Effect of smoking cessation on pulmonary carbon monoxide diffusing capacity and capillary blood volume.

We studied 16 smokers, with a mean age of 41 yr (SD, 12 yr) and a mean DLCO of 81% predicted (SD, 19%), before and after smoking cessation. Two subjects were able to stop smoking for only 24 h, whereas 14 subjects abstained for 1 wk, 11 for 1 month, and five for 3 months. The initial mean DLCO in ml/min/mm Hg was 18.9 (SD, 4.6) after correction for COHb back pressure and the reduction in hemoglobin because of COHb. A week after smoking cessation there was a significant increase in DLCO, to 20.8 (SD, 5.4), p = 0.001. There was no further increase in DLCO at 1 month or at 3 months. In four subjects tested while they were still smoking and 24 h after smoking cessation, there was a significant increase in DLCO after correction for COHb, from 17.4 (SD, 1.5) to 19.8 (SD, 1.3), p = 0.02. These results indicate that after smoking cessation there is a rapid improvement in DLCO, suggesting that smoking had previously decreased DLCO. However, there may also be an irreversible component to the reduction of DLCO in some of the subjects in whom the DLCO remained abnormal even after continued smoking cessation for 1 month.


Lung mechanics and gas exchange during pressure-control ventilation in dogs. Augmentation of CO2 elimination by an intratracheal catheter.

Increased awareness of pressure-related injury to the alveolar-capillary interface has renewed interest in modes of ventilation that limit alveolar distention such as pressure-controlled ventilation (PCV). We examined respiratory system mechanics and gas exchange during PCV in six dogs. Our data conformed to the predictions of our single-compartment mathematical model of respiratory dynamics during PCV (J Appl Physiol 1989; 67:1081-92). For a fixed pressure (Pset) and inspiratory time fraction (Tl/Ttot) (15 cm H2O and 0.3, respectively), minute ventilation (VE) reached a well-defined plateau as frequency (f) increased from 10 to 50 breaths/min and tidal volume (VT) fell progressively. Concomitantly, the physiologic dead-space fraction (VD/VT) increased from 0.50 +/- 0.04 to 0.85 +/- 0.04, and arterial PCO2 (PaCO2) rose from 39 +/- 4 to 76 +/- 12 mm Hg. At a fixed combination of frequency, applied pressure, and Tl/Ttot (40 breaths/min, 15 cm H2O, and 0.3), VE did not change when we introduced fresh gas continuously from an intratracheal catheter. However, PaCO2 and VD/VT fell progressively as catheter flow increased from zero to 14 L/min (60 +/- 12 to 40 +/- 12 mm Hg and 0.83 +/- 0.03 to 0.25 +/- 0.14 mm Hg, respectively). We conclude that during PCV at a fixed Pset and Tl/Ttot increasing frequency caused VT to fall and VE to reach a plateau. Declining VT was associated with a rise in PaCO2 because of a subsequent fall in alveolar ventilation. Insufflating fresh gas by an intratracheal catheter increased alveolar ventilation and improved CO2 elimination by washing out the anatomic dead space.(ABSTRACT TRUNCATED AT 250 WORDS)


Use of the Blasius resistance formula to estimate the effective diameter of endotracheal tubes.

To early detect mucus deposition in endotracheal tubes (ETT), we propose using a geometric, flow-independent parameter, i.e., diameter of the ETT, based on a precise knowledge of ETT flow regime, instead of using the classic flow-dependent ETT resistance based on the empirical, nonlinear Rohrer equation. From the estimated slope of -0.24 derived from Moody diagrams characterizing the pressure-flow relationship in ETT of various inner diameters (D), we first assessed that the Blasius resistance formula slope of -0.25 could be applied to adult-size ETT, meaning that flow remains fully developed, turbulent, and hydraulically smooth (0.5 L/s less than or equal to V less than or equal to 1.4 L/s). Insertion into the ETT of a pressure catheter (external diameter: d) to stimulate in vivo measurements did not modify these results, provided the hydraulic diameter, D* = D - d, was substituted for D in the Blasius formula. The Blasius formula was then used to determine, from in vitro pressure and flow measurements in ETT before intubation and in ETT lined with dry mucus secretions, the effective diameter, shown here to be highly correlated to the actual diameter measured by volumetric water displacement. The effective ETT diameter was measured in eight patients at different stages after oral or nasal intubation. Compared with the actual ETT diameter measured before insertion, the effective diameter was slightly reduced (2.6 +/- 2.5%) during the first week of intubation and was strongly reduced (12.2 +/- 2.8%) during the second week.(ABSTRACT TRUNCATED AT 250 WORDS)


Respiratory responses to chest compression in human subjects.

To test the hypothesis that respiratory compensation for chest compression in the conscious state is different from that in the unconscious state, a range of chest compression was applied to eight conscious and eight anesthetized subjects. Chest compression was carried out by inflating a pneumatic cuff inserted under a chest corset and placed over the anterior chest wall for 5 min. Cuff inflation pressures were 25, 50, and 100 mm Hg: light, moderate, and heavy chest compression, respectively. In both conscious and anesthetized subjects, chest compression immediately caused a decrease in tidal volume (VT) and a concomitant increase in respiratory frequency (f). These changes stabilized within 2 min and remained nearly steady for the rest of the sustained chest compression. The decrease in VT was more prominent the greater the loads, and the change in f was in reverse proportion to the change in VT. In conscious subjects the increase in f was due to shortening of both inspiratory time (T1) and expiratory time (TE), whereas in anesthetized subjects the increase in f was due solely to shortening of TE. In conscious subjects, the values of minute ventilation (VI) and end-tidal PCO2 (PETCO2) during light and moderate chest compression were not different from the control values, whereas VI increased and PETCO2 decreased during heavy chest compression. In anesthetized subjects, the values of VI and PETCO2 were not different from the control values at any different magnitudes of chest compression.(ABSTRACT TRUNCATED AT 250 WORDS)


Increased serum catalase activity in septic patients with the adult respiratory distress syndrome.

Excessive hydrogen peroxide (H2O2) generation appears to contribute to the development of the adult respiratory distress syndrome (ARDS), but H2O2-combatting antioxidant defenses have not been evaluated. We found that serum from septic patients with ARDS scavenged more (p less than 0.05) H2O2 in vitro (82.7 +/- 3.8%) than did serum from septic patients without ARDS (56.9 +/- 3.1%) or control subjects (20.2 +/- 2.4%). Serum from septic patients with ARDS also had more (p less than 0.05) catalase activity (54.9 +/- 10.9 U/ml) than did serum from septic patients without ARDS (28.6 +/- 3.4 U/ml) or control subjects (7.3 +/- 0.8 U/ml). In contrast, serum from septic patients with or without ARDS and control subjects had the same glutathione peroxidase (GPX) activity. Serum H2O2 scavenging activity correlated with serum catalase (r = 0.77) but not GPX (r = 0.33) activity and was inhibitable (greater than 90%) by sodium azide, a catalase inhibitor. Increases in serum catalase activity did not appear to be derived from erythrocytes (RBC) because septic patients with or without ARDS and control subjects had similar RBC hemolysis in response to osmotic stress in vitro and serum haptoglobin concentrations. Serum from septic patients with ARDS also protected endothelial cells against H2O2-mediated damage (34.5 +/- 2.2% 51Cr release) better (p less than 0.05) than serum from septic patients without ARDS (47.3 +/- 7.4%) or control subjects (82.1 +/- 10.2%), but killing of bacteria by neutrophils in vitro was the same in serum from patients and control subjects. Our findings indicate that patients with sepsis and/or ARDS have increased serum catalase activity, which may alter H2O2-dependent processes.


Subpopulation of hyperresponsive polymorphonuclear neutrophils in patients with adult respiratory distress syndrome. Role of cytokine production.

To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), we studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, nine with severe pneumonia uncomplicated by ARDS, and seven mechanically ventilated with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, we identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor-alpha (TNF alpha) in plasma, and both spontaneous and lipopolysaccharide-induced TNF alpha production by cultured monocytes. These biologic expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF-alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.


Effect of sulfidopeptide leukotriene receptor antagonists on endotoxin-induced pulmonary dysfunction in awake sheep.

We studied the effects of two structurally unrelated sulfidopeptide leukotriene receptor antagonists on endotoxin-induced pulmonary dysfunction in chronically instrumented unanesthetized sheep. The agents employed were L-660,711 (MK-571) (Merck-Frosst, Canada) and SK&F 104,353 (Smith Kline and French, King of Prussia, PA). The efficacy and specificity of the agents were verified in sheep by administering boluses of exogenous leukotrienes (LTB4, LTC4, LTD4, and LTE4) in doses as great as 100 micrograms while monitoring lung mechanics and vascular pressures. The antagonists blocked the changes in lung mechanics and pulmonary hemodynamics induced by the sulfidopeptide leukotrienes (LTC4, LTD4, and LTE4) while having no effect on the animals' responses to LTB4. The endotoxin studies were performed by administering endotoxin alone (Escherichia coli endotoxin 0.75 microgram/kg) or endotoxin after pretreatment with one of the sulfidopeptide leukotriene receptor antagonists. In control studies, each animal received a continuous infusion of one of the receptor antagonists for a duration identical to that of the endotoxin studies. Neither L-660,711 nor SK&F 104,353 significantly altered the endotoxin-induced changes in pulmonary hemodynamics, lung mechanics, lung fluid and solute exchange, oxygenation, or leukopenia. Peak lung lymph thromboxane B2 levels were significantly lower in sheep pretreated with L-660,711. When the antagonists were given alone, no effects were seen. We conclude that (1) sulfidopeptide leukotrienes do not measurably contribute to endotoxin-induced pulmonary dysfunction in chronically instrumented sheep; (2) sulfidopeptide leukotrienes may contribute to thromboxane release after endotoxin.


The clinical spectrum of lymphangiomas and lymphangiomatosis of the spleen.

