Serum lipid and lipoprotein cholesterol grids for cardiovascular risk screening of children

We determined serum lipid and lipoprotein percentiles from a total community study of 5,250 fasting children (35% black, 65% white), aged 2 to 19 years. A serum turbidity index was used as a rapid, inexpensive screening test for hyper-beta-lipoproteinemia and hyper-pre-beta-lipoproteinemia. Percentile grids for the turbidity index and serum total cholesterol and beta-lipoprotein cholesterol levels may be used for either black or white children. Triglyceride and pre-beta-lipoprotein cholesterol level percentile grids were reported by race because of lower levels in black children, while grids for alpha-lipoprotein cholesterol levels were reported separately by sex for black and white subjects. A five-step method was outlined for screening children for lipid and lipoprotein abnormalities. Those with hyper-beta-lipoproteinemia and hyperpre-beta-lipoproteinemia would be candidates for therapy and indicate screening of other family members, after secondary causes are excluded.     

Unsulfated DTPA- and DOTA-CCK analogs as specific high-affinity ligands for CCK-B receptor-expressing human and rat tissues in vitro and in vivo

Receptors for regulatory peptides such as somatostatin or vasoactive intestinal polypeptide are expressed by a number of human neoplasms and can be visualized in vivo with peptide receptor scintigraphy. Recently, the CCK-B receptor, which binds both gastrin and cholecystokinin with high affinity, was shown using in vitro methods to be overexpressed in a number of human tumor tissues, including medullary thyroid carcinomas, small cell lung cancers, astrocytomas, gastrointestinal tumors, and stromal ovarian cancers. In the present study, we have designed novel, unsulfated CCK octapeptide analogs linked to the metal chelating DTPA and DOTA, and have tested them for their binding affinity to CCK-B receptor-positive tissue from human tumors: The most potent compounds assayed were DTPA-[Nle^28,31]-CCK(26–33) (MP2286) and DTPA-[d-Asp²⁶,Nle^28,31]-CCK(26–33) (MP2288) with an IC₅₀ of 1.5 nM. For comparison, analogs with C-terminal DTPA, such as [Nle^28,31,Aphe³³(p-NH-DTPA)]-CCK(26–33) and CCK-(26–33)-NH(CH₂)₂ NH-DTPA, had an IC₅₀ of >100 nM. DOTA-[d-Asp²⁶,Nle^28,31]-CCK(26–33) had an IC₅₀ of 3.9 nM. The compounds were selective for CCK-B receptors as they did not bind with high affinity to CCK-A receptors expressed in human tumors (meningiomas or gastroenteropancreatic tumors). In vivo rat biodistribution studies with indium-111 labeled MP2286 and MP2288 showed that the primary mode of clearance was renal, and the primary sites of uptake (% ID/g 24 h p.i.) were kidneys (0.270 and 0.262, respectively) and the gastrointestinal tract. The CCK-B receptor-expressing gastric mucosa showed specific in vivo accumulation of ¹¹¹In-labeled MP2288 which could be blocked in the presence of excess unlabeled MP2288. ¹¹¹In-labeled MP2286 and MP2288 were also found to be stable in human plasma whereas both compounds were degraded in urine (>40% after 3 h at 37°C). The affinity, specificity, biodistribution, and stability of these two DTPA-CCK analogs indicate that these compounds have substantial promise for use in the in vivo visualization of CCK-B receptor-expressing tumors. Received 22 December 1997 and in revised form 28 January 1998     

Transdermal iontophoretic drug delivery: mechanistic analysis and application to polypeptide delivery

Three factors are of primary importance in determining the iontophoretic flux of a charged solute: the electrochemical potential gradient across the skin, an increase in skin permeability to passive transport due to iontophoresis (loosely defined as skin damage), and a current-induced water flux. The latter two factors can also affect the transport of uncharged solutes during iontophoresis. A method of correcting for the skin damage effect is introduced. The contributions of the water transport effect relative to that of the applied voltage drop for charged solutes is estimated. It is shown that the water transport contribution is generally lower than the contribution due to the applied voltage drop. The observed iontophonetic flux of the enhancement factors due to the applied voltage drop alone are compared with the theoretical predictions based on the constant field assumption. It is shown that the theoretical predictions are higher than the experimental observations. This work also examines, for the first time, a synergism of iontophoresis and pretreatment with a chemical penetration enhancer as a means for delivering high molecular weight polypeptides. It is shown that a 2-h pretreatment with absolute ethanol followed by iontophoresis dramatically increases the permeability coefficient of insulin through human skin.     

Should a lower treatment line be used when treating paracetamol poisoning in patients with chronic alcoholism?: a case for.

A lower threshold for treatment of paracetamol (acetaminophen) poisoning has been advocated in chronic heavy users of alcohol, based originally on animal studies indicating that chronic alcohol ingestion increased hepatotoxicity. This was attributed to increased production of the toxic metabolite, N-acetyl-p-benzoquinoneimine, by cytochrome P450 (CYP)2E1 induction. The clinical evidence for increased risk is limited to four retrospective studies with potential for referral and reporting bias and conflicting results. No study has specifically addressed the issue of the treatment threshold for acute paracetamol overdose in chronic alcohol users. However, animal studies in multiple species have consistently shown a lower dose of paracetamol is required to produce hepatotoxicity after chronic alcohol use. The knowledge of potential mechanisms has expanded to include effects of other alcohols, such as isopentanol, induction of CYP enzymes other than CYP2E1 and glutathione depletion. There are no convincing reasons or data to suggest these findings do not apply to humans. However, further human toxicokinetic and clinical research is required to quantify the extent of the interaction. Arguments about treating overdoses should not be confused with those about whether there is an alcohol-paracetamol interaction at therapeutic doses. Halving the threshold dose/concentration for treatment is a conservative educated guess that has been widely adopted. In overdose, the potential benefits of treatment at this lower threshold clearly outweigh the minimal risks of acetylcysteine.     

Vernal ulcer

Vernal ulcer is a rare entity not reported in Indian ophthalmic literature. 76 patients in the age group ranging from 3-43 years diagnosed as having vernal conjunctivitis had been referred from general ophthalmology clinic to cornea service of the same institute during 1988-89. Among them 60 were males and 16 were females. 55 of the 76 patients had corneal involvement in the form of vernal keratitis or vernal ulcer. 16 had typical vernal ulcers. vernal ulcer was found more in the palpebral type of vernal conjunctivitis and affects males more frequently. One patient had an inferior vernal ulcer. It also occurred in the bulbar type of spring catarrh.     

Preparing for an Increased Need for Abortion Access in India during and after COVID-19: Challenges and Strategies

Access to safe abortion is a reproductive rights and justice issue, and it is imperative that safe abortion access during and after the COVID-19 pandemic is a reality for all. India imposed a lockdown in March 2020 to contain the spread of the pandemic. Limited mobility, lack of clarity about abortion as an essential service and abortion as a service permitted through telemedicine, shut down of services providing long-acting and permanent methods of contraception, and changes to decision-making about birthing and parenting during a pandemic are factors that may impact the demand for abortion during and after the lockdown. Shortage of raw materials and limited inter- and intra- state transport of drugs may result in breakages in the supply of medication abortion. Given that 73 percent of abortions in India in 2015 occurred outside of health facilities, the pandemic may have several implications on the need for evidence-based information and quality abortion services, as well as if and how medication abortion is accessed in India, and what self-managed abortion looks like in the COVID-19 era. We discuss factors contributing to reduced access to abortion, changes in abortion need, and suggest strategies to respond to an increased demand for abortion in India.