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Biomedical subjects

J McCormack

Publications and source records attributed to J McCormack.

At least 181 records · Page 10Linked to original sources

Prenatal diagnosis of severe osteogenesis imperfecta.

The ultrasound findings in a series of 15 prenatally diagnosed cases of severe osteogenesis imperfecta types IIA, IIB, IIC, and III are described, eleven being detected on routine scans of women with no relevant history. As most cases of osteogenesis imperfecta type IIA are dominant sporadic mutations, the importance of prenatal diagnosis during routine scanning at a local level is emphasized. In addition to characteristic broad, shortened and fractured long bones, striking features of the chest and head are highlighted which may be encountered during a routine scan, prompting further assessment.

Female↗

Comparative audit of booking and mid-trimester ultrasound scans in the prenatal diagnosis of congenital anomalies.

During 1988 and 1989, 3565 women booked under consultants who performed an ultrasound scan at booking, whilst 4984 booked under consultants who performed a formal mid-trimester scan between 16 and 18 weeks. All significant anomalies diagnosed prenatally and in the neonatal period were recorded, the incidence in each group being 12.9/1000 and 9.83/1000, respectively (NS). The sensitivity of diagnosis before 20 weeks was 45 percent in the 'mid-trimester' group (kappa 0.62) compared with 30 percent in the 'booking' group (kappa 0.46), overall sensitivity of prenatal diagnosis, however, being similar in both groups (63 vs. 65 percent, kappa 0.77 vs. 0.79). Cardiac anomalies were the single largest group which were not detected equally prenatally in both groups. This study shows that formal mid-trimester scanning leads to anomalies being detected significantly earlier in the antenatal period. Although not statistically significant, three lethal anomalies were missed prenatally in the 'booking' group which we would have expected to diagnose on a mid-trimester scan. These figures are discussed in the light of previous reports.

Congenital Abnormalities↗

Presentation of antigen, foreign major histocompatibility complex proteins and self by thymus cortical epithelium.

In mouse and man most peripheral T cells bear clonally variable receptors made up of alpha- and beta-chains which bind ligands on target cells consisting of peptide fragments of foreign antigens, complexed with cell surface proteins encoded by the major histocompatibility complex (MHC) of the individual. In the thymus, developing T cells are selected to mature only if their receptors will be able to participate in self-MHC plus antigen recognition in the periphery. This positive selection occurs in the presence of self-MHC, but in the apparent absence of antigen, leading to the paradoxical conclusion that developing thymocytes must be positively selected by engagement of their receptors and self-MHC alone, although thymocytes that react too well with self-MHC are eliminated. To account for this, it has been suggested that MHC molecules in the thymus are not identical to those found elsewhere. To test this and other hypotheses, we have examined the ability of the presumed selecting cells, those of the thymus cortical epithelium, to present various MHC complexes to T cells. Our results indicate that MHC molecules on thymus epithelium are not always the same as those found elsewhere.

Animals↗

Comparisons of the electrophysiological effects of intravenous sotalol and propranolol on the immature mammalian heart.

Sotalol is a beta blocker that has also been reported to exert class III antiarrhythmic effects. To evaluate the effects of sotalol on the immature heart, and specifically to assess the relative importance of its class III action, the electrophysiologic effects of incremental doses of intravenous dl-sotalol (cumulative dose of 8 mg/kg) were studied in 11 intact canines (ages 4-15 days) utilizing intracardiac programmed stimulation and electrogram recording techniques. These results were compared to the electrophysiologic effects obtained in an additional 14 neonatal canines given 0.6 mg/kg of the beta blocker propranolol intravenously. Sotalol caused a greater increase than propranolol in the resting sinus cycle length (45 vs. 4%). Importantly, sotalol resulted in greater increases in atrial and ventricular muscle refractoriness than did propranolol (AERP--77 vs. 4%, AFRP--57 vs. 6%; VERP--53 vs. 4%, VFRP--51 vs. 7%). Thus, the electrophysiologic effects of sotalol include large changes in myocardial refractoriness that are not observed with simple beta blockade induced by propranolol. These results suggest that sotalol exerts a significant class III effect in the immature mammalian heart, and thus may be useful as an antiarrhythmic agent in the neonate.

Analysis of Variance↗

The non-catecholamine-mediated electrophysiological effects of intravenous bethanidine sulfate on the immature mammalian heart.

