Plasmapheresis in hereditary angioneurotic edema and systemic lupus erythematosus.

A patient had hereditary angioneurotic edema coincident with systemic lupus erythematosus. This condition resulted in loss of hair, arthralgia, leukoplakia, collitis, and a nephrotic syndrome due to proliferative glomerulonephritis. The renal lesion was resistant to treatment with high-dose prednisolone and cyclophosphamide; however, sustained remission occurred after plasmapheresis. The patient has remained well for over two years since this procedure.

Stereospecific assignments of the leucine methyl resonances in the 1H NMR spectrum of Lactobacillus casei dihydrofolate reductase.

A general method is described for the stereospecific assignment of methyl resonances in protein NMR spectra based on selective deuteration procedures. A selectively deuterated dihydrofolate reductase from L. casei was prepared by incorporating stereoselectively deuterated L-leucine, (2S,4R)[5,5,5-2H3]leucine. By comparing the COSY spectra of the dihydrofolate reductase-methotrexate complexes formed using deuterated and non-deuterated enzyme the stereospecific assignments for resonances of all 13 leucine residues were obtained by noting the absence of cross-peaks in spectra from the deuterated proteins.

CNS malformation in a child with Kabuki (Niikawa-Kuroki) syndrome: report and review.

Kabuki (Niikawa-Kuroki) syndrome (KS) comprises characteristic facial changes, developmental delay, skeletal anomalies, mental retardation, and abnormal dermatoglyphics. We report on a 5-year-old Caucasian boy with KS who required surgery for a giant left temporoparietal subarachnoid cyst at age 5 1/2 years. Review of the 143 published cases shows that while malformations may be found in the endocrine, cardiac, genitourinary and skeletal systems, this is the first case of Kabuki syndrome with a major central nervous system malformation.

Distinctive Menkes disease variant with occipital horns: delineation of natural history and clinical phenotype.

To delineate further the clinical spectrum of Menkes disease, an X-linked recessive disorder of copper transport, we studied 4 related males, ranging in age from 4-38 years, with a unique phenotype that combines manifestations of classical and mild Menkes disease and occipital horn syndrome (OHS). The propositus, and 18-year-old man, was evaluated following an intracerebral hemorrhage at age 15 years and was noted to have marked hypotonia, motor delay with mental retardation, bladder diverticula, failure to thrive, and diarrhea from infancy; seizures from age 3 years; and abnormal hair (pili torti) and face, cutis laxa, and multiple joint dislocations. Radiographic abnormalities included occipital exostoses, tortuous cerebral blood vessels with multiple branch occlusions, and hammer-shaped clavicles. Biochemical studies demonstrated reduced copper and ceruloplasmin levels in serum, and abnormal plasma catecholamine ratios. We reported previously the molecular defect in this family, a splice-site mutation that predicts formation of approximately 20% of the normal Menkes gene product [Kaler et al., 1994: Nat Genet 18:195-202]. Here, we detail the clinical course and physical features and radiographic findings in these 4 individuals, and compare their phenotype with classical and mild Menkes and OHS. Unusual Menkes disease variants such as this may escape recognition due to anomalies that appear inconsistent with the diagnosis, particularly prolonged survival and later onset of seizures. Males with mental retardation and connective tissue abnormalities should be evaluated for biochemical evidence of defective copper transport.

The relationship between autoantibodies to triiodothyronine (T3) and thyroglobulin (Tg) in the dog.

The relationship between T3 autoantibodies (T3AA) and thyroglobulin autoantibodies (TgAA) in dogs was investigated by determining the inhibitory effect of triiodothyronine (T3), thyroxine (T4) and thyroglobulin (Tg) on T3AA and TgAA binding activity and by determining the pattern of occurrence of the two activities in canine serum samples. Strong similarity in binding characteristics between the two activities, as one might expect if T3AA activity were merely a cross-reactivity of TgAA, was not observed. Canine T3AA activity exhibited a cross-reactivity to purified canine Tg that was intermediate between that of T3 and T4, indicating an antigenic relationship to an epitope of Tg. Average affinity constants of canine T3AA (N = 11) for T3, Tg and T4 were 1.76 x 10(10) M-1, 2.29 x 10(9) M-1, and 1.02 x 10(8) M-1, respectively. Canine TgAA activity, however, did not cross-react significantly with T3 or T4. Canine TgAA (N = 21) binding to canine Tg was not inhibited by T4 or T3 at concentrations up to 2 x 10(-4) M. Each of 23 canine serum samples containing T3AA also exhibited TgAA activity, although there was poor correlation between the magnitudes of the two activities. Neither T3AA nor TgAA activity was observed in serum samples from 16 euthyroid dogs; however, 46.7% of the samples from 15 hypothyroid dogs had detectable TgAA activity. T3AA is so rare that is was not observed in this small population of samples from hypothyroid dogs. The [125I] T3 binding in serum from hypothyroid dogs was elevated compared to that in euthyroid dogs, but was considerably lower than in samples generally designated as containing T3AA. These results suggest that T3AA found in occasional canine serum samples are due to the presence of autoantibodies recognizing a T3 containing epitope of Tg that is different from the epitopes involved in eliciting the predominant population of canine Tg autoantibodies.