Lymphangiomas of the spleen are infrequent neoplasms of the spleen with clinical manifestations ranging from insignificant incidental findings to large, symptomatic cystic masses requiring surgical intervention. An associated syndrome may be lymphangiomatosis, in which the lymphangiomatous process involves other sites or organs, such as the liver, spleen, axilla, and mediastinum. Vasoformative neoplasms (hemangioma, lymphangioma) are relatively uncommon tumors or hamartomas of the spleen. Although well reported in the literature, their surgical significance is not well recognized. These lesions present a broad spectrum of pathologic findings of varied surgical importance. As incidental findings, they may be mistakenly considered as a valid indication for splenectomy. On the contrary, more extensive involvement of the spleen may cause symptomatic splenomegaly, which is a valid indication for splenectomy. When the spleen is diffusely involved (lymphangiomatosis), it may be part of a syndrome of generalized lymphangiomatosis involving structures and organs other than the spleen. This syndrome should be considered in obscure cases of splenomegaly in which the usual hematologic causes have been ruled out.


Colonic diverticular disease in patients 40 years old or younger.

Diverticular disease in patients 40 years of age or younger has been described as rare but virulent. Previous studies, based on age, on diverticular disease are often confusing because of inexact definitions of the disease status. With these criticisms in mind, the authors studied 322 clinical records on patients admitted with a diagnosis of colonic diverticulosis or diverticulitis to the University of New Mexico Hospital and the Lovelace Medical Center. Of these patients, 285 had documented evidence of colonic diverticula with only 6 per cent of these being 40 years of age or younger. The criteria for acute diverticulitis were met by 86 patients, 17 of whom were 40 years of age or younger. The younger group had disproportionately more men, particularly Hispanics. The authors conclude that acute diverticulitis is more common in the young than suggested by previous reports, but the behavior of the disease is not distinctive.


Massive gastrointestinal hemorrhage in pancreatitis secondary to visceral artery aneurysms.

Thirty-six pancreatic patients with massive gastrointestinal bleeding have now been identified as having pancreaticoduodenal and gastroduodenal artery aneurysms as causative. In the past decade, seven of the patients have been encountered at the authors' institution and seven presented in the literature. Of these 14, there was a predilection for men (85%) with an average age of 48.1 years, who had complications of pancreatitis (75%), that is, abscess or pseudocyst. Eleven of these patients underwent surgery with an 81 per cent survival rate. Previous reports had shown a 47 per cent survival rate in 19 similar patients. Embolization of the aneurysm was attempted in four patients with two successes. The authors believe that early diagnosis by arteriography and early operative intervention were responsible for the improved survival. A high index of suspicion in this patient population is crucial for early diagnosis and improvement in survival.


Abdominal vascular trauma: a review of 106 injuries.

A retrospective analysis of acute abdominal vascular injuries was performed to review outcome variables and treatment principles. The authors review their most recent 5-year experience with 106 major abdominal vascular injuries in 64 patients treated at a combined Army and Air Force urban medical center. The majority of the patients were young men who sustained penetrating injuries. There were 41 (64%) gunshot wounds, 17 (27%) stab wounds, and 6 (9%) sustained blunt trauma. Forty-five patients (71%) came to the hospital in shock. The inferior vena cava in 26 patients (41%) and the aorta in 11 patients (17%) were injured most frequently. Suture repair was possible in 53 (50%) injuries. Ligation was performed in 41 (39%). Overall mortality for the series was 39 per cent. Hemorrhagic shock was the cause of death in 23 patients (92%) with only two late deaths. Transfusion requirement, presence of shock, and number of vessels injured all affected outcome. Immediate stabilization in the emergency department includes appropriate crystalloid and blood product resuscitation with minimal delay for diagnostic studies. Prompt abdominal exploration to control hemorrhage and particular attention to factors associated with coagulopathy remain the key elements in saving the lives of these severely injured patients.


The role of laparoscopy in the diagnosis of acute appendicitis.

Patients with acute appendicitis who present with an atypical clinical picture are frequently subjected to a series of laboratory and x ray tests and sometimes to prolonged observation before surgery. There is a significant number of normal appendixes found at laparotomy, particularly in some subgroups of patients such as the immunocompromised, the elderly, and the young woman. Laparoscopy was done in 38 patients with right lower quadrant pain of undetermined cause after extensive diagnostic efforts. This group of patients included men and women with an even distribution of ages between 20 and 78 years. Laparoscopy was done under local anesthesia to better establish the site of pain if no obvious pathology could be visualized. Acute appendicitis was confirmed in only 26.3 per cent of the cases, and a wide variety of nonappendiceal diseases were identified, the majority of them requiring no surgery. Diagnostic laparoscopy performed under local anesthesia should be considered in patients suspected to have acute appendicitis, regardless of age and sex, who present with an atypical picture and who still offer diagnostic doubts after other available conventional tests.


Primary lymphoma of the rectum.

Primary lymphoma of the rectum is rare. Its usual grouping with primary lymphoma of the gastrointestinal tract leaves little in the literature that deals specifically with a primary rectal lymphoma. Various treatments have been reported ranging from abdominoperineal resection with adjuvant chemotherapy and radiation therapy to chemotherapy or radiation therapy alone. A case of primary rectal lymphoma is presented and the literature is reviewed. In the few cases reported in the literature, patients treated surgically had a better prognosis than those treated nonsurgically with an overall 5-year survival of 50 per cent. Recommended treatment includes varying forms of surgical therapy ranging from local resection to abdominoperineal resection. Adjuvant chemotherapy, radiation therapy, or both should be considered.


Ileocolonic anastomosis: a comparison of the patency of stapled versus hand-sewn techniques.

This study compared strength of hand-sewn sutures to that of staples for end-to-end anastomoses of ileocolostomies in 20 mongrel dogs. In ten dogs, the authors used four applications of staples for the anastomoses. In the other ten, they performed single-layer anastomoses using 4-0 polypropylene sutures. Half the dogs were sacrificed on the third postoperative day; half were sacrificed on the fifth postoperative day. Bursting strengths were obtained by infusing air through a catheter inserted into the colon. Results showed the single-layer hand-sewn anastomosis was significantly stronger than the stapled anastomosis. In addition, a histologic comparison of the two closures showed no difference in inflammatory responses.


An unusual complication of laparoscopic cholecystectomy.

An unusual series of complications of laparoscopic cholecystectomy is presented. The complications occurred after use of laparoscopic technique in the treatment of acute cholecystitis. The authors feel that this is a problem that points up the need for experience and caution in the use of laparoscopic cholecystectomy in the setting of acute cholecystitis.


Resident education in surgical endoscopy.

Under the auspices of the Resident Education Committee of the Society of American Gastrointestinal Endoscopic Surgeons, 158 of 298 (53%) of surgical training program directors responded to a survey on the current status of endoscopy in residency programs. Although 100 per cent claim that gastrointestinal endoscopy is provided by their program, only 76 per cent have formal endoscopy training, usually centered around the PGY 3 level, with only 23 per cent having didactic lectures in endoscopy. Directors claim to have trained nearly all of their residents by the completion of residency, averaging 44 esophagogastroscopies, 37 colonoscopies, and 46 flexible sigmoidoscopies per resident. However, they feel only 71 per cent of trainees are able to perform esophagogastroscopies and 67 per cent to perform colonoscopies in clinical practice. Ninety-seven per cent of directors feel endoscopy is important to surgical residency training, and 87 per cent have full-time faculty doing endoscopy. Only 44 per cent have a director of endoscopy; endoscopy is supervised by surgeons exclusively in only 48 per cent. Only 35 per cent have ongoing endoscopy research. When surgeons are not performing endoscopy, 66 per cent feel that the gastrointestinal (GI) service provides adequate service or training. Gastroenterology has a monopoly in endoscopy at 28 per cent of institutions, and 67 per cent of program directors feel there would be resistance to the formation of a separate surgical endoscopy service. Surgeons work in their own surgical endoscopy suite in only 15 per cent of institutions; in a GI suite in 13 per cent; and in a combined suite in the remainder.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of proximal gastric vagotomy plus duodenoplasty on duodenogastric reflux.

Alkaline reflux gastritis is a clinical syndrome that results from a mucosal injury by duodenal contents. In this study, the amount of duodenogastric reflux was assessed in patients who previously underwent proximal gastric vagotomy (PGV group; n = 11) and PGV plus duodenoplasty (PGV+D group; n = 10) as a treatment for duodenal ulcer. The control group (A) consisted of 11 healthy volunteers without endoscopic abnormalities. A quantitative index of duodenogastric reflux was obtained in each case by determining the percentage of the injected dose of 99mTechnetium-DISIDA that was recovered by continuous aspiration of gastric juice in fasting subjects. In the PGV group, the percentage of administered 99mTechnetium-DISIDA recovered from the stomach (median: 0.69%; range: 0.09%-3.61%) did not differ significantly (P > 0.05) from that of the PGV+D group (median: 0.49%; range: 0.09%-3.91%) and from that of the A group (median: 1.47%; range: 0.22%-3.01%). The results show that proximal gastric vagotomy plus duodenoplasty did not increase duodenogastric reflux.


Orthotopic liver transplantation with abdominal situs inversus and dextrocardia.

Anatomic anomalies may present technical difficulties during orthotopic liver transplantation. Abdominal situs inversus was considered a contraindication to liver transplantation. A successful liver transplant in a patient with both situs inversus and dextrocardia is described, along with a technical review.


Cost containment in the operating room: use of reusable versus disposable clothing.

The need for fiscal austerity has prompted the re-evaluation of many aspects of medical care. Recent events in the northeastern United States have caused an increased awareness of the need for environmental responsibility as well. With these considerations in mind, the costs incurred by the operating suites of two comparable teaching hospitals in New Jersey, one of which uses disposable operating room attire, were examined; the other employs reusable scrub suits and gowns. The reusable scrub suits and gowns resulted in a savings in excess of $100,000 compared to the center using disposables. The authors conclude that hospitals should re-evaluate their use of disposable operating room attire to reduce operating costs and the amount of medical waste generated.


