Synthesis of the protected tridecapeptide (56–68) of the VH domain of mouse myeloma immunoglobulin M603 and its reattachment to resin supports

A protected tridecapeptide, representing a new peptide corresponding to residues 56–68 of the V_H domain in the mouse M603 myeloma protein, has been prepared by solid phase peptide synthesis. The protected tridecapeptide was prepared using the photolabile 4-bromomethyl-(3-nitro)-benzamidomethyl-resin and the multidetachable 2-[4-bromomethyl)phenylacetoxy] propionyl-resin as solid supports. The synthetic protocol and protecting groups were the same for both syntheses. The protected tridecapeptide was removed photolytically from both supports and the sequence integrity was determined by preview analysis using the solid phase Edman degradation procedure. The protected tridecapeptide-OMPA was purified to homogeneity by DMF/H₂O precipitation and LH-60 chromatography. The purity of the protected peptide was further demonstrated by high pressure liquid chromatography on the free peptide after HF deprotection. The protected tridecapeptide was reattached to 4-bromomethyl-(3-nitro)-benzamidomethyl-resin to give the photolabile Boc-(protected) peptidyl-4 - oxymethyl - (3 - nitro) benzamidomethyl - resin in 25% yield. The protected tridecapeptide-oxymethylphenylacetic acid derivative was reattached to aminomethyl-resin to give Boc -(protected)peptidyl-2-[(4-oxymethyl)phenyl]acet-amidomethyl-resin in 45% yield and to 2-bromopropionyl-resin generating the multidetachable Boc - (protected)peptidyl - 2 - [(4 - oxymethyl) phenylacetoxy] propionyl-resin in 80% yield. The reactivity of these reattached peptides was demonstrated by the quantitative coupling of Boc-leucine to the protected peptide-resin. The advantages and disadvantages of the different resins with respect to solid phase fragment synthesis are discussed.     

Malnutrition and Clinical Outcomes: The Case for Medical Nutrition Therapy

Malnutrition is not a new or a rare problem. In studies involving more than 1,327 hospitalized adult patients, 40% to 55% were found to be either malnourished or at risk for malnutrition, and up to 12% were severely malnourished. Surgical patients with likelihood of malnutrition are two to three times more likely to have minor and major complications as well as increased mortality; and their length of stay can be extended by 90% compared with the stay of well-nourished patients. Hospital charges are reported to be from 35% to 75% higher for malnourished patients than for well-nourished patients. Obtaining data to assess the nutritional status of patients is essential to optimal patient care, especially for patients at high risk for malnutrition. Nutrition assessment can be done with readily available and relatively inexpensive methods. But it is not enough to assess and identify malnutrition. Outcomes are improved and costs are saved only when appropriate intervention follows. This article identifies many well-conducted, published studies that support the findings that health outcomes of malnourished patients can be improved and that overall use of resources can be reduced by nutrition counseling, oral diet and oral supplements, enteral formula delivered via tube, and parenteral nutrition support via central or peripheral line. Early nutrition assessment and appropriate nutrition intervention must be accepted as essential for the delivery of quality health care. Appropriately selected nutrition support can address the problem of malnutrition, improve clinical outcomes, and help reduce the costs of health care. J Am Diet Assoc. 1996; 96:361-366,369.     

