Clinical profiling of recombinant follicle stimulating hormone (rFSH; Puregon): relationship between serum FSH and efficacy

Single-dose and multiple-rising dose studies of recombinantfollicle stimulating hormone (rFSH) in hypogonadotrophic maleand female volunteers demonstrated that the rate of FSH absorptionafter i.m. injection is higher in men than in women. In theabsence of endogenous FSH, a correlation between serum FSH andbody weight became apparent. The elimination half-life of rFSHwas not different between the sexes and was comparable withurinary FSH. However, the in-vitro bio:immuno ratio of serumFSH was significantly higher after the administration of rFSHthan after urinary FSH. When rFSH was administered daily witha fixed dose, steady state levels were reached within 3-5 days.Serum FSH concentrations increased in a dose-dependent mannerwhen the daily dose was increased weekly over 3 weeks from 75to 225 IU. In hypogonadotrophic women, rFSH induced normal folliculargrowth whereas oestrogen synthesis was impaired. In women pituitarysuppressed by a high-dose oral contraceptive, the daily administrationof 150 IU rFSH for 1 week induced more and larger antral folliclesthan the same regimen with urinary FSH, whereas the serum immunoactiveFSH concentrations measured 24 h after each dosing were similar.It is concluded that even though equal or lower serum immunoactiveFSH concentrations were obtained following the administrationof rFSH compared with urinary FSH, circulating bioactivity FSHconcentrations were higher. Therefore, the conventional ideathat serum immunoreactive FSH correlates positively with themagnitude of the ovarian response should be reconsidered.     

A nasal whole-cell pertussis vaccine induces specific systemic and cross-reactive mucosal antibody responses in human volunteers

A whole-cell pertussis vaccine, each dose consisting of 250 microg of protein, was given intranasally four times at weekly intervals to six adult volunteers. All vaccinees responded with increases in nasal fluid IgA antibodies to Bordetella pertussis whole-cell antigen. Three vaccinees with high nasal antibody responses also developed increased serum IgA and IgG antibodies to this antigen. Salivary antibody responses to the whole-cell antigen, as well as antibodies in serum and secretions to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were negligible, except for a moderate increase in nasal fluid antibodies to FHA. Unexpectedly, the same vaccinees developed significant rises in nasal and salivary IgA antibodies to meningococcal outer-membrane antigens, whereas corresponding serum IgA and IgG antibodies were unchanged. Thus it appears that mucosal immunisation may induce secretory antibodies with broader specificities than can be found in serum.     

Transition to virtual clinic: Experience in a multidisciplinary clinic for Down syndrome

The COVID‐19 pandemic necessitated a rapid transition from in‐person office visits to virtual visits in the Down syndrome specialty program at Massachusetts General Hospital (MGH DSP). We describe the clinic transition to virtual visits in April 2020 and reflect on our six‐month experience in virtual visits. Clinic metrics were tracked. Electronic survey responses were collected from caregivers attending virtual visits. Input from the MGH DSP team was collected. From April to September 2020, we maintained patient volume (45 visits per month) and overall satisfaction score (6.7 out of 7) following a sudden, unanticipated transition to virtual visits. Survey of 17 caregivers attending virtual visits found that most were equipped with technology, had access to a private location, and most were able to access visit without any limitations. Caregivers appreciated the convenience of virtual visits but sometimes missed the personal connection of an in‐person visit. Overall, though, virtual visits were frequently viewed as no different than office visits. Team members identified benefits and challenges of virtual visits, as well as lessons learned from this transition. We were able to maintain multidisciplinary, specialty care with optimal caregiver feedback and sustained number of patient visits.     

