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Biomedical subjects

J Freeman

Publications and source records attributed to J Freeman.

At least 19 recordsLinked to original sources
PubMed1992

A noninvasive method of predicting pulmonary-capillary wedge pressure.

BACKGROUND: The noninvasive prediction of pulmonary-capillary wedge pressure (PCWP) is important for the recognition and treatment of a variety of cardiovascular disorders. The response of the arterial pressure to the Valsalva maneuver has been shown to correlate with the PCWP. We therefore devised a noninvasive method to measure this pressure response at the bedside and correlated these measurements with the PCWP measured directly with a pulmonary-artery catheter. METHODS: Simultaneous, blinded, noninvasive measurements of the ratio of the final amplitude to the initial amplitude of the pulse wave form during the stress phase of the Valsalva maneuver (pulse-amplitude ratio) and direct measurements of the PCWP were obtained in 20 clinically stable patients and in 14 clinically unstable patients who were receiving vasoactive agents, 12 of whom also had endotracheal tubes in place. RESULTS: Using linear regression analysis, we found that the pulse-amplitude ratio strongly correlated with the measured PCWP over a range of base-line values from 4 to 32 mm Hg for the 20 clinically stable patients (R2 = 0.80) and the 14 clinically unstable patients (R2 = 0.85). The method also correctly predicted changes in the PCWP after the administration of nitroglycerin or furosemide and after expansion of the intravascular volume (R2 = 0.79). CONCLUSIONS: These preliminary data indicate that a simple noninvasive method can accurately predict the PCWP and changes in the PCWP in response to medical therapy.

Blood Pressure↗
PubMed1992

Tumors arising in SCID mice share enhanced radiation sensitivity of SCID normal tissues.

We addressed the question of whether cancers arising in an abnormally radiation sensitive normal tissue are also abnormally sensitive to ionizing irradiation. Germ line mutation-carrying mice with an enhanced radiation sensitivity of the normal tissue, the severe combined immunodeficient (SCID), and normally radiation sensitive mice (C3H) were used to study the sensitivity of normal and tumor tissues in vivo and in vitro. The lethal dose for 50% of the irradiated animals after single dose whole body irradiation was 2.6-fold higher in C3H compared to SCID mice. The dose for an isoeffective acute skin reaction after single dose irradiation was end point dependent 1.7 to 3.7 times higher in C3H than in SCID mice. Embryonic fibroblast and methylcholanthrene induced soft tissue sarcomas derived from C3H and SCID mice were established in vitro and colony-forming assays after single dose irradiation were carried out. Choosing mean inactivation dose as the end point, SCID fibroblast lines were 3.0-fold and SCID tumor cell lines 2.7-fold more radiation sensitive than C3H fibroblast lines and C3H tumor cell lines. Tumor control and growth delay assays for 110-mm3 tumors were used to compare the radiation sensitivity of SCID and C3H tumors in vivo. The doses for 50% local tumor control and a growth delay of 40 days were 2.6 times higher in C3H tumors compared to SCID tumors. Tumors arising in an abnormally radiation sensitive normal tissue are also sensitive to irradiation. The difference in radiation sensitivity of normal tissues predicted the difference in tumor tissues in these two murine systems.

Animals↗
PubMed1992

High expression of transforming growth factor-beta long cell cycle times and a unique clustering of S-phase cells in patients with acute promyelocytic leukemia.

