Neuralgic amyotrophy or an isolated lesion of the anterior interosseal nerve?]

OBJECTIVE: Considerable evidence exists to suggest that tumor hypoxia results in radioresistance. Historically, it has been difficult to assess tumor oxygen tension levels reliably. These levels can now be assessed in head and neck malignancies using the Eppendorf pO2 histograph, which uses a fine-needle electrode and a computerized micromanipulator. This technology was used to compare the pretreatment tumor oxygen tension level in lymph node metastases of patients with head and neck cancer to measurements taken during nonsurgical treatment after a partial response had been achieved. STUDY DESIGN: Prospective study. METHODS: Oxygen tension levels were measured in the cervical lymph nodes of 10 patients with biopsy-proven head and neck squamous cell carcinoma and cervical metastases who were being treated with nonsurgical management. These levels were obtained using the Eppendorf pO2 histograph system. Measurements were taken before the start of treatment and were repeated when the size of the cervical metastatic node had decreased by 50%. Normal subcutaneous tissue was measured during the same session. The mean and median pO2 levels, as well as the percentage of measurements with pO2 less than 5 mm Hg were determined. RESULTS: A mean of 72.6 measurements per session was taken from each lymph node. The median tumor pO2 measurement fell from a mean (+/-SD) of 13.9+/-8.0 mm Hg to 7.3+/-9.9 mm Hg. Even more dramatic, however, was the substantial increase in the percentage of values less than 5 mm Hg, a rise from 29% to 52%. CONCLUSIONS: While there is variability both in the pretreatment oxygenation of head and neck cervical metastases and in the change in tumor oxygen tension during treatment, there appears to be a decrease in the overall oxygenation of the tumors. The dramatic increase in very low oxygen measurements may reflect selective survival of radioresistant or chemoresistant hypoxic tumor cells. Cells at the very low level would be expected to be radiobiologically hypoxic (resistant to radiation-induced cell kill).     

A 2-week pretreatment with 13-cis-retinoic acid + interferon-alpha-2a prior to definitive radiation improves tumor tissue oxygenation in cervical cancers

BACKGROUND: We have evaluated the tumor tissue pO2 in cervical cancers in patients treated with 13-cis-retinoic acid and interferon-alpha-2a prior to and during radiotherapy. PATIENTS AND METHODS: From June 1995 through April 1997, 22 patients with squamous cell carcinoma FIGO IIB/III of the cervix who were scheduled for definitive radiotherapy with curative intent received additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) plus interferon-alpha-2a (IFN-alpha-2a) as part of a phase-II protocol. cRA/IFN-alpha-2a started 14 days prior to radiotherapy (1 mg per kilogramme body weight cRA orally daily plus 6 x 10(6) IU IFN-alpha-2a subcutaneously daily). After this induction period, standard radiotherapy was administered (external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus HDR-brachytherapy). During radiotherapy, cRA/IFN-alpha-2a treatment was continued with 50% of the daily doses. Tumor tissue pO2-measurements were performed prior to and after the cRA/IFN-induction period as well as at 20 Gy and at the end of radiotherapy with an Eppendorf-pO2-histograph. RESULTS: In 11 out of the 22 patients, pO2-measurements were performed prior to the cRA/IFN-induction therapy. The median pO2 of these untreated tumors was 17.7 +/- 16.3 mm Hg. The relative frequency of hypoxic readings with pO2-values below 5 mm Hg ranged from 0% to 60.6% (mean 24.3 +/- 21.0%). After the 2-week induction period with cRA/IFN, the median pO2 had increased from 17.7 +/- 16.3 mm Hg to 27.6 +/- 19.1 mm Hg (not significant). In all 5 patients with hypoxic tumors prior to cRA/IFN (median pO2 of 10 mm Hg or less), the median pO2 was above 20 mm Hg after the 2-week cRA/IFN-induction. In this subgroup of hypoxic tumors, the median pO2 increased from 6.3 +/- 2.7 mm Hg to 27.0 +/- 5.6 mm Hg (p = 0.004, t-test for paired samples). The frequency of hypoxic readings (pO2-values < 5 mm Hg) decreased from 44.7 +/- 17.1% to 2.0 +/- 2.5% (p = 0.012, t-test for paired samples). There was, however, no obvious volume reduction after 14 weeks of cRA/IFN on clinical examination. A complete clinical remission of the local tumor was observed in 19/22 patients after radiotherapy and additional cRA/IFN-alpha-2a-treatment. In primarily hypoxic tumors (with a median pO2 below 10 mm Hg prior to treatment), 4/5 achieved complete remission. CONCLUSIONS: Pretreatment with cRA/IFN improves oxygenation of primarily hypoxic cervical cancers. The mechanisms of action remain unclear and further investigation of the combination regimen is recommended.     