Pinprick and Light Touch Are Adequate to Establish Sensory Dysfunction in Patients with Lumbar Radicular Pain and Disc Herniation

BackgroundThe frequency with which sensory disturbances occur in patients with radicular leg pain and disc herniation is not well known, and the efficacy of tests to identify such changes are not firmly established. The presence of sensory disturbances is a key sign of nerve root involvement and may contribute to the diagnosis of a lumbar disc herniation, identify patients for referral to spinal imaging and surgery, and improve disease classification.Questions/purposesIn this study, we sought: (1) to determine the frequency with which abnormal sensory findings occur in patients with lumbar disc herniation–related radicular pain, using a standard neurological sensory examination; (2) to determine what particular standard sensory test or combination of tests is most effective in establishing sensory dysfunction; and (3) to determine whether a more detailed in-depth sensory examination results in more patients being identified as having abnormal sensory findings.MethodsBetween October 2013 and April 2016, 115 patients aged 18 to 65 years referred to secondary health care with radicular leg pain and disc herniation were considered potentially eligible for inclusion in the study. Based on these inclusion criteria, 79% (91) were found eligible. Ten percent (11) were excluded because of other illness that interfered with the study purpose, 3% (3) because of cauda equina syndrome, 2% (2) because of spinal stenosis, 2% (2) because of prior surgery at the same disc level, and 2% (2) because of poor Norwegian language skills. Three percent (4) of the patients did not want to participate in the study. Of the 91 eligible patients, 56% (51) consented to undergo a comprehensive clinical examination and were used for analysis here. The sample for the purposes of the present study was predetermined at 50. These patients were first examined by a standard procedure, including sensory assessment of light touch, pinprick, vibration, and warmth and cold over the back and legs. Second, an in-depth semiquantitative sensory testing procedure was performed in the main pain area to assess sensory dysfunction and improve the detection of potential positive sensory signs, or sensory gain of function more precisely. Sensory loss was defined as sensations experienced as distinctly reduced in the painful side compared with the contralateral reference side. In contrast, sensory gain was defined as sensations experienced as abnormally strong, unpleasant, or painful and distinctly stronger than the contralateral side. Ambiguous test results were coded as a normal response to avoid inflating the findings. The proportions of abnormal findings were calculated for each sensory modality and for all combinations of the standard examination tests.ResultsThe standard examination identified at least one abnormal finding in 88% (45 of 51) of patients. Sensory loss was present in 80% (41), while sensory gain was present in 35% (18). The combination of pinprick and light touch identified all patients who were classified as having abnormal findings by the full standard examination. The semiquantitative procedure identified an additional three patients with an abnormal finding.ConclusionWe suggest that the combination of pinprick and light touch assessment is an adequate minimal approach for diagnostic and classification purposes in patients with lumbar radicular pain.Level of EvidenceLevel I, diagnostic study.     

Lead-based paint testing technologies: summary of an EPA/HUD field study.

The U.S. Environmental Protection Agency and the U.S. Department of Housing and Urban Development sponsored a field study of portable technologies for testing for lead in paint in three U.S. cities in 1993. Six chemical test kits and six X-ray fluorescence instruments, which represented the two main types of portable technologies available for residential lead testing at that time, were evaluated. Painted building components in single-family and multifamily housing units were selected to assess the performance of these products under real-world conditions. The study found that the chemical test kits were not effective in distinguishing lead-based paint, as defined by federal standards, from nonlead based paint. The X-ray fluorescence instruments were, under certain circumstances, found to be effective. The study filled an informational gap about the accuracy and precision of the portable lead-testing technologies. This article describes the design of the study and its major findings.     