Expression of transforming growth factor-beta (TGF-beta), which inhibits the proliferation of hematopoietic progenitors, was investigated simultaneously with cell cycle characteristics in 63 bone marrow biopsies from 23 cases with acute promyelocytic leukemia (APL). Bromodeoxyuridine (BrdU) was administered to every patient (17 newly diagnosed) for determination of the labeling index (LI) and the durations of S-phase (Ts) and the cell cycle (Tc) of leukemic promyelocytes. APL cases had lower LI both in the bone marrow aspirate (6.1% v 11.4%, P = .008) and biopsy (21.1% v 28.0%, P = .001) and longer Tc (93.6 hours v 56.0 hours, P = .002) when compared with other French-American-British subtypes. TGF-beta expression (detected by a monoclonal anti-TGF-beta 2/beta 3 antibody) was dramatically high, especially in interstitial areas of the biopsies. S-phase cells were found as geographically restricted islands of proliferation (GRIPs) in 20 of 22 cases. Weekly biopsies showed an increment in TGF-beta on day 7 of therapy in 13 of 17 cases, while in vivo differentiation was noted in 9 of 15. We conclude that the presence of high TGF-beta expression may explain the biologic basis for the slowly cycling nature of leukemic promyelocytes in APL as well as the unique clustering of S-phase cells observed in GRIPs.

Adult↗
PubMed1992

Abnormal regulation of the myc gene in myeloid leukemia.

To study the regulation of expression of the myc protooncogene, cells from normal individuals and patients with acute myelogenous leukemia (AML), and chronic phase and blastic crisis of chronic myeloid leukemia (CML) cells were put in overnight culture in the presence or absence of fetal calf serum. Myc expression in normal marrow cells and chronic phase CML cells fell after culture in vitro. In contrast, myc expression was maintained or increased in a majority of the AML and blastic crisis CML specimens. These data demonstrate that the regulation of myc expression is disordered in many AML and blastic crisis specimens but not in chronic phase CML cells.

Base Sequence↗
PubMed1992

Cutaneous copper and zinc losses in burns.

To measure the exudative cutaneous copper (Cu) and zinc (Zn) losses in burns, 10 patients, aged 36 +/- 9 years (mean +/- s.d.) with burns covering 33 +/- 10 per cent of the total body surface area, were studied from the first postburn day (D1) until D7. All intakes and losses were analysed for Cu, Zn and nitrogen (N) content. Cutaneous losses were extracted from textiles surrounding the patients. Urinary excretions were 0.12 +/- 0.06mg/24h for Cu, 0.9 +/- 0.6mg/24h for Zn, and 14.1 +/- 4.4g/24h for N. Mean daily exudative losses through wound seepage from D1 to D7 were 4.7 +/- 2.1mg/24h for Cu, 27.1 +/- 14.4mg/24h for Zn, and 8.7 +/- 3.8g/24h for N. The cumulated mean losses over 7 days were 37mg for Cu, and 212mg for Zn, representing respectively 20-40 per cent and 5-10 per cent of normal body content. Serum Cu and Zn levels were strongly depressed. The urinary Cu/N ratios correlated with clinical improvement. We conclude that the exudative Cu and Zn losses during the first week postburn contribute significantly to the increased nutrient requirements in burns.

Adult↗
PubMed1992

Response of xenografts of human malignant gliomas and squamous cell carcinomas to fractionated irradiation.

The response of xenografts of five human malignant glioma cell lines and two human squamous cell carcinomas to fractionated irradiation was studied. For this, the tumors were transplanted into nude mice which had been further immunosuppressed by 6 Gy whole-body irradiation. Radiation was given as 30 fractions applied under normal blood flow conditions in two sessions per day over 15 days. Absolute and specific tumor growth delay after 48 Gy, and tumor control dose 50% (TCD50) were evaluated. Using local tumor control as experimental endpoint, four out of five malignant gliomas were more resistant to fractionated radiation therapy than the two squamous cell carcinomas. The TCD50s of these four gliomas ranged from 73 Gy to more than 120 Gy, whereas the TCD50s of the squamous cell carcinomas were 51 and 60 Gy. Absolute tumor growth delay correlated well with TCD50, but no correlation was obtained between specific growth delay and TCD50. The response of the human tumor xenografts in vivo did not correlate with the surviving fractions at 2 Gy of the same cell lines in vitro which have been previously obtained in our laboratory. The results suggest that the unique radioresistance observed in malignant gliomas in patients is at least in part reflected in human tumor xenografts. The lack of correlation between the surviving fraction at 2 Gy in vitro and the tumor response in vivo could be a consequence of an immune response by the host, a difference in cell radiation sensitivity between cell lines and xenografted tumors, or of differences of parameters such as hypoxic fraction, rate of repopulation, and cell cycle effects between the different tumor lines studied. It illustrates the difficulties which might be involved in the prediction of the response of individual tumors to radiation therapy based solely on the intrinsic radiosensitivity of the tumor cells as assayed by in vitro assays of colony formation.

