Do hyporesponsive genetic variants of the melanocortin 1 receptor contribute to the etiology of multiple sclerosis?

Hyporesponsive genetic variants of the melanocortin 1 receptor result in pigmentary phenotypes exhibiting light skin and light color hair, including red hair. These variants are common in populations with high rates of multiple sclerosis, while rare in populations with low rates. Alpha-melanocyte stimulating hormone, the major ligand for this receptor, is responsible for phenotype determination, but is also known for its anti-inflammatory and immune modulating effects, including inhibition of factors implicated in multiple sclerosis pathology. As the melanocortin 1 receptor is expressed on various cell types involved in immune response, it is possible that carriers of hyporesponsive variants of this receptor lack the full anti-inflammatory and immune modulating effects of alpha-melanocyte stimulating hormone. It is proposed that these variants are part of a spectrum of genes involved in the etiology of multiple sclerosis. Related aspects of multiple sclerosis epidemiology are examined.

Symptomatic relief of migraine: multicenter comparison of Cafergot P-B, Cafergot, and placebo.

A multicenter, randomized, double-blind trial was conducted to compare the efficacy of Cafergot P-B with that of its components, Cafergot, pentobarbital, and Bellafoline, and with placebo for the treatment of migraine. Patients with vascular headaches of the migraine type who regularly experienced nervous tension and some form of gastrointestinal distress with their headaches were randomized to one of five treatment groups. They were given treatment packets containing their assigned drug for use during two separate migraine attacks. Patients made pretreatment evaluations of the following symptoms: head pain, nervous tension, nausea, vomiting, anorexia, abdominal cramps, and photophobia. They made posttreatment evaluations of these symptoms 0.5, 1.0, 1.5, 2.0, and 3.0 hours after ingesting their assigned drug. Improvement scores were calculated from the differences between the pretreatment and the posttreatment ratings. Patients also made a final global assessment of their drug's efficacy. All patients who took at least one dose of the study medication and completed a baseline evaluation and at least one postdose evaluation of severity of pain were included in the analysis (n = 254). The comparisons of particular interest were those between Cafergot P-B and Cafergot and between Cafergot P-B and placebo. Cafergot P-B was significantly more effective than Cafergot in relieving head pain at hours 2 and 3, nervous tension, nausea, vomiting, anorexia, and photophobia. Cafergot P-B was significantly more effective than placebo in relieving head pain, nervous tension, nausea (second headache only), vomiting, and photphobia. The incidence of reported adverse effects was no greater with Cafergot P-B than with Cafergot; however, patients given Cafergot P-B reported less vomiting than did patients given Cafergot. The results of this study show that addition of pentobarbital and Bellafoline to Cafergot provides greater relief of pain, vomiting, nervous tension, photophobia, and other symptoms associated with migraine, while reducing the severity of the nausea that may accompany a migraine headache or Cafergot therapy.

Fiorinal with codeine in the treatment of tension headache--the contribution of components to the combination drug.

The contribution of the Fiorinal and codeine phosphate components to the effectiveness of the Fiorinal with Codeine combination in the treatment of tension headache symptoms was evaluated in a randomized, placebo-controlled, multicenter double-blind study. Patients admitted to the trial took two capsules of Fiorinal with Codeine, Fiorinal alone, codeine alone, or placebo during each of two tension headache attacks. Immediately before and at intervals up to four hours after drug ingestion, patients rated pain severity, pain relief, the tense and uptight feeling, and muscle stiffness. The response to treatment was evaluated in 154 patients. Despite a high placebo response, a factor known to obscure the contribution of components, Fiorinal and codeine were each found to contribute significantly to the therapeutic effect of the Fiorinal with Codeine combination. Statistical or borderline superiority of the combination drug over Fiorinal alone was seen most frequently at the early evaluations, a finding that reflected the rapid onset of action of codeine. Statistically significant differences between Fiorinal with Codeine and codeine alone seen principally at the later assessments reflected the long duration of action of the Fiorinal component. The frequency of adverse reactions did not differ significantly among the four study groups.

Fiorinal with Codeine in the management of tension headache: impact of placebo response.

