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Calcium and contractile responses to phorbol esters and the calcium channel agonist, Bay K 8644, in arteries from hypertensive rats. This study examined the calcium dependency of contractions in arteries from rats made hypertensive by aortic coarctation and in rats with genetic hypertensive (stroke-prone spontaneously hypertensive rats). Mesenteric artery and aortic strips were suspended in tissue baths for isometric force recording and contractions to two drugs were characterized: 1) a phorbol ester, TPA (12-O-tetrade-canoylphorbol-13-acetate), and 2) the calcium channel agonist, Bay K 8644. Thoracic aortae and mesenteric arteries from hypertensive rats were more sensitive to the contractile properties of the protein kinase C activator TPA than comparable arteries from normotensive rats. In thoracic aortae from coarcted rats, the contractile activity of Bay K 8644 was potentiated compared to normotensive values. In the presence of 19.2 mmol/L KCl, responses to Bay K 8644 in thoracic aortae from normotensive rats were potentiated and did not differ from coarcted values. In contrast, contractions to Bay K 8644 and TPA in abdominal aortae obtained below the coarctation were not different from normotensive values. Upon exposure to 26.2 mmol/L KCl, contractions to Bay K 8644 in abdominal aortae were potentiated and those in aortae from coarcted rats did not differ from sham values. Contractile responses to both drugs were blocked by nifedipine and verapamil and responses were attenuated in calcium-free solution. We conclude that calcium channel function and its regulation by protein kinase C contribute to altered vascular reactivity in hypertension. Further, these abnormalities have a pressure dependency, because they did not occur in abdominal aortae from coarcted rats.
Hyaluronan in pleural effusions and in serum. It has been suggested that a high level of hyaluronan (hyaluronic acid, HYA) in pleural fluid is an indicator of malignant mesothelioma. In 78 consecutive patients with pleural effusion of various causes the HYA concentration was measured in pleural fluid samples and in serum. Nine patients had malignant pleural mesothelioma, and in three of them the HYA level in pleural fluid was 100 mg/l or more. In 42 patients with effusions due to metastatic malignancy, the mean HYA in the pleural fluid was 75 mg/l, and in five the HYA level was above 100 mg/l. Cardiac insufficiency caused the effusion in 11 patients, of whom two had a level above 100 mg/l in pleural fluid. Four patients had a serologically confirmed viral infection and had HYA levels in pleural fluid of 8, 157, 335, and 554 mg/l, respectively. One patient had postinfectious effusion with an HYA level in pleural exudate of 748 mg/l, the highest in this investigation. Two patients had benign asbestos pleural effusions, and both had high pleural HYA levels (256 and 490 mg/l, respectively). The serum HYA values were much lower than in the pleural fluid, namely from 15 to 480 micrograms/l; the levels were independent of the levels in the pleural fluid. Thus, a high level of HYA in pleural fluid is not specific for mesothelioma but can occur in other malignant or benign diseases, and a low level does not exclude mesothelioma.
Increased platelet membrane sodium-proton exchange rate in spontaneously hypertensive rats. It has been proposed that increased Na-H exchange activity is involved in the pathophysiology of genetic hypertension. We studied platelets of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY), and domestic Wistar rats (DWR), since platelets have similarities to smooth muscle cells and have been shown to have potentially related ion metabolism abnormalities, such as increased intracellular calcium activity. We determined the exchange rate by the intracellular acidification-dependent, extracellular sodium-dependent volume increase. The rate of increase during the first 3 min is linear and is shown to be higher in SHR (0.475 X min-1) than in WKY (0.410 X min-1) or DWR (0.389 X min-1). We conclude that the Na-H activity is increased in platelets of SHR. Similar findings in lymphocytes and neutrophils of SHR, and analogous findings in platelets of humans with essential hypertension, suggest that this abnormality is expressed by several cell types, some of which may be involved in the pathophysiology of genetic hypertension in both rats and humans.
The vascularized fibula graft in mandibular reconstruction. The use of a vascularized graft from the fibula for mandibular reconstruction is presented. The great strength, pliability, and long vascular pedicle that characterize such grafts make them particularly suitable for this type of repair. The results in six cases were highly satisfactory. Masticatory function was well restored, without alteration of the facial contour, and with minimal sequelae at the donor site.
