Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy.

BACKGROUND: Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. CASE PRESENTATION: We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient's disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. CONCLUSIONS: Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.

Monocytes are essential for the neuroprotective effect of human cord blood cells following middle cerebral artery occlusion in rat.

Systemic administration of human umbilical cord blood (HUCB) mononuclear cells (MNC) following middle cerebral artery occlusion (MCAO) in the rat reduces infarct size and, more importantly, restores motor function. The HUCB cell preparation is composed of immature T-cells, B-cells, monocytes and stem cells. In this study we examined whether the beneficial effects of HUCB injection were attributable to one of these cell types. Male Sprague Dawley rats underwent permanent MCAO followed 48 h later by intravenous administration of HUCB MNC preparations depleted of either CD14(+) monocytes, CD133(+) stem cells, CD2(+) T-cells or CD19(+) B cells. Motor function was measured prior to MCAO and 30 days post-stroke. When CD14(+) monocytes were depleted from the HUCB MNC, activity and motor asymmetry were similar to the MCAO only treated animals. Monocyte depletion prevented HUCB cell treatment from reducing infarct size while monocyte enrichment was sufficient to reduce infarct size. Administration of monocyte-depleted HUCB cells did not suppress Iba1 labeling of microglia in the infarcted area relative to treatment with the whole HUCB preparation. These data demonstrate that the HUCB monocytes provide the majority of the efficacy in reducing infarct volume and promoting functional recovery.

A probability model of vector behavior: effects of DDT repellency, irritancy, and toxicity in malaria control.

A probability model of how DDT residues may function within a malaria control program is described. A step-wise organization of endophagic behaviors culminates in a vector acquiring a human blood meal inside the house. Different vector behaviors are described, epidemiologically defined, temporally sequenced, and quantified with field data. Components of vector behavior and the repellent, irritant, and toxic actions of insecticide residues are then assembled into a probability model. The sequence of host-seeking behaviors is used to partition the total impact of sprayed walls according to the three chemical actions. Quantitatively, the combined effect of repellency and irritancy exert the dominant actions of DDT residues in reducing man-vector contact inside of houses. These relationships are demonstrated with published and unpublished data for two separate populations of Anopheles darlingi, for Anopheles gambiae and Anopheles funestus in Tanzania, and Anopheles punctulatus in New Guinea.

A comparison study of house entering and exiting behavior of Anopheles vestitipennis (Diptera: Culicidae) using experimental huts sprayed with DDT or deltamethrin in the southern district of Toledo, Belize, C.A.

An investigation of the house entering and exiting behavior of Anopheles vestitipennis Dyar and Knab was undertaken in the Toledo District of Belize, Central America, between March and December of 1998. Three untreated experimental huts were either fitted with exit or entrance interception traps or used as a control for human landing collections. Human landing collections showed that An. vestitipennis exhibited a high level of biting activity shortly after sunset and continued biting at high levels throughout the night. Under unsprayed conditions, the use of exit and entrance interception traps demonstrated that doors, windows, and eaves were the primary mode of entry; whereas, cracks in the walls served a secondary role. The peak entrance time for An. vestitipennis occurred between 6:45 P.M. and 9:45 P.M. and a peak exit time occurred between 11:45 P.M. and 4:45 A.M. Additional trials were conducted after spraying one of the huts with DDT and another with deltamethrin. The excito-repellent properties of deltamethrin did not affect entrance times but did result in a peak exiting behavior that was five hours earlier than under pre-spray conditions. Deltamethrin also exhibited a repellency effect, showing 66% fewer An. vestitipennis entering the hut two weeks post-spray. DDT had an even more powerful repellency effect resulting in a 97% post-spray reduction of An. vestitipennis females entering the hut up to two weeks post-spray. The control hut showed only a 37% reduction in An. vestitipennis as compared to pre-spray conditions.

Successful use of the total artificial heart as a bridge to transplantation with no mediastinitis.

