The ability of heat stress and metabolic preconditioning to protect primary rat cardiac myocytes

Primary rat cardiocytes were subjected to either thermal preconditioning for 30 min at 43°C or 20 min metabolic preconditioning (10 mM deoxyglucose, 20 mM lactate, pH 6.5). Eighteen hours later cells were analysed either for hsp 70i expression or subjected to a subsequent lethal heat stress or simulated ischaemia (10 mM deoxyglucose, 20 mM lactate, 0.75 mM sodium dithionite, 12 mM potassium chloride, pH 6.5) for 2 hours and assessed for survival by trypan blue exclusion.Hsp 70i was induced over 100 fold by thermal preconditioning and 30 fold by metabolic preconditioning (p<0.001, p<0.05), hsp 90 was induced 2.71 fold and 2.24 fold (p<0.001, p<0.001) by thermal and metabolic preconditioning respectively, while hsp 60 was not induced by either treatment. Preconditioned cultures had improved survival against subsequent lethal heat stress or simulated ischaemia: Thermal preconditioning reduced death from 69.22% to 52.46% upon subsequent lethal heat stress and from 49.13% to 36.66% upon subsequent lethal simulated ischaemia. Metabolic preconditioning reduced cell death from 51.29% to 33.8% against subsequent lethal heat stress, and from 69.09% to 55.61% upon subsequent lethal simulated ischaemia. A second marker of cell death, the release of lactate dehydrogenase activity into the culture media, was reduced to 65% and 60% of control values for thermally preconditioned cells subjected to lethal heat or lethal simulated ischaemia respectively. Metabolically preconditioned cells demonstrated lactate dehydrogenase activity of 59% and 51% that of control values, when subjected to lethal heat or lethal simulated ischaemia respectively.Abbreviations hsp heat stress protein - hsp 70i inducible 70 kDa heat stress protein - LDH lactate dehydrogenase - PBS phosphate buffered saline     

Impairment of monocyte “lectin-like” receptor activity in Type 1 (insulin-dependent) diabetic patients

Summary In order to investigate whether the ability of peripheral blood monocytes to bind bacteria is impaired in diabetes, we studied carbohydrate-binding (lectin-like) receptors and the receptor for the Fc portion of immunoglobulin on monocytes from 25 male Type 1 (insulin-dependent) diabetic patients and 10 age-matched healthy control subjects. Peripheral blood monocytes from the diabetic patients expressed lower levels of lectin-like receptors compared to the control subjects, whereas the expression of the receptor for the Fc portion of immunoglobulin was similar in both populations. There was no correlation between the degree of lectin-like binding activity and plasma glucose concentration or glycaemic control. Recognition of unopsonized bacteria by the lectin-like receptor is impaired in Type 1 diabetes; this may affect the efficient elimination of potential pathogens.     

Heterogeneous glycaemic and insulinaemic responses to oral glucose in non-diabetic men: interactions between duration of obesity,body fat distribution and family history of diabetes mellitus

Summary The interaction between environmental and genetic factors in the alterations of glucose-insulin homeostasis was studied in 104 non-diabetic men. Family history of diabetes mellitus was used as an index of genetic predisposition to diabetes. Body composition was measured by under-water weighing whereas subcutaneous and visceral adipose tissue areas were measured at the abdominal and femoral levels by computed tomography. The sample was first divided into two groups. The first group included subjects with normal glycaemic and insulinaemic responses during a 75 g oral glucose tolerance test. The second group was composed of subjects either with a high glucose response or high insulin response or both. Men included in the second group were different from the normal subjects for almost all body fatness variables. They also presented a prevalence of a positive family history of diabetes which was significantly higher than normal subjects. The second group was then divided into three distinct subgroups based on insulin and glucose responses of the subjects during the oral glucose tolerance test. Subjects with high insulin but normal glucose responses were characterized by significantly higher levels of total body fat and deep abdominal adipose tissue when compared to the normal group (p<0.05). Men with both high insulinaemic and glycaemic responses displayed higher body fatness values and higher deep and subcutaneous abdominal adipose tissue areas (p<0.05) in comparison with normal subjects. They also had a higher body mass index at age 20 years than control subjects and subjects with high insulin but normal glucose responses. In contrast, subjects with normal insulin but with high glucose responses were not different from the normal group with regard to body fat and adipose tissue areas. These results show the heterogeneous origin of altered glucose-insulin homeostasis in non-diabetic men. Finally, subjects in the altered glucose-insulin homeostasis group with no family history of diabetes displayed a higher body mass index at age 20 years (p<0.05) in comparison with subjects who had a positive family history of the disease. They also presented a greater abdominal-to-thigh fat ratio measured by computed tomography. These results suggest that in men with alterations of glucose-insulin homeostasis, the relationship of body fat distribution to glucose tolerance and plasma insulin levels is different in those with no family history of diabetes than in subjects with a positive family history of diabetes.     