Simple choristoma of the anterior segment containing brain tissue.

We report an unusual case of a simple choristoma of the anterior segment that contained only brain tissue. The clinical characteristics and findings of pathological examination of this unusual ocular malformation were reviewed. A newborn girl was seen with a fleshy, highly vascular cystic mass arising from the inferior limbus and extending across the cornea. On a computed tomographic scan, gross disruption of the anterior segment was present, with subluxation of the lens into the cyst. Excision of the abnormal tissue was followed by evisceration; polyglactin (Vicryl) ball implantation; patch graft of the globe; and, later, prosthetic fitting. Pathologic findings showed a choristomatous malformation, containing only mature brain tissue. To our knowledge, a choristoma in which the sole constituent is brain tissue has not previously been reported.

Molecular forms of alpha-melanocyte-stimulating hormone in the canine pituitary anterior and intermediate lobe.

Reverse-phase high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA) were used to determine the distribution of naturally occurring forms of alpha-melanocyte-stimulating hormone (alpha-MSH) in acid extracts of pars intermedia (PI) and anterior lobe (AL) tissue from canine and rat pituitary. Similarly, intracellular and secreted forms of alpha-MSH were determined using cultured canine PI and AL cells. Rat PI tissue contained predominantly diacetyl-alpha-MSH, while monoacetyl-alpha-MSH was the most abundant form in canine PI. In both canine and rat AL tissue extracts desacetyl-alpha-MSH was the major form of alpha-MSH. The profile of alpha-MSH contained in and secreted into culture medium by canine PI cells was found to be very similar to that in PI tissue extracts. The proportion of monoacetyl-alpha-MSH and diacetyl-alpha-MSH secreted by cultured canine AL cells and contained in extracts of AL cells in culture, however, was much higher than that in tissue extracts. These results indicate that in the dog, as in all other mammalian species studied, acetylated forms of alpha-MSH predominate in PI tissue, while nonacetylated alpha-MSH is the major form in AL tissue. It appears, however, that acetylation of alpha-MSH may occur in cultured canine AL cells, possibly as a result of the absence of factors that normally inhibit acetyltransferase in vivo or as a consequence of culture conditions.

Properties of velocity-mechanosensitive neurons of the cat ventrobasal thalamic nucleus with special reference to the concept of convergence.

Neurons in the ventrobasal (VB) thalamic nucleus of lightly anesthetized cats were studied in order to analyze their discharge properties in response to controlled mechanical stimuli. Properties of the vast majority of the neuronal population largely resemble those of peripheral sensitive mechanoreceptors in their response to the velocity and, to a more limited extent, the amplitude component, of skin and hair displacement within restricted receptive fields. Detailed examination reveals some 'complex' characteristics suggestive of central integration in about 11% of VB neurons. Complex properties appear to indicate convergent input reflecting receptive field organization, the variety of velocity-related discharges and patterns of inhibition. The rarity of isolated 'surround' inhibition and the definition of what constitutes 'lemniscal' properties are discussed in the context of these and other related findings.

The antineutrophil antibody in uveitis.

Ninety eight patients with uveitis of various types were tested for the presence of the antineutrophil antibody or ANCA by an indirect immunofluorescence method. This antibody is found in patients with diseases associated with small vessel vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. Eleven true positive cases were found. A positive test was not associated with the anatomical site of the uveitis but was related to the time course of the disease. In particular single/repeated rather than nonrecurrent uveitis was associated with a positive test. Three groups of patients seem more likely to have positive tests: those with bilateral chronic posterior uveitis; a group with an anterior uveitis which is single/repeated who were younger than 46 at disease onset and had isolated eye disease; and an older group, aged 60 years or more at onset, with single/repeated uveitis and systemic features.

Soluble interleukin-2 receptors in retinal vasculitis.

