Glutaric acidemia, type I, missed by newborn screening in an infant with dystonia following promethazine administration.

We report a child initially diagnosed with promethazine-induced dystonia despite a lack of response to diphenhydramine therapy. On further evaluation, the child was diagnosed with glutaric acidemia, type I (GA-I), an autosomal recessive inborn error of metabolism caused by the deficiency of glutaryl-CoA dehydrogenase. The characteristic clinical feature of GA-I is an acute encephalopathic and neurologic crisis typically occurring during a catabolic state. Despite slow improvement, many patients do not fully recover from a neurologic crisis, and residual neurologic morbidity can be significant. Although newborn screening using tandem mass spectrometry is expected to enable presymptomatic diagnosis of GA-I, this patient was not detected by newborn screening with tandem mass spectrometry. Therefore, a high suspicion of GA-I must be maintained in the evaluation of childhood dystonia, even when newborn screening results are reportedly normal.

Lessons from in vitro testing of spinal needles.

In vitro testing of spinal needles is intended to identify a best buy, but such tests are not necessarily good indicators of clinical performance and some bench tests appear to conflict with mock clinical assessments. Discrepancies can be explained by examining the role of the hub. The Visual Probability Test, which assesses the needle as a complete unit, would appear to be more useful than the more complex measurements of shaft flow. Not all needle manufacturers use the same gauge, creating confusion when comparisons are made. Packaging frequently fails to give adequate information. Changes in hub design could permit earlier identification of dural puncture.

An evaluation of a 30-gauge needle for spinal anaesthesia for caesarean section.

A 30-gauge spinal needle was evaluated for Caesarean section, using a combined epidural/spinal technique, in 50 mothers. Spinal anaesthesia failed in six mothers and was inadequate in another six. General anaesthesia was required on one occasion. A 25% overall failure rate suggests that a 30-gauge needle is not a practical proposition for routine clinical practice.

Predicting difficult intubation.

The amount of larynx seen at intubation was assessed in 633 adult patients undergoing routine surgery. Various measurements of the head and neck were made in an attempt to discover which features were associated with difficulty with laryngoscopy (defined as the inability to see even the arytenoids). In addition 38 patients, reported by colleagues because they had been "difficult to intubate", were measured. Five useful risk factors, measured at three levels of severity, were identified. A simple predictive rule was developed and tested on a prospective set of 778 patients, in 1.5% of whom laryngoscopy was found to be difficult. Depending on the threshold chosen, the rule allowed the detection of, for example, 75% of the "difficult" laryngoscopies at a cost of falsely identifying 12% of the "not difficult" patients.

Laryngeal trauma vs length of intubation.

The frequency histograms of six patients' laryngographs were studied pre- and post-endotracheal intubation. The changes were correlated with the length of intubation. The post-operative hoarse voice was seen as an increase in the spread of the lower frequencies, and an increase in the fundamental frequency. The latter change was thought to be a subconscious compensation for the hoarseness. The increased lower frequency spread as measured by standard deviation was directly proportional to the length of intubation.

Lethal enhancement of therapeutic doses of acetaminophen by alcohol.

A 47-year-old man undergoing supervised alcohol detoxification developed severe liver disease after receiving small doses of acetaminophen. Autopsy revealed extensive hepatic necrosis. Proposed mechanisms for alcohol potentiation of acetaminophen hepatotoxicity are described. We feel acetaminophen should not be routinely used for patients with active alcoholism unless its safety can be established.

Cholangiocarcinoma as related to chronic intrahepatic cholangitis and hepatolithiasis. Case report and review of the literature.

A case of cholangiocarcinoma is described in a patient with underlying hepatic lithiasis and cholangitis. The possible pathogenesis of cholangiocarcinomas is discussed and the importance of endoscopic retrograde cholangiography in the diagnosis of this malignancy is emphasized.

Phenytoin and phenobarbital concentrations in saliva and plasma measured by radioimmunoassay.

Saliva and plasma levels of phenytoin (DPH) and phenobarbital (PB) in a series of epileptic patients were compared by means of a radioimmunoassat (RIA) that required only 10 mul of saliva or plasma. There was an excellent linear relation (r = 0.98) between the logarithms of the concentrations of DPH in the two fluids. The ratio saliva/plasma was remarkably constant at 0.10 and was unaffected by varying levels of PB. The ratio was close to the fraction of DPH reported unbound in plasma at 37 degrees. PB plasma and saliva levels were also closely related (r = 0.98 for logarithm of plasma and saliva levels). This relation was nonlinear [plasma ocncentration = 4.43 X (salivary concentration)0.86], but could be approximated by the ratio plasma/saliva = 3.4. The simplicity of sample collection and the sensitivity of the RIA procedure suggest that clinical monitoring of these anticonvulsant levels may be carried out by RIA on saliva samples.

The pathogenesis of pulmonary edema in acute pancreatitis.

