Pregnancy following gamete intra-fallopian transfer (GIFT) with cryopreserved semen from infertile men following therapy to lymphomas or testicular tumour: report of three cases

Cryopreserved spermatozoa from men having treatment for lymphoma or testicular tumour have been reported to function sub-optimally. We report on three successful pregnancies following gamete intra-Fallopian transfer (GIFT) using such cryopreserved sperm samples. In one case, ovum donation was required since the woman had premature ovarian failure.     

Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease

Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in onset ages above 55 years, with one segregating in an autosomal dominant family with mean onset age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with onset age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.      

Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency.

Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in abnormal neurites and perikarya along the periphery of, or scattered within, the lesion. Prompted by these data and our previous findings of a genetic variation in the development of TD symptoms, we extended our studies to mice. C57BL/6, ApoE knockout, and APP YAC transgenic mice received thiamine-deficient diet and pyrithiamine injections. Unlike rats, APP/APLP2-immunoreactive neurites in all strains of mice were sparsely scattered within damaged areas and did not delimit the thalamic lesion. In addition, abnormal clusters of intensely immunoreactive neurites occurred only in areas of damage including the thalamus, mammillary body, and inferior colliculus. The clusters appeared as either irregular clumps or round or oval rosettes that strikingly resembled the neuritic component of Alzheimer amyloid plaques. However, immunostaining using various antisera to synthetic amyloid beta-protein (A beta 1-40) and thioflavine S histochemistry failed to show evidence of a component of A beta Neither APP/APLP2-immunoreactive clusters nor amyloid plaques were observed in the brain from patients with Wernicke-Korsakoff syndrome, the clinical manifestation of TD in man. Our results demonstrate species (i.e., genetic) differences in the response to TD-induced damage and support a role for APP and APLP2 in the response to brain injury. This is the first report that chronic oxidative deficits can lead to this novel pathology.     

Examination of trisomy 13, 18 and 21 foetal tissues at different gestational ages using FISH

In man high levels of aneuploidy are seen in spontaneous abortions. Very few autosomal trisomies survive to birth, the three most common being those for chromosome 13, 18 and 21 giving rise to the syndromes named Patau, Edwards and Down respectively. Since the majority of these spontaneously abort, what makes the survivors different from the aborters? Could it be that they have tissue specific mosaicism with the additional normal cell line supporting survival? In this study fluorescence in situ hybridisation was used as a convenient way to detect trisomy in interphase cells. To study the level of mosaicism across gestation, different tissues from 21 trisomic foetuses were analysed using probes for chromosome 13, 18, 21, X and Y. Two trisomy 18 foetuses exhibited mosaicism. Two others, one trisomy 13 and one trisomy 18 had mosaic placentas. There was no clear association between the limited mosaicism seen and severity of the phenotype. We conclude that at least for this sample set, tissue-specific mosaicism was not likely to be responsible for potential survival to birth.     

Rapid screening method for detection of bacteria in platelet concentrates

Public awareness has long focused on the risks of the transmission of viral agents through blood product transfusion. This risk, however, pales in comparison to the less publicized danger associated with the transfusion of blood products contaminated with bacteria, in particular, platelet concentrates. Up to 1,000 cases of clinical sepsis after the transfusion of platelet concentrates are reported annually in the United States. The condition is characterized by acute reaction symptoms and the rapid onset of septicemia and carries a 20 to 40% mortality rate. The urgent need for a method for the routine screening of platelet concentrates to improve patient safety has long been recognized. We describe the development of a rapid and highly sensitive method for screening for bacteria in platelet concentrates for transfusion. No culture period is required; and the entire procedure, from the time of sampling to the time that the final result is obtained, takes less than 90 min. The method involves three basic stages: the selective removal of platelets by filtration following activation with a monoclonal antibody, DNA-specific fluorescent labeling of bacteria, and concentration of the bacteria on a membrane surface for enumeration by solid-phase cytometry. The method offers a universal means of detection of live, nondividing, or dead gram-negative and gram-positive bacteria in complex cellular blood products. The sensitivity is higher than those of the culture-based methods available at present, with a detection limit of 10 to 10(2) CFU/ml, depending upon the bacterial strain.     

Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30-58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.     

Familial occurrence of the Wiedemann-Beckwith syndrome and persistent fontanel

We describe a family in which 3 sisters gave birth to 8 infants with the Wiedemann-Beckwith syndrome. The clinical manifestations in all the affected individuals included macroglossia, macrosomia and omphalocele, while their mothers all were entirely normal. Pedigree analysis suggests that familial occurrence of the Wiedemann-Beckwith syndrome may be due to delayed mutation.     

Mental illness and the media: an assessment of attitudes and communication

Media coverage of psychiatric issues will reflect or influence public perceptions of the mentally ill. In order to explore the relationship between psychiatry and the media, an attitudinal questionnaire was administered to a systematic sample of 20 reporters, 20 psychiatrists, 20 medical outpatients with no psychiatric history, and 40 psychiatric inpatients. In addition, 4 psychiatric patients who had personal experience with media coverage were interviewed to determine the impact. Their stories are presented as clinical vignettes. The results of the questionnaire survey show that media reporters are no less accepting of mental illness than the other groups. A regression analysis of attitudinal predictors elicit education as more significant than age and media exposure. Yet low scores for the coverage by the media of mental illness were given by all groups with psychiatrists tending to be most critical. Reasons offered by reporters included "sensationalism sells" along with cost and time factors. Recommendations for both reporters and psychiatrists groups were collated, aiming at improving communication and ensuring a more positive emphasis and greater accuracy of media coverage of mental health issues.     

Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy.

A recent necropsy study has shown that 80% of patients with the Wernicke-Korsakoff syndrome were not diagnosed as such during life. Review of the clinical signs of these cases revealed that only 16% had the classical clinical triad and 19% had no documented clinical signs. The incidence of clinical signs in this and other retrospective pathological studies is very different from that of prospective clinical studies. This discrepancy may relate to "missed" clinical signs but the magnitude of the difference suggests that at least some cases of the Wernicke-Korsakoff syndrome may be the end result of repeated subclinical episodes of vitamin B1 deficiency. In order to make the diagnosis, clinicians must maintain a high index of suspicion in the "at risk" group of patients, particularly alcoholics. Investigations of thiamine status may be helpful and if the diagnosis is suspected, parenteral thiamine should be given.