GvL effects in T-prolymphocytic leukemia: evidence from MRD kinetics and TCR repertoire analyses.

Allogeneic stem cell transplantation (alloSCT) is used for treating patients with T-prolymphocytic leukemia (T-PLL). However, direct evidence of GvL activity in T-PLL is lacking. We correlated minimal residual disease (MRD) kinetics with immune interventions and T-cell receptor (TCR) repertoire diversity alterations in patients after alloSCT for T-PLL. Longitudinal quantitative MRD monitoring was performed by clone-specific real-time PCR of TCR rearrangements (n=7), and TCR repertoire diversity assessment by next-generation sequencing (NGS; n=3) Although post-transplant immunomodulation (immunosuppression tapering or donor lymphocyte infusions) resulted in significant reduction (>1 log) of MRD levels in 7 of 10 occasions, durable MRD clearance was observed in only two patients. In all three patients analyzed by TCR-NGS, MRD responses were reproducibly associated with a shift from a clonal, T-PLL-driven profile to a polyclonal signature. Novel clonotypes that could explain a clonal GvL effect did not emerge. In conclusion, TCR-based MRD quantification appears to be a suitable tool for monitoring and guiding treatment interventions in T-PLL. The MRD responses to immune modulation observed here provide first molecular evidence for GvL activity in T-PLL which, however, may be often only transient and reliant on a poly-/oligoclonal rather than a monoclonal T-cell response.

Are the elderly different? Factors influencing mortality after percutaneous coronary intervention with stent implantation.

BACKGROUND: The aim of this study was to investigate factors influencing mortality after percutaneous coronary intervention (PCI) in patients aged ≥ 75 years compared to younger patients. PATIENTS AND METHODS: A total of 1,809 coronary heart disease (CHD) patients after PCI with stent implantation in our hospital were assessed. Kaplan-Meier analyses with log-rank test and Cox regression analyses were performed on three predefined models concerning primary endpoint of all-cause mortality. Model 1 was a univariate analysis of the influence of age dichotomized by age 75 years on the primary endpoint. Model 2 included age and classical cardiovascular risk factors (CVRFs, e.g., body mass index (BMI), smoking, diabetes, and hypertension). Model 3 consisted of age, classical CVRFs, and additional factors (e.g., medication; hemoglobin, peripheral arterial disease (PAD), low-density lipoprotein cholesterol (LDL-C) and creatinine levels, and left ventricular ejection fraction (LVEF)). RESULTS: In the mean follow-up of 137 ± 61 weeks 375 patients died. Age ≥ 75 years was significantly related to mortality in all models. In model 3, previous stroke, PAD, diabetes, elevated levels of serum creatinine, and increased LDL-C were related to elevated mortality, higher hemoglobin levels, and LVEF > 50% were associated with decreased mortality in all patients and in patients < 75 years. In patients ≥ 75 years arterial hypertension was associated with poor outcome (hazard ratio (HR) 7.989, p = 0.040), previous antiplatelet therapy showed reduced mortality (HR 0.098, p = 0.039). CONCLUSION: Although risk factors such as previous stroke, PAD, diabetes, renal insufficiency, and anemia were predictors for death in all patients and patients < 75 years, in the elderly only arterial hypertension increased, whereas treatment with platelet inhibitors decreased mortality.

Health care systems in Japan and Germany provide facts, not theories.

Germany and Japan are touted as models for health care reform in the United States, largely because of perceived cost-savings and near-universal insurance coverage. Both systems have been in place longer than U.S. Medicare and Medicaid. Both countries spend less of their gross domestic product on health care than does the U.S. Both are government mandated but at least partially administered through the private sector; in both systems the medical societies have taken on a quasi-governmental role. Both have expanding costs, multiple tiers of care and artificial separation between general and specialty care, short visits because of poor physician reimbursement, and lengthy hospital stays. Despite claims to the contrary, neither system would succeed in the United States.

Primary angiosarcoma of the brain.

