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Biomedical subjects

J Kohler

Publications and source records attributed to J Kohler.

At least 73 records · Page 4Linked to original sources
PubMed1984

Chronic hypoxemia depresses global ventricular function and predisposes to the depletion of high-energy phosphates during cardioplegic arrest: implications for surgical repair of cyanotic congenital heart defects.

Persistence of impaired ventricular function after repair of cyanotic congenital heart defects may be due to previous exposure to chronic hypoxemia or to perioperative ischemic injury. Clarification of this phenomenon was sought in a canine model of cyanotic cardiovascular disease (Group I), in which the left atrium was anastomosed proximal to the banded pulmonary artery. Animals that had pulmonary artery banding alone (Group II) or no prior surgical intervention (Group III) served as controls. All Group I animals became cyanotic during the study period (arterial oxygen tension, 38 +/- 4 mm Hg; hematocrit, 55 +/- 5%). Radionuclide-determined ejection fractions performed three months after operation showed significant depression of global biventricular function by 16 to 29% (p less than 0.05) compared with groups II and III. On cardiopulmonary bypass, all hearts were subjected to 4 degrees C potassium cardioplegic arrest and reperfusion with serial assays for myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels. The ATP and CP stores in each ventricle were similar at all sampling intervals, and preischemic levels were comparable in cyanotic and control groups. However, ATP levels were significantly depressed 37 to 43% from preischemic levels (p less than 0.02) after arrest and reperfusion in cyanotic dogs, but they were preserved in Groups II and III. During ischemia, CP stores were depleted to 27% of preischemic values in Group I but only to 46 to 63% of preischemic levels in the control groups (p less than 0.05). These data indicate that chronic hypoxemia impairs global ventricular function and predisposes to the accelerated depletion of high-energy phosphates during cardioplegic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1983

Prevention and reperfusion injury following cardioplegic arrest by pulsatile flow.

To assess the efficacy of pulsatile flow in minimizing reperfusion injury following cardioplegic arrest, 20 dogs supported by cardiopulmonary bypass underwent 60 minutes of hypothermic, hyperkalemic crystalloid cardioplegic arrest. The effects of pulsatile flow (Group 2), initiated during 30 minutes of reperfusion, on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content were compared with the effects of linear flow reperfusion (Group 1). Myocardial ATP stores were maintained at preischemic levels by this mode of myocardial protection. However, pulsatile flow prevented the significant decline in ATP levels incurred during linear reperfusion. Creatine phosphate stores, although depleted during arrest, were restored equally, regardless of the mode of reperfusion. The decline in ATP stores was associated with no pathological increase in myocardial water content, but was associated with persistent reactive hyperemia. In contrast, after 30 minutes of pulsatile reperfusion, coronary blood flow was significantly decreased compared with preischemic flow. These data indicate that pulsatile reperfusion can prevent the unique decline in ATP levels associated with the restoration of coronary flow after cardioplegic arrest (reperfusion injury), and support its continuing evaluation as an adjunct to adequate intraoperative myocardial protection.

Adenosine Triphosphate↗
PubMed1983

Beneficial metabolic effect of nucleoside augmentation on reperfusion injury following cardioplegic arrest.

Restoration of coronary flow after hyperkalemic cardioplegic arrest (HCA) is associated with a unique metabolic reperfusion injury (RI) manifested by declining nucleotide stores despite their end-ischemic preservation. Prevention of this RI by exogenous provision of adenosine with or without inhibition of adenosine's major catabolic enzyme was assessed in 27 dogs subjected to 60 minutes of HCA. The effect of aortic root infusion of 40 mg/kg of adenosine in addition to adenosine deaminase inhibition by 10 mg/kg of EHNA (group 2) initiated during 60 minutes of reperfusion on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores and coronary blood flow (CBF) were compared to animals having adenosine infusion alone (group 3) or controls (group 1). Although ATP levels were preserved at the end of HCA in all groups, adenosine infusion with or without EHNA prevented the significant 23 percent decline in ATP stores incurred during unmodified reperfusion (p less than 0.01, group 1). The CP stores decreased (p less than 0.05, all groups) during arrest, but were restored to preischemic levels during reperfusion. When measured 60 minutes after aortic unclamping, CBF was 312 percent of preischemic flow in group 3 (p less than 0.01), only 170 percent in group 2 (p less than 0.05), and unchanged in controls (group 1). The data indicate that provision of adenosine as a nucleotide precursor prevents the metabolic RI following HCA. In addition, inhibition of adenosine catabolism is not necessary for this salutary effect, nor is adenosine's efficacy solely mediated by augmentation of CBF.