UNLABELLED: High rates of infection, especially mediastinitis, have been reported with the use of the total artificial heart (TAH), thereby limiting its usefulness. We have used the TAH as a bridge to transplantation with only minor infectious complications and a zero incidence of mediastinitis. Between February 1988 and August 1990, the TAH was inserted at Loyola University Medical Center in 19 patients, ages 16 to 64 years (mean, 44 years). Seventeen patients (89%) underwent transplantation within 1 to 34 days (mean, 9.8 days). Of the patients who did not undergo transplantation, one was brain dead and the other died of bleeding diathesis. Early (30-day) deaths occurred in two patients (11.7%): acute rejection at 18 days and multiple cerebral infarcts at 14 days. Three late deaths (17.6%) occurred: one patient, cytomegalovirus and pneumocystis pneumonia at 4 months; one patient, bronchopneumonia and multisystem failure at 9 months; and one patient, chronic rejection at 14 months. Minor infectious complications during the TAH implantation included Enterobacter pneumonia treated with antibiotics and positive sputum cultures (Escherichia coli; Candida), with no clinical evidence of infection in two patients. No cases of mediastinitis occurred either while the TAH was implanted or after transplantation. All patients were on antibiotics while the device was in place. CONCLUSION: Our experience with the TAH shows this to be an excellent device for successful bridging of patients for heart transplantation. We have had minimal infectious complications and none directly attributed to the use of this device. This device should continue to be used safely as a bridge to transplantation.

Comparison of results after heart transplantation: mechanically supported versus nonsupported patients.

Between March 1984 and July 1990 our team transplanted 168 hearts. One hundred twelve patients did not require mechanical support (group I). Fifty-six patients required mechanical support (group II). Intraaortic balloon counterpulsation was used in 37 patients (66%). The total artificial heart (TAH) was used in 16 patients (29%), and the ventricular assist device (VAD) was used in three patients (5%). The time spent on the device ranged from 1 to 35 days. No statistical difference was noted on the survival between the two groups. The 30-day and 1-year survival rate was 95% (106 patients) and 71% (79 patients) in group I and 91% (51 patients) and 68% (38 patients) in group II. As of July 31, 1990, 70% in group I and 68% in group II are alive. No significant differences were found between the two groups for the following variables (after heart transplantation): length of stay, 30-day survival, 1-year survival, and complications. The only significant difference found between the two groups was the incidence of infections: group I, 23%; group II, 51.7% (p = 0.001). Mechanical support as a bridge to transplantation provides excellent support until a donor becomes available. No difference was found in the 30-day and 1-year survival between the two groups.

Orthotopic cardiac transplantation in two patients with previous malignancy.

This report presents 2 patients with previous malignancy in whom congestive cardiomyopathy developed secondary to doxorubicin toxicity. Both patients underwent orthotopic cardiac transplantation 3 and 5 years ago and are now in functional class I with no evidence of malignant recurrence.

Defensive behavior of eastern chipmunks against Aedes triseriatus (Diptera: Culicidae).

Eastern chipmunks (Tamias striatus L.) were placed in Plexiglas cages with 0, 2, 5, 10, or 20 female Aedes triseriatus Say mosquitoes for 2 h. Previously published studies demonstrated little effective mosquito defensive behavior because of pause behavior by the chipmunks. By recording chipmunk behavior on videotape, pause behavior was reduced, and the chipmunks exhibited effective mosquito defense. The chipmunks defended themselves actively by attacking mosquitoes in flight, biting, head shaking, body turning, face grooming, hindfoot scratching, and flicking the tail. These defensive behaviors were correlated positively with the number of mosquitoes exposed to the chipmunks and with the number of mosquitoes killed.

Use of the total artificial heart and ventricular assist device as a bridge to transplantation.

The proliferation of transplant programs has not been paralleled by a similar increase in the availability of organ donors. This has significantly prolonged the waiting period and consequently has resulted in increased mortality of the patients with end-stage heart disease who are awaiting transplantation. Between 1984 and 1987, 104 orthotopic heart transplants were performed at Loyola University Medical Center. During the same period, 25 patients died while waiting for a suitable donor. To reduce the mortality of our patients waiting for transplantation, we began using the total artificial heart and a ventricular assist device as a bridge to transplantation in 1988. Of 29 patients who underwent transplant procedures in 1988, 18 required either a total artificial heart (15) or a ventricular assist device (3) as a bridge to transplantation. The underlying heart conditions were ischemic cardiomyopathy (11), dilated cardiomyopathy (5), giant cell myocarditis (1), and allograft failure (1). The average duration of mechanical support was 10 days (range, 1 to 35 days). Seventeen of the supported patients had successful transplants. One patient had brain death and did not receive a heart transplant. Of the 17 patients who survived surgery, two died within 30 days: one at 17 days because of acute rejection, the other at 14 days because of a cerebral vascular event. Fifteen patients (83%) were long-term survivors. Nine of the supported patients required reoperation because of bleeding after device implantation. There was no mediastinal or incisional infection. While the mechanical device was in place, the activated clotting time was maintained between 170 and 200 seconds with the administration of heparin (400 to 1000 units per hour).(ABSTRACT TRUNCATED AT 250 WORDS)

