Severe postpartum osteoporosis with increased PTHrP during lactation in a patient after total thyroidectomy and parathyroidectomy.

We present a 27-year-old woman with hypoparathyroidism following total thyroidectomy for papillary carcinoma, who presented postpartum during lactation with several vertebral osteoporotic fractures, increase in bone turnover markers, and measurable parathyroid hormone-related protein (PTHrP) levels. Cessations of lactation led to gradual decrease in bone turnover markers and PTHrP and improvement in bone mineral density. Pregnancy- and postpartum-associated osteoporosis is an uncommon condition characterized by the occurrence of fractures during late pregnancy or the puerperium. The patient presented postpartum with severe back pain and multiple vertebral fractures. Metabolic evaluation performed at presentation revealed hypercalcemia, hypercalciuria, increased alkaline phosphatase, vitamin D insufficiency, normal serum protein immunoelectrophoresis, and a detectable level of PTHrP. Serum levels of bone turnover markers were markedly increased. Bone mineral density at the lumbar spine was severely reduced. After cessation of lactation, the PTHrP level became undetectable. Bone turnover markers gradually decreased to normal and bone mineral density improved. Several factors contributed to the reduced bone mass in this patient, including amenorrhea treated with oral contraceptives, suppressive levothyroxine treatment, and lactation of twins with increased PTHrP. Patients with severely reduced bone mass need surveillance during pregnancy and lactation and should possibly consider avoiding breastfeeding. Patients with hypoparathyroidism should temporarily reduce their alphacalcidiol dose while lactating.

Interindividual heterogeneity in the hypoxic regulation of VEGF: significance for the development of the coronary artery collateral circulation.

BACKGROUND: The coronary artery collateral circulation may be beneficial in protecting against myocardial ischemia and necrosis. However, there is a tremendous interindividual variability in the degree of new collateral formation in patients with coronary artery disease. The basis for this interindividual heterogeneity is not understood. In this study we test the hypothesis that failure to generate collateral vessels is associated with a failure to appropriately induce with hypoxia or ischemia the angiogenic factor, vascular endothelial growth factor (VEGF). METHODS AND RESULTS: We correlated the VEGF response to hypoxia in the monocytes harvested from patients with coronary artery disease with the presence of collaterals visualized during routine angiography. We found that there was a highly significant difference in the hypoxic induction of VEGF in patients with no collaterals compared with patients with some collaterals (mean fold induction 1.9+/-0.2 versus 3.2+/-0.3, P<0.0001). After subjecting the data to ANCOVA, using as covariates a number of factors that might influence the amount of collateral formation (ie, age, sex, diabetes, smoking, hypercholesterolemia), patients with no collaterals still have a significantly lower hypoxic induction of VEGF than patients with collaterals. CONCLUSIONS: This study provides evidence in support of the hypothesis that the ability to respond to progressive coronary artery stenosis is strongly associated with the ability to induce VEGF in response to hypoxia. The observed interindividual heterogeneity in this response may be due to environmental, epigenetic, or genetic causes. This interindividual heterogeneity may also help to explain the variable angiogenic responses seen in other conditions such as diabetic retinopathy and solid tumors.

Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty.

We have demonstrated that a genetic polymorphism in the antioxidant protein haptoglobin is important in determining which patients develop restenosis after percutaneous transluminal coronary angioplasty. Knowledge of the haptoglobin phenotype may be useful in the assessment and utilization of new therapies to reduce restenosis, particularly in patients who are homozygous for the haptoglobin 2 allele.

The cognitive use of language by disadvantaged and nondisadvantaged children.

The cognitive use of language was evaluated among sixth-grade disadvantaged and nondisadvantaged children by eliciting spontaneous language samples in response to a series of 14 auditory stimuli, each depicting one or more human and/or mechanical sounds. -responses were analyzed according to the following dimensions: (a) units of thought: (b) concept formation; (c) parts of the sound responded to; (d) integration; (e) manner of verbalization; and (f) identification. Disadvantaged children manifested significantly fewer units of thought than their advantage counterparts. Several significant trends were noted for several of the remaining dimensions and were discussed. The general cognitive styles of the subject groups were related to the field-dependency-independency dichotomy described in the literature by Witkin and his associates.

Post-meningitic hearing loss: report on three cases.

Three children with post-meningitic hearing loss were seen for evaluation and aural rehabilitation over a 4-yr period. Fluctations in hearing levels during that time period were noted. The hearing of one child improved, while that of the other two children decreased. Changes in sensitivity were documented and discussed with reference to the habilitation process. The need for frequent monitoring and for otologic intervention in the post-meningitic child is emphasized.

Expanding the definition of hypothalamic obesity.

