Occult myocardial injury is prevalent amongst elderly patients in the hospital-at-home setting. A retrospective analysis of 213 patients.

Background: Hospital-at-Home (HAH) is a valid alternative for in-hospital stay for a wide variety of clinical indications. Occult myocardial injury, associated with acute illness, mainly occurs in patients with a background of non-obstructive coronary disease. The aim of this study was to describe the prevalence of this phenomenon in our HAH population. Methods: A retrospective description and analysis of data collected for patients admitted to the Sheba beyond's HAH services during 14 months. Results: During a period of 14 months (7/10/21-6/12/22), blood troponin measurements were available for 213 patients (median age 78 years, 52% males) hospitalized mainly for infectious causes. The median HS (highly sensitive) troponin level was 7.7 ng/L (IQR = 13.2 ng/L) (the normal upper limit is 12 ng/L) with 31% of all patients demonstrating an abnormally increased troponin level (68/213). Of all patients, 64% had a background diagnosis of a cardiovascular disease (138/213), of whom, 49% had abnormal HS troponin levels (68/138). No patient suffered from acute cardiac function deterioration and no patient died during their hospital-at-home stay. Conclusion: The prevalence of occult myocardial injury amongst elderly patients admitted to hospital-at-home stay for diagnoses other than myocardial infarction is relatively high but it is not associated with worse short-term clinical outcomes.

"Staying at Home": A pivotal trial of telemedicine-based internal medicine hospitalization at a nursing home.

Background: In-hospital stay of acutely ill elderlies could be reduced by increasing the availability of community-based hospitalizations. The feasibility of remotely managing these patients by specialized internists, without leaving their nursing homes should be sought. In the current pivotal study, we aimed to evaluate the aforementioned model. Methods: This was a prospective, open-label study at a tertiary medical center and a nursing home. The study aimed at comparing clinical outcomes of patients hospitalized in each location. Results: Over a period of 5.5 months, we recruited 18 patients designated for hospitalization, meeting our inclusion criteria to either in-hospital stay or staying in their nursing home and treated by means of telemedicine from our tertiary medical center. The mean age was 85.3 years. Out of 114 hospitalization days, 44 days (48%) were at the nursing home. No significant difference was noted in terms of age, gender, and length of stay between the patients who were hospitalized in either location. In almost all cases, diagnosis changed during hospitalization. Three patients died during the study, all included in the in-hospital group. No safety breaching events happened in the nursing home-hospitalization group. Conclusions: Remote, telemedicine-based hospitalization of nursing home-dwelling elderlies is safe and feasible, potentially reducing the length of in-hospital stay by almost 50%. Larger studies in this realm are warranted.

The effect of pressure on the lipid microviscosity and phase transition of lung surfactant.

The effect of pressure on the lipid dynamics of the rat lung surfactant was studied in liposomes made of the natural lung surfactant of the rat and of model phospholipid mixture. The determined parameter was the lipid microviscosity, monitored by the fluorescence polarization of the probe 1,6-diphenyl-1,3,5-hexatriene. Osmotic pressure of up to 47 atm, as well as hydrostatic pressure of up to 1.4 kbar, were applied at a constant temperature. The effect of pressure was monitored by the change in the lipid microviscosity of the system. The maximal change achieved with osmotic pressure at a constant temperature was only 30%. This suggests that the conversion of melted lipid to its solid phase above the lipid critical temperature requires several hundred atmospheres. Similarly, measurements of lipid microviscosity under increased hydrostatic pressure revealed transitions which occurred at above 400 atm. Since such pressures are far beyond the physiological scale, it excludes the possibility that pressure alone can be responsible for a full phase transition of the lung surfactant during respiration. Upon decompression, microviscosity of the examined lipid system was found to return to its original values, confirming the reversibility of the process.

Prolactin (PRL)-releasing peptide stimulates PRL secretion from human fetal pituitary cultures and growth hormone release from cultured pituitary adenomas.

