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Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment. Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma.
A follow-up study of intractable seizures in childhood. One hundred forty-five children with seizures that were refractory to medical therapy for at least 2 years were followed 5 to 20 years after onset. The majority of children with uncontrollable seizures (61%) were mentally retarded, and most of these (73%) had onset of seizures at younger than 2 years of age. Age of onset was significantly later (mean 5.0 +/- 0.5 yr [SEM]) in the group of children with borderline to normal intelligence. Follow-up data showed remission of seizures in a significant proportion of children with borderline or normal intelligence, with a linear decrease of the percentage with persistent seizures at a rate of about 4% per year. Remission of seizures was much less frequent (1.5%/yr) in the group with mental retardation. Seizure type had some effects on outcome. Children with focal atrophic brain lesions did no worse than those without definable pathology on brain-imaging studies.
Thoracoscopic treatment of spontaneous pneumothorax using carbon dioxide laser. In an effort to improve the success rate of the previously described thoracoscopic electrocautery ablation technique of spontaneous pneumothorax, the carbon dioxide laser was evaluated in 12 patients. The recurrent (5 patients) or persistent (7 patients) spontaneous pneumothoraces were caused by rupture of (1) blebs in 6 patients, (2) intrapulmonary apical type II bullae in 3 patients, and (3) diffuse bullous emphysema, type III, in 3. The air leaks were successfully sealed in all but 1 patient with ruptured type II bulla. Surgical specimen from this single failure suggested that the entire inner lining of the bullae must be thermocoagulated. This technical modification led to successful outcome in 2 subsequent cases. With the use of carbon dioxide laser, it was possible to treat not only small blebs but all types of bullae causing spontaneous pneumothorax. Laser thoracoscopy is effective and safe in treating spontaneous pneumothorax.
Surgical treatment of active native valve endocarditis. A report is presented of 24 patients (23 male), mean age 38 years, who underwent surgery for active native valve endocarditis of the left heart in 1975-1988. The aortic valve was affected in all patients, and also the mitral valve in five. Pre-existing aortic valve disorder was present in 17 cases (13 congenitally bicuspid 4 rheumatic affection). There were five hospital deaths (20.8%). Staphylococci as causal organism and extensive infection predicted the highest mortality and morbidity. The mean follow-up time was 39.7 (range 2-114) months. Two reoperations because of prosthetic valve dehiscence revealed endocarditis of the implanted valve. Strong correlation was found between favourable postoperative course and rapid normalization of C-reactive protein levels, which did not fall in patients with persistent infection. Early surgery is recommended if the course of bacterial endocarditis is severely complicated.
Decreased local toxicity with subcutaneous diamorphine (heroin): a preliminary report. We report the cases of 5 patients who developed severe local toxicity during the subcutaneous administration of morphine sulphate and hydromorphone hydrochloride. All patients required site changes more frequently than once every 24 h due to redness, swelling, or pain while receiving morphine or hydromorphone. All patients showed prolongation in the duration of sites of infusion once an equianalgesic dose of diamorphine hydrochloride (heroin) was started. No change in pain control or systemic toxicity was detected with diamorphine. These findings suggest that diamorphine could be a useful alternative for patients who develop severe toxicity to subcutaneous morphine or hydromorphone.
Effect of antiplatelet and anticoagulant therapy on patency of femorotibial bypass grafts. In a retrospective study, 210 autogenous femorotibial saphenous vein grafts inserted during the 15 years from 1967 to 1982 were followed-up for a mean period of 62.3 +/- 5.7 months. Seven patients, who had had eight grafts died in hospital. The remaining 202 grafts fell into three groups: (1) Sixty grafts in patients who received 325 mg of dipyridamole and 1.0 g of acetylsalicylic acid daily, starting on the second postoperative day and continuing for six months. (2) One hundred and two grafts in patients on no antithrombotic therapy. (3) Forty grafts in patients on warfarin therapy to maintain the prothrombin time (prothrombin-proconvertin method) within the therapeutic range (0.10 to 0.20). Medication was continued for six months. This group included more high-risk patients than the other two groups. The mean ages and the incidence of risk factors did not vary significantly between the groups. The patency rates in three groups at five years were 62.5%, 44.0% and 26.0% and at ten years 48.5%, 25.0% and 21.5% for the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups, respectively. The limb salvage rates were 100%, 96% and 85% in the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups respectively. Thus, the best results were seen in the aspirin/dipyridamole group.