Hypothalamic obesity (HyOb) was first defined as the significant polyphagia and weight gain that occurs after extensive suprasellar operations for excision of hypothalamic tumours. However, polyphagia and weight gain complicate other disorders related to the hypothalamus, including those that cause structural damage to the hypothalamus like tumours, trauma, radiotherapy; genetic disorders such as Prader-Willi syndrome; side effects of psychotropic drugs; and mutations in several genes involved in hypothalamic satiety signalling. Moreover, 'simple' obesity is associated with polymorphisms in several genes involved in hypothalamic weight-regulating pathways. Thus, understanding HyOb may enhance our understanding of 'simple' obesity. This review will claim that HyOb is a far wider phenomenon than hitherto understood by the narrow definition of post-surgical weight gain. It will emphasize the similarity in clinical characteristics and therapeutic approaches for HyOb, as well as its mechanisms. HyOb, regardless of its aetiology, is a result of impairment in hypothalamic regulatory centres of body weight and energy expenditure. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as, leptin on the one hand and dysfunctional afferent signals, on the other hand. The most important afferent signals deranged are energy regulation by the sympathetic nervous system and regulation of insulin secretion. Dys-regulation of 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) activity and melatonin may also have a role in the development of HyOb. The complexity of the syndrome requires simultaneous targeting of several mechanisms that are deranged in the HyOb patient. We review the studies evaluating possible treatment strategies, including sympathomimetics, somatostatin analogues, triiodothyronine, sibutramine, and surgery.

Most comfortable listening for the loudness and intelligibility of speech.

The effect of instructional set upon most comfortable listening (MCL) was investigated among normal listeners. MCL level and range were determined (method of limits) in relation to listening for comfortable speech loudness versus comfortable speech intelligibility. The results indicate that instructional set does influence listener performance. the mean MCL level for comfortable speech intelligibility was significantly higher (4.96 dB) than the mean level for comfortable speech loudness; the mean MCL range for comfortable speech intelligibility was higher by 7.33 dB and wider by 7.10 dB than the mean range for speech loudness. Ascending stimulus presentation obtained comparable MCL levels for both listening conditions, whereas descending presentation obtained a mean MCL level almost 10 dB higher for comfortable speech intelligibility than for comfortable speech loudness. Males achieved slightly higher MCL levels than did females for both loudness (4.32 dB) and intelligibility (4.96 dB) criteria. It was concluded that the nature of the instructional set be taken into account when interpreting comfortable listening measures.

Perception of speech pattern contrasts using a multichannel cochlear implant.

The ability to perceive for suprasegmental and eight segmental speech pattern contrasts was measured on 16 adult cochlear implantees using the Nucleus multichannel prosthesis with either F0-F2 (n = 9) or F0-F1-F2 (n = 7) coding. The results of this study indicated the following: (1) The Nucleus device provided significant access to the majority of suprasegmental and segmental speech contrasts. (2) Both one- and two-format coding strategies provided good access to speech pattern contrasts. (3) Considerable intersubject differences in performance were observed, but there was no evidence to suggest that these were related to either processing scheme. (4) Although the accessibility of speech contrasts varied, the pattern of perceptual performance was interpreted in terms of an acoustic/phonetic hierarchy. (5) The Speech Pattern Contrast (SPAC) test appears to be a practical procedure for analyzing the perception of phonologically salient information about the suprasegmental and segmental components of speech.

Effect of text complexity on connected discourse tracking rate.

The effect of three levels of text complexity upon connected discourse tracking rates was investigated in normal listeners who tracked by lipreading alone and by lipreading with auditorily presented voice pitch. Text complexity affected connected discourse tracking under both lipreading conditions, with tracking rates decreasing as the level of text complexity increased. The improvement in tracking rate with the addition of voice pitch information was found to be invariant over changes in text complexity when expressed as a simple difference between the two tracking rates.

Children's perception of speech in reverberation.

Recordings of nonsense syllables (VCV construction) were presented to groups of children aged 5, 7, 9, 11, and 13 years and young adults under monaural (reverberation time = 0.6s) and binaural (reverberation times = 0, 0.4, and 0.6 s) conditions of reverberation. Phoneme identification performance was affected by age, reverberation, and mode of presentation (monaural versus binaural). The major findings were (1) phoneme identification scores in reverberant conditions improved with increasing age and decreased with increased reverberation time; (2) children's performance in reverberant conditions did not reach asymptote until age 13; (3) binaural performance was consistently better than monaural performance for all age groups, with 5-year-olds showing the largest binaural advantage.

Binaural and monaural speech discrimination under reverberation.