The hypothalamic peptide PRL-releasing peptide (PrRP) has recently been cloned and identified as a ligand of an orphan pituitary receptor that stimulates in vitro PRL secretion. PrRP also induces PRL release in rats in vivo, especially in normal cycling females. However, no information on the effects of PrRP in the human is available. To elucidate the role of PrRP in regulating human anterior pituitary hormones, we used human PrRP-31 in primary cultures of human pituitary tissues, including fetal (20--27 weeks gestation) and normal adult pituitaries, as well as PRL- and GH-secreting adenomas. PrRP increased PRL secretion from human fetal pituitary cultures in a dose-dependent manner by up to 35% (maximal effect achieved with 10 nM), whereas TRH was slightly more potent for PRL release. Coincubation with estradiol resulted in enhanced fetal PRL response to PrRP, and GH release was only increased in the presence of estradiol. Although PRL secretion from PRL-cell adenomas was not affected by PrRP, PrRP induced PRL release from cultures of a GH-cell adenoma that cosecreted PRL. PrRP enhanced GH release in several GH-secreting adenomas studied by 25--27%, including GH stimulation in a mixed PRL-GH-cell tumor. These results show for the first time direct in vitro effects of PrRP-31 on human pituitary cells. PrRP is less potent than TRH in releasing PRL from human fetal lactotrophs and is unable to release PRL from PRL-cell adenomas in culture, but stimulated GH from several somatotroph adenomas. Thus, PrRP may participate in regulating GH, in addition to PRL, in the human pituitary.

Comparative genomic hybridization analysis of nonfunctioning pituitary tumors.

Clinically nonfunctioning pituitary adenomas constitute about one third of pituitary neoplasms and are considered monoclonal tumors. The molecular mechanisms of tumorigenesis in these neoplasms are poorly understood, as evidenced by the paucity of reported somatic genetic alterations. Furthermore, the somatic mutations detected to date were primarily ascribed to candidate genes or chromosomal regions: gsp, ras, p53 mutations, and allelic losses of 11q and 13q. To gain insight into which chromosomal regions bear genes involved in nonfunctioning pituitary tumorigenesis, we examined 23 such tumors by comparative genomic hybridization. Four tumors showed no genetic abnormality, and the rest (17 of 23, 74%) exhibited at least one chromosomal region of abnormality. Gains and losses affected all chromosomes (except for chromosome 14). Notably, 8 of 23 tumors (34.7%) displayed sex chromosome and chromosome 18 aberrations (amplifications or deletions). Nonrandom DNA amplification of sub-chromosomal regions on 4q, 5q (5q13-->5q23), 9p (9p21-->9pter), 13q (13q21-->13q32), and 17q were detected in 10-30% of the tumors. Noteworthy, no tumor displayed deletion of 11q, the MEN1 gene locus. These findings suggest that genes localized to previously undescribed chromosomal regions play a role in the tumorigenesis of nonfunctioning pituitary adenomas.

Germline mutational analysis of presenilin 1 and APP genes in Jewish-Israeli individuals with familial or early-onset Alzheimer disease using denaturing gradient gel electrophoresis (DGGE).

Germ line mutations in three genes have been detected in patients with familial Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2). The relative proportions in which mutations in these genes occur among AD patients in Israel has not been evaluated. To that end, we screened 52 Jewish-Israeli patients with AD: 22 with sporadic, early-onset disease (below 65 years), and 30 with FAD. Mutation screen employed denaturing gradient gel electrophoresis (DGGE) of exon-specific PCRs and restriction enzyme digest. Five patients from three different families displayed mutations within the PS-1 gene: three patients of one family showed a mis-sense mutation in codon 120 (Glu 120Lys), and two other unrelated patients showed an identical mis-sense mutation in codon 318 (Glu318Gly). No patient showed an abnormal migration on DGGE (for APP) or mutant restriction digest pattern (for PS-2) genes. These data may indicate the existence of another familial Alzheimer disease (FAD) gene locus in the Israeli Jewish population.

Studies on sperm chromosomes in patients with severe male factor infertility undergoing assisted reproductive technology treatment.

The aim of the study was to determine the rate of chromosome abnormalities in testicular sperm after intracytoplasmic sperm injection due to severe male factor infertility. The study groups included patient with non-obstructive azoospermia (n=9), obstructive azoospermia (n=10), Klinefelter's syndrome (n=5) and normal controls (n=6, groups I-VI, respectively). The mean serum levels of FSH 17.5+/-8.2 (P<0.05), 3.5+/-2.6, 29.8+/-13.0 (P<0.05) and 3.1+/-0.4 mIU/ml, respectively. The rates of chromosome abnormalities were 19.6% (P<0.001), 8.2% (P<0.001), 6.3 and 1.6%, respectively. Chromosomes X and Y were significantly more involved in the aneuploidy than chromosome 18 in groups I and II. The present findings demonstrate a linkage between gonadal failure (high serum FSH levels) and sperm chromosome abnormalities. Our findings may explain the increased incidence of perinatal sex chromosome abnormalities found in severe male factor patients. Patients with non-mosaic Klinefelter's syndrome have comparable risk for sex chromosomes aneuploidy as the rest of the patients with azoospermia. Therefore, genetic screening during pregnancy or before embryo replacement should be carefully considered in severe male factor patient following in vitro fertilization (IVF).

