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Biomedical subjects

P Richard

Publications and source records attributed to P Richard.

At least 91 records · Page 5Linked to original sources
PubMed1998

Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein C gene.

BACKGROUND: Little information is available on phenotype-genotype correlations in familial hypertrophic cardiomyopathy that are related to the cardiac myosin binding protein C (MYBPC3) gene. The aim of this study was to perform this type of analysis. METHODS AND RESULTS: We studied 76 genetically affected subjects from nine families with seven recently identified mutations (SASint20, SDSint7, SDSint23, branch point int23, Glu542Gln, a deletion in exon 25, and a duplication/deletion in exon 33) in the MYBPC3 gene. Detailed clinical, ECG, and echocardiographic parameters were analyzed. An intergene analysis was performed by comparing the MYBPC3 group to seven mutations in the beta-myosin heavy-chain gene (beta-MHC) group (n=52). There was no significant phenotypic difference among the different mutations in the MYBPC3 gene. However, in the MYBPC3 group compared with the beta-MHC group, (1) prognosis was significantly better (P<0.0001), and no deaths occurred before the age of 40 years; (2) the age at onset of symptoms was delayed (41+/-19 versus 35+/-17 years, P<0.002); and (3) before 30 years of age, the phenotype was particularly mild because penetrance was low (41% versus 62%), maximal wall thicknesses lower (12+/-4 versus 16+/-7 mm, P<0.03), and abnormal T waves less frequent (9% versus 45%, P<0.02). CONCLUSIONS: These results are consistent with specific clinical features related to the MYBPC3 gene: onset of the disease appears delayed and the prognosis is better than that associated with the beta-MHC gene. These findings could be particularly important for the purpose of clinical management and genetic counseling in familial hypertrophic cardiomyopathy.

Adolescent↗
PubMed1998

Vasopressin regularizes the phasic firing pattern of rat hypothalamic magnocellular vasopressin neurons.

Vasopressin (AVP) magnocellular neurons of hypothalamic nuclei express specific phasic firing (successive periods of activity and silence), which conditions the mode of neurohypophyseal vasopression release. In situations favoring plasmatic secretion of AVP, the hormone is also released at the somatodendritic level, at which it is believed to modulate the activity of AVP neurons. We investigated the nature of this autocontrol by testing the effects of juxtamembrane applications of AVP on the extracellular activity of presumed AVP neurons in paraventricular and supraoptic nuclei of anesthetized rats. AVP had three effects depending on the initial firing pattern: (1) excitation of faintly active neurons (periods of activity of <10 sec), which acquired or reinforced their phasic pattern; (2) inhibition of quasi-continuously active neurons (periods of silences of <10 sec), which became clearly phasic; and (3) no effect on neurons already showing an intermediate phasic pattern (active and silent periods of 10-30 sec). Consequently, AVP application resulted in a narrower range of activity patterns of the population of AVP neurons, with a Gaussian distribution centered around a mode of 57% of time in activity, indicating a homogenization of the firing pattern. The resulting phasic pattern had characteristics close to those established previously for optimal release of AVP from neurohypophyseal endings. These results suggest a new role for AVP as an optimizing factor that would foster the population of AVP neurons to discharge with a phasic pattern known to be most efficient for hormone release.

Action Potentials↗
PubMed1998

Genotype-phenotype analysis in four families with mutations in beta-myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease in which one of the most frequently implicated gene is the gene encoding the beta-myosin heavy chain. To date, more than 40 distinct mutations have been found within this gene. In order to progress on the determination of genotype-phenotype relationship, we have screened the beta-myosin heavy chain gene for mutations in 18 probands from unrelated families. We identified the mutation implicated in the disease in four families. Two of them, the Glu930 codon deletion and the Ile263Thr mutation, are reported here for the first time. The two other mutations are the Arg723Cys mutation, that was previously described in a proband as a de novo mutation, and the Arg719Trp mutation. A poor prognosis was associated with the Glu930codon deletion (mean maximal wall thickness (MWT) = 19.5 mm +/- 5) and the Arg719Trp mutation (mean MWT = 15.3 mm +/- 7), whereas a good prognosis was associated with the Arg723Cys mutation (mean MWT = 20.1 mm +/- 7). The combination of clinical and genetic characteristics of each family member suggests that prognosis is related neither to the degree of left ventricular wall thickness nor to a change in the net electrical charge of the protein. Additional family studies are needed to confirm these findings and to contribute to stratify the prognosis according to the mutation involved.