This study investigated the effects of reverberation upon the speech discrimination performance of 30 normally hearing subjects and 30 persons with bilateral sensorineural hearing loss. Following preliminary tests, the Modified Rhyme Test was administered monaurally and binaurally at reverberation times of 0, 1, 2 and 3 sec. All stimuli were administered under earphones. The lists and conditions were appropriately randomized and counterbalanced so that each subject heard a test list at each reverberation time (RT) monaurally and binaurally. The expected gain due to binaural summation of loudness was simulated in order to test the possibility that any binaural enhancement of intelligibility might be due to binaural loudness summation. For all conditions, the normally hearing subjects performed significantly better than the hearing-impaired group. However, in relative terms, the two groups were remarkably similar. Binaural scores were significantly higher than monaural scores at each RT for both groups (in spite of homophasic conditions). For both groups, monaural and binaural scores decreased with increasing RT. Monaural scores decreased at a significantly faster rate with RT than did the binaural scores (the binaural advantage, however, was larger for the normal group). Increasing the monaural presentation levels to simulate the binaural loudness gain did not result in higher scores. It was concluded that speech discrimination under reverberation is better binaurally than monaurally for both normally hearing and hearing-impaired persons. This is due, at least partly, to the ability of the binaural auditory system to squelch the effects of reverberation. A tentative model is suggested for the binaural squelch of reverberation. The current findings are compared with existing data; and suggestions are offered for clinical application.

Effects of noise and noise suppression on speech perception by cochlear implant users.

The recognition of phonemes in consonant-vowel-consonant words, presented in speech-shaped random noise, was measured as a function of signal to noise ratio (S/N) in 10 normally hearing adults and 10 successful adult users of the Nucleus cochlear implant. Optimal scores (measured at a S/N of +25 dB) were 98% for the average normal subject and 42% for the average implantee. Phoneme recognition threshold was defined as the S/N at which the phoneme recognition score fell to 50% of its optimal value. This threshold was -2 dB for the average normal subject and +9 dB for the average implantee. Application of a digital noise suppression algorithm (INTEL) to the mixed speech plus noise signal had no effect on the optimal phoneme recognition score of either group or on the phoneme recognition threshold of the normal group. It did, however, improve the phoneme recognition threshold of the implant group by an average of 4 to 5 dB. These findings illustrate the noise susceptibility of Nucleus cochlear implant users and suggest that single-channel digital noise reduction techniques may offer some relief from this problem.

Regulation of VEGF in diabetic patients with critical limb ischemia.

Diabetic patients are at a 10- to 20-fold increased risk for the development of critical limb ischemia. Vascular endothelial growth factor (VEGF) is critical for the development of collateral blood vessels, which can effectively bypass peripheral arterial occlusions. We therefore set out to determine if the regulation of VEGF in patients with peripheral vascular disease differs in diabetic and nondiabetic patients. Diabetic and nondiabetic patients with peripheral vascular disease were divided into those with or without critical limb ischemia as defined by clinical criteria (rest pain, nonhealing ulcer). Monocytes from peripheral blood were isolated from all patients and the hypoxic induction of VEGF was determined in vitro. In patients without diabetes, we found that there was no significant difference in the hypoxic induction of VEGF between patients with or without critical limb ischemia. However, in diabetic patients we found that patients with critical limb ischemia produced significantly more VEGF than patients without critical limb ischemia (6.3 +/- 1.3 vs. 2.1 +/- 0.3, p < 0.015). We conclude that diabetic patients with critical limb ischemia do not have an impairment in the ability to produce VEGF with hypoxia. Contrary to current dogma, treatment paradigms directed at increasing VEGF production in the diabetic patient with critical limb ischemia might not be beneficial.

Haptoglobin phenotype and diabetic nephropathy.

AIMS/HYPOTHESIS: To determine if the haptoglobin 2 allele is associated with an increased risk for the development of diabetic nephropathy. METHODS: This study included 110 consecutive normotensive subjects with Type I (insulin-dependent) diabetes mellitus and Type II (non-insulin-dependent) diabetes mellitus seen in two outpatient clinics in Israel. Diabetes duration was greater than 10 years for Type I diabetes and more than 5 years for Type II diabetic subjects. Microalbuminuria was defined as urinary protein excretion of 30 to 300 mg/24 h, and macroalbuminuria was defined as urinary protein excretion of greater than 300 mg/24 h. Serum was taken from subjects for haptoglobin typing by gel electrophoresis. RESULTS: Of the participating subjects 54 had Type I and 56 had Type II diabetes. None (0/18) of the subjects homozygous for the haptoglobin 1 allele (1-1) showed any sign of diabetic nephropathy, as compared with 34 % (19/55) of subjects homozygous for the haptoglobin 2 allele (2-2) and 27 % (10/37) of heterozygous subjects (2-1) (p < 0.04). Of the subjects 29 showed macroalbuminuria. The risk of developing macroalbuminuria was found to be greater in subjects with two haptoglobin 2 alleles (22 %) (12/55) as compared with one haptoglobin 2 allele (8 %) (3/37) or no haptoglobin 2 alleles (0%) (0/18) (p < 0.03). CONCLUSION/INTERPRETATION: By showing a graded risk relation to the number of haptoglobin 2 alleles in Type I and Type II diabetic subjects, these studies further support our hypothesis that the haptoglobin phenotype is a major susceptibility gene for the development of diabetic nephropathy.