An evaluation of gastric hypothermia

Conclusions Gastric cooling is an acceptable, sustaining procedure beneficial in the control of upper gastrointestinal bleeding of known or obscure origin. In its present mode of application, gastric freezing is not entirely satisfactory for management of intractable duodenal ulcer. This technic inconsistently alters symptoms of ulcer, causes acute gastric mucosal damage, and may so influence some factor related to ulcer diathesis as to provide adjunctive therapy. Gastric freezing is deserving of further evaluation and development under more rigidly controlled circumstances.This study was supported by grants AM-07624 and AM-07539 from the National Institute of Arthritis and Metabolic Diseases, Bethesda, Md.Presented at a postgraduate course. Current Therapy in Gastroenterology. (Nov. 16–17, 1963) sponsored by Louisiana State University School of Medicine, New Orleans. La.Trainee in gastroenterology under a grant from the National Institute of Arthritis and Metabolic Diseases.     

Follow-up of “non-diabetic” relatives of diabetics by retesting oral glucose tolerance after 5 years

Summary Of 743 first degree relatives of diabetics in whom oral glucose tolerance tests had been performed in 1967 488 were re-tested in 1972. Among the original normals (n = 353) 17.6% had developed a subclinical and 1.3% an overt diabetes within 5 years. The original subclinical diabetics (n = 118) showed a remission to normal in 35.6% and a progression to overt diabetes in 13.6%. 3 out of the 17 formerly overt diabetics were found to be normal after 5 years and 3 were subclinical diabetics. Thus the performance of an oral glucose tolerance test is of limited prognostic value in the individual case. In both studies a higher prevalence of abnormal test results occurred in the older age groups and in overweight subjects. Remission or deterioration did not depend, however, on age or on weight changes. The frequency of abnormal tests was higher in males than in females, but the tendency towards the development of diabetes was more pronounced in females, in accordance with a previous observation of a higher age dependance of glucose tolerance in females.     

Acute insulin response to intravenous glucose,glucagon and arginine in some subjects at risk for Type 1 (insulin-dependent) diabetes mellitus

Summary The relationships between first-phase insulin secretion to i.v. glucagon and i.v. arginine were studied in 19 healthy adult volunteers (Group I) and in 21 subjects at risk for Type 1 (insulin-dependent) diabetes mellitus with either a normal (n=11; Group II a) or a low insulin response to i.v. glucose (n=10; Group II b). Groups I and II a displayed similar insulin responses to the three secretagogues. In contrast, Group II b demonstrated lower insulin responses to both glucagon and arginine than control subjects (p}<0.007 and (p}<0.04 respectively) orthan normo-responders to glucose (#x007D;<0.007 and p<0.04 respectively). In Group II b however, arginine-stimulated insulin release was increased compared to the response to glucose (p}<0.006), while glucagon and glucose led to non-statistically different responses. Five low-responders developed Type 1 diabetes. As a group, they displayed lower responses to glucagon and to arginine than subjects who up to now have not developed the disease (p<0.05 and p<0.0003 respectively). In the subjects who progressed to diabetes, the responses to glucose and glucagon were similarly blunted. In the low-responders who have not developed the disease, no statistical difference could be detected between mean responses to glucagon and glucose, but four out of these five subjects had a glucagon-stimulated response within the control range and higher than their corresponding response to glucose. Arginine led to a higher stimulation than glucose, in subgroups that either progressed to diabetes (p<0.006) or did not (p<0.002). Finally, low-responders who did not develop diabetes displayed similar responses to both glucagon and arginine than normo-responders to glucose. A progressive decrease of arginine-stimulated insulin response may be a later event during pre-Type 1 diabetes than a blunted response to glucose, while a loss of glucagon-stimulated insulin release may be intermediate. Diminished response to all secretagogues may offer better prediction than a low response to glucose alone.     

