Deprenyl in the treatment of symptom fluctuations in advanced Parkinson's disease

Deprenyl, a selective inhibitor of monoamine oxidase, type B, which is free of the "tyramine effect," may ameliorate symptom fluctuations in advanced Parkinson's disease (PD). We randomized 96 patients with marked symptom fluctuations at three centers to receive either deprenyl 5 mg b.i.d. or placebo in parallel fashion in addition to a previously optimized levodopa/carbidopa (Sinemet) regimen. Disability was recorded hourly at home by patients 3 days weekly during the 2-week baseline and the 6-week treatment period. Disability during the "on" state was assessed each week by examination. Mean hourly self-assessment of gait improved in 28 of 50 patients (56%) receiving deprenyl (mean degree of improvement 0.25 points on a 0-2 scale) and in 14 of 46 (30.4%) taking placebo (mean 0.15). Mean hourly overall symptom control improved in 29 (58%) taking deprenyl (mean 0.34) and in 12 (26.1%) taking placebo (mean 0.15) (p less than 0.01 for each parameter). No significant improvement occurred in the objective quality of the "on" state with deprenyl. Mean daily Sinemet dosage decreases were 17% in the deprenyl group and 7% in the placebo group. Adverse effects included nausea, light-headedness, dyskinesias, and hallucinations, all of which abated after the Sinemet dose was reduced. We conclude that deprenyl is of moderate benefit in a majority of patients with symptom fluctuations complicating PD and is generally well tolerated.     

Advanced Parkinson's disease: use of partial dopamine agonist, ciladopa

Ciladopa is a partial dopamine agonist that is effective in patients with advanced Parkinson's disease who are no longer satisfactorily responding to levodopa. Thirty-one patients participated in a double-blind randomized study of ciladopa (added to levodopa) versus placebo. Among 21 patients randomized to treatment with ciladopa and levodopa, there was a 32% decrease in symptoms on the Modified Columbia University Disability Scale. This change was significant, p less than or equal to 0.05. Eight of the 21 patients (38%) improved by at least 50%. The mean number of hours "on" increased by 20%. This change was significant, p less than or equal to 0.05. Five of the 21 patients (24%) were on for at least 4 hours more than at baseline. Dyskinesias were not increased. The mean dose of ciladopa was 19.5 mg/d. The mean dose of levodopa in Sinemet was decreased by 10%. Studies with ciladopa in humans had to be discontinued because of the occurrence of microscopic testicular tumors in some rodents. Although improvement in patients taking ciladopa was modest, there were few adverse effects. These results are encouraging, because two other partial agonists are now available, and they may be as effective as ciladopa.     

Combined use of benserazide and carbidopa in Parkinson's disease

The pharmacokinetics of levodopa differs when it is combined with benserazide or carbidopa. Peak dopa levels are higher, occur sooner, but decline more rapidly with benserazide. Although many patients respond better to one drug than the other, we sought to exploit the differences in pharmacokinetics by giving both drugs to the same patient. Benserazide was combined with carbidopa in 38 patients who were experiencing a diminished response to carbidopa, including 22 patients with diurnal oscillations in performance, "wearing off" or on-off phenomena. Previous attempts to change the dose, sequence, or ratio of levodopa to carbidopa in these patients had been unrewarding. Ten of the patients improved on the combination of benserazide and carbidopa, with a 30% decline in disability. The mean dose of levodopa:carbidopa before benserazide was 910:100 (9 to 1 ratio); the mean dose of levodopa:benserazide was 355:90 (4 to 1 ratio). The mean dose of levodopa:carbidopa + benserazide was 925:155 (6 to 1 ratio). The combination of carbidopa with benserazide is useful in some parkinsonian patients.     

Bromocriptine in Parkinson disease: further studies

Bromocriptine was administered to 66 patients with advanced Parkinson disease (PD) and increasing disability despite optimal treatment with levodopa/carbidopa (Sinemet). Forty-five patients tolerated at least 25 mg per day of bromocriptine (the "adequately treated" group) in addition to Sinemet and had significantly decreased rigidity, tremor, bradykinesia, gait disturbance, and total score, but increased involuntary movements. Twenty-five of these 45 patients improved by at least one stage. Among the 45 patients, 27 had "on-off" effects, and in 19 the "on-off" effects decreased on bromocriptine. The mean dose of bromocriptine in adequately treated patients las 47 mg, permitting a 10 percent reduction in the dose of levodopa. Twelve adequately treated patients received bromocriptine for at least 1 year, and 8 continued for longer than this. Bromocriptine was discontinued in 29 of 66 patients because of adverse effects, including mental changes (14 patients) and involuntary movements (9 patients). All adverse effects were reversible. Despite adverse effects, expense, and scarcity, bromocriptine, when added to levodopa, is useful in patients with advanced disease who no longer respond satisfactorily to levodopa, and for whom no other treatment is available.     

Burkholderia pseudomallei in Environment of Adolescent Siblings with Melioidosis,Kerala, India, 2019

In 2019, Burkholderia pseudomallei was isolated from the backyard of 2 siblings with melioidosis in Kerala, India. This finding highlights the value of healthcare providers being aware of risk for melioidosis in febrile patients, of residents taking precautions when outside, and of increasing environmental surveillance for B. pseudomallei in this region.     

A ‘toxin mantle’ as defensive barrier in a tropical bird: evolutionary exploitation of the basic permeability barrier forming organelles

Birds in the genus Pitohui and Ifrita carry potent neurotoxins that are most abundant in skin and feathers. It was unknown precisely how or where in the skin these chemicals are stored. Here, we report high‐resolution electron microscopy using OsO₄ staining to visualize the location of alkaloids. Our images suggest that toxic alkaloids accumulate in multigranular bodies of epidermal cells and are likely secreted as part of the avian epidermal barrier, where they are made available for chemical defense.     

Flow-diverter in radiation-induced skull base carotid blowout syndrome: do not write it off!

Post-radiotherapy carotid blowout syndrome (CBS) of the skull base is a rare but often catastrophic complication of head and neck malignancies. The existing literature on the treatment of this condition with flow-diverting devices (FDD) is extremely limited and disappointing. We present a case of impending CBS in a patient previously irradiated for nasopharyngeal cancer that was successfully treated with use of multiple FDDs, adjunctive endonasal packing and delayed reinforcement with pedicled naso-septal flap, yielding an excellent outcome at 14-months follow-up. Notwithstanding the discouraging results in literature, our anecdotal experience suggests that endovascular reconstruction using FDD could be an option with long-term viability in post-radiotherapy CBS involving the skull base when reinforced with a vascularised naso-septal flap.     

Bilateral periorbital and cervicofacial emphysema following retinal surgery and fluid gas exchange in a case of inadvertent globe perforation

Surgical emphysema is defined as gas or air trapped in the subcutaneous tissue plane. Here, we report a rare case of bilateral periorbital and cervicofacial subcutaneous emphysema following a vitreoretinal surgery for inadvertent globe perforation during the administration of peribulbar anesthesia. This condition, although self-resolving when restricted to the subcutaneous plane has the potential to spread into deeper tissue planes such as the retropharyngeal space. The presence of crepitus helps to distinguish it from angioneurotic edema. Ophthalmologists must be sensitive to the fact that surgical emphysema can be a very rare, but possible complication of an intraocular surgery following globe perforation.