Sources of disparity in the spectrum of diabetes mellitus at incidence and prevalence.

In a population-based study in Rochester, Minnesota, the clinical characteristics of 1135 patients newly diagnosed with diabetes (1945-69) were compared with those of 810 residents with diabetes mellitus on prevalence day (1 January 1970). The prevalence patients were older and the male: female ratio was reduced from that seen among incidence cases. The prevalence patients were more likely to be on oral agents, had lower fasting blood glucose levels, were less likely to be symptomatic, but were more likely to have macrovascular and microvascular complications. These differences seemed to come about as a result of variation in survival rates among patients with specific characteristics, differential migration of certain groups of patients, and changes in the status of individuals.

Referral bias in diabetes research.

Of all the known diabetic individuals residing in the community of Rochester, Minnesota, only about one-half would have been recognized through a review of the medical records of 1 yr. Only one-fifth of the diabetic residents were hospitalized during the index year and a similarly small proportion were attended in a diabetes clinic. This selective process produced distortion in the apparent clinical spectrum of diabetes observed at different levels in the medical care system. Notable was overestimation of the relative importance of insulin-dependent diabetes and of the vascular complications of diabetes among hospital and diabetes clinic patients. Referral bias should be taken into account when differences are noted in the epidemiologic features of diabetes as reported from different types of medical care settings.

A population-based study of diabetes mortality.

In a population-based investigation among the residents of Rochester, Minnesota, the diabetes mortality rate was 8.5 per 100,000 person-years with diabetes as the underlying cause of death, 31.5 per 100,000 person-years with diabetes as an underlying or contributory cause, and 82.7 per 100,000 person-years if all deaths among diabetic individuals were counted. Diabetes was not mentioned on the certificate in 62% of the 428 diabetic deaths during 1965-1974. When the clinical characteristics of the subgroup of mortality cases in 1969 were compared with those of the prevalence cases on 1 January 1970, it was found that mortality cases tended to be older, were more often on insulin therapy, and were more likely to have macro- and microvascular complications. Because mortality data are sometimes used to infer trends and characteristics for the diabetic population at large, it is important to recognize these biases.

Topographical distribution of neurons containing endothelin type A receptor in the rat brain.

Endothelin (ET) was originally identified as a vasoactive peptide biosynthesized in vascular endothelial cells. Because ET has also been found in the brain as a neuropeptide, it has been thought to belong to the group of brain-vascular peptide hormones. To date, type A and type B receptors for ET have been found. To elucidate the topographic distribution of type A receptor (ET-AR) in the brain, we raised a specific antibody to the C-terminal (64 amino acids) peptide of rat ET-AR and immunostained rat brain sections with this antibody. Immunoreactivity for ET-AR was detected in neuronal cell bodies and also in the many proximal and some distal parts of their fibers. Nerve cell bodies containing strong ET-AR-immunoreactivity were distributed in the lateral part of the reticular formation, the nucleus of the solitary tract and its surrounding area, the dorsal midline area and medial longitudinal fasciculus, the subependymal layer of the fourth ventricular roof, the caudolateral area of the pontine tegmentum, the locus coeruleus, the rostral pontine area of the lateral reticular formation, the retrorubral area, the substantia nigra, the ventral tegmental area, the periventricular region lateral to the rostral mesencephalic aqueduct and caudal third ventricle, the arcuate hypothalamic nucleus, the caudomedial area of the zona incerta, the periventricular hypothalamic nucleus, the parvocellular portion of the paraventricular hypothalamic nucleus, and the periglomerular region of the olfactory bulb. In addition, the Purkinje cells of the cerebellar cortex, the nerve cells in the mesencephalic trigeminal nucleus, and the magnocellular neurons of the supraoptic and paraventricular hypothalamic nuclei showed weak immunoreactivity. The distribution of highly ET-AR-immunoreactive neurons is quite similar to that ofcatecholamine neurons.

Low-dose ACTH therapy for West syndrome: initial effects and long-term outcome.