Enhancement of acetylcholine release by homoanatoxin-a from Oscillatoria formosa

The strain NIVA-CYA 92 of Oscillatoria formosa Bory ex Gormont produces phycotoxins with neurotoxic properties. Chemical analysis by gas chromatography/mass spectrometry of a water extract of lyophilized material of the organism showed the presence of only homoanatoxin-a. The mechanism of action of homoanatoxin-a on peripheral cholinergic nerves is so far not known. The neurotoxicity of O. formosa containing homoanatoxin-a was investigated in rat bronchi, rat brain synaptosomes and in GH(4)C(1) cells. The water extract of lyophilized material of the organism produced a concentration-dependent reversible increase in the release of [(3)H]acetylcholine from both K(+) (51 mM) depolarised and non-depolarised cholinergic nerves of the rat bronchial smooth muscle. The K(+)-evoked release of [(3)H]acetylcholine was enhanced by about 75% by a water extract from 15-20 mg/ml of lyophilized algal material. The enhanced release of [(3)H]acetylcholine was substantially reduced by the L-type Ca(2+)-channel blocker verapamil (100 μM) and not by the N-type Ca(2+)-channel blocker ω-conotoxin GVIA (1.0 μM) or the P-type Ca(2+)-channel blocker ω-agatoxin IV-A (0.2 μM). Chelation of intra-cellular Ca(2+) by 1,2-bis-(aminofenoxi)etan-N,N,N',N'-tetraacidic acid/acetoxymethyl (BAPTA/AM) (30 μM) had no effect on the phycotoxin-induced release of [(3)H]acetylcholine, indicating that an extracellular pool of Ca(2+) was important for the action of the phycotoxin on the release of [(3)H]acetylcholine from peripheral cholinergic nerves. In rat brain synaptosomes the algal extract enhanced the influx of (45)Ca(2+) in a tetrodotoxin (1.0 μM) and ω-conotoxin MVIIC (blocker of N-, P- and Q-type Ca(2+) channels) (1.0 μM) insensitive manner. Patch-clamp studies showed that the phycotoxin opened endogenous voltage dependent L-type Ca(2+) channels in neuronal GH(4)C(1) cells. These Ca(2+) channels and the effect of the toxin on the channels were blocked by the L-type Ca(2+)-channel antagonist gallopamil (200 μM). The present results suggest, therefore, that the investigated strain of O. formosa contains homoanatoxin-a, which enhances the release of acetylcholine from peripheral cholinergic nerves through opening of endogenous voltage dependent neuronal L-type Ca(2-) channels.     

Increased levels of intercellular adhesion molecules and vascular cell adhesion molecules in pre-eclampsia

Objective To investigate the correlation between soluble forms of the intercellular adhesion molecule (SICAM-1) and vascular cell adhesion molecule (sVCAM-1) and the severity of pre-eclampsia or its possible consequences for fetal growth.
Design Prospective observational study.
Setting Institute of Medical Genetics, University of Oslo, Department of Medical Genetics and Haematological Research Laboratory, Ullevål University Hospital; and the Department of Obstetrics and Gynaecology, The National Hospital, Oslo, Norway.
Participants Seventy-six women with normotensive pregnancies and 157 women with pre-eclampsia divided into three subgroups: mild, severe and pre-eclampsia with fetal growth retardation.
Methods ELISA-measurements of plasma SICAM-1 and sVCAM-1 were performed in a group of healthy pregnant normotensive women and three groups of women with varying degrees of pre-eclampsia.
Results SICAM-1 concentrations were higher in the pre-eclampsia group compared with the control group, but this difference was not statistically significant. Plasma concentrations of sVCAM-1 were significantly greater ( P < 0.0001) in all pre-eclampsia subgroups (835.34, 855.25 and 964.05 ng/mL) compared with the control group (667.62 ng/mL). Within the pre-eclampsia group, plasma concentration of sVCAM-1 was significantly higher in the subgroup exhibiting fetal growth retardation ( P = 0.03) compared with mild pre-eclampsia.
Conclusion The observed increases in plasma concentrations of sVCAM-1 suggest that measurements of this adhesion molecule may be useful in monitoring pregnancies with respect to the development of pre-eclampsia or fetal growth retardation.     

X-radiation induces 8-hydroxy-2'-deoxyguanosine formation in vivo in rat mammary gland DNA

Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8- Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic lesion that is widely regarded as a reliable index of oxidative DNA damage. The purpose of this study was to examine the effects of X- radiation on levels of 8-OHdG in the context of an experimental model for breast cancer in which chronic radiation exposure has been shown to be carcinogenic in Sprague-Dawley rats. A secondary objective of this study was to determine if the use of phenol during DNA isolation affected the concentration of 8-OHdG subsequently measured. Our results indicate that a profoundly carcinogenic dose of radiation induced a small but significant increase in 8-OHdG concentration in mammary gland DNA, and that the use of a phenol-based versus a salt-based method of DNA isolation had no significant impact on the levels of 8-OHdG detected in either control or irradiated tissue.