Adenine↗
PubMed1983

Cardioplegia does not prevent reperfusion injury induced by intracoronary platelet deposition.

We have shown that after global myocardial ischemia, reperfusion injury may be related to platelet deposition in the coronary microcirculation. The purpose of this study was to determine whether multidose hypothermic potassium cardioplegia suppresses platelet deposition during postischemic reperfusion. Platelets labeled with 111In and erythrocytes labeled with 51Cr were injected into dogs subjected to either 120 min of continuous cardiopulmonary bypass (control, n = 4), 60 min of global normothermic myocardial ischemia followed by 50 min of reperfusion (n = 6), or global ischemia with cardioplegia (n = 5). Intracoronary platelet deposition was determined by comparing the double-labeled isotope activity of myocardial biopsy specimens to peripheral blood. Reperfusion after global myocardial ischemia resulted in substantial deposition of platelets within the coronary vasculature in both the cardioplegia-treated (215 +/- 40 platelets/mg) and untreated (269 +/- 95 platelets/mg) groups. These increases were significantly greater than those measured during continuous bypass (48 +/- 2 platelets/mg; p less than .01). Cardioplegia, despite apparent washout of the microcirculation, does not alter platelet deposition. Thus other platelet-stabilizing measures must be used to prevent platelet deposition-induced reperfusion injury after surgical global ischemia.

Animals↗
PubMed1982

Somatostatin-like immunoreactivity in the cerebrospinal fluid of neurological patients.

Using a specific radioimmunoassay we have measured somatostatin-like immunoreactivity (SLIR) of CSF in patients with brain atrophy, spinal spasticity, seizures, brain tumors and inflammatory disorders. Patients with marked brain atrophy had significantly decreased somatostatin levels in CSF. In patients with spinal spasticity significantly higher levels were observed. Seizure patients had reduced levels but the difference was not significant. In patients with inflammatory disorders and malignant brain tumors SLIR levels were significantly elevated but not in patients with benign brain tumors. A possible pathophysiologic meaning of SLIR in spasticity and seizures is discussed. The altered levels in brain atrophy, tumors and inflammatory disorders are probably indirect signs of altered somatostatin turnover or increased somatostatin leakage from damaged CNS.

Adolescent↗
PubMed1982

Drinking water and cancer incidence in Iowa. I. Trends and incidence by source of drinking water and size of municipality.

Age-adjusted, sex-specific cancer incidence rates for the years 1969-1978 were determined for municipalities in Iowa having a population of 1000 or over and public water supply that had remained stable for a minimum of 14 years. The incidence rates for the municipalities were examined according to major source of water supply (surface or ground) and depth of well. As municipality size increased, incidence rates increased for cancer of the lung among males and females. A slight gradient of increasing cancer incidence was seen for cancer of the bladder among males and females. When stratified for population size, incidence rates for cancers of the lung and rectum among males and females were higher for municipalities on surface water compared with those on ground sources. Incidence rates for cancer of the prostate rose as well depth increased, while a trend was seen toward decreasing incidence rates for cancer of the colon among females as well depth increased. When time trends were examined, an increase in cancer rates over time was seen for several cancer sites, with the increase most noticeable in municipalities supplied by surface water or shallow wells. These results are not always consistent with the hypothesis of an association between cancer and chlorinated water.

Epidemiologic Methods↗
PubMed1982

Drinking water and cancer incidence in Iowa. II. Radioactivity in drinking water.

Iowa towns of 1000-10,000 population, whose water came solely from wells of over 500 feet (152 meters) in depth and was not treated by a process that would remove radioactivity, were identified. Age-adjusted, sex-specific, cancer incidence rates were determined for these towns for the years 1969-1978 (excluding 1972) and related to the mean level of radium-226 in the municipal water supply. Incidence rates of cancers of the lung and bladder among males and of cancers of the breast and lung among females were higher in towns with a radium-226 level in the water supply exceeding 5.0 pCi/l. A gradient of increasing cancer incidence associated with rising radioactivity level for three time periods was also seen for lung cancer among males. The associations between cancer incidence and radioactivity of water supply could not be explained by smoking patterns, water treatment factors, other water quality measurements, or known socio-demographic features.

Aged↗
PubMed1982

Pulsatile reperfusion does not modify global myocardial ischemic injury.

