Measurement of Carboxyhemoglobin and Methemoglobin by Pulse Oximetry: A Human Volunteer Study

Background: A new eight-wavelength pulse oximeter is designed to measure methemoglobin and carboxyhemoglobin, in addition to the usual measurements of hemoglobin oxygen saturation and pulse rate. This study examines this device's ability to measure dyshemoglobins in human volunteers in whom controlled levels of methemoglobin and carboxyhemoglobin are induced.

Methods: Ten volunteers breathed 500 ppm carbon monoxide until their carboxyhemoglobin levels reached 15%, and 10 different volunteers received intravenous sodium nitrite, 300 mg, to induce methemoglobin. All were instrumented with arterial cannulas and six Masimo Rad-57 (Masimo Inc., Irvine, CA) pulse oximeter sensors. Arterial blood was analyzed by three laboratory CO-oximeters, and the resulting carboxyhemoglobin and methemoglobin measurements were compared with the corresponding pulse oximeter readings.

Results: The Rad-57 measured carboxyhemoglobin with an uncertainty of +/-2% within the range of 0-15%, and it measured methemoglobin with an uncertainty of 0.5% within the range of 0-12%.     

Partial Adrenalectomy for Renal Cell Carcinoma With Bilateral Adrenal Metastases

Resection of the adrenal glands precludes participation in many immunotherapy protocols for metastatic renal cell carcinoma. We performed radical nephrectomy with adrenalectomy and contralateral partial adrenalectomy, including adrenal vein ligation for a 4 cm. hilar metastasis without perioperative complications or local recurrence after 30 months. Adrenal function, measured by cosyntropin stimulation tests 6 weeks and 10 months postoperatively, was normal. Partial adrenalectomy with preservation of adrenal function is possible.     

Development of HPLC plasma assays for CAM 4515 and CAM 4750, two new nonpeptide tachykinin antagonists, and application to bioavailability studies

CAM 4515 and CAM 4750 are new nonpeptide tachykinin NK₁ receptor antagonists with different lipophilicities. Two separate, simple, and sensitive HPLC methods for the quantitation of these two compounds in plasma and the evaluation of their oral bioavailability in rats were developed and validated. Extraction of CAM 4515 from plasma involved protein precipitation with acetonitrile, while that for CAM 4750 involved a one-step liquid-liquid extraction with methylene chloride. The analytes in extracts were chromatographed on a C18 column using two different separation buffers, 47% 0.02 M sodium citrate (pH 3.5)-53% acetonitrile for CAM 4515 and 59% 0.02 M potassium phosphate dibasic (pH 7.0)-41% acetonitrile for CAM 4750, and both compounds were detected by fluorescence (excitation 278 nm; emission 342 nm). Stability profiles of both drugs at −20°C or room temperature in plasma and in reconstituted buffers were good. The limit of quantitation for both drugs was 5 ng ml⁻¹ with good linearity from 5 to 1000 ng ml⁻¹ using 100–200 μl of plasma. Excellent precision (relative standard deviation < 8.3%) and accuracy (relative error ± 9.2%) were observed for both CAM 4515 and CAM 4750. Oral bioavailability studies were conducted for each compound in rats receiving a p.o. dose of 20 mg kg⁻¹ and an i.v. dose of 5 mg kg⁻¹. The absolute oral bioavailability of CAM 4750 (80%) was estimated to be 40-fold greater than that of CAM 4515 (2%). The experimental results suggest that incorporation of a pyridine group into the structural backbone may greatly improve bioavailability.     

Pleiotropy in Coffin-Lowry syndrome: Sensorineural hearing deficit and premature tooth loss as early manifestations

We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin-Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These “;new”; clinical manifestations expand the phenotype of Coffin-Lowry syndrome and constitute an additional indication of pleiotropy. © 1993 Wiley-Liss, Inc.     

In VivoStudies of Adenovirus-Based p53 Gene Therapy for Ovarian Cancer

Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD₁₀₀dose of 1 × 10⁷cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 10⁸pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 10⁸pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.     