Soluble interleukin-2 receptor (sIL-2R) levels were measured in the serum of 27 patients with retinal vasculitis, 16 with vasculitis purely isolated to the eye (RV) and 11 with vasculitis associated with a systemic inflammatory disease (RV+SID). Levels of sIL-2R were statistically significantly increased (mu 986, SD 845 U/ml, p = 0.013) only in the RV+SID group as compared to healthy controls. The highest levels being found in patients with sarcoidosis (mu 1436, SD 1083 U/ml). There was no correlation with disease activity or with systemic corticosteroid therapy. Serum sIL-2R measurements appear to be of limited use in the management of patients with retinal vasculitis, but may be of value in those patients with sarcoidosis. Longitudinal measurements with larger numbers of patients are required to confirm this. Serum sIL-2R levels were also statistically significantly increased (mu 843, SD 171 U/ml, p less than 0.0001) in 21 patients with Fuchs' heterochromic cyclitis. As this is a chronic condition with mild inflammatory activity and no associated systemic disease, the explanation for this finding is unknown.

Anti-neutrophil cytoplasmic antibodies in uveitis.

The antineutrophil cytoplasmic antibody test has become available over the past 4 or 5 years. It is positive in a limited number of conditions whose characteristic feature is the presence of a small vessel vasculitis. These include Wegener's granulomatosis and microscopic polyarteritis. The test was applied to 63 patients with uveitis of various types. 14 positive tests were found amongst which anterior uveitis was the most common disease present.

Differential referral of women and men to employee assistance programs: the role of supervisory attitudes.

Potential factors underlying sex differences in the referral of problem-drinking subordinates to employee assistance programs (EAPs) were explored in interviews with 120 supervisors in four organizations. Analyses of data obtained in these interviews assessed the relative ability of eight variables to predict supervisor's actual identification and referral of female and male problem drinkers. In addition to numbers of employees supervised, the supervisors' judgment of the EAP's effectiveness was the best predictor of referral and identification, regardless of the sex of the referred subordinate. Knowledge and training in the EAP was a secondary contributor to referral of men, but played no role in female referrals. When controlling for all other variables, the extent to which supervisors held an egalitarian attitude toward women's rights and roles was found to be marginally positively related to identification of female drinkers. Similarly, a less stigmatized, stereotyped view of women's use and abuse of alcohol was marginally associated with a greater likelihood of referral of a female drinker to the EAP. Neither of these attitudinal variables was related to identification or referral of male problem drinkers.

Baseline hematologic, endocrine, and clinical chemistry values in ducks and roosters.

Venous blood samples were collected at 3-day intervals for a total of six samples from each of five adult male pekin ducks and five adult Ross roosters. Twenty biochemical, six hematologic, and three endocrine determinations were performed on each blood or serum sample collected. The data obtained provide reference values for future studies of avian species and illustrate the utility of an automated clinical chemistry analyzer in assessing multiple serum biochemistry values in small sample volumes obtained from birds.

Von Willebrand factor, endothelial damage and ocular disease.

Plasma von Willebrand factor (vWF), a marker for vascular damage, was measured in patients with giant cell arteritis (GCA), central retinal vein occlusion (CRVO), and active intraocular inflammation (AII), vWF was highest in GCA (median 3.52 kIU/L) relative to age matched controls (1.08 kIU/L, p<0.0001), with elevated levels in 75% of patients, the highest values found at disease presentation. Longitudinal measurements showed prolonged elevation of vWF, and increased levels were also found in 50% of patients with clinically inactive disease. In CRVO, raised levels were found in 53% of patients (median 2.32 kIU/L, p = 0.0002), but could not differentiate between an ischaemic and non-ischaemic sub-group. There was no statistical difference between those patients with and without systemic disease. Although vWF was raised in 34% of patients with AII (median 1.26 kIU/L, p = 0.0114), it was not different in uveitis (median 1.26 kIU/L), as compared to retinal vasculitis (median 1.58 kIU/L) or in those patients with and without systemic disease. vWF did not correlate with C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) in any of the groups studied. It appears a sensitive test for detecting vascular damage in GCA and may have a role in monitoring the disease where either a prolonged elevation or alteration of vWF levels may be of importance, particularly if ESR and CRP levels are normal. vWF measurement may be limited to more widespread vascular disease, such as in GCA as it was unable to differentiate between different types of CRVO or AII.

Molecular forms of gastrin in antral mucosa of the horse.