The Wessex Growth Study: First Report

Voss, L., Walker, J., Lunt, H., Wilkin, T. and Betts, P. (Department of Paediatrics and the Endocrine Section, Department of Medicine II, General Hospital, Southampton, UK). The Wessex growth study: first report. Acta Paediatr Scand [Suppl] 349: 65, 1989.
The Wessex Growth Study is a community-based longitudinal survey of short children recruited from two Health Districts in Wessex during 1985–86 (cohort I) and 1986–87 (cohort II). Screening of new school entrants during 1985–86 identified only 1.3% who were at or below the 3rd centile for height as defined by Tanner and Whitehouse, suggesting a strong secular trend and an urgent need for updated height charts. After exclusion of the small number of children with underlying organic pathology and those from ethnic minorities, there were 84 children in cohort I on whom this report is based. These apparently normal, short children were sex- and age-matched with normal controls (10th-90th centile) from the same school class. Forty-two per cent of cohort I had a delayed bone age, and 34% lay above the 3rd centile after correction for parental height. Forty-four per cent were of low birth weight. The correlation between two successive height velocities measured at 6 and 12 months was only -0.14 for cohort I and -0.15 for their controls. Twelve-month mean height velocity SD scores (SDS) were -0.45 and +0.25, respectively, corresponding to the 33rd and 60th centiles, and rather higher than the 25th and 50th centiles expected in view of the heights of these children. Thirty-eight per cent of cohort 1 had a 12-month height velocity below the 25th centile, and in 16% height velocity was below the 10th centile. As a group, the children in cohort I grew more slowly than their controls, hut the height velocity in 88% of cases lay within the control range. For any individual, therefore, 12-month height velocity was not a useful discriminant of growth failure. Repeated measurements are indicated.     

Arousal thresholds during human tonic and phasic REM sleep

The goal of the present study was to investigate arousal thresholds (ATs) in tonic and phasic episodes of rapid eye movement (REM) sleep, and to compare the frequency spectrum of these sub‐states of REM to non‐REM (NREM) stages of sleep. We found the two REM stages to differ with regard to behavioural responses to external acoustic stimuli. The AT in tonic REM was indifferent from that in sleep stage 2, and ATs in phasic REM were similar to those in slow‐wave sleep (stage 4). NREM and REM stages of similar behavioural thresholds were distinctly different with regard to their frequency pattern. These data provide further evidence that REM sleep should not be regarded a uniform state. Regarding electroencephalogram frequency spectra, we found that the two REM stages were more similar to each other than to NREM stages with similar responsivity. Ocular activity such as ponto‐geniculo‐occipital‐like waves and microsaccades are discussed as likely modulators of behavioural responsiveness and cortical processing of auditory information in the two REM sub‐states.     

The diurnal distribution of sleep propensity: experimental data about the interaction of the propensities for slow-wave sleep and REM sleep

The aim of the present study was to assess the diurnal variation of sleep propensity by evaluating the temporal distribution of sleep onset latency (SOL) and REM- and slow-wave sleep (SWS) parameters in systematically scheduled daytime naps for 12 young males. To reduce the effect of prior SWS on subsequent REM sleep, a double-nap technique was used, i.e. two adjacent naps A and B, which were separated by a 10-min break. Nap duration was adjusted in such a way that nap A allowed 30 min of sleep and nap B one complete NREM–REM cycle. EEG slow wave activity (SWA, power density from 0.5–4 Hz) was estimated from nap A and REM sleep parameters from nap B. The time span between 08.00 hours and 24.00 hours was covered by nine double-naps at 2 h intervals. The order of the nap sessions was systematically varied within and across subjects. For each subject, the time between successive double-nap recordings was at least three days. SOL was shortest in the time interval 12.00 hours to 16.00 hours and significantly longer between 20.00 hours and 24.00 hours. REM sleep duration and the percentage of sleep onset REM episodes decreased continuously from 08.00 hours to the interval 18.00–20.00 hours and increased thereafter, with a time course inversely related to the one of body temperature, which was also measured continuously. SWA showed a steady, threefold increase from 08.00 hours to 24.00 hours. The study offers new data on the diurnal variation of sleep propensity which seems to be a composite function of the drives for SWS and REM sleep.     

PREVALENCE, MORPHOLOGY AND BIOLOGY OF RENAL CELL CARCINOMA IN VON HIPPEL-LINDAU DISEASE COMPARED TO SPORADIC RENAL CELL CARCINOMA

Purpose

Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology.

Materials and Methods

We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease.

Results

The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p <0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm.

Conclusions

Von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.