Human chorionic gonadotrophin and trisomy 18.

Estimation of maternal serum beta-hCG is used in conjunction with alpha-fetoprotein (AFP) and estriol (E3) for estimating the risk of Down syndrome (DS) affected fetuses. However, low hCG levels have not been regarded as having clinical significance. We report on 2 patients with trisomy 18 fetuses in whom antenatal screening showed extremely low hCG levels (0.05 and 0.15 MOM). Low hCG levels might indicate increased risk for trisomy 18 despite low estimated risk for DS.

Pulmonary agenesis, microphthalmia, and diaphragmatic defect (PMD): new syndrome or association?

We present the prenatal diagnosis of a 22-week-gestation fetus with unilateral pulmonary agenesis, diaphragmatic hernia, microphthalmia, pulmonary vessel agenesis, and intrauterine growth retardation. The "association" of pulmonary agenesis, diaphragmatic defect, and microphthalmia was described previously in two patients but the resemblance was not noted by the authors. While each case differs slightly in some of the associated anomalies, it is evident that the mainstay of diagnosis is similar to the case presented here and that this represents a new syndrome or association.

Perceived personal control (PPC): a new concept in measuring outcome of genetic counseling.

Many researchers have tried to establish criteria for the evaluation of genetic counseling and the assessment of its success. Most studies focused on counseling outcomes mainly educational and reproductive variables. In the present study we introduced the concept of "perceived personal control" (PPC), which captures a wider and more meaningful range of effects of genetic counseling. It was found to be central to coping with health threats and to adapting to a broad spectrum of health problems. This study investigated 154 counseling cases. Counselees were requested to complete pre- and post-counseling questionnaires consisting of a knowledge test, measures of PPC, expectations/evaluations of counseling, and satisfaction with the procedure. Comparisons of mean PPC scores before and after counseling showed significant increases. Higher post-counseling PPC was found among counselees who had been given a definite diagnosis, a specific recurrence risk, and been offered prenatal diagnosis. Post-counseling PPC also correlated with knowledge, satisfaction, counseling evaluations, and expectation fulfillment. The findings suggest that PPC is a valid measure for the evaluation of genetic counseling outcomes. The psychometrically reliable scales developed in this study can become helpful tools for assessing genetic counseling both in research and in clinical practice, helping the counselor evaluate the counseling session and focus on the counselees' needs.

Concordance of auriculo-cardiovascular-skeletal malformations: a new malformation complex in an infant of a diabetic mother?

The incidence of malformations among infants of diabetic mothers (IDM) is known to be higher than in the general population. These malformations usually involve several organ systems and in the past few years there has been an attempt to group them into distinct "syndromes." The present report concerns a child with a specific constellation of findings not yet reported in the infant of a diabetic mother, and we urge our colleagues to look for other associations existing in these infants, rather than just listing series of individual malformations.

Congenital diaphragmatic hernia in a family segregating a reciprocal translocation t(5;15)(p15.3;q24).

Congenital diaphragmatic hernia (CDH) is a relatively common malformation of unknown cause with high mortality due to hypoplasia of the lungs and pulmonary hypertension. We studied a family in which two fetuses had CDH, and two pregnancies resulted in first trimester missed abortions. Both fetuses with CDH had an apparently normal karyotype. In a subsequent pregnancy, fluorescent in situ hybridization analysis of amniocytes showed a balanced translocation 46,XY, t(5;15) (p15.3;q24) also present in the mother and in a normal child, suggesting that the diaphragmatic hernia in the first two fetuses was caused by a cryptic unbalanced translocation. This hypothesis is supported by a previous observation of CDH in a distal deletion of 15q as part of a multiple congenital anomalies syndrome. It is suggested that a gene distal to 15q21 is important for the normal development of the diaphragm.

Use of interphase fluorescence in situ hybridization in third trimester fetuses with anomalies and growth retardation.