In a preliminary study, we found that bethanidine sulfate had important electrophysiologic effects on the neonatal canine heart, specifically that bethanidine increased atrial effective and functional refractory periods. Other effects (increase in heart rate blood pressure and enhanced atrioventricular conduction) were thought to be due to a release of endogenous catecholamines. To investigate the non-catecholamine-mediated effects of bethanidine, we administered 10 mg/kg i.v. bethanidine to eight neonatal puppies ages 6-14 days pretreated with 0.6 mg/kg of propranolol and compared them with a control group of six neonates that received propranolol followed by a placebo. In the bethanidine group, the mean atrial effective and functional refractory periods increased significantly from 58 to 109 ms and from 108 to 185 ms, respectively (p less than 0.0001). Bethanidine also caused a decrease in resting heart rate (from 154 beats/min postpropranolol to 144 beats/min postbethanidine, p less than 0.002). These effects were not observed in the placebo group. Wenckebach periodicity during incremental atrial pacing did not change significantly. There was a modest increase in the ventricular refractory periods following bethanidine. Thus, the direct electrophysiologic effects of bethanidine in the neonate include a significant prolongation of atrial refractoriness and a decrease in sinus node automaticity. Ventricular refractory periods, while increased, did not show the dramatic prolongation exhibited by the atrium. The atrial specificity of bethanidine is unique and may prove useful in the treatment of supraventricular arrhythmias in the neonatal period.

Animals↗

Atrioventricular nodal function in the immature canine heart [corrected and republished article orginally printed in Pediatr Res 1987 Nov;22(5):616-20].

Previous studies have suggested that the atrioventricular nodal functional refractory period in the neonate is equal to or shorter than that of the ventricle, providing little or no protection to the ventricle against rapid atrial rates and allowing closely coupled atrial beats to fall within the ventricular vulnerable period. We evaluated atrioventricular node function in 21 mongrel neonatal puppies, 3-15 days old, and 15 adult dogs utilizing intracardiac His bundle recording and stimulation techniques. The mean atrioventricular nodal functional refractory period (173.1 +/- 20.0 ms) exceeded both the ventricular effective refractory period (139.5 +/- 14.3) and ventricular functional refractory period (163.3 +/- 14.5) in the neonates. Furthermore, the atrioventricular node was the site of limiting antegrade conduction in all neonates. No ventricular arrhythmias were induced by atrial extrastimulation in any of the neonates. The site of conduction delay during atrial extrastimulation was confined to the atrioventricular node in 15/16 neonates (94%) while 1/16 (6%) had combined nodal and infranodal delay. The neonates developed Wenckebach, at significantly faster heart rates than the adults, but both groups developed Wenckebach at approximately twice the resting heart rate. Retrograde conduction was a consistent finding in the neonates. However, antegrade Wenckebach occurred at a significantly faster heart rate than retrograde Wenckebach suggesting different functional properties. Our data suggest that in the neonatal canine, the atrioventricular node functional refractory period is longer than both the ventricular effective refractory period and ventricular functional refractory period. Furthermore, the degree of protection offered by the neonatal atrioventricular node to the ventricle appears to be comparable to that of the adult.

Animals↗

In vivo demonstration of maturational changes of the chronotropic response to alpha-adrenergic stimulation.

In vitro studies suggest that neonates and adults may have different cardiac chronotropic responses to alpha-adrenergic stimulation. To investigate these differences in vivo, three groups of dogs were studied. Group I = 12 puppies, ages 3-7 days; group II = 12 puppies ages 8-15 days, and group III = seven adult dogs. Heart rate and blood pressure determinations were made in the control setting and then after combined beta-adrenergic and parasympathetic blockade (propranolol 0.6 mg/kg and bilateral vagotomies). Alpha-stimulation was then achieved with phenylephrine given in doses of 0.5, 1.0, and 10.0 micrograms/kg/min. A second, high dose of propranolol (1.0 mg/kg intravenously) was administered after the highest phenylephrine infusion dosage to assure complete beta-blockade. Finally, alpha-blockade was achieved with phentolamine (groups I and II: 0.5 mg intravenously; group III: 5.0 mg intravenously). An alpha-mediated positive chronotropic effect was observed in 42 and 100% of subjects in groups I and II, respectively, but never observed in the adults. Whereas alpha-blockade with phentolamine resulted in a large decrease in heart rate of all puppies (groups I and II), it had no effect on adults. Blood pressure responses were similar in all three groups. Thus, there are important maturational changes in the chronotropic response to alpha-adrenergic stimulation and blockade demonstrable in the intact neonatal canine.

Aging↗

The electrophysiologic effects of propafenone hydrochloride in the neonatal canine.