The minimal sequence needed to define a functional DNA terminator in Bacillus subtilis

BACKGROUND: We wished to determine whether transcutaneous oximetry or laser Doppler flowmetry (LDF) could identify patients at risk for wound failure after conservative, limb-sparing surgery for extremity sarcomas. METHODS: Studies were performed on postoperative days (PODs) 1, 4/5, 7, and 9. Measurements of transcutaneous oxygen pressure (tcPO2) were taken at breathing room air (BL) and 100% oxygen (rate tcPO2). LDF measurements were taken at multiple sites along the wound, and a perfusion index was calculated. RESULTS: Twenty-four patients were studied. Four (17%) had nonhealing wounds. There was no difference in tcPO2 (BL) values between healed and nonhealing wounds. Measurement of rate tcPO2 on POD 1 was significantly lower in the nonhealing wounds than in those with normal healing (28.5 +/- 12.1 mm Hg vs 14.3 +/- 16.2 mm Hg, mean +/- SD, p = 0.03). Rate tcPO2 values increased significantly in healing wounds from POD 1 to PODs 7 and 9 (p = 0.006, p = 0.009). This increase was absent in nonhealing wounds. A clear separation was noted in rate tcPO2 values between groups, with a minimum rate tcPO2 value recorded in a healed wound of 9 mm Hg/min, compared with the maximum value in a nonhealing wound of 7 mm Hg/min. The LDF perfusion index failed to predict wound healing at any of the measured time points. CONCLUSIONS: This study showed that measurement of tcPO2 during oxygen inhalation can accurately predict wound healing in patients after excision of an extremity sarcoma.     

Decline of sexual behavior in castrated male rats: effects of female precopulatory behavior

Ventricle cells from neonatal rats were cultured in a medium preventing cell proliferation on a modified Roller apparatus with a defined pericellular oxygen partial pressure (pO2) of 38 or 0.6 mm Hg for about one week. The cells were harvested after the second and eighth day of culture (corresponding to one or seven days of culture under a defined pO2) and prepared for electron microscopy. Electron micrographs of this material were examined by stereologic techniques. The obtained results showed some deviations of mitochondrial fine structure of heart muscle cells depending on oxygen supply. During cultivation with a pO2 of 0.6 mm Hg (hypoxic conditions) we observed a proportional increase in mitochondria without cristae and an increase in size accompanied by a more irregular shape. On the contrary, the mitochondria of cells cultured with a pericellular pO2 of 28 mm Hg, which we consider to be a normoxic condition, did not show any deviation of inner membrane arrangement, but an increase in number and a decrease of size during cultivation was apparent. The mitochondria-myofibrils ratio decreased during cultivation in both conditions of oxygen supply. The ratio between sarcoplasmatic reticulum and myofibrils decreased markedly at a pO2 of 0.6 mm Hg.     

19F chemical shift imaging technique to measure intracellular pO2 in vivo using perflubron

