Analysis of known crystals to design polymorph prediction strategies.

Computational analysis of known crystals was used to provide insight into polymorph prediction strategies. It was hypothesized that intermolecular crystalline interactions are inadequately accounted for in current computational strategies. The QEq method of partial charge assignments was applied to the crystal milieu (CMc) and to the isolated molecule (IMc). For 90 known crystal structures, these two partial charging methods showed that the unit cell energy was almost always lower (more stable) with CMc partial charge assignments. In simulations on a model drug, the CMc charging re-ranked the unit cell energies of possible polymorphs in a way that aided the identification of physically reasonable packings more easily than IMc. Decomposing the unit cell energy for known crystals showed that the cohesive IMc deviation from CMc was dominant. On the other hand, for simulations, the corresponding IMc conformational component of unit cell energy dominates when conformational adaptive strategies (CA) are used; this was not apparent with rigid-body simulations (RB). Furthermore, evidence is presented that polymorph strategies that use unit cell energy for optimizing are especially prone to this undesired conformational bias. Suggestions are made for polymorph strategies that might enhance the probability of identifying physically relevant polymorphs in the future.

Aortic valve replacement in von Willebrand's disease.

A patient with von Willebrand's disease having aortic valve replacement was managed with cryoprecipitate infusions and monitoring of factor VIII levels. This disorder is associated with low factor VIII levels and abnormal platelet function. There may be no history of bleeding, as the severity of the bleeding tendency varies greatly and fluctuates temporally. The partial thromboplastin time is frequently prolonged, but more detailed studies are necessary to establish a diagnosis (bleeding time, platelet adhesiveness to glass beads and ristocetin, von Willebrand's antigen, ristocetin-von Willebrand's factor, and factor VIII clotting activity). Elevation of factor VIII levels to 50 to 100% of normal allows adequate clotting and is best accomplished with cryoprecipitate or fresh frozen plasma rather than commercial concentrates of factor VIII, whose activity is unpredictable.

Scanning electron microscopic evaluation of variably angled end-to-side microvascular anastomoses.

A comparison of right-angled and opposing oblique-angled end-to-side microvascular anastomoses with both patent and occluded recipient vessels was performed in rats. Patency rates after 3 weeks were comparable in all types of anastomoses (average, 92%). However, scanning electron microscopic evaluation revealed a variety of both nonspecific (pits, craters, folds, etc.) and angle-dependent (mounds, erosions, bridges, etc.) endothelial alterations. It is concluded that, in proximally patent recipient vessels, the functional integrity of the anastomosis is not related to the grafting angle; however, in proximally occluded recipient vessels, retrograde-directed oblique angles may lead to progressive embarrassment of anastomotic function.

A new technique for closure of the dura following transsphenoidal and transclival operations. Technical note.

Watertight closure of the dura following transsphenoidal operations for pituitary adenoma or hypophysectomy and following transclival operations for paraclival tumors has been technically very difficult. This is true both immediately after the initial approach and later for the treatment of delayed cerebrospinal fluid leakage. An innovative practical technique and special suture-tying instruments and needle designed by the principal author for this purpose have greatly facilitated this procedure. This technique has been applied to both direct dural closure and dural patching with watertight dural closure. The technique is also widely applicable for closing (or suturing) the dura following any procedure through a small opening, such as the dural tears occasionally encountered during lumbar or cervical discectomy, or tacking the tentorium during a craniotomy. The technique and suture-tying instruments are described in detail.

Lumbar hemangioendothelioma.

A case of hemangioendothelioma encountered in the lumbar region of a child is presented. Clinically, the tumor could not be differentiated from a dermoid cyst. This lesion must be included in the differential diagnosis of benign lumbar tumors.

Traumatic occlusion in fibromuscular dysplasia of the carotid artery.

A patient with fibromuscular dysplasia involving the cervical carotid artery developed subtotal occlusion after a trivial head injury. An association between occlusion in fibromuscular dysplasia-diseased carotid arteries and trivial blunt head injuries is suggested and appropriate treatment options are discussed.

A comparison of carvedilol with atenolol in the treatment of mild-to-moderate essential hypertension. INT-CAR-07 (U.K.) Study Group.

The efficacy and safety of carvedilol, a beta-blocker with vasodilating properties, were compared at a dosage of 25 to 50 mg once daily with those of atenolol at a dosage of 50-100 mg once daily in a double-blind, randomized, parallel-group, multicenter study. After a single-blind placebo phase of 3 to 6 weeks, 47 patients (median age, 59 years) were randomized to receive carvedilol and 52 patients (median age, 57 years) were randomized to receive atenolol for an 8-week study period. Patients on carvedilol received 12.5 mg for the first 2 days and then 25 mg as a once-daily dosage. The initial dosage of atenolol was 50 mg once daily. The dosage of each treatment could be doubled (to 50 and 100 mg once daily, respectively) at week 4 if the response was inadequate. Sitting and standing blood pressures and heart rates were recorded 24 h after the dose at weeks 4 and 8. Data from 90 of 98 patients who completed the study were eligible for per-protocol analysis. Approximately one-third of the patients in each group required upward dose titration at week 4 because of inadequate response. At week 8, 84% patients receiving carvedilol and 91% receiving atenolol had sitting diastolic blood pressure less than or equal to 90 mm Hg or decreased their blood pressure by greater than or equal to 10 mm Hg (95% confidence intervals for difference between carvedilol and atenolol, +7% and -21%). Safety profiles were similar between treatments. One patient withdrew; a skin rash developed during the fourth week of treatment with atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Solitary subcutaneous meningioma appearing as an osteolytic skull defect.

