Odor identification in Huntington's disease patients and asymptomatic gene carriers

Odor identification was assessed in 20 Huntington's disease (HD) patients, 20 normal adults with the genetic mutation that causes HD, and 20 mutation-negative adults. The University of Pennsylvania Smell Identification Test (UPSIT) revealed substantial odor identification deficits only in HD patients.     

Concerns and expectations in patients presenting with physical complaints. Frequency, physician perceptions and actions, and 2-week outcome

BACKGROUND: Specific concerns and expectations may be a key reason that people with common physical complaints seek health care for their symptoms. OBJECTIVES: To determine the frequency of symptom-related patient concerns and expectations, physician perceptions and actions, and the relationship of these factors to patient satisfaction and symptom outcome. METHODS: This was a prospective cohort study of 328 adult outpatients presenting for evaluation of a physical complaint. The setting was a general medicine clinic in a teaching hospital. Measures included previsit patient questionnaire to identify symptom-related concerns and expectations; a postvisit physician questionnaire to determine physician perceptions and actions; and a 2-week follow-up patient questionnaire to assess symptom outcome and satisfaction with care. RESULTS: Pain of some type accounted for 55% of common symptoms, upper respiratory tract illnesses for 22%, and other physical complaints for 23%. Two thirds of patients were worried their symptom might represent a serious illness, 62% reported impairment in their usual activities, and 78%, 46%, and 41% hoped the physician would prescribe a medication, order a test, or provide a referral. Physicians often perceived symptoms as less serious or disabling and frequently did not order anticipated tests or referrals. While symptoms improved 78% of the time at 2-week follow-up, only 56% of patients were fully satisfied. Residual concerns and expectations were the strongest correlates of patient satisfaction. CONCLUSIONS: Improved recognition of symptom-related concerns and expectations might improve satisfaction with care in patients presenting with common physical complaints.     

Escalation of a fetish: coprophagia in a nonpsychotic adult of normal intelligence

The possibility of a dyschondroplastic syndrome should be considered in any patient presenting with a cartilagenous tumor in the head and neck. Classification of the patient as Maffucci's syndrome or Ollier's disease increases the need for vigilant observation for the development of sarcomatous lesions and can help differentiate between low-grade chondrosarcoma and atypical enchondroma.     

Cyclic AMP-dependent protein kinase enhances hippocampal dentate granule cell GABAA receptor currents

1. The effects of activation of endogenous adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA), intracellular application of PKA and inhibition of endogenous PKA by protein kinase inhibitory peptide (PKIP) on hippocampal dentate granule cell gamma-aminobuturic acid A (GABAA) receptor (GABAR) currents were characterized. 2. GABAR currents evoked by repeated application of GABA (30 or 100 microM) were enhanced by application of 1 mM norepinephrine (52 +/- 26%; mean +/- SE; n = 11) and of 500 mM 8-bromo cAMP (15 +/- 2%, n = 7). 3. GABA concentration response curves were obtained from six dentate granule cells before and after application of 500 microM 8-bromo cAMP. The maximal current was increased significantly by 89 +/- 36%, but the mean EC50 was not significantly changed (68 +/- 42 microM vs. 25 +/- 10 microM). 4. The GABA concentration response relationship was studied in a group of 7 granule cells recorded with pipettes containing PKIP and 2 mM ATP and compared with another group of 12 cells recorded with 2 mM ATP in the pipette. When currents were recorded with intracellular PKIP, the mean EC50 for GABA was no different (43 +/- 9 microM vs. 45 +/- 16 microM); however, the maximal current obtained was smaller, (961 +/- 102 pA vs. 658 +/- 104 pA). 5. Concentration response data were obtained from four granule cells using recording pipettes containing the cPKA and an ATP regeneration system and compared with seven cells recorded with the ATP regeneration system. With cPKA, the maximal GABAR current was significantly larger (1,224 +/- 132 pA vs. 718 +/- 56 pA), but the EC50 for GABA was not significantly altered (21 +/- 2.0 microM vs. 79 +/- 25 microM).     

Effect of multiple coil closure of patent ductus arteriosus on blood flow to the left lung as determined by lung perfusion scans

This paper describes a combined inpatient and partial hospital program, with a ten-bed short-term inpatient unit and a partial hospital program that can accommodate 24 patients. Inpatients and partial hospital patients are treated together by the same staff in a program located in the partial hospital. The authors highlight features of the program that address the five elements of continuity: place, personnel, program, patient-peers, and plan for treatment. The discussion focuses on the importance of continuity in sustaining a combined unit; potential benefits for patients, families, staff, and trainees; attractiveness to third-party payers; and impediments to fully realizing the potential of the unit.     