Experimentelle Untersuchungen zur Frage der Seltenheit von Geschwulstmetastasen in der Skeletmuskulatur

Summary Authors injected a suspension of Brown-Pearce cancer cells into the left ventricle of 10 rabbits. The venous blood of the lower extremities of these first rabbits was injected into the ear vein of 20 intact second rabbits. In the surviving 7 first rabbits metastases in the skeletal muscles frequently developed. The majority of second rabbits developed tumors indicating a transmuscular passage of tumour cells emboli in the first rabbits. Transmuscular passage of tumour cell was found not only immediately after the injection of the tumour cells, but also three minutes later.These facts contradict the rather speculative theory according to which the skeletal muscle is an unsuitable soil for the development of secondary tumours.     

Zur Epidemiologie und Ätiologie des Oesophaguscarcinoms in China

Ohne Zusammenfassung

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The epidemiology and etiology of esophageal cancer in China

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Stipendiaten der Alexander von Humboldt-Stiftung aus der Volksrepublik China

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The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.Die Zeitschrift Journal of Cancer Research and Clinical Oncology bringt in zwangsloser Folge Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autors wieder.     

Interpretation of blood cultures yielding staphylococcus aureus

Summary Forty-eight patients with blood cultures positive for Staphylococcus aureus were classified according to clinical criteria in three groups: definite, possible, and doubtful septicemia. Using traditional blood culture sets with two bottles (thioglycollate and tryptic soy broths), we found that patients with definite septicemia always showed more than one positive bottle per day if more than one set was drawn, that the mean detection time was 1.7 days, and that 95% of the first positive bottles and 92% of all positive bottles grew within two days of incubation. Patients with doubtful septicemia were more often (88%) positive in one bottle only, the mean detection time for all bottles was 3.7 days, and only 35% of the first positive bottles and 33% of all positive bottles yielded growth within two days. Possible cases took a position between these two extremes but tended more towards the doubtful cases. The implications of these findings for the interpretation of blood cultures with S. aureus are discussed.

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Interpretation von Blutkulturen mit Staphylococcus aureus

Zusammenfassung 48 Patienten, aus deren Blutkulturen Staphylococcus aureus gezüchtet worden war, wurden nach klinischen Kriterien in drei Gruppen eingeteilt: unzweifelhafte, mögliche und zweifelhafte Septikämie. Bei Verwendung eines traditionellen Blutkultursystems mit zwei Flaschen pro Kultur (Thioglykolat- und Tryptic Soy-Bouillons) ergab sich, daß Patienten mit unzweifelhafter Septikämie stets mehr als eine positive Flasche pro Tag aufwiesen — sofern mehr als eine Kultur pro Tag entnommen worden war —, daß die mittlere Bebrütungsdauer bis zur Positivität 1,7 Tage betrug, und daß 95% der ersten positiven Flaschen und 92% aller positiven Flaschen innerhalb von zwei Tagen Wachstum von S. aureus zeigten. Patienten mit zweifelhafter Septikämie zeigten häufiger (in 88%) Wachstum in nur einer Flasche, die mittlere Bebrütungsdauer betrug 3,7 Tage, und nur 35% der ersten positiven Flaschen und 33% aller positiven Flaschen ergaben Wachstum innerhalb von zwei Tagen. Mögliche Septikämien nahmen eine Zwischenstellung ein, tendierten jedoch mehr nach der zweifelhaften Kategoric. Folgerungen für die Interpretation von Blutkulturen mit S. aureus werden diskutiert.

     

Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes

Summary Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration (diffuse, cluster, and large) were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was diffuse in 18, cluster in 48, and large in 40 cases. RAEB-t patients accounted for about half of the large cases, and none had a diffuse pattern (p<0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by cluster blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of large cases (p<0.001) and in none of the cluster cases with severe BM fibrosis (p<0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with cluster BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy.     

Early and Late QRS Morphology and Width in Biventricular Pacing: Relationship to Lead Site and Electrical Remodeling

