Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type (HCHWA-D): I - A Review of Clinical, Radiologic and Genetic Aspects

Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article     

Late denervation in patients with antecedent paralytic poliomyelitis

The development of new weakness, fatigue, and pain decades after acute paralytic poliomyelitis is a recognized syndrome. We conducted a controlled study of this syndrome by analyzing clinical, electromyographic, and muscle-biopsy features in 18 patients with a history of poliomyelitis--13 reporting 1 to 20 years of new weakness and 5 without new symptoms. The patients with new weakness also reported new muscle atrophy (9 of 13) and fatigue (10 of 13), symptoms not reported by the controls. The age at the time of acute poliomyelitis, severity of poliomyelitis, residual disability, number of years since acute poliomyelitis, and age at the time of study were comparable in the weakening and control groups. Evidence of remote denervation consistent with antecedent poliomyelitis was demonstrated in all patients by electromyography or muscle biopsy or both. In addition, active denervation (as evidenced by spontaneous activity on conventional electromyography, increased jitter on single-fiber electromyography, or atrophic myofibers) was found in 12 patients in the weakening group and in all 5 controls. Immunohistochemical detection of myofibers expressing the neural-cell adhesion molecule corroborated ongoing denervation in both patient groups. When muscle data from both groups were pooled, correlations were observed between the extent of past reinnervation and the degree of ongoing motor-unit instability. We conclude that the extensive reinnervation of denervated muscle that occurs in paralytic poliomyelitis may be followed by late denervation of the previously reinnervated muscle fibers. Electromyographic and muscle-biopsy evidence of ongoing denervation does not distinguish between stable patients with prior paralytic poliomyelitis and those with new weakness.     

Influence of gastrostomy on the colonization of the stomach: Impact on neonatal septicaemia

Summary Quantitative bacterial counts were carried out on 161 gastric aspirates of 65 neonates with gastrostomy. In comparison to 101 controls — cultures of premature infants without gastrostomy —Enterobacteriaceae, enterococci,Pseudomonas andCandida were found far more frequently (p<0.01). The colonization of the stomach was influenced by the duration of gastrostomy and by the pH of the gastric juice but not by systemic antibiotic therapy or the kind of food. Six newborns with gastrostomy developed septicaemia caused by the same organisms as we had found in elevated numbers in their gastric aspirates. The influence of non-absorbable antibiotics was studied prospectively in 72 gastric aspirates and 48 stool specimens. There was no highly significant difference between infants who had been treated with these antibiotics and those who had not.

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Einflu der Gastrostomie auf die Kolonisation des Magens — Sepsisquelle beim Neugeborenen?

Zusammenfassung Es wird über 161 quantitative bakteriologische Untersuchungen des Mageninhalts bei 65 gastrostomierten Neugeborenen berichtet. Im Vergleich zu 101 Untersuchungen an nichtgastrostomierten Frühgeborenen fanden sich hochsignifikant häufigerEnterobacteriaceae, Enterokokken,Pseudomonas undCandida (p<0.01). Die Kolonisation des Magens wurde von der Dauer der Gastrostomie und dem pH-Wert des Magensaftes beeinflußt, nicht aber von intravenöser Antibiotika-Gabe oder der Art der Ernährung. Sechs gastrostomierte Kinder erkrankten an einer Sepsis mit dem gleichen Erreger in der Blutkultur, der sich auch in hoher Konzentration im Mageninhalt zeigte. Der Einfluß schwer resorbierbarer Antibiotika wurde prospektiv an 72 Aspiraten von Mageninhalt und 48 Stuhlproben untersucht. Hierbei zeigten sich keine hochsignifikanten Unterschiede zwischen behandelten und nictbehandelten Kindern.

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This paper is dedicated to Prof. Dr. med.W. Marget on the occasion of his 65th birthday.     

The role of interleukin-2 in proliferative responses in vitro of T cells from patients after bone marrow transplantation. Evidence that minor defects can lead to in vitro unresponsiveness