The well-known difficulty in distinguishing the response to a combination headache medication and its individual components in the presence of a high placebo response was again demonstrated in a randomized, double-blind, placebo-controlled, multi-center trial comparing Fiorinal with Codeine and its Fiorinal and codeine phosphate components in relieving the pain, tension, and muscle contraction associated with tension headache. In the original analysis of the study data, no distinction was apparent between patient response to Fiorinal with Codeine and the response to the individual components, a finding that appeared to conflict with the results of a similar earlier study. This apparent discrepancy was attributable to a high placebo response in the later study. Separation of study subjects according to their baseline level of anxiety and pain identified a subset of less anxious patients with mild to moderate pain severity who were least likely to respond to placebo. Analysis of data from these patients showed that Fiorinal with Codeine was significantly better than placebo in improving patients' self-ratings of various symptoms of tension headache at 0.5, 1, 2, 3, and 4 hours after ingestion of the study medication. The combination drug was also consistently superior to Fiorinal alone and codeine alone in improving the patients' self-evaluation items, and differences between the combination and its components were generally of statistical or borderline significance during the last half of the study. The investigators' assessments of the effect of treatment on the three principal variables in tension headache (namely, headache pain, psychic tension, and muscle contraction of the head, neck, and shoulders) at the final patient visit also showed Fiorinal with Codeine to be not only significantly superior to placebo but also consistently superior to either component. The superiority of the combination over Fiorinal alone achieved borderline significance for headache pain and psychic tension.

Symptomatic treatment of chronically recurring tension headache: a placebo-controlled, multicenter investigation of Fioricet and acetaminophen with codeine.

A double-blind, randomized, multicenter investigation was conducted to compare the efficacy and safety of Fioricet, acetaminophen with codeine, and placebo for the symptomatic treatment of tension headache. At the onset of a typical headache, the patients took two capsules of their assigned study medication and rated responses over the next four hours in three target symptoms areas: pain, emotional or psychic tension, and muscle contractions or stiffness in the head and neck. Physicians made global assessments of the same symptom responses and of adverse reactions for each patient. One hundred ninety-eight patients were evaluated. Both active analgesic preparations were more effective than placebo in relieving pain and muscle stiffness or contractions. Fioricet, but not acetaminophen with codeine, was significantly better than placebo in alleviating emotional or psychic tension; Fioricet was also significantly better than acetaminophen with codeine in relieving this symptom. Certain analyses suggested the possibility that Fioricet had a faster and more sustained analgesic effect than acetaminophen with codeine. By the end of the four-hour trial, significantly more patients achieved complete pain relief with Fioricet than with acetaminophen with codeine. The quality and quantity of adverse reactions did not differ significantly among the treatment groups. None was serious, and all abated without medical intervention.

Assessment of Fiorinal with Codeine in the treatment of tension headache.

A randomized, double-blind, placebo-controlled, multicenter study was conducted to ascertain the contribution of Fiorinal and codeine phosphate to the efficacy of Fiorinal with Codeine in relieving the pain, tension, and muscle stiffness associated with tension headache. Patients were given Fiorinal with Codeine, Fiorinal alone, codeine alone, or placebo for use during two separate headache attacks at least 24 hours apart and were asked to rate the effectiveness of the assigned medication on each occasion. The various symptoms of tension headache were evaluated by the patient 0.5, 1, 2, 3, and 4 hours after ingestion of the study medication. At the final patient visit, the investigator assessed the effect of treatment on the three chief components of tension headache, head pain, psychic tension, and muscle contraction. Fiorinal with Codeine was generally significantly more effective than placebo or Fiorinal alone in improving all patient-evaluated items between the second and the fourth hours after administration. The combination was also generally significantly better than codeine alone with respect to pain severity, pain relief, the ability to perform daily activities, and average pathology. The three variables rated by the physician also were generally reduced significantly more with the combination than with placebo or Fiorinal alone. Side effects occurred in only one patient treated with Fiorinal with Codeine.

Distichiasis, congenital heart defects and mixed peripheral vascular anomalies.

We report on a previously apparently unreported syndrome of distichiasis with congenital heart defects and with mixed peripheral vascular anomalies in a mother and her four children. The mother had a ventricular septal defect; both daughters had surgery for patent ductus arteriosus. Sinus bradycardia alone (elder son), with stress induced asystole (younger son), and with wandering atrial pacemaker (both daughters) are documented electrocardiographically. Three of the five have edema, two have visible varicosities, three have symptoms consistent with chronic venous disease of the legs, and the older daughter has complaints consistent with arterial disease in the legs. Doppler flow studies demonstrated post-phlebitic syndrome in all but the younger daughter, and vasospastic disease in the mother, older daughter, and second son.

Asymmetric horseshoe kidney in the infant: value of renal nuclear scanning.

Five infants with an abdominal mass were found to have asymmetric horseshoe kidney. In all five, ultrasound and excretory urography were inconclusive; only after renal nuclear imaging was the diagnosis confirmed and planned surgery cancelled.

Renal manifestations of Kawasaki's disease.