The electrophysiologic effects of the new antiarrhythmic agent, propafenone, were investigated in 10 mongrel canine neonates, ages 5 to 11 days. Utilizing standard His bundle recording and stimulation techniques, assessments of sinus and atrioventricular (AV) node function and atrial, AV nodal, and ventricular refractory periods were performed prior to (control) and after cumulative intravenous doses of 1, 2, and 4 mg/kg of propafenone. Propafenone depressed the spontaneous heart rate and prolonged the postatrial pacing recovery times. AV nodal function was depressed as manifested by Wenckebach periodicity occurring at slower pacing rates, increases in AV nodal conduction time, and increases in AV nodal refractoriness. Atrial and ventricular refractory periods were prolonged significantly in a dose-dependent fashion. Prolongation of the His-Purkinje conduction time occurred at the highest dose. Thus, propafenone exerts a generalized depressant effect on neonatal myocardial conduction and refractoriness which suggests that this agent may be useful in the therapy of atrial and ventricular dysrhythmias in the immature heart.

Animals↗

Atrial vulnerability in the immature canine heart.

The induction of repetitive atrial responses during atrial extrastimulation (atrial vulnerability) was studied in 3 groups of dogs. Group I consisted of 19 neonatal puppies (age 3 to 15 days), group II of 10 older puppies (age 5 to 11 weeks) and group III of 10 adult dogs. In all dogs, atrial extrastimulation was performed coupled to a constant paced rhythm that was 85 +/- 7% of the sinus cycle length at rest in group I, 86 +/- 6% in group II and 83 +/- 10% in group III. In all groups, atrial repetitive responses were observed as the atrial functional refractory periods were approached during extrastimulation; however, the number of repetitive atrial responses was greater and the duration of repetitive firing longer in the neonates. In the neonatal group as many as 28 repetitive atrial responses were induced (9.4 +/- 8.2 beats) and the duration of repetitive atrial firing averaged 838 ms (range 120 to 2,425). In contrast, in only 1 of 20 older puppies and adult dogs were more than 2 repetitive atrial beats observed (number of repetitive atrial beats in group II, 1.7 +/- 1; in group III, 1.2 +/- 0.5). Thus, the normal neonatal atrium is more susceptible to intraatrial reentry in response to premature extrastimulation than the more mature canine atrium. This enhanced atrial vulnerability may be related to the shorter atrial refractory periods of the neonate and may be of importance in understanding the genesis of certain dysrhythmias in the human neonate.

Aging↗

Thallium poisoning in group assassination attempt.

The use of thallium in an attempted assassination of four members of a political organization is described. The intended victims first complained of abdominal pain within two days of eating a snack prepared by their host; painful peripheral neuropathy occurred within one week and loss of hair within three weeks. Swelling of the optic disk was observed in one patient. The diagnosis was made on clinical grounds and confirmed by the detection of high levels of thallium in serum, urine, and hair and/or nail samples. All patients recovered completely. The possibility of thallium poisoning should be considered in patients who present with acute onset of gastrointestinal symptoms, pain and paresthesias in the legs, and hair loss, so that appropriate treatment can be initiated at an early stage.

Adult↗

Glycosylation and secretion of an altered immunoglobulin heavy chain in mouse myeloma MOPC 315.

A variant line (LV-1) of mouse myeloma MOPC 315 (IgA, lambda 2) has lost the ability to synthesize L chain. It synthesizes an altered H chain (H' chain) that is turned over intracellularly and is not secreted. Rescue of H' chain secretion can be accomplished by fusion of LV-1 to a variant of another myeloma line, MPC 11 (IgG2b, kappa), which only synthesizes a light chain. The hybrid (X-2) secretes the H' chain in a four chain structure (kappa 2 alpha' 2). In wild-type MOPC 315 cells, it was reported previously that inhibition of core sugar addition blocks the secretion of the H chain polypeptide. We have studied glycosylation in MPOC 315 wild-type, LV-1 variant, and X-2 hybrid cell lines. The ability of all three lines to add the core sugars mannose and glucosamine to heavy chain was demonstrated. Due to the instability of the H' chain in LV-1, it is difficult to assess H' chain fucosylation directly. To study fucose addition in LV-1, the enveloped virus vesicular stomatitis (VSV), which can infect the three lines, was utilized. The fucosylation and secretion of VSV glycoprotein G was discernible in all three lines; however, only LV-1 cannot activate free fucose, and instead fucosylates through conversion of the mannose intermediate. Normal fucose addition to H chain in a wild-type cell occurred immediately before secretion. The fact that degradation of H' chain in LV-1 begins before fucosylation suggests that the rescue of H' chain secretion by formation of the X-2 hybrid is due to the acquired presence of a suitable L chain rather than complementation of a sugar defect. These observations indicate that proper assembly of the polypeptide components of some secretory proteins, e.g., Ig molecules, is required for the secretion of the individual chains.

Animals↗