Rheumatic fever and rheumatic heart disease; incidence in California

The statistics quoted in this and other published reports appear to substantiate the impression that rheumatic fever in California, although still an important public health problem which varies widely from one locality to another, is of lower incidence and perhaps of more benign character than in most other parts of the United States. It also appears that in California aortic insufficiency may be of higher relative incidence and occurs more frequently as a clinically diagnosable sequel of rheumatic fever than does classical mitral stenosis. Congenital defects of the heart constitute a large proportion of the cases of organic heart disease in children and young adults in this state.     

Congenital heart disease cyanotic children

Cyanosis is often the only apparent symptom of congenital heart disease for which a child is brought to a physician. Some of the more common anomalies can be diagnosed from this and other symptoms by a general practitioner. Squatting after exertion is a sign of tetralogy of Fallot; severe disability with relatively mild cyanosis may indicate pure pulmonary stenosis. A brisk, short, rasping systolic murmur is characteristic of these conditions and of tricuspid atresia. Tetralogy of Fallot is further symptomatized by a boot-shaped heart, not greatly enlarged, and right axis deviation on electrocardiograms. Typically the lung fields are clear. The author's treatment of choice is aortic-pulmonary or subclavian-pulmonary anastomosis as indicated, preferably done after the child is three years old if the condition is not so severe as to require earlier operation. Pure pulmonary stenosis, which in some cases cannot be distinguished from tetralogy of Fallot except by cardiac catheterization and angiocardiography, may in more typical cases be diagnosed by convexity rather than concavity in the pulmonary segment and by differences in electrocardiograms. An expanding valvulotome is used to open the stenosed pulmonary valve, which is then dilated.A systolic murmur, a round heart and left axis deviation are usually found in tricuspid atresia. Shunt operations performed for relief of this condition may lead to later heart failure because of the devious rerouting of blood through the heart. The operations here outlined and others are statistically evaluated.     

Lipoprotein(a), family history of cardiovascular disease,and incidence of heart failure

Lipoprotein(a) (Lp(a)) is a largely genetically determined biomarker for cardiovascular disease (CVD), while its potential interplay with family history (FHx) of CVD, a measure of both genetic and environmental exposures, remains unclear. We examined the associations of Lp(a) in terms of circulating concentration or polygenetic risk score (PRS), and FHx of CVD with risk of incident heart failure (HF). Included were 299,158 adults from the UK Biobank without known HF and CVD at baseline. Hazards ratios (HRs) and 95% Cls were estimated by Cox regression models adjusted for traditional risk factors defined by the Atherosclerosis Risk in Communities study HF risk score. During the 11.8-year follow-up, 5,502 incidents of HF occurred. Higher levels of circulating Lp(a), Lp(a) PRS, and positive FHx of CVD were associated with higher risks of HF. Compared with individuals who had lower circulating Lp(a) and no FHx, HRs (95% CIs) of HF were 1.36 (1.25, 1.49), 1.31 (1.19, 1.43), and 1.42 (1.22, 1.67) for those with higher Lp(a) and a positive history of CVD for all family members, parents, and siblings, respectively; similar results were observed by using Lp(a) PRS. The risk estimates for HF associated with elevated Lp(a) and positive FHx were attenuated after excluding those with incident myocardial infarction (MI) during follow-up. Lp(a) and FHx of CVD were independent risk factors for incident HF, and the highest risk of HF was observed among individuals with both risk factors. The association may be partly mediated by myocardial infarction.     

Rediscovery of Anthias salmopunctatus Lubbock & Edwards, 1981, with comments on its natural history and conservation

After c. 30 years without sighting or capture, Anthias salmopunctatus was rediscovered at the type locality, St Peter and St Paul's Rocks, Mid-Atlantic Ridge. To date, the known distribution is restricted to depths varying from 35 to 55 m in vertical drop offs around the perimeter of the islands ( c. 400 m). This may be the smallest geographic range known for a marine fish species.     

