Pyrogenic reactions in patients undergoing cardiac catheterization associated with contaminated glass medicine cups.

Pyrogenic reactions are potentially life-threatening complications caused by bacterial endotoxin. After two cardiac catheterization patients developed rigors the same day, the procedures were halted and a case control study was conducted. To identify case patients (persons with rigors < or = 3 hr after catheterization during September 25-November 9, 1995), we reviewed medical records of all cardiac catheterization patients who had a blood culture or received intravenous meperidine. Twelve case patients and 40 randomly selected control patients were identified. No specific catheter was associated with case patients, but exposure to intracoronary-nitroglycerin (NTG) was (odds ratio = 12.0; 95% confidence interval 2.2, 75.6). NTG or indocyanine green dye was poured into glass medicine cups previously washed in an enzyme cleaner and then sterilized. The cleaner, used for an entire day, had elevated levels of gram-negative bacteria (> 10(4) colony forming units/mL) and endotoxin (434 endotoxin units [EU]/mL]); the reprocessed cups had no live bacteria but had elevated endotoxin levels (median 2,250 EU). Exposure to contaminated glass medicine cups probably resulted in pyrogenic reactions and contributed to death in two critically ill patients.

Update on counseling the family with a first-degree relative with a congenital heart defect.

Updated recurrence risks figures are presented for genetic counseling of families with a congenital heart defect (CHD) in a first-degree relative. Substantial changes are recommended for counseling the family in which a parent has CHD. The risk is much greater if it is the mother rather than the father who has the heart defect. The updated figures for recurrence risks in sibs have been revised, but are not greatly changed. Our central tenet in counseling is to base risk projections on the genetic and teratogenic history in the individual family and pregnancy.

Maternal transmission of congenital heart diseases: new recurrence risk figures and the questions of cytoplasmic inheritance and vulnerability to teratogens.

A review of 8 studies involving 3,996 offspring of parents who have congenital heart disease revealed that the risk for all defects was substantially higher if the affected parent was the mother rather than the father. The risk ratio ranged from a high of 6.39 for aortic stenosis to a low of 1.48 for patent ductus arteriosus, and the ratio was statistically significant in aortic stenosis (p = 0.025) and ventricular septal defect (p less than 0.001). Despite the relatively large number of cases, there were still too few patients to reveal statistical significance for a malformation such as atrioventricular canal, in which there were 5 affected offspring among 36 children of mothers who had atrioventricular canal and no affected children among 16 offspring of affected fathers (p = 0.12). The possible reasons for the preponderance of affected offspring of mothers with a congenital heart disease was studied in the context of various modes of inheritance and maternal physiology. The preliminary conclusion is that although many familial cases of congenital heart disease are compatible with multifactorial inheritance and vulnerability to teratogens, an important subset of cases, particularly in some high-risk families, may be better explained by cytoplasmic inheritance than by multifactorial or mendelian modes. Current genetic counseling should take into account the differences in risk to offspring of affected mothers while confirmation and further investigation proceeds.

Clinical studies in a kindred with a kinetic LDL receptor mutation causing familial hypercholesterolemia.

We have studied a family carrying a variant of the class 2 mutation of familial hypercholesterolemia (FH) in which there is unusual longevity and in which obligate heterozygotes did not express constant or statistically significant hypercholesterolemia. The heterozygotes have the same kinetic defect in the processing of low density lipoprotein (LDL) receptors in their fibroblasts and the reduced fractional catabolic rate for apoLDL that is characteristic of other patients with heterozygous FH. However, their plasma lipid and lipoprotein levels are not as strikingly abnormal because they have normal or near normal rates of apoLDL synthesis.

Familial hypercholesterolemia with "normal" cholesterol in obligate heterozygotes.

We have investigated the family of a 15-year-old proposita with a homozygous, receptor-defective, familial hypercholesterolemia and found that her consanguineous, obligate heterozygous parents have "normal" cholesterol levels and a family history of unusual longevity. Documentation of paternity and the presence of the heterozygous biochemical disorder in the parents is firm. The implications are that, at least in this family, relatively low serum cholesterol and high levels of HDL cholesterol are protective against the risks associated with having a mutant allele for heterozygous familial hypercholesterolemia.