The use of the Jarvik-7 total artificial heart and the Symbion ventricular assist device as a bridge to transplantation.

The proliferation of transplantation programs has not been paralleled by a similar increase in the availability of organ donors. Between 1984 and 1987, 104 orthotopic heart transplantations were performed at Loyola University Medical Center. During the same period, 25 patients died while awaiting a donor organ. To reduce the mortality, we began using the total artificial heart (TAH) and a ventricular assist device (VAD) as a bridge to transplantation in 1988. Of 29 patients who underwent transplantation, 15 patients required a TAH and three patients required a VAD as a bridge. The underlying heart conditions were ischemic cardiomyopathy (11 patients), dilated cardiomyopathy (5 patients), giant cell myocarditis (1 patient), and allograft failure (1 patient). The average duration of mechanical support was 10 days (range, 1 to 35 days). Of the 17 patients who successfully underwent transplantation, 1 patient died at 17 days because of acute rejection of the transplanted heart, and another patient died at 14 days because of a cerebral vascular event. Fifteen patients (83%) were long-term survivors. Nine patients required reoperation for bleeding. While the mechanical device was in place, the activated clotting time was maintained between 170 and 200 seconds with heparin. Dipyridamole was given. We conclude that the TAH and VAD are excellent mechanical bridges to transplantation.

Pacing lead fracture after a deceleration injury.

Acute pacemaker malfunction is potentially lethal. A high index of suspicion must be maintained in physicians caring for traumatized patients utilizing permanent pacing systems. We present a case of transvenous pacemaker lead fracture sustained in a vehicular deceleration injury.

Ventricular aneurysm due to blunt chest injury.

A left ventricular aneurysm developed in 3 patients sustaining blunt chest injury. Evidence of an acute myocardial infarction on the electrocardiogram and enzyme analysis prompted cardiac catheterization, which revealed total occlusion of the left anterior descending coronary artery in 2 of the 3 patients. Ventricular aneurysmectomy was performed in each patient. A review of the literature revealed 32 previously reported patients with left ventricular aneurysm caused by blunt trauma. Clinical features, catheterization or autopsy findings, and outcome are examined.

Cardiac transplantation.

Cardiac transplantation is now an accepted therapeutic procedure in the management of patients suffering from end-stage congestive heart failure. The advances in myocardial preservation, long-distance procurement, immunosuppression, improvement in the treatment of infectious diseases, and utilization of endomyocardial biopsy in the diagnosis of rejection have made its application widespread and resulted in improved survival.

Perioperative dissection of the ascending aorta: types of repair.

Iatrogenic aortic injury occurring during either coronary bypass grafting or valve replacement is a well-recognized complication of cardiac surgery. We retrospectively reviewed our experience and found 11 cases occurring in a case load of 8,945 hearts (incidence of 0.12%). All 11 cases were repaired, with 10 patients surviving. The type of repair used usually was determined by when the diagnosis was made. When an intraoperative diagnosis was made, a local repair was done in four of six cases. If a postoperative diagnosis was made, then all five patients needed the ascending aorta replaced. With early diagnosis and rapid repair, good surgical results can be achieved.

Aortic valve replacement in patients 75 years old and older.

A consecutive group of 100 patients in the eighth decade of life who had aortic valve replacement (AVR) from 1975 through 1986 were retrospectively studied. Eighty-five of them were in New York Heart Association (NYHA) Functional Class III or IV. Isolated AVR was performed in 44 patients and AVR with concomitant procedures, in 56. Perioperative mortality (30 days) was 3%, and perioperative morbidity included 83 complications in 60 patients. Long-term follow-up was available on 93 patients, 71 of whom were alive and 22 of whom were dead. Sixty-eight of the 71 long-term survivors are now in NYHA Class I or II. The low rate of perioperative mortality and the improved quality of life after AVR support the performance of this procedure in this older population.