Endoscopic papillotomy while the gallbladder is in situ.

The authors report on their experience with 25 patients who underwent an endoscopic papillotomy with gallbladder in situ and review the current literature on this topic. Twenty-four out of 25 patients in this study had their common bile duct cleared of stones. Five patients (24%) required cholecystectomy on follow-up at an average of 14.4 months. There was no mortality associated with the procedure. The authors' experience and review of the literature suggest that endoscopic papillotomy plays an important role in the removal of common bile duct stones in persons who have their gallbladder in situ, especially in those patients who are at high risk for surgery, either because of advanced age or other medical problems. However, the use of endoscopic papillotomy alone in young, healthy persons is more problematic because of the relatively high rate of cholecystitis or recurrent biliary colic necessitating a cholecystectomy at a later date. The authors suggest that, in the future, the ideal treatment regimen for common bile duct stones in patients with their gallbladder in situ may be urgent endoscopic papillotomy with a scheduled elective laparoscopic cholecystectomy.


[Differentiated thyroid carcinoma in childhood].

We report the cases of 6 patients, all younger than 14 years of age, with differentiated thyroid carcinoma. None of the patients had a previous history of radiation exposure. All patients presented with an enlarged thyroid gland as a solitary nodule, with or without cervical nodes. The fine-needle aspiration cytological examination was found to be the most sensitive and specific, evidencing 5 pure papillary adenocarcinoma and 1 follicular. Our standard preoperative evaluation included thyroid scintiscan and ultrasound examination, laboratory studies of thyroid function and serum calcitonin, chest x-ray, fine needle aspiration and vocal cord examination. The treatment was total thyroidectomy and bilateral modified neck dissection. A whole body scan (WBS) with 131I was performed 6 weeks after surgery, followed by radioiodine therapy for ablation of thyroid remnants and treatment of metastases when present. Patients then began thyroid replacement treatment. The follow-up of the patients consisted of thyroglobulin and WBS. The microscopic carcinoma was found in the contralateral lobe in 100%. Lung metastases were detected in 2 patients. All of the patients have survived during a follow-up period ranging from 6 to 108 months.


[Marfan syndrome in childhood: cardiovascular manifestations. Echocardiographic changes].

We report the cases of eight children with Marfan syndrome. Seven (87.5%) were diagnosed with cardiopathy, everyone with auscultatory findings. Electrocardiographic patterns were nonspecific. Enlargement of the aortic root was present in two of the cases as seen by thorax x-rays. Echocardiography detected the presence of mitral valve prolapse in 87.5% of the patients (7 cases) and aortic enlargement in 75% of the patients (6 cases). Echocardiography also detected the presence of aortic dysplasia, tricuspid valve prolapse and right and left ventricular hypertrophy. During the follow-up period, no case had cardiac failure. There was no mortality. The aortic enlargement was progressive and was not modified by propranolol treatment. Surgical treatment was not needed. Family history related to this condition was present in a very small percentage (37.5%). We comment on one infantile form of Marfan syndrome with its own phenotype different from that of classical Marfan syndrome.


[Evaluation of the western blot test in the follow up of children born to HIV seropositive mothers].

We have made a follow-up study of 65 children born to HIV seropositive mothers. These children were studied during the first quarter of life and subsequently every three months thereafter to measure the usefulness of the Western Blot technique in the detection of the gradual development of seroreversion, as well as in HIV infection. The study of 25 mother-child pairs allowed us to anticipate seroreversion up to three months, showing an earlier and quicker finding than by indirect immunofluorescence. In the HIV diagnosis during the first 15 months of life, the sequential study of serum by Western Blot is able to detect the reappearance of new bands, indicating the endogenous production of antibodies in the child. The circunstance is observed in 7 out of 10 infected children, showing the reappearance of bands corresponding to antibodies against p-31 and/or p-55 proteins between the second and fourth quarter of life.


[Anemia and depletion of iron reserves in healthy 12-month-old infants].

A prospective study was made which included 287 infants, 12 months of age and patients of two Vizcaya Health Centers, in order to determine the prevalence of anemia and/or depletion of iron stores. The study design included somatometry and a review of the clinical records, dietary habits and the socio-economic status of the family. Laboratory tests included: hematocrit, hemoglobin, mean corpuscular volume, number of erythrocytes, serum iron, transferrin, iron saturation percentage and serum ferritin. Anemia was present in 9.3% of these children and 6.9% had iron-deficiency anemia. Depletion of iron stores was found in 12.4%. Prematurity, socio-economic status, infants fed low-iron milk, early introduction of cow's milk and the weight at 12 months were all variables that correlated significantly with the anemic or iron deficient states. However, the number of infections during the first year of life did not show a significant correlation. A question about the necessity of routine screening is raised and recommendation is made for iron supplementation in the infants in the high risk group.


[Attempted suicide in childhood and adolescence: epidemiologic characteristics].

Suicide attempts among children and adolescents are occurring more frequently in the last years. In fact, in some countries suicide is the third leading cause of death for adolescents between 15 and 19 years of age, in spite of the fact that it is probably significantly underreported. The present study aimed at examining the factors related to suicide attempts in thirty children and adolescents between 6 and 16 years old. These patients were compared to a randomly selected control group. A systematic review of the patients' charts was performed. We found that suicide attempts increased with age, 83% of those patients attempting suicide were female, the medical lethality of the means used in the attempt did not correlate with the patient's perception of the risk of dying, and recent stressful life events could often be identified as precipitators for attempting suicide.


[Neurologic alert signals in one-year-old infants: relation to signs of intrapartum hypoxia].

As a method to evaluate the neurologic evolution and to establish if there exists any differences in the relation with the signs of intrapartum hypoxia, we have explored the neurologic "alert signs" at a certain age (12 months of life) in 80 full-term newborn infants with normal weight and without criteria of neurologic risk. We did not find statistically significant differences in the presence of alert signs in regards to sex, gestational risk, type of amniotic fluid, way of delivery, one-minute and five-minute Apgar scores or acid-base state in the umbilical artery at birth. We did find a significant increase in the number of alert signs in patients with cardiotocographic patterns that were suspicious or not tranquil in relation to those whose cardiotocographic patterns were tranquil.


[Type 1 diabetes mellitus and nephropathy. Predicting factors in pediatric age].

To find the existence of early relationships between alterations in the glucidic metabolism and the glomerular and tubular basal function in diabetic insulin-dependent children without clinical evidence of diabetic nephropathy (DN). We determined blood pressure, basal plasma concentrations of glucose, glycosilated hemoglobin and total proteins, glomerular filtration rate (GFR), and the glucose, proteins, calcium, phosphorus, uric acid, sodium, potassium and chloride excretions in diurnal, nocturnal and 24-hour urine samples in 43 diabetic children and 13 healthy controls. The microproteinuria mean value in all urine samples (always less than 15 micrograms/min/1.73 m.2), the GFR and blood pressure were similar in both groups. In the diabetic children, we found an inverse correlation between age and 24-hour urine microproteinuria (r-0.33; p less than 0.05) and between age and nocturnal urine microproteinuria (r-0.35; p less than 0.05). There was also a highly significant correlation between microproteinuria and the albumin/creatinine ratio in urine samples (r = 0.94, p less than 0.0001). Diabetic children showed a greater nocturnal excretion of calcium (p less than 0.05) and phosphorus (p less than 0.05). Our results suggest that microproteinuria, GFR and blood pressure have not served as predictors of DN in pediatric patients.


[Fibro-bronchoscopy without general anesthesia in pediatric patients].

Flexible bronchofiberoscopy is at present an indispensable technique in pediatric pulmonology departments. The fact that it can be used outside of the operating theater without general anesthesia or additional oxygen has greatly increased its field of pediatric applications. Thirty-three fibrobronchioscopies were performed during a period of one year on a group of children under 14 years of age. The most common indications for the procedure were atelectasis (27.3%), recurrent pneumonia (15.1%) and a possible foreign body (15.1%). The most usual sedation (82%) was the combination of Diazepan with Ketamine. Sixteen patients did not require oxygen and only one suffered a serious complication. The benefit of this technique was shown since the treatment of 22 children (67%) was changed following this procedure.


[Recurrent familial amyotrophic neuralgia of the brachial plexus. Report of a family and review of the literature].

A family with hereditary neuralgic amyotrophy of the brachial plexus throughout three generations is described. Outstanding features are early onset occurring during childhood or adolescence, unlike the idiopatic sporadic form of the disease, and the association with a peculiar physiognomy that reminds one of the facial expression found in Modigliani's paintings. Clinical evolution is not always favorable since relapses and long-lasting sequelae are common. The disease is inherited through an autosomal dominant gene with high penetrance and the neuropathy is always associated with the phenotypic features. The possible relationship with other pathological entities of very different clinical expression, such as tomacular neuropathy, is discussed, as well as the distinguishing peculiarities between the inherited and the sporadic forms of brachial plexus neuropathy.


[Hyperapo-beta-emia in children. Study of 17 families].

Apolipoprotein (apo)-beta is an atherosclerotic risk factor in adults and children. In families with Familial Combined Hyperlipidemia (FCH) it has been described as a lipoprotein phenotype called Hyperapobetalipoproteinemia (Hyperapo-beta) and characterized by increased numbers of small, dense and apo-beta enriched low density lipoproteins. In our Lipids Clinic, we have studied 267 children, but for the purpose of this paper we have only taken into account the 19 of these children who showed increased plasma total apo-beta levels (Hyperapo-beta-emina). To investigate the type of dyslipoproteinemia of these children, we divided them into two groups: 1) Group 1: 10 children with apo-beta levels greater than mean + 2 standard deviations (SD); 2) Group 2: 9 children with apo-beta levels greater than mean + 3 SD. We have also studied the fathers, mothers, brothers and sisters of all the children. Only one child (Group 1) had type IIb hyperlipoproteinemia. The other children had type IIa hyperlipoproteinemia. In each group, 4 families had FCH and the others had either Familial Hypercholesterolemia or Polygenic Hypercholesterolemia. Families with FCH could also have hyperapo-beta. It is possible that in the future some children of FCH families and those with type IIa hyperlipoproteinemia will have increased plasma triglyceride levels. This could be prevented by a proper diet.


