Change in prevalence of preterm birth in Israel following publication of national guidelines recommending routine sonographic cervical-length measurement at 19-25 weeks' gestation.

OBJECTIVE: To compare the prevalence of preterm birth (PTB) (delivery before 37 weeks) in Israel before and after publication of national guidelines recommending second-trimester sonographic cervical-length (CL) measurement. METHODS: The Israeli Society of Obstetrics and Gynecology (ISOG) guidelines, issued on 1 January 2012, specified that CL should be measured transabdominally or, if this is not possible, transvaginally, at the 19-25-week ultrasound anomaly scan and that CL < 25 mm should indicate further work-up and treatment, although the type of treatment was unspecified. In 2000, the Israel Ministry of Health issued a legal requirement for the submission of delivery records to a national registry. These data were used to compare PTB prevalence in the period before (2000-2011) and that after (2012-2020) publication of the guidelines, as well as trends within each time period. Information was available on singleton and multiple pregnancy and maternal age and parity, as well as low birth weight (< 2500 g). RESULTS: During the period 2000-2020, there were 3 403 976 infants liveborn in Israel: 1 797 657 before and 1 606 319 after publication of the ISOG guidelines. There were 247 187 PTBs overall, with a prevalence of 7.64% (95% CI, 7.52-7.77%) before publication of the guidelines and 6.84% (95% CI, 6.43-7.24%) afterwards (P < 0.0002, two-tailed). The annual PTB prevalence was static in the first time period but declined by 0.18% per annum during the second period, after publication of the guidelines. The proportionate reduction in PTB prevalence after compared with before publication of the guidelines was 10% overall, 9% for PTB at 33-36 weeks, 18% for PTB at 28-32 weeks and 24% for PTB at < 28 weeks. After publication of the guidelines, reduced prevalence of PTB was observed among singletons (5.49% before vs 4.83% after, P < 0.0001), but not among infants in twin or higher-order multiple pregnancy. There was a statistically significant reduction in the rate of PTB following publication of the guidelines in both nulliparous and parous women and in the 19-39-year-old maternal-age group. Although reductions in PTB prevalence were also noted in high-risk age groups (maternal age < 19 years and ≥ 40 years), these did not reach statistical significance. Following publication of the guidelines, there was a statistically significant reduction in the prevalence of birth weight under 2500 g, of a magnitude similar to that for PTB prevalence. CONCLUSIONS: The publication of national guidelines recommending routine CL measurement at the time of the second-trimester anomaly scan was associated with a fall in PTB prevalence in singleton pregnancies. Whilst direct evidence linking screening with this fall in prevalence is lacking, it is likely that implementation of routine CL screening played an important role in the reduction of PTB rate. Our experience indicates that screening can be incorporated into the second-trimester anomaly scan. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Motivations and perceptions of early adopters of personalized genomics: perspectives from research participants.

BACKGROUND/AIMS: To predict the potential public health impact of personal genomics, empirical research on public perceptions of these services is needed. In this study, 'early adopters' of personal genomics were surveyed to assess their motivations, perceptions and intentions. METHODS: Participants were recruited from everyone who registered to attend an enrollment event for the Coriell Personalized Medicine Collaborative, a United States-based (Camden, N.J.) research study of the utility of personalized medicine, between March 31, 2009 and April 1, 2010 (n = 369). Participants completed an Internet-based survey about their motivations, awareness of personalized medicine, perceptions of study risks and benefits, and intentions to share results with health care providers. RESULTS: Respondents were motivated to participate for their own curiosity and to find out their disease risk to improve their health. Fewer than 10% expressed deterministic perspectives about genetic risk, but 32% had misperceptions about the research study or personal genomic testing. Most respondents perceived the study to have health-related benefits. Nearly all (92%) intended to share their results with physicians, primarily to request specific medical recommendations. CONCLUSION: Early adopters of personal genomics are prospectively enthusiastic about using genomic profiling information to improve their health, in close consultation with their physicians. This suggests that early users (i.e. through direct-to-consumer companies or research) may follow up with the health care system. Further research should address whether intentions to seek care match actual behaviors.

Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder.

OBJECTIVE: This is a study estimating diagnostic accuracy of CSF asialotransferrin to transferrin ratio measurement in eIF2B related disorders by using clinical evaluation and EIF2B mutation analysis as the reference standard. eIF2B-related disorder is a relatively common leukodystrophy with broad phenotypic variation that is caused by mutations in any of the five EIF2B genes. There is a need for a simple and clinically valid screening tool for physicians evaluating patients with an unclassified leukodystrophy. METHODS: CSF two-dimensional gel (2DG) electrophoresis analyses to measure asialotransferrin to transferrin ratios were performed in 60 subjects including 6 patients with documented EIF2B gene mutations, patients with other types of leukodystrophy, and patients with no leukodystrophy. RESULTS: All six patients with mutation proven eIF2B-related disease showed low to nearly undetectable amounts of asialotransferrin in their CSF when compared to 54 unaffected controls by CSF 2DG analyses in this study. eIF2B-like patients, with clinically similar presentations but no mutations in EIF2B1-5, were distinguished from patients with mutations in EIF2B1-5 by this biomarker. Patients with mutations in EIF2B1-5 had asialotransferrin/transferrin ratio levels significantly different from the group as a whole (p < 0.001). Using 8% asialotransferrin/transferrin ratio as a cutoff, this biomarker has a 100% sensitivity (95% CI = 52-100%) and 94% specificity (95% CI = 84-99%). CONCLUSION: Decreased asialotransferrin/transferrin ratio in the CSF of patients with eIF2B-related disorder is highly sensitive and specific. This rapid (<48 hours) and inexpensive diagnostic tool for eIF2B-related disorders has the potential to identify patients with likely eIF2B-related disorder for mutation analysis.

The ABC's of limb-girdle muscular dystrophy: alpha-sarcoglycanopathy, Bethlem myopathy, calpainopathy and more.

Limb-girdle muscular dystrophy is a class of disorders encompassing many forms of this disease. Variation exists between the inheritance patterns, genes responsible, course of disease and symptoms, with the cohesive factor among these disorders being the predominance of proximal muscle weakness. Here we review each form of limb-girdle muscular dystrophy with attention to molecular genetics, clinical features, inheritance, and diagnostic issues pertaining to each primary genetic cause.

Coronary heart disease mortality among Arab and Jewish residents of Jerusalem.

Information on coronary heart disease (CHD) in the Palestinian population is sparse. We compared mortality rates in the largely Palestinian Arab population of Jerusalem with the Jewish population of the district between 1984 and 1997 based on official Israeli statistics. CHD mortality and all-cause mortality rates were significantly higher among Arab residents than among Jewish residents aged 35-74 years. Whether the excess CHD mortality reflects increased incidence of events, higher case fatality, or both remains to be established. Possible explanations include a higher prevalence of conventional risk factors such as diabetes, obesity, and smoking in Palestinians, stress effects related to the complex political situation and socioeconomic inequalities, and suspected differences in medical care.

Determination of paroxetine levels in human plasma using gas chromatography with electron-capture detection.

A simple, rapid and sensitive procedure using gas chromatography with electron-capture detection to measure paroxetine levels in human plasma has been developed. The analyte was extracted from plasma with ethyl acetate after basification of the plasma and then derivatized with heptafluorobutyric anhydride before gas chromatographic separation. The calibration curves were linear, with typical r2 values >0.99. The assay was highly reproducible and gave peaks with excellent chromatographic properties.

Effect of injected versus iontophoretic corticosteroid on the rabbit tendon.