Adolescent↗
PubMed1998

New aspects of firing pattern autocontrol in oxytocin and vasopressin neurones.

In the rat, oxytocin (OT) and vasopressin (AVP) neurones exhibit specific electrical activities which are controlled by OT and AVP released from soma and dendrites within the magnocellular hypothalamic nuclei. OT enhances amplitude and frequency of suckling-induced bursts, and changes basal firing characteristics: spike patterning becomes very irregular (spike clusters separated by long silences), firing rate is highly variable, oscillating before facilitated bursts. This unstable behaviour which markedly decreases during hyperosmotic stimulation (interrupting bursting) could be a prerequisite for bursting. The effects of AVP depend on the initial phasic pattern of AVP neurones: AVP excites weakly active neurones (increasing burst duration, decreasing silences) and inhibits highly active neurones; neurones with intermediate phasic activity are unaffected. Thus, AVP ensures all AVP neurones discharge with moderate phasic activity (bursts and silences lasting 20-40 s), known to optimise systemic AVP release. V1a-type receptors are involved in AVP actions. In conclusion, OT and AVP control their respective neurones in a complex manner to favour the patterns of activity which are the best suited for an efficient systemic hormone release.

Animals↗
PubMed1998

Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy.

Five disease genes encoding sarcomeric proteins and associated with familial and classical forms of hypertrophic cardiomyopathy have been determined since 1989. In 1996 two other genes encoding ventricular regulatory and essential myosin light chains were shown to be associated with a particular phenotype of the disease characterized by mid left ventricular obstruction. The aim of the present study was to search for mutations in the ventricular regulatory myosin light chain gene (MYL2), located on chromosome 12q23q24.3, in a panel of 42 probands presenting a classical phenotype of familial hypertrophic cardiomyopathy. Single-strand conformation polymorphism analysis was used to search for mutations in the coding segments of the MYL2 gene, and the abnormal products were sequenced. Two novel missense mutations, Phe18Leu in exon 2 and Arg58Gln in exon 4 were identified in three unrelated families. None of the affected patients had hypertrophy localized only at the level of the papillary muscle with mid left ventricular obstruction. By analysis of genetic recombinations, one of these mutations identified in a large family allowed us to refine the localization of the MYL2 gene on the genetic map, in an interval of 6 cM containing six informative microsatellite markers. In conclusion, we show that mutations in the MYL2 gene may be involved in familial and classical forms of hypertrophic cardiomyopathy, and we provide new tools for the genetic analysis of patients with familial hypertrophic cardiomyopathy.

Adolescent↗
PubMed1998

Transplantation for Fanconi's anaemia: long-term follow-up of fifty patients transplanted from a sibling donor after low-dose cyclophosphamide and thoraco-abdominal irradiation for conditioning.