RATIONALE AND OBJECTIVES: There is a linear relation between the T1 relaxation rate of fluorine-19 (19F) of perfluorochemicals (PFCs) and the partial pressure of the oxygen (pO2) dissolved in the PFC. A line scan technique was used to overcome the significant chemical shift and low signal-to-noise ratio (SNR) of in vivo 19F magnetic resonance imaging. This study was designed to determine whether the line scan technique could detect the effect of oxygen on 19F T1. In addition, its ability to detect changes in intracellular pO2 when the inspired gas was raised from 20% to 100% O2 also was investigated. METHODS: The T1 relaxation rate of samples of perflubron emulsion diluted from 3.5% to 70% w/v and equilibrated with N2-O2 gas mixtures (pO2 range = 10-450 mm Hg) was measured using the line scan technique. The gas and emulsion pO2 were measured with a blood gas analyzer. The liver T1 relaxation rate was measured in three rabbits given 5 ml/kg perflubron emulsion 4 and 8 days earlier as they breathed room air and then 100% O2. We used a prototype cylindrical coil double-tuned to hydrogen-1 (1H) and 19F and selected a line through the liver. The scanning parameters yielded a voxel size of 20 x 20 x 15.6 mm. Liver and blood samples were obtained postsacrifice for perflubron concentration measurement. RESULTS: A linear relation between the 19F T1 relaxation rate (1/T1) of the 3.5% w/v emulsion and dissolved pO2 was established with a slope of 0.0033 (sec-1/mm Hg) and a correlation coefficient of .991. As the PFC concentration increased by 1,900%, the slope increased by 21.2%. The 1/T1 for the liver was 0.182 +/- 0.004 sec-1 at baseline. It increased to 0.247 +/- 0.022 sec-1 when rabbits breathed 100% O2 (p = .023), which corresponded to an increase in intracellular pO2 of 19.7 mm Hg. The liver-to-blood PFC concentration ratio was 500:1. CONCLUSION: In vitro measurements with the line scan technique replicated the established linear dependence of 1/T1 on pO2. In vivo measurements indicated a 20-mm Hg increase in intracellular pO2 of liver phagocytes when the inspired gas was changed from 20% to 100% O2.     

The optimal combination of hyperthermia and carbogen breathing to increase tumor oxygenation and radiation response

PURPOSE: To determine the most effective combination of carbogen breathing with mild temperature hyperthermia (MTH) to increase the oxygenation and radiation response in murine tumors. METHODS AND MATERIALS: MTH at 41.5 degrees C for 60 min was applied by immersion of the tumor in a precisely controlled water bath. The tumor pO2 was measured with a polarographic microelectrode. The radiation response of the tumor was determined using the in vivo/in vitro assay for surviving tumor cells. RESULTS: In the FSaII fibrosarcoma the median pO2 increased from a control value of 6.5 +/- 0.5 mm Hg to 16.6 +/- 1.1 mm Hg immediately after MTH and was 10.9 +/- 1.3 mm Hg 24 h later. Carbogen breathing for 5 min increased the FSaII pO2 to 19.9 +/- 2.1 mm Hg. Carbogen breathing for 5 min beginning immediately after MTH increased the median pO2 more than 5 times to 35.4 +/- 3.8 mm Hg. This combined treatment also substantially increased the response of the tumors to a radiation exposure of 20 Gy. In another tumor model, the SCK mammary carcinoma, MTH treatment increased the median pO2 from the control level of 4.4 +/- 0.2 mm Hg to 12.6 +/- 1.2 mm Hg, and it returned to 4.3 +/- 0.3 mm Hg 24 h later. Carbogen breathing for 5 min increased the SCK tumor pO2 to 17.1 +/- 1.4 mm Hg. The median SCK pO2 was increased about 7 times to 31.2 +/- 4.2 mm Hg when MTH was followed immediately with carbogen breathing for 5 min. The radiation response was also markedly increased by this combination. When the animals breathed carbogen for 15 or 30 min, the pO2 and radiosensitivity in both tumor types either remained the same or was lower than that after 5 min of breathing. In addition, both FSaII and SCK tumors were radiosensitized 24 h after MTH treatment alone or with 5 min of carbogen breathing. CONCLUSIONS: A shorter carbogen breathing time immediately after MTH causes the most tumor radiosensitization. The results of this study also demonstrate that MTH increases radiosensitivity with and without carbogen breathing up to 24 h after the mild hyperthermia treatment.     

Physiologic changes associated with ligation of the ductus arteriosus in preterm infants

Cardiorespiratory and transcutaneous oxygen monitors were used on 13 preterm neonates to examine physiologic changes during ductus arteriosus ligation. Transcutaneous oxygen decreased 30 seconds after left lung deflation; all infants required increases in inspired oxygen and ventilation to correct abnormal values after the left lung was compressed. Transcutaneous oxygen decreased 30 seconds after ductus arteriosus ligation (mean delta tcPO2 = -17 mm Hg +/- 11.4) but increased 150 seconds after left lung inflation (mean delta tcPO2 = 46.9 mm Hg +/- 28.8). Arterial blood pressure increased (mean delta systolic BP = 17.9 mm Hg +/- 9.5) and heart rate decreased 10 seconds after ductus arteriosus ligation. In five neonates, gradual closure of the ductus arteriosus over 40 to 75 seconds resulted in a more gradual increase in blood pressure. Intraventricular hemorrhage was confirmed in two patients after surgery. Ligation of the ductus arteriosus results in an abrupt increase in blood pressure, which may be related to the pathogenesis of intraventricular hemorrhage. We suggest that the ductus arteriosus be closed gradually to allow a more gradual increase in blood pressure.     

Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group

BACKGROUND: Improvement of angina pectoris symptoms after cholesterol lowering has raised questions as to the underlying mechanisms. METHODS: Rabbit experiment: We compared arterial blood samples from New Zealand White cholesterol-supplemented rabbits (n = 6) with nonsupplemented rabbit samples (n = 4) in a closed-loop circulation diffusion system. The pH and partial pressures of oxygen (pO2) and carbon dioxide (pCO2) were measured continuously. The samples were first oxygen (O2) saturated (pO2, 160 mm Hg; pCO2, 4 mm Hg) and then desaturated in 100% nitrogen. Cholesterol levels were determined in whole blood, plasma (P Chol), red blood cells (RBCs), and RBC membranes. Human experiment: We exposed quadruple desaturated venous blood samples (n = 4) with P Chol levels of 87 to 400 mg/dL in a gas exchanger to capillary gas conditions (pO2, 23 mm Hg; pCO2, 46 mm Hg). After 15 minutes we performed blood gas analyses and compared our results to baseline values. RESULTS: In the rabbit experiment the cholesterol-supplemented group as compared to the control group showed higher plasma pO2 levels during the saturation phase and lower plasma pO2 levels during the desaturation phase. It also had a markedly increased RBC membrane cholesterol content: 121 +/- 3 (standard error of the mean [SEM]) mg/dL versus 22 +/- 1.7 mg/dL in the control group (P < .05). This barrier to RBC membrane O2 diffusion caused delayed O2 entry into the RBCs during saturation, with a higher plasma pO2, and delayed O2 release from the RBCs during desaturation, with a lower plasma pO2. In the human experiment the P Chol level was inversely correlated with the percentage change of O2 content in milliliters of O2 per deciliter of blood (P < .05). CONCLUSIONS: Increased RBC membrane cholesterol in hypercholesterolemia appears to decrease the transmembrane O2 diffusion rate.     

Intratumor pO2, S-phase fraction and p53 status in cervix carcinomas

PURPOSE: Investigation whether tumor tissue oxygenation is influenced by proliferation or p53-status in cervical cancers. MATERIAL AND METHODS: From April 1995 through December 1996, 28 patients with locally advanced cervical cancers (age 36 to 78 years; FIGO stages: 10 patients IIB, 16 patients IIIB, 2 patients IVA) underwent intratumoral measurement of pO2 prior to definitive radiotherapy. The histological specimens were examined for grading and quantitative immunohistological expression of the MIB-antigen and p53-protein. Proliferation was estimated by measuring the S-phase fraction with flow cytometry. RESULTS: The median pO2-values showed a broad variation from 2.2 through 60.4 mm Hg, median 19.7 mm Hg. The S-phase fraction varied from 4.2 through 34.2% (median 11.6%), MIB-positive cells from 20 through 100% (median 74%), and immunohistologically p53-positive cells from 0 through 95% (median 2%). The patients were divided in 2 groups according to the pretreatment pO2. Tumors with a pO2 above the median had a lower S-phase fraction than tumors with a pO2 below the median, 10.4 +/- 3.8% versus 16.3 +/- 5.5%, p < 0.02. MIB and p53 were not different in both groups (MIB: 68.1 +/- 27.7% versus 75.0 +/- 18.4%, p = 0.1; p53: 26.4 +/- 38.5% versus 18.1 +/- 19.8%, n. s.). Grade of differentiation and FIGO stage had no impact on pO2. CONCLUSION: Locally advanced cervical cancers with a poor oxygenation have a higher proliferative activity. Tumor proliferation may play a causative role for the development of hypoxia as suspected from radiobiological theories.     

Toxicity of oxygen to mitochondrial respiratory activity in hypothermically perfused canine kidneys

Respiratory activity of kidney cortex homogenates was measured after various periods of hypothermic pulsatile preservation of dog kidneys with cryoprecipitated plasma. There was a progressive loss of pyruvate plus malate-stimulated respiration (30 to 40% at 3 days and 70 to 80% at 5 days) and succinate-stimulated respiration (15 to 20% at 3 days and 50 to 60% at 5 days). Perfusion under conditions of low pO2 (30 to 40 mm Hg) or with inhibitors of the toxic effects of hyperbaric oxygen (CO2+ Mn2+) preserved homogenate respiratory activity better than with normal pO2 (150 mm Hg) or high pO2 (300 mm Hg). The results suggest that oxygen toxicity (lipid peroxidation) and the progressive loss of respiration in homogenates may be limiting factors in obtaining long-term preservation.     