We have described a 32-year-old black woman who had a primary angiosarcoma of the right occipital lobe. All three previously reported cases have been fatal within 1 year. Our patient is doing well more than 3 1/2 years after surgery.

Nonfulminant herpes simplex encephalitis as a cause for mesial temporal sclerosis.

Although mesial temporal sclerosis has been recognized for more than 100 years, its etiology remains unknown. It is proposed that a common infectious agent, herpes simplex virus type-1, may cause this disorder by means of a nonfulminant infection of mesial temporal lobe structures, which is resolved by the immune system and becomes gliotic in the course of healing by the central nervous system. Brain sections from a long-term experiment in a model of herpes simplex encephalitis reveal such a scar, which shows a high concentration of glial fibrillary acidic protein, without any evidence of residual herpes antigen, by immunocytochemistry.

Small central cervical disc syndrome: evaluation and treatment of chronic disabling neck pain.

In this retrospective study of 22 patients with severe disabling neck, interscapular, and shoulder pain we evaluated the effectiveness of magnetic resonance imaging (MRI) for the diagnosis of small central cervical disc ruptures, and anterior cervical discectomy for the treatment of this condition. Conservative therapy had failed for all patients. All had been disabled for their normal activities for at least 6 months. MRI demonstrated two patterns of mid- or parasagittal disc disease. Anterior cervical discectomy produced nine excellent, six good, five fair, and two poor results. All but one patient returned to his/her former occupation. MRI is essential in the evaluation of patients with chronic neck pain who have failed conservative therapy and present with axial rather than appendicular complaints. Anterior cervical discectomy can be useful in well-selected patients with this syndrome.

Invasive basal cell carcinoma of the temporal bone.

Basal cell carcinomas involving the ear represent a spectrum of diseases, from a small superficial auricular lesion to an advanced destructive malignancy invading the temporal bone. The biologic activity of the morphea-form basal cell carcinoma variant of tumor and a postauricular location predispose to an aggressive biologic pattern. Management requires a thorough evaluation with determination of the degree of cranial and possible intracranial invasion. These lesions usually can be managed with partial temporal bone resections, although prognosis for patients with advanced lesions may be poor.

Brachial plexus injuries associated with cervical spine fractures.

The concomitant occurrence of brachial plexus injuries and cervical spine fractures in three recent patients is reviewed. The injuries included a fracture or dislocation of the upper portion of the cervical spine and damage to the upper roots of the brachial plexus. All of the patients had associated head injuries and two suffered a spinal cord injury. Recognition of the brachial plexus injury was delayed in each case because of the associated injuries. Probable mechanisms of injury include forced lateral bending of the cervical spine, with or without rotation, combined with forcible depression of the shoulder. All three patients required surgical fusion and/or halo bracing. Two have persistent Erb-type palsies. Brachial plexus injuries must be suspected in all cervical spine injury patients.

Brain abscess following dilatation of esophageal stricture.

A case of right parietal abscess following esophageal dilatation for peptic stricture secondary to hiatus hernia with reflux in an 18-month-old male child is reported. Prior cases of brain abscess following esophageal dilatation are reviewed. The combination of history, clinical findings, and computed tomography scan in the current case allowed confident preoperative diagnosis of brain abscess and allowed emergency treatment of the lesion by simple aspiration through a burr hole.

Cervical butterfly-block vertebra. A case report.

A new type of block vertebral malformation is described. A 42-year-old woman presented after an akinetic seizure. Routine cervical spine films, obtained because of a recent history of abnormal head posture, disclosed a vertebral anomaly. Computed tomography and conventional polytomography revealed that the lesion was composed of a butterfly vertebra as the upper portion of a pair of nonsegmented vertebrae. Vertebral fusion and segmentation anomalies are reviewed and compared with the specific features of this case.

Osteoplastic pterional craniotomy.