In the last few years, attention has been focused on the use of interphase fluorescence in situ hybridization (FISH) for prenatal diagnosis with chromosome-specific DNA probes in the second trimester. This technique is accurate, rapid, and detects the most common aneuploidies. We present a preliminary study using FISH technique on uncultured amniotic cells derived from 30 fetuses with ultrasonographic evidence of intrauterine growth retardation (IUGR) in the third trimester. Fifteen fetuses were males and 15 were females. Seven fetuses (23.3%) had abnormal chromosomal constitution: five (18.6%) had trisomy 21, one (2.35%) had trisomy 18, and one (2.35%) showed a mosaic trisomy 18. No abnormalities were detected in the other 23 fetuses. Amniocentesis combined with FISH appears to be a safe, rapid, and accurate alternative to blood sampling in the third trimester, reducing the clinical and emotional stress of the time required to complete chromosome analysis by routine cytogenetics.

Molecular cytogenetic studies in three patients with partial trisomy 2p, including CGH from paraffin-embedded tissue.

We report on three cases of partial trisomy 2p in which the identification and exact localization of the duplicated chromosome segment was possible only by application of molecular cytogenetic techniques. These included fluorescence in situ hybridization by use of wcp2, N-myc, and subtelomeric 2p probes and comparative genomic hybridization with DNA isolated from blood samples, frozen fetal tendon, and formalin fixed, paraffin-embedded fetal lung tissue. Two of the cases concerned fetuses of gestational week 20 and 24 with duplication of nonoverlapping terminal (2pter-->p24) and more proximal (2p25-->p23) segments and with distinctly different phenotypes. The third case was due to a de novo inverted duplication of 2p25-->p23, with loss of the subtelomeric region of 2p. This 53-month-old girl was a Bloom syndrome carrier. The patient had prenatal growth failure, borderline microcephaly, dilated lateral horns of the cerebral ventricles, transient cortical blindness, myopia, muscle hypotonia, and dilatation of the left renal collecting system. Dermal cysts were found on the glabella, the soles of both feet, and the vocal cord, causing respiratory embarrassment. Previously reported cases of pure trisomy 2p are reviewed, in an attempt to correlate clinical findings to overlapping regions in 2p. These cases illustrate the effectiveness of molecular cytogenetic methods in resolving subtle chromosomal aberrations in order to coordinate more accurately a chromosome regionspecific phenotype.

Low-dose aspirin does not influence the clinical course of women with mild pregnancy-induced hypertension.

The effect of low doses of aspirin on women with mild pregnancy-induced hypertension was investigated by means of a prospective, randomized, double-blind trial. Forty-seven women hospitalized at 30-36 weeks' gestation because of mild pregnancy-induced hypertension were treated by a daily dose of either 100 mg aspirin or placebo. The mean blood pressure values, rates of development of severe preeclampsia, gestational ages at delivery, newborn weights, and 5-minute Apgar scores were similar in the aspirin-treated and the placebo-treated groups. We conclude that low-dose aspirin is not curative but is essentially a preventive treatment which, in order to be effective, should be started weeks before clinical signs of preeclampsia are present.

Internal podalic version with unruptured membranes for the second twin in transverse lie.

Internal podalic version of the second twin in transverse lie has usually been performed after first rupturing the membranes of the second amniotic sac. In a prospective study on internal podalic version with unruptured amniotic membranes, 11 second-born twins in transverse lie were successfully delivered, with good neonatal outcome and without birth injuries. From our experience, it appears that this modified technique, when used within the presented guidelines, offers a reasonable alternative for the safe delivery of the second twin.

Fetal lateral ventricle choroid plexus cysts: the dilemma of amniocentesis.