Variability in blood flow and pO2 in tumors in response to carbogen breathing

PURPOSE: There is speculation that the CO2 in carbogen (95% O2, 5% CO2) can block the vasoconstrictive effects of oxygen. However, it has recently been shown that blood flow in human tumors is variable while patients breathe carbogen. Furthermore, we have shown a consistent decrease in tumor blood flow (TBF) with carbogen breathing in the rat window chamber model. Also, we have previously shown that there is no significant difference in tumor growth time after radiation with air vs. carbogen breathing. This study was designed to investigate the effects of carbogen breathing on blood flow and oxygen levels in a solid tumor. METHODS: Measurements were made in Fischer-344 rats with 8-10 mm diameter R3230Ac tumors transplanted either within the quadriceps muscle (n = 16) or subcutis (n = 14). Nontumor-bearing quadriceps muscle was studied in six other rats. After a 20-minute air-breathing baseline, rats breathed carbogen for an additional 40 minutes. Partial pressure of oxygen (pO2) was continuously monitored at one position for 60 minutes using 9-12 microm diameter oxygen microelectrodes. Blood flow was simultaneously monitored in all animals using laser Doppler flowmetry (1-2 probes/tumor). RESULTS: Blood flow changes during carbogen breathing were variable in all tissues and intratumoral heterogeneity was observed. Despite variability in blood flow, pO2 consistently increased in normal muscle but varied in both tumor sites. During carbogen breathing, the percent pO2 measurements greater than the baseline average were 99.5% +/- 0.4% (mean +/- SEM), 42.7% +/- 13.8%, and 79.8% +/- 11.0% in normal muscle, subcutaneous tumor, and muscle tumor, respectively. To show the magnitude of change, average pO2 values during air and carbogen breathing were calculated for each site. Normal muscle increased from 14.9 +/- 2.3 to 39.0 +/- 6.4 mm Hg (paired t-test; p = 0.009). Muscle tumors showed a rise from 14.6 +/- 3.2 to 34.5 +/- 8.2 mm Hg (p = 0.019). However, pO2 in subcutaneous tumors remained unchanged, with a pO2 of 7.3 +/- 2.0 mm Hg on air and 7.3 +/- 4.1 mm Hg (p = 0.995) during carbogen breathing. CONCLUSIONS: Carbogen had no consistent effect on blood flow and was ineffective at increasing tumor pO2. These results may partially explain why carbogen breathing failed to improve the efficacy of radiation in this tumor model when transplanted subcutaneously.     

Adenine nucleotides and inhibition of protein synthesis in isolated hepatocytes incubated under different pO2 levels

Hepatocytes incubated at a pO2 of 0 mm Hg (N2/CO2, 95%/5%) loose their intracellular ATP content and their ability to synthesize RNA and proteins. Protein synthesis is virtually inhibited from the beginning of the incubation, while ATP content is gradually lost, thus suggesting a primary response of the cell to the absence of O2 rather than to ATP depletion. Such an early decrease of protein synthesis (as estimated as the incorporation of [14C]Leu into cell proteins) is unlikely the result of inhibition of amino acids uptake, enhanced protein degradation, or decreased RNA synthesis. Reoxygenation of such previously hypoxic cells with O2/CO2 at 95%/5% (pO2 of 700 mm Hg), leads to the recovery of both ATP and protein synthesis, even better the hypoxic period is not longer than 30 min. In hepatocytes incubated for 30 min under a pO2 of 700, 80, or 50 mm Hg, cell survival and ADP content are almost identical. Incorporation of radiolabelled leucine is linear in cells incubated under 700 mm Hg O2, but it rather stops at a pO2 of 80 or 50 mm Hg. The time course of both ATP and GTP content behaves in a similar way: it is fairly constant at a pO2 of 700 mm Hg, but a depletion is initiated after 20 min of incubation at a pO2 of 50 or 80 mm Hg. Finally, incubation of hepatocytes either at 700 or 0 mm Hg O2, in the presence of fructose (10 mM), shows that ATP content is maintained at the same level whatever the pO2 level. AMP content is increased only in cells incubated at 0 mm Hg O2 in the absence of fructose. Incorporation of radiolabelled leucine is stopped in such hypoxic cells incubated or not in the presence of fructose. From these results it appears that the presence or the absence of O2 might represent a turn on/off signal to which hepatocytes respond immediately by important metabolic changes like the inhibition of protein synthesis.     

