[Changes in the collagen structures of human heart valves in relation to age and hypertension]. / Veränderungen der kollagenen Strukturen menschlicher Herzklappen in Abhängigkeit von Alter und Hypertonie.

Using polarization microscopy and morphometrical methods, the influence of hypertension on the collagenous structures in the Lamina fibrosa of bicuspid valves of 14 middle-aged persons (30 to 50 years) were examined. The measurements were performed on histological sections. A group of 14 middle-aged subjects free from heart disease served as the control group. Furthermore, the results were compared to earlier findings on the histological biomorphosis of the atrioventricular valves. The following changes were observed and quantitatively determined: a) an enhancement of the percentage of the mechanically more resistant collagenous fibers (unsilvered, type I collagen), b) a stronger lateral aggregation of the collagenous fibrils of both types I and III collagen, c) a significant decrease of the total numbers of collagenous fibers per measuring area, and d) a significant decrease of the portion of silvered fibers (type III collagen) per measuring area for both sexes. The fiber density distributions confirm the observed changes: in the hypertension group the collagenous fibers are less densely distributed than in the control group. The observed regression of the content of collagenous fibers in the hypertension group is probably due to the anti-hypertensive treatment. Following the findings the turn-over of type III collagen is stronger influenced than that of type I collagen. The initial results determined in human heart valves confirm findings in animal models and characterize them with regard to the collagen types mentioned.

[Laser scanning topography and polarimetry with implantation of intraocular lenses before and after cataract surgery]. / Scanning-Laser-Topometrie und Polarimetrie vor und nach Katarakt-Operationen mit Implantation von Intraokularlinsen.

BACKGROUND: In the last years, scanning laser measurements were established in glaucoma diagnostics. Techniques of special interest are scanning laser topometry (SLT) for exact measurements of the optic disc and its cup and scanning laser polarimetry (SLP) for precise assessment of the retinal nerve fiber layer thickness. As glaucoma patients often suffer from a cataract, too, and a trabeculectomy additionally favors the advance of lens opacities, in the follow up of glaucoma patients cataract surgery is often necessary. PATIENTS AND METHODS: The influence of cataract surgery in phacotechnique with intraocular lens implantation (31 PMMA-IOLs, Pharmacia/Upjohn, model 811 B, and 25 HEMA/MMA-IOLs, Technomed, Memory Lens) on SLT and SLP was evaluated before and 3 to 4 weeks after cataract surgery in 56 eyes of otherwise healthy patients. Lens opacities were classified according to LOCS III. For SLT, we applied a TopSS, and for SLP a Nerve Fiber Analyzer II and a GDx (LDT, USA). RESULTS: Our results show that SLT and SLP are mostly performable at lens opacities with visual acuity reductions down to 0.16. In SLT, we usually found no big differences in the assessed parameters before and after cataract surgeries with IOL implantation. Standard deviations between three single measurements were mostly smaller postop. In SLP, nerve fiber layer patterns were very similar before and after cataract surgeries with IOL implantation whereas total nerve fiber layer thickness values postoperatively were slightly higher. CONCLUSIONS: Our results indicate that cataract surgeries with IOL-implantation have only mild influence on SLT and SLP. These findings seem to be of clinical interest especially in the follow up of glaucoma patients.

Proliferation and survival of mammary carcinoma cells are influenced by culture conditions used for ex vivo expansion of CD34(+) blood progenitor cells.