Intraosseous meningiomas rarely present with osteolytic skull lesions. This case shows that meningioma must be added to the differential diagnosis of an osteolytic skull lesion.

"Window technique" for approximation during end-to-end vascular anastomosis.

A new, simple, and atraumatic technique for prevention of tension at the site of an anastomosis during end-to-end vascular anastomoses without using an approximator clamp is described.

A scanning electron microscopic study of arterial endothelial repair under turbulent flow conditions.

In order to study the role of hemodynamic factors on the healing and native morphology of endothelium in vivo, turbulent arterial flow was created using a loop bypass model, with and without occlusion in the recipient vessel. In this model, several different patterns of turbulent arterial blood flow resulted. The scanning electron microscope (SEM) was used to evaluate endothelial morphology in the area of the anastomoses at 3 and 14 days post-operatively. Morphological changes in the native endothelium along the recipient vessel correlated well with the direction of blood flow and predicted patterns of turbulence. The morphology of the native endothelium was altered to reflect the direction and pattern (laminar versus turbulent) of blood flow by 3 days postoperatively. Based on endothelial morphology, very narrow zones of separation could be demonstrated between areas of laminar and turbulent blood flow. The degree of reendothelialization across the suture itself was greatly variable at 3 days and there seemed to be no relationship to the location of turbulent flow.

A multicenter comparison of carvedilol with hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension.

The efficacy and safety of carvedilol, a beta-blocker with vasodilatory properties, were compared with that of hydrochlorothiazide (HCTZ) both at a once-daily dose of 25-50 mg in a double-blind, randomized, parallel-group, multicenter study. Following a single-blind placebo phase of 3-6 weeks, 201 eligible patients (aged 27-88 years) were randomized to receive 8 weeks of treatment with either carvedilol or HCTZ, 25 mg doubling to 50 mg at week 4 if the respone was inadequate. Sitting and standing blood pressure and heart rate were recorded 2 h after the first dose and 24 h postdose at weeks 4 and 8. The analysis included 179 patients (11 having withdrawn, including 5 for adverse events, and 11 excluded for protocol violations). There were no statistically or clinically significant differences between treatment groups. Eighty-six percent of patients in the carvedilol group and 88% in the HCTZ group had an 8-week sitting diastolic blood pressure less than or equal to 90 mm Hg or decreased by greater than or equal to 10 mm Hg. Safety profiles were similar for both agents, with a tendency to lower uric acid and total cholesterol levels with carvedilol. Carvedilol and HCTZ at doses compared in this study have similar efficacy and tolerability, with laboratory evidence to suggest a more favorable metabolic profile for carvedilol.

Effects of long-term preservation of frankia strains on infectivity, effectivity, and in vitro nitrogenase activity.

Frankia strain HFP ArI3 which had been preserved for 27 months by being lyophilized, frozen in glycerol, or stored in complex medium was successfully used as an inoculum after being subcultured for inducing nodulation and nitrogen fixation of Alnus rubra. Glycerol-preserved HFP ArI3 produced significantly lower rates of nitrogenase activity than did lyophilized or complex-medium-preserved inocula. Bacteria that had been preserved by all three methods were successfully induced to fix atmospheric nitrogen by being cultured in nitrogen-free medium. Subculturing of these cells in nitrogen-free medium a second and third time yielded increasing rates of nitrogenase activity. Initial nitrogenase activity was detected on days 5, 4, and 3 during the first, second, and third subcultures after preservation, respectively. Maximum activity was observed on days 11, 10, and 8 during the first, second, and third subcultures, respectively. A description is given of standard culture techniques used in our laboratory for Frankia isolates, and methods used to distribute Frankia cultures by mail are described.

Surgical decompression after cerebral hemispheric stroke: indications and patient selection.

Decompressive craniotomy has a place in acute hemispheric infarctions. Patient selection should be guided by CT to exclude those with huge dominant hemispheric lesions that make reasonable neurologic recovery unattainable. Intracranial pressure monitoring should reduce the severity of neurologic sequelae by providing earlier, more timely operative intervention.

In search of the "perfect" anastomosis.

Forty-five end-to-side microvascular anastomoses were completed in rat carotid arteries of 0.7-0.8 mm diameter (anastomosing the distal end of the left common carotid to the side of the right common carotid). For comparison both 10-0 and 11-0 sutures were utilized in different anastomotic techniques: interrupted, direct-continuous, and diagonal-continuous sutures, plus total mural thickness vs. partial mural thickness (piercing only the adventitia and outer media, excluding the intima). Anastomoses were evaluated for patency and scanning electron microscopic appearance after 10 to 12 weeks. The results indicate complete patency in all anastomoses. Ultrastructural observations revealed nearly normal intimal appearance in the partial medial technique and only minimal evidence of intimal injury in the other techniques. It is concluded that 100% patency can be obtained regardless of suture size or anastomotic technique. The most important factor in anastomotic patency is the operator's technical skill.

Ventriculo-peritoneal shunt pseudocyst causing ureteropelvic junction obstruction in a child with myelomeningocele and retrocaval ureter.

We report on a boy with myelomeningocele and a ventriculo-peritoneal shunt, who presented with progressive ureteropelvic junction obstruction and an enlarging right upper quadrant mass. Exploration revealed a large pseudocyst around the distal portion of the shunt, causing obstruction of an unsuspected retrocaval ureter. To our knowledge this is the first reported case of an upper urinary tract complication due to a ventriculo-peritoneal shunt as well as the first case of a retrocaval ureter associated with myelomeningocele.