Ventricular septal defect: results after repair in infancy.

During the 19 years from 1957 through 1975, there have been 106 patients under age 2 years who have undergone surgery for repair of a large ventricular septal defect at the University of Michigan Medical Center. The majority of the patients had either severe pulmonary hypertension or intractable congestive heart failure. Eighty-three infants survived operation; there has been one late death. The greatest mortality occurred in patients under age 6 months and in those with severe pulmonary hypertension. Surviving infants showed marked symptomatic improvement and change in growth patterns. Complications included the development of complete right bundle branch blodk or left anterior hemiblock in approximately 50 percent of patients and, in one instance, complete atrioventricular block. Forty-five patients have undergone cardiac catheterization 1 to 8 years postoperatively. Although 17 were found to have residual septal defects only 3 of these had a pulmonary to systemic flow ratio of 1.5:1 or more, and reoperation was accomplished without incident in these 3 patients and in 3 others with smaller shunts. With one exception, postoperative pulmonary arterial pressures and pulmonary to systemic vascular resistance ratios were normal or near normal, thus representing a significant contrast with findings in patients operated on after age 2 years. Whereas the complications of surgery appear no greater in the infant than in the older patient, many of the benefits can be realized only with operation at the earlier age.

Increased spinal monoamine concentrations after chronic thoracic dorsal rhizotomy in goats.

In goats, bilateral thoracic dorsal rhizotomy (TDR) causes severe ventilatory failure during exercise, followed by progressive functional recovery. We investigated spinal neurochemical changes associated with TDR and/or functional recovery by measuring spinal concentrations of the monoamines serotonin (5-HT), norepinephrine, and dopamine via HPLC. Changes in 5-HT and calcitonin gene-related peptide were visualized with immunohistochemistry. Goat spinal cords were compared 4-15 mo after TDR from T(2) to T(12) (n = 7) with sham-operated (n = 4) or unoperated controls (n = 4). TDR increased the concentration of cervical 5-HT (C(5)-C(6); 122% change), caudal thoracic norepinephrine (T(7)-T(11); 53% change), and rostral thoracic dopamine (T(3)-T(6); 234% change). TDR increased 5-HT-immunoreactive terminal density (dorsal and ventral horns) and nearly eliminated calcitonin gene-related peptide immunoreactivity in the superficial laminae of the dorsal horn in rostral thoracic segments; both effects became less pronounced in caudal thoracic segments. Thus TDR elevates monoamine concentrations in discrete spinal regions, including possible compensatory changes in descending serotonergic inputs to spinal segments not directly affected by TDR (i.e., cervical) but associated with functionally related motor nuclei (i.e., phrenic nucleus).

A direct magnocellular-preopticospinal pathway in goldfish: implications for control of sex behavior.

Neurons in the pars magnocellularis and gigantocellularis of the goldfish magnocellular preoptic nucleus concentrate horseradish peroxidase by retrograde transport following its placement into sectioned spinal cord. Implants at rostral levels labeled the greatest number of preoptic cells. The pathway demonstrated is primarily ipsilateral and appears equivalent to the paraventricular-spinal system of tetrapods. In goldfish it may control sperm release and other stereotyped reproductive responses.

Colchicine reduces myelin thickness and axoplasm volume.

A Silastic cuff containing either colchicine (1% w/v) or no colchicine was placed around the lingual disorder tympani nerve of the Mongolian gerbil. After 3 days of exposure to colchicine, the mean period of the myelin sheaths was 23% less than the period observed in nerves treated with cuffs lacking colchicine, while the average number of lamellae was unaltered. At the same time colchicine reduced the volume of axoplasm by an average of 19%, an effect which was independent of fiber diameter.

5-Hydroxytryptophan (5-HTP) augments spontaneous and evoked phrenic motoneuron discharge in spinalized rats.