Effects of doxazosin on blood pressure, renin-angiotensin-aldosterone and urinary kallikrein. Doxazosin, a new quinazoline-derivative postsynaptic alpha 1-adrenoceptor antagonist, was studied in this randomized, double-blind, placebo-controlled 12-week study. Its effects on blood pressure (BP), heart rate, metabolic functions and renal hormones were analyzed after administration of a single oral morning dose in a 3-phase fashion when administered to 17 patients (11 women, 6 men, 21 to 59 years) with mild to moderate uncomplicated essential hypertension. After titrating the antihypertensive effective dose biweekly from 1 to 8 mg/day and a mean end titration-point dose of 4.14 +/- 0.1 mg (mean +/- standard error of the mean) at week 8 of treatment, it was adjusted to maintain diastolic BP at levels less than or equal to 90 mm Hg for up to 12 weeks of treatment when, at a final mean dose of 4.35 +/- 0.2 mg/day, BP decreased in all patients by a mean 31 +/- 3/17 +/- 2 (supine) and 39 +/- 3/15 +/- 3 (standing) mm Hg (p less than 0.005) with no increase in heart rate and no "first-dose phenomenon." Neither the renin-aldosterone system nor electrolyte excretion was significantly affected. Renal function and metabolic parameters also remained unchanged. Urinary kallikrein excretion was augmented 2.47-fold (p less than 0.002). There was good tolerance; 1 patient discontinued the study because of dry nose. These results suggest that long-term monotherapy with doxazosin is an effective and safe antihypertensive agent for mild to moderate essential hypertension that stimulates urinary kallikrein excretion.
Lipomatous hamartoma of the orbit. Proliferations of mature adipose tissue, while common in retroperitoneal and subcutaneous sites, rarely occur in the orbit. We describe the clinical, radiographic, and histopathologic findings of a nonencapsulated lipomatous tissue overgrowth of the right orbit in a 35-year-old man. The mass had caused proptosis since childhood and was apparently present since birth. Due to the age at onset, the histologic similarity to normal orbital fat, and the lack of encapsulation or choristomatous elements, we propose the term lipomatous hamartoma for this entity.
Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. The role of perfusion pressure and flow during cardiopulmonary bypass with moderate hypothermia and hemodilution in the development of new postoperative renal or clinically apparent cerebral dysfunction was examined in 504 adults. Cardiopulmonary bypass flow was targeted at greater than 40 mL.kg-1.min-1 and pressure at greater than 50 mm Hg. Flows and pressures less than target occurred in 21.6% and 97.1% of patients, respectively. Fifteen patients (3.0%) suffered new renal and 13 (2.6%) new central nervous system dysfunction. Low pressure or flow during cardiopulmonary bypass, expressed in absolute values or in intensity-duration units, were not predictors of either adverse outcome. Multivariate analysis identified use of postoperative intraaortic balloon counterpulsation (p less than 10(-6], excessive blood loss in the ICU (p less than 10(-4], need for vasopressors before cardiopulmonary bypass (p less than 10(-4], postoperative myocardial infarction (p less than 10(-3], emergency reoperation (p less than 0.002), excessive postoperative transfusion (p less than 0.02), and chronic renal disease (p less than 0.03) as independent predictors of postoperative renal dysfunction. Independent predictors of postoperative central nervous system dysfunction were cardiopulmonary resuscitation in the intensive care unit (p less than 10(-6], intracardiac thrombus or valve calcification (p less than 0.02), and chronic renal disease (p less than 0.03). Age greater than 65 years (40.7% of patients) did not predict either outcome. We conclude that failure of the native circulation during periods other than cardiopulmonary bypass rather than the flows and pressures considered here is the major cause of renal and clinically apparent central nervous system dysfunction after cardiac operations.