48 patients (40 Male), mean age 68 ± 8 years, in III–IV class, with intraventricular conduction delay, received a biventricular pacemaker. Heart failure aetiology was non-ischemic in 60%. Left ventricular lead positioning was inferior in 5 patients (10%), posterior in 12 (25%), lateral in 18 (37%) and anterior in 13 (27%). QRS duration and axis were evaluated in sinus rhythm, and during right ventricular pacing, left ventricular pacing and biventricular pacing, the last early after implant and late after 8.8 ± 4.3 months. QRS duration (ms) was 154 ± 29 in sinus rhythm, 175 ± 28 during right ventricular pacing, 196 ± 31 during left ventricular pacing, 122 ± 23 during biventricular pacing early and 120 ± 18 during biventricular pacing late. All the differences were statistically significant, but not between early and late biventricular pacing. Mean QRS axis (°) was –27 ± 32 in sinus rhythm, –75 ± 4 during right ventricular pacing, 112 ± 41 during left ventricular pacing, –82 ± 51 during biventricular pacing early and –80 ± 42 during biventricular pacing late. Only the difference between left ventricular pacing and all the other groups was statistically significant. QRS axis did not significantly differ according to left ventricular lead site during left and biventricular pacing. Late compared with early biventricular pacing axis showed variation >30° in 35% of patients, in spite of no significant changes in QRS duration and x-ray positioning. Conclusion: Biventricular pacing significantly reduced QRS width, which persisted long-term. Left and biventricular pacing axis was poorly related to left ventricular lead positioning. Biventricular pacing axis variability over time may suggest a role of electrical remodeling.     

Use of cultured human tissues and cells in carcinogenesis research

Summary A variety of approaches are used to study carcinogenesis. Recent advances in techniques for culture of human tissues and cells have provided additional experimental systems of study the process of carcinogenesis and the genetics of cancer.The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.     

Converting enzyme inhibitors (captopril,enalapril, perindopril) prevent early-post infarction ventricular fibrillation in the anaesthetized rat

Summary The angiotensin-converting enzyme inhibitors, captopril, enalapril and perindopril, exert antiarrhythmic effects on early post-infarction arrhythmias in anaesthetized rats. These studies support the hypothesis that converting enzyme inhibitors could have a cardioprotective effect, but the doses used are probably high in relation to those therapeutically applicable to man.     

Slow metabolic deterioration towards diabetes in islet cell antibody positive patients with autoimmune polyendocrine disease

Summary We studied metabolic progression to IDDM in a cohort of adults who are ICA-positive and have associated autoimmune endocrine disease or circulating organ-specific autoantibodies (the Polyendocrine Study). Of the 186 individuals recruited 27 developed overt diabetes after a median follow-up of 4.5 years (range 0.4–12). Of these, eight patients did not require insulin treatment until at least 6 months after clinical diagnosis, with an interval of 1.8 years (1.2–5.7). An IVGTT was performed in 38 subjects and 23 had sequential studies. Of the initial 38 subjects six developed diabetes and only three showed a loss of FPIR to glucose (below the first percentile of a normal control group) before clinical onset of the disease. An additional three subjects showed a loss of the FPIR, and all still have normal glucose tolerance after median follow-up of 28 months (22–95). A whole or mixed pattern of islet cell staining was found in five of the six patients who developed diabetes and antibodies against an islet 37 k-antigen were detectable in four patients, all of whom required insulin soon after diagnosis. A beta-cell selective ICA staining pattern was seen in 14 of 17 subjects who did not develop diabetes and the mixed pattern in only three. None of this group had detectable 37k-antibodies. We conclude that metabolic deterioration is slow in polyendocrine patients, and that the IVGTT has less prognostic significance in this group than in first degree relatives of patients with IDDM. In contrast, the presence of the whole or mixed ICA staining pattern or of 37k-antibodies can identify a high risk of progression to IDDM within this polyendocrine population and may indicate the rate of metabolic deterioration.Abbreviations IDDM Insulin-dependent diabetes mellitus - ICA islet cell antibodies - IVGTT intravenous glucose tolerance test - FPIR first phase insulin response - OGTT oral glucose tolerance test - GAD glutamic acid decarboxylase - JDF Juvenile Diabetes Foundation     

Binding of lectins to “young” and “old” human erythrocytes

Summary Old human erythrocytes showed a 21.2% decrease in cell surface area and a 2% decrease in the number of WGA receptor sites, but a 27% increase in the distribution density of the WGA (lectin) receptor site, when compared with young human erythrocytes. For a list of lectin abbreviations, see Materials and methods). Both young and old erythrocytes exhibited very weak binding activity for ¹²⁵I-labeled PNA, but there was no difference in binding activity for PNA between young erythrocytes and old ones. Compared with young erythrocytes, decreases in the number and distribution density of receptor sites for five lectins including LPA, Con A, RCA-II, SBA and BPA on the cell surface were observed in aged erythrocytes. Old erythrocytes also showed a decrease in the number of PHA-E receptor sites, while the distribution density of the same receptor site remained unchanged. In view of these and other observations, it is thought that human erythrocyte aging is accompanied by elimination of some glycoconjugates which have affinity for six lectins, LPA, Con A, RCA-II, PHA-E, SBA and BPA, whereas no WGA receptor-containing glycoconjugates are released from erythrocyte membranes. Elimination of the glycoconjugates results in shrinkage of erythrocytes to reduce their cell surface areas.     