The predominant form of gastrin in the antral mucosa of the stomach of virtually all species previously examined is the 17 amino acid peptide little gastrin (G17). This report describes the occurrence in equine antral mucosa of an immunoreactive form of gastrin with elution properties on Sephadex G-50 superfine similar to human unsulfated big gastrin (G34-I). This putative equine big gastrin was a major component of the gastrin immunoreactivity present. A second peak of activity in equine antral mucosa eluted in an identical manner to human little gastrin (hG17-I). Inhibition curves of equine big and little gastrin, with the gastrin radioimmunoassay utilized in this study, were parallel. This observation indicates that there was no spurious increase in the apparent relative amount of big gastrin due to significant differences in the RIA antibody cross-reactivity to big and little equine gastrin. The equine big gastrin peak was resolved by ion exchange chromatography into unsulfated and sulfated forms in approximately equal amounts. This data implies that posttranslational processing of gastrin in horses may differ from that of species previously studied.

High resolution computed tomography of the temporal bone in infants and children: a review.

Pathologic conditions involving the temporal bone in infants and children are now commonly diagnosed by computed tomography (CT). The importance of utilizing high resolution computed tomography (HRCT) with magnified, thin (1.5 mm) scans in both the axial and coronal planes is stressed in order to obtain the maximal anatomic information that is critical for proper diagnosis. A retrospective analysis of 388 cases reveals a positive diagnostic yield ranging from 65% in temporal bone trauma to 20% in clinically suspected neoplasm. Selected case reports of congenital abnormalities, inflammatory processes, traumatic lesions, and tumors will be presented. We conclude that HRCT is an excellent diagnostic modality and should be used liberally to evaluate the temporal bone in children.

Postprandial serum gastrin concentrations in normal foals.

Postprandial gastrin concentrations were assayed in serum samples from a group of six foals at one day, one week, one month and three months of age. Before sampling, each foal was prevented from feeding for 2 h and was then allowed to suck for 15 mins. Blood samples were taken at the start of the meal and at 30 min intervals for the next 3 h. Feeding increased serum gastrin concentrations at one day, one week and one month, with the greatest increases detected at one day. Mean pre-feeding gastrin concentrations were 25.2 +/- 2.3 pg/ml at one day, 22.8 +/- 3.9 pg/ml at one week, 15.2 +/- 2.3 pg/ml at one month and 15.6 +/- 7.5 pg/ml at three months. Highest mean post prandial concentrations were at 60 mins on Day one (47.4 +/- 15.2 pg/ml) and one month (25.2 +/- 4.1 pg/ml) old foals. There was no apparent post prandial increase in serum gastrin concentrations in foals at three months of age. Precise reasons for changes in postprandial serum gastrin concentrations remain unknown. Factors that could be important include maturation of G cell function, alterations in gastrin metabolism and excretion, and changes in gastrointestinal motility with increasing age.

Urine cortisol:creatinine ratio in healthy and sick cats.

Urine cortisol:creatinine ratios (UCCR) were determined from single urine samples obtained by cystocentesis in 47 cats allotted into 2 groups: 31 healthy cats and 16 sick, hospitalized cats with assorted clinical illnesses. The mean (+/- standard deviation) UCCR for healthy cats was 5.9 +/- 7.0 (median, 3.2; range, 0.6 to 27.8). Age or gonadal status had no significant effect on the magnitude of UCCR within this group. However, sick cats had significantly higher UCCR (P = .002) when compared with healthy cats. The mean UCCR for sick cats was 19.6 +/- 19.2 (median, 14.8; range, 1.7 to 75.1). This report establishes a reference range for UCCR in 31 normal cats and provides evidence that health status affects UCCR in cats.

Prospective reimbursement and the hospital power equilibrium: a matrix-based management control system.

Prospective rate-setting programs have not yet made significant inroads in containing hospital cost inflation. Because these programs are essentially hospital management control systems, they must be conceptually grounded in general management control theory if they are to succeed. Specifically, a rate-setting agency must: 1) perceive itself as "top management" of the hospitals being controlled, 2) incorporate hospital physicians into a matrix-based control structure that assigns physicians financial as well as clinical responsibilities, and 3) develop hospital budgeting and reporting systems that disaggregate costs according to their controlling forces, thereby permitting the alignment of responsibility with controllability.

The ratio of costs to charges: how good a basis for estimating costs?

This study evaluates the accuracy of costs derived from the ratio of costs to charges (RCCs), using costs based on relative value units (RVUs) as the "gold standard." We found that RCC-calculated costs were not a good basis for determining the costs of individual patients. However, when examining average costs per diagnosis-related group (DRG), RCCs performed better. For almost 70% of the DRGs, average RCC-calculated costs were within 10% of average RVU-calculated costs. RCCs were even more reliable for comparing the relative cost of patients in a DRG in one hospital to the average cost of patients in that DRG in a group of hospitals. Charges, or an overall hospital RCC (as opposed to the departmental RCCs we used in most of our analyses), were not a good basis for determining relative hospital costs.