[Intracardiac mycetoma induced by central catheterization].

We report a case of an infective endocarditis presented as a right atrial mass which pathological study showed a big vegetation of candida albicans (mycetoma). We think its presence was related to a great central vein catheterization during the neonatal period. The clinical feature was completed with pulmonary fungal embolism and later tricuspid valve afectation. With this work we wish to remark the necessary careful management of patients with central vein catheters to avoid this severe complication. We review the pharmacological and surgical treatment of this uncommon entity.


[HIV infection in infants under 15 months of age. Value of the p-24 antigen as a prognostic marker].

We have studied 65 children, born to HIV seropositive mothers, during the first quarter of life and afterwards every three-months. During this time, ten of the children (13%) became infected with the virus. The study of p24 antigen during the first 15 months of life showed an inverse relationship between the permanent presence of P24 antigen in the serum and the absence of anti-p24 antibodies. Since both markers were related to a bad prognosis, it is useful to carry-out the routine study of p24 antigen and its level in serum. Of the infections detected, 3 cases were early onset and the other 7 cases later onset. The three children from the first group died between 4 and 8 months of life, while the second group had a much more stable clinical situation. The children with early onset infections had T4 lymphocytes lower than 500 cell/mm3, detectable p24 antigen, and a fatal progression of the disease.


[Evaluation of the bone mass by dual-photon absorptiometry in children under prolonged anticonvulsant therapy].

We have evaluated, in a prospective study, the total and per unit area mass, measured in lumbar spine by Dual Photo-absorptiometry, in a group of 62 children on long-term anticonvulsant treatment. A second group of 58 normal children was used as a control. The total and per unit area bone mass increased with age, weight, height and bone maturity in all of the children studied. There were no significant differences found between the two groups. Children on multi-therapy and that were over six years of age showed statistically significantly less bone mass per area when compared th the control group (p less than 0.01). Phenobarbital, Carbamazepine and Valproic acid in monotherapy did not statistically diminish bone mass. Of these anticonvulsants, Phenobarbital was responsible for the most statistically significant decline in bone mass per area (p = 0.027). After six year of treatment, whether on mono-therapy or on poly-therapy, bone mass was lower with respect to the control series, although this was not statistically significant.


[The limit of pediatric age in primary health care. A problem to be solved].

The true definition of the term Pediatrics, implies comprehensive care up to the end of adolescence; in practice, however, treatment is usually only available up to the age of seven. In this study, the medical records of children born between 1976 and 1983 were examined with respect to the four areas of General Practice covered by a pediatrician. The characteristics of this conurbation and the nature of medical advice sought were also studied. A survey of the situation in the remainder of the country was also carried out by means of telephone conversations with pediatricians nationwide. Of the 519 children considered, 150 did not consult their doctor during 1990. Those that did seek medical attention did so on 802 occasions, which represents 3.6% of all consultations by general practitioners. However, it would have amounted to 25.3% of the visits to pediatricians. Raising the age limit of pediatric patients, as an isolated measure, would therefore overload pediatric offices and thus lead to a lower standard of medical care. Such a measure should not be implemented hastily.


[Pancreatic echography in infantile diabetes].

Our objective was to investigate the pancreatic ultrasonographic size in diabetic children in order to compare in with a healthy population of children and to relate it to the characteristics of their disease. Fifty-four children (age 8.59 +/- 3.38 years) with insulin-dependent diabetes mellitus of short evolution and 23 healthy children of similar ages and sex were investigated. Anteroposterior measurement of pancreatic head, body and tail with real time ultrasonography were performed searching for a relationship of these factors with the acinar and residual insular function. The pancreatic measurements in the diabetic patients were sizeable smaller than in the healthy children with no relationship to age, height, weight or body surface. There were no differences in the pancreatic measurements in relationship to the evolution time or residual insular function in the diabetics.


[Results of a study of the presence of spontaneous otoacoustic emissions in the newborn].

An otoacoustic emission is that part of sound that can be detected in the ear canal and is produced by the physiological cochlear activity involved in the auditive process. Some people have spontaneous oto-emissions (SOAE), which are emissions that can be registered without any stimulus. These are normal functional sounds of some cochleae. he aim of this study was to assess the presence of SOAE in newborns, as well as to study its incidence and relationship with the auditive process. The number of tested neonated was 364, 209 of whom had at least one ear with SOAE+ (57.4%). It was possible to do a bilateral test in only 324 newborns, 114 of whom had SOAE+ in both ears (35.18%). The total number of ears tested was 961 and in 453 of these a SOAE+ was detected (47.1%). This high incidence of SOAE corresponds to a very good cochlear condition compared to that of older people.


[Acute otitis media in childhood. Clinical and microbiological study of 50 cases].

Fifty cases of acute otitis media effusion (AOME) in children less than 14 years of age are reported. The largest age group consisted of children less than 22 months of age (22 cases). Otolgia or irritability (80%) and fever (66%) were the most common symptoms. Tympanocentesis of the middle-ear effusion was performed in all of the cases. Haemophilus influenzae was recovered in 13 patients (26%), S. pneumoniae in 12 (24%), S. pyogenes in 4 (8%), P. aeruginosa in 2 (4%), anaerobic bacteria in 2 (4%) and mixed cultures in 4 children; 2 cases of H. influenzae and S. pneumoniae, 1 case of S. pneumoniae and E. coli, and 1 case of E. coli and P. aeruginosa. There were no cases of M. catarrhalis or S. aureus. We conclude that H. influenzae and S. pneumoniae are the most frequent pathogens (60% of all patients and 81% of the positive cultures).


[Neurologic changes or vertebral malformations in children with anorectal malformations].

We present a prospective study of 40 patients with anorectal malformations. We have studied the correlation between neurological impairment and vertebral anomalies. We did not find a statistical correlation.


[Congenital syphilis and syphilitic mothers. Survey of the past 10 years].

Two hundred and sixty-two newborn infants, born to mothers with a positive syphilis serology, have been studied. Twenty-six newborn infants had congenital syphilis and two hundred and thirty-six were considered as newborn infants from syphilitic mothers. This study has demonstrated that the newborn infants with congenital syphilis have been born to mothers with greatest risk factors. Newborn infants with congenital syphilis born to mothers on treatment during the pregnancy had a milder case of congenital syphilis than newborn infants born to mothers without treatment during the pregnancy. A diagnostic test for the treatment in these newborns has been proposed; if the test score is less than 5, we are dealing with a child of a syphilitic mother that does not need treatment and if the test results are higher than 5 we can confirm the diagnosis of congenital syphilis and immediate treatment must be started.


[Five cases of Goldenhar-Gorlin syndrome].

Five patients with Goldenhar-Gorlin's syndrome (facio-auriculo-vertebral dysplasia) are presented in this study. Their clinical characteristics are commented on along with an illustrative iconography. The literature on this subject has been reviewed and we make some comments on the possible ethiopathogeny of this disease.


[Wolff-Parkinson-White disease in childhood: follow up of 36 cases].

We have studied 36 patients (19 females and 17 males), controlled between 1973 and 1989, who suffered Wolff-Parkinson-White (WPW) pattern in their electrocardiogram. Epidemiological, clinical, diagnostic, therapeutic and evolutional data were reviewed. The mean age at the time of diagnosis was 4 years and 3 months, with 48% younger than six months of age. The average time for the follow-up period was 4 years and 2 months. There was not familiar occurrence. Six (16%) of the patients had associated heart disease. Seventeen (47%) had type A of WPW, 12 (33%) type B and 7 (20%) were not defined. An echocardiographic study was done in 20 patients (61%). Twenty-seven patients (75%) showed supraventricular tachycardia (SVT), which in 22 of these cases was the reason for seeking consultation. Children without SVT, 9 (25%), did not need any form of treatment. Twenty-four (889) of the patients with SVT required treatment to prevent recurrence. In the 27 studied episodes of SVT, Verapamil IV (55%) and vagal manoeuvres were the most efficient treatments. Seventeen (47%) of the patients presented a persistent WPW pattern and 11 (31%) experienced a normalization of their electrocardiogram with a mean time of 2 years-2 months.


The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis.

To explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis. Case series of patients with seropositive rheumatoid arthritis. The outpatient clinic of the Division of Rheumatology, Mayo Clinic. One hundred and two patients with seropositive, erosive rheumatoid arthritis and a minimum disease duration of 3 years. Patients were genotyped for both HLA-DRB1 alleles and were categorized according to the expression of one or two disease-linked HLA-DRB1 alleles. Identification of HLA-DRB1 alleles was done by the polymerase chain reaction and subsequent oligonucleotide hybridization. Homozygosity for allelic variants was confirmed by sequence analysis. Immunogenetically defined patient subgroups were retrospectively evaluated for joint destruction and patterns of disease manifestation, including rheumatoid organ disease. Of 102 patients, 98 (96%) expressed the disease-linked sequence polymorphism. Forty-seven patients (46%) carried a double dose of the relevant sequence stretch: Twenty-eight patients expressed HLA-DRB1*04 variants on both alleles, and 19 combined an HLA-DRB*04 variant with HLA-DRB1*0101 or DRB1*1402. Nodular disease was present in 100% of patients typed as HLA-DRB1*04/04 and in 59% of patients typed as HLA-DRB1*04 and who had inherited only a single dose of the disease-linked sequence polymorphism (P < 0.0001). Major organ systems were involved in 61% and 11% of these two patient groups, respectively (P < 0.0001); and joint surgery was required in 61% and 25% (P < 0.002), respectively. Patients typed as HLA-DR*04/01 had intermediate clinical courses. Genotyping patients with rheumatoid arthritis for both HLA-DRB1 alleles identifies clinical subsets with distinct profiles of disease manifestations.


Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus.

To compare plasma androgen levels in diabetic and nondiabetic men and to determine their relation to diabetic dyslipidemia. A population-based, case-control study. Community. Men 53 to 88 years of age from the Rancho Bernardo, California, cohort who were screened for diabetes using an oral glucose tolerance test. Plasma androgen levels were compared in 44 men with untreated non-insulin-dependent diabetes mellitus and 88 age-matched men who had a normal glucose tolerance test. The relation of lipid and lipoprotein levels to androgen level and diabetic status was assessed before and after adjusting for covariates. Men with diabetes had significantly lower plasma levels of free (4.96 nmol/L compared with 5.58 nmol/L) and total testosterone (14.7 nmol/L compared with 17.4 nmol/L), dihydrotestosterone (428 pg/mL compared with 533 pg/mL), and dehydroepiandrosterone sulfate (DHEA-S) (1.92 mumol/L compared with 2.42 mumol/L) than nondiabetic men. They also had significantly lower high-density lipoprotein (HDL) cholesterol and significantly higher triglyceride levels. Differences were not explained by obesity, alcohol use, or cigarette habit. Overall, the total testosterone level, but not the free testosterone level, was positively correlated with the HDL cholesterol level (P = 0.009) and negatively correlated with the triglyceride level (P = 0.0001). Similar associations were seen in analyses restricted to the men without diabetes. Lower levels of endogenous androgens are seen in older diabetic men, and low androgen levels are associated with diabetic dyslipidemia.


A waterborne outbreak in Missouri of Escherichia coli O157:H7 associated with bloody diarrhea and death.

To describe and determine the source of a large outbreak of Escherichia coli O157:H7 (ECO157) infections in Missouri. A case-control study and a household survey. A small city in a rural Missouri township that had an unchlorinated water supply. Case patients were residents of or visitors to Burdine Township with bloody diarrhea or diarrhea and abdominal cramps occurring between 15 December 1989 and 20 January 1990. Escherichia coli O157 was isolated from 21 stool specimens. All isolates were resistant to sulfisoxazole, tetracycline, and streptomycin; produced Shiga-like toxins I and II; and had one 60-megadalton plasmid. Among the 243 case patients, 86 had bloody stools, 32 were hospitalized, 4 died, and 2 had the hemolytic uremic syndrome. In the case-control study, no food was associated with illness, but ill persons had drunk more municipal water than had controls (P = 0.04). The survey showed that, during the peak of the outbreak, bloody diarrhea was 18.2 times more likely to occur in persons living inside the city and using municipal water than in persons living outside the city and using private well water (P = 0.001). Shortly before the peak of the outbreak, 45 water meters were replaced, and two water mains ruptured. The number of new cases declined rapidly after residents were ordered to boil water and after chlorination of the water supply. This was the largest outbreak of ECO157 infections, the first due to a multiply resistant organism, and the first shown to be transmitted by water. System-wide chlorination as well as hyperchlorination during repairs might have prevented this outbreak. Both bloody and nonbloody diarrhea may be common manifestations of this infection, which is probably underdiagnosed because of the failure of routine stool cultures to identify the organism. Cities with deteriorating water systems using untreated water risk widespread illness from contaminated drinking water.


Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study.

To describe changes in negative emotions among participants of a cholesterol-lowering study. Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. Community-dwelling families of the Family Heart Study, Portland, Oregon. One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat "American diet." Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels.


The contribution of gastroesophageal reflux to chest pain in patients with coronary artery disease.

To describe the effectiveness of investigating and treating the cause of refractory chest pain in patients with coronary artery disease who are receiving optimal antianginal therapy. Cohort study. Tertiary referral center. Between January 1988 and December 1989, 34 patients were identified as having angiographically proven coronary artery disease and atypical chest pain symptoms despite their having received aggressive medical or surgical antianginal therapy, or both. Patients with confirmed acid-related symptoms were treated with high-dose histamine-2 (H2) blockers or omeprazole for 8 weeks in an open-label study. Esophageal manometry and simultaneous 24-hour pH and Holter studies; global improvement in or disappearance of chest pain. Of the 34 patients, 30 (88%) experienced their identical chest pain symptoms during the study. A total of 164 pain episodes was recorded: 38 (23.2%) correlated with acid reflux; 6 (3.7%) were related to cardiac ischemia; and the remaining 120 (73.2%) had no identifiable cause. Of these 30 patients, 20 (67%) had some of their episodes of chest pain (range, 14% to 100%) secondary to acid reflux. After 8 weeks of vigorous acid suppression, 13 of these 20 patients had marked improvement or resolution of chest pain. Four other patients had ischemia-related episodes of chest pain that responded to more aggressive antianginal therapy. No episodes of acid reflux were clearly followed by ischemic chest pain. One patient had both acid- and ischemic-related episodes of chest pain that were indistinguishable. Overall, 24 of 34 (71%) patients had a definite cause of chest pain identified by combined pH and Holter monitoring. Gastroesophageal reflux disease is a common, treatable cause of chest pain in patients with coronary artery disease who have atypical symptoms and remain symptomatic despite aggressive antianginal therapy. Combined Holter and 24-hour esophageal pH studies are complementary investigations for elucidating the cause of chest pain in these patients.


The prognostic role of left ventricular hypertrophy in patients with or without coronary artery disease.

To examine the association between echocardiographically determined left ventricular hypertrophy and mortality in patients with and without coronary artery disease. Cohort study with a mean follow-up period of 4 years. An inner-city public hospital in Chicago. A cohort of 785 patients, most of whom were black and had hypertension. Coronary arteriography for presumed coronary artery disease and echocardiography. All-cause and cardiac mortality. Left ventricular hypertrophy, based on left ventricular mass corrected for body surface area, was present in 194 of 381 patients (51%) with coronary artery disease and in 162 of 404 patients (40%) without coronary artery disease. Patients with left ventricular hypertrophy had worse survival than those without hypertrophy in both the group with coronary artery disease and the group without coronary artery disease. After adjustment was made for age at baseline, sex, and hypertension, the relative risk for death from any cause in patients with hypertrophy compared with patients without hypertrophy was 2.14 (95% CI, 1.24 to 3.68) among those with coronary artery disease and 4.14 (CI, 1.77 to 9.71) among those without coronary artery disease. Echocardiographically determined left ventricular hypertrophy is an important prognostic marker in patients with or without coronary artery disease. The effect of reversing ventricular hypertrophy in patients with and without coronary disease deserves further study.


The downsizing of internal medicine residency programs.

A variety of forces are converging to reduce the number of internal medicine residency positions offered in this country. This reduction, referred to as downsizing, has been proposed as the solution to several of the problems facing internal medicine. We examine the forces that underlie the current enthusiasm for downsizing; we consider the alternative strategies by which downsizing might be implemented; and we consider the implications of these alternatives on different groups of stakeholders. Although downsizing may represent a legitimate approach to real problems, any mechanism to reduce the number of training positions in internal medicine will have broad implications for medical education and patient care well into the next century. Special efforts must be taken to ensure that downsizing will not exacerbate the existing problem of overspecialization and limited access to care.


Detection of renovascular hypertension. State of the art: 1992.

To review recent advances in detecting renovascular hypertension. Original English-language reports obtained through a MEDLINE search for the years 1987 to 1991. Also, a manual search through Index Medicus as well as bibliographies of original reports and selected review articles. Cited studies were critically reviewed with emphasis on study size, patient sample, methods, diagnostic criteria, and reproducibility of results. Where applicable, reviews that combined the results of smaller studies are cited. A sensitivity of 74% and a specificity of 89% have been reported for the captopril test and of 93% and 95%, respectively, for captopril scintigraphy with diethylenetriaminepentaacetic acid (DTPA). The sensitivity and specificity of renal vein renin determination are 80% and 62%, respectively and may increase with the use of stricter technical criteria and maneuvers to stimulate renin secretion. These tests differentiate renovascular hypertension from essential hypertension more reliably than from asymmetric renal parenchymal disease; however, they do not reliably distinguish unilateral from bilateral stenosis. Other tests are less widely used. Intravenous pyelography (sensitivity, 74.5%; specificity, 86.2%) has the disadvantages of radiation and dye load exposure. Intravenous angiography is expensive and invasive and does not always enable visualization of the origin of the renal artery. The roles of duplex ultrasound and magnetic resonance angiography remain to be clarified. Noninvasive tests are cost effective and have a high predictive value in patients with clinical clues suggestive of renovascular hypertension. These tests are not recommended for use in patients with a low likelihood of disease.


The stress response and the regulation of inflammatory disease.

The molecular and biochemical bases for interactions between the immune and central nervous systems are described. Immune cytokines not only activate immune function but also recruit central stress-responsive neurotransmitter systems in the modulation of the immune response and in the activation of behaviors that may be adaptive during injury or inflammation. Peripherally generated cytokines, such as interleukin-1, signal hypothalamic corticotropin-releasing hormone (CRH) neurons to activate pituitary-adrenal counter-regulation of inflammation through the potent antiinflammatory effects of glucocorticoids. Corticotropin-releasing hormone not only activates the pituitary-adrenal axis but also sets in motion a coordinated series of behavioral and physiologic responses, suggesting that the central nervous system may coordinate both behavioral and immunologic adaptation during stressful situations. The pathophysiologic perturbation of this feedback loop, through various mechanisms, results in the development of inflammatory syndromes, such as rheumatoid arthritis, and behavioral syndromes, such as depression. Thus, diseases characterized by both inflammatory and emotional disturbances may derive from common alterations in specific central nervous system pathways (for example, the CRH system). In addition, disruptions of this communication by genetic, infectious, toxic, or pharmacologic means can influence the susceptibility to disorders associated with both behavioral and inflammatory components and potentially alter their natural history. These concepts suggest that neuropharmacologic agents that stimulate hypothalamic CRH might potentially be adjunctive therapy for illnesses traditionally viewed as inflammatory or autoimmune.