Animals↗
PubMed1992

Effects of major depression on estimates of intelligence.

This study examined whether patients with major depressive disorder manifest deficits in intelligence during affective episodes and following clinical improvement. WAIS-R scores were contrasted in 100 patients in an episode of major depression with 50 normal controls, matched to the patient sample in terms of demographic variables and estimates of premorbid IQ. The groups were equivalent in verbal IQ, but, in line with previous studies, the depressed patients had a pronounced deficit in performance IQ. A patient subsample was administered the WAIS-R under unlimited time conditions to determine whether the time constraints of performance IQ subtests contributed to the magnitude of the verbal-performance IQ discrepancy. This discrepancy was only slightly reduced with untimed scoring. Subgroups of depressed patients were retested with the WAIS-R within one week (n = 26) or two months (n = 33) following treatment with electroconvulsive therapy. In both subsamples, IQ scores were improved at posttreatment testing relative to pretreatment, but with little change in the verbal-performance IQ discrepancy. These and related findings suggested that a performance IQ deficit is characteristic of depressed patients regardless of affective state.

Adult↗
PubMed1992

Evaluation of the consistency of Acute Physiology and Chronic Health Evaluation (APACHE II) scoring in a surgical intensive care unit.

OBJECTIVES: To determine the applicability of the Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system in a Swiss ICU, and to evaluate its utility in evaluating data from 2 yrs of consecutive admissions to show that the predictability of outcome is similar to that predictability observed by Knaus et al. in 1985 (in 5,815 patients), with the provision that large numbers of patients are studied. DESIGN: Prospective clinical trial over 2 yrs, with statistical analysis of the Swiss patients, and between the Swiss patients and the patients studied by Knaus et al. Receiver operating characteristic curves were calculated. SETTING: Surgical ICU in a Swiss university hospital. PATIENTS: A total of 2,061 consecutive patients admitted to the surgical ICU who were classified as postoperative (elective or emergency) and nonoperative. Hospital mortality rate was considered. RESULTS: Patients were 53 +/- 16 yrs of age. Mean APACHE II score was 10.5 +/- 7.0. The mean APACHE II score was significantly (p < .001) lower in the 1,813 survivors (9.0 +/- 5.2) than in the 248 nonsurvivors (21.5 +/- 8.5). The mortality rate was higher among the Swiss patients when compared with the patients studied by Knaus et al. who had postoperative scores of 20 to 29 and nonoperative scores of > 24. The distribution of the scores and mortality rates were stable during the two study periods, as were the differences in mortality rates between the Swiss population and that population studied by Knaus et al. Sensitivity and specificity of the scores were highest in the emergency surgery group (87% and 78%), and lowest in the elective surgery group (76% and 73%). The APACHE equation underestimated the risk of death. CONCLUSIONS: The APACHE II score, because of its consistency over time and the stability of the mortality rates, can be used in our surgical ICU without modification. The calculated risk of death gives no additional information.

Adolescent↗
PubMed1992

Thrombolysis with low dose tissue plasminogen activator.

Two cases of vena caval thrombosis in infants were successfully treated with low dose (0.01-0.05 mg/kg/hour) local infusions of tissue plasminogen activator after conventional anticoagulant treatment had been unsuccessful. This approach is useful for clots associated with indwelling intravascular catheters, and a low dose infusion of tissue plasminogen activator as a regional application is recommended to achieve clot lysis with minimal systemic effects.

Catheters, Indwelling↗
PubMed1992

Cough requiring discontinuance of angiotensin-converting enzyme inhibitors in an urban inner-city population.