We describe the long-term follow-up of 50 Fanconi's anaemia patients who were transplanted from a related donor with a median follow-up of >6 years. The survival estimate was 74.4% at 54 months and 58.5% at 100 months. All patients were conditioned with low-dose cyclophosphamide and thoraco-abdominal irradiation. Acute graft-versus-host disease (GvHD) of grade II or more developed in 26 patients and chronic GvHD developed in 30/43 (69.9%) patients. The survival of patients without chronic GvHD (n = 13) was 100%. In addition to chronic GvHD, 20 pre-transplant transfusions was shown to have an adverse impact on survival by multivariate analysis (relative risk = 7.08, P = 0.0003). Prospective follow-up of growth and endocrine function could be performed in 31 patients. Of 20 boys, six have already reached normal puberty within the expected time. Among the 11 girls, three were at the pubertal age at the time of analysis. Growth retardation was common, whereas late complications (e.g. peripheral hypothyroidism, cataract) were rare. However, the most important long-term complication was the occurrence of cancer in seven patients (8-year projected incidence 24%). Among the 32 survivors, 27 (84.5%) had a normal and four a moderately reduced performance status, and all achieved complete engraftment with donor cells. Therefore transplantation was able to cure these patients who remain at high risk for developing late complications. Clearly, a genetic predisposition and chronic GvHD could have led to the development of these cancers. However, we cannot completely rule out irradiation as a cofactor in the genesis of these cancers, and therefore no longer use irradiation for the conditioning of Fanconi's anaemia patients.

Adolescent↗
PubMed1998

Diagnostic value of electrocardiography and echocardiography for familial hypertrophic cardiomyopathy in genotyped children.

AIM: The aim of the study was to evaluate electrocardiography and echocardiography in the diagnosis of familial hypertrophic cardiomyopathy in children, using the genetic status as the criterion of reference. METHODS AND RESULTS: We analysed 35 children (<18 years) from 13 families with identified mutations: 16 were genetically affected (11.2 +/- 3 years), 19 unaffected (13.1 +/- 2.8 years). Conventional major diagnostic criteria were: left ventricular wall thickness >95% confidence interval on the echocardiogram; abnormal Q waves, left ventricular hypertrophy (voltage >95th percentile), or marked ST-T changes on the electrocardiogram. Twenty-two minor electrocardiographic and echocardiographic criteria were also analysed. Using major criteria, the specificity of the electrocardiogram and echocardiogram was excellent (100% for both) but sensitivity was particularly low (38% and 50% respectively). However, when four relevant additional criteria (QRS axis, left atrium dimension, intraventricular septum/posterior wall ratio, E/A wave ratio) were taken into account, sensitivity increased to 88% and specificity remained high (95%). CONCLUSIONS: (1) Familial hypertrophic cardiomyopathy was diagnosed in only approximately 50% of genetically affected children by conventional electrocardiographic and/or echocardiographic criteria. (2) Relevant additional diagnostic criteria were selected so that nearly all children considered as healthy carriers of a mutation (based on conventional criteria) could be identified with excellent specificity.

Adolescent↗
PubMed1998

PCR based mutation screening of the laminin alpha2 chain gene (LAMA2): application to prenatal diagnosis and search for founder effects in congenital muscular dystrophy.

Classical congenital muscular dystrophy with merosin deficiency is caused by mutations in the laminin alpha2 chain gene (LAMA2). Extended sequencing of the introns flanking the 64 LAMA2 exons was carried out and, based on these sequences, oligonucleotide primers were designed to amplify the coding region of each exon separately. By PCR-SSCP analysis, we identified eight new mutations in nine families originating from various countries. All induced a premature truncation of the protein, either in the short arm or in the globular C-terminal domain. A 2 bp deletion in exon 13, 2098delAG, was found in three French non-consanguineous families and a nonsense mutation of exon 20, Cys967stop, in two other non-consanguineous families originating from Italy. Determination of rare intragenic polymorphisms permitted us to show evidence of founder effects for these two mutations suggesting a remote degree of consanguinity between the families. Other, more frequent polymorphisms, G to A 1905 (exon 12), A to G 2848 (exon 19), A to G 5551 (exon 37), and G to A 6286 (exon 42), were used as intragenic markers for prenatal diagnosis. This study provides valuable methods for determining the molecular defects in LAMA2 causing merosin deficient congenital muscular dystrophy.

Child↗
PubMed1998

The V1a and V1b, but not V2, vasopressin receptor genes are expressed in the supraoptic nucleus of the rat hypothalamus, and the transcripts are essentially colocalized in the vasopressinergic magnocellular neurons.