BACKGROUND: The etiologic role of corticosteroid therapy in tendon rupture is controversial. This study compared the effects of injected versus iontophoretically delivered corticosteroid on the normal rabbit Achilles tendon. METHODS: Rabbits were divided into three treatment groups: (1) corticosteroid injections, (2) iontophoretically delivered corticosteroid, and (3) no treatment. One tendon of each rabbit in the treatment groups was treated with either drug injection or iontophoresis; the tendon of the other leg served as a control. Some tendons were used for testing elastic modulus, ultimate load, and ultimate stress, while the remaining tendons were evaluated histologically. RESULTS: Injections of either corticosteroid or saline into the tendon sheath resulted in short-term changes in tendon biomechanical characteristics and somewhat higher histologic severity scores; however, iontophoretic delivery of corticosteroid or saline did not affect either significantly. CONCLUSIONS: Iontophoresis using sterile water or corticosteroid resulted in minimal or no biochemical and histologic changes in the tendon compared with injection of either substance. The method of corticosteroid delivery may be as important as the actual drug effects on the biomechanical and histologic properties of tendons.

Effects of peripheral sympathectomy on thermoregulatory vascular control in the rabbit ear.

A rabbit ear model of the human digit was utilized to determine the vascular response to peripheral sympathectomy. Vascular responses were evaluated by subjecting chronically instrumented rabbits to a cold stress before and after sympathectomy surgery. The typical response to cold stress is for ear temperatures and auricular cutaneous perfusion to decrease during the cooling phase of the test and to increase toward baseline levels during the rewarming phase after cold exposure. Following peripheral sympathectomy, ear temperatures were significantly increased during both the cooling and rewarming phase of the cold stress test although overall ear perfusion and skin perfusion were not different from sham-operated rabbits. The responses observed in the rabbit ear following peripheral sympathectomy appear to mimic those noted in patients receiving digital peripheral sympathectomies for the treatment of refractory pain and ulceration. Peripheral sympathectomy may result in clinical improvements in patients because it improves both total digital and nutritional cutaneous blood flow. Peripheral sympathectomy in normal rabbit ears does not result in altered perfusion patterns with cold exposure although ear temperature is significantly higher. This pattern of changes suggests that the distribution of extremity perfusion is altered even though overall extremity perfusion and cutaneous perfusion per se are not significantly different from sham-operated controls. Complete sympathectomy was accompanied by a persistent increase in ear temperature and a dissociation between conductance and microvascular perfusion. Auricular conductance was transiently increased and then decreased to levels below preoperative control values. Microvascular perfusion is decreased immediately following amputation/replantation and thereafter increases.

Alpha adrenoceptors in the rabbit ear thermoregulatory microcirculation.

The rabbit ear microcirculation was analyzed in a chronic unanesthetized model to evaluate alpha adrenergic microvascular control in a thermoregulatory end organ. This model allowed direct measurement of microcirculatory responses without the effects of anesthetics or inflammatory responses induced by acute surgical intervention. The ipsilateral facial artery was catheterized for drug injections into the experimental ear. Microvascular diameter changes following stimulation or blockade of adrenoceptor (AR) subtypes were observed directly through a chronic microvascular chamber implanted in the rabbit ear. Vascular alpha1- and alpha2-ARs appear to be distributed differently across the arterioles and AVAs of the rabbit ear. Both alpha1- and alpha2-ARs appear to contribute to vasoconstriction of AVAs in the conscious rabbit ear. In contrast, alpha1-AR's (vs alpha2-ARs) appear to predominate in adrenergically mediated sympathetic vasoconstriction of arterioles.

Cartilage injuries: a review of 31,516 knee arthroscopies.

Although articular cartilage injuries of the knee are common, injured cartilage has a limited ability to heal. Recent data suggest that articular cartilage grafting may provide treatment for these injuries. To define the patient population that might benefit from cartilage grafting, 31,516 knee arthroscopies were reviewed. Between June 1991 and October 1995, 53,569 hyaline cartilage lesions were documented in 19,827 patients. The majority were articular cartilage lesions; grade III lesions of the patella were the most common. Grade IV lesions were predominantly located on the medial femoral condyle. Patients under 40 years of age with grade IV lesions accounted for 5% of all arthroscopies; 74% of these patients had a single chondral lesions (4% of the arthroscopies). No associated ligamentous or meniscal pathology was found in 36.6% of these patients.

Control of arteriovenous anastomoses in rabbit ear model of digital perfusion.