Angiotensin-converting enzyme (ACE) inhibitors are increasingly used to control hypertension although cough, sometimes severe enough to require discontinuance, is a well-described side effect of these drugs. Manufacturers' labeling indicates that this side effect occurs with a much lower frequency than is reported in the literature. This article describes the incidence of cough as a side effect of ACE inhibitors in a small inner-city practice and presents two reports of patients who required discontinuance of ACE inhibitors for this symptom. It is suggested that, consistent with the recent literature, the incidence of this symptom is more frequent than suggested by manufacturers' labeling, at least in this population.

Aged↗
PubMed1992

Absence of HTLV-I DNA sequences in cutaneous T-cell lymphoma/mycosis fungoides.

Recently, the presence of deleted forms of the HTLV-I provirus was described in 6 out of 6 cases of CTCL. We investigated whether the presence of these viral genomes could be verified in 20 patients with CTCL using the polymerase chain reaction (PCR) and Southern blot analysis. Only one of the 20 cases showed a band corresponding to the pX region of HTLV-I. These data indicate that in the majority of CTCL cases, sequences closely related to HTLV-I are not present, or their copy number is below the limit of detection employed in this study.

Base Sequence↗
PubMed1992

Difficult aeromedical rescue situations: experience of a Swiss pre-alpine helicopter base.

Swiss Air Rescue (REGA) teams execute more than 3000 aeromedical missions annually, of which some require the use of a winch. To evaluate the need for early medical intervention at sites where landing is impossible, we analyzed retrospectively 100 consecutive operations (10.8% of all primary missions, 110 patients) accomplished by the REGA base at Lausanne with an emergency physician of the Centre Hospitalier Universitaire Vaudois (CHUV) on board. In such difficult rescue conditions, time to call, response times, and scene times were particularly long (mean delay to admission: 114 minutes). Fourteen patients were dead on arrival, 22 were uninjured, 50 had NACA Index 1-3 injuries (moderate), 22 had NACA Index 4-6 injuries (severe). Seventeen required major intervention at the site or during rescue. We conclude that in our European pre-alpine region 22% of patients rescued by winch are severely injured. Since rescue actions are particularly long and difficult, the performance of advanced procedures at the scene and during transportation is of great value.

Aircraft↗
PubMed1992

G-induced loss of consciousness accidents: USAF experience 1982-1990.

Discussion of acceleration protection measures should be based on analysis of relevant accident data, including determination of high risk aircraft, G profiles, and pilot descriptions. There were 18 accidents (14 fatalities) attributed to G-induced loss of consciousness (G-LOC) in the United States Air Force (USAF) from 1982 through 1990. All 18 accidents occurred during single crewmember sorties, for an average rate of 2.1 per million single-seat flying hours (pmfh). The average G-LOC accident rate for 1982-4 was 4.0 pmfh, decreasing significantly to 1.3 pmfh for 1985-90. This decrease is associated with the USAF initiation of an anti-G-LOC training program. We reviewed accident records for G-LOC cofactor data and compared them to normal data for USAF pilots for age, height, weight, systolic and diastolic blood pressures, heart rate, total flying time, and aircraft-specific flying hours. Only for systolic blood pressure (higher) and aircraft-specific flying hours (shorter) were the mishap pilots significantly different from other USAF pilots. We found no evidence to support weight training vs. aerobic training, missed meals, or heat in causing G-LOC accidents. Thus the mishap pilots appeared to be a representative cross section of USAF pilots with respect to personal variables. More significant factors appeared to be G duration, G magnitude, use of G trousers, and experience in assigned aircraft.

Accidents, Aviation↗
PubMed1991

Sequence selective binding to the DNA major groove: tris(1,10-phenanthroline) metal complexes binding to poly(dG-dC) and poly(dA-dT).