Malignant cell contamination in autologous transplants is a potential origin of tumor relapse. Ex vivo expansion of CD34(+) blood progenitor cells (BPC) has been proposed as a tool to eliminate tumor cells from autografts. To characterize the influence of culture conditions on survival, growth, and clonogenicity of malignant cells, we isolated primary mammary carcinoma cells from pleural effusions and ascites of patients with metastatic breast cancer and cultured them in the presence of stem cell factor (SCF), interleukin-1beta (IL-1beta), IL-3, IL-6, and erythropoietin (EPO), ie, conditions previously shown to allow efficient ex vivo expansion of CD34(+) BPC. In the presence of serum, tumor cells proliferated during a 7-day culture period and no significant growth-modulatory effect was attributable to the presence of hematopoietic growth factors. When transforming growth factor-beta1 (TGF-beta1) was added to these cultures, proliferation of breast cancer cells was reduced. Expansion of clonogenic tumor cells was seen in the presence of SCF + IL-1beta + IL-3 + IL-6 + EPO, but was suppressed by TGF-beta1. Cocultures of tumor cells in direct cellular contact with hematopoietic cells showed that tumor cell growth could be stimulated by ex vivo expanded hematopoietic cells at high cell densities (5 x 10(5)/mL). In contrast, culture under serum-free conditions resulted in death of greater than 90% of breast cancer cells within 7 days and a further decrease in tumor cell numbers thereafter. In the serum-free cultures, hematopoietic cytokines and cellular contact with CD34(+) BPC could not protect the tumor cells from death. Therefore, ex vivo expansion of CD34(+) BPC in serum-free medium provides an environment for efficient purging of contaminating mammary carcinoma cells. These results have clinical significance for future protocols in autologous progenitor cell transplantation in cancer patients.

Circulatory and myocardial effects of different sodium antagonistic drugs in comparison to the calcium antagonist verapamil.

The hemodynamic effects of intravenous class I and class IV antiarrhythmic drugs were investigated at different doses in comparison. In open-chest rats hemodynamic measurements in the intact circulation and isovolumic registrations 5 min after infusion of flecainide (2, 4, 8 mg/kg), disopyramide (1, 2, 4, 8 mg/kg), quinidine (5 and 10 mg/kg) and verapamil (0.35, 0.7, 1.5 mg/kg) were compared to saline controls. After clinically usual doses all investigated drugs had no effects on stroke volume, cardiac output, dp/dtmax and systemic resistance. The isovolumic pressure generating capacity of the left ventricle was not decreased at these doses. High intravenous doses of the drugs, however, caused a significant depression of myocardial performance (pressure generating capacity). Furthermore, flecainide decreased mean aortic pressure and heart rate, while disopyramide had no significant effect on the peripheral circulation. Blocking of the autonomic system (1 mg/kg propranolol and 0.1 mg/kg atropine) did not change significantly the action of disopyramide. Quinidine lowered heart rate and pressures. Verapamil reduced the heart rate and tended to decrease the mean aortic pressure. Besides the negative inotropic action of high doses the different hemodynamic profiles of class I and class IV antiarrhythmic drugs might be of importance for intravenous application in patients with left ventricular dysfunction.

Neurohumorally induced cardiac dysrhythmias during nitrous oxide-oxygen-thiopental anesthesia.

Barbiturate, nitrous oxide, and oxygen are commonly used by the oral and maxillofacial surgeon to anesthetize the ambulatory oral surgery patient. The authors report three cases of ventricular dysrhythmia occurring from surgical stimulation during nitrous oxide-oxygen-thiopental anesthesia. These dysrhythmias were most likely mediated via direct neural stimulation of cardiac sympathetic nerves. Concomitant with adrenergic stimulation, a rise in the arterial plasma norepinephrine level was documented, along with an increase in the rate-pressure product. Immediate recognition and treatment of ventricular dysrhythmia is mandatory to preclude further serious cardiovascular complications or death.

Arterial plasma epinephrine concentrations and hemodynamic responses after dental injection of local anesthetic with epinephrine.

The effect of dental injection of local anesthetic on arterial plasma epinephrine concentrations and cardiovascular functions was assessed in patients having a maxillary third molar extracted. After three and five minutes, arterial plasma epinephrine concentrations were more than two times higher than baseline values in patients who were given an injection of a standard Carpule (1.8 ml) of 2% lidocaine with 1/100,000 epinephrine (18 micrograms). The heart rate and pressure-rate product increased slightly above baseline control values, and the mean arterial pressure declined slightly (P less than .05) after five minutes. Patients who received an injection of lidocaine alone had no significant change of plasma epinephrine or of the cardiovascular parameters measured. Although the hemodynamic responses to lidocaine plus epinephrine in these healthy young adults were small, the significant increase of systemic plasma epinephrine concentrations suggests that high-risk patients who receive this type of anesthesia should be monitored carefully.