Clinical evaluation for sinusitis. Making the diagnosis by history and physical examination.

To identify the most useful clinical examination findings for the diagnosis of acute and subacute sinusitis. Prospective comparison of clinical findings with radiographs. General medicine clinics at a university-affiliated Veterans Affairs Medical Center. Two hundred forty-seven consecutive adult men with rhinorrhea (51%), facial pain (22%) , or self-suspected sinusitis (27%) (median age, 50 years; median duration of symptoms, 11.5 days). Patients were examined by a principal investigator (86%) or by a staff general internist, internal medicine resident (postgraduate year 2 or 3), or physician assistant, all blinded to radiographic results. All examiners recorded the presence or absence of 16 historical items, 5 physical examination items, and the clinical impression for sinusitis (high, intermediate, or low probability). The criterion standard was paranasal sinus radiographs (4 views), which were interpreted by radiologists blinded to clinical findings. Thirty-eight percent of patients meeting entrance criteria had sinusitis. Sensitivity, specificity, and likelihood ratios were measured for clinical items. Logistic regression analysis showed five independent predictors of sinusitis: maxillary toothache (odds ratio, 2.9), transillumination (odds ratio, 2.7), poor response to nasal decongestants or antihistamines (odds ratio, 2.4), colored nasal discharge reported by the patient (odds ratio, 2.2), or mucopurulence seen during examination (odds ratio, 2.9). THe overall clinical impression was more accurate than any single finding: high probability (likelihood ratio, 4.7, intermediate (likelihood ratio, 1.4), low probability (likelihood ratio, 0.4). General internists, focusing on five clinical findings and their overall clinical impression, can effectively stratify male patients with sinus symptoms as having a high, intermediate, or low probability of sinusitis.


Octreotide treatment of acromegaly. A randomized, multicenter study.

To determine the effects of the somatostatin analog, octreotide acetate, in patients with acromegaly. Double-blind, randomized trial. Fourteen university-affiliated medical centers. One hundred fifteen acromegalic patients, 70% of whom had persistent disease after pituitary surgery or radiotherapy. Subcutaneous octreotide, 100 micrograms, or placebo every 8 hours for 4 weeks. Four weeks after the end of treatment, patients were randomized to receive 100 or 250 micrograms octreotide subcutaneously every 8 hours for 6 months. After 2 weeks of treatment, a single 100-micrograms injection reduced mean serum growth hormone (GH) to 30% of the pretreatment concentration within 2 hours. The integrated mean GH level was reduced over 8 hours from 39 +/- 11 micrograms/L to 9 +/- 2 micrograms/L (P less than 0.001). Mean plasma insulin-like growth factor-1 (IGF-1) was reduced from 5100 +/- 400 U/L to 2400 +/- 400 U/L (P less than 0.001). After 6 months, the mean GH was reduced from 39 +/- 13 to 15 +/- 4 micrograms/L by 300 micrograms of octreotide and from 29 +/- 5 micrograms/L to 9 +/- 2 micrograms/L by 750 micrograms of octreotide daily. The mean IGF-1 concentration was suppressed to 2100 +/- 300 and 2500 +/- 400 U/L after 300 and 750 micrograms octreotide, respectively. Integrated mean GH levels were reduced to < 5 micrograms/L in 53% (95% CI, 39% to 67%) and 49% (CI, 35% to 63%), and IGF-1 levels were normal in 68% (CI, 54% to 82%) and 55% (CI, 40% to 70%) of patients receiving low- and high-dose octreotide, respectively. A substantial decrease in headache, amount of perspiration, joint pain, and finger circumference occurred in two thirds of the patients. The pituitary size was reduced in 19% (CI, 5% to 33%) and 37% (CI, 22% to 52%) of patients receiving 6 months of low- and high-dose octreotide, respectively. Ten percent and 13% of patients in each treatment group developed transient diarrhea; 10% and 14%, biliary sludge; and 6% and 18%, cholelithiasis, respectively. Octreotide effectively decreased GH and IGF-1 concentrations in 53% and 68% of patients, respectively. The higher dose resulted in increased frequency of tumor shrinkage but added no biochemical or clinical benefit.


Rapid reduction of left ventricular hypertrophy in acromegaly after suppression of growth hormone hypersecretion.

To examine the possible role of growth hormone as a pathogenetic factor in the development of myocardial hypertrophy in acromegaly. An uncontrolled clinical trial. Tertiary-care medical center. Sixteen patients with acromegaly were stratified into two groups: Group I (n = 10) had left ventricular hypertrophy (LVH), and group II (n = 6) did not have LVH. Therapy with octreotide acetate (SMS 201-995), a long-acting somatostatin analog (mean dose, 538 micrograms/d), was administered for 2 months. Plasma growth hormone and insulin-like growth factor I (IGF-I) concentrations, hand volume, and echocardiographic left ventricular dimensions and mass were measured at baseline and at 1 week and 2 months after the start of therapy. Before octreotide therapy, both groups had similar hand volumes and similar growth hormone and IGF-I hypersecretion. Both groups showed a reduction in growth hormone at 2 months (mean reduction, 13.7 micrograms/L in patients with LVH [P < 0.01] and 14.1 micrograms/L in patients without LVH [P < 0.05]). Plasma IGF-I was also decreased (mean reduction, 305 micrograms/L in patients with LVH [P < 0.01] and 304 micrograms/L in patients without LVH [P < 0.05]). Reduction of growth hormone and IGF-I hypersecretion in patients with LVH was associated with a rapid decrease in left ventricular mass (339 g to 299 g, P < 0.01) within 1 week, which was sustained at 2 months (274 g, P < 0.04). Patients without LVH showed no statistical change in left ventricular mass. In patients with LVH, the decrease in left ventricular mass correlated with the octreotide-induced decrease in growth hormone (r = 0.79, P less than 0.05) but not with blood pressure. Blood pressure, left ventricular dimensions, and percent of fractional shortening were not altered by therapy in either group. Hand volume decreased in both groups. Normalization of growth hormone secretion is associated with reduction of left ventricular mass in acromegalic patients with LVH within 1 week of initiating therapy with octreotide.


Treatment of shigellosis: III. Comparison of one- or two-dose ciprofloxacin with standard 5-day therapy. A randomized, blinded trial.

To determine whether a single dose, or 2 doses, of ciprofloxacin are as effective as 5-day, 10-dose therapy for the treatment of shigellosis in adult men who are moderately to severely ill. Randomized, double-blind clinical trial. A diarrhea treatment center in the capital city of a developing country, Bangladesh. A total of 128 adult men with dysentery of less than 96 hours duration. All had Shigella organisms isolated from a culture of stool. Patients were randomly assigned to receive either a single 1-gram dose of ciprofloxacin at admission to the study (single-dose group; n = 40), a 1-gram dose of ciprofloxacin at admission and 24 hours later (2-dose group; n = 43), or 500 mg of ciprofloxacin every 12 hours for 5 days (10 dose group; n = 35). All patients were hospitalized for 6 days. Stools were collected individually; their character and consistency were recorded and cultured daily. A physical examination and recording of symptoms were done daily, and the temperature was measured every 4 hours. Therapy was considered to have failed in patients who did not have improvement in the signs and symptoms of dysentery after 72 hours of therapy or in patients who on study day 5 had more than nine stools, or more than two watery stools, or were febrile. There were no treatment failures in the 78 patients infected with species of Shigella other than Shigella dysenteriae type 1. Among the 40 patients infected with S. dysenteriae type 1, treatment failed in 4 of the 10 patients who received single-dose therapy, 2 of the 15 patients who received 2-dose therapy, and none of the 15 patients who received 10-dose therapy (P = 0.017, single-dose therapy group compared with 10-dose group; P = 0.15 for the single-dose group compared with the 2-dose group; P > 0.2 for the 2-dose group compared with the 10-dose group). A single 1-gram dose of ciprofloxacin is effective therapy for patients infected with species of Shigella other than S. dysenteriae type 1. Single-dose therapy is inferior to 10-dose therapy for treating patients infected with S. dysenteriae type 1.


Low accuracy of color Doppler ultrasound in the detection of proximal leg vein thrombosis in asymptomatic high-risk patients. The RD Heparin Arthroplasty Group.

To evaluate the ability of color Doppler ultrasound to detect proximal deep venous thrombosis (DVT) in asymptomatic high-risk patients who subsequently underwent contrast venography. Prospective cohort study using blinded observers, with contrast venography as the comparison standard. Seven medical centers (university and community hospitals) participating in a clinical trial of low-molecular-weight heparin for prevention of DVT. A total of 385 consecutive patients undergoing elective unilateral hip or knee replacement. Ten days after surgery or before hospital discharge (whichever occurred first), patients had bilateral color Doppler ultrasound examinations of the proximal veins of the lower extremities. Subsequently, a contrast venogram of the operated leg was obtained. Color Doppler ultrasound studies and venograms were both evaluable in 319 of the 385 patients. Deep venous thrombosis was identified by contrast venography in 80 patients (prevalence, 25%; 95% CI, 20% to 30%) and involved the proximal veins in 21 patients (prevalence, 7%; CI, 4% to 10%). For proximal DVT, color Doppler ultrasound showed poor sensitivity (38%; CI, 18% to 62%), moderately good specificity (92%; CI, 89% to 95%), and a poor positive predictive value for this population (26%). Color Doppler ultrasound examinations are insensitive to proximal DVT in asymptomatic high-risk patients and should not be substituted for venography for identifying proximal DVT in such patients.


Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials.

To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy. Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials. Multiple centers in the United States. Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety. Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks. Changes in mean hematocrit, transfusion requirement, and quality of life. Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections. Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.


Assessing housestaff diagnostic skills using a cardiology patient simulator.