BACKGROUND: Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan. METHODS: The medical records of 138 patients with WS, who were treated with low-dose synthetic ACTH therapy for the first time at the authors' institutions between 1989 and 1998, were analyzed. RESULTS: At the end of ACTH therapy, excellent effect on seizures was noted in 106 of 138 (76%) patients, good effect in 23 (17%), and poor effect in 9 (7%). Initial effects on EEG were excellent in 53 of 138 (38%) patients, good in 76 (55%), and poor in 9 (7%). As for seizure prognosis at the time of follow-up, 51 of 99 (52%) patients were seizure-free, whereas 48 (48%) patients had seizures. Mental outcome was normal in 6 of 98 (6%) patients, mild mental retardation in 16 (16%), moderate mental retardation in 26 (27%), and severe mental retardation in 50 (51%). The initial effects of ACTH on seizures and long-term outcome were not dose dependent (daily dosage 0.005 to 0.032 mg/kg, 0.2 to 1.28 IU/kg; total dosage 0.1 to 0.87 mg/kg, 4 to 34.8 IU/kg). The severity of adverse effects correlated with total dosage of ACTH, and the severity of brain volume loss due to ACTH correlated well with the daily dosage and total dosage of ACTH. CONCLUSION: Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects.

Ultrastructural immunolocalization of adenosine deaminase in histaminergic neurons of the tuberomammillary nucleus of rat.

Neurons in the tuberomammillary nucleus (TM) of the rat hypothalamus were immunolabelled for the enzyme adenosine deaminase (ADA) and investigated by electron microscopic immunohistochemical techniques. ADA-immunoreactivity was distributed throughout the somal and dendritic cytoplasm of TM neurons and in the karyoplasm of most, but not all of these neurons. Immunoreactive axons were rarely observed within the tightly packed cell clusters of the TM subdivisions examined. Dense deposition of immunoreaction product together with reasonable preservation of morphological detail facilitated identification of immunoreaction product together with reasonable preservation of morphological detail facilitated identification of immunoreactive profiles and allowed characterization of the ultrastructural features of labelled neurons and the relationships of these with each other and with surrounding unlabelled neuronal and glial elements. Immunolocalization of ADA therefore represents a reliable and convenient method for the identification of TM neurons in EM studies of their ultrastructure and synaptic interactions.

Dopaminergic innervation and inhibition of ciliary movement in the ciliated epithelium of frog palatine mucosa.

The effect of dopamine on ciliary movement and the existence of dopamine-containing cells in the ciliated epithelium of frog palatine mucosa were investigated pharmacologically and by means of electron and fluorescence microscopy, respectively. Ciliary movement was suppressed markedly when the perfusion medium contained 10(-6) M dopamine, thereby indicating that dopamine has a suppressive effect on ciliary movement. Electron microscopy revealed at least two types of granule-containing (GC) cells, type 1 cells containing small spherical granular vesicles (about 100-150 nm in diameter) and type 2 cells containing elongated dense granules (about 150 X 250 nm in diameter). One hour after systemic administration of dihydroxyphenylalanine-[3H(G)] [( 3H]DOPA), a large number of silver grains appeared only in type 2 GC cells, thus indicating that type 2 cells are catecholamine-storing. Blue-green fluorescent cells were detected in the ciliated epithelium. On microspectrofluorometry, catecholamine fluorescence in the cells showed a main excitation and emission maxima at 415 and 480 nm, respectively. When the fluorescent cells were exposed to HCl vapor for several s, the excitation peak shifted to 380 nm and this peak was unchanged after treatment for an additional 5 min. It may be considered that these fluorescent cells contain dopamine and correspond to type 2 GC cells. A possible functional relationship between regulation of ciliary movement and dopamine-containing cells was also discussed.

Histological study on ouabain immunoreactivities in the mammalian hypothalamus.

The endogenous digitalis-like factor (EDLF) which has recently been purified from human plasma and identified as 'ouabain', a cis-trans-cis steroid of plant origin, is thought to be similar to the hypothetical humoral factor, 'endogenous digitalis-like substance (EDLS)'. In order to examine the hypothesis that EDLS is produced in the hypothalamus, we prepared an ouabain-specific antibody, and applied it to rat and macaque brains. Ouabain immunoreactivities were observed in the hypothalamus of both species. The immunopositive neurons were distributed in paraventricular and supraoptic nuclei, and some other hypothalamic regions. Their nerve fibers were seen abundantly in the hypothalamo-neurohypophysial regions. These results strongly support the possibility of existence of cis-trans-cis steroid including EDLF in mammalian brain.