Effect of spinal anesthesia on adrenergic tone and the neuroendocrine responses to surgical stress in humans.

In order to quantitate the effect of spinal anesthesia on adrenergic tone, plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured by radioenzymatic assay in 24 patients were then compared to those of 10 patients receiving inhalation anesthesia (halothane-nitrous oxide). High thoracic dermatome spinal anesthesia caused suppression of both arterial plasma NE and EPI and a fall of mean arterial pressure (MAP); in contrast, no changes of NE, EPI, or MAP were observed in patients receiving low spinal anesthesia. Overall, there was a relationship between the sensory dermatome anesthesia level and changes of both plasma NE (r = 0.71, P less than 0.001) and EPI (r = 0.52,P less than 0.02). In the inhalation anesthesia group, plasma NE increased during the operation and plasma levels of NE, EPI, growth hormone, and cortisol were elevated during the postoperative recovery period. These neuroendocrine responses to surgical stress were not observed in patients receiving either low or high spinal anesthesia. Thus, the effect of spinal anesthesia on adrenergic tone depends on the cord level of anesthesia and can be quantitated by measurement of plasma catecholamines. The neuroendocrine responses to surgical stress were prevented in patients who received low spinal anesthesia and who had no suppression of efferent adrenergic tone. These findings indicate that neural afferents from the site of tissue injury, which were blocked by low spinal anesthesia, mediated both the adrenergic and the hormonal responses to surgical stress in the inhalation anesthesia group.

Relationship of impaired insulin secretion during surgical stress to anesthesia and catecholamine release.

Impaired insulin secretion has been observed during surgical stress in man. To determine the relationship between insulin secretion during anesthesia and surgical stress and plasma levels of norepinephrine (NE) and epinephrine (Epi), studies were performed in 16 patients before and during elective minor surgical procedures. In 8 patients studied during halothane inhalation anesthesia before operation, the acute insulin response (AIR) to glucose (5 g, IV) fell to 51 +/- 3% of the preanesthesia AIR (mean +/- SEM; P < 0.001). This inhibition of AIR appeared unrelated to increased adrenergic activity, since during anesthesia alone, plasma NE did not change significantly and plasma Epi fell from 94 +/- 11 to 34 +/- 10 pg/ml (P < 0.01). During the postoperative recovery period in these patients, after discontinuation of the anesthesia, the AIR to glucose was 50 +/- 5% of the preanesthesia baseline response (P < 0.001). At this time, both plasma NE and Epi were increased compared to preanesthesia levels [NE: 240 +/- 40 (preanesthesia) vs. 340 +/- 43 (postoperative); Epi: 219 +/- 43 (preanesthesia) vs. 94 +/- 11 (postoperative); both P < 0.05]. In eight patients undergoing similar operations during low spinal anesthesia, no inhibition of the AIR to glucose occurred, and plasma NE and Epi did not increase significantly during or after the operation. During the recovery period, there was a relationship between plasma Epi and the degree of inhibition of the AIR to glucose (r = 0.70; n = 11; P < 0.05). Thus, inhibition of insulin secretion during surgical stress may be mediated both by direct effect of the anesthesia used and by activation of the sympathetic nervous system.

Effects of anesthesia and surgical stress on insulin secretion in man.

Surgical stress with inhalation anesthesia is associated with increased circulating catecholamines, hyperglycemia, and impaired insulin secretion. These changes do not occur during surgical stress with spinal anesthesia, suggesting that they are neurally mediated due to pain initiated afferents from the site of tissue trauma. Inhalation anesthesia alone was found to suppress basal insulin levels and the insulin response to intravenous glucose with no significant increase in plasma norepinephrine and a decrease in plasma epinephrine. Thus, these changes in insulin secretion are not attributable to adrenergic mechanisms. In the postoperative period, however, suppressed insulin secretion was found to be correlated with elevated plasma epinephrine concentrations and may, therefore, be mediated by adrenergic mechanisms. Thus, these findings indicate that impaired insulin secretion during surgical stress may have two etiologies--one related to the type of anesthesia used and the other due to adrenomedullary stimulation due to pain.

