Funtabulously Frivolous Friday Five 076

• By chance…
• In the late 1980s researchers at Pfizer were investigating the therapeutic potential of PDE5 (cGMP phosphodiesterase) enzyme inhibitors. Over 1500 chemicals were screened and tested over 4 years, resulting in sildenafil, which later acquired the trade name Viagra. Pfizer’s scientists weren’t investigating sexual dysfunction. Viagra was being studied as a potential therapy for hypertension and angina. Unfortunately, Phase II trials of Viagra demonstrated that it was not suitable for the treatment of angina (of note, Viagra should not be used with nitrates for angina as profound hypotension can occur). However, the patients themselves simply didn’t want to stop taking the drug. Pfizer’s researchers soon realised the reason for this: Viagra produced prolonged erections following sexual stimulation. This led to the ‘invention’ a disorder called erectile dysfunction and the rest is history.

Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996 Jun;8(2):47-52. PMID: 8858389

• Gout due to lead poisoning.
• Lead inhibits the tubular uric acid transport system in the kidneys leading to decreased urinary excretion of uric acid. The resulting hyperuricemia predisposes to gout.
• The condition is essentially indistinuguishable from run-of-the-mill gout and requires an index of suspicion, detection of the lead exposure source and biochemical confirmation of lead poisoning in addition to standard gout therapy.

Poór G, Mituszova M. Saturnine gout. Baillieres Clin Rheumatol. 1989 Apr;3(1):51-61. Review. PMID: 2661030.

• People are correct at identifying a newborn’s sex 55% of the time, which was statistically significant when compared to chance alone.
• It turns out that pediatric nurses (59%) are better than pediatricians and non-healthcare workers.
  Babies thought to be girls were generally hairier!

Round JE, Deheragoda M. Sex–can you get it right? BMJ. 2002 Dec 21;325(7378):1446-7. PMID: 12493659; PMCID: PMC139032.

• Dr Thomas Neill Cream was a serial killer convicted of killing 4 London prostitutes by strychnine poisoning.
• Cream was born in Scotland and received medical training at McGill University in Montreal, Canada. He was an abortionist, who did a botched job on a woman he later ‘had to marry before (most probably) eventually killing her with strychnine. Prior to his UK conviction he was sentenced to life imprisonment in the United States (but was released after less than a decade) for the second degree murder of Daniel Stott. Cream poisoned Stott with strychnine after the victim found out that Cream was having an affair with Mrs. Stott.
• Cream was hanged in 1892 for the murder of 4 prostitutes in London. He claimed innocence to the end. However, a probably apocryphal story holds that his last words were “I am Jack the…”. However, Cream was in prison at the time of the Jack the Ripper murders. Cream probably had many other victims — many of his patients were plagued by convulsions, that were sometimes fatal…

Toxicology Conundrum 007 — Strychnine poisoning

• The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after treatment of onchocerciasis with the medication diethylcarbamazine (DEC). It named after Mexican parasitologist Luis Mazzotti.
• Mazzotti reactions can be life-threatening, and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, oedema, and abdominal pain that occur within seven days of treatment of onchocerciasis.
• Onchocerciasis is also known as river blindness and is caused by infection with the filarial nematode Onchocerca volvulus which is transmitted by the bite of the Simulium black fly. It is the world’s second-leading infectious cause of blindness. Bizarrely, it is actually an endosymbiont of the nematode, Wolbachia pipientis, that causes the severe inflammatory response typical of the disease when the nematodes die in various parts of the body. This manifests as keratitis, optic neuritis, onchodermatitis (including a ‘lizard skin’ appearance), edema and lymphadenopathy.
• Onchocerciasis occurs primarily in Sub-Saharan Africa, with other cases seen in the Arabian peninsula and both Central and South America.
• Today, treatment of onchocerciasis focuses on the use of ivermectin to kill the nematodes, as well as antibiotics such as doxycycline to kill the Wohlbachia endosymbionts.

River blindness (Photo by Pak Sang Lee - click image for source)

CDC — Filariasis