Somatic cell mutation frequency at the HPRT, T-cell antigen receptor and glycophorin A loci in Cockayne syndrome.

Skin fibroblasts of patients with Cockayne syndrome (CS) are hypersensitive to the lethal or mutagenic effect of ultraviolet light, which may cause genetic instability. Up to now, however, no systematic study of in vivo somatic cell mutation in CS cells has been reported. This article describes our investigation of the mutation frequencies (Mfs) at three different loci, i.e. hypoxanthine-guanine phosphoribosyl transferase (HPRT), T-cell antigen receptor (TCR) and glycophorin A (GPA), in six patients with CS. Mfs at the HPRT and TCR loci were found to be within the normal range as determined in age-matched controls. In the GPA locus of two patients, there was a slight increase, but it was much smaller than that reported in other DNA repair deficient syndromes. The frequency of spontaneous HPRT mutation in Epstein-Barr virus transformed B-lymphoblastoid cells derived from CS patients was similar to that in cells from normal children. The molecular characterization of the representative HPRT mutant T cell clones from CS patients did not show any structural alterations. These results may explain, at least in part, why CS is not associated with predisposition to cancer.

Rhinocerebral mucormycosis: results of aggressive surgical debridement and amphotericin B.

Rhinocerebral mucormycosis is a fulminant, devastating fungal disease. The use of amphotericin B, combined with aggressive surgical debridement, has increased survival rates from approximately 20% to 70%. Eleven patients with this rare disease have been treated over the past 6 years. Therapy with amphotericin B was begun in all patients as soon as the diagnosis of mucormycosis was suspected. Seven patients underwent aggressive surgical debridement; all seven had disease involving the sphenoethmoidal complex, requiring external ethmoidectomy with or without sphenoidotomy. Six patients had maxillary sinus disease, requiring Caldwell-Luc antrostomy or maxillectomy. Three patients required orbital exenteration. Surgery was performed within 24 hours of diagnosis on all but two of our patients. Despite prompt diagnosis, aggressive surgical debridement, therapy with amphotericin B, and correction of metabolic acidosis, our mortality rate was 82%. Rhinocerebral mucormycosis remains a rapidly progressive, frequently fatal disease.

Clorazepate therapy for intractable epilepsy.

Thirty-one epileptic patients with seizures refractory to conventional anticonvulsants were treated by adding clorazepate dipotassium to their regimen. Twelve cases showed improvement in seizure frequency, three of whom attained a seizure free state. Response to clorazepate was not related to the type of epilepsy, but patients with secondary generalized epilepsy tended to be less responsive than those with partial epilepsy. Among the various seizure types, generalized tonic-clonic seizures and simple partial seizures showed, although not significant, a tendency to be more responsive to clorazepate therapy than other seizure types, including complex partial seizures, atypical absence, atonic seizures, and tonic seizures. Drowsiness was the main adverse effect, of which 14 patients complained. Six patients were withdrawn from clorazepate because of drowsiness, but in the remaining 8 patients, this side effect disappeared within a week. The appearance of adverse effect was not related to the dose of clorazepate given. Clorazepate may be an effective secondary anticonvulsant in the treatment of intractable epilepsy.

Nephrogenic diabetes insipidus and tethered cord syndrome with a lipoma of the cauda equina.

The tethered cord syndrome is characterized by sensory and motor disturbances of the lower extremities and incontinence. We report a 12-year-old girl with a cauda equina lipoma and a tethered spinal cord, whose chief complaints were polyuria and polydipsia. She was diagnosed as having nephrogenic diabetes insipidus. This unusual complication of the tethered cord syndrome was most likely due to a hydronephrosis secondary to a neurogenic bladder. Thus, spinal lesions have to be considered in patients with polyuria and polydipsia.

Preservation of facial contour during parotidectomy.

Parotid surgery often leaves a facial contour deformity. Free abdominal dermal-fat grafts were used to preserve the facial contour of nine patients undergoing parotid surgery. This procedure is simple to perform and provides an improved cosmetic result without significantly increasing operative time or lengthening hospitalization. No troublesome fat absorption occurred postoperatively. The dermal-fat graft also serves as a barrier to regenerating neurons, thereby preventing postoperative gustatory sweating.

Pediatric airway reconstruction at Great Ormond Street: a ten-year review. III. Decannulation and suprastomal collapse.