Limb blood flow. The influence of temperature during halothane-nitrous oxide anesthesia.

Twenty adult patients were examined before anesthesia, during anesthesia, and at the end of surgery to determine the influence of body cooling on limb blood flow during prolonged halothane-nitrous oxide anesthesia. Measurements included temperature, mean arterial pressure, and leg blood flow. Cooling was prevented in ten patients by warmed anesthetic gases. The mean tympanic temperature at end of surgery was 37 degrees C for the warmed (W) and 35 degrees C for the unwarmed (UW) patients, a significant difference. The mean value for leg blood flow was significantly decreased in the UW patients (W = 5.0 vs UW = 3.1 mL/100 cc of tissue/min). These results indicate that body cooling during prolonged inhalation anesthesia was associated with a reduced limb blood flow. Therefore, pulmonary warming may be of potential benefit under similar conditions to help prevent intraoperative vascular complications.

Large mononuclear (veiled) cells like 'Ia-like' membrane antigens in human afferent lympn.

Studies were done to see whether large mononuclear cells in human afferent lymph possess cytoplasmic veils or Ia-like antigens on their surface. Small numbers of veiled cells were seen in lymph from five subjects: one with post-phlebitis oedema, one with trophic ulcers of the legs, one with common variable immoglobulin deficiency, and two control subjects. They were not seen in afferent lymph from two other patients with oedema of the legs, and one control subject. Only occasional large mononuclear (veiled) cells formed rosettes with IgG-coated erythrocytes, and they did not attach to glass after overnight culture. They had a distinctive nuclear structure and fluorescent antisera showed that their membranes and veils possessed large amounts of 'Ia-like' antigens. They did not have surface immunoglobulin or a monocyte membrane antigen. It was concluded that the membrane and nuclear structure of human large mononuclear (veiled) cells is in keeping with the possibility that they are derived from Langerhans' cells in the skin, and that they can become interdigitating cells in lymphoid tissues. It is suggested that these cells have an important role in the transport of antigens from the skin and the stimulation of T lymphocytes in lymphoid tissues.

Arterial-venous differences of plasma catecholamines in man.

To investigate the relationship between forearm venous levels of catecholamines and systemic levels, simultaneous arterial and forearm vein blood samples were obtained from 14 subjects undergoing elective dental procedures and assayed with a sensitive and specific radioenzymatic assay. Baseline venous levels of norepinephrine were greater than arterial levels (305 +/- 30 pg/ml versus 221 +/- 18; +/- SEM, p less than .005). Conversely, arterial epinephrine levels were higher than venous (132 +/- 17 pg/ml versus 80 +/- 10; p less than .005). There was a significant relationship between arterial and venous levels of both norepinephrine (r = .77, p less than .01) and epinephrine (r = .67, p less than .01). The arterial-venous epinephrine difference increased from the baseline value of 44 +/- 14 pg/ml to 108 +/- 16 (p less than .005) by 3 min after subcutaneous injection of epinephrine (18 microgram), but the arterial-venous difference returned to 65 +/- 24 by 5 min after injection (p = NS versus baseline). These findings indicate that under the conditions of this study, forearm tissues produced more norepinephrine than they removed, but removed more epinephrine than they produced. Baseline venous and arterial levels were related; when epinephrine production was augmented, there was a short time lag for the venous epinephrine increase.

Sequence of return of neurological function and criteria for safe ambulation following subarachnoid block (spinal anaesthetic).

Twenty-three adult men were studied during and after subarachnoid block anaesthesia for elective surgery. Measurements were obtained of mean arterial pressure and pulse, both supine and after standing for five minutes, core body (tympanic) and peripheral skin (toe) temperatures and blood flow in the leg. Time of measurements included one hour after the injection of tetracaine and after regression of the block. Results obtained indicate that the sequence of return of neurological activity following tetracaine subarachnoid block is sympathetic nervous system activity, pinprick sensation, somatic motor function followed by proprioception in the feet. This progression provides the basis for recommended criteria which indicate when it is safe for patients who have been subarachnoid block anaesthesia to become ambulatory. These criteria include: (1) return of pinprick sensation in the peri-anal area (sacral 4--5); (2) plantar flexion of the foot (while supine) at pre-anaesthetic levels of strength; and (3) return of proprioception in the big toe, always provided that the patient is not hypovolaemic or sedated.