A dosage study of the effect of the 21-aminosteroid U74006F on chronic cerebral vasospasm in a primate model

The efficacy of the 21-aminosteroid U74006F was investigated using different dosages in a restricted, randomized, placebo-controlled trial. Forty cynomolgous monkeys were divided into five groups of eight. There were two groups given treatment with placebos, one being saline and the other the vehicle in which U74006F was delivered. There were three U74006F treatment dosage groups: 0.3, 1.0, and 3.0 mg/kg. Each monkey underwent baseline cerebral angiography followed by right-sided craniectomy and subarachnoid placement of a clot around the middle cerebral artery (MCA). Treatment was administered intravenously every 8 hours for 6 days. Seven days after experimental subarachnoid hemorrhage, angiography was repeated, and the animals were killed. In both saline or vehicle placebo treatment groups, significant vasospasm (VSP) occurred on the clot side in the extradural internal carotid artery (C3), the intradural internal carotid artery, the precommunicating segment of the anterior cerebral artery (A1,) and the MCA (P less than 0.01). After U74006F treatment, significantly less VSP developed in the A1 on the clot side (0.3 mg/kg U74006F treatment group) and the MCA (all U74006F treatment groups, P less than 0.05). When the percentages of change from the baseline for the vessel diameters on the clot side were compared, VSP was attenuated in the A1 (P less than 0.05) and MCA (P less than 0.001) of all U74006F treatment groups as compared with the placebo treatment groups. Only 0.3 mg/kg of U74006F significantly prevented VSP in C3 (P less than 0.01). Although the 0.3 mg/kg dosage appeared to have the most favorable effect, no significant differences were observed among the three dosage groups. Electron microscopy of the MCA on the clot side in the animals treated with U74006F still showed luminal convolutions and morphological changes in the endothelial cells. These changes appeared less prominent in those MCAs with milder VSP. If these results in primates are applicable to humans, U74006F would be useful in reducing VSP after aneurysmal subarachnoid hemorrhage.     

Venous disease: investigation and treatment,fact or fiction?

This review looks at some clinical and experimental methods and treatments used in venous disease, and attempts to dispel some myths which have been associated with it. Over the last century numerous techniques have been introduced to aid the understanding of the physiology of normal legs and the pathophysiology of those with venous disease. Tourniquet testing along with clinical examination remains the only method of venous assessment in most hospitals. Venous ulceration in the past has been associated with deep vein incompetence, but the newer, non-invasive techniques of Doppler ultrasound and duplex examination are now identifying patients with leg ulceration who have superficial venous insufficiency and therefore a surgically correctable condition. Perforating veins and their possible role in the aetiology of venous ulceration along with invasive and non-invasive methods for their detection is reviewed. Some of the conservative compression treatments and dressings available for the treatment of venous ulceration are discussed. It is concluded that adherence to sound surgical principles remains the mainstay of the successful management of patients with venous disease.     

Ocular molecules and cells that regulate immune responses in situ

Regulation of T cell-dependent immune responses is mediated in part by bone marrow-derived antigen presenting cells (APC) that (a) process and present antigens which engage the T cell receptor and (b) secrete cytokines that influence the threshold of T cell activation. The anterior chamber of the eye is lined by the corneal endothelium (which rests on a stroma and epithelium that is devoid of class II MHC + APC) and iris/ciliary body (which contain significant numbers of bone marrow-derived cells, one third of which are class II MHC +). When tested in vitro, these potential APCs fail to present antigens in a form that activates T cells. Moreover, iris/ciliary body cells actually suppress activation of T cells exposed to antigens on conventional APC. In addition, aqueous humor under normal circumstances contains factors (one of which is TGF_B) that are potent inhibitors of antigen-driven T cell activation, but spare other aspects of T cell function. Evidence suggests that the bone marrow-derived cells in iris/ciliary body are the source of this factor. Thus, the anterior chamber contains powerful forces that can prevent induction and can suppress expression of T cell mediated immunity. It is proposed that these forces are responsible for immunologic privilege and anterior chamber associated immune deviation, and for suppressing pathologic proliferation and inflammation in the anterior segment of the eye.