduction. Increasing access to sterile syringes has been met with considerable controversy. Opponents of syringe exchange have generally argued that increasing access to sterile syringes would simultaneously increase the number of injecting drug users, increase the frequency of injection for already active IDUs, and appear to "condone" an illegal behavior. To date many research studies and four major reviews of syringe exchange literature have been conducted. All studies thus far have shown no increase in illicit drug injection associated with syringe exchanges, and significant decrease in drug risk behaviors.

Cross-Sectional Studies↗

Immunocytochemistry and in situ hybridisation of epidermal growth factor receptor and relation to prognostic factors in breast cancer.

The breast tumour distribution of epidermal growth factor receptor (EGFR) was studied in 193 patients with primary breast cancer by immunocytochemistry on frozen sections. EGFR was correlated (P = 0.0009) with growth fraction assessed by Ki-67, and negatively correlated with oestrogen receptor (ER, P = 0.0001) and progesterone receptor (PR, P = 0.0001) status. In 47 patients, in-situ hybridisation for EGFR mRNA showed good agreement with the immunocytochemically assessed EGFR protein. There were, however, several tumours in which EGFR mRNA could be detected in the absence of EGFR protein and there were differences between the ER and PR status of those tumours in which translation of EGFR mRNA was not seen. The cause of these differences is unclear, but these findings may represent a clue as to the differential control of breast cancer cell receptors.

Adult↗

A comparison between Ki-67 antibody reactivity and other pathological variables in breast carcinoma.

Methods of assessing tumor proliferation rates include mitosis counting, flow cytometry and thymidine labelling. While the former is inaccurate and poorly reproducible, the latter methods are time consuming and expensive to perform. Ki-67 is a monoclonal mouse antibody which has been shown to react with a nuclear antigen in proliferating cells. Frozen sections from 75 specimens of breast carcinoma were immunostained with this antibody using an immunoperoxidase technique. The percentage of tumor cells stained, the Ki-67 score, was then compared with a number of pathological and clinical variables in the patients concerned. A positive correlation was seen between the Ki-67 score and mitotic rate (r = 0.71); and a negative correlation was seen between Ki-67 score and estrogen receptor status (r = -0.4). Ki-67 immunostaining may represent a cheap and reproducible method of assessing proliferation rates of breast carcinomas which is applicable in routine laboratories. Further prospective studies are being undertaken to assess its contribution to prognosis.

Adult↗