We have investigated the effect of mannitol, sorbitol, methyl alpha-D-mannopyranoside, lactose, trehalose, and cellobiose on the stability and structure of the pharmaceutical protein recombinant human growth hormone (rhGH) in the lyophilized state. All excipients afforded significant protection of the protein against aggregation, particularly at levels to potentially satisfy water-binding sites on the protein in the dried state (i.e., 131:1 excipient-to-protein molar ratio). At higher excipient-to-protein ratios, X-ray diffraction studies showed that mannitol and sorbitol were prone to crystallization and afforded somewhat less stabilization than at lower ratios where the excipient remained in the amorphous, protein-containing phase. The secondary structure of rhGH was determined using Fourier transform infrared (FTIR) spectroscopy. rhGH exhibited a decrease in alpha-helix and increase in beta-sheet structures upon drying. Addition of excipient stabilized the secondary structure upon lyophilization to a varying extent depending on the formulation. Samples with a significant degree of structural conservation, as indicated by the alpha-helix content, generally exhibited reduced aggregation. In addition, prevention of protein-protein interactions (indicated by reduced beta-sheet formation) also tended to result in lower rates of aggregation. Therefore, in addition to preserving the protein structure, bulk additives that do not crystallize easily and remain amorphous in the solid state can be used to increase protein-protein distance and thus prevent aggregation.

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Ten patients with a nontraumatic spinal extramedullary hematoma are reported, nine of the hematomas localized in the epidural space. Seven of the patients were taking anticoagulant drugs and five showed signs of liver disease, mostly due to alcoholism. The invariable first symptom was an intense local pain in the spine, followed in all but one case by radicular irradiation and in all by bladder disturbances and sensory and motor deficits of the spinal cord or cauda equina. All the patients had myelography to verify the spinal mass and were operated on as fast as possible. The outcome depended mainly on the preoperative neurologic status. If there was only an incomplete sensory and motor lesion before the operation, the patients recovered fairly well or completely. The patients who did not become capable of walking again were completely paralytic preoperatively.

Nine cases of botulism B with preponderant effects upon cholinergic autonomic innervation are presented. Blurred vision and dry mouth were constant symptoms. Impairment of salivary and lacrimal secretion were detectable for months. In the absence of clinical signs, electromyographic studies did not reveal neuromuscular involvement. Administration of antitoxin in the late course of such cases is not recommended, but guanidine can be used. Doubt is cast upon a new clinical entity called "acute autonomic neuropathy."