Experiments on anesthetized, spinalized rats were conducted to determine the effects of systemic 5-hydroxytryptophan (5-HTP) administration on: (1) spontaneous phrenic nerve activity and (2) evoked phrenic responses to short latency, non-serotonergic synaptic inputs elicited by electrical stimulation of lateral funiculus. 5-HTP augmented spontaneous phrenic activity and allowed expression of a second, longer latency evoked response. Both effects were antagonized by methysergide. Our results suggest that spinal serotonin increases the efficacy of synaptic inputs to phrenic motoneurons.

Chronic impairment of axonal transport eliminates taste responses and taste buds.

A Silastic nerve cuff containing colchicine (1% w/v) was placed around the combined lingualchorda tympani nerve of the Mongolian gerbil (Meriones unguiculatus) to evaluate the role of axonal transport in the maintenance of taste buds. After 3 days the summated gustatory impulse discharges recorded from the chorda tympani nerve were reduced by 60%, while compound action potentials had not changed appreciably. The lingual-chorda tympani nerve underwent ultrastructural changes including a loss of microtubules, an increased prominence and disorientation of neurofilaments, and a significant shrinkage in the cross-sectional area of axoplasm. The shrinkage of axoplasm and the accumulation of mitochondria and cholinesterase at the nerve cuff provided evidence that the colchicine treatment acted to impair axonal transport. More substantial pathological changes were evident in nerve ultrastructure by 15 days when both the ipsilateral chorda tympani taste responses and fungiform taste buds were nearly absent. Control cuffs lacking colchicine had little effect on chorda tympani taste responses, taste buds, or nerve ultrastructure. Eight or 15 days of nerve exposure to lumicolchicine, an isomer of colchicine with low affinity for tubulin, had no significant effect on taste responses. [3H]Colchicine was used in the nerve cuff to demonstrate that colchicine must have acted directly upon the nerve trunk, rather than the taste buds, to cause the loss of taste responses and taste buds. [3H]Colchicine levels were equal in the two sides of the tongue, whereas both the functional and structural deterioration of the taste buds were restricted to the ipsilateral side. We conclude that the loss of taste responses and taste buds was caused by chronically impaired axonal transport in gustatory axons.

Fifty years' experience with esophageal atresia and tracheoesophageal fistula. Beginning with Cameron Haight's first operation in 1935.

Four hundred twenty-six patients with esophageal atresia with or without tracheoesophageal fistula have been primarily cared for at the University of Michigan Medical Center since Cameron Haight's initial experience with this entity. Over the period of observation, the incidence of new cases as well as the number of associated anomalies has remained constant. The long-term survival of these patients has steadily improved over the past half-century from 36% in the pre-1950 era to 84% during the most recent 20 years. Conversely, operative mortality has shown a progressive decline from 56% early in the authors' series to 6.9% more recently, despite a steady increase in the proportion of high-risk neonates seen at the University of Michigan Medical Center during this time span. In the last 9 years, there have been no postoperative deaths in group A or B risk infants (36 patients), while the rate has been 18.2% in group C risk babies (27 patients); almost all of these deaths were due to severe associated anomalies. During the last 10 years, the authors have changed their technique of anastomosis from a two- to a one-layer method while still advocating a primary repair via an extrapleural approach. Although this change has resulted in a modest increase in the rate of anastomotic leak (17% vs. 6.2%, p less than 0.03), the leaks have been small and asymptomatic because of the extrapleural approach and, as a result, have been managed conservatively without any untoward sequelae. Conversely, there has been a significant decrease in the rate of stricture formation with the one-layer anastomosis (4.3% vs. 23.3%, p less than 0.002). While this may in part be explained by the change in anastomotic technique, it is felt that the more aggressive diagnosis and surgical management of gastroesophageal reflux (seen in 37.9% of our recent group) have contributed greatly to this decrease. The steady improvement in survival over this 50-year period, in spite of the increasing number of high-risk infants, is attributable to major improvements in neonatal care before, during, and after operation.