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson''s disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson''s Disease (GSPD)

PURPOSE: Tumor hypoxia may be an important factor predicting relapse following radiation therapy. This study was designed to determine the relationship between the oxygenation parameters measured using a polarographic oxygen electrode, prior to and during treatment in patients with cervix cancer, and to assess these results with regard to patient survival. MATERIALS AND METHODS: Forty-three patients had pretreatment oxygen assays performed and measurements repeated following external beam radiation to a median dose of 50 Gy (range 26-52 Gy). Stage distribution showed 15 patients in Stage IB, 17 in Stage II, and 11 in Stage III. The median tumor size was 5 cm (range 3-10 cm). RESULTS: The median proportion of pO2 values <5 mm Hg (the HP5) was 41% following radiation, and the median pO2 was 12 mm Hg. These results were not significantly different from the pretreatment HP5 or pO2 of 37% and 12 mm Hg, respectively. Disease-free survival at 2 years was 50% in patients with posttreatment HP5 < or =50%, compared to 60% when posttreatment HP5 was >50% (p = 0.35). CONCLUSIONS: Unlike pretreatment results, tumour oxygenation measured following external radiation does not appear to be a useful predictive assay in patients with cervical cancer.     

Immunological effects of an arginine side chain contaminating synthetically prepared peptides

We examined the effect of a nitric oxide (NO) quencher, stroma-free human hemoglobin A (HbA0; 0.01, 0.05, 0.1, 0.2 g/kg), on the blood flow measured using the Doppler flow technique, tumor oxygen pressure (pO2) and the diameter of the arterioles using R3230Ac mammary adenocarcinoma as the tumor model. In female Fischer 344 rats with 1-cm-diameter tumors implanted in the lateral aspect of the left quadriceps, intravenous infusion of 0.1 and 0.2 g/kg HbA0 decreased both central tumor and peripheral tumor blood flow by 20-30% (P < 0.05). Tumor pO2 decreased 28% with 0.2 g/kg HbA0, from 15 mm Hg (baseline) to 11 mm Hg at 10 min (P = 0.02). Although 0.2 g/kg HbA0 increased blood flow 55% in the left quadriceps muscle proximal to the implanted tumor (P < 0.05), HbA0 had little effect on blood flow in right quadriceps muscle with no tumor implanted, and increased right quadriceps pO2, from 21 mm Hg (baseline) to 23 mm Hg at 10 min (P = 0.03). HbA0 increased mean arterial pressure 5-10% in a manner that was dependent on dose while heart rate concurrently decreased 9-19%. The diameter of the arterioles supplying the tumor was rapidly reduced 10% by 0.2 g/kg HbA0 (P = 0.037) and remained stable through 60 min of observation (P = 0.005). HbA0 selectively reduces tumor blood flow and tumor pO2 through vasoconstriction of the arterioles supplying the tumor. Vascular NO quenching provides an alternative to NO synthase inhibition as a means to achieve the goal of selective tumor hypoxia.     

Transcutaneous oxygen and carbon dioxide during treatment of critical limb ischemia with iloprost, a prostacyclin derivative

The effect of intravenous iloprost treatment (median rate: 1.6; range 1-2 ng/kg/min; 6 h daily over 4 weeks) on transcutaneous pO2 and pCO2 was studied in 8 patients with bilateral peripheral obstructive arterial disease and monolateral critical limb ischemia. Tensiometric determinations were obtained at both metatarsi in the supine and dependent position. In critically ischemic limbs, supine transcutaneous p)2 changed erratically during iloprost treatment, increasing in only three out of eight lower limbs. At variance with its inconsistent behavior in the supine position, dependent pO2 increased during drug administration (p<0.02). Transcutaneous pCO2 was unchanged by iloprost. In the contralateral, non-symptomatic limb, both supine and dependent pO2 values were increased by the drug, suggesting that systemic hemodynamic changes may participate in its effect on transcutaneous gas tension, even at infusion rates clinically titrated to avoid evident changes in blood pressure and heart rate.     