Vasopressin and oxytocin responses to illusory self-motion and nausea in man. Vasopressin and oxytocin are nonapeptides secreted from the neurohypophysis; increases in vasopressin are associated with nausea and vomiting in some, but not all, species. Our aim was to determine whether plasma vasopressin and oxytocin levels were altered in healthy volunteers who did or did not develop nausea during vection, an optokinetic stimulus which produces the illusion of self-motion. Vection was produced by rotating a drum with an inner surface of black and white vertical stripes around the seated stationary subject. Gastric myoelectrical activity was recorded continuously throughout the experiment with electrodes positioned on the abdominal surface. Plasma samples were obtained before vection and after drum rotation stopped when nausea and tachygastria were present. Vasopressin and oxytocin were extracted from plasma and quantified by RIA. During vection six subjects reported nausea and developed gastric dysrhythmias; six other subjects had no nausea and remained in normal 3-cpm myoelectrical rhythms. Vasopressin and oxytocin values before vection were similar in each group of subjects. One minute after vection stopped, plasma vasopressin levels were significantly greater (P less than 0.05) in subjects experiencing nausea and tachygastrias (35.4 +/- 26.7 pmol/L) than in those without symptoms (2.7 +/- 0.47 pmol/L). Oxytocin levels were unchanged by either vection or nausea. It is concluded that 1) vasopressin, not oxytocin, neurons in the magnocellular-neurohypophyseal system are activated during vection-induced nausea and gastric dysrhythmias; and 2) illusory self-motion may be used safely to study the neuroendocrine responses to brain-gut interactions and nausea in man.
The recalcitrant perineal wound after rectal extirpation. Applications of muscle flap closure. Perineal wounds developing after abdominoperineal resection result in chronic purulent drainage and intermittent episodes of sepsis and are generally unresponsive to conservative medical and surgical treatment. Thirteen consecutive patients (aged 27 to 74 years; mean, 48 years) who underwent debridement and immediate muscle flap closure of these wounds were analyzed to identify risk factors for delayed healing and to evaluate the effectiveness of muscle flap coverage. Three risk factors were identified: preoperative or postoperative radiation therapy, resection for recurrent carcinoma, and inflammatory bowel disease. A total of 19 muscle flaps (11 gracilis, five gluteal thigh, two gluteus maximus, and one rectus abdominis) were used to close these wounds. During an average 3.5-year follow-up, four (31%) minor complications and one (8%) recurrence were noted to occur. Muscle flaps provide safe, effective, single-stage procedures for the closure of chronic perineal wounds.
Osteotomy for osteoarthritis of the hip. A survivorship analysis. We have reviewed 368 osteotomies carried out for osteoarthritis of the hip at the Nuffield Orthopaedic Centre. Survivorship analysis showed that 10 years after osteotomy 47% had required no further surgery, and even after 20 years 23% had still not had a hip replacement. Hips with moderate arthritic change showed significantly better results than those with more severe degeneration. Osteotomies with varus angulation as well as medial displacement showed longer survival.
In vitro and in vivo evaluation of intraluminal ultrasound in normal and atherosclerotic arteries. This study evaluated the dimensional and morphologic precision of arterial images obtained using intraluminal rotating A-scan ultrasound catheters [5.0F (30 mHz) and 8.0F (20 mHz)]. Dimensions of in vitro ultrasound images from human arteries (eight normal and nine arteriosclerotic) were compared with those from histologic sections of the vessels. In addition, in vivo ultrasound studies (23 normal and 22 arteriosclerotic) of canine femoral arteries were compared with luminal dimensions obtained from angiograms of the vessels. The correlation of in vitro ultrasound images to luminal diameters (n = 22, r = 0.96), adventitial diameters (n = 19, r = 0.83), and wall thickness (n = 19, r = 0.68) in normal human vessels was significant (p less than 0.05). In vitro measurements of images and histologic specimens from human atherosclerotic arteries also correlated significantly (p less than 0.05) with luminal diameters (n = 27, r = 0.91), adventitial diameters (n = 24, r = 0.60), and wall thickness (n = 24, r = 0.62). Morphologically, in vitro images of the wall of normal human arteries had a concentric laminated appearance and atherosclerotic vessels had patchy echodense and echolucent areas. In vivo studies showed significant correlation of diameters for both normal (n = 16, r = 0.91, p less than 0.05) and arteriosclerotic (n = 16, r = 0.57, p less than 0.05) canine arteries compared with luminal dimensions measured from uniplanar angiograms. We conclude that rotating A-scan intraluminal ultrasound accurately defines both normal and atherosclerotic arterial wall morphology and dimensions. This technology may be valuable for intravascular guidance of angioplasty devices by identifying the location and consistency of lesions.