One hundred eight consecutive patients with pediatric laryngotracheal stenosis requiring airway reconstruction over a 10-year period were reviewed. Ninety (83%) of the patients were decannulated. Over three quarters of the decannulations took place within 20 months of primary reconstruction. More than half of the patients (47, or 52%) had persistent tracheocutaneous fistulae after decannulation, which required elective closure. The likelihood of a persisting tracheocutaneous fistula is directly related to duration of cannulation.

Pediatric airway reconstruction at Great Ormond Street: a ten-year review. II. Revisional airway reconstruction.

One hundred eight consecutive patients with pediatric laryngotracheal stenosis requiring airway reconstruction over a 10-year period were reviewed. Thirty-two patients required revisional airway reconstruction in an attempt to achieve decannulation. Patients underwent from one to four revisional airway reconstructions, most often laryngotracheal reconstruction with costal cartilage grafting. In the Cotton grading scheme of preoperative stenosis, those patients requiring revisional airway surgery tended to come from the more severely affected categories. Twenty-two patients of 32 (69%) achieved decannulation with revisional airway reconstruction. Thus, revisional airway reconstruction is indicated if the first attempt fails.

Pediatric airway reconstruction at Great Ormond Street: a ten-year review. I. Laryngotracheoplasty and laryngotracheal reconstruction.

One hundred eight consecutive patients with pediatric laryngotracheal stenosis requiring airway reconstruction over a 10-year period were reviewed. One hundred forty-nine operations consisting of 75 laryngotracheoplasties and 74 laryngotracheal reconstructions with costal cartilage grafting were performed. The Cotton grading scheme of preoperative stenosis was useful in predicting likelihood of decannulation. In all, 90 patients (83%) were decannulated.

An approach to the failed cricoid split operation.

The cricoid split operation is a well established treatment for subglottic stenosis; the success rate for this procedure is approximately 77%. The management of patients who fail this operation has traditionally involved tracheostomy followed by delayed laryngotracheoplasty. We have treated 22 patients using the cricoid split--6 required subsequent tracheostomy. Two-thirds of the patients with a tracheostomy have been unable to be decannulated, even after laryngotracheoplasty. In contrast, 3 patients had repeat cricoid split operations instead of tracheostomy. All 3 of these children have had no further problems with their airway. The authors propose that in patients who fail the cricoid split operation one consider repeating the procedure instead of performing a tracheostomy.

Do angiomas of the nasal septum exist?

Juvenile nasopharyngeal angiofibromas (JNA) by definition originate in the nasopharynx. Vascular tumors arising in the nasal cavity can easily be mistaken for JNA, when the correct diagnosis is hemangioma or angiofibromatous polyp. We present a case that illustrates this problem, an 11-year-old boy with a unilateral anterior nasal cavity mass associated with recurrent epistaxis. At surgery, the mass was found to arise from the anterior nasal septum and was removed easily with minimal bleeding. The initial pathologic interpretation was JNA. After extensive review of the specimen, however, the diagnosis of hemangioma was made. Similar tumors have been reported as being JNA that have been simple to remove with minimal blood loss. JNA is associated with more severe blood loss, is more difficult to expose surgically and has a higher risk of recurrence than other nasal tumors. Therefore, JNA needs to be distinguished from anterior nasal cavity masses.

Surgery for bilateral nasal valvular collapse.

The nasal valve is an important regulator of nasal airflow. Patients may suffer from nasal obstruction due to bilateral nasal valvular collapse combined with a drooping tip. A simple, effective technique of cartilage grafting to open the valve is forwarded. The advantages of this method include placing the graft in the submucosal plane which preserves mucosa and protects the graft from nasal secretions while healing.

Surgical treatment of laryngomalacia.

Laryngomalacia is the commonest cause of congenital stridor. The majority of cases are mild and do not require surgical intervention. However in approximately 10 per cent of these infants the condition is life-threatening. The standard treatment for these patients has been to perform a tracheostomy. Recent reports have shown encouraging results following endoscopic surgery to the supraglottic structures. We report a series of twelve patients in whom a tracheostomy was avoided by performing an aryepiglottic fold trim--'aryepiglottoplasty'. Dramatic improvements were seen in the respiratory obstruction and failure to thrive following surgery.