To assess the cardiovascular physical examination skills of internal medicine housestaff. Cross-sectional assessment of housestaff performance on three valvular abnormality simulations conducted on the cardiology patient simulator, "Harvey." Evaluations were done at the beginning (session I) and end (session II) of the academic year. Duke University Medical Center internal medicine training program. Sixty-three (59%) of 107 eligible internal medicine housestaff (postgraduate years 1 through 3) agreed to participate and completed session I; 60 (95%) completed session II. All volunteers were tested on three preprogrammed simulations (mitral regurgitation, mitral stenosis, and aortic regurgitation). The overall correct response rates for all housestaff were 52% for mitral regurgitation, 37% for mitral stenosis, and 54% for aortic regurgitation. No difference was noted in correct response rates between sessions I and II. For mitral regurgitation, correct assessment of the contour of the holosystolic murmur predicted a correct diagnosis (P = 0.002). For mitral stenosis, identification of an opening snap and proper characterization of the mitral area diastolic murmur predicted a correct diagnosis (P < 0.0001). No individual observations were noted for the aortic regurgitation simulation, whose identification by the housestaff was associated with a correct diagnosis. Housestaff had difficulty establishing a correct diagnosis for simulations of three common valvular heart diseases. Accurate recognition of a few "key" observations was associated with a correct diagnosis in two of the three diseases. Teaching housestaff to elicit and interpret a few critical signs accurately may improve their physical diagnosis abilities.


Carcinoma of the male breast.

The natural history and current management of carcinoma of the breast in men is reviewed. Articles published from 1942 to 1992 on the natural history, clinical manifestations, diagnosis, and treatment of carcinoma of the breast in men were identified using CANCERLINE and MEDLINE. Carcinoma of the breast affects approximately 1000 men per year in the United States; 300 men per year will die of metastatic disease. The mean age at diagnosis is 59 years. The causes of breast cancer in men are unknown. The most common clinical manifestation of breast cancer in men is a painless, firm subareolar mass or a mass in the upper outer quadrant of the breast. Diagnosis can be confirmed by fine-needle aspiration or surgical biopsy. Infiltrating ductal carcinoma is the predominant histologic type. Treatment is similar to that of women with breast cancer. Men with axillary nodal metastasis should receive adjuvant systemic combination chemotherapy or tamoxifen, or both, after primary surgical treatment. Because most men with carcinoma of the breast have estrogen- and progesterone-receptor-positive tumors, distant metastatic disease should be treated initially with hormonal therapies. The epidemiology, prognostic factors, survival by stage, pattern of metastasis, and response to treatment in men are similar to those in women with breast carcinoma. The data suggest, however, that breast cancers in men are more likely to respond to hormonal manipulation.


General internal medicine and general internists: recognizing a national need. Federated Council for Internal Medicine.

The Federated Council for Internal Medicine (FCIM) comprises the American Board of Internal Medicine, American College of Physicians, American Society of Internal Medicine, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, and the Society of General Internal Medicine. The Council was established in 1975 to speak with a collective voice for the specialty of internal medicine. In 1992, the Council developed the following statement in conjunction with its endorsement of a target of 50% of internal medicine residency graduates entering the practice of general internal medicine.


Beneficial effects of reduced oxygen tension and perfusion in long-term hematopoietic cultures.

Growth of hematopoietic stem and progenitor cells found in the MNC fraction of human cord blood was evaluated under atmospheres containing reduced (5%) and normal (20%) oxygen tension. Reduced oxygen tension increased total cell numbers by as much as 5-fold in cord blood suspension cultures, but this effect was less pronounced in cultures containing an irradiated bone marrow stromal cell layer. However, reduced oxygen tension resulted in a substantial increase in both the number and frequency of colony-forming cells observed in both types of LTHC studied. Under low oxygen, CFU-C progenitor cell numbers were as much as 10-fold higher. Finally, reduced oxygen tension slowed the rate of irradiated stromal layer degeneration, as judged by cell counts and microscopic examination. These results indicate that low oxygen, which better approximates the in vivo environment, enhances the growth and maintenance of human stromal and progenitor cells in vitro. These low oxygen findings were then applied to a murine model LTHC perfusion system. In this system, irradiated 3T3 stromal layer integrity was improved under low oxygen and was substantially further improved with continuous medium perfusion. Cell counts and flow cytometry analysis indicated that the total cell production and the production of immature cells from murine bone marrow MNC on irradiated 3T3 cells were significantly enhanced under low oxygen with perfusion. After three weeks of culture, a 24-fold higher number of Thy1.2lo F4/80- MAC1- cells (indicative of murine stem and progenitor cells) was observed in the perfusion system as compared with static culture under ambient oxygen.


Modulation of glutathione level in CHO cells. Effects of oxygen concentration and prior exposure to hypoxia.

A microtiter-plate assay has been developed for total intracellular glutathione that facilitates multiple-sample analysis and reduces the amount of time and chemicals required. Sonication time, pH, and storage conditions were identified as key parameters that affect the accuracy of the assay. Using this assay, it was found that CHO cells increase their glutathione level under higher oxygen tension. This adaptive response suggests that a rise in glutathione may be used as an indicator of oxidative stress. Based on this criterion, it was found that hypoxic and anoxic cells are sensitized to reoxygenation. This sensitization could not be attributed to a drop in glutathione during low oxygen exposure because the glutathione content reached a basal level at a PO2 of about 40 torr.


Three-dimensional cell cultures mimic tissues.

Three-dimensional cell culture using gels of type I collagen is a flexible method for studying cell behavior in a tissuelike environment. With only small changes in the basic protocol, we were able to encapsulate neutrophils, hepatocytes, and PC12 cells. As demonstrated by cell-specific assays for migration, protein secretion, and growth factor induction, the encapsulated cells were viable and functional. In future studies, we will focus on using these cell cultures to study cell movement, cell growth, and cell function in carefully controlled tissuelike environments.


Dynamic metabolic control theory. A methodology for investigating metabolic regulation using transient metabolic data.

The purposes of the dynamic metabolic control theory are to provide a theoretical basis for estimating the control coefficients using the transient metabolic responses and to gain insights into the metabolic regulation in the transient states. The numerical application of this theory is relatively straightforward: it involves a standard linear regression and a matrix multiplication. Although the equations are exact only for linear kinetics, they yield relatively good estimates of the control coefficients for nonlinear systems.


Use of magnetic resonance imaging to analyze the performance of hollow-fiber bioreactors.

Preliminary experiments were described that demonstrate that MRI is an effective tool for the noninvasive study of hollow-fiber bioreactors. Flow-compensated velocity-encoding pulse sequences were successively applied to analyze the velocity patterns in a module operated without cells, with an artificially induced flow field perturbation. Diffusion damping pulse sequences were also used to spatially resolve regions of cell growth in a bioreactor. These experiments provide the necessary basis from which future flow and spectroscopic studies can be conducted.


Alternative strategies to the scaleup of animal cells.

The use of porous microcarriers has given manufacturers the option of having a high cell density/medium volume (10-100 L)/high specific productivity/long-term process. The advantages of the system are listed in Table 7 and many of the criteria listed in Table 1 are met. The question of being able to license products from continuous processes has been addressed and guidelines are being prepared. Methods are available to compare the master and end-of-process (extended) cell banks to ensure that no change has occurred to the cell or product. Rigid attention to process definition and validation, as well as to the definition of production lots, overcomes many of the other reservations. In conclusion, the method has been demonstrated as technically feasible, economically advantageous, and licensable and the many advantages of a high density perfusion process (listed in Table 8) make porous microcarrier technology an ideal scaleup process because it is a simple, reliable, and scalable system.


The importance of cell physiology to the performance of animal cell bioreactors.

This report has pointed out the following: (1) the new animal cell products that will be produced commercially will have large dollar markets and will, together with cost containment and competitive pressures, place a greater emphasis on the reduction of the cost of production through the selection of appropriate culture technology; (2) the benefits to be gained by working with basic biological processes in animal cell culture that will increase cell density, cell productivity, and product quality; (3) the need to work with reactor technologies that can affect the basic biology of the cell in these positive ways; (4) it appears worthwhile to explore immobilized, high cell density culture technologies as a possible means to achieve the objectives by affecting the basic regulation of the cell through fundamental cell/cell environment biological processes.


Vector construction, transformation, and gene amplification in Clostridium acetobutylicum ATCC 824.

In order to alter the primary metabolism of C. acetobutylicum, we have constructed E. coli- or B. subtilis-C. acetobutylicum shuttle vectors that could be used to deliver homologous fermentative genes into C. acetobutylicum ATCC 824. The plasmid copy number and plasmid stability in C. acetobutylicum for several of these plasmids were determined. We have also developed a protocol for the electrotransformation of C. acetobutylicum ATCC 824. Difficulty in the transformation of C. acetobutylicum ATCC 824 with vectors containing DNA from E. coli plasmids was found to be due to the existence of a restriction system in this strain. This type II restriction endonuclease, named Cac824I, recognizes the sequence 5'-GCNGC-3' and cuts ColE1 plasmids frequently. One of the vectors, pFNK1, possessing a variety of unique cloning sites was used in the amplification of one acid (PTB) and one solvent (AADC) formation gene. The corresponding enzyme activities were amplified in C. acetobutylicum as shown by enzyme assays and SDS-PAGE gels of cell extracts.


Regulation of genetic expression in shear stress-stimulated endothelial cells.

There is increasing evidence that endothelial cells respond to the initiation of mechanical stress by the generation of certain second messengers and the activation of specific metabolic pathways. These rapid alterations in cellular function are accompanied by alterations in protein synthesis that are detectable several hours after initiation of the mechanical stress. The molecular mechanisms by which changes in the cytosol are converted to altered genetic expression in the nucleus are not known. Because agonist-induced modulations in the rate of synthesis of tPA and ET have been associated with the Fos and Jun protein families, it seems reasonable to propose that genetic expression in shear stress- or mechanical strain-stimulated endothelial cells is also regulated by selective induction of fos and jun gene products. Testing of this hypothesis is actively under way in our laboratory.


Complete but transient visual loss after yttrium aluminum garnet laser transscleral cyclocoagulation.