Indicator cell lines for detection of primary strains of human and simian immunodeficiency viruses

The pulmonary artery pressure (Ppa) responses to short runs of acute hypoxia at two different levels of end-tidal CO2 were measured in nine normal subjects and in 20 patients with moderate to severe obstructive sleep apnea (OSA). In normal subjects the mean increase in Ppa in response to eucapnic hypoxia was 8 +/- 2 mm Hg (SEM) and was not different from the response to hypercapnic hypoxia (9 +/- 2 mm Hg, p > 0.2). In patients with OSA, the mean increase of Ppa was 8 +/- 1 mm Hg to eucapnic hypoxia, and the response to hypercapnic hypoxia was higher at 10 +/- 1 mm Hg (p = 0.01). Pulmonary pressor response to hypoxia was augmented (> 10 mm Hg) by hypercapnia in four of 20 patients with OSA but in none of the normal subjects. Normoxic hypercapnia alone was a weak stimulus, increasing Ppa by > 5 mm Hg in only two of nine patients with OSA studied. In conclusion, Ppa increases in both normal subjects and patients with OSA exposed to a ramp of acute isocapnic hypoxia. There were clear interindividual differences in pulmonary artery response. Hypercapnia did not produce clinical significant changes in Ppa in either group.     

Arterial blood gas determination in patients with anterior packing

Twenty-two healthy males ranging in age between 18 and 43 years were studied by arterial blood sample obtained before nasal surgery and again after complete bilateral nasal obstruction produced by nasal packing. Five of these patients had a third sample drawn after pack removal. The pO2 dropped from a preoperative mean of 85 mm Hg to 74 mm Hg. This difference is statistically significant; pCO2 did not change between the two measurements. This result is attributed to hypoxia caused by acute total nasal obstruction. It suggests that anterior packing alone may cause a clinically important hypoxia in patients with inadequate pulmonary reserve and that these patients merit close observation when bilateral anterior packing is placed. The early removal of anterior packing in patients where possible seems indicated. Supplemental O2 (40%) for patients over 40 years of age requiring nasal packing is practiced at this Center.     

Continuous monitoring of brain tissue PO2: a new tool to minimize the risk of ischemia caused by hyperventilation therapy

Secondary ischemic events worsen the outcome of patients with severe head injury. Such a secondary ischemic event may be caused by a forced hyperventilation. A consequence of the induced vasoconstriction is the risk of ischemia with an adverse effect on outcome. As a reliable and on-line technique, brain tissue pO2 (p(ti)O2) is used for monitoring regional microcirculation, to detect critical hypoperfusion. On 22 patients with a severe head injury 70 hyperventilation tests were performed from day 0-9 after trauma, calculating TCD-CO2-reactivity (% change of mean flow velocity per mm Hg paCO2 change). Additionally brain p(ti)O2-CO2-reactivity (% change of brain p(ti)O2 per mm Hg paCO2 change) was calculated and introduced. Group A +2 (p(ti)O2 < or = 15 mm Hg, TCD-CO2-reactivity > or = 2.5%, p(ti)O2-CO2-reactivity > 0%) and group B +2 (p(ti)O2 > 15 mm Hg, TCD-CO2-reactivity > or = 2.5%. p(ti)O2-CO2-reactivity > 0%) was formed. P(ti)O2 values in group A+2 decreased to an ischemic level or ischemia aggravated during hyperventilation. In group B+2 no ischemic events occurred. TCD-CO2-reactivity, p(ti)O2-CO2-reactivity and decrease of paCO2 were not significantly different in both groups. 6 out of 22 patients showed, from day 0-9, at least once a risk of (aggravating) ischemia by hyperventilation therapy.     

The postoperative monitoring of intracranial pressure in patients in the acute period of aneurysmatic hemorrhage

The influence of serotonin adipinate on the mechanisms of development of tissue hypoxia, disturbances of the microcirculatory bed and smooth muscles before, during and after operative interventions was studied in experiments and clinical practice. The syndrome of serotonin insufficiency is described including smooth muscle insufficiency which can be abolished by serotonin adipinate administered at the early postoperative period irrespective of the cause of surgery, age and sex of the patient. Good results were obtained in treatment of patients after operations on the liver, pancrease, heart, in patients with the diabetic foot and in other diseases. No complications or lethal outcomes resulting from using serotonin adipinate were noted.     

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.