The perception of life events and daily stress in nonulcer dyspepsia. Previous studies on the association of nonulcer dyspepsia with major life events were performed without emphasis on the perception of these events, and have yielded conflicting results. The present study examined the perception of life events and, in addition, the role of daily "hassles" (stressful events) in patients with nonulcer dyspepsia. Thirty-three dyspeptic patients as defined by normal endoscopy and ultrasonogram and 33 controls of comparable sex, age, and social class were recruited for study. Both groups were asked to select from 56 major life events those they had experienced and to give a rating on how they perceived them. They were further asked to select similarly from 117 items of daily stress and to rate the severity of each item. The results demonstrated that the number of positive and negative events and the positive score were similar in both dyspeptic patients and controls, but dyspeptic patients had a higher perceived magnitude of negative events and a higher score of total life change as given by the summation of magnitude of positive and negative events (both p less than 0.05). The "hassles" scores were not significantly different between dyspeptic patients and controls. Analysis of individual life events revealed that dyspeptic patients had significantly (p less than 0.05) higher scores than controls in items of minor law violations, major change in closeness of family members, and major personal illness or injury. We conclude that patients with nonulcer dyspepsia have higher negative perception of major life events, which indicates that psychological factors may play a role in the pathogenesis of nonulcer dyspepsia.
Colobronchial fistula: a rare complication of Crohn's colitis. A 29-yr-old white woman presented with chronic pneumonia in the left lower lobe and with left pleural effusion. She was known to have inflammatory bowel disease, but she was asymptomatic under maintenance treatment with 5-ASA. She received numerous antibiotic regimens according to susceptibility testing of microorganisms cultured from sputum and bronchial lavage and on an empiric basis was also given antituberculosis treatment, but there was no clinical improvement or change in the chest radiographic findings. Sputum was repeatedly examined and yielded, among other organisms, Clostridium inocuum, Enterobacter, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. On one microscopic examination of sputum, the presence of feculent material was suspected. A subsequent gastrografin enema revealed a cologastric and colobronchial fistula between the splenic flexture of the colon and the greater curve of the stomach and the bronchial system. Segmental resection of the colon and resection of the lower lobe of the left lung were performed. Histologic findings of the resected colon were consistent with Crohn's disease. After a long period of postoperative recovery, the patient returned to good general health and well-being. To our knowledge, a colobronchial fistula caused by Crohn's colitis has not been previously reported.
Verapamil increases serum alkaline phosphatase in hypertensive patients. In rats, verapamil decreases intestinal absorption of calcium, increases serum parathyroid hormone (PTH), and induces osteopenia. In this prospective study, verapamil 80-120 mg three times daily was given for 2 months to 20 patients with hypertension, and the effects on calcium homeostasis were recorded. This dose of verapamil significantly reduced supine systolic and diastolic blood pressure (+/- SD) from 158/100 +/- 9/8 mmHg to 146/89 +/- 14/8 mmHg (P = 0.001). Serum alkaline phosphatase (ALP) increased significantly from 2.77 +/- 1.06 mu kat l-1 to 3.19 +/- 1.22 mu kat l-1 (P = 0.004), and isoenzymes of ALP of skeletal origin appeared after verapamil treatment. The excretion of sodium in the urine increased (Na/creatinine ratio 8.95 +/- 6.01 before and 13.16 +/- 8.26 after verapamil; P = 0.04), while the excretion of calcium, phosphate and potassium was not changed. PTH was slightly increased at the end of verapamil treatment (1.09 +/- 0.54 vs. 0.98 +/- 0.74 microgram l-1; P = 0.07), and s-1,25(OH)2D3 was also somewhat increased (22.3 +/- 14.4 vs. 17.6 +/- 4.9 ng l-1; P = 0.26). Serum Ca was not affected by verapamil (before verapamil 2.43 +/- 0.11 mmol l-1, after verapamil 2.40 +/- 0.12 mmol l-1; P = 0.28). The increase in serum ALP demonstrates that verapamil affects bone cell metabolism in man. This effect could be secondary to the enhancement of PTH secretion.
Postmortem chorionic villus sampling is a better method for cytogenetic evaluation of early fetal loss than culture of abortus material. In utero chorionic villus sampling at the time of diagnosis of intrauterine fetal death is compared with more traditional use of cultured fetal skin, products of conception, or amniocentesis. A total of 102 specimens from early fetal losses were evaluated for success in karyotyping and chromosomal results. We found postmortem chorionic villus sampling is technically possible, offers the highest likelihood of getting a cytogenetic result, and is a rapid, reliable, and safe technique. The extraembryonic component of intrauterine fetal deaths appears to remain viable and continues to grow long after the embryo has died. Samples obtained at the time of diagnosis of fetal death offer the greatest changes of successfully obtaining a karyotype. The incidence of chromosome abnormalities associated with fetal loss, particularly trisomies, is higher than previous data suggested.