Although lateral ventricle choroid plexus cysts in the second-trimester fetus have been considered a benign developmental phenomenon of no clinical significance, an association with trisomy 18 has been suggested. We designed a prospective study to determine whether karyotype analysis is indicated when such cysts are encountered on prenatal sonogram. During a 20-month period, 5400 low-risk pregnant women were examined sonographically in the second trimester to evaluate the prevalence of fetal lateral ventricle choroid plexus cysts and the incidence of ultrasonographic anomalies associated with such cysts in fetuses with trisomy 18 referred from cytogenetic laboratories. Thirty cases of fetal lateral ventricle choroid plexus cysts (0.6%) were detected during the study period; 28 newborns were normal and two had trisomy 18. One of the affected infants had other associated ultrasonographic abnormalities suggesting aneuploidy, whereas no detectable abnormalities could be found in the other. Three other pregnant women were referred to us from the cytogenetics services because fetal karyotype revealed trisomy 18; in all three cases lateral ventricle choroid plexus cysts and other sonographic abnormalities were observed. In total, we scanned five fetuses with trisomy 18, of which all had lateral ventricle choroid plexus cysts and four had associated detectable anomalies. We could not find any association between cyst size, number, or laterality and trisomy 18. In addition to the five cases of trisomy 18 described, we found 33 other fetuses reported with trisomy 18 in the second trimester; of this total, 25 (66%) had lateral ventricle choroid plexus cysts and 30% had no other detectable abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of abnormal pregnancies on fluorescence polarization of amniotic fluid lipids.

The fluorescence polarization of amniotic fluid, a measure of fetal lung maturity, was determined in 518 amniotic fluid samples obtained by amniocentesis. The subjects were divided into seven clinical groups: premature contractions, premature rupture of the membranes, pregnancy-induced hypertension, diabetes, intrauterine growth retardation, vaginal bleeding, and "other" for gestational-age groups of 30 weeks or less, 31-36 weeks, and 37 or more weeks. The proportion of mature values (fluorescence polarization 0.285 or lower) increased progressively from 12.5% at 27-28 weeks to 100% at 39-40 weeks. In the 31-36-week gestation group, the proportion of mature values in subjects with premature rupture of the membranes (84.6%) was significantly higher than in those with premature contractions (60%), severe pregnancy-induced hypertension (50%), mild pregnancy-induced hypertension (55.2%), diabetes class A (50%), insulin-dependent diabetes (60%), and other (63.5%). The mean +/- SD fluorescence polarization value was significantly lower in premature rupture of the membranes (0.256 +/- 0.030) than in premature contractions (0.274 +/- 0.032), mild and severe pregnancy-induced hypertension (0.280 +/- 0.027 and 0.280 +/- 0.035, respectively), and class A and insulin-dependent diabetes (0.285 +/- 0.018 and 0.277 +/- 0.030, respectively). The severity of pregnancy-induced hypertension and diabetes did not appear to influence either the fluorescence polarization value or the proportion of mature results. With the exception of a marked influence of premature rupture of the membranes, abnormal pregnancy conditions did not appear to have a significant effect on fluorescence polarization of amniotic fluid.

Determination of amniotic fluid microviscosity at body temperature: a predictor of fetal lung maturity.

One of the most convenient ways to determine fetal lung maturity is by measuring the fluorescence polarization (P) of the amniotic fluid at room temperature. With sensitivity fixed on 100%, specificity is relatively unsatisfactory. The present study compared the predictive power of fluorescence polarization measured at temperatures 25C (P25), 37C (P37), and 40C (P40) among 195 consecutive samples tested at both 25C and 37C, with a subgroup of 86 samples tested also at 40C. A better separation between the results for fetuses with and without hyaline membrane disease is attained at P37, demonstrated by a greater mean standardized distance (distance between P values for those patients with and the mean P value for those patients without hyaline membrane disease in unit of standard deviation of the latter; 1.597 +/- 0.528 for P25 versus 2.332 +/- 0.591 for P37). Fixing the sensitivity at 100%, the specificity of P25 and P37, were 68.9 and 94.9%, respectively; a highly significant difference (P less than .001). The specificity of P40 was 90.5%, lower than that of P37. P37 is the best predictor and adding either P25 or P40 does not improve the prediction of lung maturity. It is concluded that P37 should replace P25 as the definite index for fetal lung maturity.

High-order multifetal gestation--management and outcome.

During the period 1975-1989, 11 high-order (quadruplet or more) multifetal gestations reaching the second trimester were treated in our department. All pregnancies resulted from ovulation induction therapy. Premature contractions occurred in all cases. Two women delivered stillborn quadruplets vaginally at 25 and 26 weeks' gestation. Nine women had cesarean deliveries at 28-35 weeks; one fetus was stillborn and two of the 39 live-born infants died. Twenty-nine (74%) weighed less than 1500 g and 16 (41%) were below the tenth percentile for gestational age. Thirty infants have been followed for at least 2 years, corrected for gestational age; 21 (70%) are developing normally, two are severely handicapped with both cerebral palsy and mental retardation, four have mild motor delay, and three have mild motor and mental delay.