Acute pulmonary edema appeared 3 or more days after the onset of acute pancreatitis in 7 patients, an approximate incidence of 8%. The severity of pancreatitis in these patients was characterized by massive requirements for intravenous colloid and by marked hypocalcemia. In addition, at least 5 of the 7 patients had very high serum levels of triglycerides at the time of hospital admission. Hemodynamic studies during pulmonary edema showed normal central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance. Cardiac index was appropriately elevated. Respiratory treatment, consisting of endotracheal intubation and controlled ventilation with PEEP, was successful in allowing reversal of the pulmonary injury and recovery of respiratory function within 1-2 weeks in all cases. Two patients died later from pancreatic abscesses. The findings indicate that a distinct form of pulmonary injury may occur in acute pancreatitis, characterized by loss of integrity of the alveolar-capilllary membrane, leading to pulmonary edema. The mechanism of injury is not known but may be caused by circulating free fatty acids, phospholipase A, or vasoactive substances. The pulmonary membrane lesion appears to heal during the period of intensive respiratory support.

The hypocalcemia of acute pancreatitis.

Variables of calcium metabolism were measured in 11 patients with clearly documented acute pancreatitis. Total and ionized calcium levels were either low or in the low-normal range as were phosphorus and total magnesium levels. Parathyroid hormone levels were high, and there was a significant inverse correlation with ionized calcium. Gastrin levels were normal, calcitonin values were uniformly below the detection limit of the assay, and pancreatic glucagon levels were elevated. The hypocalcemia of acute pancreatitis was probably not caused by abnormalities of glucagon, calcitonin, or gastrin secretion. Furthermore, parathyroid hormone secretion was apparently not impaired. Hypomagnesemia possibly played a minor role. This study suggests that the hypocalcemia of acute pancreatitis is secondary to extraskeletal calcium sequestration or an as yet unidentified defect of bone metabolism, or both.

Inhibition of serum and urine amylase activity in pancreatitis with hyperlipemia.

In 6 of 7 patients with acute pancreatitis and hyperlipemia, inhibition of serum amylase activity was detected by dilution of the serum before assaying for amylase and by correcting for tthe dilution factor. In 4 patients the inhibition phenomenon disappeared within the first few days of hospitalization as the elevated serum triglycerides fell. However, in 2 others there was no relation between triglyceride level and amylase inhibition. Removal of the excess serum lipids by ultracentrifugation did not eliminate the inhibition of amylase activity. Inhibition of amylase activity also occurred in the urine of these patients. No amylase inhibition was demonstrable in lipemic serum from patients without pancreatitis or in pancreatitis serum to which excess lipids were added. The data suggest the presence of a circulating inhibitor of amylase, distinct from the elevated serum lipids, in the serum and urine of patients with acute pancreatitis associated with hyperlipemia. The diagnosis of acute pancreatitis in the patient with abdominal pain and lactescent serum can be facilitated by correcting the serum amylase activity by dilution.

Diagnosis of pancreatitis masked by hyperlipemia.

It is often difficult to confirm a diagnosis of acute pancreatitis in the presence of hyperlipemic serum because the serum amylase and lipase and the urinary amylase are frequently normal. We were able to substantiate the diagnosis of pancreatitis in seven patients with hypertriglyceridemia (greater than 1200 mg/100 ml) by the use of the simple amylase/creatinine clearance ratio and by the serial dilution of hyperlipemic serum. The amylase/creatinine clearance ration in the hyperlipemic pancreatitis patients (10.0%) was significantly (P GREATER THAN 0.001) higher than in normal patients (3.1%) and essentially the same as in nonlipemic pancreatitis patients (9.2%). The calculated serum amylase activity after serial dilution of the serum showed up to a tenfold increase in hyperlipemic pancreatitis, with no significant increase in normal controls, hyperlipemic controls, and nonlipemic pancreatitis.

Amylase clearance in differentiating acute pancreatitis from peptic ulcer with hyperamylasemia.

Thirty-four patients with abdominal pain, tenderness, and hyperamylasemia suggesting acute pancreatitis were studied prospectively to elucidate the relationship between peptic ulcer disease and pancreatitis. Confirming evidence of pancreatitis and/or ulcer was obtained either at laparotomy of by upper gastrointestinal roentgenograms. The presence or absence of pancreatitis was substantiated by measurement of the amylase/creatinine clearance ratio, which is significantly higher (p less than 0.001) in patients with acute pancreatitis (9.3 plus or minus 0.9), than in patients without pancreatitis (3.1 plus or minus 0.2). Nine of the 34 patients were found to have gastric or duodenal ulcers. However, seven of the nine, despite an elevated serum amylase, had no sign of pancreatitis at surgery, on radiological examination, or by elevation of the amylase/creatinine clearance ratio (3.1 plus or minus 0.4). It is suggested that hyperamylasemia associated with peptic ulcer disease is most often not indicative of acute pancreatitis and that treatment is most appropriately directed at the ulcer.