Scalp and limb defects with cutis marmorata telangiectatica congenita: Adams-Oliver syndrome?

We report on a boy with congenital scalp and limb defects, consistent with a diagnosis of Adams-Oliver syndrome (aplasia cutis congenita with terminal transverse limb defects). An additional finding present in this child and in his mother was cutis marmorata telangiectatica congenita. Although this boy fits the diagnostic criteria for Adams-Oliver syndrome, his mother does not. We discuss whether this condition is highly variable, or heterogeneous.

X-linked syndrome of branchial arch and other defects.

We report on two brothers and their maternal first cousin who have branchial arch defects and other anomalies. Similar physical findings in all three include microcephaly, downslanting palpebral fissures, highly arched palate, apparently lowset, protruding ears, bilateral hearing loss, slightly webbed neck, and mild short stature. In addition, two boys had cryptorchidism, and one had subvalvar pulmonic stenosis and body asymmetry. We suggest that these cousins have an X-linked syndrome of which branchial arch defects are a component. Other pleiotropic manifestations of the mutant gene include microcephaly and cryptorchidism; body asymmetry and relatively short stature may be components as well.

Successful term delivery after previous pregnancy with ruptured liver.

Liver rupture is an uncommon but serious complication of pregnancy. Preeclampsia is commonly an antecedent factor. Diagnosis is typically made late in the course of events and both mother and infant die. A case of a patient with liver rupture and fetal death is presented. She later had a successful subsequent pregnancy delivered at term. This is the second case reported of a term delivery after previous liver rupture.

Liquid chromatographic analysis of ethacrynic acid and degradation products in pharmaceutical systems.

An accurate, reproducible, and specific reversed-phase high-performance liquid chromatographic (HPLC) system was developed for the determination of ethacrynic acid and its degradation products. The method was used in stability studies of the drug in the solid state, in solution, and in dosage forms. Three degradation products were isolated by preparative chromatography and identified by several techniques, principally NMR and MS. TLC Rt and HPLC response factors are quoted. A degradation scheme consistent with the observed stability profiles is proposed.

An investigation into the use of stepwise isothermal high sensitivity DSC as a means of detecting drug-excipient incompatibility.

The use of stepwise isothermal high sensitivity differential scanning calorimetry (HSDSC) as a novel means of detecting excipient incompatibility is described using aspirin mixes with magnesium stearate and stearic acid as model systems. Aspirin, magnesium stearate and stearic acid alone and as mixes were studied in scanning mode using conventional DSC and were then subjected to a stepwise heating programme using HSDSC, whereby the samples were heated to temperatures between 45 and 70 degrees C and held for 1 h, during which the heat flow to or from the sample was measured. The data indicated that while no thermal events were detected for the individual components or mixes with stearic acid other than melting of stearic acid, 50% w/w mixes of magnesium stearate showed a marked endothermic response at temperatures above 55 degrees C. The data were fitted to an adaptation of an existing kinetic model for the degradation process and a reasonable correlation found. Mixes of the drug with the two excipients were then studied at 60 degrees C over 6 h at concentrations between 1 and 50% w/w. Incompatibilities with magnesium stearate concentrations as low as 1% w/w could be detected using this approach. Compacts of magnesium stearate and aspirin were also studied, with considerably more pronounced thermal events taking place compared to the powder mixes. It is concluded from these studies that while the study has highlighted certain limitations of the approach, stepwise isothermal DSC represents a potentially highly useful means of detecting excipient incompatibilities.

The influence of the ammonium ion on the stability of ethacrynic acid in aqueous solution.

Investigations by reversed-phase HPLC into the stability of ethacrynic acid in buffered aqueous solutions containing either sodium or ammonium ions showed that the extent of degradation was influenced both by the species and concentration of the cation. A reported incompatibility between ethacrynic acid and the ammonium ion, attributed to the influence of the ammonium ion on an equilibrium existing between ethacrynic acid and one of its known degradation products, was shown to be due to the generation of an additional degradation product in ammonium-containing solutions only. This product was isolated and identified. Different pathways of degradation were shown to be operative in sodium- and ammonium-containing solutions. The addition of formaldehyde or a formaldehyde scavenger (hydroxyammonium chloride) was found to influence the rate of loss of ethacrynic acid, but the decomposition products provided no evidence for the existence of the reported equilibrium.