Early outcome after placement of a metallic intracoronary stent: initial Mayo Clinic experience After percutaneous transluminal coronary angioplasty, 3 to 7% of patients have in-hospital coronary closure, and the risk of subsequent myocardial infarction is high, even with an urgent bypass operation. Disrupted coronary morphologic integrity, particularly with large dissections, may be associated with an increased risk of acute coronary closure. A percutaneously placed coronary vascular stent may rapidly alleviate acute or threatened coronary closure and could reduce morbidity. Between October 1989 and June 1990, placement of a balloon-expandable, flexible metallic coil (Gianturco-Roubin) coronary stent was attempted 16 times in 15 Mayo Clinic patients--for treatment of actual or threatened abrupt coronary closure in 10 patients, for primary treatment of a lesion judged to be at high risk for dissection with conventional balloon angioplasty in 1, and for elective treatment of restenotic lesions in 5. Placement of the stent was successful in 15 attempts (94%). Associated complications, which were uncommon, were similar to those noted after balloon angioplasty. No early deaths occurred, and no patient required coronary artery bypass grafting. Stents were successfully placed in both urgent and elective circumstances in native coronary arteries and saphenous vein grafts, and they were used in primary atheromatous and restenotic lesions. Our initial experience with this metallic coil stent indicates that it is efficacious for vascular disruption that is threatening or causing coronary closure after angioplasty. Furthermore, elective placement of a stent may be safely undertaken in patients with high-risk coronary lesions or recurrent restenotic lesions. The long-term outcome in all groups of patients who receive coronary stents is unknown.
Small nodular lesions in the lung periphery: new approach to diagnosis with CT. To evaluate relationships between lesions in the lung periphery and surrounding structures, particularly vessels and bronchi, axial multiplanar reconstruction (AMPR) computed tomography (CT) was used to study 26 patients who underwent surgical resection of pulmonary nodules less than 3 cm in diameter. Findings at AMPR CT, conventional CT, and digital radiographic tomography were compared with findings obtained at evaluation of the resected specimen with regard to the ability to display the relationships between vessels, bronchi, and lesions. AMPR CT was significantly superior to conventional CT and digital radiographic tomography in detecting involvement of pulmonary vessels (P less than .001). Involvement of pulmonary veins was seen in all lung cancers, whereas such involvement was seen in only one of eight nonneoplastic lesions. Thus, involvement of pulmonary veins is strongly suggestive of malignancy. AMPR CT permits three-dimensional visualization and morphologic assessment of pulmonary nodules.
Disturbed gastroduodenal motility in patients with active and healed duodenal ulceration. Disordered gastroduodenal motility may promote duodenal ulceration by allowing prolonged acid contact with the duodenal mucosa. Using a multilumen perfused catheter incorporating 3 pH microelectrodes, antral and duodenal pH and antropyloroduodenal pressure activity were recorded in 36 subjects (10 with healed duodenal ulceration, 11 with active duodenal ulceration, and 15 healthy volunteers) during fasting and after a radiolabeled solid test meal. Correct pH probe/catheter position was continuously verified by recording transmucosal potential difference across the pylorus. Patients with active and healed duodenal ulcer had similarly disordered gastroduodenal motility. The chief abnormalities consisted of an increase in postprandial duodenal retroperistalsis (healed duodenal ulceration, 12 +/- 1 events per hour; active duodenal ulceration, 12 +/- 1; control, 6 +/- 1; mean +/- SEM: healed and active duodenal ulceration vs. control, P = 0.004 and P = 0.03, respectively), a reduction in pressure waves sweeping aborally through the duodenum after the meal (healed duodenal ulceration, 22 +/- 4 events per hour; active duodenal ulceration, 23 +/- 3; control, 34 +/- 4: healed and active duodenal ulceration vs. control, P = 0.04 and P less than 0.05, respectively), and an increased incidence of atypical, complex forms of coordinated duodenal motor activity throughout the study (postprandial data; healed duodenal ulceration, 8 +/- 1 events per hour; active duodenal ulceration, 10 +/- 1; control, 4 +/- 1: healed and active duodenal ulceration vs. control, P = 0.02 and P less than 0.02, respectively). In addition, gastric emptying of the solid test meal was significantly delayed in healed, but not active, duodenal ulceration [half-emptying time, healed duodenal ulceration 185 minutes (117-235); active duodenal ulceration 102 minutes (80-200); control 107 minutes (78-130): healed duodenal ulceration vs. control, P less than 0.009]. Duodenal bulb pH was similar in controls and patients with active duodenal ulceration; however, bulb pH was less than 4 for a significantly greater period of time in healed duodenal ulceration compared with active ulcer patients, particularly after the meal. In conclusion, duodenal ulcer disease is associated with disturbed gastroduodenal motility, even when the ulcer is quiescent and when intraduodenal acidity is low. In healed duodenal ulceration, disturbed motility may promote ulcer relapse by impairing acid clearance from the bulb. However, in active ulceration other factors such as mucosal bicarbonate secretion may have a more influential role in determining intraduodenal pH.
Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index). The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation. The end point was defined as either local/regional recurrence or metastasis. Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02). Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer.
The no-scalpel vasectomy. A refined method of delivering the vas deferens for vasectomy has been developed and used in China since 1974. This method eliminates the scalpel, results in fewer hematomas and infections, and leaves a smaller wound than conventional techniques. An extracutaneous fixation ring clamp encircles and firmly secures the vas without penetrating the skin. A sharp curved hemostat punctures and dilates the scrotal skin and vas sheath. The vas is delivered, cleaned and occluded by the surgeon's preferred technique. The contralateral vas is delivered through the same opening. The puncture wound contracts to about 2 mm., is not visible to the man and requires no sutures for closure. The reported incidence of hematoma in 179,741 men followed in China was 0.09%. No hematomas or infections were identified in the first 273 procedures performed by a surgeon in the United States. The operating time in China and for the last 50 United States procedures has ranged from 5 to 11 minutes. The disadvantage of the technique is the hand-on training and number of cases necessary to gain proficiency. However, the advantages for surgeons and patients should enhance the popularity of vasectomy.
Transcardiac release of leukotriene C4 by neutrophils in patients with coronary artery disease. Leukotriene C4 is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4 release by neutrophils in patients with coronary artery disease, neutrophils were separated from blood samples taken from the coronary sinus and aorta in 20 patients with stable exertional angina and angiographically documented coronary artery narrowings (group I). Eight patients with normal coronary arteries were also studied (group II). To assess leukotriene C4 generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 microM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4 by radioimmunoassay. Patients in group I had a significantly lower release of leukotriene C4 from neutrophils separated from the coronary sinus blood than from those separated from aortic blood (4.33 +/- 0.69 versus 5.92 +/- 0.54 ng/ml, p less than 0.025), whereas patients in group II had a similar release of leukotriene C4 by the neutrophils separated from coronary sinus blood and from aortic blood (6.0 +/- 0.72 versus 6.4 +/- 0.66 ng/ml, p = NS). Moreover, in group I patients, a significant correlation was found (p less than 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4 released from neutrophils separated from coronary sinus blood as compared with leukotriene C4 produced by neutrophils separated from aortic blood. These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4 after stimulation by calcium ionophore A 23187.
Comparative study of the effects of three angiotensin converting enzyme inhibitors on the cough reflex. To compare the effects of three different angiotensin converting enzyme (ACE) inhibitors on the cough reflex, capsaicin and citric acid challenge tests were done in normal subjects and hypertensive patients before and after administration of delapril, captopril, or enalapril. Two groups of 7 normal subjects (single dose study: 15 mg delapril v 18.75 mg captopril or 2.5 mg enalapril) and a group of 6 mildly hypertensive patients (1 week study: cross-over administration of 30 mg/day delapril, 37.5 mg/day captopril, or 5 mg/day enalapril) were studied. Another group of 6 patients with essential hypertension was treated with three ACE inhibitors for 4 weeks in a randomized order, with a 2 week washout period between active therapies. Aerosols of 1 mumol/L and 3 mumol/L capsaicin and 0.68% citric acid in 0.9% NaCl were generated by an ultrasonic nebulizer, and the frequency of cough was counted during inhalation. Delapril treatment resulted in substantially fewer patients with a significant increase (greater than or equal to 4 coughs during treatment than during the control period) in the frequency of cough than did captopril treatment. In the 1 and 4 week studies, enalapril and captopril had substantially more occurrences of significantly increased capsaicin-induced cough than did delapril. These results indicate that delapril has the least cough stimulatory effect among these ACE inhibitors, which may be clinically beneficial.