Platelet-binding immunoglobulins in pregnancy-induced hypertension I. Platelet-associated IgM on fetal platelets: evidence of a fetal autoimmune reaction?

Pregnancy-induced hypertension (PIH) can be complicated by maternal or fetal thrombocytopenia, or both. In order to investigate possible immunologic causes of these thrombocytopenias, platelet-associated IgG (PAIgG) and IgM (PAIgM) were measured in mothers with PIH and in their infants and compared with those from patients with autoimmune thrombocytopenic purpura (ATP), a known immunodestructive platelet disorder. Many PIH patients (33.3%) and most ATP patients (68.1%) had elevated levels of maternal PAIgG. In both diseases, the amount of PAIgG was directly proportional with the degree of thrombocytopenia (r = 0.446 in PIH and R = 0.668 for ATP). But in neither disease did the degree of maternal thrombocytopenia correlate with the degree of neonatal thrombocytopenia (r = 0.153 for PIH and R = 0.175 for ATP). Umbilical cord samples from PIH patients contained PAIgG (53.3%) and PAIgM (53.8%), whereas the umbilical cord samples from ATP patients had elevated amounts of PAIgG but not PAIgM. PAIgM in the umbilical cord blood could not be accounted for by IgM rheumatoid factors, IgM-containing immune complexes, or non-specific adsorption because of elevated total IgM levels. The umbilical cord blood PAIgM was probably not of maternal origin because it was observed even when the maternal blood contained no PAIgM and maternal IgM is not normally transported transplacentally. Therefore, the PAIgM appears to be of fetal origin. These results suggest that both maternal and fetal immunologic mechanisms may be involved in PIH-induced thrombocytopenia; if so, this is one of the first reported examples of a possible fetal autoimmune response.     

Reversible Quantitative EEG Changes in a Case of Cyclic Vomiting: Evidence for Migraine Equivalent

Medical experts have disputed whether childhood cyclic vomiting is a manifestation of epilepsy or a migraine equivalent. Quantitative EEG provides an objective measure of changes in brain activity during and between episodes. This paper reports reversible changes involving two episodes in a patient whose history included cyclic vomiting and emotional/behavioural problems. Abnormal delta activity seen during both episodes resolved at follow-up, when the patient asymptomatic. The brain wave changes counter the hypothesis that vomiting in these patients is psychosomatic, and support the interpretation of cyclic vomiting as a migraine equivalent.     

Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.      

Therapeutic considerations in childhood idiopathic thrombocytopenic purpura

This monograph reviews the literature regarding therapy for childhood idiopathic thrombocytopenic purpura (ITP). The role and mechanism of action are discussed for corticosteroids, splenectomy, and intravenous gamma globulin. Alternative therapies with potent immunosuppressive agents are also mentioned. Guidelines for the management of children with ITP are presented.     

Dose-Response Characteristics of Spinal Bupivacaine in Volunteers: Clinical Implications for Ambulatory Anesthesia

Background: Small doses of bupivacaine may be a reasonable choice for spinal anesthesia for patients having ambulatory surgery. However, few dose-response data are available to guide the selection of reasonable doses of bupivacaine for different ambulatory procedures.

Methods: Eight volunteers per group were randomized to receive 3.75, 7.5, or 11.25 mg of 0.75% bupivacaine with 8.25% dextrose in a double-blind manner. Sensory block was assessed with pinprick, transcutaneous electrical stimulation equivalent to surgical incision at the ankle, knee, pubis, and umbilicus, and with duration of tolerance to pneumatic thigh tourniquet. Motor block at the quadriceps and gastrocnemius muscles was assessed with isometric force dynamometry. Times until recovery from spinal anesthesia were recorded. Dose-response relationships were determined by linear regressions. Mean (95% confidence intervals) for durations of sensory and motor block per milligram of bupivacaine administered were calculated from linear regressions.

Results: Significant dose-response relationships (P < 0.006) were determined for sensory block, motor block, and time until recovery (R from 0.6 to 0.9). Within the range of doses studied, each additional milligram of bupivacaine was associated with an increase in duration of tolerance to transcutaneous electrical stimulation of 10 (7 to 13) min, an increase in tolerance to tourniquet of 7 (2 to 11) min, an increase in duration of motor block of 8 (5 to 12) min, and an increase in time until recovery of 21 (17 to 25) min.     

von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.

Variant von Willebrand disease designated as type I New York or type Malmö is characterized by enhanced ristocetin-induced platelet agglutination with normal von Willebrand factor multimeric distribution in plasma. We have studied four such patients belonging to three unrelated families and found in all of them a unique cytosine-to-thymine transition changing the codon for Pro503 (CCG) to Leu (CTG). In three patients the mutant allele also had a silent mutation in the codon for Ser500 (TCG-->TCA). Both nucleotide changes are present in the von Willebrand factor pseudogene; however, the characterization of distinctive markers where the gene and pseudogene differ, as well as the examination of amplified cDNA derived from platelet mRNA, confirmed that the abnormality occurs in the von Willebrand factor gene of the patients. Moreover, recombinant expression of the isolated glycoprotein Ib-binding domain of von Willebrand factor provided direct evidence that the Pro503-->Leu mutation is responsible for enhanced platelet reactivity to lower ristocetin concentrations. These results define a new structural element affecting the affinity of von Willebrand factor for glycoprotein Ib and establish the molecular basis of a variant form of von Willebrand disease.     

Q-tip pap smear: Should it be done routinely in patients who have developmental disabilities?

In some patients with mental retardation, a Q-tip pap smear obtained blindly from the upper vagina may be the only cytologic smear obtainable without subjecting the patient to heavy sedation or to examination under anesthesia. The efficacy of blind Q-tip smears has not been previously determined. Of 31 Q-tip smears obtained from patients with CIN, the Q-tip smear identified the abnormality in 10 (32%) patients. For those patients who will not submit to examination without anesthesia or sedation, routine screening with multiple smears, obtained on an annual basis has the potential to identify many cases of CIN which otherwise would not be identified at all, and in certain patients, this method outweighs the risks of heavy sedation or general anesthesia. Because of the greatly reduced sensitivity of the Q-tip pap, every effort should be made to help the patient and/or her family or guardian to understand the implications and risks of this method. However, if an examination under anesthesia is performed for other indications, a complete gynecologic examination and a direct smear should be obtained at that time.