We describe a new method for small frontotemporal craniotomies. Adequate exposure is obtained. Sparing of the trunk of the frontotemporal branch of the facial nerve as it passes near the eyebrow preserves forehead mimetic function, and maintenance of the blood supply to the bone flap helps to prevent resorption.

Multiple complications from an intracranial epidermoid cyst: case report and literature review.

Intracranial epidermoid and dermoid tumors are unusual benign lesions that are potentially curable. Subtotal removal carries a high incidence of recurrence, plus the rare possibility of carcinomatous degeneration of the remnants. Aseptic meningitis from spillage of cyst contents into the subarachnoid space is frequent after operation and has been reported to occur spontaneously. A case of a patient with a posterior fossa epidermoid cyst presenting with multiple bouts of aseptic meningitis in which squamous cell carcinoma arose in recurrent tumor 5 years after subtotal removal of the benign lesion is described.

The small midline occipital encephalomeningocele: definition of a syndrome.

An unusual group of encephalomeningoceles is described. Two children were noted at birth to have a raised area of abnormal skin at the occipital midline. Both of these lesions were found to perforate the superior sagittal sinus and to end between the leaves of the falx cerebri, and to contain a small amount of abnormal cerebral tissue with no connection to either occipital lobe. Previous case reports are reviewed; these lesions are true encephalomeningoceles, rather than glial heterotopias. The embryology of such lesions is considered, and likely differs from the much more common occipital encephalocele arising from one or both occipital lobes.

Craniofacial approach for the neonatal management of frontonasal encephalocoeles.

Three nasofrontal encephalocoeles managed at the University of South Alabama Medical Center are presented. Each consisted of abnormal brain originating from one frontal lobe, although the amount of cerebral tissue and the accompanying skin and meningeal layers varied. The encephalocoeles protruded through a defect in the anterior skull base near the cribiform plate. Repair in the neonatal period was required in two of the infants because of the size of the lesion and obstruction of the nasal airway. The operative approach utilized a bifrontal craniotomy with resection of the encephalocoele intradurally, repair of the anterior cranial fossa dura and osteoplastic repair of the foramen cecum defect. The closure of the facial defect depended upon the nature of the skin covering the herniation; either absence or excess of skin occurred. The preoperative evaluation disclosed associated congenital deformities in 2 of 3 patients in this series. Computerized tomographic scanning was of importance in preoperative planning. The operative technique can be modified to allow for each child's unique anatomy. Repair of nasofrontal encephalocoeles in the neonatal period may simplify the required operative procedures.

Black and white photography of horseradish peroxidase-stained histological slides.

Utilizing a new film and paper system, produced by the Eastman Kodak Company, and a simple enlarger, histologic slides stained by horseradish peroxidase techniques can be reproduced in black and white photographs, without loss of detail and with good contrast.

Malignant transformation in craniopharyngioma.

Malignant transformation in a craniopharyngioma has not been described previously. A 49-year-old woman presented with recurrence of a suprasellar craniopharyngioma diagnosed 35 years previously. The patient had been treated surgically for recurrence on five occasions. Radiation therapy had been administered 7 years before the final presentation. Tissue obtained from the fifth operation revealed malignant degeneration in a typical craniopharyngioma.

Neurovirulence in an experimental focal herpes encephalitis: relationship to observed seizures.

An animal model of focal herpes simplex encephalitis was used to study several strains of type-1 herpes simplex virus. Rabbits were inoculated in the olfactory bulb by a standardized technique. Virus strains resulting in mortality of greater than 70% produced seizures of 3 types, and all animals that seized became moribund or died. In contrast, a virus strain resulting in a 20% mortality produced no seizures. Administration of 60 mg phenobarbital intramuscularly daily reduced mortality significantly in animals given the epileptogenic viruses. Cultures from temporal and frontal lobes showed viral growth more frequently than did cultures of other brain areas. Microscopic examination of routine and immunoperoxidase-stained brain sections confirmed the focal nature of the infection. Clinical syndromes such as seizures arising from viral brain disease may influence mortality in animal model systems.