We have identified and visualized the vasopressin (VP) receptors expressed by hypothalamic magnocellular neurons in supraoptic and paraventricular nuclei. To do this, we used RT-PCR on total RNA extracts from supraoptic nuclei or on single freshly dissociated supraoptic neurons, and in situ hybridization on frontal sections of hypothalamus of Wistar rats. The RT-PCR on supraoptic RNA extracts revealed that mainly V1a, but also V1b, subtypes of VP receptors are expressed from birth to adulthood. No V2 receptor messenger RNA (mRNA) was detected. Furthermore, the single-cell RT-nested PCR indicated that the V1a receptor mRNA is present in vasopressinergic magnocellular neurons. In light of these results, in situ hybridization was performed to visualize the V1a and V1b receptor mRNAs in supraoptic and paraventricular nuclei. Simultaneously, we coupled this approach to: 1) in situ hybridization detection of oxytocin or VP mRNAs; or 2) immunocytochemistry to detect the neuropeptides. This provided a way of identifying the neurons expressing perceptible amounts of V1a or V1b receptor mRNAs as vasopressinergic neurons. Here, we suggest that the autocontrol exerted specifically by VP on vasopressinergic neurons is mediated through, at least, V1a and V1b subtype receptors.

Animals↗
PubMed1997

L-, N- and T- but neither P- nor Q-type Ca2+ channels control vasopressin-induced Ca2+ influx in magnocellular vasopressin neurones isolated from the rat supraoptic nucleus.

1. The role of voltage-dependent Ca2+ channels during vasopressin and oxytocin actions on their respective neurones has been analysed by measuring intracellular Ca2+ concentration ([Ca2+]i) in individual, freshly dissociated magnocellular neurones from rat supraoptic nucleus (SO) using microspectrofluorimetry. 2. Pre-incubation of vasopressin-sensitive neurones with Cd2+ (100 microM), a non-discriminatory high-voltage-activated Ca2+ channel antagonist, or Ni2+ (50 microM), a blocker of T-type Ca2+ current, reduced [Ca2+]i responses by 77 and 19%, respectively. When Cd2+ was given together with Ni2+, the response was blocked by 92%. Similarly, when Ni2+ was pre-incubated with Cd2+, the response was blocked by approximately 84%. 3. Exposure of vasopressin sensitive neurones to a specific Ca2+ channel blocker, nicardipine (L-type) reduced vasopressin responses by 48% at 1 microM and 62% at 5 microM. Similarly, omega-conotoxin GVIA (omega-CgTX, N-type; 500 nM) inhibited the response by 46% with a stronger inhibition (75%) at 800 nM. By contrast, neither omega-agatoxin IVA (omega-Aga IVA; 300 nM), which blocks both P- and Q-type channels, nor synthetic omega-conotoxin MVIIC (omega-MVIIC; 100 or 500 nM), a Q-type blocker, affected vasopressin-induced [Ca2+]i responses. These antagonists, given together (nicardipine 5 microM + omega-CgTX 800 nM + omega-Aga IVA 300 nM), decreased vasopressin-induced [Ca2+]i responses by 76%. 4. In vasopressin-sensitive neurones, the presence of both nicardipine and omega-CgTX, reduced the K(+)-evoked [Ca2+]i increase by 61%. This blockade was increased by a further 21% with omega-Aga IVA, suggesting that N-, L- and P-type channels contribute to the depolarization-induced [Ca2+]i rise. In addition, omega-MVIIC alone reduced the K(+)-evoked [Ca2+]i release by 24%. Also the remaining K+ responses were further reduced by 60% when pre-incubated with L-N- and P-type blockers, suggesting the involvement of Q-type channels. 5. In oxytocin-sensitive neurones, the peak amplitude of the [Ca2+]i response was not affected by Cd2+ alone, by combined Cd2+ and Ni2+, or by the mixture of nicardipine, omega-CgTX and omega-Aga IVA. By contrast, the responses evoked by depolarization with K+ were blocked by Cd2+. Both nicardipine and omega-CgTX blocked 65% of K+ response and an additional block of approximately 18% was obtained with omega-Aga IVA, suggesting the involvement of L-, N- and P-type channels. In combination, these antagonists strongly inhibited (approximately 80% reduction) the K+ responses. Further reduction to 18% was made by the Q-type blocker omega-MVIIC. Pre-incubation with L-, N- and P-type blockers caused an additional block of 71%. 6. Some supraoptic neurones (5-10%) responded to both vasopressin and oxytocin, with only the [Ca2+]i responses induced by vasopressin blocked (> 90% inhibition) by the mixture of Ca2+ channel antagonists. 7. In conclusion, both vasopressin and oxytocin magnocellular SO neurones have been shown to express T-, L-, N-, P-, Q- and R-type Ca2+ channels in their somata. Our results show that the vasopressin-induced [Ca2+]i increase in vasopressin-sensitive neurones is mediated by L-, N- and T-type Ca2+ channels and not by P- and Q-type channels; Ca2+ channels are not involved in oxytocin action on oxytocin-sensitive neurones and L-, N-, P- and Q-type channels control the K(+)-induced [Ca2+]i increase in SO neurones.