A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease

Recent clinical studies of Crohn's disease patients demonstrated dramatic clinical responses following one i.v. infusion of a chimeric mAb to TNF-alpha (cA2). To assess the role of TNF-alpha in mucosal cytokine regulation, the effects of TNF-alpha on lamina propria mononuclear cell (LPMC) Th1 production were determined. Increased IFN-gamma production was demonstrated in anti-CD2-stimulated LPMC cultured in TNF-alpha. To determine the effects of cA2 on cytokine production, TNF-alpha- and IFN-gamma-producing cells were quantitated in LPMC from five Crohn's disease patients treated with cA2. In all four patients who demonstrated clinical and endoscopic improvement, decreased numbers of LPMC producing IFN-gamma and TNF-alpha following CD2/CD28 activation paralleled improvement in disease activity over 8 wk. In one patient who did not improve, increased numbers of TNF-alpha- and IFN-gamma-secreting LPMC were observed. In three of four responding patients, CD2/CD28-activated PBMC demonstrated increased IFN-gamma production over 8 wk. These observations suggest that TNF-alpha may be a cofactor for mucosal Th1 responses, and improvement in clinical parameters and intestinal inflammation induced by cA2 in Crohn's disease may be mediated by down-regulation of mucosal Th1 cytokines.     

Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode

Temporal summation of sensory intensity was investigated in normal subjects using novel methods of thermal stimulation. A Peltier thermode was heated and then applied in a series of brief (700 ms) contacts to different sites on the glabrous skin of either hand. Repetitive contacts on the thenar or hypothenar eminence, at interstimulus intervals (ISIs) of 3 s, progressively increased the perceived intensity of a thermal sensation that followed each contact at an onset latency > 2 s. Temporal summation of these delayed (late) sensations was proportional to thermode temperature over a range of 45-53 degrees C, progressing from a nonpainful level (warmth) to painful sensations that could be rated as very strong after 10 contacts. Short-latency pain sensations rarely were evoked by such stimuli and never attained levels substantially above pain threshold for the sequences and temperatures presented. Temporal summation produced by brief contacts was greater in rate and amount than increases in sensory intensity resulting from repetitive ramping to the same temperature by a thermode in constant contact with the skin. Variation of the interval between contacts revealed a dependence of sensory intensity on interstimulus interval that is similar to physiological demonstrations of windup, where increasing frequencies of spike train activity are evoked from spinal neurons by repetitive activation of unmyelinated nociceptors. However, substantial summation at repetition rates of > or = 0.33 Hz was observed for temperatures that produced only late sensations of warmth when presented at frequencies < 0.16 Hz. Measurements of subepidermal skin temperature from anesthetized monkeys revealed different time courses for storage and dissipation of heat by the skin than for temporal summation and decay of sensory intensity for the human subjects. For example, negligible heat loss occurred during a 6-s interval between two trials of 10 contacts at 0.33 Hz, but ratings of sensory magnitude decreased from very strong levels of pain to sensations of warmth during the same interval. Evidence that temporal summation of sensory intensity during series of brief contacts relies on central integration, rather than a sensitization of peripheral receptors, was obtained using two approaches. In the first, a moderate degree of temporal summation was observed during alternating stimulation of adjacent but nonoverlapping skin sites at 0.33 Hz. Second, temporal summation was significantly attenuated by prior administration of dextromethorphan, a N-methyl-D-aspartate receptor antagonist.     

Regulation and expression of human Fabs under the control of the Escherichia coli arabinose promoter, PBAD

BACKGROUND: The L-arabinose operon from E. coli contains an inducible promoter PBAD which has been extensively studied for the control of gene expression. PBAD has a number of potential advantages over Plac, and has been used successfully to promote high level expression of recombinant proteins. OBJECTIVES: The aim of this study was to investigate PBAD as an alternative system to Plac for the bacterial expression of recombinant Fabs. STUDY DESIGN: The promoter PBAD from the E. coli arabinose operon araBAD and the gene encoding the regulator of this promoter, were cloned into the phagemid expression vector MCO1. Expression of human recombinant tetanus toxoid (TT) and c-erbB2 Fabs under the control of PBAD was compared at two induction temperatures with the same Fabs produced under the control of Plac. RESULTS: Expression of TT and c-erbB2 Fabs under the control of PBAD was comparable to Fab expression from Plac. However, highly expressed TT Fab under the control of PBAD was localised to the soluble periplasmic fraction whereas under the control of Plac, there was greater leakage of Fab into the culture supernatant. In addition, Fab expression from PBAD could be more tightly repressed than from Plac. CONCLUSION: PBAD is a useful and cheaply inducible alternative to the more commonly used Plac for the rapid expression of soluble recombinant human antibody fragments.