Submandibular gland resection and bilateral parotid duct ligation as a management for chronic drooling in cerebral palsy.

The control of chronic drooling in cerebral palsy has been difficult in the past. Previous methods to control drooling include the Wilkie procedure, which diverts the salivary flow from the parotid glands by means of surgically created tunnels to the tonsillar fossa, along with submandibular gland resection. An alternative is submandibular gland resection with bilateral parotid duct ligation. Previous published studies using this method have resulted in good to excellent results, but population sizes were felt to be too small to be conclusive. Since 1979, a total of 58 patients have been treated by parotid duct ligation with submandibular gland resection, and 86 percent have shown good to excellent results. These results compare favorably with those published by Wilkie. Also, parotid duct ligation is technically easier, associated with less postoperative morbidity, and has shown a decreased duration of hospitalization compared to parotid duct transposition.

The effect of low-energy laser on skin-flap survival in the rat and porcine animal models.

Low-energy lasers are currently being used in the therapy of rheumatoid arthritis, chronic pain, muscle strain, and the promotion of wound healing in human and veterinary medicine. This study examined the effects of low-energy laser on skin-flap survival in a controlled interspecies study using the rat and porcine models. Twenty dorsal skin flaps based caudally were performed in 20 rats (10 laser-treated and 10 control flaps). The wounds were closed, and the flaps were sutured over the skin. Forty dorsal pig skin flaps based medially were raised in five pigs. The flaps were treated once per day for 10 days: 4 days preoperatively, the day of surgery, and 5 days postoperatively (30 s/cm3 per day). The average surviving rat flap surface area for the laser-treated flaps was 653 +/- 112 mm (mean +/- SD) and 580 +/- 60 mm in the control flaps, which was not significant (p greater than 0.05). In the porcine model, the average surviving area for the 20 laser-treated flaps was 949 +/- 174 mm, and the control average (n = 20) was 969 +/- 147 mm, also not significant. No beneficial effect was seen with low-energy laser preoperative and postoperative treatment of skin flaps in the rat and porcine models.

Amylase polymorphism: studies of sera and duodenal aspirates in normal individuals and in cystic fibrosis.

Prior genetic studies of the human pancreatic amylase (Amy2) locus have been directed principally to the electrophoretic analysis of serum and urine, on the assumption that these fluids receive negligible contributions from the salivary (Amy 1) locus. In support of that assumption was the observation that the isozyme bands were lacking in patients with cystic fibrosis and in a postpancreatectomy patient. We have examined the sera of 97 patients having cystic fibrosis and find normal levels of serum amylase. On electrophoresis, three-quarters of the cystic fibrosis patients have a pattern (F-pattern) not observed in normal sera. The pattern is characterized by the absence of Pa 1. Comparative electrophoresis and mixing experiments indicate that the F-pattern is of salivary origin and is unmasked in cystic fibrosis by the absence of a pancreatic contribution. The normal serum pattern is considered to be an admixture of salivary and pancreatic amylase. On the assumption that duodenal fluids might more closely reflect the pancreatic (Amy 2) locus, electrophoretic studies were performed on 148 normal individuals and 37 individuals with cystic fibrosis. Electrophoretic phenotypes in duodenal aspirates are more complex than previously reported in studies of urine and serum; presumably because of the higher concentrations of amylase in the aspirates. Comparative electrophoresis and mixing experiments indicate that the phenotypes observed in duodenal aspirates also reflect admixture of pancreatic and salivary amylase. This recognition of pancreatic and salivary admixture in sera fortunately does not alter our prior understanding of the genetics of the Amy 2 polymorphism. The extensive studies which led to the delineation of the Amy 2 polymorphism were essentially based on the presence or absence of a variant band which proves now to be outside the zone of admixture.

