Alloantibodies against low-frequency human platelet antigens do not account for a significant proportion of cases of fetomaternal alloimmune thrombocytopenia: evidence from 1054 cases

BACKGROUND: Maternal alloantibodies against the five common human platelet antigen (HPA) systems (HPA-1 to -3, -5, and -15) are found in only 20% of cases referred for fetal and neonatal thrombocytopenia (FMAIT) investigations. The question asked was whether mismatches for the remaining 11 low-frequency HPAs (HPA-4 and -6bw to -17bw) might in part explain the remaining 80% of cases.
STUDY DESIGN AND METHODS: A total of 1054 paternal DNA samples from referred FMAIT cases (among which 223 cases where antibodies against a common HPA were found) were genotyped for 11 low-frequency HPAs as well as a recently discovered polymorphism ( ITGA2B -C2320T). The initial genotyping was carried out by TaqMan and potential heterozygotes were confirmed by DNA sequencing. Clinical and serologic data were collected for each case with a heterozygote father.
RESULTS: In total, eight heterozygous fathers were identified: four for HPA-6w, one each for HPA-10w and -11w, and two for HPA-12w. Maternal antibodies against the corresponding antigen were identified in four of the eight cases. In two of these cases, antibodies against HPA-1a and HPA-1b were also found.
CONCLUSION: It was concluded that the minor alleles of HPA-4 and -6bw to -17bw are exceptionally rare in the Caucasian population and therefore do not explain the large number of FMAIT referrals which test negative for the common HPA antibodies.     

Development of innovative teaching materials: clinical pharmacology problem-solving (CPPS) units: comparison with patient-oriented problem-solving units and problem-based learning--a 10-year review

The First Teaching Clinic in Clinical Pharmacology, sponsored by the American College of Clinical Pharmacology in September 1992, was designed for the preparation and development of new clinical pharmacology problem-solving (CPPS) units. CPPS units are case histories that illustrate pertinent principles in clinical pharmacology. Each unit consists of the following sections: introduction, learning objectives, pretest, four clinical pharmacology scenarios, posttest, answers to pre- and posttest questions, and selected references. The clinical pharmacology content of the CPPS units place greater emphasis on clinical information, drug selection, and risk/benefit analyses, and thus they complement the basic pharmacology presented in the patient-oriented problem-solving (POPS) units. In general, the CPPS units are intended for use by students more advanced in clinical pharmacology than first- and second-year medical students. The CPPS unit "Clinical Pharmacology of Antiepileptic Drug Use: Clinical Pearls about the Perils of Patty" was developed for use by third- and fourth-year medical students doing rotations in neurology or clinical pharmacology; advanced pharmacy students; residents in neurology, pediatrics, internal medicine, and family practice; fellows in clinical pharmacology, and those taking the board examination in clinical pharmacology. The CPPS unit titled "Geriatric Clinical Psychopharmacology" was written for third- and fourth-year medical students; residents in psychiatry, family practice, and internal medicine;fellows in clinical pharmacology; and those studying for boards in clinical pharmacology. The CPPS unit "Anisocoria and Glaucoma" was written for more advanced students of clinical pharmacology. The CPPS unit titled "Antiepileptic Drugs" was intended for second-year medical students. The second teaching clinic was held in November 1993 and focused on the development and editing of the CPPS units and their evaluations by faculty and students from academic centers. Evaluations by faculty and students have been overwhelmingly positive. Requests to use the CPPS units in various clinical pharmacology teaching programs were received from numerous schools within the United States and from abroad. The third teaching clinic in September 1995 included a follow-up focused on the uses of drug information databases in case problem exercises. These examples are presented to demonstrate the variety of educational activities the American College of Clinical Pharmacology is sponsoring to fulfill its strategic initiative dedicated to offer innovative teaching programs and to develop new teaching materials in clinical pharmacology. Collectively, all of the teaching clinics, symposia, and workshop efforts, sponsored by the various academic professional societies alone or together over the past decade, are necessary if new and innovative teaching materials in the field of basic science and in the fields of pharmacology and clinical pharmacology are to be continuously developed to keep pace with the new, rapidly changing developments in medicine to provide the best treatment for patients in the 21st century.     

Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures

Summary: Purpose: To evaluate the safety and efficacy of intravenous valproate (VPA) loading in children with status epilepticus (SE) or acute repetitive seizures. Methods: Retrospective review was performed on 40 pediatric patients with intravenous VPA loading. Patients were classified into two groups: SE (n = 18) and acute repetitive seizures (n = 22). Thirty‐one patients were VPA naïve and received a full loading dose of 25 mg/kg; nine had subtherapeutic plasma VPA levels and received a partial loading dose. Average infusion rate was 2.8 mg/kg/min. Heart rate and blood pressure were measured before, during, and after infusion. Results: Intravenous VPA loading stopped seizures in 18 patients with SE within 20 min. All 18 patients regained baseline mental status within 1 h of seizure cessation. Among 22 patients with acute repetitive seizures, only one had further seizures after VPA infusion. One patient in the SE group complained of transient tremors. No significant changes in blood pressure or heart rate were found in either group. Postinfusion plasma VPA levels ranged from 51 to 138 μg/ml (mean ± SD = 88 ± 21.5 μg/ml). Conclusions: Intravenous VPA loading is safe and effective for treating acute seizure emergencies in children.     

Toxoplasmic myositis as a presenting manifestation of idiopathic CD4 lymphocytopenia

Toxoplasma gondii encysts in skeletal muscle. Although only rarely found at muscle biopsy, this parasite has previously been regarded as a possible cause of polymyositis. We report a case of biopsy-proven toxoplasmic myositis in a non-HIV-infected patient that led to recognition of idiopathic CD4 lymphocytopenia (ICL), a rare condition typically associated with opportunistic infections. Interestingly, the CD25(+) subset that corresponds to the CD4(+) regulatory T cells controlling autoimmune processes was lacking. Steroid and antiprotozoal therapy led to recovery.     

On the development of CNS lesions in natural canine distemper encephalomyelitis

Acute lesions within spinal cord white matter have been studied by light and electron microscopy in 3 dogs suffering from the acute form of canine distemper encephalomyelitis (CDE). Prominent features of these lesions were viral inclusions, giant cell formation, cellular degeneration, myelin breakdown and phagocytic activity by cells believed to be derived from local glia. The viral inclusions occurred in giant cells, many astrocytes, macrophages and occasional oligodendroglia. Only suggestions of active viral replication from cell membranes were present. On the basis of the above features, these CDE lesions were classed as being acute. Perivascular inflammation and parenchymal invasion by haematogenous cells were lacking. However, older, gliotic, demyelinated lesions were always associated with inflammation. The pattern of demyelination in acute CDE lesions differed from those seen in other conditions, in particular the autoimmune demyelinating diseases. In acute CDE lesions, individual fibres became separated from others by rings of cells, the processes of which systematically stripped the myelin from the outer layers of the sheath inwards until a naked segment of axon remained. Some of the macrophages were recognisable as astroglia. Elsewhere, unequivocal astrocytes containing myelin debris were common. The results suggest that inflammation in acute CDE lesions is not a primary event, and that viral invasion causes breakdown of tissue which is accompanied pari passu by myelin destruction. The latter might be related to the non-specific release of host factors (viz. hydrolytic enzymes) or humoral factors during the cellular degeneration. Local cells appeared to participate in the process of myelin phagocytosis. Overt inflammation and damage by haematogenous cells were features only of chronic lesions and have been described previously in studies on chronic CDE lesions. The results are interpreted in terms of their relevance to the study of human subacute sclerosing panencephalitis, of which CDE is considered the animal analogue, and multiple sclerosis, the paradigm of the human demyelinating diseases.     

Observations on the pharmacology of cholinoceptive neurones in the rat brain stem.

The pharmacology of spontaneously active cholinoceptive neurones in the brain stem of rats anaesthetized with urethane has been investigated using microiontophoresis to administer muscarinic and nicotinic agonists and antagonists. 2. Acetylcholine (ACh) excited most cells but occasionally depressed their activity. Muscarine, and the muscarinic agonists methacholine and bethanechol produced prolonged excitation or inhibition of cells whereas nicotine produced prolonged excitations but no inhibitions. 3 Atropine selectively antagonized ACh excitations and both excitation and inhibition of neuronal activity produced by muscarine and muscarinic agonists, but not the excitations produced by nicotine, glutamate or DL-homocysteic acid. 4 Dihydro-beta-erythroidine (DHBE) and tubocurarine antagonized both ACh and nicotine excitations but not those induced by glutamate or DL-homocysteic acid. Inhibitions by ACh or muscarine were not affected. 5 It is concluded that excitations of cholinoceptive neurones in the rat brain stem may be mediated by activation of both muscarinic and nicotinic receptors whereas inhibitions are mediated by activation of a muscarinic receptor.