Congenital heart disease and the specification of left-right asymmetry

Complex congenital heart disease (CHD) is often seen in conjunction with heterotaxy, the randomization of left-right visceral organ situs. However, the link between cardiovascular morphogenesis and left-right patterning is not well understood. To elucidate the role of left-right patterning in cardiovascular development, we examined situs anomalies and CHD in mice with a loss of function allele of Dnaic1, a dynein protein required for motile cilia function and left-right patterning. Dnaic1 mutants were found to have nodal cilia required for left-right patterning, but they were immotile. Half the mutants had concordant organ situs comprising situs solitus or mirror symmetric situs inversus. The remaining half had randomized organ situs or heterotaxy. Looping of the heart tube, the first anatomical lateralization, showed abnormal L-loop bias rather than the expected D-loop orientation in heterotaxy and nonheterotaxy mutants. Situs solitus/inversus mutants were viable with mild or no defects consisting of azygos continuation and/or ventricular septal defects, whereas all heterotaxy mutants had complex CHD. In heterotaxy mutants, but not situs solitus/inversus mutants, the morphological left ventricle was thin and often associated with a hypoplastic transverse aortic arch. Thus, in conclusion, Dnaic1 mutants can achieve situs solitus or inversus even with immotile nodal cilia. However, the finding of abnormal L-loop bias in heterotaxy and nonheterotaxy mutants would suggest motile cilia are required for normal heart looping. Based on these findings, we propose motile nodal cilia patterns heart looping but heart and visceral organ lateralization is driven by signaling not requiring nodal cilia motility.     

Clinical epidemiology and natural history of gastroesophageal reflux disease

In the MUSE classification of gastroesophageal reflux disease (GERD), esophagitis is assessed by the presence of metaplasia, ulcer, stricture, or erosion, each being graded as absent, mild or severe. Daily reflux symptoms affect about 4 to 7 percent of the population; erosive esophagitis occurs in about 2 percent; the prevalence rate of Barrett's metaplasia is 0.4 percent; and esophageal adenocarcinoma leads to two deaths per million living population. In persons with GERD symptoms, about 20 percent are found to have erosive esophagitis, while ulcers or strictures are found in less than 5 percent of all patients with erosive esophagitis. No clear-cut temporal progression exists between successive grades of disease severity, as the most severe grade of GERD is reached at the onset of the disease. Mild forms of GERD tend to be more common in women than men, while severe GERD characterized by erosive esophagitis, esophageal ulcer, stricture or Barrett's metaplasia are far more common in men than women. All forms of GERD affect Caucasians more often than African Americans or Native Americans. The prevalence of GERD is high among developed countries in North America and Europe and relatively low in developing countries in Africa and Asia. During the past three decades, hospital discharges and mortality rates of gastric cancer, gastric ulcer and duodenal ulcer have declined, while those of esophageal adenocarcinoma and GERD have markedly risen. These opposing time trends suggest that corpus gastritis secondary to Helicobacter pylori infection protects against GERD. This hypothesis is consistent with the geographic and ethnic distributions of GERD. Case-control studies also indicate that cases with erosive esophagitis are less likely to harbor active or chronic corpus gastritis than controls without esophagitis.     

An early- and late-stage convolution model for disease natural history

The standard convolution model of disease natural history posits an asymptomatic (preclinical) and a symptomatic (clinical) state. An augmented model includes, in both the preclinical and clinical states, an early and late stage of disease. In the case of cancer, the early stage would generally correspond to the organ-confined stages before there is evidence of cancer spread. We compute the number of screen-detected (preclinical) and clinical cases in the early and late stages expected under a given screening program and show how the model can be fit to data from a screening trial using maximum likelihood. We also develop expressions for sojourn time, lead time, and overdiagnosis in the context of the model, where each of the above concepts incorporates disease stage. As an example, we fit the model to data from the Mayo Lung Cancer Screening trial.     

Congenital heart disease and prenatal exposure to exogenous sex hormones.