Renal sonographic evaluation of seven patients with mucocutaneous lymph node syndrome were performed and correlated with clinical and laboratory data either supporting or not supporting renal disease associated with this entity. Four of seven patients demonstrated significant elevations of the BUN, creatinine and/or significant proteinuria. These four patients had renal sonographic findings of increased cortical echogenicity, enlarged kidneys and enhanced corticomedullary differentiation. This complication of mucocutaneous lymph node syndrome has heretofore not been noted.

The sonographic appearance of the hemorrhagic ovarian cyst in adolescents.

Pelvic sonography was performed on ten teenaged girls who were proven by surgery to have hemorrhagic ovarian cysts. Pathologically, four were follicular ovarian cysts, while three were corpus luteal cysts, and the exact nature of three was undetermined. At sonography, these masses had variable appearances, ranging from anechoic to moderately echoic with septa and thick walls. All these features are nonspecific and can be encountered in other adnexal masses. The changing sonographic appearance of the hemorrhagic ovarian cyst due to clot lysis is helpful in establishing the diagnosis, and was demonstrated in two cases. These ten cases are discussed, the varied sonographic appearances are described and a review of pertinent literature is included.

Pelvic masses in girls: an 8-year retrospective analysis stressing ultrasound as the prime imaging modality.

Pelvic masses in girls have been the subject of much discussion in the ultrasound-computerized tomography literature. Specifically, ultrasound has confirmed that cystic masses tend to be benign while solid masses are considered malignant until proven otherwise. Complex masses still remain an area of diagnostic difficulty and clinical data are essential in reaching a reasonable diagnosis. This paper reviews pediatric pelvic masses in girls and the role ultrasound plays in their evaluation.

Nonobstructive hydrocolpos: sonographic appearance and differential diagnosis.

Hydrocolpos in the pediatric patient almost invariably occurs secondary to fluid distending the vaginal canal proximal to an obstructive lesion, usually an imperforate hymen. There are, however, other causes for fluid filling and sometimes markedly distending the vagina; many of these are not pathologic. Sonographically, fluid in the vaginal canal often has a confusing appearance and may be mistaken for a pathologic mass. Ways of differentiating hydrocolpos from other normal and abnormal pelvic fluid collections are described. Five adult patients are presented who showed a varied sonographic spectrum of nonobstructive hydrocolpos.

Sonography of vesical and perivesical abnormalities in children.

Pelvic sonograms of 40 children who had abnormalities related to the bladder and perivesical region were reviewed. The lesions detected were categorized into three groups, intramural, intravesical, and perivesical; in each category, conditions not related to vesical or perivesical anomalies that could mimic such anomalies were encountered. Real-time ultrasonography was most helpful in identifying ectopic ureteroceles. Aperistaltic loops of bowel were found to mimic perivesical cysts.

Clavicular periostitis: an unusual complication of percutaneous subclavian venous catheterization.

The first three cases, to the authors' knowledge, of benign clavicular periostitis resulting from percutaneous subclavian venous catheterization in children and the mechanism of this iatrogenic trauma are discussed.

Sonographic evaluation of non-inflammatory neck masses in children.

A review of the sonographic findings in 17 children with non-inflammatory neck masses suggests that while ultrasound is nonspecific with regard to the differential diagnosis, it can show whether a mass is cystic, solid, or complex. Sonography is also useful in clarifying the anatomical extent of a lesion and involvement of underlying normal structures.

The ultrasonographic spectrum of fetal omphalocele.

Four cases of fetal omphalocele diagnosed in utero by ultrasonography represent variations in the sonographic appearance of this rare anomaly. A possible pathogenesis of omphalocele is presented, with a discussion of the associated complications and the effect of diagnosing omphalocele prenatally on the management of the pregnancy itself. The association between fetal omphalocele and elevated alpha-fetoprotein is significant, and may prompt a search for a small omphalocele that would otherwise be missed on a routine obstetric sonogram. The differentiation of omphalocele from gastroschisis is difficult, yet the two anomalies can be reliably differentiated sonographically.

Sonography of scrotal masses in healed meconium peritonitis.

Although sonography is the procedure of choice in evaluating testicular masses in infants, x-ray examination can confirm the diagnosis of healed meconium peritonitis by showing scattered intra-abdominal as well as intrascrotal calcifications. Failure to include an abdominal radiograph early in the evaluation of 2 infants admitted with hard scrotal masses resulted in delayed diagnosis of healed meconium peritonitis. The clinical progression of meconium peritonitis involving the scrotum starts with soft hydroceles at birth and progresses, as the meconium calcifies, to hard "tumor-like" masses at age 4-5 weeks. This paper stresses the sonographic characteristics of meconium peritonitis in the scrotum and the need for confirming radiographs of the abdomen.