Molecular modelling and energy minimisation calculations that incorporate solvent effects have been used to investigate the complexation of delta and lambda-[Ru(1,10-phenanthroline]2+ to DNA. The most stable binding geometry for both enantiomers is one in which a phenanthroline chelate is positioned in the major groove. The chelate is partially inserted between neighbouring base pairs, but is not intercalated. For delta, though not for lambda, a geometry with two chelates in the major groove is only slightly less favourable. Minor groove binding is shown to be no more favourable than external electrostatic binding. The optimised geometries of the DNA/[Ru(1,10-phenanthroline]2+ complexes enable published linear dichroism spectra to be used to determine the percentage of each enantiomer in the two most favourable major groove sites. For delta 57 +/- 15% and for lambda 82 +/- 7% of bound molecules are in the partially inserted site.

Base Sequence↗
PubMed1991

A comparison of the results following oromandibular reconstruction using a radial forearm flap with either radial bone or a reconstruction plate.

Fifteen cases of oromandibular reconstruction using a radial osteocutaneous flap were compared with 16 in which the mandible was replaced with a reconstruction plate and a forearm flap was used for intraoral lining. All cases involved oral cancer; most had been irradiated. Nine survived in each group. Complications included one infected nonunion in addition to two bone exposures in the bone group, compared with three cases of plate exposure and two bone exposures in the plate group. Functional results were similar in both, but osteointegrated implants were possible only in the patients receiving bone. Cosmesis seemed somewhat better in the plate group. Donor-site problems were common but minor, and long-term forearm function was slightly reduced in both groups. Although the sample sizes were small, the reconstruction plate together with a radial forearm flap appeared to provide effective reconstruction following composite resection. However, we would not recommend this for the younger patient or in benign disease.

Adult↗
PubMed1991

Therapy of refractory/relapsed acute leukemia with cytosine arabinoside plus tetrahydrouridine (an inhibitor of cytidine deaminase)--a pilot study.

Thirty two patients with refractory or recurrent acute leukemia or blast crisis of chronic myelocytic leukemia were treated with 1-beta-D-arabinofuranosylcytosine (Ara-C), 100 mg/m2 [group I (n = 15)] or 200 mg/m2 [group II (n = 18)], and tetrahydrouridine (THU) 350 mg/m2, given concurrently as a 3 h continuous intravenous infusion at 12 h interval for eight doses. Two of 13 (15.3%) evaluable patients in group I achieved a complete response, both of whom had acute myelocytic leukemia. In group II, seven of 14 evaluable patients (50%) obtained objective responses--six with complete responses (42.8%) and one with partial response (7%). Myelosuppression was seen in all patients with a median duration of 32.5 days (group I) and 36.3 days (group II), respectively. Non-hematologic toxicity consisted of nausea, vomiting, diarrhea, conjunctivitis, skin rash, hepatocellular toxicity, hemorrhage, and renal toxicity. Pharmacokinetic studies revealed, for group I, mean peak plasma Ara-C levels at 3 h (Cp3h) of 1254 ng/ml, area under the curve (AUC) 4651 ng x h/ml, total body clearance (TBC) 32.65 l/h/m2, renal clearance (RC) 7.04 l/h/m2 with a mean of 12.36% of the injected amount of Ara-C excreted unchanged in urine over the first 24 h. The corresponding mean values for group II are Cp3h 3305 ng/ml, AUC 15080 ng x h/ml, TBC 20.48 l/h/m2, RC 7.02 l/h/m2 and 26.23%. Ara-C 200 mg/m2 combined with THU gave serum Ara-C levels and response rates comparable to those achieved with high dose Ara-C (HiDAC) (greater than or equal to 1 g/m2). Central nervous system toxicity associated with HiDAC was not seen. Pharmacokinetics for uracil arabinoside (Ara-U) in patients treated with Ara-C 200 mg/m2 plus THU, were comparable to values seen with Ara-C for Cp3h, AUC and 24 h urine, amounting to 3160 ng/ml, 21717 ng x h/ml and 23.62% whereas TBC was significantly lower (p less than 0.001) for Ara-U than for Ara-C (3.02 versus 20.48 l/h/m2).

Adult↗