We report the case of a patient who had no light perception after neodymium:yttrium aluminum garnet (Nd:YAG) laser transscleral cyclocoagulation. To the best of our knowledge, no similar cases have been reported previously. A 56-year-old man with intractable open-angle glaucoma had intraocular pressures of 42 mmHg OD and 35mmHg OS. The patient rejected a recommended filtering operation, although argon laser trabeculoplasty and maximal medication had been ineffective OU. We used the free-running mode of an Nd:YAG laser to treat this patient. After the tenth application, the patient suddenly noticed acute visual loss OD. He was admitted to the hospital immediately. His retinal vessels and papilla OD could not be seen during fluorescein angiography. We administered pulsed corticosteroids and a stellate ganglion block. Gradually, his symptoms improved. The indications for using Nd:YAG laser cyclocoagulation have been expanded. However, as a result of our experience in this patient, we concluded that such therapy should be limited to cases not amenable to other forms of medical and surgical treatment.


Silicone oil-induced corneal hydrops?

A 27-year-old man with a personality disorder, who did not have keratoconus previously, recently presented with a clinical picture resembling acute corneal hydrops OS three years after silicone oil injection for a complicated retinal detachment. Although self-induced trauma could not be excluded completely, this case might represent a newly described late corneal complication of intracameral silicone oil.


Retinoblastoma, microphthalmia, coloboma, and neuroepithelioma of the pineal body.

A one-month-old infant boy was examined early in life because his mother had bilateral retinoblastoma and his father had bilateral microphthalmia. The ophthalmologist found his right eye was normal size with a coloboma of the iris, choroid, and retina. The left eye was microphthalmic with a coloboma of the uveal tract and retina. A vascularized fluffy white mass in the posterior pole was diagnosed clinically as a retinoblastoma. The tumor regressed with radiation. When the patient was four years of age, a large tumor was found in the region of the pineal recess, causing hydrocephalus and seizures. A biopsy showed an undifferentiated malignant neuroepithelial neoplasm. The patient died within three months of diffuse central nervous system tumor. The unusual findings of a retinoblastoma in a microphthalmic eye with bilateral colobomas and a neuroepithelial neoplasm of the pineal gland are discussed.


Leukemic infiltrate versus anterior uveitis.

Anterior segment leukemic infiltrate (ASLI) is rare; it is found in 0.5% to 2.5% of all leukemic relapses. Its clinical manifestations, at times, are similar to those of anterior uveitis (AU). We report the cases of three patients, all of whom had ASLI as their primary manifestation of relapse. We observed some major clinical differences between ASLI and AU that may help differentiate these two conditions without using anterior chamber paracentesis and/or iris biopsy. The development of resistance to leukemic therapy is the major factor in treatment failure.


New high-index visolett magnifier.

The high-index Visolett magnifier (index, 1.806) is an optically designed glass paperweight magnifier. It magnifies 2.49x, is 32mm in diameter, nonfocusable, and rests on paper. All Visoletts commercially available are made of crown glass (index, 1.523). The 32mm high-index Visolett has become commercially available recently. The use of high-index material increases the image size by 39%.


Toxicity of methyl methacrylate monomer in orbital and cranial surgery.

Methyl methacrylate (plastic bone cement) can be prepared by mixing a vial of liquid monomer with a powder. The monomer can release a toxic vapor. We measured the exposure of operating room personnel to this toxic substance. We believe that an awareness of the potential toxicity of the monomer is important and that devices to limit its exposure to personnel should be used in operating rooms.


X-linked pathologic myopia.

We examined a patient with decreased visual acuity and macular changes attributable to pathologic myopia. Thirteen additional family members were examined, and historic information was obtained on their relatives. A pedigree spanning six generations was constructed that demonstrated an X-linked mode of inheritance. This finding has important genetic and therapeutic implications for similarly affected patients.


Orbital cellulitis and cavernous sinus thrombosis after cataract extraction and lens implantation.

Orbital cellulitis as a complication of ophthalmic surgery is uncommon. We treated a patient who had orbital cellulitis and cavernous sinus thrombosis three weeks after uncomplicated cataract extraction and lens implantation. Sinus x-rays showed sphenoid sinus opacification. Computed tomographic scan confirmed the sphenoid sinus disease, and no abscess was found. The patient recovered completely after treatment with intravenous antibiotics. Most orbital cellulitis is secondary to sinus disease. The trauma of surgery and the retrobulbar block must be considered possible causative factors in this patient, but sinus disease is still the most likely cause. Intraocular inflammation did not increase during the illness although the intraocular pressure rose from 14 to 23mmHg.


Intraoperative laryngeal electromyographic assessment of patients with immobile vocal fold.

The differential diagnosis of laryngeal ankylosis versus paralysis is occasionally difficult in patients with immobile vocal folds. Eight patients with acute and chronic evidence of vocal fold immobility were investigated by intraoperative electromyography (IEMG) during planned microlaryngoscopy. Bipolar hook wire electrodes were inserted into the thyroarytenoid muscle, of which the electrical activity was monitored during neuromotor blockade and emergence from anesthesia. The normal side and the side with ankylosis or stenosis showed normal IEMG activity. There was progressive recruitment of larger motor units during recovery from muscle relaxation. Patients with laryngeal paralysis failed to show such recruitment patterns. Thus, IEMG can be used as a diagnostic tool during operative laryngoscopy to differentiate neuromotor injury from anatomic causes of vocal fold immobility. The advantages of IEMG are its ease of application and certainty of electrode position. It can also be used to monitor recurrent nerve integrity and detect early laryngospasm. Further IEMG clinical study is warranted.


Experimental tracheal replacement using a revascularized jejunal autograft with an implantable Dacron mesh tube.

Defects comprising more than 50% of the trachea cannot be reliably reconstructed by any current technique or prosthesis. A composite tracheal replacement implant consisting of a Dacron-urethane mesh tube and revascularized jejunal autograft was applied to this problem. This composite implant was used to replace 7 to 10 cm of trachea in eight dogs. The implant was sewn to the outside (serosal surface) of the jejunum to provide permanent structural support to the autograft, and an intraluminal silicone tube was placed inside the jejunal segment and left for 4 weeks following reconstruction. Six of eight animals survived the predetermined time periods and were killed painlessly in groups of two animals at 1, 2, and 6 months after removal of the intraluminal silicone tube. Postoperative intubation, ventilation, or tracheostomy was not necessary. Excessive secretions were not seen in any of the animals, and a fair to good performance status was maintained until death in all but one animal. Histologic examination revealed slight thinning of the jejunal mucosa, with no change in the jejunal muscularis. These data suggest that with further refinement this composite implant may be a viable reconstructive option in humans.


Subglottic ulceration and healing following endotracheal intubation in the neonate: a morphometric study.

In neonates, acquired subglottic stenosis is the most serious long-term complication of endotracheal intubation and is due primarily to posttraumatic fibrosis of the infant larynx. We have examined 78 larynges, 75 of which were intubated, from infants ranging in gestation from 22 to 40 weeks, and who survived from a few hours to up to 300 days. Each larynx was morphometrically assessed for the extent of acute injury, indicated by the percentage of epithelial loss, and healing, indicated by the percentage of a subglottic ulcer covered by metaplastic squamous epithelium. Results show that acute injury is almost invariable, and up to 100% of the subglottic epithelium may be lost within a few hours of intubation, but that progression of injury is relatively short-lived. Ulcer healing starts after a few days, rapidly progresses from day 10, and in the majority of cases is complete after 30 days. This study suggests that long-standing acute injury in the subglottis is the exception rather than the rule, even with the endotracheal tube remaining in place.


Causes of facial nerve paresis after translabyrinthine surgery for acoustic neuroma.

Forty-six consecutive video-recorded translabyrinthine operations at Gentofte Hospital, for tumors of 5 to 25 mm, were investigated for possible damage to the facial nerve from cauterization, suction, stretching, pushing, and other instrumental trauma at the following regions: fundus, internal meatus, porus, cerebellopontine angle, and brain stem. House-Brackmann grading of the postoperative facial nerve function was determined from the patient records for the 1st, 3rd, and 10th days and 3 months and 6 months postoperatively, as well as the final status. Suction on the nerve seems to be the most important factor for perioperative facial nerve damage. The most common site of damage was the porus region. This investigation shows thermic drilling lesions to be very relevant. There was no correlation between the degree and character of damage and the postoperative facial nerve function. In eight patients we cannot explain the postoperative facial palsy.


Recovery from repeated sudden hearing loss with corticosteroid use in the presence of an acoustic neuroma.

Sensorineural hearing loss of sudden onset may be the presenting symptom in up to 14% of patients with acoustic neuroma. We present the first reported case of sudden hearing loss in an only hearing ear with recovery to normal levels after steroid therapy on four separate occasions. Evaluation revealed a 1.5-cm acoustic neuroma. After middle cranial fossa decompression, a fifth episode with recovery after steroid use was documented. A review of the recent literature is presented, emphasizing the possible causation of sudden sensorineural hearing loss with recovery to normal in patients with acoustic neuroma. Modalities of therapy for the dilemma of the acoustic neuroma in an only hearing ear are discussed, including surgery, radiotherapy, and chemotherapy. An aggressive approach to the evaluation of the cause of sudden hearing loss is suggested.


Single motor unit activity of human intrinsic laryngeal muscles during respiration.

Individual motor units in the thyroarytenoid (TA) and cricothyroid (CT) muscles were studied in 10 normal human volunteers during quiet respiration. Both tonic and phasic firing patterns were found in both TA and CT units. The rate of firing was higher during inhalation than during exhalation in phasic TA units and in tonic CT units. Tonically active units had a higher firing frequency than phasically active units in both TA and CT muscles. Phasically active units corresponded with the respiratory cycle, with firing associated with inhalation in both the TA and CT muscles. A variety of firing patterns were found between units in both the TA and CT muscles, and in one subject, units recorded from the same muscle had very different firing patterns. The results suggest that although laryngeal motoneurons are modulated by the respiratory cycle, they do not respond uniformly to respiration.