Animals↗
PubMed1997

Diagnostic value of electrocardiography and echocardiography for familial hypertrophic cardiomyopathy in a genotyped adult population.

BACKGROUND: The diagnostic value of ECG and echocardiography for familial hypertrophic cardiomyopathy (FHC) has not been reassessed since the development of molecular genetics. The aim of the study was to evaluate it in adults, with the genetic status used as the criterion of reference. METHODS AND RESULTS: Ten families with previously identified mutations were studied (9 mutations in 3 genes). ECG and echocardiography were analyzed in 155 adults, of whom 77 were genetically affected and 78 unaffected. The major diagnostic criteria were, for echocardiography, a left ventricular wall thickness > 13 mm and, for ECG, abnormal Q waves, left ventricular hypertrophy, and marked ST-T changes. Minor ECG and echographic abnormalities were also analyzed. (1) Sensitivity and specificity of major criteria were 61% and 97% for ECG and 62% and 100% for echocardiography. (2) Sensitivity but not specificity was age related (from 50% at < 30 years to 94% at > 50 years old, P < .01) and sex related (83% in men versus 57% in women, P = .01). (3) Sensitivity was improved by the addition of minor criteria and by the association of ECG and echocardiography. The negative predictive value was therefore very good (95%) at > 30 years of age. (4) Healthy carriers without any ECG or echocardiographic abnormality represented 17% of genetically affected adults. CONCLUSIONS: ECG and echocardiography have similar diagnostic values for FHC in adults, with an excellent specificity and a lower sensitivity. The association of the two techniques allows a better evaluation of the risk of being genetically affected in families with hypertrophic cardiomyopathy.

Adult↗
PubMed1997

Prevention of surgical infections in dogs with a single intravenous injection of marbofloxacin: an experimental model.

Eighteen healthy beagle dogs of both sexes were each given 0, 2 or 4 mg/kg marbofloxacin intravenously before the subcutaneous implantation of a silicon tissue cage. Two millilitres of a suspension containing 1.3 x 10(4) colony forming units (CFU)/ml of Staphylococcus intermedius were then injected into the cage 15 minutes after the intravenous injection. The dogs were clinically assessed immediately, and then two, four, eight and 24 hours after the challenge. Samples of inflammatory fluid were harvested at the same times in order to count staphylococci and to assay marbofloxacin concentrations. Blood samples were taken in order to assay plasma marbofloxacin levels. The staphylococcal counts were lower in both treated groups than in untreated dogs (P < 0.01). All the clinical criteria were similar in the three groups. The concentration of marbofloxacin was similar in plasma and inflammatory fluid. Both doses were well tolerated and no adverse reactions were observed.