Glucose and fat metabolism during short-term starvation in cirrhosis. To evaluate the metabolic consequences of short-term (i.e., less than 24 hours) starvation, glucose and fat metabolism were studied in eight healthy subjects and in eight patients with stable cirrhosis after 16-hour and again after 22-hour starvation by 3-[3H]glucose and [14C]palmitate turnover and by indirect calorimetry. Although patients and controls showed significant increases in free fatty acid concentration (respectively, 48% +/- 12% and 53% +/- 17%) and turnover (55% +/- 14% and 71% +/- 21%) during short-term starvation, the values after 16- and after 22-hour starvation were higher in cirrhosis. Fat oxidation was enhanced in the patients, but did not increase during fasting in contrast to controls (increase 19% +/- 17%, P less than 0.05). Net glucose oxidation was decreased in postabsorptive cirrhotics (P less than 0.05). Although postabsorptive glucose turnover was not different from controls, starvation induced a greater decrease in glucose turnover in the patients (25% +/- 3% vs. 10% +/- 3%, P less than 0.05). This was not reflected in plasma glucose concentrations. In conclusion, the effects of starvation on glucose and fat metabolism are enhanced in cirrhosis; fasting hypoglycemia is prevented by decreased use of glucose. It remains to be established whether these changes are merely explained by defective liver function, per se.
Improved cannulation method for extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation has been shown to be useful for patients in reversible cardiogenic shock. Effective arterial cannulation techniques for infants have been developed that are simple to use and require minimal subsequent vascular repair or reconstruction after removal. Groin cannulation in adults frequently requires bidirectional arterial cannulation to ensure adequate distal perfusion as well as frequent complex arterial repairs after discontinuation. We describe a simple arterial cannulation technique using a single right-angle, high-flow arterial cannula. With this technique adequate bidirectional arterial perfusion is maintained with a single arterial cannula while the need for vascular repairs or reconstruction is minimized.
A comparison between single and double dose intravenous Timentin for the prophylaxis of wound infection in elective colorectal surgery. A prospective, randomized, single-blind, controlled clinical trial was undertaken to determine whether two doses of systemic Timentin provided superior prophylaxis against postoperative sepsis in elective colorectal surgery compared with a single dose of the same antibiotic. Timentin, a combination of ticarcillin and clavulanic acid was administered intravenously (3.1 g) at the commencement of operation to all patients, and this was repeated after 2 hours in those patients randomized to receive a second dose. The wound infection rate was 11 percent in the 143 patients completing follow-up and receiving a single dose, and 13 percent in the 128 patients receiving two doses of Timentin (P greater than 0.05). The rates of postoperative septicemia 3 vs. 4 percent and intra-abdominal abscess 5 vs. 8 percent were similar. Multivariate analysis of the factors likely to affect postoperative would infection rate demonstrated an association with the type of hospital, public or private, wound infection rate 16 and 6 percent, respectively (P less than 0.01), and the surgeon group defined by the number of patients contributed greater than 25 or less than 25, wound infection rate 6 and 18 percent, respectively (P less than 0.05). We concluded that a single dose of intravenous Timentin was as effective as two doses for prophylaxis against surgical infection and that the surgeon group and the hospital in which the operation took place were statistically significant predictors of postoperative wound infection.
Coronary angioplasty in patients with severe left ventricular dysfunction. The applications for coronary angioplasty have greatly expanded and the procedure is now increasingly used in complex and potentially high risk conditions. This report describes the short- and long-term effects of coronary angioplasty in 61 patients with severely depressed left ventricular function (ejection fraction less than or equal to 35%) with unstable or refractory anginal symptoms, or both, in whom revascularization was necessary despite increased risk. In a retrospective analysis of 1,260 patients undergoing angioplasty between January 1985 through December 1987, 61 had an ejection fraction less than or equal to 35%. The common clinical presentation was unstable angina (70%) with or without recent myocardial infarction. Mean left ventricular ejection fraction was 27 +/- 6%. Forty-five patients (74%) had multivessel disease. Clinical success after angioplasty was achieved in 55 patients (90%). Major complications (death, infarction and emergency bypass surgery) occurred in five patients (8.2%), with death in two (3.2%). During long-term (mean 21 +/- 11 months) follow-up study of the 55 patients with successful angioplasty, 13 (23%) died, including 3 of noncardiac causes, and 11 (20%) had clinically symptomatic recurrence. Continued clinical success was present in 39 patients (71%), of whom 28 (51%) were event-free patients and 11 (20%) had clinical recurrence; a successful second angioplasty procedure was performed in 9 because of restenosis. Thus, in patients with depressed left ventricular function, coronary angioplasty can be performed with a short-term success rate comparable to that of routine angioplasty or surgical procedures. However, acute complications are more frequent and the late mortality rate is higher than in patients with less depressed function.