In an attempt to arbitrate the reputed clinical efficacy of pulsatile flow during reperfusion in minimizing ischemic injury, 32 mongrel dogs supported by normothermic cardiopulmonary bypass were subjected to 30 minutes (Groups IC and IP) or 60 minutes (Groups IIC and IIP) of global myocardial ischemia. The effect of pulsatile flow (P) initiated during 30 minutes of reperfusion on the recovery of myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content (MWC) was compared to the effect of linear reperfusion (C) in another group of animals. ATP stores, which significantly decreased to 43% and 53% of preischemic levels (Groups IC and IP, respectively, p less than 0.01) and 36% and 31% of control values (Groups IIC and IIP, respectively. p less than 0.001), did not increase with either pulsatile or linear reperfusion. CP stores, depleted 97% during ischemia in all groups, returned to preischemic levels regardless of the mode of reperfusion flow. Coronary blood flow measured 30 minutes after aortic unclamping was not significantly different from control flow in any group. MWC significantly decreased during ischemia from 80.5% +/- 0.8% to 76.5% +/- 1.1% in Group IC and from 81.8% +/- 1.2% to 76.8% +/- 0.8% in Groups IP (p less than 0.05) and returned to preischemic levels with reperfusion. However, following 60 minutes of ischemia, pulsatile reperfusion prevented the significant increase in MWC that accrued after linear reperfusion (80.7% +/- 1.5% to 84.0% +/- 0.7%, p less than 0.05). These data indicate that pulsatile reperfusion initiated after an ischemic injury that results in a 50% or greater depletion of myocardial ATP stores does not restore myocardial nucleotide levels or enhance coronary blood flow, although the pathological increase in MWC may be avoided.

Adenosine Triphosphatases↗
PubMed1982

Pulmonary extraction of biogenic amines during septic shock.

The effect of live Escherichia coli on the pulmonary extraction of the biogenic amines 14C 5-hydroxytryptamine, (5-HT) and 3H-epinephrine was investigated. The labeled isotopes were injected into a central venous catheter and collected from an aortic catheter. One hundred per cent of the labeled epinephrine was recovered in the control and septic state. Only 32.8 +/- 3.6% SEM of the 5-hydroxytryptamine was recovered before sepsis and 42.5 +/- 4.9% SEM after sepsis. During sepsis, mean arterial pressure fell to 58 mm Hg from 121 mm Hg. Pulmonary shunt increased from .7 +/- .05 SEM to .33 +/- .09 SEM.

Animals↗
PubMed1982

Platelet deposition after surgically induced myocardial ischemia. An etiologic factor for reperfusion injury.

Despite meticulous adherence to presently known principles of myocardial preservation, reperfusion after aortic cross-clamping results in a unique injury manifested by decreasing high-energy phosphate levels and increased coronary resistance. We hypothesize that platelet deposition into the coronary microvasculature is a major factor in reperfusion injury. To differentiate platelet deposition due to subendocardial hemorrhage from deposition due to vascular entrapment, we infused 111In-labeled platelets together with 51Cr-labeled erythrocytes into 15 dogs that were on normothermic bypass and subjected to 60 minutes of global ischemia followed by 30 minutes of reperfusion. Platelet deposition is indicated only when the proportion of platelets to erythrocytes in tissue exceeds that measured by peripheral blood. Myocardial biopsy specimens were obtained after 10 minutes of bypass, 120 minutes of continuous bypass (Group I), and at the end of reperfusion after global ischemia (Group II). In five dogs (Group III), dipyridamole (1 mg/kg), an antiplatelet activation agent, was administered in the preischemic period. Platelet deposition was expressed as the number of radioactive-labeled platelets deposited per gram of tissue. Bypass for 120 minutes resulted in only a minimal increase in platelet deposition. However, normothermic ischemia followed by reperfusion resulted in over a twofold increase in platelet deposition compared to controls. Pretreatment with dipyridamole appeared to avoid platelet deposition. These data indicate that platelet deposition in the coronary microcirculation following surgically induced myocardial ischemia may be associated with reperfusion injury and that antiplatelet drugs after this sequence.

Animals↗
PubMed1981

Huntington's chorea-- measurements of somatostatin, substance P and cyclic nucleotides in the cerebrospinal fluid.

Somatostatin, substance P, cyclic AMP and cyclic GMP were determined in the cerebrospinal fluid of patients with Huntington's disease, in first generation relatives of choreic patients and in neurological control patients. Substance P levels were not significantly altered, but somatostatin levels were markedly decreased both in affected patients and symptom-free offspring. Cyclic AMP was decreased only in patients with advanced stages of the disease while cyclic GMP was normal. Evidence is discussed which may support a role of somatostatin deficiency in the pathophysiology of chorea.

Adult↗
PubMed1981

Decreased serum angiotensin converting enzyme in adult respiratory distress syndrome associated with sepsis: a preliminary report.