Animals↗
PubMed1997

Scopolamine impairs the ability of parturient ewes to learn to recognise their lambs.

Within a 4-h period after parturition, the ewe learns the odor of her lamb that will later allow recognition of her offspring from an alien lamb. This study investigated the involvement of the cholinergic system in this olfactory learning. At parturition and 2 h later, ewes received IM injections of saline (C group, n = 21), scopolamine methylbromide (METSCOP group, 100 micrograms/kg, n = 14) a peripherally acting muscarinic antagonist, a low dose of scopolamine hydrobromide (SCOP32 group, 32 micrograms/kg, n = 15) or a higher dose of scopolamine hydrobromide (SCOP100 group, 100 micrograms/kg, n = 18). Maternal behavior was observed at parturition and selective behavior was tested after 4 h of mother-young contact. No differences in maternal behavior at parturition were found between groups. By contrast, the proportion of ewes showing selectivity was significantly lower in the SCOP100 group (7/18) than in the METSCOP group (12/14, P = 0.01), SCOP32 group (12/15, P = 0.03), or C group (17/21, P = 0.01). In addition, saline-treated ewes, after having established their selective bond, received 100 micrograms/kg scopolamine and were again tested for selectivity 20 min later. Only one out of the 17 tested ewes failed to recognize their lambs after this treatment. These results indicate that intact central muscarinic transmission of the brain is required for the learning of individual lamb odor at parturition but not for the recall of this information.

Animals↗
PubMed1997

Increased incidence of moderate stenosis among patients with diabetes: substrate for myocardial infarction?

Persons with diabetes are at higher risk for myocardial infarction and sudden death than are persons without diabetes. It has been demonstrated that the artery that occludes during acute myocardial infarction generally had less than 75% stenosis on a previous angiogram. The extent of coronary artery stenosis was analyzed for 820 consecutively examined patients who underwent coronary angiography at our institution. The patients were categorized according to the presence or absence of diabetes mellitus. The severity of stenosis was taken into consideration. Patients with diabetes had moderate (50% to 75% narrowing) stenosis much more frequently than patients without diabetes (50.6 versus 30.3%, p < 0.001). Moreover diabetes mellitus was an independent risk factor for moderate stenosis. The lesions were more frequently located on distal arteries, more frequently had a pattern of three-vessel disease, and had a trend toward more diffuse disease than described 25 years ago. This greater amount of moderate stenosis may be considered a substrate for future acute plaque rupture. It may explain the high prevalence of acute myocardial infarction and sudden death among patients with diabetes without an increase in the incidence of angina pectoris.

Aged↗
PubMed1997

Activation of N-methyl-D-aspartate receptors regulates basal electrical activity of oxytocin and vasopressin neurons in lactating rats.

The control of suckling-induced bursting activity of oxytocin neurons and of phasic activity of vasopressin neurons by N-methyl-D-aspartate receptors was investigated in anaesthetized lactating rats. Receptor antagonist or agonist was applied in the vicinity of supraoptic neurons recorded extracellularly. The basal activity of oxytocin neurons was tonically decreased and increased by sustained application of the antagonist and agonist respectively. These effects occurred independently of the effectiveness of suckling to trigger the bursting pattern. When drugs were applied during an ongoing series of milk-ejection-related bursts, these changes were accompanied by parallel modifications in burst amplitude, but burst periodicity was unaffected. In rats failing to milk-eject, antagonist or agonist application did not facilitate the occurrence of bursts. Simultaneous recordings from oxytocin neurons in the contralateral supraoptic nucleus showed that neither their basal nor their bursting activity were affected, indicating the absence of cross-talk between nuclei during such application. The excitatory effect of N-methyl-D-aspartate differed from that induced in the same neurons by i.c.v. injection of oxytocin, which enhanced basal level of activity and burst amplitude, but also increased burst frequency. Furthermore, the distribution of interspike intervals indicated that N-methyl-D-aspartate, but not oxytocin, induced a regularization of the spike pattern. For vasopressin neurons, application of the receptor antagonist inhibited phasic activity by decreasing burst duration and increasing silences. Conversely, N-methyl-D-aspartate enhanced phasic activity, increasing both the duration of the active phases and the frequency of spikes during active phases. When applied to silent vasopressin neurons, N-methyl-D-aspartate induced a regular phasic activity. These results provide evidence that functional N-methyl-D-aspartate receptors regulate the excitability of both oxytocin and vasopressin neurons in lactating rats. These receptors play a paramount role in maintaining a certain level of basal activity which will favour appropriate discharge patterns, tonic for oxytocin neurons and phasic for vasopressin neurons. For oxytocin neurons, this sustained control by ambient glutamate influences the amplitude of bursts, but N-methyl-D-aspartate receptors are probably not involved in the generation of the bursting pattern.