Transient neuromuscular impairment resulting from prolonged inhalation of halothane and enflurane. Inhalation anesthesia first with halothane followed by enflurane relieved a patient with status asthmaticus who was refractory to conventional therapy including mechanical ventilation. After 13 days of anesthesia while on mechanical ventilation and employing nondepolarizing muscle relaxants, significant neuromuscular impairment, manifested by tetraplegia and sensory disturbance, developed. Anesthesia was discontinued on day 14, and the patient was weaned from mechanical ventilation on day 16. Over the next two months, the neuromuscular impairment markedly improved. Halothane was associated with cardiac arrhythmias and hepatitis necessitating replacement by enflurane. Enflurane appeared to be as effective a treatment for refractory asthma as halothane. The most probable cause of the neuromuscular impairment in our patient was the long-term use of inhalation anesthetics or nondepolarizing muscle relaxants.
Control of interleukin-1 beta expression by protein kinase C and cyclic adenosine monophosphate in myeloid leukemia cells. We have examined the signal transduction pathways leading to the expression of the interleukin-1 beta (IL-1 beta) gene in human myeloid leukemia cells lines. Two cell lines representing different stages of differentiation were used (HL-60, promyelocytic, and THP-1, mature monocytic). In accordance with previous studies, it was observed that a protein kinase C (PKC) activator, phorbol myristate acetate (PMA), was a sufficient stimulus for induction of the IL-1 beta messenger RNA (mRNA) expression and IL-1 beta protein production in both of these cell lines. A structural analog of cyclic adenosine monophosphate (dbcAMP) or agents elevating the endogenous cAMP levels (prostaglandin E2, forskolin) were not alone able to induce IL-1 beta expression, but they strongly enhanced the PMA-induced IL-1 beta production and IL-1 beta mRNA accumulation. Nuclear run off analysis showed that this elevation in IL-1 beta mRNA levels was due to an increased rate of transcription. If dbcAMP was added 6 hours before PMA to the cultures, no enhancement in the IL-1 beta production was seen, implying that for this enhancing effect both of these signals must be present simultaneously. PKC inhibitor, H7, also blocked effectively the PMA plus dbcAMP induced IL-1 beta production, while the protein kinase A (PKA) inhibitor, HA1004, had no effect, suggesting that PKA activation is not involved in the mechanism of action of cAMP in this case. Collectively, the present findings show that cAMP-dependent signals can have a positive regulatory effect on the PKC-dependent activation of the IL-1 beta gene in cells derived from different stages of myeloid differentiation.
Fetal death due to nonlethal maternal carbon monoxide poisoning. Fetal death due to acute carbon monoxide poisoning is rarely reported in the medical literature. Of the eight cases found in literature review, only one documented the fetal carboxyhemoglobin concentration. This paper reports a fetal death due to accidental nonlethal maternal carbon monoxide intoxication in which both maternal and fetal carboxyhemoglobin concentrations were obtained. The corrected carboxyhemoglobin concentration was 61% at the time of death in utero, while the maternal carboxyhemoglobin was measured at 7% after one hour of supplemental oxygen. The authors review the mechanisms of fetal death and emphasize the different carbon monoxide kinetics in the fetal circulation.
Nonpigmented congenital iris stromal cyst. A nonpigmented iris stromal cyst was observed in the right eye of a 6-week-old girl. There was no past history of trauma or use of topical miotics, and the remainder of the ocular examination was normal. The pathophysiology and management of this rare developmental anomaly are controversial.