Identification of Harper-Cawston factor as thymidine phosphorylase and removal from media of substances interfering with susceptibility testing to sulfonamides and diaminopyrimidines.

Rich media support the growth of bacteria in the presence of concentrations of sulfonamides and diaminopyrimidines that are highly inhibitory when the organisms are grown on minimal media. Many such rich media can be made more suitable for susceptibility testing by the incorporation of lysed horse blood. Harper and Cawston characterized the active substance, Harper-Cawston factor (HCF), and later studies indicated it to be a protein. It has now been identified as thymidine phosphorylase. The identification follows from the identical purification pattern of HCF and thymidine phosphorylase activities from horse blood to a high degree of purity. Blood of goats, sheep, oxen, geese, chickens, cows, dogs, rats, and humans had neither biological activity. The identification of HCF as thymidine phosphorylase is consistent with the earlier findings of Koch and Burchall (1971) that most of the interfering effects of rich media could be accounted for by their thymidine contents, and that thymidine is much more active in this respect than is thymine.

Bilateral striopallidodentate calcinosis: cerebrospinal fluid, imaging, and electrophysiological studies.

We report the genetic, clinical, electrophysiological, and imaging studies in a family with bilateral striopallidodentate calcinosis (Fahr's disease). The intracerebral calcium deposits occurred before onset of the symptoms in the third decade of life. Progressive neurological deterioration occurred in the fifth decade of life in the proband. Cerebrospinal fluid homocarnosine, a central nervous system-specific peptide, was increased twofold in patients with autosomal dominant bilateral stripallidodentate calcinosis; in sporadic cases, there was no detectable homocarnosine and a decreased level of histidine. With advancing age, the amount of calcification increases, but it has not been determined if a critical amount must be reached before symptoms occur. Computerized tomography is superior to magnetic resonance imaging for radiological diagnosis. Despite diffuse striatal calcification, striatal 6-[18F]fluoro-L-dopa uptake did not reveal any difference between patients and control subjects, from which we infer persisting integrity of the nigrostriatal dopaminergic pathway.

Magnetic resonance imaging of severe frostbite injuries.

Frostbite injury causes damage by direct ice crystal formation at the cellular level with cellular dehydration and microvascular occlusion. Acute treatment is well defined with rapid tissue rewarming. Definitive surgical therapy is usually delayed until a clear level of demarcation is seen. Technium (Tc)-99 bone scanning has become the standard imaging study employed within the first several days to assess tissue perfusion and viability. We present 2 patients with severe frostbite injury in which magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) were compared to Tc-99 bone scans. MRI/MRA appears to be superior to bone scanning by allowing direct visualization of occluded vessels, imaging of surrounding tissues, and by showing a more clear-cut line of demarcation of ischemic tissue. MRI/MRA may also allow early intervention in cases of severe frostbite, thus preventing secondary infection and increased cost.

Characterization of immune effector cells present in early murine decidua.

It has been suggested that murine decidual cells act as an important immunoregulatory population localized to the pregnant uterus. We have examined early murine decidua to determine if immune effector cells occur in the decidual environment in proximity to the conceptus. High levels of natural killer (NK) cell activity were found consistently in decidual cell suspensions with peak activity occurring on Day 6.5 of gestation. NK activity declined as pregnancy proceeded and was not significant by Day 12.5 of gestation. Decidual cell suspensions did not appear to contain significant numbers of functional B or T effector cells. No antipaternal T-cell response could be demonstrated even in the decidua of immune mice. Lack of T-cell responses was attributed to the absence of T cells from decidua rather than to their inactivation because precursors of cytotoxic T lymphocytes (pCTL) could not be detected in decidual cell suspensions. Furthermore, the levels of pCTL detectable in spleen cell suspensions could not be reduced by mixing spleen cells with 7.5-day decidual cells. These results suggest that B cells and T cells may not occur in early decidua while NK cells are present and regulated independently.