2-Amino-5-phosphonovalerate↗
PubMed1997

Compound heterozygote for both rare apolipoprotein E1 (Gly127-->Asp, Arg158-->Cys) and E3(Cys112-->Arg, Arg251-->Gly) alleles in a multigeneration pedigree with hyperlipoproteinaemia.

1. A French multigeneration pedigree with hyperlipoproteinaemia was investigated for the transmission of the rare apolipoprotein E1(Gly127-->Asp, Arg158-->Cys) variant. The proband, a 46-year-old male carrying the rare apoE1 variant, presented a severe type III hyperlipoproteinaemia like his three brothers and his sister. 2. ApoE phenotyping and genotyping showed a discrepancy in the second allele carried by the proband's wife and two of her children, thus suggesting another apoE gene mutation. Cloning and sequencing of the entire exon 4 demonstrated a point mutation at codon 251, leading to an apoE3(Cys112-->Arg, Arg251-->Gly) allele. The proband's wife was normolipaemic and heterozygous for this rare isoform and the common apoE3 protein. The rare apoE3(Cys112-->Arg, Arg251-->Gly) allele has been transmitted to her two daughters. The first, aged 19, was normolipaemic and heterozygous for this allele and the common apoE2 allele. The second, carrying both the rare isoforms apoE1(Gly127-->Asp, Arg158-->Cys) and apoE3(Cys112-->Arg, Arg251-->Gly), presented a hypertriglyceridaemia at the age of 10. 3. The exploration of apoE status associated with plasma lipid levels and lipoprotein profiles in this three-generation pedigree made it possible to describe a compound heterozygote for two mutated alleles, one mutation being located in the N-terminal domain of the apoE protein and the other arising in the C-terminal domain.

Adult↗
PubMed1997

Long-term follow-up of patients hospitalized for schizophrenia, 1913 to 1940.

From a sample of 1357 schizophrenic patients hospitalized between 1913 and 1940 at the Phipps Clinic, we particularly studied 484 patients with follow-ups of 5 or more years. Of the sample of 1357 patients, 28 (10%) committed suicide. None of the suicides were included in the sample of 484, which also eliminated all patients with any previous psychiatric admissions or episodes of mental illness, even without hospitalization. On follow-up, only 13% of the 484 were rated recovered, whereas 58% were rated unimproved. Long-term global follow-up was highly correlated with discharge status. Subgroups retrospectively diagnosed by DSM-IV criteria were significantly related to long-term follow-up in the sample of 484 patients, there being a continuum of poor outcome ranging from the diagnoses schizophrenia through schizophreniform to schizoaffective. Poor follow-up was significantly correlated with poor premorbid history, gradual onset, lack of depressive symptoms and heredity, seclusive personality, lack of precipitating events, lack of confusion, single status, onset before age 21, delusions of control, onset 6 months or more before admission, and emotional blunting. These variables were used to construct a validated prognostic scale. More recent treatment results have been contrasted with these findings from an earlier non-drug treatment era.

Adult↗