Exogenous sex hormones and birth defects: continuing the dialogue.

PIP: Physicians are placed in a difficult situation regarding the use of drugs, specifically exogenous sex hormones, during pregnancy. Equal numbers of studies have been conducted to both support and refute claims of teratogenic effects. The use of low level teratogens during pregnancy, which may cause malformations in only 1-2% of those exposed, poses an unacceptable and unnecessary burden on the individual and on society. Sufficient animal data exists to suggest a causal link between sex hormones and malformations in animal models. Epidemiological studies that fail to find a significant association between sex hormones and birth defects use inappropriate methodology which fails to associate time of exposure to the hormone with the vulnerable period of embryogenesis for the defect in question. The requirement must include cases with malformations to establish that the putative causal exposure occurred at the vulnerable period for production of the defect and exclude cases not resulting in malformations if the hormone exposure occurred outside the vulnerable period. Studies which use the 1st trimester as the vulnerable period when the 1st month is appropriate are subject to a 67% mismodeling bias. The need for precision in design is emphasized. The extent of the presence of sex hormone receptors is of additional concern. Sex hormone receptors may be present in almost all tissues, including the liver and hypothalamus. The potential of a widespread effect of sex hormone influence derived through these axes is obvious. Also the adverse effects of many drugs may not be derived from the drugs themselves but from their metabolites, as with thalidomide. The concerns raised by studies that have shown a strong positive correlation between hormone use and birth defects emphasize the judicious use of indicated hormonal therapy.^ieng

Genetic--epidemiologic study of early-onset ischemic heart disease.

A genetic-epidemiologic study was undertaken of a white Colorado population of 207 patients who had a myocardial infarction before age 55 years. Nineteen independent variables were compared between the 207 cases and 621 controls, matched 3:1. The highest risk ratios were associated with a positive family history for ischemic heart disease (IHD). The heritability of IHD was 63% when families with the monogenic forms of hyperlipoproteinemia were included, and 56% when they were excluded. A risk index was developed that incorporates family history into a data base of risk factors, which can be readily assessed by the clinician obtaining a screening history, physical and standard laboratory tests. A scale of 0-10 was devised and the predictive value of the index was tested against another data set. The efficiency of the index was maximal at a screening level of 5. This study suggests that it is logistically feasible to seek patients at high risk for intensive management in a clinical setting (high-risk strategy) using risk indices similar to the one developed for this study, which emphasize the very important familial component to IHD.

Exogenous progestogen and estrogen implicated in birth defects.

A five-year study of possible teratogenicity of exogenous female sex hormones included three case-control studies and one cohort study. The first case-control study disclosed an estimated relative risk of 8.41 and a highly significant difference in maternal hormonal exposure (P less than .001) between controls and infants with three major anomalies of the VACTERL group (V, vertebral; A, anal; C, cardiac; T, tracheal; E, esophageal; R, renal; and L,limb). Relative risk (RR) estimates of 5.58 (P = .017) and 3.35 (P less than .001) were found in two case-control studies involving maternal hormonal exposure and patients with congenital heart lesions without other malformations. A controlled, single-blind prospective study disclosed an excess of patients with major malformations (RR = 2.75), congenital heart anomalies (RR = 6), and neurological and neural tube disorders preponderant in the presence of a precipitously declining exposure rate during a three-year period in our referral area.

The silent ductus arteriosus.

Preterm infants at risk of developing a patent ductus arteriosus were followed sequentially by physical examination, echocardiographic determinations of the LA/AO ratio, and chest roentgenograms. The results show that a significant number of infants who have no clinical signs or symptoms of a PDA have large left-to-right shunts. The presence of this shunt was suggested by acute increase in left atrial size by ECHO determination and confirmed by retrograde single-film aortography. Clinical signs and symptoms often developed several days after documentation of the left-to-right shunt.