Prevention of post-anaesthesia shivering.

This study involves ventilation of the lungs with warmed humidifed anaesthetic gases during prolonged elective abdominal operations. Tympanic, oesophageal and toe temperatures were compared bewteen twenty warmed and twenty un-warmed patients at various times during operation and recovery. Fifty per cent (10/20) unwarmed patients shivered in the recovery room, while none of the warmed patients shivered. Our data indicate that pulmonary ventilation with warm humidified anaesthetic gases provides heat transfer by the lungs, preventing hypothermia during operation and post -anaesthesia shivering is prevented by maintaining the patient normothermic in both the operating room and the recovery room.

Physiopathology and control of postoperative pain.

Potent systemic (narcotic) analgesics, when given in doses sufficient to produce ample pain relief, usually also produce mental and respiratory depression and, at times, circulatory impairment, that prolong postoperative morbidity. Complications due to morphine sulfate or meperidine hydrochloride can be minimized by titrating the patient's pain with small intravenous doses of narcotics (morphine sulfate, 2 to 3 mg, or meperidine hydrochloride, 15 to 25 mg) administered slowly at 15- to 20-minute intervals until the pain is relieved. On the third or fourth postoperative day, acetaminophen tablets usually suffice to provide relief of pain with little or no risk to patients. Continuous segmental epidural block or intercostal block, with or without splanchnic block, provide excellent pain relief that, in contrast to the narcotic, is complete. These are especially useful after operations on the chest or abdomen or the lower extremity. Regional analgesia is especially indicated in patients not adequately relieved from severe postoperative pain with narcotics, or when these drugs are contraindicated by advanced pulmonary, renal, or hepatic disease. Continuous caudal analgesia is also effective to completely releive severe postoperative pain in the lower limbs and perineum.

Early reversal of postoperative hypoxemia.

Peridural analgesia was combined with the respiratory-stimulant effect of doxapram for intermittent hyperinflation of the lungs to reverse early postoperative (PO) hypoxemia following inhalation anesthesia for upper abdominal operations. Twenty unpremedicated men undergoing upper abdominal operations were studied for 5 hours in the recovery room. Ten of these patients received doxapram plus peridural analgesia; the other 10, doxapram plus morphine analgesia. Rectal temperature, PaO2, PaCO2, respiratory rate, exhaled minute ventilation (VE), tidal volume (VT), and blood pressure and pulse were measured. The mean increase from control for VE was 9.6 L/min and for VT, 356 ml/breath during doxapram therapy for the morphine group. Corresponding values for the peridural group were 14.4 L/min for VE and 660 ml/breath for VT. Mean PaO2 for the morphine group decreased significantly from the corresponding preoperative value (p less than 0.005). Lack of significant change between preoperative and PO values for PaO2 for the peridural group would indicate that under the conditions of this study, early PO hypoxemia can be reversed by the combination of peridural analgesia with doxapram therapy.

Pethidine revisited: plasma concentrations and effects after intramuscular injection.

Plasma concentrations of pethidine following i.m. gluteal injection were measured in surgical patients and volunteers. The mean plasma concentrations tended to be higher in the patients than in the volunteers; this may be a result of a slower initial absorption rate. At least 80% of the dose was absorbed from the injection site over the 6-hr period of the study. Fluctuations in plasma pethidine concentration were observed, probably caused by variations in local and systemic blood flow. This effect was more noticeable in the patient group. In general, the time-course of subjective effects in volunteers could be related to maximum plasma pethidine concentrations. However, patients appeared to be less sensitive to these effects at similar plasma drug concentrations, possibly because of catecholamine-mediated stimulus, suggesting that plasma concentrations may be a poor guide to the clinical response in patient-volunteer comparison.