The arteriovenous anastomoses (AVA) of the cutaneous microcirculation of the hands and feet are fundamental determinants of thermoregulatory blood flow and may be involved in cold intolerance. These direct microvascular studies are an initial characterization of adrenergic receptor subtypes participating in control of AVA in the ears of anesthetized male New Zealand White rabbits. Adrenergic alpha 1-stimulation with phenylephrine produced AVA constriction, whereas terazosin (an alpha 1-antagonist) produced dilation and attenuated the responses to phenylephrine. Adrenergic alpha 2-stimulation with UK-14304 produced constriction of the AVA, whereas atipamezole (an alpha 2-antagonist) produced dilation and attenuated the responses to UK-14304. When equimolar concentrations of antagonists were studied, the AVA dilation produced by alpha 2-blockade was greater than that produced by alpha 1-blockade. Norepinephrine (a mixed alpha 1- and alpha 2-agonist) also produced vasoconstriction, which was attenuated by both prazosin (an alpha 1-antagonist) and atipamezole. In summary, 1) AVA contain a heterogeneous mixture of both alpha 1- and alpha 2-receptors, and 2) alpha 2-receptors may have a greater influence than alpha 1-receptors on overall tone in AVA.

Antibiotic resistance in staphylococci adherent to cortical bone.

The surface-adherent mode of bacterial growth has been shown to play a pivotal role in the persistent nature of infections involving retained foreign bodies, biomaterials, or dead bone (e.g., osteomyelitis). The hypothesis tested herein is that bone and implant materials--polytetrafluoroethylene (PTFE), and polymethylmethacrylate (PMMA)--provide a surface environment that promotes a type of bacterial growth characterized by an enhanced antibiotic resistance. The antibiotic resistance estimates of three staphylococcal subtypes were determined for organisms grown in an adherent state on the aforementioned surfaces as well as in their nonadherent or suspended state. Antibiotic resistance was found to vary with mode of bacterial growth. Secondly, for the staphylococcal subtypes, antibiotics and modes of growth studied herein, adherent growth on bone was associated with the most antibiotic resistance.

Electronic stethoscope with frequency shaping and infrasonic recording capabilities.

A small electronic stethoscope with variable frequency response characteristics has been developed for aerospace and research applications. The system includes a specially designed piezoelectric pickup and amplifier with an overall frequency response from 0.7 to 5,000 HZ (-3 dB points) and selective bass and treble boost or cut of up to 15 dB. A steep slope, high pass filter can be switched in for ordinary clinical auscultation without overload distortion from strong infrasonic signal inputs. A commercial stethoscope-type headset, selected for best overall response, is used which can adequately handle up to 100 mW of audio power delivered from the amplifier. The active components of the amplifier consist of only four opamp-type integrated circuits.

Familial Kallmann syndrome with unilateral renal aplasia.

On the basis of studies in two brothers and their double first cousin, the Kallmann syndrome (KS) is discussed as an X-linked syndrome of anosmic hypogonadotropic hypogonadism. The anosmia is thought to represent agenesis or hypoplasia of the olfactory lobes, the mildest form of the alobar holoprosencephaly developmental field defect; this is supported by the finding of hypotelorism in two of the patients and their mother. The endocrine defect is thought to represent a hypothalamic abnormality of the luteinizing hormone releasing hormone; borderline normal intelligence may represent another pleio-tropic CNS manifestation of the KS gene. All three affected males had unilateral renal aplasia, associated in one with ipsilateral absence of the testis. The presence of at least two developmental field defects (involving the CNS and urogenital system) makes it likely that the KS is a true multiple congenital anomaly syndrome; this is supported by the finding of additional, mostly minor, anomalies reported by other investigators. Heterozygous females may also show manifestations of anosmia, hypogonadism, possibly even internal genital malformation; however, genetic heterogeneity of anosmic hypogonadism is possible, and for the time being it is probably better to designate sporadic female cases of anosmic hypogonadism as examples of the olfacto-genital syndrome of DeMorsier. Linkage studies are urgently needed to clear up the question of genetic heterogeneity and to help develop empiric recurrence risk figures in anosmic hypogonadism.