Successful reversal of acute cardiac allograft rejection with OKT*3 monoclonal antibody.

The efficacy of OKT*3 monoclonal antibody in reversing acute cardiac allograft rejection was investigated in 10 cardiac transplant recipients aged 5 to 57 years (mean 34 +/- 18) and treated with the same induction and maintenance immunosuppression. Serial endomyocardial biopsies, right heart catheterization, and echocardiograms were performed for rejection surveillance. After intensified immunosuppression with equine antithymocyte globulins and steroids, nine patients showed persistent rejection (lymphocytic infiltration and myocyte necrosis). Conventional immunosuppression was contraindicated in one patient. OKT*3 (5 mg by intravenous push daily for 14 days) resulted in complete resolution of rejection in nine of 10 patients (90%). After therapy with OKT*3 mean right atrial and pulmonary arterial wedge pressure were significantly lower (9.1 +/- 4.0 vs 4.8 +/- 2.0 mm Hg and 13.4 +/- 4.3 vs 8.0 +/- 3.3 mm Hg, respectively; p less than .05). Cardiac index was doubled in two patients with rejection-induced cardiac dysfunction (1.5 vs 3.2 and 1.6 vs 2.7 liters/min/m2). Only two patients developed antibodies to OKT*3. Fever, nausea and headache occurred with the first three doses of OKT*3 and did not recur. One patient developed aseptic meningitis. OKT*3 effectively reverses refractory cardiac allograft rejection before the development of irreversible graft dysfunction. Patients who do not develop antibodies to OKT*3 can be retreated with this drug. Adverse reactions to OKT*3 are self-limited.

Early myocardial revascularization for postinfarction angina.

In 1983 and 1984, coronary artery bypass grafting (CABG) was performed on 107 consecutive patients for postinfarction angina. In each instance, CABG was done within 30 days of infarction. Sixty-three patients (59%) required intravenous administration of nitroglycerin and/or the intraaortic balloon pump (IABP) for relief of angina. Oral medications relieved angina in the remaining 44 patients. Thirty-eight patients underwent CABG 7 days or less after the infarction (Group 1), 25 received it between 8 and 15 days later (Group 2), and 44 had CABG between 16 and 30 days later (Group 3). There were 9 in-hospital deaths: 4 in Group 1, 2 in Group 2, and 3 in Group 3. Thirteen patients needed the IABP for hemodynamic stability as well as relief of angina. Even when the patient was stable hemodynamically, death was more likely to occur among these 13 patients if CABG was conducted within 7 days of infarction. Follow-up was 94% complete at 29.4 months. Eighty-six percent of patients were asymptomatic or in New York Heart Association Functional Class I, and 6% were in Class II. There were 2 late deaths. CABG for angina can be accomplished within 30 days of an acute infarction with good results. The exception to this rule is the patient in whom shock develops after a myocardial infarction and who, despite stabilization, receives CABG within 7 days of the infarction.

Multivariate discriminant analysis of risk factors for operative mortality following isolated coronary artery bypass graft. Loyola University Medical Center experience, 1970 to 1984.

The Loyola Open-Heart Registry is a fully operational database that contains detailed data on approximately 9,000 patients who have undergone coronary bypass or cardiac valve replacement from January 1970 to December 1984. We analyzed the registry data using multivariate discriminant analysis to identify and quantitate those factors that might predict operative mortality (OM) for patients undergoing coronary artery bypass grafts at Loyola University Medical Center: Operative mortality was defined as death within 30 days following surgery. A total of 50 clinical and angiographic variables were analyzed for possible univariate association with operative mortality. Twenty-two variables were found to have significant univariate association with OM, and these 22 variables were subjected to multivariate discriminant analysis. For patients undergoing isolated, elective coronary artery bypass, the factors found to be predictive of OM are age (greater than 70) (F = 11.57), severe (more than six stenoses) coronary artery disease (F = 5.81), diffuse disease (F = 5.54), positive family history (F = 5.17), and number of coronary arteries bypassed (F = 4.78).