Serum angiotensin converting enzyme (ACE) levels were obtained in 24 control patients who were critically ill, in 11 patients with cardiogenic pulmonary edema, in 8 patients with status postcardiopulmonary bypass, and in 12 patients with adult respiratory distress syndrome (ARDS). Mean values in cardiogenic pulmonary edema (24.3 +/- 3.9 SD) in cardiopulmonary bypass (19.5 +/- 3.1) and in patients with ARDS and no sepsis (n = 7, 19.0 +/- 5.5) were not significantly different from controls (20.7 +/- 2.8). In contrast, patients with ARDS and sepsis had markedly decreased serum ACE levels which fell outside of control range (n = 5, 8.6 +/- 2.3). The authors speculate that decreased ACE levels in the combination of sepsis and ARDS are due to the presence of circulating inhibitors of ACE. The finding of decreased serum ACE can be of potential clinical usefulness by raising the possibility of sepsis as the etiology of ARDS before results of blood cultures are available.

Adult↗
PubMed1980

Malignant mesothelioma: a metastasis to the face.

Malignant mesothelioma can be a confusing disease, resembling either carcinoma or sarcoma. Although it usually causes death rapidly by local and regional spread, distant metastases may be seen more frequently as more effective therapy controls local disease and prolongs life. Our patient's local and then regional mesothelioma was controlled by aggressive treatment, which allowed him nearly two years of productive life before a metastasis to the right infraorbital region occurred. He died shortly thereafter with widesspread metastases. This is the first reported case of mesothelioma metastatic to the face. This case also emphasizes the association of malignant mesothelioma with asbestos exposure, and points out advances in pathologic techniques that aid in the diagnosis of the disease.

Facial Neoplasms↗
PubMed1980

Noninvasive measurement of pulmonary transvascular protein flux in normal man.

Onset of lung edema is usually associated with increase in the pulmonary transvascular flux of water and proteins. Clinical measurement of these parameters may aid in early diagnosis of pulmonary edema, and allow differentiation between "cardiogenic" and "noncardiogenic" types base on the magnitude of the detected changes. We have previously described a noninvasive method for estimating transvascular protein flux in lung (Gorin, A. B., W. J. Weidner, R. H. Demling, and N. C. Staub, 1978. Noninvasive measurement of pulmonary transvascular protein flux in sheep. J. Appl. Physiol. 45: 225-233). Using this method we measured the net transvascular flux of [113mIn]transferrin (mol wt, 76,000 in lungs of nine normal human volunteers. Plasma clearance of [113In]transferrin occurred with a T1/2 = 7.0 +/- 2.6 h (mean +/- SD). The pulmonary transvascular flux coefficient, alpha, was 2.9 +/- 1.4 X 10(-3) ml/s (mean +/- SD) in man, slightly greater than that previously measured in sheep (2.7 +/- 0.7 X 10(-3) ml/s; mean +/- SD). The pulmonary transcapillary escape rate is twofold greater than the transcapillary escape rate for the vascular bed as a whole, indicating a greater "porosity" of exchanging vessels in the lung than exists for the "average" microvessel in the body. Time taken to reach half-equilibrium concentration of tracer protein in the lung interstitium was quite short, 52 +/- 13 min (mean +/- SD). We have shown that measurement of pulmonary transvascular protein flux in man is practical. The coefficient of variation of measurements of alpha (between subjects) was 0.48, and of measurements of pulmonary transcapillary escape rates was 0.39. In animals, endothelial injury commonly results in a two- to threefold increase in transvascular protein flux. Thus, external radioflux detection should be a suitable means of quantitating lung vascular injury in human disease states.

Adult↗
PubMed1977

[Preventive-medicine screening methods in the examination of blood donors].

From a blood transfusion service with ca. 7000 donors a year, there was a loss of donors whose blood, having undergone medical tests, was found to be unsuitable. Details of all such donors were carefully documented. The results were ascertained by attentive control of the health of the donors which, in part, exceeded the minimum requirements laid down by the existing regulations. The relatively high loss of donors and the kind of disease underline the importance of these control checks, as an aspect of preventive medicine. This is of particular importance with regard to the results of so-called "new donors", who register for the first time. They had to undergo examination, and were only allowed to give blood when all the results of the tests had been submitted. The question then arises as to whether the regulations for the differing minimum requirements for the examination of "occasional donors" and "regular donors" can be maintained. A reduction of the expenditure on the present regulation examination of donors is not advocated because of both responsibility towards the blood donors, and in view of the increasing significance, to the medical care of patients, of the proximity of a clinic to an expedient transfusion service.

Anemia, Hypochromic↗