One-hundred and four infants with congenital heart disease were identified from their birth certificates and matched with normal controls. Their gestational histories were examined to see whether they had been exposed to exogenous sex hormones. Exposure was 8-5 times more common among the infants with malformations than among controls. A history of hormone exposure was more common among those patients with multiple malformations, and the exposed infants were also more likely to have died (and to have died earlier) than those who had not been exposed, which suggests that hormone exposure causes severe types of malformations. The commonest type of exposure was to hormone pregnancy tests, which was needless exposure. Only two of the mothers of malformed infants had inadvertently used oral contraceptives in the first trimester.     

Husbandry and breeding of the Puerto Rican toad (Peltophryne lemur) with comments on its natural history

The methods used in the breeding and rearing of Peltophryne lemur along with comments on reintroduction efforts are described. Breeding was induced by injections of leutinizing releasing hormone, and fertile eggs were produced. Eggs hatched in approximately 24 h. Newly hatched tadpoles were small (5.0 mm) and delicate. Metamorphosis occurred in 20–30 days, and newly metamorphosed toads grew evenly and quickly to maturity in about 1 yr. Seventy-five 20-mm young were returned to Puerto Rico in May 1983. These toads were released at a pond where adult and young P lemur were seen. The successful maintenance and breeding of this species indicate it can survive in captivity. Future work on P lemur should concentrate on its status and survival in the wild.     

Congenital heart disease in sibships ascertained by two affected siblings

Summary Families containing at least 2 children affected by cardiologically diagnosed congential heart disease were selected from the files of the Children's Memorial Hospital, Chicago, Willis J. Potts Children's Heart Center. From the data of 54 such families a recurrence rate of CHD for additional children of between p (K=0, r_(min)=2)=0.0554±0.0256 and p (K=1, r_(min)=2)=0.0801±0.0349 was calculated. Incompleteness of families or voluntary termination of reproduction after the second affected child was born could be excluded as effective bias-inducing factors. In the great majority of cases, sibs displayed identical or closely related malformations. No paternal or maternal age effect was found. Consanguinity was not noticeably increased, but the material was unsuitable for the study of this question. A recurrence rate which was definitely higher in families with at least two affected children than in families selected by a single proband, is taken as further evidence for the importance of genetic factors in congenital heart disease. Any single-gene hypothesis can be fitted to the actual data only if far-reaching additional assumptions are made. A multifactorial genetic system explains the observations more easily. This work has been carried out in part during the author's stay at the Genetic Clinic of the Children's Memorial Hospital, Dept. of Pediatrics, Northwestern University Medical School (Prof. D. Y.-Y. Hsia, M.D.). Data have been collected in collaboration with Dr. M. H. Paul, director of the Dept. of Cardiology of the Children's Memorial Hospital, Willis J. Potts Children's Heart Center. The author was supported in part by a grant from the US Public Health Service, National Institutes of Health and a Fulbright Travel Grant.     

The natural history of Beauchêne Island

Beauchêne Island is the most isolated of the Falkland Islands archipelago and until the authors' visit there in 1980 little was known or published about the island and its biota apart from its avifauna. The first collections and identifications of various plant and invertebrate groups were made and a brief account of their ecology and interrelationships is given; many of the arthropods are first records for the Falkland Islands and some are new to science. More detailed information is presented for tussock grass (or tussac), Poa flabellata , which reaches a height of 3.5 m and covers two-thirds of the island with a unique monospecific grassland. The underlying deep peat, in places reaching 13 m depth, was investigated and radiocarbon dates obtained at various levels through the profile, indicating that the grassland has existed virtually unchanged for 12 500 years. The status of the avifauna was assessed. The black browed albatross and rockhopper penguin colonies were counted reasonably accurately and calculated to contain up to 170000 and 300000 pairs, respectively. A population of about 250 striated caracaras was counted, together with 67 nests, possibly the largest concentration of these rare raptors anywhere. The recently discovered population of fairy prions was estimated at several thousand birds. Sea lions were not abundant and fur seals, once said to occur in large numbers on the island, were absent. The biological simplicity of the exceptionally uniform tussac ecosystem offers ideal conditions for testing ecological hypotheses, especially those related to trophodynamics and predator-prey interrelationships, and its potential for research is emphasized. The importance of applying strict conservation measures to protect this unique island is stressed in view of the possible future economic development of the Falkland Islands.