We have studied lectin-induced interleukin-2 (IL-2) production and proliferation of peripheral blood mononuclear cells from patients who had undergone a successful allogeneic bone marrow transplantation. Shortly after transplantation, the T cells show a decreased proliferative response and a decreased IL-2 production. However, addition to the culture of exogenous IL-2 does not result in restoration of the proliferative response, which indicates that the low proliferative response is not due to decreased IL-2 production alone. Longitudinal studies show a substantial variation between patients in the time in which the capacity to produce IL-2 is restored; however, in all patients there is a period in which IL-2 production is still diminished, but the proliferative capacity, as measured upon addition of exogenous IL-2 to the culture, is almost within the normal range. Also during this period, the proliferative response of the T cells can be restored by the addition of irradiated "feeder cells" obtained from the bone-marrow donors, as these cells secrete IL-2 without consuming it. Because peripheral blood samples from patients after bone marrow transplantation show great imbalances in the distribution of T4/T8 subpopulations, we have studied the influence of an artificially produced "reverse T4/T8" ratio on the proliferative response to mitogen and (allos-)antigen stimulation of healthy donor T lymphocytes. Even at very low proportions of T4 cells, normal responses were obtained in the proliferation assays with polyclonal mitogens. Only the response to soluble antigens, such as tetanus toxoid, was impaired. However, a low proportion of T4 cells resulted in a low IL-2 production so that, when IL-2 is a limiting factor due to intrinsic defects of patient cells, an inverse T4/T8 ratio can cause a nonresponsiveness in in-vitro assays.     

Cervical cytology screening after tubal ligation

Tubal ligation has become one of the most frequently performed surgical procedures, and estimates suggest that over 50 percent of all women will undergo surgical sterilization by age 45. Preventive health procedures such as Pap tests are often performed when women visit physicians for family planning and obstetric care. Since women do not visit physicians for these reasons following tubal ligation, it is important to know how their physician contact and Pap test coverage is affected by this surgery. We used data from the Manitoba Health Services Commission to construct health-services-use histories for the two years before and the two years after surgery for all women aged 25-44 who underwent tubal ligation in 1974 (n = 4,553) and for a comparison group of women who did not have the surgery (n = 5,161). Women visited physicians after surgery at the same rate as they had before surgery. However, the proportion of women receiving Pap tests fell in the years after surgery for the tubal ligation women but remained the same for the comparison group. The reasons for this decline in testing were a decline in the number of visits for gynecologic and obstetric reasons and a decline in testing because of high rates of "screening" prior to surgery. This study demonstrates both the importance of the one-time surgical event as an opportunity to offer Pap tests to women who might otherwise not visit physicians and the possibility of overtesting among some women.     

Mindfulness-based interventions for eating disorders: The potential to mobilize multiple associative-learning change mechanisms

Mindfulness is a two-component skill that includes mindful awareness (attentional monitoring of present moment experience) and mindful acceptance (adopting an attitude of acceptance toward this experience). Although mindfulness-based interventions (MBIs) are efficacious for many conditions, there is a lack of research on MBIs for eating disorders (EDs). We propose that MBIs may be promising for EDs given their potential to mobilize not one, but multiple associative-learning change mechanisms in EDs–defined as adaptive processes of change involving one of two forms of associative-learning: Pavlovian and operant learning. We hypothesize how MBIs–via increasing either mindful awareness or mindful acceptance–may mobilize up to eight associative-learning change mechanisms, two involving Pavlovian learning, and six involving operant learning. We also elaborate on similarities and differences between MBIs and CBT approaches for EDs, as well as opportunities for synergy. Finally, we present recommendations for future research related to the development and evaluation of novel MBI interventions for EDs and the testing of mechanisms and patient-treatment matching hypotheses.     

Lymphocyte concanavalin A capping in hereditary cerebral haemorrhage with amyloidosis — Dutch type

Summary Lymphocyte capping with concanavalin A was studied in 11 patients with hereditary cerebral haemorrhage with amyloidosis (Dutch type) and 10 controls. No difference in capping was found between patients and controls. Abnormal lymphocyte concanavalin A capping has been reported in patients with the Icelandic type of cerebral amyloidosis and in patients with Alzheimer's disease, a disease in which cerebral amyloid angiopathy can also be found. The results suggest a difference in pathogenesis between the Dutch type of cerebral amyloidosis and the other amyloid diseases.Members of the Amyloid Research Group, Leiden     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Current Status of the VU MFEL Compton X-Ray Program

The Vanderbilt University medical FEL (free electron laser) Compton x-ray program is close to being operational. The FEL modifications necessary for this new capability are near completion. The transport and detection systems for electron and IR beams have been designed, delivered, and tested. We initially expect to produce 108 x-ray photons per second in the 15- to 20-keV region.     

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies

Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium- 111-OV-TL-3 F(ab)₂]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for ¹¹¹ In-OV TL-3 and between 0.13 and 0.68 mGy/MBq for ¹³¹I-16-88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation. Correspondence to: M.A.B.D. Plaizier