Unspezifische Phosphatasen und Esterasen im Melanoblastom der Chorioidea

Zusammenfassung Melanoblastome der Chorioidea bestehen aus wenig pigmentierten Melanocyten und stark pigmentierten als Makrophagen bezeichneten perivasculären Zellen. In sieben histochemisch untersuchten Melanoblastomen der Chorioidea besaßen die Makrophagen eine starke Aktivität unspezifischer Esterasen und saurer Phosphatasen, in den Melanocyten war die Aktivität schwach. Ein Melanoblastom vom epitheloiden Typ enthielt vorwiegend Zellen mit starker Enzymaktivität und zeigt außerdem alle Übergänge zwischen Melanocyten und Makrophagen. In allen Melanoblastomen waren die Fraktionen der isodynamen Esterasen und sauren Phosphatasen (Zymogramme nach Agarelektrophorese des Tumorextraktes) gleichartig, lediglich die Aktivität der einzelnen Fraktionen ist etwas verschieden. Die als Makrophagen bezeichneten Zellen sind ebenso wie die Melanocyten tumoreigene Zellen. Die starke Phosphataseaktivität wird auf den verstärkten Einbau von Phosphat (P³²) in die Tumorzellen bezogen.

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Summary The malignant melanoma of the choroid consists of melanocytes with slight pigmentation and of tumor cells (macrophage-like) that are heavily pigmented and perivascularly localized. In 7 malignant melanomas of the choroid belonging to the spindle cell and epithelioid type (Reese), the macrophage-like tumor cells histochemically showed a high activity of nonspecific esterases and acid phosphatases; the activity in melanocytes was low. A malignant melanoma of the epithelioid type chiefly contained tumor cells with high enzymatic activity and showed all transitional cells from melanocytes to macrophages. Zymograms of all melanomas (electrophoresis of tumor extract on agar-agar) showed similar fractions of isodynamic esterases and acid phosphatases which differed only in activity. The macrophage-like cells and the melanocytes were tumor cells. A relation presumably existed between the high activity of phosphatases and the increased incorporation of phosphate (P³²) into the tumor cells.

     

Extrarenal nephroblastomas

Summary The cases of extrarenal nephroblastoma published in the world literature have been tabulated and reviewed, and are discussed from a historical point of view.The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author     

Hormonal factors in human carcinogenesis

Summary A synopsis is presented of hormone-cancer relationships as seen by an epidemiologist. Emphasis has been placed on reproductive risk factors and cancers of the endometrium, ovary and breast. Although there are definite parallelisms in this regard the aetiological mechanisms for these three sites may be different.Evidence is accumulating that the protective effect of an early first birth and of subesequent pregnancies on breast cancer risk can be understood biologically in terms of interference with the occurrence of preneoplastic lesions.The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.Presented at the EACR mecting, Copenhagen, 21 September 1983     

The treatment of hypertension: New lamps for old?

Summary Meta-analysis of clinical trials does not help the clinician to treat individual patients. A general conclusion that the reduction of high blood pressure is beneficial has to be matched by specific information about the level of blood pressure that is acceptable and about the effect of particular doses of specific drugs. Results obtained from trials of old-fashioned antihypertensive drugs cannot confidently be extrapolated to modern agents. Sufficient data do not exist to encourage universal drug treatment for patients with mild hypertension.     

Reversible Prolonged Pacemaker Failure Due to Electrocautery

Despite improved technology, permanent pacemakers remain susceptible to electromagnetic interference, including electrocautery. We describe sudden, apparently irreversible output loss in a pacemaker associated with the use of electrocautery, despite standard precautionary measures. When tested by the manufacturer several weeks later, pulse generator function was normal and it was functioning in the reset mode. We postulate that pacemaker failure was related to current drain causing lockout of the voltage control oscillator, the mechanism responsible for regulating pulse width. Further reduction in battery voltage, due either to exposure to cold temperatures while the device was being transported to the manufacturer or to further use of electrocautery during device explantation, may have allowed it to reach the reset level, permitting normal function to resume.